Response to Comments: Skin Substitute Grafts/Cellular and Tissue-Based Products for the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers

Multiple comments were received requesting clarification of the evidence bar and understanding how evidence is analyzed for policy coverage. They are requesting specificity in study design, study endpoints, sample size calculations, and level of evidence required. Many commenters support use of real-world data/evidence to be considered. Others request retrospective study designs and some request that all evidence regardless of study design be given equal consideration. Many interpreted the Local Coverage Determination (LCD) as requiring a randomized controlled trial (RCT) for coverage and elaborate on challenge and concerns of the RCT design.

The LCD evidence review is a critical process that seeks to ascertain the efficacy of medical interventions by evaluating evidence of sufficient power and quality. This approach is designed to ensure that outcomes are attributed to the intervention. Importantly, the LCD is not prescriptive about the study design required to meet this standard, recognizing that various methodologies can yield the necessary information.

While RCTs are often considered the gold standard in research, the LCD does not mandate that studies must be RCTs to be considered. This flexibility is intentional, allowing for a broader range of study designs and accommodating future research avenues. The current absence of alternative study designs, such as comparative cohort studies with adequate controls, sample size, and data quality, is not due to a lack of potential but rather to the unavailability of such manuscripts. To provide further clarity on this objective the term high-quality evidence has been replaced with high-certainty evidence which best describes the objective that a study needs to reach to be considered for coverage.

Real-world Evidence (RWE) and Real-World Data (RWD) are broad terms representing multiple different study designs that collect data from various sources already in existence, such as medical records, claims data, product or disease registries, and other data gathering sources like digital health technologies. These are often retrospective or observational studies. A benefit to RWE and RWD is that it can offer valuable insights into patients often excluded in clinical trials. This may also reduce health care disparities if clinical trials do not have representative demographics. Therefore, published peer reviewed RWD/RWE may support the use of these products, fill in gaps in evidence, and address real-life settings. There are limits to RWD based on the study design. Without a control group, it is difficult to attribute outcomes to the product under investigation definitively. Controlling variables, accounting for missing data, reducing bias, and ensuring adequate group sizes are complex tasks. While comparative effectiveness research can be conducted from RWD sets there are many challenges to overcome. A section inclusive of RWE submitted during the open comment period has been added to the LCD.

To be considered for coverage, each product must have published clinical trial(s) that evaluate a well-defined patient population of sufficient sample size and use a robust study design to convey confidence in the results. In this data set, only RCT met this criterion. We employed a standardized tool, RoB2, to provide assessment of each RCT using the same criteria and measures to evaluate if the individual product had meaningful level of supporting evidence that it is effective for wound healing. Additionally, we looked for at least 1 additional clinical trial that showed equivalent healing rates to the RCT confirming the utility of each product.

Several products are supported by literature with a high risk of bias. This is based on consideration that the overall body of literature is low quality and these studies had adequate sample size and measures to reduce the impact of the potential bias were addressed. Each of these products had at least 1 additional clinical trial that showed equivalent healing rates to the RCT confirming the utility of each product. In further analysis as a result of input during the comment period, we identified 1 included product that did not reach this threshold as the study had a small sample size and high risk of bias without a supporting clinical trial; therefore, this was removed from the covered list (OASIS Tri-Layer). Three products met this threshold that were added to the covered list (Derma-Gide, Kerecis and NuShield).

Designing studies is not the role of the MACs who are responsible for reviewing the published studies to support coverage decisions. To aid researchers in understanding the evaluation criteria, an educational article titled "Principles of Study Design" has been published by the MACs. Additionally, investigators can reference the AHRQ Technical assessment “Guiding Question: What best practices in study design could be used to produce high-quality evidence on skin-substitutes?,” the Journal of Wound Care International Consensus Document, Wound Care Collaborative Community 15 priority wound care endpoints, International Working Group on the Diabetic Foot, and Serena et al (2012)’s consensus principles for wound care research. Finally, Cochrane and GRADE offers education and tools that are widely accepted standards for study design and evaluation.

Multiple stakeholders have requested to delay implementation of the LCD. These requests range from 12 weeks to 4 years. The 12 weeks request is to avoid interruption to beneficiaries within an episode of care. These requests are designed to allow stakeholders time to conduct and publish further product investigations.

We acknowledge concerns raised by stakeholders regarding potential treatment disruptions for patients within an episode of care; therefore, the notice period for policy changes will be extended from the standard 45 days to 90 days. This extension will mitigate any interruptions in patient care due to a shift in product use mid-treatment and ensure continuity of care for Medicare beneficiaries during this transition.

The LCD aims to provide Medicare beneficiaries with access to scientifically supported skin substitute grafts and Cellular and Tissue-Based Products (CTP) that have proven effective in accelerating ulcer healing, thereby enhancing healthcare outcomes. This initiative aligns with the statutory requirement for the Medicare program to cover services that are reasonable and necessary (R&N), as stipulated by the Social Security Act, while non-covered services are deemed investigational. Products without supporting evidence are not considered R&N and further delay of the LCD implantation is not appropriate as there are commercially available products that meet the R&N requirements.

Alcon J states 67% of patients will lose access to the current care and many other comments on the potential impact of the LCD to those in rural and underprivileged areas. They state this can cause a disparity among Medicare patients.

No supporting literature was included that can validate these statements. The LCD includes a section to address health care disparities. This is particularly significant for rural and underserved communities, where access to healthcare can be challenging. The LCD's emphasis on the use of effective products for ulcer healing can lead to better patient outcomes through enhanced wound healing and potentially reduced need for frequent application changes. Moreover, the LCD's requirements for comprehensive wound care and the management of underlying medical conditions are fundamental not only for the healing of the current ulcer but also for the long-term health outcomes of patients. Such measures are expected to positively impact populations in rural and underserved areas.

Multiple comments were received expressing concern on the evidence used to support the frequency limitation of 4. Several commenters state the 2021 Armstrong study to limit the maximum number of applications to 4 based on the average number of applications cited in the study is statistically inappropriate. The average number of applications was 3.7 with a standard deviation of 3.6. Armstrong and others explain “mean number of applications found was 3.7, but with a wide standard deviation (SD) of 3.6. If this were a normal distribution, you would apply the 68-95-99.7 rule (percentage of the distribution across 1, 2, and 3 standard deviations), suggests that 68% of patients are within 1 SD of the mean, needing 1 to 7 grafts before closure. To further explain, it means that 1 SD (34% of patients) required less than the mean, and 1 SD (34%) required more than the mean of 3.7 grafts. Then if you add the remaining 32% of patients that fall outside of 1 SD, it suggests that 66% percent of patients required more than the mean of 3.7 graft applications.” Therefore, the maximum number of applications should be set to 8 to accurately interpret the results of the study, with exceptions for wounds that are known to be larger as indicated by CPT^® codes 15272, 157273, 15277 and 15278. Another concern is the use of an average to set frequency limits and not specific wound factors like size and co-morbidities. 

Based on the logical outgrowth of the feedback and evidence received during the open comment period, the following changes have been made to the LCD. We have changed the application limit from 4 to 8 applications/per episode of care. The 12-week duration has been changed to 12 to 16 weeks allowing providers greater discretion on frequency of applications based on the needs of the individual patient.

Establishing application limits is challenging and reflects the shortcomings of the current evidence. Lack of standardized protocol, missing data on frequency of application, and lack of studies directed at this specific area limit the current data. This is further complicated as products have set parameters for weekly application changes, despite lack of evidence to support this labeling so the true number of applications necessary for the product may not be known. Many reports do not include information on consistent outcome measures, co-morbidities, or other risk factors that may impact application frequency. Future investigations will hopefully address these questions with more robust data to help determine optimal frequency.

The evidence analysis includes 30+ papers covering over 34 products with published data on application frequency and can be found in the evidence summaries for the individual products. This ranges 1-9.92 (over 4-20 weeks) with the majority of products reporting application changes for 12-week episodes of care with 4 or less applications. This literature is challenged with a wide variability of study designs and these studies were not designed to address frequency. Some studies report means while others report averages. Duration of time was also variable, so we cannot pool this data, however 22/34 products reported 4 or less applications, while 8 products reported 5 or more. Therefore, application frequency greater than 4 is not the standard within the current published evidence. The retrospective cohort studies used by Medicare claim that Armstrong provides data on frequency limits reporting an upper limit of 7-8 (3.7 ± 3.6) addressing most cases. Internal Medicare national data demonstrates a median of 4 sessions (applications) per episode of care further indicating the difficulty in determining the optimal frequency.

During the open comment period, stakeholders, providers, and societies emphasized the need for >4 applications especially for larger, more complex wounds. Additional literature demonstrates larger wounds were more likely to need more applications (Raspovic 2018). The duration of time to heal is typically 12 weeks and the time used on most study protocols. The mean duration to closure of the largest wounds (>25) in Raspovic 2018 was 105 days. A retrospective cohort in the Medicare population investigating application frequency showed “the mean number of applications to achieve closure was 5.77 ± 2.71 with 6.06 ± 2.74 for DFU and 5.57 ± 2.69 for VLU over 16 weeks (Carpenter 2024).” Based on this supporting literature, the 2022 Medicare claims data by Armstrong et al., and expert input received from stakeholders, providers, and societies, it is evident the upper limit of 8 incorporates most wounds. The exact percentage of wounds that may utilize greater than 8 applications is not delineated within the literature, but consistently represents a very small portion of overall ulcers. The literature also suggests the effectiveness of additional applications past this point is low.

Additionally, there is a lack of literature on criteria for product re-applications including when and if they should be reapplied. Some products remain in place with 1-2 applications per episode of care. Other products are reapplied weekly or biweekly and some studies report changes only when there has been a slowed progression of healing. Because the labeled use for the products is left to manufacturer discretion and not based on evidence, this creates a dilemma on understanding what factors should be considered to change applications and what application frequency is optimal for wound healing. This is exemplified by EpiFix, which is the most extensively studied product. The label recommends weekly applications, yet subsequent research demonstrates weekly application is not always necessary to achieve wound healing. In fact, a median of 2.5 applications in 12 weeks has been reported to complete wound healing.

The additional documentation requirements for greater than 4 applications have been removed as documentation should be completed for any additional application. Use of more than 4 applications require an attestation from the provider that requirements specified in the medical policy have been met. This attestation can be provided at the claim level using the KX modifier. This is not considered burdensome as measurement of the wound’s progression, documentation of decreasing size of the wound to determine if the wound is healing, and the rationale as to why additional applications are necessary should be part of the routine care of these wounds. Input received during the comments with recommended wording to provide more specific measures of wound healing has been added to the B&C article.

As communicated through the comments received, fraud, abuse, and overutilization are rampant with skin substitute grafts/CTP products. It is the responsibility of the MAC to ensure access to R&N care, while avoiding improper payment, which is clearly challenging. We strive to reduce provider burden, but also must execute payment per requirements of the Medicare program. To this goal, the B&C article has expanded instructions on the use of the KX modifier. B&C instructions: with 1-4 applications no additional steps are necessary, using 5-8 applications requires the addition of the KX modifier to attest that the criteria outlined in the LCD has been met when submitting claims. The KX modifier may be used at MAC discretion to identify aberrant practices, review claims, and provide education as needed. We believe these changes represent a strategy that can provide maximum flexibility to providers caring for this challenging population, while ensuring appropriate care and payment for the Medicare beneficiaries we serve. 

Many commenters state that MACs should reconsider the requirement of evidence and coverage that should be determined by FDA regulatory pathways. They request all products with a TRG letter, PMA approval, and/or 510k and a product-specific Q-code assigned by the HCPCS committee be covered. Many commenters provide elaborate details of the various FDA regulatory pathways.

The existence of a HCPCS code or approval via an FDA regulatory pathway does not translate to Medicare coverage. The item or service must satisfy the R&N standards for coverage. The 2024 coverage policy proposal emphasizes an evidentiary review for each product, aligning with the 21st Century Cures Act's mandate for evidence-based policy decisions. This approach ensures that covered products possess at least short-term safety data, addressing a critical gap since certain FDA regulatory pathways may not mandate comprehensive assessments of effectiveness or safety for these products. Such a policy is crucial for Medicare beneficiaries, as it upholds the standard of evidence-based coverage, thereby safeguarding their health interests by ensuring access to safe and effective medical products.

MACs face coverage decisions on items and services that are off label on a regular basis. In these cases, evidence to determine if the service is R&N is considered to ascertain whether coverage is appropriate. If the products are being used and billed as skin substitute grafts/CTP, the evidence must demonstrate effectiveness and improved health outcomes to be considered for coverage.

Multiple Billing and Coding (B&C) questions are asked throughout the comment letters.

B&C questions will be addressed in the B&C article as well as by the individual MACs after the final LCD is published.

Multiple commenters asked if products on the NOT COVERED list can be used for indications outside DFU and VLU? 

Managing claims for products used outside the LCD falls within the discretion of individual MACs. The MACs are responsible for ensuring that services meet the R&N criteria for coverage as established by Medicare. Therefore, any product, regardless of if it is on the covered or non-covered list for this LCD, must be R&N for the indication. Some commenters misunderstood that products which are non-covered in the LCD only apply to DFUs or VLUs. Other product uses for different wounds (not DFUs or VLUs) may be considered on a case-by-case basis.

A comment letter was received from Regenerative Technologies/Geistlich which states “they commend the commitment to covering CTP in the treatment of chronic wounds supported by peer-reviewed, randomized controlled trials. Evidence based medicine ensure patients receive the highest quality of care…” They provide a summary of published literature regarding their product HCPCS Q4203 Derma-Gide. They provided 4 published papers to support this product including a 2024 RCT and a summary of the evidence. They ask for the product to be included for coverage.

We apologize for the omission of these papers which were missed in the literature search since the product was identified by its generic descriptor, purified reconstituted bilayer matrix (PRBM), and not linked to Derma-Gide in the papers. These papers have been reviewed and added to the LCD. One unpublished paper was not reviewed. The product has been added to the covered list based on evidence.

A letter was received from RedDress which states: “The Proposed LCD appropriately balances the need for patient access to high quality wound healing products with a requirement for literature documenting improved clinical outcomes. The Final LCD should provide additional clarity on the quality of evidence that must be provided to support coverage of individual products.” The commenter provides suggestions on standards for evidence to consider.

Thank you for your support of the LCD and evidence-based decision making. We appreciate your commitment to high-quality study design and research. For the type of literature needed and evidence to support a product, see Comment #1.

Comments were received from Dr. Lantis, first author on several of the included studies, who states that many of the guidelines within the document outline best clinical practice and are appropriate. He agrees with 4 weeks of conservative therapy, but states wounds that are 2 times standard deviation in size and those open for greater than a year may require earlier interventions. He says the median number of applications for most of these products is 6 not 4. He also recommends outlining provider type which might include DPMs. He notes that most studies are industry sponsored and that it is difficult to conduct this type of research without such funding. He argues that his study, Lantis et. al., 2023, published in Wound, should be included in the LCD bibliography.

Thank you for your valuable input and for contributing to the advancement of healthcare practices. The approach to managing exceptional medical cases, such as unusually large or prolonged wounds, underscores the importance of allowing for clinical discretion when necessary (see Comment #4).

The LCD outlines the qualifications required for providers, emphasizing the need for adherence to their scope of practice and licensure, which includes DPMs. The reference to nurse practitioners was removed from the LCD under non-physician provider to prevent confusion as it was not intended to limit any qualified providers.

The use of the Risk of Bias 2 (RoB2) tool in evidence analysis was chosen specifically for this analysis, as it does not automatically associate industry funding with a higher risk of bias. Instead, it meticulously examines the study's design to pinpoint any potential biases, ensuring that well-conducted research, irrespective of funding sources, is recognized for its contribution to evidence-based medicine.

The recently published omitted paper has been added to the LCD. Thank you for submitting this important work. The product has been added to the covered list based on the literature-based evidence.

A comment letter from Cellularity recommends that Biovance should be considered for coverage. They support the evidence-based pathway to policy development and explain the benefits of RWD and request it be used for consideration of coverage of Biovance. The commenter explains “We believe that the proposed LCD misinterpreted and mischaracterized the peer reviewed evidence for Biovance…The Biovance group was compared to the control group, which was the physicians’ choice of SOC (collagen dressing, wet to dry, and other non-graft therapeutics).” They also emphasize that RWD is more likely to include underserved and minority populations which are often poorly represented in RCTs. Supporting literature is submitted.

That you for your comments. For further information on evidence use for coverage including RWD, see comment #1, and for health care disparities, see Comment #2.

The submitted papers on total ankle replacement, thoracic outlet syndrome, and tendon tears are not within the scope of the LCD and we do not consider review papers or product labels for coverage determinations. We do not believe the Smiell et. al., study was misinterpreted. The paper notes: “This study was observational; there was neither treatment randomization nor blinding, and there were no control groups.” In the conclusion it states, “The study did not have a control arm nor were the wound measurements provided at regular intervals but done only on enrollment and at the end of the study. Therefore, it is difficult to determine how the application of DDHAM compares to other treatment regimens with respect to wound closure outcomes.” Without a control group, the percentage of wounds that would have healed with SOC alone is unknown. While we commend the investigators inclusion of the most complex wound type, we cannot adequately determine from this study if the improvement reported is from the product or other factors received in the care. There were multiple other factors that could have impacted the reported outcomes. Finally, there is a high risk of bias in the absence of randomization or blinding. Therefore, this literature is not considered sufficient for coverage.

Comments were received from Ekareinc, manufacturers of a digital tool for wound measurement including photographic documentation. They support the policy and endorse the evidence-based pathway for coverage. They acknowledge the LCDs objective measurement of healing and suggest standardized measurement tools are essential to gather this data and support treatment decisions. They are concerned that while the LCD requires documentation of these measures, reliability cannot be established. They request the integration of advanced digital measurement tools into the final LCD to ensure all documentation is accurate and verifiable.

Thank you for your comments and overall support of the policy. While the LCD requires documentation of ulcer healing, the modality to perform these measurements is outside of the scope of the LCD which is focused on skin substitute grafts/CTP products for DFUs and VLUs. An LCD reconsideration request can be made with peer-reviewed published literature included to address this specific area of wound care.

An anonymous comment letter was received that expressed concern that the policy permits the use of skin substitutes for indications beyond chronic ulcers. They are concerned that “enables aggressive and abusive practices by physicians and mobile wound care providers, inflates cost and undermines the efficient allocation of healthcare resources.” They suggest bundled payment to mitigate the current profit-driven strategy by manufacturers and mobile wound companies. They state, “It's distressing to witness taxpayer dollars being utilized to fund skin substitutes with exorbitant ASPs, resulting in exorbitant wound care costs, especially when there are more conservative and cost-effective clinical modalities available for wound treatment.” They feel the current policy favors a specific wound society whose membership is made up of those who may profit from these products. “In summary, it's imperative for Medicare MACs to address this reimbursement abuse promptly and implement measures to prevent the exploitation of current policies for financial gain at the expense of taxpayers and the integrity of healthcare delivery.”

Thank you for comments and expressing your concerns regarding abuse within this area. The policy's focus on evidence for wound healing products is a critical step in ensuring that only those products that demonstrate safety and effectiveness are covered. By limiting applications to the number supported by current evidence, it helps to prevent the misuse of these products. The policy's application to DFUs and VLUs covers most cases where these products are used, which streamlines the process. Indications outside of DFU/VLU are left to the discretion of the individual MACs, who must also adhere to the reasonable and necessary standard (see Comment #7). This approach ensures that all products are evaluated fairly, without bias towards any product or group.

Multiple providers sent in similar letters requesting Restrata be added to the covered list. No literature was submitted. They state it is a synthetic product and effective in trauma settings to cover tendon, bone, and even infected wounds. The benefit of this product being fully synthetic is that it can go in dirtier wound beds and mimics the extracellular matrix to allow them to rebuild. No literature was submitted.

Thank you for your comments. See the Restrata section for complete review of this product in the LCD. If there is additional peer-reviewed published literature to demonstrate the product is effective, safe and improves outcomes, it can be considered for coverage via the LCD reconsideration process. 

A DPM and researcher comments in support of Restrata stating it is synthetic, resistant to enzymatic degradation with few applications required, has a microscopic structure, and is easy to store. He was the author on 2 papers on this product that were submitted for review.

The prospective cohort study involving 24 patients with a DFU and a retrospective case series of 23 patients with lower extremity wounds have been added to the LCD. However, the current evidence does not ensure a high level of certainty for Restrata. If future evidence is published it can be submitted via the LCD reconsideration process for potential coverage.

Microvascular Tissues, Inc. comment letter expresses concern about “quality supporting evidence” but does not provide clear direction as to what is acceptable evidence for policy coverage.

The commenter provides multiple examples of study designs for covered products in the LCD. They suggest using a specific paper as an example while prioritizing level 1 evidence.

