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

A provider commented their concern that the products discussed in the LCD are not separated by skin substitute graft/cellular and tissue-based products (CTP) type. It is stated in their letter that these products vary in what they can provide the patient. They compare the products Kerecis and Grafix as being unique and different, not the same type of product. No literature was submitted with this comment.

Thank you for your comment. Medicare Administrative Contractors are required to base their coverage determinations on scientific evidence. The proposed LCD provides a summary of evidence and analysis of evidence to support our coverage decisions. Providers may submit peer reviewed full-text articles to support coverage for skin substitute grafts/CTP via the reconsideration process outlined on our website once the LCD is finalized. There are a variety of skin substitute grafts/CTP with sufficient evidence for coverage that the provider may choose from to ensure autonomy for the provider to select the products that are most appropriate for the patient. Please refer to response to comments #10, #20, and #56 for information on the evidence process.

Several comments were received with concerns regarding the restriction of use of skin substitute grafts/CTP for indications outside the scope of DFUs and VLUs. One commenter specifically asked if products in the non-covered list could be used for indications other than DFU or VLU if they are FDA approved for those indications.

Thank you for your comments. Implementation of this LCD will not restrict use of these products for conditions other than diabetic foot ulcers and venous leg ulcers. Services outside the scope of the LCD must adhere to Medicare’s reasonable and necessary (R&N) criteria.

A comment was submitted regarding the product Theraskin. The commenter feels that it is an error to categorize this product as ‘covered’ in our LCD and is concerned that the use of this product is not supported by high-quality, non-biased, peer-reviewed, published evidence.

Thank you for your comment. Medicare Administrative Contractors are required to base their coverage determinations on scientific evidence. The coverage decisions for this LCD were made based on the best evidence available at the time. Local Coverage Determinations clearly identify what services are covered and what services are non-covered. Providers may submit peer reviewed full-text articles related to any skin substitute grafts/CTP via the reconsideration process outlined on our website once the LCD is finalized.

A comment was submitted expressing concern about providers using “covered” products (that have high quality peer-reviewed studies to support safety and efficacy) in a non-payable manner as dressings. The commenter suggested that the “Coverage requirements for skin substitute graft” section should clearly state that the product must be put on securely with sutures and left in place to stay. The commenter also suggested that the “Limitations” section should clearly state that any product that is removed and replaced with any regularity is a dressing and is not considered a skin sub. Lastly, the commenter recommends that applications be limited to 2.

Thank for your comments. Applications are addressed in the LCD and response to comments #12. Sutures are not required to secure the products. However, while the product is not intended to be removed, occasionally there may be a medical reason to do so. Reference is also made to the AMA CPT codebook regarding Skin Replacement Surgery related to Skin Substitute Grafts indicating that the graft is anchored based upon the preference of the provider.

A comment was received in agreement that 510k approval alone is not sufficient supporting evidence for use of a product. The commenter specifically mentions Theraskin but did not submit any supporting evidence. They go on to state they feel that most of the studies listed in the LCD are not “quality” studies. They suggest that products having not gone through the full FDA process should not be covered otherwise there is no way to ensure the criteria of the Social Security Act have been met.

Thank you for your comments. FDA approval/clearance is not sufficient for Medicare coverage alone. Section 361 of the PHS Act bypasses the FDA vetting process because it is a self-determination by the manufacturer that the product fits within the definitions set forth in 21 CFR 1271 et. seq. The manufacturers of these products are self-registered under Section 361 with the FDA and self-determine whether their products meet the HCT/P criteria of Section 361. Even FDA acceptance and listing of this registration does not constitute a finding that the product complies with applicable rules and regulations or that the HCT/P is licensed or approved by the FDA. See, 21 CFR 1271.27(b). If products fall outside the scope of this regulatory frame, they are considered to require FDA approval and evidence that they are safe and effective under Section 351 of the PHS Act. For Medicare coverage, a product or service must be reasonable and necessary for ulcer or wound treatment in this instance. This requires a review of the literature-based evidence supporting the product.

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. Medicare Administrative Contractors 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 reasonable and necessary is considered to ascertain if coverage is appropriate. If these products are being used and billed as skin substitute grafts/ CTP, the evidence must demonstrate that function to be considered for coverage.