The comment also explains that 6 papers were cited in terms of application frequency. They explain that wound size can have a significant impact on the amount of product needed. The methodological limitations of the studies are also noted but do not feel there is sufficient support for this limitation.

Finally, they suggest using ASTM Standard 2312-11, Standard Terminology Relating to Tissue Engineered Medical Products definition for scaffold: scaffold, n—a support, delivery vehicle, or matrix for facilitating the migration, binding, or transport of cells or bioactive molecules used to replace, repair, or regenerate tissues.

Thank you for your comments. See comment #1 regarding evidence requirements and comment #4 for application limits. One of the primary functions of a MAC is to pay claims; therefore, while there are many definitions of skin substitute grafts/CTP, the policy relies on the AMA CPT^® code book describing the CPT^® codes used to outline the services being billed. Aligning the definitions in the LCD and CPT^® code book ensures accuracy when billing for the product and service provided. Coverage criteria do not require demonstration of scaffolding, but the product must be effective for wound healing when it is being used for this purpose. Thank you for submitting a definition of scaffolding. We have added this language to the LCD.

Vivex requests clarification of the quality of evidence standards used for coverage and request an additional 36-month time frame for companies to conduct research before the policy becomes effective. They comment that NCDs have published Appendix A to provide evidence guidelines for researchers. They state the lack of clear evidentiary standards and endpoints in the Proposed LCD creates special process issues for manufacturers of human cells, tissues, and cellular and tissue-based products (HCT/Ps). They request an established expedited mechanism to authorize coverage for products once evidence is developed. They express concern regarding the application limit of 4 for large/complex wounds. They are worried about the supply chain when the majority of currently marketed products are no longer covered.

They compare the proposed LCD to existing LCDs. They are concerned that the policy represents an abrupt change in course and not enough time has been provided for adjustment to the proposed policy. They argue that ample time for negotiation has not been allotted. They express concern that the collaboration of all MACs to issue the same LCD is equivalent to an NCD, which they find objectionable.

Transition of a product from non-covered to covered occurs through the LCD reconsideration process. Once there is substantive evidence published in peer-reviewed journals, a product can be submitted for LCD reconsideration. A product code cannot be added to the B&C Article without going through the reconsideration process since Medicare requirements mandate that a coverage change must go through the entire process, including open meetings and comment. It is the intention of the MACs to review literature at least once every 12 months.

MACs host open meetings several times a year, providing many opportunities for stakeholders to present new evidence and discuss potential coverage updates. Mechanisms are in place to expedite the process when necessary, such as opening an LCD to comments for a new section only. We also prefer a process that is more efficient and less labor intensive than the LCD reconsideration process to add items to coverage; however, to comply with laws governing the LCD process this is not feasible. The MACs intend to work together to streamline this process, reduce duplicity, and provide timely responses within the constraints of the requirements for LCDs. However, despite the MACs’ best efforts, the LCD reconsideration process takes approximately 4-6 months.

A comment letter addresses an existing LCD (specifically CGS’s). Not all MACs have current LCDs on this topic. CGS has determined that the existing LCD is outdated and does not meet current 21^st Century Cures standards, so it will be retired.

We do not believe the LCD will impact supply chains. Optimization of conservative care measures and treatment of systemic disease, application limits, and steps to minimizing wastage are expected to curtail the misuse of products which will in turn reduce demand by eliminating overutilization and improper use. Additionally, from a supply chain perspective, the products covered under these policies are produced in high volumes, reflecting their widespread acceptance and utilization in clinical practice. No suppliers of the covered products expressed concern regarding supply chain during the comment period. Several of the manufacturers have noted in their comments that they are confident in their ability to meet this demand and recommend avoidance of delays due to supply chain concerns.

There are no restrictions on collaboration among MACs in policy development and many multi-MAC policies precede this LCD. Many stakeholders strongly support collaboration to ensure consistency in coverage across state borders. The LCD was developed according to the process required by the Medicare Program (Medicare Program Integrity Manual Chapter 13). As compared to the NCD process, each MAC must conduct their own open meeting, comment period, and consider unique needs of their jurisdictions in the development of an LCD.

In regard to the request for an additional comment period, there is no perceived benefit in doing so. Changes from Proposed to Final LCD are based on logical outgrowth from the comments. The response to comments article and rationale for decision making are included to ensure communication of these changes as a result of public input and scrutiny.

For evidence standards, see Comment #1, for delay in implantation, see Comment #2, for application limits and frequency, see Comment #4, for the FDA regulatory process, see Comment #5.

Multiple APRNs submitted similar comments sharing their experience in treating ulcers with these products and urge that the proposed LCD is not finalized. They cite the Armstrong study as evidence that all products accelerate wound healing. They state that the policy interferes with their ability to utilize clinical judgement in caring for their patients and encourages input from wound care providers. Some suggest that the LCD jeopardizes patient care. Some commenters inquire as to the use of the products outside of DFU/VLU and express concerns regarding application limits. They recommend a consideration of 10% improvement per week without other restrictions. No evidence was included.

Thank you for your comments. The policy's focus on evidence-based literature for products for wound healing aligns with Medicare's coverage, which supports the use of medically necessary treatments. Feedback from wound care societies, healthcare providers, and stakeholders has been valuable in this process as evidenced by the evolution of this LCD from previous drafts. The goal is to expedite the healing process, minimize treatment applications, and improve the overall quality of life for Medicare beneficiaries. Clinicians retain the flexibility to choose from a variety of product options from various classes of skin substitute grafts/ CTP, maintaining the capacity for clinical judgment and personalized patient management strategies.

For application limits, see Comment #4, for use of products not involving DFUs/VFUs, refer to Comment #7. If evidence is published to demonstrate outcome improvement using 10% improvement criteria, this can be considered via the LCD reconsideration process.

A comment letter was received from a physician medical director from private insurance entity who encourages the MACs to reconsider the FDA requirements. They feel MACs are stepping into the FDA’s role of addressing safety and efficacy. She recommends Premarket Approval (PMA) from FDA be required for the use of these products which should be considered Class III medical devices and 510K and HCTPS are not sufficient. She says there should be no payment made without evidence the product is safe and effective which she feels should be established by the FDA not the MACs. She says Apligraf got full PMA and all others should do the same. She states product use as skin substitutes as HCTPS do not qualify to be regulated under CFR 1271 and gives examples of several existing products which she does not feel work. She states if they are truly grafts and not dressings there is no reason more than 2 should ever need to be applied and if more than 2 applications are required it should be considered a dressing. She advocates for lower limits on ABI values. She argues there is no role for provisional coverage which is coverage without evidence.

She states there are no access issues or health care disparities except in the eyes of manufacturers or providers with “something to gain.” She explains “it is an absolute fabrication that patients will be negatively impacted by limiting the use of skin substitute grafts. I have reviewed thousands of pages of records across the entire range of skin sub-Q codes, and these products do not work in real life. On the contrary, medical record review has revealed that the use of these products harms patients, prolongs healing time, and makes wounds larger.” All those who say, this “LCD will harm patients are not speaking truly and cannot back up or substantiate these claims.” She also argues those who state this “limits innovation says so falsely; innovation is not at the cost of the patient, and it is unacceptable to experiment on human patients.” The letter concludes: “Without limits, the skin sub companies will advertise these unproven products for every reason under the sun, and again, this will result in human experimentation as use in these ways does not have sufficient evidence of safety or efficacy.”

A summary of risk from the LifeNet Health website is provided that reviews potential risk of allograft dermal tissue, a paper and cartoon on sample size calculations, and multiple FDA reference provided. 

Thank you for your comments. For further discussion of the FDA role, see Comment #5. We agree that PMA requirement from the FDA wound be highly beneficial; however, the MACs cannot instruct the FDA process and therefore, need to ensure that improper payment for services that do not meet the R&N threshold are not made as a result. Your arguments further the support the need for rapid initiation of this LCD to provide immediate limitations while improved evidence is developed. The supporting materials have been reviewed but not incorporated into the LCD as there was no peer-reviewed published literature provided except the sample size article. We agree that provisional coverage would allow experimentation without consent and understanding of risk and benefits, as well as not meeting the R&N criteria mandated by the Medicare program. 

The American Association of Tissue Bank (AATB) and the American Association of Tissue Bank’s Policy Group (TPG) request changes to the application limits, clarity on level of evidence products need to be covered, clarify the process of transitioning from non-covered to covered status, and delay the effective date of the LCD. They request clarification of how the modifiers will be used. They request clarification of the ICD-10-CM codes for DFU above the ankle and recommend additional ICD-10-CM codes for VLU. Several of these codes represent ulcers with extension to muscle or bone.

Billing and Coding questions have been clarified after additional input and questions received during the open comment period. This also provides further instructions on the use of modifiers.

ICD-10-CMs: The policy is limited to DFU and VLU. For DFU, ulcers above the ankle, like other locations that are not DFU or VFU, are at individual MAC discretion. Literature demonstrating the use of these products with improved healing with exposed bone and muscle has been submitted; therefore, these codes were added to the B&C article. Only products with labelled indications for these indications are eligible for coverage for these codes.

For evidence bar, see Comment #1, for disparities, see Comment #2, application limits, see Comment #4, for transition to coverage, see Comment #17.

A comment letter was received from Drs. Rogers, Lavery and Armstrong who are also investigators and authors on many of the included papers They suggest the following:

• Provider a disclaimer for the “Standard of Care” to avoid LCD becoming evidence in malpractice cases.
• Do not require ankle-brachial index (ABI) as a condition of coverage as there are clinical circumstances such as recent bypass this is contraindicated and they can be falsely elevated in diabetes. Recommended language is provided to replace this requirement.
• The comments recommend increasing the number of graft application to 8 and Dr. Armstrong explains the rationale from his paper that supports this recommendation.
• The LCD should encourage best practice of offloading in conjunction with skin substitutes. They also suggest a total contact cast is considered separately reimbursable on the same day of service as a skin substitute.
• The authors comment that the role of these products in complex wound with deeper structures exposed, in combination with negative pressure wound therapy or contaminated wounds differs from the role in the outpatient setting. They propose use in the inpatient setting is not applied to the number of grafts considered R&N.

Dr. Lullove who is also an investigator in several of the included papers submitted a similar letter but brings up some additional concerns:

• The documentation requirements are stringent and include “This includes documented positive treatments and response to therapy after the maximum 4 applications and detailed assessments of the ulcer and underlying conditions” and if subject to review may impair or delay continuation of advanced treatments.
• He is concerned with application of the policy to codes beyond those for DFU/VLU and states not all applicable ICD-10-CM codes are included.
• There is a comment regarding specifying the licensure of providers and that DPM should be included in all policy language as qualified health providers and allowed to manage DFU/VLU.

Multiple providers also express similar concerns regarding ABI.

Thank you for your comments and advancements in this area as investigators. Language was added to clarify that the term Standard of Care (SOC) used in this policy refers to a Best Practice recommendation and it is not to be interpreted as the legal definition of SOC for either DFU or VLU. The recommended language on vascular assessment has been incorporated in the LCD. The work provided by Armstrong et al. has been included in the LCD and consideration of application limits, see Comment #4.

We agree with the importance of offloading. The LCD requires offloading as indicated in Covered Indications #3 which requires documentation of evidence of offloading for DFU as part of the implemented treatment plan. Language to clarify that the implemented treatment is expected to be continued throughout the course of treatment has been added to the LCD to ensure clarity. Thank you for pointing this out. The billing and coding instructions regarding a contact cast Is beyond the scope of this LCD and should be directed to the provider’s individual MAC.

The literature for Kerecis Omega3 has been added the LCD and this product added to the covered list. The evidence for Restrata has also been added but does not provide sufficient evidence for coverage as explained in the Restrata section of the LCD.

There was no evidence submitted to support the use of skin substitute grafts/CTP in contaminated wounds. There is a paucity of literature addressing use of these products with exposed muscle and bone, and the policy limits use to products with labeled indication for such use, see comment #20. The policy Limitation Section explains that the placement of these products in infected, ischemic, or necrotic wound beds is not considered R&N and therefore, ICD-10-CM codes representing necrosis are not added to the B&C article. The application number applies to use both the inpatient and outpatient setting for an episode of wound treatment and Place of Service added to the B&C for clarity.

The documentation requirements align with what would be expected in the care of a patient with chronic non-healing ulcers. Documenting response to treatment and assessment of the wound is to be expected and should not result in any delays or interference with patient care. In regard to coding this is covered in the B&C article. For ICD-1O-CM codes see Comment #20.

It is not the place of an LCD to define State Scope of Practice; however, there are no restrictions within the LCD that would limit a DPM ability to care for patients with DFU/VLU and the policy language adapted to clarify this (see Comment #10).

Tides Medical and other commenters suggest that only products on the national ASP drug file should be reimbursed. Tides Medical comments “An analysis of the 2023 Medicare claims data provided by data analytics companies such as Purple Labs and Definitive Healthcare found that over 67% of patients treated with a skin substitute will lose access to their current care and treatments which will be non-covered by the draft LCD.” They state this can result in health care disparities.

They also comment on concerns with application limits and FDA regulation and suggest a role of TRG letters in coverage decisions. They inquire on the transition from non-covered to covered with evidence development and use of skin sub products outside of DFU/VFU.

Tides medical expresses concerns in how “auditors and MACs have used arbitrary lines in the current LCDs to deny claims” and request bulleted checklist for documentation requirements. They request clarifying information regarding documentation and reporting of wastage.

They also note 2 products that are currently under investigation and inquire if exemption may be made for products under investigation currently. Tides Medical request use of retrospective and RWD and explanation of how evidence is used in coverage determinations.

No published supporting literature is submitted. The existence of a price, including national ASP file, does not equate to coverage. Coverage is based on a product or service being R&N and this is demonstrated by evidence. Therefore, being on the ASP drug file does not ensure reimbursement.

There are no exceptions for products under current investigation. While we applaud investigators efforts for future investigations, provisional payment is not feasible as we do not know if the product is effective for wound healing until the study is completed. It is not R&N to cover services without this information especially when there are commercially available products with supporting evidence (see Comment #19).

For evidence requirements including RWD, see comment #1, for delay in implementation of the policy, Comment #2, for health care disparities, Comment #3, for application limits and frequency, Comment #4, for FDA concerns/TGR letter requirements see Comments #5 & 19, transition to covered list, see Comment #17, and for product use outside of DFU/VFU, Comment #7. Documentation requirements and instructions, including wastage, are explained in the B&C Article, and not contained with the LCD. The individual MACs will provide education and can develop tools if necessary to aid in compliance with documentation requirements.

A DPM in Ohio expresses concerns on potential harm to his patients as a result of the policy with limiting access to care. He advocated for InnovaMatrix to be covered. He expresses concerns regarding application limits. He requests withdraw of the LCD.

There was no literature submitted to support the addition of InnovaMatrix. If additional evidence is developed in the future, it can be considered via the LCD reconsideration process. For application limit, see Comment #4 and access to care, Comment #3.

A patient comments that skin substitutes have had positive outcomes for their father with diabetes. They ask the decisions for products be left to the discretion of the providers.

A series of letters from patients in multiple jurisdictions expressed concern with access to the products that they have had success with in the past, adequate applications allowing their doctors to make their choices for their care.

The LCD aims to provide Medicare beneficiaries with access to scientifically supported skin substitute grafts/CTP that have proven effectiveness in accelerating ulcer healing, thereby enhancing healthcare outcomes. Providers will still have a variety of products, all which have evidence to support effectiveness, to choose from to care of Medicare beneficiaries, such as your father.

For application limits, see Comment #4. 

Multiple MDs and DPMs submitted the same comment letter stating the policy disregards evidence and will impede their ability to care for their patients. They state the restrictive coverage limitations contradict published clinical studies citing the 2021 Armstrong retrospective report and explaining “the 2021 study by Dr. Armstrong clearly demonstrated the value, both in terms of health outcomes and cost savings, of “advanced treatment,” which Dr. Armstrong defined as “cellular and acellular dermal substitutes, which are mostly coverings derived from human placental membranes and animal tissue sources.” The letters share their personal positive clinical experience with skin substitute products and concern that the MACs are “Ignoring that clear study, your proposed LCD recommends the opposite.” 

We do not agree that the LCD disregards compelling evidence. For how evidence is used for coverage determination, see Comment #1. The policy offers a transparent review of all studies reviewed and utilized established tools to access quality of evidence (risk of bias assessment) to ensure studies have equal consideration regardless of funding source. It is of particular importance to access the quality of studies in a setting such as skin substitutes where the large majority of studies are funded by industry, elaborated on in Comment #10. In regard to the 2021 Armstrong report this is a retrospective report and while the authors conclude positive benefit of “advance treatments” this study design does not account for other variables that may have impacted the patients’ outcomes. For instance, are patients who are receiving regular applications more compliant with SOC measures since they are seeing their provider regularly? Only a controlled design where the care is equal in both groups can determine this with confidence. Additionally, it does not evaluate individual products for effectiveness and which products result in positive outcomes is not reported. The Analysis of Evidence section of the LCD highlights additional challenges within the current literature.

A comment letter from BioTissue is submitted. The commenters explain that Neox graft products for DFU/VLU are most effective when left alone on the wound bed to resorb versus weekly application and can remain visible for 3-4 weeks. They instruct providers to only replace if there is no graft visible on the wound surface. They state that none of the covered products had evidence to support 3+ week intervals. They state that published clinical outcomes and findings demonstrate a high percentage of patients achieve complete closure with 4 or less applications of Neox graft and literature were submitted. They explain that they have a Biologics Licensing Application with FDA and have Phase II outcomes which are included in the LCD (Marston 2019, 2020). They conclude “grafts should remain covered by the MAC as the only products that are designed for four (4) or fewer applications and already have a documented and published history of closing DFUs and VLUs with fewer than four (4) graft applications over 12 weeks.” The request the LCD includes coverage for products with published non-RCT outcomes that demonstrate healing including Neox 1K, Neox RT and Neox 100.” They support the application frequency limit of 4 applications in 12 weeks.

An executive from BioTissue explains a correction of the product name is needed in the table and which evidence aligns with each product.

Multiple providers wrote to express support for Neox 100 sharing clinical experience stories. Several provider advocate for use for Wagner grade 3-4 wounds and one provide 9 references which include hyperbaric oxygen, vacuum assistance, and several retrospective reports on use of Neox for these complex wounds.

A provider from Georgia explained they have treated over 100 wounds with Neox 1K with average healing time of 4-6 months with about 3 applications. They report the product stands out for “exceptional ability to provide efficient wound healing for the most aggressive and debilitating Grade IV ulcerations often complicated by osteomyelitis, and in some cases, gangrene. The unique properties of Neox 1K make it an indispensable tool in managing these severe conditions”. They request coverage of Neox 1K.

Thank you for your comments. Product labels are created by the product manufacturers and do not require evidence to recommend frequency. Some RCT protocol requires applications weekly even if not clinically indicated. So, while these factors may suggest more frequent application, we rely on what has been determined by published evidence to date. If new literature supports a change this can be considered via the LCD reconsideration process. For additional discussion on application frequency, see Comment #4.

The MACs appreciate BioTissue’s commitment to high quality research as demonstrated by the Biologicals Licensing Application and ongoing Phase II study. We cannot utilize unpublished literature for coverage determinations. The LCD includes a multi-centered prospective study by Marston et. al. on Neox. The evidence is reviewed in the LCD and the 2 reports are the same population. The study is commendable in that they investigate complex wounds with exposed muscle or bone and follow the patient's out to 1 year; however, the very small sample size of 32 subjects and the retrospective design without blinding, randomization or controls does not provide high certainty that the improvement seen in the study population is due to the product and not by other factors therefore, not sufficient for coverage. We expect that the ongoing investigation may provide further insight and future peer-reviewed published evidence can be submitted through the LCD reconsideration process. For further discussion on application limits and frequency, see Comment #4. The product name and citations are corrected in the tables thank you for providing clarification.

Several providers states that product labels, RCT protocols and other factors indicate use of the products more frequently than 4 applications/12 weeks and suggest increasing to 8 applications per weeks. They request clarification on the use of the KX modifier and documentation requirements. Additional ICD-10-CM codes are requested to be added to B&C article. They also suggest alternative options to requiring ABI, request extension of policy effective date and inquires on transition of a product from non-covered to covered in timely fashion. 

Clarification on the use of the KX modifier has been added to the B&C article.

For additional ICD-10-CM codes, see Comment #20, for ABI requirements, see Comment #21, for delay in implementation, see Comment #2, for transition to coverage, see Comment #17, for documentation requirements, see Comment #21 and #22.

A letter from Dr. Padula and Dr. Armstrong request withdrawing the LCD. They cite the research they have conducted as part of the USC Schaeffer Center but the letter contains a disclaimer stating, “this does not necessarily reflect the view of USC Schaeffer Center.” They state their research demonstrates “we have shown that the application of skin substitutes is associated with faster healing times, reduced amputation rates, reduced infection rates, reduced mortality rates, and increased cost-effectiveness compared to traditional methods for treating these wounds.” They state maximum benefit was achieved when the skin substitutes are applied “following parameters” with an application of skin substitute every 1-7 days until wound closure. They feel the application limit does not align with this data and will adversely impact patients. Supporting literature is cited. 

Thank you for your comments. Data on per parameter for use is challenged as the parameter for use as described in product labeling is not based on evidence, as exemplified by the existence of many products that have specified instruction for application frequency but without literature to support it. While the Medicare claims data retrospective report by Armstrong et al. is very valuable in understanding practice patterns this report was not designed to understand if the product application frequency causally improves outcomes. The parameter for use group (n=1131) was much smaller than the non-parameter group (n=12,676) and there is no standardization of application number in either group to draw confident conclusions of the proposed effect. The Padula 2024 paper has been added to the LCD; however this database is limited to a single product and not generalizable to all products. For further information on application limits and frequency, see Comment #4.

Several providers with experience in wound care states retrospective data supports application limit of >4 applications and suggest 6-8 applications is more realistic and suggest a maximum of 8 CTP/12 weeks.

A provider says they have used many of the products on the not approved list with success including Helicol, Axolotl, Amniowrap 2, PalinGen. They also are concerned about the application limit and that 4 is not near enough saying they use up to 10.

A plastic surgeon is concerned about the application limit and suggest 8 applications in a 12-week episode of care based on current evidence. They have several questions regarding the use of the KX modifier and documentation requirements. They provide suggestions that constitute progression of wound closure. They also have several suggestions for additional ICD-10-CM codes, inquire about codes not covered under the LCD, ABI requirements, see Comment #21, Class III compression, see Comment #81, and extending duration to become effective, see Comment #2, for PuraPly, see Comment #76.

A provider suggests that less than X% change from baseline could be used to determine if additional applications are necessary and ensuring healing is occurring given the high cost of these products.

A provider writes in support of AmnioBand Membrane, AlloPatch Piable, Dermagraft and Organogenesis and request addition of PuraPly AM. They are concerned with application limits and documentation of ABI.

A provider expresses concerns about demonstrating absence of infection and suggest utilizing the word ”non-infected” wound unless there are specific parameters for requirement that the wound is not infected which is challenging since many wounds are colonized. She expresses concerns regarding access to vascular appointments and that physical exam may be sufficient in certain cases. She expresses concern about lack of evidence of coordination of care with other medical practices as a reason for denial. She requests better definition of wastage and that CMS remove product line items from the sequester but change to the ASP pricing on product size rather than per square centimeter. Also feels that ASP pricing should be expanded to cover individual size as built by the manufacturer. They provide several examples of claim denials from UPIC. She also is concerned about the language about risk of potential harm from these products states that none of these are documented in the literature. 

Thank you for your comments. For evidence requirements including retrospective data, see Comment #1, for application limits and frequency, see Comment #4. Products on the non-covered list can be considered for coverage with supporting evidence (see Comment #17). Additional instructions on billing and coding including use of the KX modifier and documentation requirements have been added to the Billing and Coding article. For ICD-10-CM, see Comment ABI, Comment #21, for extension, Comment #2, for Class III device language, Comment #76.

Thank you for the suggestion of utilizing a percent change from baseline. This approach is not currently supported by evidence. We have modified language in documentation requirements to Billing and Coding article to ensure documentation must support the progression of wound closure under the current treatment plan and that medical necessity for additional applications should be documented for each additional application.

Language has been updated in the LCD for infection (see Comment #81). Additional guidance for wastage has been added to the Billing and coding article. There are no requirements for “coordination of care with other medical practices.” We do not have any jurisdiction on UPIC audits and pricing is not within the scope of the LCD which is on coverage. Regarding potential harm, this is established in the evidence, see Comment #36, for ABI requirements, see Comment #21.

Multiple letters were received from an unspecified source with identical letters and different names. The letter comments on concerns over limiting access to skin substitute products adversely affecting patient care, and the impact of the industry and jobs. They request the policy prioritize patient care over cost-savings and allow time for manufacturers to submit the necessary evidence. They state they feel the FDA market clearance for HCT/Ps is mischaracterized. They recommend a minimum follow-up of 6 months for effectiveness studies. 

The intent of the LCD is to prioritize patient care and ensure Medicare beneficiaries have access to scientifically supported skin substitute grafts and CTP that have proven effective in accelerating ulcer healing, thereby enhancing healthcare outcomes. We agree that longer-term data is necessary to understand the long-term outcomes of these products and future studies should follow patients for 6 months and ideally several years to understand recurrence rates, impact on morbidity and amputations and true assessment of potential safety risk related to these products. For access to care, see Comment #17 , for a delay in implantation, see Comment # 2, for FDA concerns, see Comments #5 & 19.

StimLabs comment letter expresses concern regarding an abrupt change to coverage of skin substitute grafts and CTP and limitation of options. They request clarification of evidence requirements, provide time for evidence development of a least 24 months, not limit evidence to RCT, to include RWE, expediated mechanism to authorize coverage for products that develop evidence, and that the number of applications of 4 is inappropriately low and not supported by evidence. They also explain that Corplex P should be listed as Corplex. They explain multiple MACs during open meeting explain that the policy allows investigators multiple options for future investigations and inquire how parameters are weighted. They feel evidence standards within the LCD are arbitrary and criticize the exclusion of retrospective studies, uncertainly on requirements for sample size, impact of bias on coverage, required duration of follow-up and acceptable loss to follow-up. They inquire how MACs consider liquid and gel products and how are they reimbursed. They express concern with beneficiaries having to change products during the course of treatment. They request FDA regulatory pathway as part of coverage decisions. They request removal of application limits or at least increasing the number of applications allowed. They are concerned with all MACs collaborating on the LCD is a “de facto NCD.” 

Thank you for pointing out error on Corplex P which has been corrected to Corplex. Liquid and gel products are non-covered for DFU/VLU per LCD and not reimbursable.

For clarification of evidence requirements, see Comment #1, for delay in implementation, see Comment #2, for application limits and frequency, see Comment #4, for FDA concerns, see Comment #5, for access to care, see Comment #10, for transition to coverage and collaboration among MACs, see Comment #17, for rationale of evidence for coverage with rigorous methodology (not arbitrary), see Comment #35.

A DPM expresses concerns over potential overutilization of these products related to rebate programs resulting in significant increase in utilization over recent years. He believes the products can be highly beneficial in certain clinical circumstances but necessitates stringent guidelines for use. He recommends future policy provides a clear clinical indication supported by evidence, requirements for full disclosure with rebate programs to ensure transparency and financial incentives, utilization monitoring to track usage patterns and investigation of potential overuse as well as provider education on the appropriate use of these products. He feels this will provide a “balanced approach that would safeguard against overuse while still allowing patients to benefit these wound care products when clinically appropriate.”

Thank you for comments and commitment to ethical and evidence-based practice. The policy intends to achieve the goals you suggest ensuring Medicare beneficiaries have access to these products when clinically appropriate while enforcing the statutory requirement for the Medicare program to cover services that are R&N, as stipulated by the Social Security Act, while non-covering services that do not reach this threshold.

The total invoice price is the amount a provider pays for an item or service including all discounts including rebates. In the event the total invoice amount is paid and the provider receives a rebate from a third party this is considered overpayment and the provider is obligated to report and voluntary refund the overpayment amount. The individual MACs will place measures to enforce the policy and address potential concerns such as these within their jurisdictions. Further enforcement measures outside the MACs may also be utilized to address these concerns.

Multiple letters were received from an unspecified source with the following comments: they are concerned the proposed LCD has conflicts of interest within MACs, especially associated with Medicare Advantage Plans. They suggest the FDA should be responsible for the safety and effectiveness of each product and “the list of investigators used by the Agency for Healthcare Research and Quality (AHRQ) to evaluate skin substitutes for treating chronic wounds, adopted for inclusion in the covered category, appears inadequate for assessing the safety and efficacy of each product.” Another letter states there were missing clinical outcomes and missing data from the LCD tables. The commenter expresses concerns over lack of expert contributors and oversight.

The commitment to transparency is evident throughout the policy's development, including an open comment period which allows for diverse input from stakeholders and is instrumental in refining and improving the policy to better serve the needs of the healthcare community and the beneficiaries.

The AHRQ technical assessment is a pertinent contributing literature to the LCD. However, the list of products selected for coverage are based on independent assessment of each of these products by the MACs and their research teams. This process involves using standardized tools to evaluate the reliability of study results, ensuring that only evidence that has high confidence for effect informs coverage policies. The exclusion of studies from coverage due to inadequate evidence underscores the commitment to evidence-based practice. Further discussion on the role of industry sponsorship within these studies can be found in Comment #10.

The commenters do not provide any examples of missing outcomes or data from the LCD which prevents the opportunity to address any specific concerns and no missing data points are identified by the MACs or any other commenters. The LCD promotes transparency by inclusion of published tables with summaries of the evidence which is discussed in further detail for each product within the LCD. Each study is reference so interested parties can seek additional details beyond this summative information from the original report if further interest prevails. The LCD was guided by expertise from societies, stakeholder and providers contributing to input on prior LCD versions and through the open comment period.

FDA concerns, are addressed in Comments #5 & 19.

A letter from Aroa Biosurgery Limited (Aroa) request coverage for the product Symphony (A2009). They request a clear description of evidence requirements and coverage for products in which investigation is pending. They express concerns that the limitations within the policy may have an impact on access to care and healthcare advancement. They are concerned with how products will be added from non-coverage to coverage with the development of evidence in a timely manner. They request a delay in the implementation of the new LCD, and they request consideration of unpublished evidence for coverage. They request case to case adjudication of products where a registered trial is underway.

Unpublished literature is not considered in the LCD process. The outcomes of investigations cannot be assumed and without scrutiny by the peer-reviewed process validation is challenged. Requesting case to case adjudication is not an option as there is not sufficient evidence for coverage in which to adjudicate claims. Coverage is based on a product or service being R&N and this is demonstrated by evidence. Paying a service without sufficient (and published) evidence does not meet the definition of R&N which is a requirement for the MACs (see Comment #22).

For evidentiary requirements, see Comment #1, for delay in implementation, see Comment #2, for access to care, see Comment #3, for transition to coverage, see Comment #17.

BioWound provides detailed explanation of their products bio-ConneKt and state those with 510(k) should be included in coverage. They explain their product was included in the evidence table as “no literature found” and they state they have extensive pre-clinical testing to demonstrate it is substantially equivalent to predicate devices. They feel that coverage should be determined by the FDA pathways. They express concern that the standards for coverage are arbitrary and further described some included studies have high risk of bias and all listed studies were deficient in some meaningful way. They express concern the LCD will adversely impact patient care and result in supply chain issues. They request MACs work with CMS to develop uniform standards for evaluating all 510(k) products. They request a 4-year transition to the new policy. The request withdrawal of the LCD. 

FDA coverage does not ensure an item or service meets the definition of R&N to obtain coverage within the Medicare program. The LCD specifically states that a predicate product is not considered sufficient evidence for coverage since these products have a wide range of variability due to proprietary processing that may impact the effectiveness and potential for outcome improvement for the individual product. Further explanation of FDA processes, see Comments #5 & 19.

In regard to unpublished literature, see Comment #34, evidence requirements, see Comment #1, concern for access to care and supply chain, see Comments #3 & #17.

The LCD is rationale with rigorous methodology applied uniformly across all studies and limitations clearly disclosed, emphasizing transparency and adherence to evidence-based practices. The LCD's exclusion of studies lacking robust evidence further underscores this commitment. While we agree the overall literature for skin substitutes/CTP have methodological challenges and lack well designed, high-quality studies, there is also a positive trend within the body of literature of potential benefit to the beneficiaries as explained in the Analysis of Evidence section of the LCD. To further clarify the systematic and rationale approach to the literature evaluation the analysis section to explain how each covered product was supported by meaningful level of supporting evidence that it is effective for wound healing. Additionally, we looked for at least 1 additional clinical trial that showed equivalent healing rates to the RCT confirming the utility of each product. These were most often not RCT but represented multiple study designs demonstrating the variety of evidence considered in the evaluation of evidence. To summarize, for consideration for coverage, each product had a published clinical trial(s) that evaluate a well-defined patient population of sufficient sample size and use a robust study design to convey confidence in the results. Further investigation with more robust design, larger sample sizes and longer-term follow-up can refine the understanding of these products, but in the interim ensuring access to those products with supporting evidence is prioritized.

Legacy Medical Consultants expresses concerns regarding potential supply chain issues and access to care. The state they feel the LCD is overly restrictive of qualifying clinical evidence to support coverage decisions and multiple forms of evidence should be considered including RWD. They feel that evidence there is evidence on human amniotic membranes for DFU and VFU that validates the class of products for clinical utility. They reference an analysis that they commissioned on the benefits of amniotic membranes for DFU which includes 3 RCT and 2 additional systematic reviews and meta-analysis including Mohammed et. al. (2022) which was not included in the LCD. They state the LCD makes additional unsubstantiated representations about risk and disparate safety and effectiveness profiles among skin substitutes. They state that the products are “interchangeable in all characteristics relevant to product safety and effectiveness.” They object to the application limit and encourage 8 applications/12 weeks. They state the LCD lacks prior notice of requirements and transparency on coverage decision process. They request products including Orion be covered while investigation is ongoing. They state dividing classes of products is inappropriate, confusing, and undermining of trust with providers and patients and all products with HCT/P should be covered equally. They also request a 24-month extension to LCD implementation. 

The LCD section on “Product classification” explains the rationale as to why the LCD looks at products individually rather than as a class and explains why products within the same class are not interchangeable. “Products within the same class vary significantly and impact on the product’s function indeterminant in many cases.” The LCD explains “Even products derived from the same origin are variable since these products undergo proprietary processing. Skin substitute grafts/CTP may share similarities, but they are individually unique in their proprietary processing, thickness, cell count, presence of living cells and other features.” Unique products go through separate applications for FDA regulation and products are assigned unique HCPCS codes. There are few studies that compare products to each other which may help understand if products within the same class share similar function despite these differences. In the AHRQ technical assessment, 76 products were classified using the Davison-Kotler classification system, a method structured according to cellularity, layering, replaced region, material used, and permanence. The found cellularity is a significant difference among skin substitute grafts as the presence of cells raises the rejection risk and production complexity with 8 products being classified into the cellular group. Both the 2012 and 2020 AHRQ reports that conclude due to processing variations each product must be studied in a “properly conducted clinical trial”. A 2024 SR/MA (Banerjee et. al.) concludes “Enough evidence is still lacking to determine a statistical difference between broad categories of CAMPs; and hence, decision makers should consider published head-head comparative studies, real-world evidence and cost-effectiveness evidence between individual CAMPs to decide on which to use in practice.” The International Consensus Document in Journal of Wound Care explains “differences in product composition and the proprietary processing methods used by manufacturers make each CAMP unique, creating a need for more comparative studies.”

Mohammed (2022), the excluded reference, was added to the LCD. This systematic review and meta-analysis conclude that dehydrated human amnion and chorion allografts improved wound healing for DFU. This finding is derived from 11 included RCTs representing products on the proposed LCD’s covered list with the exception of AmnioExcel^® which was not covered due insufficient evidence and makes up a very small number of the subjects in the meta-analysis. As this paper represents products with evidence it cannot be extrapolated to all products including those that have not been investigated. Therefore, this finding is consistent with the evidence assessment within the LCD.

We do not agree that the LCD makes unsubstantiated representation regarding potential harm. The risk of bacterial and viral transmissions is a documented and known risk for human product transfer including skin substitute product/CTP and why the products go through processing procedures to reduce this risk. The FDA pathway for regulation of these products does not investigate safety and the large majority of the products do not have any safety data to support their use. Even those that do have evidence, it is often limited to short-term evidence leaving the potential of long-term outcomes unknown. Retrospective studies and RWD are particularly useful in studying harm that may not be seen in RCTs where patients may be excluded with higher risk factors representing a potential role for this type of literature. There is also risk of bias in the reporting of these outcomes and overall lack of research leaves this area largely uninvestigated.

We disagree the LCD “lacks prior notice of requirements and transparency on coverage decision process going forward including products soon to initiate RCTs.” The LCD is based on clinical evidence and coverage decisions that align with the Medicare requirements for R&N. It is not the role of an LCD to explain processes for the LCD implementation. This is part of the educational component of an LCD and education is usually undertaken during the notice period as it would not make sense to provide education until the policy is finalized. The questions the commenters seek clarification for are addressed within this Response To Comment article and will be further addressed by the education conducted by the individual MACs.

It is our opinion that the policy is not “undermining of trust with providers and patients” but just the opposite, as it ensures Medicare beneficiaries access to scientifically supported skin substitute grafts/CTP that have proven effective in accelerating ulcer healing, thereby enhancing healthcare outcomes which can foster trust and confidence.

In regard to unpublished literature, see Comment #34, evidence requirements, see Comment #1, access to care and supply chain, see Comments #3 & 17 , application limits and frequency, Comment #4, transition to coverage, see Comment #17, and extension of notice period, see Comment # 2. 

A letter from LifeNet Health was received with 34 PDF files of supporting literature. They support the collaborative policy and 4 applications over 12 weeks, which is supported by clinical evidence with 9 citations. They state the KX modifier offers a viable solution for more severe wound(s). Several of their studies included evidence that aligns with the 4 application/12 weeks for TheraSkin, DermACELL and TheraGenesis for large and complex wounds.

They have several additional comments:

• Although all 15 HCPCS codes included in Group 2 of the LCA appear to be covered for both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) as identified by the specifically listed ICD-10-CM diagnosis codes(s), more clarity is needed within Table 1 of the LCD when the policy only provides evidence for 1 ulcer type (i.e., DFU and not VLU or vice-versa).
• They provide supporting evidence for TheraSkin for coverage for both DFU and VFU and request inclusion in coverage for VLU where they feel that additional evidence for review is applicable for coverage.
• They provide both the included literature and additional literature in support of DermACELL for both DFU and VLU.
• The LCD lists no literature found for TheraGenesis and evidence does exist. “A keyword search of TheraGenesis alone may have yielded no results because TheraGenesis is sold outside of the U.S. under the brand name Pelnac and all of the currently published studies are under the Pelnac brand name, instead of TheraGenesis.”
• The explain that the Brigido reference supports GraftJacket and not an appropriate reference for Matrion.
• They request description of the process manufacturers should follow to submit published evidence in the future to ensure all 7 MACs provide uniform reviews and consider coverage.
• They request clarification on if non-covered products will be considered for non DFU/VLU applications or only if they are on the covered list and request how such claims will be covered by the MACs.
• They comment on the potential of the LCD to impact Medicare Advantage plans and feel the policy will improve access. They recommend avoiding any delays to implementation of the LCD.

The letter concludes “By utilizing evidence of proven products to limit covered CTP to 4 applications over a 12-week episode, the draft LCDs encourage appropriate use of Medicare resources, limiting risk of misuse, abuse and/or overuse of ineffective (and often more costly) products. Conversely, not adopting these limitations on the number of covered products and applications perpetuates incentives for use of less clinically effective products that require more applications and drive unnecessary costs to the Medicare program and its beneficiaries with chronic DFUs and VLUs.”

They also recognize the LCDs intend as summarized by the following “CMS, MACs and Medicare Advantage plans are committed to improving health outcomes to address diversity, equity, and inclusion for all patients in all clinical settings, without prejudice to social determinants of health which may result in the need for utilization beyond the policy stated limits, including but not limited to co-morbidities and/or size or duration of chronic wound(s) at the initial start of CTP therapy.”

Thank you for your support of the policy and recognition of the extensive literature review within the LCD. See Comment #4 for response to application limits and frequency. The alignment of the literature in your letter (9 citations), including DermACELL and TheraSkin which are both on the covered list, is reassuring.

The LCD intent is to cover the products with evidence for the specific condition. The products that have demonstrated evidence for DFU are covered under DFU ICD-10-CM codes. Similarly, products with evidence supporting their use in treating VLU are covered under VLU ICD-10-CM codes. To enhance clarity, the LCD has separated the evidence into 2 distinct tables listing products covered for DFU and VLU separately. Additionally, these products are now categorized separately in the billing and coding guidelines to further elucidate which products are eligible for coverage based on the indications.

The additional citations for TheraSkin and DermACELL have been added to the LCD. The literature for TheraGenesis has been added to the LCD but not sufficient for coverage for DFU/VLU. The Matrion reference has been relocated to GraftJacket. If there is future literature to support these products it can be submitted via the LCD reconsideration process.