Many comments were received requesting the revision or removal of the Ankle Brachial Index (ABI) requirement for standard of care (SOC). There is concern that the ABI measurement can be falsely elevated and that using this measurement as a requirement to determine care is outdated. There are comments requesting more vascular perfusion testing options be put in the LCD such as toe-brachial with waveform analysis, transcutaneous oximetry, skin perfusion pressure, or near-infrared spectroscopy. Suggested language submitted states: “… 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.” One commenter suggested that there should be a lower limit of an acceptable ABI value included in the LCD. The commenter expressed concern that without the lower limit providers may put skin substitutes on wounds where it would not be beneficial, such as situations where there is no blood flow or adequate oxygenation.

Thank you for your comments. The covered indications in the LCD are to ensure that an appropriate physical examination, as determined by the provider managing the patient, is performed and that SOC treatment has been provided for at least 4 weeks. The term comprehensive patient assessment is used to emphasize that it is a physical examination that must be completed. As noted in the covered indications, ulcers must have failed to respond to SOC for at least 4 weeks.

We agree there may be situations in which alternative tests to ABI may be clinically indicated. Language regarding vascular assessments has been incorporated into the LCD. We strive to provide clear language without being overly prescriptive so to not interfere with provider judgment or add additional burden.

A comment was submitted requesting that the layout of the covered indications be changed to separate the indications for non-infected DFU and non-infected VLU.

The commenter also indicated that the following Notice contradicts the initial coverage guidance statements: “Notice: Services performed for any given diagnosis must meet all the indications and limitations stated in this LCD, the general requirements for medical necessity as stated in CMS payment policy manuals, all existing CMS national coverage determinations, and all Medicare payment rules.” They indicate that it cannot be applicable based on the initial statements made under “Coverage Guidance” under “History/Background and/or General Information” of “Application of skin substitute grafts/CTP for ulcer care indications other than DFUs or VLUs are not addressed by this LCD.”

Thank you for your comment. The indications for coverage are set forth in the LCD with clear distinction between DFUs and VLUs. We do not feel there is a benefit from separating covered indications even further into non-infected vs infected ulcers. 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 skin substitute grafts/CTP for DFUs and VLUs so specific measures regarding wound bed preparation are not within the scope of the policy.

The Notice language you reference is the standard language that is contained in LCDs and is a recognition that all Medicare covered services must comply not only with the LCD, but with CMS and Medicare policies and payment rules. Only the services addressed in the LCD would need to comply with the LCD, but any services outside the scope of the LCD must also comply with CMS and Medicare policies and payment rules.

A comment was submitted suggesting that in their opinion, after years of being in wound centers, this LCD would prevent many patients from healing, leading to many complications increasing the cost to our health system. They suggest that if anything, developing a better payment system will be more efficient in preventing abuse while continuing to give patients the ability to receive top treatments.

Thank you for your comment. This policy only relates to the medical necessity of skin substitute graft products, not payment. Reimbursement and payment are outside the scope of this policy. The LCD distinguishes between those products with peer-reviewed published evidence of wound healing and those that lack such evidence. This drives providers and beneficiaries to utilize covered products that heal wounds and improve outcomes thus preventing abuse.

A commenter indicated that they have seen multiple applications heal and change the lives of patient's numerous times. They believe that implementing changes such as the number of distributors or the number of applications is a huge disservice to the Medicare population who desperately need this treatment.

Thank you for your comment. Medicare Administrative Contractors are required to base their coverage determinations on the preponderance of publicly available peer-reviewed literature evidence. The proposed LCD provides a summary of evidence and analysis of evidence to support our coverage decisions for each product.

Comments were received requesting the MAC to consider retrospective studies and additional levels of evidence in its analysis for product coverage. They request clarification on the clinical trial criteria requirements and definitions of high and low risk in the data analyses.

The Local Coverage Determination (LCD) evidence review is a critical process that seeks to ascertain the reasonableness and necessity of health interventions for a specific disease. MACs evaluate the relevant literature in the public domain and based on the certainty of the authors’ conclusions, render determinations for coverage. This approach is designed to ensure that health outcomes of interest can be attributed to the intervention in a patient population applicable to Medicare beneficiaries. Importantly, the LCD is not prescriptive about the study design required to meet this standard, recognizing that various methodologies and combinations thereof can yield the necessary information.