Transition to covered list, see Comment #17, for use outside of DFU/VLU, see Comment #7, for delay to implementation, see Comment #2.

The LCD applies to Medicare Part A and B. Medicare Advantage plans and commercial plans are separate entities. Bundling and APC payment concerns are determined by CMS and not at MAC discretion.

A provider opposed the LCD and submitted multiple papers to support the use of CEAP for VLU. He opposed limitations on number of applications and feels the literature is “cherry picked.” He cites a paper that report 12 applications in 12 weeks and 6 applications in 12 weeks for VLU. He states other papers support more frequency applications for DFU with reported application frequencies ranging from 1.0 – 6.7 and several protocols with weekly or biweekly applications. 

Thank you for your comments. For discussion on application limits and frequency, see Comment #4. All of the submitted literature is included in the LCD. The literature search criteria and all evaluated products are present in the LCD ensuring that literature selection was not arbitrary. 

A DPM sends a letter in support of Phoenix Wound Matrix and expresses concerns with coverage limited to 15 products. He states the synthetic products are a solution for patients with moral or religious objections to allografts, amniotic and xenografts. Phoenix product label and prospective case series with 38 patients was included.

Thank you for your comments. The LCD coverage is based on evidence to demonstrate effectiveness, improvement in patient outcomes and safety. The small prospective study has been added to the LCD but not sufficient for coverage. If there is future literature to support this product it can be submitted via the LCD reconsideration process. 

Omeza comments with a request to remove their product from the LCD as they feel it does not meet the inclusion criteria for the LCD. “Our product, the drug/device combination product Omeza OCM, does not meet the definitions utilized in this LCD according to the CMS comments in the 2023 OPPS rule and Omeza is currently seeking an alternative CMS coverage modality. We, therefore, believe we have been erroneously included in the proposed LCD.” They state Omeza has 510(k) clearance for wound healing and literature to support the product are underway. They explain that Omeza is an amorphous solid, not a graft skin substitute product even if the product forms a sheet-like layer after application. They request transitional pass-through designation as a new category of product. A lab report on the product is included and added to LCD references.

There is no evidence that Omeza is an exception and should be excluded from the LCD. The 510(k) letter from the FDA was reviewed and found the predicate devices for which the 510(k) clearance is based the product being used as a skin substitute graft/CTP for management of chronic ulcers including DFU/VLU. The submitted paper (lab study) also describes the product for use in wound healing. If the products are being used and billed as a skin substitute graft/CTP for DFU/VLU evidence for use must be demonstrated to be considered for coverage (see Comment #5). There is not sufficient evidence to cover this product for management of chronic DFU/VLU so it remains on the non-covered list. If there is future literature to support this product it can be submitted via the LCD reconsideration process.

A comment from Kent imaging addresses concerns about requiring ABI and the limitations of ABI measurements. This includes risk of false elevation with medial artery calcification. They suggest “an objective, non-invasive measure of perfusion/oxygenation should be performed which could include an ankle-brachial index (ABI) and/or toe-brachial index (TBI) with waveform analysis, transcutaneous oximetry, skin perfusion pressure, or near-infrared spectroscopy.” They state SnapshotNIR is useful tool to conduct near-infrared spectroscopy imaging and measurements of wound and these imaging codes should be added to coverage within the LCD/LCA. 

We agree with there may be situations in which alternative means to ABI may be clinical indicated as explained in Comment #21. Regarding the proposed technology the modality to perform these measurements is out of the scope of the LCD which is on skin substitute grafts/CTP products for DFU and VLU. An LCD request can be made with included peer-reviewed published literature to address this specific area of wound care. 

The comments explain the properties of Talymed. They request inclusion in the covered product list. They explain Talymed was placed on the non-covered list as explained in the policy “based upon the finding that the clinical studies of the product included a “sample size too small to determine effect.” They feel the coverage requirements for evidence are not clear and there was additional literature not considered which was submitted with the comments. They explain the FDA pathways for the product and that the product is “substantially equivalent” to a product that is on the covered list. They review the literature for the predicate product (OASIS Wound Matrix).

Thank you for your comments and the investigation that has been undergone so far regarding Talymed. The additional literature provided has been added to the LCD and includes a case report, 2 bench reports and 2 animal studies. The RCT by Kelechi et al. was already included in the LCD and the evidence analysis reviewed. While we commend the efforts of the RCT design each of the study arms only contained 20 subjects resulting in insufficient sample size to draw definitive conclusions on the effectiveness of the product. While 1 of the 3 intervention groups (biweekly) showed positive results compared to the SOC arm it was unclear why the other groups did not show results. Due to the small sample size in the trial, the results may be influenced by random variation and should be interpreted with caution, as they may be attributable to chance rather than a true effect. Within the report the authors acknowledge that this was a pilot study and there was a need for a larger study to confirm the findings. The literature on OASIS Wound Matrix is not considered for evaluation of Talymed as the policy states “Predicate products are not sufficient evidence for an individual product” (see Comment #35).

For evidence requirements, see Comment #1, and FDA requirements, see Comments #5 & 19.

Tiger BioSicence comment letter expresses concerns regarding access to care and supply chain if the policy is to become effective. They state the lack of outreach to manufacturers and patients, and that coverage should align with FDA regulatory criteria. They state the LCD seeks evidence regarding the products role as a scaffolding. They claim misunderstanding of wound healing mechanisms and the treatment of equivalent products is arbitrary. The state all placental products should be classified equally based on FDA HCT/P regulatory status. They express concern about the MACs collaboration, application limits and request grace period to allow companies time to develop evidence. They state the policy mandates RCT and request extension of comment period and CAC meeting. They claim the LCD states placental products are superior citing a systematic review. They claim the policy will shift utilization to dermal products which have worse outcomes. They request withdrawal of the LCD.

The comment explains Tiger BioSciences/Extremity Care’s products are supported by case studies and no RCT since this was not required by the FDA. Supporting studies are included. They include FDA related documents of their products some which are redacted. 

The policy coverage is evidence based and not linked to FDA requirements. See Comment #5 & 19 and discussion on the definition of scaffolding in Comment #16.

The commenter incorrectly asserts the LCD claims placental products are superior. There are no head-to-head comparisons of multiple products in the literature and systematic reviews have marked limitations as discussed in the LCD. There was no supporting evidence that dermal products have worse outcomes and we cannot predict the impact of the policy on product selection except that products with supporting evidence will be utilized. The commenter also incorrectly asserts a requirement for RCT, which is not accurate and explained with evidence requirements in Comment #1.

We disagree with the statement the policy is arbitrary in the treatment of equivalent products. Each product goes through proprietary processing that impacts the final product as explained in the LCD section “Product Classification” with supporting literature. Variations between products can be significant as demonstrated by studies with substantial differences between products. Therefore, these products are not equivalent and require evidence for the individual product, even if they are from the same class. See Comment #36.

The LCD is rationale and has followed the LCD process, for further discussion see Comment #35. For access to care, see Comments #3, supply chain concerns and pricing vs coverage, see Comments #17 & 22, stakeholders’ input and contributions to the policy, Comment #33, extension of notice period, Comment #2, multi-MAC collaborative policy development and reconsideration process, see Comment #17, and application limits, see Comment #4.

Submitted literature was reviewed and include a bench study and an unpublished case series of 11 patients for Meso Wound Matrix which is not listed in the LCD due to lack of related code. 

A DMP comments that application limit should be 10/12 weeks and that the 4-application limit is not supported by research, they also state no evidence that a high ABI correlates to successful wound healing, they request delay in implantation to ensure no disruption to patients’ treatment and that PuraPly AM is covered. 

Thank you for your comments. No literature was submitted. If there is peer-reviewed published literature to demonstrate the product is effective, safe and improves outcomes it can be considered for coverage via the LCD reconsideration process. For application limits, see Comment #4, for ABI, see Comment, #21 and extension, see Comment #2.

A comment letter is received from the Avalere requesting addition to coverage of Kerecis with supporting literature submitted. They state Lantis 2023 was excused from the analysis and would address the concerns reviewed for Kerecis in the evidence review. They provide an analysis of the literature in the LCD and how the literature of the products on the covered list compare to Kerecis. They express concerns about access to care explaining Kerecis addresses populations that are unable to use human derived skin substitute products, such as Indian tribe members and increases access to rural beneficiaries because it does not need to be specially stored or refrigerated.

They request clarification of the evidence requirements for coverage. They state there is some confusion regarding the definition of skin substitute due to variability between the FDA, CMS, and proposed LCD definitions. They suggest removing synthetic products from the definition of skin substitutes as they do not feel they accurately represent the characteristic and function of biological substitutes and would be better represented in other categories. They recommended greater clarity on what the expectations would be in terms of describing unsuccessful treatment for additional applications requirements and to ensure the inclusion of DPM as providers. They inquire to the process of movement of products from the non-covered to covered list after submission of adequate evidence. They also state additional research on Kerecis is undergoing.

Multiple providers also submitted the Lantis paper and share positive outcomes in their experience using the product in their practices.

Thank you for your comments. The Lantis 2023 study has been added to the LCD. We appreciate the extensive summary and we agree this manuscript addresses our concerns. Additionally, a recently published study by Dardari et al. was added to the LCD. The product has been relocated to the covered list, see Comments #10 and 21.

Regarding the definition of skin substitute/CPT the LCD acknowledges lack of clarity and the definition of skin substitute but determine the definition that aligns with the CPT^® book is most appropriate as these are the codes that are addressed by the LCD. If additional evidence is developed in the future that justifies a change to the definition this may be considered through the LCD reconsideration process (see Comment #16). There is no evidence to exclude synthetic products from the definition if they are being used in this capacity (see Comment #45). If the products are being used and billed as a skin substitute graft/CTP for DFU/VLU evidence for use must be demonstrated to be considered for coverage (see Comment #5).

For evidence requirements, see Comment #1, for the transition from non-covered to covered list, see Comment #17, for application limits, see Comment #4, for the inclusion of podiatry, see Comment #10.

ProgenaCare comments that ProgenaMatrix should be covered. They suggest using the definition of skin substitute per the 2021 OPPS Final Rule which differs from that in the LCD and does not require the product function as a skin substitute graft. The are concerned the application limit is too restrictive and could slow the appropriate use of skin substitutes and impact patient care and patient outcomes. They state the appropriate number of applications may vary significantly depending on wound characteristics including size and age. They are concerned the exceptional cases may not be an adequate solution especially if this requires a pause in treatment. They feel that requirements for evidence is unduly restricted and unclear and threatens patient care.

They stated they are highly supportive of using evidence for clinical decision making and committed to developing evidence to support the use of its products but that no advanced warning was provided. They expressed concern that RCT requirements may not be generalizable or practical and other study designs including RWE should be considered. They inquire into the process of how new evidence will be considered for coverage period. They also inquire into the handling of wound types other than DFU/VLU.

They explained that ProgenaCare is supported in multiple clinical studies demonstrating effectiveness and positive clinical outcomes including a prospective multi-centered clinical trial in which it was applied to 26 patients with DFU and compared to SOC that was recently presented at a conference and has been submitted for publication. They state that it is indicated for large and complex wounds and VLU. They also report a case series with 10 patients with positive outcomes for DFU and another series including 6 VLUs. A retrospective study includes 16 ulcers was recently presented at a conference. 

Thank you for your comments. While we appreciate the summary of literature on ProgenaCare unpublished literature and case series are not sufficient evidence for coverage; therefore, it will remain on the non-covered list. If additional investigation demonstrates effectiveness in well-designed studies this can be submitted through the LCD reconsideration process.

For evidence requirements, see Comment #1, for movement from non-cover to covered list, see Comment #17, for application limits, see Comment #4, for timing of implementation, see Comment #2, and for definition of skin substitute, see Comment #45. Regardless of the definition of skin substitute, coverage is based on evidence, not function as a scaffolding; therefore, even under the suggested alternative definition evidence is required to demonstrate effectiveness and clinical benefit for coverage. 

RegenTX comment letter states that their products should be covered since they have identical basic function to several amniotic membrane products for which there is evidence. They explain that HCT/Ps utilizing the same tissue are inherently equivalent under the FDA's regulatory framework and elaborate on the FDA regulatory processes. They conclude that products of the same category should be equally covered. They claim failure to do so is capricious decision making. They state the policy must define high quality and that study designs other than RCTs should be considered. They request an extended time period for implementation to allow manufacturers to submit evidence. FDA regulatory information for their products was included.

Thank you for your comments. For evidence requirements, see Comment #1, for extension, see Comment #2, for FDA regulatory requirements, see Comments #5 and 19, for discussion of rationale of the policy, see Comment #35, and for classification of products and why this is not sufficient for coverage, see Comment #36. 

Biolab comment letter inquiries as to the plans for transition of care when the LCD is effective and later in their comment letter requests a 3-year delay in implementation to allow companies to conduct research. They expressed concerns about the proposed application limit of 4 and that larger complex wounds may require more applications and longer durations of time than 12 weeks. They are concerned that if the studies require demonstrating that the product functions as a scaffolding that conflicts with the requirements, they need for FDA 361 HCT/P and they may not get approval. They disagree with the blanket statement to exclude gels and that if a gel is incorporated into the wound bed and provide cellular growth it should be allowed and this limits expansion of new products. They state that obtaining evidence on products individually is not necessary because there are dozens of studies showing efficacy and safety and that this is going to take extensive time and that we should utilize the FDA designations for these products. They also ask for clarification on what is acceptable level of evidence for coverage and how products will be considered when new evidence is developed. They inquire about RWD they also inquire if studies need to be done for both DFU&VLU or just 1 study for either. They ask if every MAC will need to review published data when available. They are concerned the LCD will stifle new innovations. They expressed concern about supply chain issues with implementation. They state the products on the covered list are less expensive and that they feel that the LCD is designed to save money rather than benefit patients. They also explained they have been collecting data with their product and working to create a more robust data collection system to collect RWD.

Thank you for your comments. Cost analysis studies or product cost were not included in the evidence review or considered for determining products on the covered list. The policy is based entirely on evidence on how well the product works for wound healing as demonstrated by studies. The LCD does not require studies that are designed to demonstrate scaffolding, see Comment #16. We do not believe this threatens FDA regulatory requirements as there are several placental based products which are on the covered list regulated through the 361 HCT/P pathway. For discussion of off-label use and FDA requirements, see Comment #5 & 19. Gels are not intended to remain in place and therefore, do not function as a skin substitute graft/CTP. Evidence to the contrary can be considered through the LCD reconsideration process.

We do not believe that this policy will stifle innovation but create a more robust body of literature to help provide evidence-based decision making and improved products to the benefits of Medicare beneficiaries. In fact, there is potential to foster innovation as more research offers greater insights into mechanism of wound healing and understanding of factors that prohibit and accelerate healing which may lead to even more effective products in the future.

For evidence requirements, see Comment #1, for delay in implementation, see Comment #2, for application limits and frequency, see Comment #4, for the requirements for DFU & VFU requiring separate evidence, see Comment #37, for the process of transition from non-covered to covered, see Comment #17 and for classification of products, see Comment #36.

A comment letter from PolyMedics Innovations explains that the LCD recommendations are based on SR/MA which do not include any synthetic skin substitutes and that these reports do not include products after 2020. They submit a prospective RCT on their product Supra SDRM. They expressed concern that the policy may limit access to care and that the application limitations are restrictive.

Several providers share positive results and supports coverage for Supra SDRM and Suprathel. A plastic surgeon provides the Liden et al. paper for support.

The LCD basis for coverage decisions is based on evidence for the individual products and does not base this decision on the included SR/MA which are fraught with heterogeneity making it difficult to draw definitive conclusions and summarized in the section of the LCD on SR/MA.

Thank you for the submission of the Liden et al. 2023 paper which was not found in the search since the paper did not use product brand name. This paper has been added to the LCD, but not sufficient evidence for coverage. If future evidence is developed, it can be considered through the LCD reconsideration process.

For application limits and frequency, see Comment #1.

A comment letter from Pinnacle Transplant Technologies explains the FDA regulatory requirements for the amniotic membrane and human skin products. They state many of these provide scaffolding for the wound site and are supported by literature and exclusion of many of the existing products with HCT/Ps will have a significant impact on management of DFU/VLU.

They have several questions seeking clarification on how evidence is used and study design for future studies including if only RCT are accepted or RWE considered, and request guidance on study design from the MACs. They ask how manufacturers will evaluate manufacturer bias and if data must be published. They are concerned journals may not accept multiple similar studies which they feel is an arbitrary requirement from the MACs for coverage and creates undue burden. They ask how products will be moved from non-covered to covered. They have multiple questions on reimbursement. They express concern regarding access to care, transition to the policy during a course of treatment and if there will be a “grandfathering” plan. They express concern over stifling innovation. 

Thank you for your comments. Manufacturer bias is addressed using RoB2 which does not automatically downgrade a study based on being industry sponsored as essentially all studies are in this area, see Comment #10. Regarding theoretical concern that journals will be reluctant to publish articles that are similar, each of these products are individual with proprietary processing that may impact their function and therefore, each are unique a factor that typically appeals to the journals, see Comment #36.

For FDA regulations, see Comments #5 & 19, for access to care and transition to coverage, see Comment #17, for innovation impact, see Comment #48. For the use of evidence and RWD, see Comment #1 and only published peer-reviewed literature can be considered. Questions regarding reimbursement will be addressed in the Billing and Coding article and by the individual MACs. For delay in implementation, see Comment #2. There will not be any “grandfather” plans, see Comment #22.

A comment letter from Mimosa diagnostics and a provider expresses concern about ABI requirements. They say that ABI has multiple pitfalls and is outdated as a requirement for vascular assessment. They explained that multiple clinical conditions in which ABI may not be measurable or accurate. This is supported by 22 references. The commenter supports the use of non-contact near-infrared spectroscopy (NIRS) with 2 supporting reference included.

We agree that there are exceptions to ABI and the policy has been modified to allow alternatives to ABI including, but not limited to NIRS (see Comment 21).

A comment letter from Nuo Therapeutics states that CMS and OIG recognize coverage and payment issues associated with CTP and an attempt to correct this was made by mandatory reporting of Average Selling Price (ASP) to CMS in 2022. However, many manufacturers refused to comply. “In the absence of enforcement of ASP reporting, excessive payment for and disproportionate use of CTP continues in a manner that is not in the best interest of Medicare beneficiaries. There is an immediate need to implement policies to provide appropriate coverage and payment for CTP. In the absence of a NCD, Nuo Therapeutics, Inc. is highly supportive of the draft proposed LCD that addresses the fraud, waste and abuse stemming from the inappropriate coverage/payment for CTP that continues to advantage manufacturers of CTP and certain healthcare providers while disadvantaging patients and the United States taxpayer.”

• They request clarification of coverage in addition to DFU and VLU requirement expressing concern of lack of evidence for use of CTP outside of DFU and VLU. “When CTP are used to treat wounds for which there is insufficient or no clinical evidence to support a benefit to the Medicare population, we suggest that coverage should be an exception and determined on a case-by-case basis.”
• They support an evidence-based approach to coverage requiring high-quality evidence and state “This requirement is of particular importance for products that have not been evaluated for safety and efficacy by the FDA but that are regulated as human cells, tissues, and cellular and tissue-based products (HCT/Ps)….We agree that LCD correctly identifies a majority of commercially available CTP proposed as “Non-Covered” due to an absence of high quality supporting evidence.” However, they express concern there are products on the covered list that have a high risk of bias or small patient populations while Kerecis Omega 3 was not included due to small sample size. They suggest these should all be non-covered.
• They provide an example of marketing from manufacturers of CTP aimed with discounts being offered to increase profits fraudulently.
• They are concerned “the excessive payment may often drive utilization of certain CTP and this “Induced Demand” diminishes patient access to other more effective treatments.” They provide the example of autologous blood-based therapy covered under NCD as an alternative and express concerns regarding variability in MAC payments for this service.
• They explain the RCT that support the covered product exclude wounds with exposed tendon and muscle and fewer of the studies address VFU. They suggest coverage should depend on evidence for that indication only and not intended for severe/complicated wounds in which there are other options that has this indication.
• They are concerned “The absence of defined requirements for evidence to support coverage may lead to future abuse and/or may inhibit development of potentially effective innovations,” and recommend clarification of evidence requirements suggest requiring at least 1 high-quality RCT. 

Thank you for your support of the policy and recognition of the value of evidence-based medicine. We share your concerns regarding fraud and abuse in this space and aim to provide greater regulation to ensure access to care and best practices for Medicare beneficiaries.

Kerecis has been added to coverage with additional literature submitted, Comment #45. We agree coverage should align with the evidence, including exposed bone and tendons, and type of ulcer, see Comment #37.

For use of CTP outside of DFU/VLU, see Comment #7, and for evidence requirements, including how papers with high risk of bias were assessed, see Comment #1.

A letter from Wound Care IQ request withdrawal of the policy. They state the benefit they have seen as a provider (and CEO) from these products and express concern about the application limits and frequency not being consistent with literature. They feel the policy restricts provider’s choices and access to care.

Thank you for your comments. No literature was submitted. For application limits and frequency, see Comment #1 and for access to care, see Comment #17.

A comment letter is received from ExtremityCare with request to cover for Resolve Matrix. This product is approved via the 510(k) pathway with OASIS Wound Matrix as the predicate device. They feel that Resolve Matrix should be covered because the predicate product is covered based on RCT, and the FDA pathway considers it substantially equivalent and both products have the same intended use. A literature review of OASIS Wound Matrix is included as well as supporting articles. 

FDA coverage does not ensure an item or service meets the definition of R&N to obtain coverage within the Medicare program. The LCD specifically addresses concerns with predicate products which is not considered sufficient evidence for coverage since the products have a wide range of variability due to proprietary processing that may impact the effectiveness and potential for outcome improvement for the individual product, see Comment #35 & 36. Further explanation of FDA processes is explained in Comments #5 & 19.

A comment letter from Samaritan Biologics requested clarification regarding the type of evidence required for products to be added to the covered list, clarity regarding how CTP allografts and wound dressings or coverings are defined, requested time for implementation and transitioning non-covered to covered status, utilization parameters of the total number of allowable skin substitute applications and addressing wound care allograft pricing concerns. They state that these products have been allowed as covered based on HCT/P and should be considered as a class. They feel their products offer benefits over the products on the covered list and provide detailed explanation of the histology differences between MLG Complete and EpiFix^®. They explain they are currently in the process of drafting manuscripts to highlight the basic science of their products. After the last draft LCD, they began to self-fund a RCT evaluating the outcomes of their products. They request an extension of coverage of 24-36 months to complete their investigation for products that have ongoing clinical trials registered with Clinicaltrials.gov. They state that their product meets the definition of scaffolding which would have allowed coverage in the previous draft LCD for several MACs. They inquire about the standard of care group in studies and does this group need to represent a true control or if they can utilize historical data, and request consideration of RWD. Clinical cases are shared with positive outcomes. They expressed concern that the LCD will harm small companies and cause supply chain disruption. They recommend an application limit of 7 as they feel 4 is not adequate and that coverage decision should be made in 48 hours or less to not interfere with care if preapproval is necessary for additional applications. They recommend removal of uncontrolled diabetes from the exclusion criteria. They also suggest there be a capped total price increase of no more than 20% annually to prevent price gouging, remove ASP reporting mechanism and implement a “quality modifier” if wound is healed in less time than published mean.

Thank you for your comments and initiative to seek high-quality evidence to support your products. For evidence requirements see Comment #1, for extension of implementation, see Comment #2, for healthcare disparity, access to care and transition from non-covered to covered, see Comments #3 & 17, for application limits and frequency, see Comment #4, for the role of FDA regulatory pathways, see Comments #5 & 19, for “grandfather clause,” see Comment # 50, for products being considered by class, see Comment #36, for scaffolding and definition of skin substitute, see Comments #16 & 45.

Pricing is beyond the scope of this LCD. In regard to study design, this is determined by the investigators but historical control groups are not equivalent to active control groups and introduce risk of recall bias, missing data, and without standardized SOC procedures applied to the groups they are not truly randomized and controlled. Uncontrolled diabetes has been removed from the exclusion criteria.

A comment letter was received from the makers of Mirragen Advanced Wound Matrix. They explained that the 40 patients RCT is sufficient evidence for coverage and that further data collection on 100 patients is ongoing with anticipated publication later this year. They state that the subjects in the SOC arm were withdrawn per protocol as the wounds were not healing and did not drop out. They feel products under investigation should retain coverage. They also provide case series, national presentations, and pre-clinical study results to support Mirragen. 

The submitted paper has been acknowledged in the evidence review of this product. Additionally added to the LCD, is the explanation that the sample size is below threshold for confidence with only 12 remaining patients in the SOC arm precluding sufficient evidence for coverage. The additional patients being investigated should provide further clarification of the impact of this product and when that data is published can be submitted via the LCD reconsideration process for consideration, see Comment #17. For delay in implementation, see Comment #2. Only peer-reviewed published literature will be considered for product evaluation and those have been added to the LCD.

Birth Tissue Recovery comments that products should be considered for coverage as a class and according to FDA regulatory pathways. They are suppliers of placental tissues to many of the manufacturers of placental based products. “BTR considers the distinctions that the Proposed LCD draws between FDA-regulated amniotic tissue products – all manufactured from identical material, specifically donated placental tissue, and required by the FDA to perform the same functions – to be un-justified.”

The coverage determination within the LCD is based entirely on evidence for the individual products. Proprietary features among the products make them unique and not linked to FDA regulatory pathways, see Comment #36. For more discussion regarding the FDA pathways, see Comments #5 & 19. 

A comment letter from Lucina Biologicals is not in support of the policy and that it is ”unfair and punitive in its narrow approach to coverage determination.” They discuss their product Procenta covered under HCT/P and imply coverage must be consistent with FDA regulatory pathways and RCT should not be required unless required by FDA. They express lack of clarity for understanding the definition of evidence as well as unsuccessful therapy. They recommend the policy cover the FDA pathways HCT/P, 510(k) and 351 for all products. 

Coverage for Medicare is determined by meeting R&N criteria and therefore, MACs must determine if an item or service meets this definition which is not based on FDA regulatory pathways. For further discussion of the FDA role, see Comments #5 & #19. For the evidence requirements, see Comment #1. Clarification of documentation of wound healing has been added to the Billing and Coding article. 

A comment letter was received from MolecuLight with supporting literature. MolecuLight is makers of a fluorescent wound imaging system. They state, “This device provides reliable, timely information to enable accurate and rational use of skin substitute grafts/CTP, ensuring a higher probability of skin substitute grafts/CTP success, increasing wound closure rates with less resource use for the healthcare system.” The commenter agrees that FDA clearance does not equal R&N and therefore, coverage. As the policy requires conventional wound care for at least 4 weeks before skin substitute graft placement and does not permit placement in infected, ischemic, or necrotic wound beds. The manufacturer states this product can aid in identifying appropriate wound beds for skin substitute placements. They feel this can improve clinical outcomes by providing a quantitative and objective measurement to confirm if the wound contains bacteria and support whether or not to use CTP. They request that fluorescent imaging technology is referenced in the LCD as a diagnostic tool to rule out placement of skin substitute grafts/CTP with high bacterial colonization.

Thank you for your comments. While the LCD requires documentation of ulcer healing, the modality to perform these measurements is out of the scope of the LCD which is on skin substitute grafts/CTP products for DFU and VLU. An LCD request can be made with included peer-reviewed published literature to address this specific area of wound care, see Comment #12.

The American Board of Wound Healing (ABWH) applaud the efforts to enhance the SOC as related to the proper and appropriate utilization of Cellular, Acellular, and Matrix-like Products (CAMPs) /Skin Substitutes/Cellular and Tissue-Based Products (CTP). They expressed concern that Medicare claims data demonstrates that over 90% of wound care providers do not utilize these in optimal fashion. Their organization is committed to providing certification and highest level of care for wound care and hyperbaric medicine.

They comment that ABWH has the only educational and training program that specifically addresses the clinical decision-making knowledge to optimize CAMP utilization and patient outcomes. They offer certification for physicians and advanced practice providers specific to this area and provide details of the certification program. They recommend that clinicians be required to obtain CAMP Certification of Added Qualifications. 

Thank you for your comments and support of the policy. We commend your offering robust training in this area. We agree all providers need appropriate training and leave the modality for that training to the individual training programs, residency, fellowships, and state scope of practice requirements which vary from state to state.

NextGen expresses concern about the policy limiting access to their product and proposed an additional pathway for coverage based on products of the same class. They explain the FDA pathways and evidence availability for products within the class. They are concerned that RCT is required and that this is not efficient in advancing innovation. This includes several tables with factors to be considered for coverage determination utilizing this pathway period. They also provide a case study for NeoMatriX Wound Matrix. They explain challenges in conducting RCT, that all wound care products afford some benefit to patients based on mechanism of action and are concerned with the impact on of the policy on healthcare access. 

Thank you for your thoughtful comments. Because of proprietary differences in products that may affect their function the LCD is based on evidence for the individual products and not as a class, see Comment #36, and FDA regulation, Comments #5 & 19. While RCT is considered gold standard it is not the only type of evidence that may be considered, see Comment #1. For access to care, see Comment #17, and impact on innovation, see Comment #48.

A comment letter from Acera requests coverage for Restrata based on supporting evidence. Restrata is a synthetic fiber matrix, does not require refrigeration or special handling and is not from animal or human eliminating the risk of viral transmission. They review the RCT Hussain 2024 which they state has a low risk of bias and was not included in the LCD. They report this study has similar characteristics to other studies with positive coverage outcomes. Additional studies supporting the product were also submitted. A provider also writes to support Restrata.

Thank you for your comments and submission of the manuscript which was added to the LCD. While we appreciate the RCT design for this work, the study was not powered to determine effectiveness which is acknowledged in the paper. It is unclear what potential harm can be caused by a new synthetic product that remains in place as the wound closes and longer term follow-up would provide further understanding of the safety and outcomes related to the novel technology. The additional studies which are retrospective case reports and case series and a lab study were added to the LCD citation if they reported on DFU/VLU but not other conditions. 

A comment letter from Sweet Bio requesting APIS be covered and increase the number of applications from 4 to 8. They include supporting literature and request reevaluation of this study. They also have several case reports and lab studies to support the product. 

Thank you for your comments and submitting literature. We have reanalyzed the paper but conclude insufficient evidence for coverage as explained in the evidence section of the LCD. The additional supporting article was also referenced. If literature is developed that provide further clarification on the product this can be submitted through the LCD reconsideration process. For application limits and frequency, see Comment #4. 

A comment letter from Integra applauds the use of evidence-based medicine to make coverage decisions on the coverage of CTPs. The request provisional payment for products that are currently under investigation. They request further clarification on the process for approval of additional applications.

Thank you for your overall support of the policy. Provisional payment is not feasible as we do not know if the product is effective for wound healing until the study is completed. It is not R&N to cover services without this information especially when there are commercially available products with supporting evidence. Once evidence is developed this can be submitted through the LCD reconsideration process for consideration for coverage. For additional applications, the provider should meet the documentation requirements as outlined in the Billing and Coding article and any additional processes determined by the individual MACs will be part of their education when the policy becomes effective. For delay in implantation, see Comment #2.

A comment letter from multiple providers postulates an increase in amputation based on the LCD especially affecting elderly in nursing homes. “We urge you to allow time for additional examination of the existing scientific evidence supporting the use of cell-based tissue wound coverings and, if required, more research to demonstrate the product efficacy that our providers see day in and day out.” Successful cases are described. They are concerned the LCD may affect staffing and burnout and limit supply and encourage expanding coverage to the entire class of currently covered skin substitutes. 

Thank you for your comments. No supporting evidence was submitted. There is no evidence that the LCD will cause a strain on staffing or burnout. Since the LCD requires use of products that have proven efficacy and potential decreased number of applications required to wound healing it may improve this situation. For disparities, see Comment #3, concerns about access, Comment #17, and coverage of products by class, see Comment #36. 

The American Academy of Dermatology state the dermatologist utilizes skin substitute grafts/CTP for various indications including the treatment of VLU. They indicate support of the evidence-based approach to the policy. They request further definition of the evidence standards to determine coverage as well as the process for movement from non-covered to covered status stating new products are essential for innovation. They encourage a transition under which group 3 codes would remain covered to allow time to develop evidence. They encourage inclusion of dermatology in future CAC meetings as subject matter experts in this area.

Thank you for your comments and explaining the role of dermatologists in this area and invitation to consult AAD for future expertise. For evidence requirements, refer to Comment #1, for extension of implementation, Comment #2, for transition from non-covered to covered status, see Comment #17.

A plastic surgeon and co-author of a consensus document on CAMPS objects to the proposed LCD. He states the proposed LCD does not have an acceptable definition of skin graft that describes and reflects the diversity of products and that scaffolding lacks clinical relevance. He feels the requirement to require multiple, redundant, and costly RCT for 361 products is without merit and the FDA pathway is well established and appropriate for coverage decisions for the products. He states that the Armstrong study was not interpreted correctly and does not justify only 4 applications and that the requirement for specialty care for complex atrial venous care and diabetes will result in unacceptable delays due to a shortage of vascular surgeons and endocrinologist. He claims the policy ignores instructions for debridement prior to initial or subsequent reapplication. He says delaying care can result in malpractice cases. 

Thank you for sharing the International Consensus Document published in The Journal of Wound Care which has been added to the LCD under societal input. The policy does not require that vascular evaluation or diabetes management be conducted with a vascular surgeon or endocrinologist but a qualified provider who can ensure that the underlying conditions are being appropriately managed to improve health care outcomes and increase the chances of success with wound healing. For application limits and frequency, see Comment #4, for FDA regulations, see Comments #5 & 19, for definition of skin substitute and discussion of scaffolding, see Comments #16 & 45, and for coverage of products as a class, see Comment #36. The definition of CAMP has been added to the LCD, but the LCD refers to skin substitute graft/CTP throughout to be consistent with the current literature/guidelines as this new terminology has not been fully adopted at this time or reflected in most literature.

RenovoDerm makes electrospun synthetic matrices and comments on the importance of innovation, avoiding disruption of availability of current products and negative impact on patient care. They request manufacturers that have research ongoing get continued reimbursement while the studies are ongoing. They share that there is published evidence to support Phoenix^® Wound Matrix with a prospective case series with positive outcomes for 50 wounds. They state they support the transition to evidence-based coverage decisions and efforts to correct egregious misuse of CTP, however they are concerned the abrupt elimination of novel technologies from marker will stifle innovation and interrupt patient care and access. They request clarity on evidence requirements and inclusion of RWD. The include supporting literature. 

Thank you for your comments. The prospective case series have been added to the LCD but does not represent sufficient evidence for coverage. The cost analysis report (Carter 2023) was reviewed, but not added to the LCD as cost analysis are not included for coverage determinations. For innovation, see Comment #48, for evidence requirements, see Comment #1, for extension and provisional payment, see Comments #2 & 64, for access, see Comment #17.

Smith and Nephew thank the MACs for the incorporation of previous suggestions into the proposed LCD. They support the evidence-based criterion for coverage and a pathway for additional applications when necessary. To summarize the 189-page letter they request:

1. Remove language stating additional applications would be considered “exceptional.” The cite Raspovic et al. 2018 stating they reported >4 applications for wound closure. They also explain VLU takes longer to heal with larger mean size at baseline.
2. Increase the number of applications to eight (8), beyond which additional applications can be covered with supporting medical necessity.
3. Regardless of the application limit established, provide a more detailed description outlining the clinical criteria and documentation requirements for exceeding the established limit.
4. Provide a timely and clear pathway that is not dependent on Reconsideration Requests for new products entering the market to be added to the covered list of skin substitutes.
5. Further define the evidence criteria for a product to be covered.

They request review of the submitted literature before finalizing the LCD. Suggest evidence requirements is provided.

Thank you for the comments and submitted literature. For application limits and frequency, see Comment #4, for documentation requirements, see Comments #21, #22 & #29, for evidence requirements, see Comment #1, and for transition to coverage, see Comment #17. The submitted literature was reviewed and includes: Raspovic 2018, Serena 2022, Marston 2013, Falanga 1999, Towler 2018, Harding 2013, Bianchi 2017, Serena 2014, Mostow 2005, Romanelli 2010, and Armstong 2022 and were already included in the LCD. A SR/MA on prevalence and incidence of VLU and Medicare data sets that were not added since it did not address treatment, nor a lab report on Dermagraft. A Medicare dataset was not added since it does not distinguish products and there was too much variability to pool this data for conclusive results. A 2024 SR/MA (Banerjee 2024) supports the policy concluding that head-to-head comparative studies are needed for determine the evidence between individual products to determine what to use in practice and was added to the LCD. A large 2024 retrospective study by Padulo was also added to the LCD. Therefore, all submitted literature was evaluated before finalizing the LCD as requested. 

Access Pro Medical supports the LCD and agrees with application limits of 4/12 weeks with exceptional cases allowed. They request inclusion of MatriDerm on the covered list. They explain that the product will have a HCPCS code prior the final LCD being published and therefore, not included in the evidence review. Supporting evidence is submitted and they explain the product as a similar design to products on the covered list.

Several providers express concern MatriDerm was non-covered and reports positive outcomes. There was not a RCT as stated but a single arm prospective study. 

MatriDerm is a porous 3D dermal matrix consisting of bovine collagen and elastin. A 2013 single arm prospective study includes 60 subjects with chronic DFUs. In this study subjects had a layer of MatriDerm applied followed by split thickness skin graft or split thickness skin graft alone. The investigators reported reduce time to complete wound closure and higher rate of complete closure than skin graft alone (Jeon 2013). MatriDerm’s function was to aid in wound healing when placed with a split thickness skin graft and does not meet the definition of skin substitute graft/CTP. Additional literature includes a case study in DFU, VLU, and mixed leg ulcers.

Porcine dressings are covered as an occlusive dressing for burns, donor sites of a homograft, decubiti, and other ulcers per NCD 270.5, but are not covered as skin substitute grafts/CTP under the NCD or and there is no evidence they function in this capacity. If such evidence is developed it can be submitted through the LCD reconsideration process.

Reprise Biomedical comments the proposed LCD disadvantages patients and providers by restricting access to innovative technologies like Miro3D and MiroDerm. They state these products are covered under NCD 270.5, have 510(k) clearance and HCPCS code. They request clarification of clinical evidence requirements and are concerned these conflicts with FDA regulatory pathways. They feel FDA regulatory status should be used for coverage determinations. They explain it takes time to publish evidence and have a study underway and request at least 36-month phase-in-period.

They object to the LCD classification of MiroDerm as insufficient evidence and reviews the 2 studies that are cited in the table which include a prospective pilot study with 7 patients and an observational study with 20 subjects. They explain they are in the process of publishing the results of a retrospective case series on Miro3D. All of these report positive results with the products. They also have received positive feedback from providers using the products and case examples are provided. They feel that the policy restricts provider autonomy and negatively impacts patient care. They object to limitations on graft applications. They believe the LCD will cause a supply chain issue and stifle innovation. They are concerned the covered products favor those with HCT/P over 510(k) since there are more covered with HCT/Ps. They request their products be relocated to the covered list.

NCD 270.5 is a coverage policy for porcine skin and gradient dressings but does not cover skin substitutes grafts/CTP; therefore, there is no conflict between the LCD and NCD. Definitions of skin substitute and dressings are in the definition section of the policy. The products can be used and billed as dressings per the NCD, but not as skin substitutes/CTP. The CPT codes consistent with skin substitute grafts listed in the Billing and Coding article are non-covered for these products in absence of evidence to support this function. Consistent with Medicare requirements for R&N this policy is based on evidence for product efficacy and not FDA regulatory processes, see Comments #5 & 19.

We appreciate the commitment to developing evidence on your products. The current evidence is not sufficient to determine if the impact of these products is due to the products themselves and therefore, further studies are necessary to determine their effectiveness is require before coverage can be considered. The coverage determination within the policy is based entirely on evidence and not FDA pathways; therefore, the number of products covered under different pathways is irrelevant to the coverage decisions.

For evidence requirements, see Comment #1, for delay in implantation, see Comment #2, for application limits, see Comment #4, for access to care/supply chain and innovation, see Comments #17 & 48. 

Merakris comments they agree with many principles in the proposed LCD but also have serious concerns with the severe limitations of coverage for treatment of DFU/VLU. They explain the product Dermacyte Liquid is currently going through active phase II clinical trials for VLU. They state the shared commitment to improving health and outcomes for patients suffering from DFU/VLU. They state the product Dermacyte Matrix is supported by quality evidence as demonstrate by an exemplary safety record with more than 17,000 packages used since 2019 without a single reported adverse event, a recently published peer reviewed study in wound healing for DFU/VLU using RWD, and the ongoing RCT further investigating the products effectiveness. Supporting literature is submitted. They also request a timely process to review evidence as it becomes an available, as well as suggesting a 2-year transition to the policy to allow companies to complete their studies or providing provisional coverage in the interim.

Thank you for your commitment to developing high quality evidence as demonstrated by conduction of Phase II trial and ongoing investigations for your products. The recently published work by Ditmars et al. has been added to the LCD; however, this small retrospective comparative report does not determine that the effects are causal to the product or other factors and therefore, not sufficient for coverage. The low number of applications and overall positive findings are encouraging and true effect may be determined by the ongoing RCT. Future published evidence can be considered via the LCD reconsideration process. For transition to coverage see Comment #17, and delay in implementation, see Comment #2.