While randomized controlled trials (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. Risk of bias refers to the possibility that study design, conduct, or analysis of a study has introduced systematic errors or deviations from the truth, which can distort the study’s findings. This distortion reduces validity and confidence (i.e., certainty) that differences in measured outcomes are attributable to the treatment under investigation. A body of evidence based on studies with a considerable risk of bias (e.g., retrospective studies or case series) would generally be considered weak or unreliable evidence. (Page, 2018). In principle, rankings of research design have been based on the ability of each study design category to minimize these biases. The primary criterion for methodological strength or quality is the extent to which differences between intervention and control groups can be attributed to the intervention studied. In determining whether an intervention is reasonable and necessary, it is required for MACs to assess the literature confirming that the outcomes of interest are attributed to the intervention of interest resulting in a reported effect size with a high degree of certainty. For the purposes of this LCD, this assessment is challenged by the variations of products and study designs such that the most equitable way to evaluate each product's effect is by the RCT outcomes.

Real-world evidence (RWE) and real-world data (RWD) describe data that is collected outside the realm of clinical trials from various sources such as medical records, claims data, product or disease registries, and other data gathering sources like digital health technologies. While comparative effectiveness research can be conducted from real world data sets, there are many challenges to overcome, including controlling for confounding variables, accounting for missing data, reducing bias, and ensuring adequate group sizes. A benefit to RWE and RWD is that this data can offer valuable insights into patients excluded in clinical trials and provide evidence for the efficacy and safety of a product in an actual clinical setting. Therefore, RWE and RWD can be important evidence to consider because it can fill in gaps in the evidence and address the use of an intervention or technology in a real-world setting. This contractor included alternative study designs as part of the evidentiary basis for the determinations. Specifically, clinical studies of any design and adequate sample size whose results corroborated an RCT were considered confirmatory allowing for coverage.

Page MJ, Boutron I, Hansen C, Altman DG, Hróbjartsson A. Assessing risk of bias in studies that evaluate health care interventions: recommendations in the misinformation age. J Clin Epidemiol. 2018 May;97:133-136. doi: 10.1016/j.jclinepi.2018.01.004. Epub 2018 Jan 17. PMID: 29352995.

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

Thank you for your comment. The existence of a HCPCS code or approval via FDA regulatory pathway does not translate to Medicare coverage. The item or service must satisfy reasonable and necessary standards for coverage. The 2024 coverage policy 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 that function to be considered for coverage.

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 was 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, 15273, 15274, 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.

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 28 papers covering 34 products with published data on application frequency and can be found in the evidence summaries for the individual products. This ranges from 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 the number of applications. Some studies report means while others report averages. Duration of time was also variable, so we cannot pool this data. However, 22 of 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, stakeholder, provider, and societal input emphasized the need for greater than 4 applications for larger, more complex wounds. Additional literature demonstrates larger wounds were more likely to need more applications (Raspovic, 2018) and 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 (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 small portion of overall ulcers.

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.

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 16 weeks based on literature provided during the open comment period allowing providers greater discretion on frequency of applications based on the needs of the individual patient.

The additional documentation requirements for greater than 4 applications have been removed as documentation should be completed for any additional application. 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 there are concerns with overutilization of skin substitute grafts/CTP products. It is the responsibility of the MAC to ensure access to reasonable and necessary 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 related billing and coding article has expanded instructions on the use of the KX modifier. Billing and coding instructions have been clarified to include: 1-4 applications no additional steps are necessary, using 5-8 applications requires the addition of the KX-modifier 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 the use of the KX modifier can provide maximum flexibility to providers caring for this challenging population, while ensuring appropriate care and payment for the Medicare beneficiaries we serve.

A comment was submitted regarding the instructions in the corresponding billing and coding article regarding box 19. The commenter questioned if the instructions for box 19 should be used on all claims regardless of the HCPCS code being listed on the ASP drug file. Additionally, the commenter asked if this instruction was for all part B claims in non-HOPD settings as there is not a box 19 on the UB-04 form, in addition to the products being bundled into the CPT code for reimbursement.

Thank you for your comment. The instructions in the related billing and coding article are specific to HCPCS codes A4100 and Q4100. However, it is advisable for providers to include any information in box 19 that may help in processing the claim correctly. We recognize that box 19 is specific to Part B claims. Therefore, there are instructions for Part A claims in the article as well.

A comment was submitted with concerns regarding the statement in the billing and coding article under documentation requirement #9: “The HCPCS code of the applicable skin substitute graft/CTP and the units billed must be consistent with the medical record regarding wound description and size.” The commenter pointed out that there have been claim denials by auditors indicating that the only amount that can be billed as “used” is the exact same size as the wound and the amount “wasted” should be the remainder of the graft- REGARDLESS if the provider folded the excess in the wound or discarded. The commenter indicated that this is problematic because claims are being wholly denied rather than adjusting the JW line (even though the claim payment would remain the same and in instances when the provider used the closest size of product to fit the wound). This requirement should be clarified so that auditors do not erroneously deny claims or so that providers document usage and wastage appropriately.