The American Podiatric Medical Association states APMA supports “all these criteria for covered indications” with the following recommendations:

• They support the criteria for covered indications with the suggestion to change the word “measurable” to “significant” in describing SOC measures. They feel this is clarifying language to ensure that patients would not be denied coverage with very minimal measurable change.
• They feel that the description of medical necessity is vague and that the use of these products outside of DFU/VLU is unclear and seeks clarification.
• They do not agree with the limitation of 4 applications or feel this is supported by peer-reviewed evidence and can lead to poor patient outcomes. They provide several citations supporting higher application frequencies. They also state the Society of Vascular Surgeons and American Venous Forum clinical practice guidelines suggest reapplication of cellular therapy should continue as long as venous leg ulcers continue to respond on the basis of wound documentation and that the frequency of application should remain at the discretion of the clinician.
• They suggest that the limitation of 4 applications is not consistent with the intended use.
• They appreciate that additional applications can be utilized in exceptional cases with documentation add a indicated by the KX modifier allowing flexibility.
• They have questions regarding the JZ/JW modifiers that are currently being used by some MACs and suggest addressing these modifiers in the final Billing and Coding article.
• They point out that in the LCD failure to respond is set at 4 weeks of standard therapy; however, in the Billing and Coding article it states 30 days and request clarification.
• They object to limitation #3 that unsuccessful therapy includes recurrence of the ulcer and the same location within 12 months from the initial application and feel that if they responded to products initially this may be their best treatment course for a recurrence and ask for this limitation to be removed.
• They support the importance of identifying correcting systemic causes of impaired healing; however, suggest replacing the word “correcting” to “optimizing.”
• They also suggest the word “substantial” used to describe ulcer improvement is not defined and ambiguous and explain that the literature refers to 50% reduction in size after 4 weeks of conservative therapy and a recommended definition for this response.

Thank you for your careful review of the LCD and thoughtful feedback.

• We agree with the suggested clarification in terms throughout the LCD and these changes have been made based on this feedback specifically changing correcting to optimizing and replacing substantial with 50% or more. The word measurable has been removed as suggested and the language clarified that the application is appropriate for failed or stalled wounds as defined in the LCD.
• Regarding the use of products outside of DFU/VLU, explained in comment #7, this is based on meeting criteria for R&N and at individual MAC discretion. Therefore, further clarification of these requirements is out of the scope of this LCD, but should align with evidence-based practices.
• The many challenges in addressing application limits and frequency are discussed in comment #4. The cited literature is included in the LCD.
• JZ/JW modifier clarification has been added to the Billing and Coding article.
• The Billing and Coding article has been corrected to 4 weeks (not 30 days) for consistency.
• We appreciate your expertise in advising on recurrence and that it is medically appropriate to proceed with repeat application for recurrence if previously successful. Limitation language that included recurrence of an ulcer on a same location within 12 months as unsuccessful treatment has been removed from the LCD. 

MIMEDX expresses strong support for the proposed LCD overall and applauds effort for evaluating skin substitutes individually and the requirement for clinical evidence for coverage. They state they do not believe delays in implementation are necessary or appropriate and recommend immediate implementation. They have 6 recommendations: clarify the process for adding products to the covered list, increased benchmark for exceptional cases, clarify the use of the KX modifier, expand covered diagnosis list, clarify discrepancy between the LCD Summary of Evidence and Billing and Coding article (DFU/VLU coverage by indication) and provide alternatives to ABI requirements which are each elaborated in the comment letter. They state that the requirements for products to have quality supported evidence is consistent with both the 2012 and 2020 AHRQ reports that conclude due to processing variations each product must be studied in a “ properly conducted clinical trial”. They feel that manufacturers have had sufficient time and the ability to anticipate the need for high quality clinical evidence in this space. They point out that the first proposed LCD by Novitas/First Coast was in 2022 so there has been ample warning of the potential changes. They state there is zero supply chain issues. “MIMEDX reminds the MACs that the proliferation of skin products is recent. For example, 15-17 products were listed on the Medicare Part B Drug file as recently as 2022. We remind the MACs that there were no supply chain issues with this lesser number of products. While the number of available products has skyrocketed, the growth of application codes (patients actually receiving these products) has been modest. The manufacturers of the listed covered products will be able to meet this modest increase in demand” and supporting data is provided.

There are 4 “Big Data Analysis” of Medicare Claims data and they encourage inclusion of all 4 in the LCD and literature is submitted. They highlight the benefit of this RWD as inclusive of patient comorbidities and complexities that are not often possible within RCT. They feel these papers may further contribute to the number of applications as well as skin substitute usage on large or deeper ulcers.

They request development of a centralized reconsideration process rather than needing to approach all 7 MACs individually suggesting a process such as MolDx utilizes as an example to streamline the process. They suggest the benchmark for use of the KX modifier as exceptional cases be set at 8 and if the benchmark is below this that the term exceptional cases is removed as they do not feel that this is consistent with current evidence. They request clarification on the use of the KX modifier with concerns that this could result in delays to patient care especially if it triggers ADRs. They suggest adding the documentation requirements to LCD and Billing and Coding article for measures of wound healing and suggest adding reduction in wound depth as an additional marker. They suggest expansion of the covered diagnosis list to include diabetic lower extremity ulcer, and codes to include deeper ulcers without necrosis for which these products are highly beneficial. They request clarification as the LCD list evidence for DFU and VLU separately but this is not in the Billing and Coding article. They suggest that the products are covered for both indications as well as all other diagnosis at MAC discretion. They recommend appropriate alternatives to ABI requirement. 

Thank you for your support of the policy. As the manufacturer of several of the products on the covered list the support to avoid delays and assurance there is no risk of supply shortage is appreciated. For delays in implementation, see Comment #2. Thank you for submission of the additional literature which has been incorporated into the LCD. While we appreciate the suggestion of a centralized reconsideration process, MolDX is a separate entity, and this policy is being issued by 7 individual Part A/B MACs. Efforts to reduce burden and foster timely reviews will be made by the MACs and instructions provided to streamline the process, see Comment #17. Additional clarification on the use of modifiers is incorporated in the final Billing and Coding article. The suggestion of including signs of wound healing has been added to Billing and Coding article. The LCD is specific for DFU/VLU for use outside this area see Comments #7. Pertinent diagnoses within the anatomical scope of the LCD were added for skin substitute grafts/CTP with supporting evidence and labeled indications for use over exposed muscle, tendon, or bone, see Comment #20. For the intent of the policy to cover the indications with evidence only, see Comment #37, for ABI requirement, see Comment #21, for documentation requirements, see Comments #4, #12, #21, #22 & #29.

Skye Biologics is committed to ensuring their products align with the highest standards for clinical evidence and deliver optimal patient outcomes therefore requests clarification regarding the transparency on requirements for clinical evidence. Additionally, they request limitations on skin substitute applications to be increased to 8 based on RWE described by Raspovic et al. (2018). The request ample time to complete investigations. 

Thank you for your commitment to high quality evidence development. For how evidence is considered, see Comment #1, for timing, see Comment #2, for application limits and frequency, see Comment #4. The cited study which investigated Grafix had a mean application frequency of 4, provides data on larger wounds and was included in the LCD.

Organogenesis applauds the evidence-based approach in the draft LCD and coverage of Apligraf, Dermagraft, and Affinity based on high quality evidence (RCT). Apligraf and Dermagraft have FDA PMA approval process. They request coverage for NuShield and PuraPly, based on recently published peer review RCT that was not included in the draft LCD and submitted for consideration. Supporting literature for NuShield was published 6/6/24 and a publication supporting PuraPly also published in early 2024 so not included in the draft literature search. They request clear criteria for coverage and include recognition of RWE, provide timely process for adding new products to the LCD (30 days), increase the number of permitted products, ensure access, and clarify the scope of coverage and statement on excessive waste to avoid confusion. They suggest increasing application limits to 8 citing Raspovic et al. data that larger wounds require more applications. They recommend a 1-year notice period or allowing coverage for products with currently registered trials to aid in transition time. They request clarification if products that are covered are covered for both DFU & VLU. They recommend the LCD should make it clear that clinicians have the ability to exercise judgment in the management of woman's outside of DFU & VLU. They suggest some clarifying language in regard to excessive wastage. 

Thank you for your thoughtful comments and submitted literature. The newly published literature for NuShield and PuraPly have been added to the LCD. We agree there is sufficient literature to support the addition of NuShield to the covered list; however, we feel the literature for PuraPly is not sufficient as explained in the LCD. If additional evidence is published it can be submitted via the LCD reconsideration process.

For evidence requirements, see Comment #1, for delay and implementation, see Comment #2, for application limits and frequency, see Comment #4, for coverage of DFU & VLU, see Comment #37, for management of wounds outside of the LCD, Comment #7, for transition to coverage, see Comment #17.

The American Society of Plastic Surgeons, Merakris Therapeutics, Pinnacle Transplant technologies, SereneGroup Inc, Stimlab, LLC, Tides Medical, LLC, and Vivex Biologicals send a joint letter with concerns about the following issues:

• They feel the application limit is arbitrary and not based on evidence and suggest increasing application limits or removing it altogether leaving decision making to the providers. The are concerned the use of the modifier can result in additional burden to providers.
• Request clarification on evidence requirements for coverage and payment and process and timeline for moving products from non-covered to covered status.
• Delay implementation for 2 years to always transition to the evidence-based coverage policy.

They review the burden of DFU and VLU to patients and the healthcare system, noting ethical minority populations have a higher risk and are concerned the LCD would create unnecessary barriers to wound management and issues with access to treatment options. They discussed the potential impact of the policy on patients and providers expressing that healthcare providers would abruptly have fewer treatment options and have to sometimes shift from products they have already become familiar with or prefer and also subject to the application limit that could interfere with their treatment decisions. They also are concerned about inventory of the preferred skin substitute which they may not be able to fully utilize before the policies are implemented leaving them with a financial liability. They expressed concern on manufacturers whose products are non-covered. They explained that they need more clarity on what is required in future studies and timelines to aid in planning appropriately.

Thank you for your comments. We acknowledge concerns raised by stakeholders regarding potential treatment disruptions for patients within an episode of care; therefore, the notice period for policy changes will be extended from the standard 45 days to 90 days. This extension will mitigate any interruptions in patient care due to a shift in product use mid-treatment and ensure continuity of care for Medicare beneficiaries during this transition. It is not appropriate to further delay implementation, as explained in Comment #2. For evidence consideration, see Comment #1, for application limit, Comment #4, for transition from cover to non-coverage, access to care and supply chain, see Comments #3 & 17, for health care disparities, see Comment #3.

HealthTech Wound Care state that CMS has not instructed manufacturers to have completed clinical studies and this is in contradiction to the FDA regulatory pathways for which their products have been evaluated. They do not feel they have had ample warning or opportunity to prepare for evidence requirements and that the product being non-covered will limit patients access to care. They feel this contradicts the 21st Century Cures Act which was designed to help accelerate medical product development and bring new innovation and advances to patients who need them faster and more efficiently. They request RWD be included in evidence consideration. They feel that the covered products within the LCD are subject to bias. They describe their product DermaBind TL and that RWD is being collected and studies pending. They report positive feedback from providers on their product.

Thank you for your comments. The existence of a FDA regulatory pathway for the product does not translate to Medicare coverage. The item or service must satisfy the R&N standards for coverage, see Comments #5 and #19. We support innovation; however, this must be done in a way that ensures beneficiaries are treated with products that are supported by clinical evidence and demonstrate improved outcomes as defined in the 21^st Century Cures Act, see Comment #48. Multiple manufacturers have published level 1 evidence to support their products demonstrating that the need for evidence has been evident within this space, for evidence consideration see Comment #1. As additional evidence is collected for DermaBind TL or other innovative products this can be considered through the LCD reconsideration process with submitted evidence. We acknowledge there are limitations in research and hope future study designs can better address these limitations. The covered products all have demonstrated effectiveness and improved outcomes in a controlled manner and supported by additional published clinical evidence. The LCD offers a transparent review of all studies reviewed and utilized established tools to access quality of evidence (risk of bias assessment) to ensure studies have equal consideration regardless of funding source, see Comments #13, #25, #35, & #52.

A comment letter from the Institute for Quality Resource Management expresses concerns with disrupting wound care treatment plans based on the policy. They state preparation of the wound bed begins 4 weeks prior to any placement of skin substitute graft/CTP and requires a standardized approach of treatment and diagnosis. They request guidelines include greater details of wound bed assessment, and treatment to be provided during the four weeks before grafts are applied. They provide reference to Matthew Regulski, DPM publication from Today’s Wound Clinic (TWC) Prepare to Repair “Preparing to Repair Diabetic Foot Ulcers” (May 2023 Feature article).

The commenter expresses “that in review of over 500 patients many wounds do not respond to 12 or more applications and believes this is related to inadequate preparation of the wound bed with signs of impending necrosis and clinicians’ uncertainty on how to bring the wound to closure. They recommend enhanced training of wound care clinicians, guidance on best practices and wound bed preparation full accounting for the variations in patient comorbidities, suggested metrics to aids in determining when the wound bed is prepared for a skin substitute graft/CTP, providing transparency and clinical design and selecting standard treatment cover and including key parameters of wound bed preparation to ensure products are used on wounds that have the highest probability of closure over a planned 12 weeks.” Additionally, they inquire about transition of care for patients who are already receiving a course of therapy when the policy becomes effective suggesting a phase in period of 12 weeks, providing guidance on path to coverage and reimbursement including evidence requirement, and suggestions on appropriate control populations.

They suggest the following limitations are not R&N: placement of graft/CTP in infected, ischemic, or necrotic wound bed. They state that utilizing diagnostics to understand the levels of bacteria can help to identify appropriate wound beds for graft placement. This can be accomplished with fluorescent imaging currently available by 1 FDA cleared device and supports the policy.

Thank you for your comments. We agree meticulous preparation of the wound bed is essential for best wound management as described in the LCD under covered requirements #3. For evidence requirements, see Comment #1, for transition to coverage, see Comment #17, for fluorescent imaging, see Comments #12 & #59. We thank you for the educational article; however, since this is not peer-reviewed it was not added to the LCD. There was not supporting evidence to support removal of the limitation of grafts in infected, ischemic, or necrotic wounds.

Healogics, LLC manages 600 hospital-based Wound Care Centers nationwide and submits the following comments: they support evidence-based approach to coverage determinations but have concerns about certain language and provisions and the potential consequences. They are concerned the collaboration among the MACs create de facto NCD and variations in the requirements between LCD and NCD regarding MEDCAC and consultation with outside experts. They state there is no evidence in the LCD of outside engagements with experts. They feel that MACs have taken away their opportunity to leverage local clinical experts to inform coverage decisions. They feel that the term adjunctive therapy is inappropriate and that CTP should be considered advanced therapy. They suggest the time frame of 4 weeks for SOC should be changed to 30 days. They recommend the requirements for ABI be changed to non-invasive vascular testing. They feel that the limitation frequency is not appropriate, and while they appreciate a path for additional applications, they state the conclusion of 4 applications is misinterpreted, not evidence based and can jeopardize care. They suggest an upper limit of applications be 6-8 with the ability for more in exceptional cases. They recommend removal of the limitation for recurring ulcers as this is common within this population and may limit these patients’ treatment options and is not supported by evidence. They feel that 12 months is not supported by evidence in terms of how long a recurrence would be defined. They recommend expansion of the covered product list and are concerned about supply chain with the limited list. They recommend a path to coverage without having to go through the LCD reconsideration process and suggest the LCD be rewritten so that this is not required and new products can be added directly to the Billing and Coding articles. They believe there are some confusing words in the Billing and Coding article and suggest replacements. They also request an expansion in ICD-10-CM codes and suggested additions are included. They suggest extending the policy notice period to ensure patients care is not disrupted during a 12-week episode of care and allowed hospitals time to obtain replacement products from the covered list.

Thank you for your participation in the LCD development process. The MACs had followed the process required for LCD development according to the Program Integrity Manual (PIM) Chapter 13. Stakeholder input was sought through the process and changes from previous draft LCDs were made based on this input. Comment letters from previous open comment including major societies, and over 23 presentations including a public listening session, were considered in the LCD draft development. The proposed LCD has gone through the required open comment period with many opportunities for public comments and feedback. Changes made from the proposed to final LCD are made based on the input from stakeholders, such as yourself, during this process. While not required for LCD development, an educational article titled "Principles of Study Design" has been published by the MACs. Additionally, several sources for guidance on study design have been added to the Analysis of Evidence section of the LCD, see Comment #17.

The LCD only refers to skin substitute graft/CTP as advanced therapies. The only time they are referred to as adjunctive therapy is in the “Societal Input” section and this is to be consistent with the wording from the guidelines being referenced. The timeline of 4 weeks was selected because this is the time duration that was utilized in the majority of the studies and with few studies utilizing 30 days as the SOC time frame before considering advanced treatments. We agree with the suggested changes regarding ABI measurements, see Comment #21. For application limits and frequency, see Comment #4, definition and management of ulcer reoccurrence, Comment #73, for concerns regarding transition to coverage and supply chain, see Comment #17. We thank you for your suggested improvements to the Billing and Coding article which have been made. For ICD-10-CM expansion, see Comment #20, for delay in implementation, see Comment #2. 

The Alliance of Wound Care Stakeholders comment letter comments on the following:

• “The Alliance is in agreement with the MACs that skin substitutes/CTP which do not have any peer-reviewed published evidence demonstrating their safety and efficacy should not be covered.” They are concerned that the MACs only used RCTs for coverage purposes and should consider other well designed studies including RWE, especially if there is a RCT for predicate device used in FDA clearance.
• The MACs state they used GRADE methodology but they are concerned they did not follow the protocol for GRADE as there was no process description by the MACs on how they decided to cover the products. Their expert does not feel the protocol for GRADE was followed in reviewing CTP evidence and suggests that the decision making was arbitrary. They provide recommendations on evidence to include: criteria used to judge the studies and equally and consistently apply this criteria, accept well designed studies that are not RCT, coverage for Kerecis^® based on evidence, do not exclude products without RCT and they state some studies are of good quality when GRADE methodology applied and would be covered, provide transparent and reasonable mechanism for review of new evidence in timely manner, meet with manufacturers to discuss trial designs before studies begin and if one MAC agrees to design it is to be accepted by all the MACs.
• They cite there is peer-reviewed published clinical evidence that prove CTP is effective as a class of products and all of the RCT included show positive benefit for wound healing. They state, “the proposed LCD levels many criticisms at various trials (including lack of blinding, lack of controls, insufficient power, short-term follow-up, retrospective design, and risk of bias) without establishing any parameters on what is considered an effective and ineffective study.” They are concerned that the MACs did not have any identified protocols when reviewing evidence for coverage of these products. The are concerned no criteria for coverage was described, some RCT were eliminated due to lack of “long term follow-up” which was not defined and process for which decisions were made is not transparent. They provide a list of items used in GRADE that were not included within the LCD. They also express concerns regarding inconsistencies in the CTP products covered between the previous draft LCD/LCA and the current draft. The Alliance recommends that a consensus document published in 2012 ““Consensus Principles for Wound Care Research Obtained Using a Delphi Process” be used as a guide.
• They express concern with the need to go through the reconsideration process to move a code from covered or non-covered status. They do not feel this aligns with the intent of moving codes to the Billing and Coding article. They request clarification of the process, to not require the LCD reconsideration process to relocate codes, provide a timeline and address how the MACs will work together.
• They express concerns that implementation after 45 days of the LCD being finalized is problematic as this can disrupt care of patients currently under treatment. They also are concerned providers may not have sufficient time to obtain covered products and make formulary changes. They recommend at least a 1-year delay.
• The Alliance recommends the application limit is increased to 6-8 and understand those with more complex wounds will require more applications and longer duration of care. They feel this is consistent with evidence and the 4-application limit is not evidence based.
• They request more information on required measurable signs of healing and remove the word exceptional for additional applications.
• They state the policy used the word adjunct and should refer to the products as advanced therapies.
• They request clarification of the use of products outside of DFU/VLU.
• They express concerns regarding medical review and the documentation requirements auditors may use in these reviews. They explain auditors may use LCD language to deny claims and provide examples of areas of concern. They explain “free of infection” does not represent colonization of the wound and that no infection present is clearer and recommend avoiding requiring test or study that infection has been managed as clinical judgement is adequate to determine this. They are concerned that vascular evaluation is too broad and standards to confirm perfusion is adequate should be defined. They state there are CMS approved quality measures for nutritional assessment that can be used to clarify this area.
• They express concern regarding “substantial” ulcer improvement and request definition of what is considered substantial.
• They state venous studies are not needed to diagnosis venous ulcers and care should not be delayed conducting such assessments. They request how the provider should document no evidence of osteomyelitis and any required studies. “The Alliance requests that the MACs tell us if a statement by the physician regarding patient compliance is sufficient or define any other metrics that are needed.” “The Alliance agrees that all patients with venous stasis ulcers should be treated with at least 20 mmHg compression. We want to ensure that auditors will not deny payment for CTP because a Class 3 garment was not utilized since this level of compression may not be clinically appropriate for all patients.“
• They request clarification of smoking requirements and provide suggested language.
• They also express concern that the example of uncontrolled diabetes under contraindications to skin graft may result in exclusion of those patients from receiving CTP.
• The recommend changing the word correcting to optimizing for management of underlying systemic conditions.
• They advise changing to Billing and Coding article to align with LCD in terms of the days of SOC.
• The Alliance suggest removing the section from the article that explains how to bill Q4100 and A4100.
• The Alliance objects to inclusion of Winkler paper in the LCD and states it is not specific to CTP. They state extensive use of CTP demonstrates their safety and objects to inclusion of potential harm in the LCD.
• The Alliance does not feel the term “skin replacement therapy” is correct and suggest using the CPT term “skin replacement surgery” to be consistent.
• They provide suggested language to clarify use of the KX modifier.
• They explain there is no evidence to support requirement for ABI and recommends vascular assessment prior to treatment with CTP. They provide reference to Alliance and CMS approved quality measures to require non-invasive vascular assessment.
• The Alliance explains that recurrences are common and the language that recurrence within the last 12 months represents unsuccessful treatment if the patient had favorable response to CTP and would limit patients access to appropriate treatments.
• They feel that the wording for documentation requirements for additional applications “The current treatment plan has resulted in wound healing and expectation that the wound will continue to heal within this plan” is flawed. They state if the wound were healed, it would not need additional applications. They also object to the use of the word “time.” They recommend “the MAC to strike “has resulted in wound healing” from the documentation requirement. They point out ulcer type is missing from some products in the Table.
• They request expansion of ICD-10-CM codes and provide recommended codes to add to the article.
• The Alliance feels that there is need for further stakeholder engagement and CAC meeting.
• They express the need for a delay in implementation beyond 45 days to allow patients within an episode of care to complete care, and facilities and providers to adjust to the changes with a recommendation of 1 year.
• They also express concerns of the LCD on patient access and health equity.

Thank you for your comments and commitment to evidence-based decision making. The MACs must critically evaluate literature in order to make coverage determinations based on evidence as mandated for policy development. The fundamental basis for the policy is: do we have reasonable confidence the study outcome is due to the intervention (product or device) and does it benefit the patient? Therefore, to be considered for coverage, each product must have published clinical trial(s) that evaluate a well-defined patient population of sufficient sample size and use a robust study design to convey confidence in the results.

GRADE recommendations were not performed in the develop of the LCD by the MACs but AHRQ, IWGDF and SVS/APMA/SVM have conducted this analysis concluding the literature is low quality. Therefore, understanding the lack of high-quality studies, the objective of the analysis was to utilize a standardized tool, RoB2, to provide assessment of each study in an identical manner to evaluate if the individual product had a minimum level of supporting evidence that it is effective for wound healing. To be considered for coverage, studies must have a sufficient sample size to begin to have some confidence in the results although most were under sampled with lower than desired confidence levels. Using the RoB2 tool risk of bias and measures to reduce risk was determined and how this may have impacted the study results considered. Each covered product also had at least 1 additional clinical trial showing equivalent healing rates to the RCT to confirm utility of the product. See Comments #1 and #10.

We certainly understand investigators desire and need to understand how coverage determinations are made and how evidence is used. The MACs have developed an education article to elaborate on the principles of study design which is published on their website. However, this is not prescriptive and based on established standards for research. It is beyond the MACs role to advise researchers on how to design and conduct studies, but to utilize established methodologies to evaluate the outcome of this work. For this evaluation we utilize tools that are nationally recognized and without risk of bias inherent to the tool itself. We do not endorse specific protocols or guidance documents; however, multiple potential sources for guidance including the recommended consensus document by Serena et al. have been added to the LCD under the Analysis of Evidence section.

We refute the statement the evidence review was arbitrary for these reasons and further explained in comments #1 & #35.

Through the open comment period additional literature was identified that was not included in the initial search and incorporated into the final LCD. This highlights the importance of the open comment period to ensure completeness. There are several months from the time a MAC completes the proposed LCD before it is published so it is certainly possible new publications will be published during that time. Several products have been added to the covered list with submission of high-confidence literature demonstrating the effectiveness of the process. A section has also been added to the LCD which reviews RWE received during the open comment period.

We do not agree that products can be classified as a class. We acknowledge that there are studies that demonstrate effectiveness of these products grouped as a class but methodological flaws and marked limitations may conflate the conclusions. For instance, in many of the SR/MA included only the RCTs so it would be expected to see a positive outcome but does not represent the products that have not been studies with this rigor. The AHRQ technical analysis which was conducted with rigorous methodology concludes these products must be considered individually as well as multiple additional publications that have evaluated these products as a group. In addition, there are multiple referenced papers on how products are different despite being in the same class as elaborated in Comment #36. No studies were excluded based on lack of long-term follow-up; all of the studies included in the proposed LCD share the limitation of short-term follow-up. In regard to concern regarding inconsistencies between the previous draft LCD and the current draft, coverage must be consistent with evidence as required for policy development. The new proposed LCD was drafted with the iterative knowledge from the comments on the retired draft and it offers a transparent review of all studies reviewed leading to development of an evidence-based policy that represents the logical outgrowth of the LCD development process.

We understand auditors may utilize the LCD for their reviews but this use is beyond the scope of the MAC especially for auditors outside of the Medicare program. We strive to provide clear language and measures without being overly prescriptive so to not interfere with provider judgment or add additional burden. The policy is on CTPs for DFU/VLU so specific measures regarding wound bed preparation are not within the scope of the policy, see Comments #12 & #59. Assessment of nutritional status, assessment of infection or osteomyelitis, and decisions regarding venous studies are left to provider discretion, clinical practice standards and individual patient needs. We were not able to identify the term “free from infection” in the LCD. Substantial ulcer improvement has been defined based on stakeholder input, see Comment #73. Documentation requirements are outlined in the Billing and Coding article and regarding conservative therapy states documentation should include “the type of standard of care treatment given and the response.” We agree with vascular assessment over requiring ABI, see Comment #21. We encourage providers to utilize quality measures such as those the Alliance has worked on for optimal patient care. We agree with the Alliance’s interpretation of smoking cessation and will include clarification in the education on the policy. The word measurable has been removed and clarified, see Comment #73. Uncontrolled diabetes has been removed from the example of contraindications. Correction of systemic pathologies has been replaced with optimizing (see Comment 73). The Class III compression was replaced with most supportive in the discussion. There are no evidence-based standards established to set as guidelines or submitted literature to support specific metrics; however, we have added further measurements of wound healing based on input from the comment period to the Billing and Coding article. For clarification there is not a “local coverage article or LCA,” but a Billing and Coding and Response to Comment articles associated with the LCD. The number of days of SOC required, 4-weeks, has been corrected in the Billing and Coding article. The suggested KX modifier language has been added to the Billing and Coding article.

We disagree with the Alliance objection to the discussion of potential harm associated with CTP. The current research does not adequately address safety which is not required to be proven in several of the FDA regulatory pathways covering these products. The Winkler paper was submitted by stakeholders and several CTP products have published bench studies demonstrating they interact with the extracellular matrix as part of their mechanism for wound healing so is pertinent to the better understanding potential risk of these products. There are published papers that include adverse events related to products, documented infections, allergies, and hypersensitivities and recall of product demonstrating potential harm. This area is also fraught with publication bias as almost all studies are industry sponsored and few will voluntarily report negative outcomes, so publication of risk is potentially underrepresented. Finally, there is a lack of long-term data (>1 year) on most products so the long-term effects are not fully understood, see Comments #19 & #36. We also feel that skin replacement therapy is the appropriate terminology and consistent with published literature.

Specific training requirements and settings for providers is beyond the scope of the LCD as this is determined by residencies, training programs and state scope of practice laws. The LCD requires those providers performing these services have the required training necessary for their credentialing and state scope of practice requirements, see Comment #10.

The Billing and Coding article will retain the information on not otherwise specified codes Q4100 and A4100 to enable a MAC to identify the product used in the claim and educate on how it should be reported. For documentation requirements for additional applications, we disagree with removing this requirement from the Billing and Coding article as it is critical to understand if the wound is responding to the treatment to determine if additional applications are R&N. This language has been modified to “progression of wound closure” to provide further clarification. The tables have been divided based on ulcer type to provide further clarification on evidence for each type of ulcer and missing ulcer type added, see Comment #37.

For discussion of relocation of codes, see Comment #17. For delay in implementation, see Comment #2, for application limits, see Comment #4, for the term adjunct vs advance, see Comment #80, for use of products outside of DFU/VLU, see Comment #7, the definition of recurrence has been removed, see Comment #73, for expansion of ICD-10-CM codes, see Comment #20, for stakeholder engagement, see Comment #80, for disparities, see Comment #3.

AdvaMed comments on the following areas of the LCD: change the allowed frequency of skin substitute applications, process for group reevaluation, implementation timeline and therapy disruption and clarifying the evidence criteria for products seeking coverage under these LCD's. They submit Raspovic 2018 that indicates the number of applications required to heal a wound increases with graft size and wounds up to 10 cm² requires 7 applications while wounds up to 25 cm² require up to 10 applications. They request further clarification on the requirements for additional applications including what is sufficient progression of wound closure. They advocate for additional applications stating that private payers do not have limits or those limits are up to 10 applications and not set a specified time limit. They expressed that this creates additional work for the MACs and burden to the practitioners. They emphasize that any decision making should not result in delays that can impact patient care and recommend upper limit of is 6-8 applications. They encourage a transition to coverage process that does not require LCD reconsideration and the associated delays as well as streamlining this process for all MACs to work together.

Raspovic 2018 is cited in the LCD and additional data has been added regarding application number and wound size. The application numbers of 7 for wounds up to 10 cm² and 10 for those >25 cm² were with the ranges reported but most wounds <25 cm² required 4 applications in this report. For application limits, see Comment #4, for timeline, see Comment #2, for evidence requirements, see Comment #1. MACs are committed to work together on LCD reconsiderations and efforts to facilitate this in a timely manner. The removal of codes from the LCD does allow us to add code changes more efficiently, but does not align with the LCD reconsideration process since these changes would reflect change in coverage based on evidence, see Comment #17. 

Surginex expresses concerns and how the policy may impact patient care restricting access to critically important treatments for wound management and limiting physician choices. They make the following recommendations: explain and clarify the process used to determine the evidence for coverage, include RWE, and extend the time frame for implementation of the LCD to at least 24 months to allow evidence development. They are concerned that the national policy has not followed the NCD process. They expressed concern that this would eliminate the ability to have the authority for coverage under evidence development (CED) which is only applicable to NCDs. They feel that many of the products have homologous function and requiring individual investigation is not necessary. They express that the FDA requires homologous use and since these products are utilizing the same tissue type (e.g., amniotic membrane) they must possess the same original characteristics and have the same donor tissue. Therefore, they feel that the entire class of products should be covered rather than individual consideration. They discuss how RWE can help address healthcare disparities including underserved and minority populations.

Thank you for your comments. For evidence including use of RWE, see, Comment #1, timeline, see Comment #2, for health care disparities, see Comment #3 and thank you for providing supporting literature, for LCD vs. NCD, see Comment #17, for FDA requirements, see Comment #5 and #19, for classification as groups, see Comment #36. Regarding CED, while this decision can only be determined by CMS this pathway has typically been reserved for services in which there is not existing commercial products as compared to those that already have evidence available. 

Royal Biologicals expresses support of an evidence-based approach and recommends an 18-to-36-month timeline to allow in process studies to be completed. They inform they have submitted a protocol for a RCT for Dermal Allograft. They are concerned that the supply chain for the covered products will not be sufficient for demand resulting in supply chain shortages and elaborate on details of the processing and why this may be an issue. They request clarification of clinical study design components used to evaluate for coverage. They ask specific study design questions. They ask if other study designs such as retrospective studies will be considered. They inquire if the MACs will only reimburse the type of wounds treated within the presented studies. They implore MACs to consider impacts to the patient outcome as a result of quickly implementing the policy. They suggest consultation with the FDA in terms of clinical requirements for 510(k) and predicate devices. They inquire if an HCT/P is rebranded will the MAC accept the study with an explanation from the tissue bank the brand name covered by the reimbursement code is the same as that referenced in the study. 

HCT/P coverage is based on evidence for the indication investigated. If an HCT/P is rebranded, the MACs will accept the studies referenced as long as the proprietary processing for the product is the same as that used in the original investigation of the product. In most of these cases the HCPCS code is retired and a new code assigned to reflect the product’s new name. For evidence including use of RWE, see Comment #1, timeline, see Comment #2, for supply chain concerns, see Comment #17, for predicate devices, see Comment #35, for MACs role in study design, see Comments #81 and #37.

The Coalition of Wound Care Manufacturers opens with “we appreciate the efforts being put forward by the Medicare Administrative Contractors (MACs) in issuing this latest draft LCD and LCA and for incorporating many of the recommendations made by the Coalition from previous draft policies” but have additional issues to address. They explain their support for evidence coverage and surprise that coverage was permitted without evidence in the past but have concerns that the draft does not include a clear criterion requiring the data/evidence necessary for coverage. They state that they “the MACs identified that the GRADE methodology was utilized to evaluate the evidence and yet the protocols that were used are not publicly available.” The Coalition recommends that the MACs remove the product-by-product evaluation from the LCD and instead place it in an Appendix or even the B&C article so the entire LCD does not have to be reopened every time new evidence is reviewed. They also request a single and efficient mechanism for manufacturers to submit the evidence for reconsideration. They expressed support of the use of the KX modifier but provide suggested revision to the language to provide further clarity for this requirement. This suggested language includes “Such services qualify for an automatic claims processing exemption by the MAC or Medicare Advantage plan. “Automatic” refers to the manner in which the claim is processed and does not indicate that the exemption itself is automatic. Supporting documentation must be supplied upon request.” The Coalition suggest providing ample time for implementation to ensure patients in the midst of a current episode of care to complete the plan of care. They request confirmation if products identified in Group 2 are covered for both DFU and VLU. They request clarification for evidence requirements including allowing RWE and provide some suggested language:

Preferred Evidence Level: Level 1 Evidence – Prospective Randomized Controlled Study (RCT for DFU OR VLU OR DFU/VLU (in the same study) compared to standard of care. The study must be statistically powered.

Minimum Evidence Level – Prospective Study enrolling patients with DFU OR VLU wounds refractory to standard of care.

Adjunctive Evidence- Real World Evidence enrolling patients with DFU OR VLU wounds refractory to standard of care may be used as adjunct evidentiary support to RCTs and/or Prospective Studies.

Thank you for your support of an evidence-based approach to coverage. Regarding methodology to evaluate literature and address GRADE, see Comment #81 and evidence for coverage, Comment #1. While having to expand coverage through the LCD reconsideration process creates additional work there is not a feasible alternative as the coverage decisions are based on evidence which mandates going through the LCD process, see Comment #17. A process to outline how this will flow is not appropriately placed in an LCD but will be part of the educational process once the LCD is finalized.

For KX modifier and changes made to application frequency, see Comment #4. Use of more than 4 applications require an attestation from the provider that requirements specified in the medical policy have been met. This attestation can be provided at the claim level using the KX modifier. In average ulcers will heal with 4 applications on an episode of care. Use of >4 applications require an attestation from the provider that requirements specified in the medical policy have been met. Documentation of progression of wound closure under the current treatment plan and medical necessity for additional applications should be recorded for each additional application. In absence of an attestation indicating that medical policy requirements leading to additional applications have been met, denials of the additional applications will occur. MACs have no jurisdiction over how Medicare Advantage plans may utilize this.

We appreciate the clarification for evidence suggestions; however, we are cautious not to be prescriptive in study design as there are multiple different potential ways to conduct research and achieve high certainty of evidence, see Comment #1 and for MACs role is suggesting study designs, Comment #81. We agree it is necessary to delay implementation to ensure no disruption to care, see comment #2, and coverage is based on evidence per indication, see Comment #37. 

RestorixHealth comments on the positive impacts CTP have made in the management of wound care an improvement in patients’ health and quality of life as a result. This is driven by a variety of different evidence types (level I RCT, Level IV, claims data) as detailed in the letter. They feel that the manufacturers package inserts, RCT protocols and peer-reviewed retrospective evaluations demonstrate weekly or biweekly applications are the best practices and the minimum should be 8 applications in a 12-week episode of care not 4. They explained that the ability to utilize a KX modifier is helpful and request further clarity in its use as well as expected documentation. They provide suggestive terminology to provide clarification on demonstratable progression of wound closure. They inquire to how multiple wounds being treated at the same time will be managed and if this should be identified with the KX modifier as well? They request a process that does not utilize appeals. They request expansion of the ICD-10-CM list to include non-pressure ulcers with muscle or bone involvement and recommended ICD-10-CMs are provided. They request efforts to ensure that diagnosis not related to DFU or VLU are accidentally denied by claims edits. They suggest removal of the ABI requirement and replace with alternative noninvasive technologies. They also request removal of the exclusion for uncontrolled diabetes. 

Thank you for your comments. For application limits and frequency, see Comment #4, for ICD-10-CM expansion, see Comment #20, we agree with suggestion for ABI, see Comment #21, we removed uncontrolled diabetes from exclusion, and additional terminology to clarify progression of wound closure and use of KX-modifier has been added to the Billing and Coding article. Thank you for the submitted literature, all literature addressing DFU/VLU is represented in the LCD except review papers, commentaries and cost-analysis which are not used for LCDs.

Tissue Regenix comments that their product DermaPure typically requires 1 application shifting use to inpatient settings and use in diabetic limb salvage cases and highest risk patients. They have been compliant with ASP reports with consistently low cost. While single study on DermaPure was included in the LCD with conclusion of insufficient evidence additional manuscripts were excluded and submitted with the comments.

The single application product seems promising. While current evidence, which has been added to the LCD, is insufficient for coverage, we look forward to additional investigation which can be submitted through the LCD reconsideration process. 

Biostem Technologies states the value of these products and that the LCD shifts to an arbitrary small subset of products that generate a “skin scaffolding” based solely on a CPT^® code descriptor. They state the LCD fails to provide any evidence that this narrow class of covered products has greater clinical utility than the 361 HCT/Ps they intend to exclude. They feel that the LCD is fundamentally flawed. They request clarity on covered versus non covered products and the support for RWD/RWE.

They request defining a skin substitute as functioning like “scaffolding for skin growth” is contrary to FDA regulatory framework for 361 HCT/P. They elaborate on the regulatory process for HCT/P and homologous use. The state there is not a reason explanation of why the “skin scaffolding” limitation was adopted or cite evidence in support of adopting “skin scaffolding” requirement. They state that the proposed LCD does not identify new material or information that undermines the current LCD's conclusions that these products promote healing. They state the only support for scaffolding is based on the AMA CPT^® code definition. They explain that only RCT were utilized despite that MACs said at open meeting that multiple pathways or opportunity for coverage would be considered. They request Vendaje and Amniowrap2 be covered based on “FDA’s Tissue Reference Group to these comments. The letter constitutes satisfactory evidence that VENDAJE and AmnioWrap2 meets FDA regulatory requirements of skin replacement surgery for wound care of diabetic foot ulcers and venous leg ulcers.” They provide a table of clinical and scientific data to support their products consisting of presentations, submitted papers and 2 trials currently underway. 

The proposed LCD is based entirely on evidence and not related to FDA regulatory processes. The existence of an HCT/P does not equate coverage and nor alone meet the definition of medically reasonable and necessary, see Comment #5. Currently only 1 LCD allows coverage of HCT/P and this MAC has determined the LCD is outdated as it was developed prior to the majority of the products on the market today and without evidentiary basis, see comment #16. The proposed LCD does not evaluate products for function as scaffolding, but effectiveness in wound healing, see comment #16. Due to the unique properties of the different products, they cannot be classified as a group, see comment #36. For evidence requirements, see comment #1. The evidence to support these products is unpublished and if peer-reviewed published literature is available it can be submitted through the LCD reconsideration process for consideration for coverage.

MASS Coalition submits comments stating that Medicare has historically covered these products and “fails to provide a reasoned explanation” such as new evidence or rationale to change from existing coverage. They state that the LCD is flawed because they arbitrarily treat products differently without explanation exemplified by placing a product in Group 2 (covered) while placing another virtually identical product in group 3 (non-covered) despite existing evidence to support coverage of both products. They state that not covering by classification is not rationale. The commenter explains a previous LCD allowed coverage based on FDA classification, but this LCD does not. They also provide examples of current LCDs classification into groups for coverage decisions. They recognize the current LCD requires classification based on each product’s evidence rather than as a class. The feel the MACs do not have a reasonable explanation to support this change. They say the MACs did not follow appropriate process in issuing the proposed LCDs. The commenter addressed concerns regarding the definition of skin substitute, role of scaffolding, and role of FDA regulatory processes. Mass Coalition claims that MACs determinations for covered product is arbitrary. They state that the same 361 HCT/P products under different names appear in both Group 2 and Group 3 of the Proposed Article. They provide an example of GraftJacket and AlloDerm. They state that products of same class should be covered if there is evidence for a similar product for effectiveness. They state some products cannot prove they function as a scaffolding. They state a covered animal xenograft is rejected by the human host. They claim there are products in the non-covered group with evidence for safety that are not covered specifically Mirragen, Talymed and Kerecis.

They object to the application limits sharing concerns that many of the covered products were not studied in large wounds, question the interpretation of the Armstrong study for application limits, and contradicts some products labeling.

The letter concludes expressing concern the LCD will cause harm to vulnerable populations. They state that requirement to receive care from specialist for management of systemic illness can result unacceptable delays. They state the ICD-10-CM codes are too limited and exclude ankle and lower limbs. They suggest UPIC and RAC have been applying coverage standards from the 2023 and proposed draft in current claim reviews inappropriately. 

MACs are required to cover services determined as R&N as described in the Chapter 13 of the PIM. Since the revision of Chapter 13, MACs have developed LCDs based on evidence. As MACs modernize LCDs, multiple previously covered items from other services that lack evidence to support R&N criteria have been removed or limited, so this process is not arbitrary or limited to skin substitutes. The only remaining current LCD that permits coverage for HCT/P is not in line with 21^st Century data driven policy, see Comment #17. The decision to adopt an evidence-based LCD is not arbitrary but driven by clear needs for evidence-based guidance to ensure optimal care and outcomes for Medicare beneficiaries and that MACs comply with R&N requirements for coverage.

We disagree that the policy classifies products as arbitrary and defend the policy’s rationale application of evidence-based coverage decisions, see Comment #35. The commenter does not provide an example of any product that was placed on the non-covered list despite high certainty supporting evidence. The commenter states products should be considered as a class, rather than individual products. The decision to consider products individually arose from logical outgrowth from stakeholder input, literature cited in the LCD, and societal guidance. These products are unique due to proprietary processing and therefore, considered individually, see Comment #36. Additionally, this aligns with the requirements for coverage decisions based on evidence as required to meet the definition of R&N per Medicare.

We challenge the statement that the MACs did not follow the process for LCD development, see Comment #80. Many stakeholders have commented in writing a contradictory view as they acknowledge the proposed LCD addresses many of the concerns expressed through the 2023 listening sessions, open meeting and stakeholder meetings and supports that the proposed LCD was a logical outgrowth derived from stakeholder engagement in the process.

For explanation of definition of skin substitute, role of scaffolding, FDA, and classification of products as a group see Comments #5, #16, #36 and #87.

As explained in Comment #35 the process for coverage decisions in the LCD is rationale, transparent and utilize nationally recognized standard tools to evaluate evidence equally. It is essential to understand the policy is based on evidence for the individual and unique products. GraftJacket is supported by evidence, while AlloDerm does not have supporting evidence for use in DFU/VLU. As explained in the other comment letter some manufacturers prepare tissue for multiple other entities after which proprietary processing takes place bringing the unique properties and variations to the products. If a product has a letter from the tissue bank confirming they are indeed identical and an explanation as to why they have different HCPCS codes they would be considered equal for coverage. Coverage decisions are not determined by a definition of scaffolding, see Comment 36. Coverage is based on evidence for wound healing only. The commenter provides no supporting evidence of graft rejection or complications for the mentioned animal xenograft nor has that been found in any of the reviewed literature or other stakeholder input. The rationale for why the evidence is not sufficient for Mirragen and Talymed, are within the LCD in both the evidence review and tables. Kerecis has been moved to coverage based on submission of new literature, see Comments #42 & #45. Additional understanding of how evidence is used for coverage determinations can be found in Comment #1.

The intent of the LCD is to improve health outcomes for Medicare beneficiaries by evidence-based coverage for products with high certainty of effectiveness. For application limits and frequency, see Comment #4, for challenges with product labelling, see Comment #27. For further discussion on disparities and access to care, see Comments #2 and #17. The policy does not mandate care from specific specialist, see Comment #67. For discussion of use of product outside DFU/VLU, see Comment #7 and for ICD-10-CM codes, see Comment #20. Current and individual claim adjudication are not within the scope of the Proposed LCD. The concerned party should address the concerns with the individual MAC, UPIC, or RAC. 

International Tissue request that AmniPly be added to the covered list based on 361 HCT/P. Supporting documents include the FDA TGR letter for this product, instructions for use and a meta-analysis that concludes DFU can benefit from dehydrated human amnion and chorion allograft. They request that if evidence for individual products is required that an 18-24 months “phase-in” period be allowed or “grandfathering policy” to allow products currently covered to continue coverage.

Thank you for your comments. The existence of a HCPCS code or approval via an FDA regulatory pathway does not equate coverage for Medicare where an item or service must meet the definition of R&N for coverage, see Comment #5. Products of the same class are not equal, see Comment #36. For delay in implementation, see Comment #2. Thank you for your submission of the meta-analysis this has been added to the LCD, see Comment #36.

The Musculoskeletal Transplant Foundation is a nonprofit tissue bank aimed at safe and high-quality product. They support coverage of AmnioBand and AlloPatch and full clinical dossiers are provided. They disagree with the application limit of 4 and recommend increasing the initial applications to 6 before the KX modifier is applied. They recommend additional ICD-10-CM codes to be added to the Billing and Coding article and list provided. They also explain that the descriptor for AlloPatch is incorrect and the HCPCS has corrected this by removing Matrix HD for Q4128 which is now separate. 

Thank you for your comments and support of the policy. For application limits and frequency, see Comment #4, for ICD-10-CM code, see Comment # 20, and the descriptor for AlloPatch has been corrected. All supporting literature is included in the LCD.

A letter from Dr. Tettelbach representing Wound Care Plus, LLC and mobile wound care providers express concern that the LCD limits access to patients who need this modality and this is dangerous. He states the standards used within the policy are outdated and needs a wound care advisory panel. He states eliminating this modality from pressure ulcers/injuries and stalled surgical wounds is not appropriate. He states the opportunities for stakeholder interaction did not allow ample time to fully express their concerns. He states: “I understand the Medicare Trust Fund is hemorrhaging money due to inappropriate LCDs over CTP/CAMP use. However, this approach is wrong and does not have to be this way.” He suggests “appropriately revamping the reimbursement and governing the approvals of grafts to those who report their ASPs” as a solution. A consensus document “Best practice for wound debridement by Mayer et al. and letter to the editor “A review of the proposed draft CAMPs LCDs compared to evidence-based medicine: a letter to the MACs for consideration” published in the June 2024 edition for the Journal of Wound Care” were submitted.

While the LCD does not expand scope to indications outside of DFU/VLU that does not imply lack of coverage for R&N care for wounds outside of DFU/VLU, see Comment #7. For access to care, see Comment #17. Reimbursement is beyond the scope of the LCD. For stakeholder engagement, see Comment #33. The consensus document is added to the LCD and the letter to editorial has been read, but not added since it is not peer-reviewed. This letter questions the policies, proposed application limits and frequency and duration and recommends inclusion of RWD for study design. For responses to these concerns, see Comments #1 & #4. Clarification of documentation requirements have been done to the Billing and Coding article as requested, see Comments #4, #21, #22 and #29. For ICD-10-CM codes, see Comment #20, for Class 3 suppression, see Comment #81. 

Convatec comment letter expresses concern that stakeholder input was not considered in the development of the policy. They have concerns regarding the evidence evaluation process and conclusion within the LCD, such as limiting to only RCTs and ignoring other valid sources of relevant information. They state that InnovaMatrix predicate device is supported by 6 RCTs and should be sufficient for coverage and the MACs are dismissive of the FDA’s 510(k) clearance process. They state that the MACs are dismissive of physician judgment and limiting products will have an adverse impact on access to care which will affect minority populations disproportionately. They state products with HCPCS codes should be covered and not doing so adds an unclear hurdle to the Medicare population and innovations. They feel that requiring costly RCT and going through the reconsideration process is unnecessarily burdensome and that the 4-application limit is not justified and a higher limit should be considered. They state that the LCD criticizes the Armstrong Medicare database report for lack of blinding and randomization and that propensity matched cohorts are sufficient to address this concern. They also state that some of the guidelines from societies are based on older literature and does not include all products. They include “With respect to InnovaMatrix, it is a unique product in that it is the only skin substitute device that utilizes porcine placental material and the TriCleanseTM process designed to reduce immune response by limiting residual cell components.”

This policy is based entirely on evidence and not on FDA pathways, for FDA requirements, see Comments #5 & #19. Predicate devices are not sufficient for coverage, see Comments #36, #42 & #54. In the comment letter it is mentioned that InnovaMatrix is unique and the only device to go through the Tri Cleanse process- this is exactly the point of requiring evidence for individual products because proprietary processing creates properties unique to each product that needs to be investigated individually to ensure efficacy, outcome improvement and safety. They are not identical to the predicate device.

The policy does not mandate RCT, see Comment #1 for evidence and role of RWD. For access to care and disparities, see Comments #2 & #17, for stakeholder engagement, Comment #33, rationale for coverage, Comment #35, and application limits, Comment #4, delay in implementation, see Comment #2, innovation, see Comment #48.

We disagree that retrospective propensity matched cohorts address concerns related to lack of randomization and blinding. The retrospective design of the database creates multiple opportunities for inaccurate reporting (missing data points, selection bias, lack of outcome data, lack of a control group that receives the same intervention, lack of standardized protocols, variable in inclusions/exclusions, reporting, measurements, risk of bias and others) that established concerns in study methodology and why retrospective studies are considered low quality.

We recognize that not all products were included in the societal guidance and one of many reasons that we conducted independent reviews of each product to ensure every product with individual consideration for coverage based on evidence.

Axolotl Biologix explains that within the policy it states no literature was identified for their product; however, there has been published literature which is submitted with the comments. They also have presented at several trade meetings and have had technical presentations on their products Axolotl Graft and DualGraft. They request a delay in implementation of 18 to 24 months to conduct further research which they already have planned.

Thank you for your comments and the inclusion of submitted literature which include case reports, a review paper on amnion-derived membranes, a paper related to use in Mohs surgery, a bench paper, and an unpublished conference report. We have updated the section of the LCD with published literature related to DFU and VLU but this is insufficient for coverage. If additional literature is developed this can be submitted through the LCD reconsideration process. For a delay in implementation, see Comment #2.

Representatives for Senators Tuberville and Britt offices comment that the draft LCD is a significant improvement over previously proposed LCDs because of its evidence-based approach and the Senators hope that we retain much of the draft in the final LCD. They encourage that we consider stakeholder input to cover products that have not only RCT, but favorable RWE as well as encouragement to provide more specific criteria for acceptable study design and a delay in implementation to allow adjustments to the coverage changes. 

Thank you for your comments and we share the concern for Medicare beneficiaries impacted by severe chronic wounds. The LCD does not require RCT and we consider peer-reviewed published RWE. For evidence utilization for policy, see Comment #1, for delay in implementation, see Comment #2, for health care disparities, see Comment #3. 

A comment letter from Clinical Wound Care Committee of the US Foot and Ankle Specialists and Affiliated Doctors expresses concern with the drastic decrease in the number of covered products and limiting options for providers. They are concerned that the application limit should be 7 not 4. They feel that the LCD conflicts with the International Guidelines from the International Working Group on the Diabetic Foot (IWGDF) support the use of advanced therapies, including placental-derived products, when standard care fails. They feel that the LCD will negatively impact patient care and suggest collaborating with experts to develop more evidence-based guidelines.

The IWGDF Guidelines are included in the LCD under the section Societal Input. This explains that the recommendations from IWGDF from the GRADE analysis they conducted that determined a weak recommendation based on low quality evidence. The guidelines are consistent with the LCD’s evidence-based assessment of the literature; therefore, we do not agree that there is a conflict. For application limits, see Comment #4, for disparities and access, see Comments #2 & #10, for evidence-based rationale, see Comment #35, and for stakeholder input in the LCD, see Comment #18.

MedCentris, a wound care delivery company, report that they recently completed a real-world retrospective analysis of Medicare patients receiving CTP which was accepted 6/4/24. They provide a summary of the report in the letter. This literature is unique as it specifically addresses application limits not addressed elsewhere in the literature. They ask for this newly published literature to be utilized for consideration to support an increase in application limit as well as removing criterion for exposed muscle bone or tendon which was common in this population, they report on. They also want to ensure that uncontrolled diabetes is not an exclusion, inclusion of RWD and retrospective studies.

Thank you for comments and initiative to provide evidence-based guidance for application frequency and address this gap in the current body of evidence. The submitted paper has been added to LCD and utilized for the change to application limit from 4 to 8, see Comment #4. While the inclusion of patients with exposed bone or muscle is valuable information the very small sample size of this population is not sufficient to draw definitive conclusions on the role of these products in that population. Address uncontrolled diabetes, see Comment #55 and for RWE, see Comment #1. 

Imbed Bioscience state they appreciate the movement to a more evidence-based approach however have recommended changes. They feel that the requirements for evidence are burdensome and unnecessary for products under the510(K) FDA regulatory pathway, lack clarify and need to allow an in-phase period. They expressed concern with the policy impacting fair access and innovation. They encourage acceptance of prospective peer-reviewed published data for consideration for coverage. They state non-coverage of Microlyte Matrix limit choices for those with religious, cultural, or ethical objections to human/animal-based CTP. They also expressed concern regarding the 4-application limit. They explain there is a published prospective pilot study on this product and a recent poster presentation.

Utilizing an evidence-based approach ensures products being utilized as skin substitute grafts/CTP, as defined in the LCD, are equally considered under this policy, including synthetics. Therefore, we do not agree that Microlyte Matrix is inaccurately grouped. We appreciate the evidence that is currently available on this product (Manning 2020) but as discussed in the evidence review section of the LCD this is not sufficient for coverage. If additional evidence is developed this can be submitted through the LCD reconsideration process. We cannot consider poster presentations and only utilize peer-reviewed published literature for coverage. For FDA regulation and evidence requirements, see Comments #1, #5 & #19. For classification of products, Comment #36, for access concerns, Comment #17, for innovation, Comment #48, application limits, see Comment #4, and delay in implementation, see Comment #2.

“Integra LifeSciences supports the LCD’s limitations on the number of applications but urges more clarity on the approval process for additional applications. We continue to applaud the use of evidence-based medicine to make decisions on the coverage of CTP’s.” They encourage that companies that have ongoing trials receive provisional payment while studies are being conducted and request AmnioExcel be included.

Thank you for your support of an evidence-based approach for coverage. For more discussion on provisional payment see Comment #22. The evidence on AmnioExcel is reviewed in the LCD and not sufficient for coverage.

Curitec Services, a wound care company, request MACs to implement stricter requirements and oversight for the use of Cellular and/or Tissue-Based Products (CTP) in wound care, including evidence of proper wound preparation and cost-effectiveness considerations for repeated applications. “We often see providers using CTP week after week after week with very minimal improvement. Often, they are not meeting the requirements for coverage indications (appropriate wound bed preparation) and have often performed sub-standard care (for example no advanced dressing may be used prior to attempting CTP). There should be some mechanism to require that the provider provide evidence of good wound bed preparation and an attempt to control bacteria and biofilm prior to initiation CTP. While it says previous treatments and the failure should be documented. But there is a large difference between providing gauze and tape (and failing) and providing collagen and super absorbent dressings with an aggressive wound cleansing program.” They are also concerned for clear necessity for repeat applications. They recommend “it should also consider that a less than X% change from baseline is a very expensive treatment for relatively no changes.”

Thank you for your insightful comments on wound care practices and CTP utilization. We share your concerns about ensuring appropriate use of these advanced therapies while providing access to effective treatments. The LCD requires documentation of failed prior treatments before initiating CTP. We will continue monitoring usage patterns and may consider additional safeguards in future updates if needed.

To further add in this effort proper preparation of wound bed prior to CTP is outlined in the LCD under Covered Indication #3. Clarifying language for documentation of wound healing progression has been added to the Billing and Coding article. To receive repeat application there must be documentation of failed or stalled wound as defined in the LCD Covered Indication #4. The precise mechanism for the wound care is beyond the scope of the LCD which is on the products being used for skin substitute graft/CTP. 

The Wound Care Collaborative Community (WCCC) comments with “recommendation to consider a wider range of valid, evidence-based clinically relevant and patient-centered endpoints for wound care in addition to total wound closure as indicators of safety and efficacy when evaluating the quality and outcomes of these studies. This work is based on the clinical wound care community concerns for some time about the lack of a sufficient number of endpoints to address issues important to patients and the various aspects of the wound healing process. The WEF-CEP initiative identified, evaluated, and confirmed 15 clinically meaningful and/or patient-centered endpoints for wound care through a process agreed upon in collaboration with the FDA, by surveying both clinicians and patients and evidence research. We encourage you to consider the 15 priority wound care endpoints identified as you evaluate the evidence presented by the manufacturers of those skin substitutes considered experimental and investigational in the proposed LCDs/LCAs.”

Thank you for your comments and contributions to evidence-based medicine with your work on more specific outcome measure for wound. These type of data points can further enhance further research and provide greater standardization in studies. We have added the 3 papers to the LCD under Societal Guidance under WCCC and reference within LCD as a source to consider for future study design. Additional language is added to the Billing and Coding to provide clarity on documentation of wound healing that utilize several of these measures. The LCD focus in on skin substitute graft/CPT products so requirements for any specific tools for wound preparation is outside the scope of the LCD.

Duperon Wound LLC advocates for coverage of extracellular matrix (ECM) skin substitute products in treating chronic venous ulcers in a nursing home patient. The commenter, a wound care specialist, describes cases in which severe, persistent leg wounds were successfully healed using ECM products after traditional wound care failed. The comment letter aims to demonstrate the superior efficacy of ECM products in complex wound management and to advocate for their broader acceptance and application in the LCD.

Thank you for your comment. We appreciate your commitment to patient care. Peer-reviewed journal articles were not submitted, but rather individual case studies of patients treated by the commenter. While the case studies provide valuable insights into the potential benefits of extracellular matrix placental amniotic membrane skin substitute products, it does not meet our criteria for evidence to warrant coverage. Single-patient case studies are considered low-level evidence in our evaluation framework, and the lack of a control group or randomization makes it difficult to attribute improvements solely to the ECM product. 

Both commenters expressed concern that the proposed LCD could eliminate coverage for over 200 skin substitute products, including many made from amniotic membranes used to treat chronic wounds such as diabetic foot ulcers and venous leg ulcers. 

Thank you for your response. The LCD aims to ensure that only scientifically supported skin substitute grafts and CTP are covered, enhancing healthcare outcomes for Medicare beneficiaries. Regarding the concern about the number of applications, the LCD allows for up to 8 applications within 16 weeks which provides flexibility aimed to accommodate patients who may require more treatments to achieve healing.

The LCD also emphasizes individualized treatment plans and comprehensive patient assessments to tailor treatments to each patient's unique condition, aligning with the commenters’ advocacy for personalized care.

While the LCD does limit coverage to certain product types, it includes a range of non-autologous human, non-human, and biological products applied as sheets. This approach focuses on treatments with proven efficacy to ensure the best outcomes for patients. Also, see response to #4.

The commenter recommends revising the LCD language to include hyperspectral imaging devices as an additional diagnostic tool for assessing wound healing potential. He suggests adding this technology to the list of "acceptable benchmarks" for predicting ulcer healing, citing its ability to produce spatial maps of deoxy and oxyhemoglobin. The commenter argues that hyperspectral technologies offer advantages over some other mentioned technologies and could help clinicians better select optimal patients for skin replacement products. 

Thank you for your comments multiple modalities may be beneficial in assessing wound healing potential. While the LCD requires documentation of ulcer healing, the modality to perform these measurements is out of the scope of the LCD which is on skin substitute grafts/CTP products for DFU and VLU. If there is peer-reviewed published literature demonstrating improved outcomes or patient selection for skin substitute grafts/CTP specifically related to hyperspectral imaging an LCD request can be made to address this specific area of wound care, Comment #12.

Ohio Life Science comments that they appreciate the change to an evidence-based approach as compared to previous proposed LCDs. They request inclusion of RWE especially to address health care inequities. They also request more detail on the criteria for evidence for coverage. 

Thank you for your comments. Please see Comment #1 for the role of evidence including RWE.