Providers should use the closest size of product to fit over the wound and should then discard any excess. Providers should follow the appropriate methods for reporting usage and wastage using the JW and JZ modifiers as outlined in the article. It would not be appropriate to fold a product over and report it as used.

Multiple commenters requested clarification on licensure levels of qualified providers. There were specific concerns related to the inclusion of podiatrists (DPMs) and non-physician practitioners (NPPs) related to managing underlying conditions such as diabetes or venous insufficiency. Additionally, a commenter requested that the MAC specify what is considered appropriate training and in what setting services are appropriate.

The LCD outlines the qualifications required for providers, emphasizing the need for adherence to their scope of practice and licensure, which includes podiatrists. 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 appropriate training would be referenced in the scope of practice and licensure. 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. It is not the place of an LCD to define State Scope of Practice. There are no restrictions within the LCD that would limit a podiatrist’s ability to care for patients with DFUs and VLUs and policy language was adapted to clarify this.

Multiple providers sent in similar letters requesting that Restrata be added to the covered list. They state it is a man-made 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 it to rebuild. It was also mentioned that Restrata does not require refrigeration or special handling and is a non-animal, non-human product eliminating the risk of viral transmission.

Thank you for your comments and submitted literature. The current evidence does not ensure a high level of certainty for this product. 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. The Husain (2024) study is reviewed extensively in the LCD detailing the rationale of why Restrata will not be covered in the policy based upon a high risk of bias due to lack of investigator blinding, high dropout rate, and the fact that the study was insufficiently powered to determine the effectiveness of the product.

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.

Comments were received related to pricing and reimbursement of skin substitute grafts/CTP. Multiple commenters were concerned with aggressive and abusive practices by providers prioritizing Average Sales Price (ASP) increasing wound care costs. A suggestion was made to consider reimbursement only for products listed on the national ASP drug file or other methodologies such as capping the ASP reimbursement. A concern related to increased cost due to wound care, infection, and amputation rather than an upfront investment in skin substitute grafts was also submitted. A comment was submitted indicating that the MAC may want to include a statement that products are only covered when there is sufficient evidence that the products are safe and effective per 1862 (a)(1)(A).

Additionally, the commenter feels that it would be beneficial to include discussion in the billing and coding article about the total invoice price. The commenter suggests that the LCD contains language that a total contact cast is considered separately reimbursable on the same date of service as a skin substitute graft/CTP as indicated by CPT 29445 to avoid providers confusion. Additionally, the commenter mentioned a report by the Office of Inspector General from March 2023 that discussed ASP data showing that if ASP past payments were fully applied there would be a cost savings of $365 million per year for skin substitute products alone. In conclusion, the commenter provided potential consequences that this LCD may have on the US healthcare economy and key stakeholders in the health system.

Thank you for your comments. No literature was submitted with this comment. The products that are covered in the proposed LCD meet the reasonable and necessary standard as reflected in the language of the indications for coverage. Cost analysis studies or product cost were not included in the evidence review or considered for determining products on the covered list. Pricing and cost do not come into consideration in the LCD process. The LCD is based upon evidence-based literature that supports products that foster wound healing in DFUs and VLUs only. The LCD is limited to covering those products that support wound healing based upon the medical literature and will not cover those that fail to do so. Providers should render services that are reasonable and necessary and are in the best interest of the patient. Driving the use of products that demonstrate improved wound healing will ultimately decrease costs as less time and effort will be wasted upon products that do not promote wound healing. As referenced in the LCD, there is insufficient evidence that the non-covered products heal wounds and improve outcomes.

A comment from SKYE Biologics was submitted requesting coverage of Wound Plus (Q4277). The commenter states they have seen great outcomes. It is stated that data and research from SKYE Biologics support similar findings. No literature was submitted.

Thank you for your comment. No literature was submitted with this comment. Once there is peer-reviewed evidence to support the use of this product in DFUs and VLUs, we recommend pursuing the LCD reconsideration process. Coverage under the proposed LCD must be supported by literature-based evidence.

A group of wound care providers submitted a comment containing their concerns for the proposed LCD. They state that Mircrolyte is a product used prior to placental grafts that has shown great success in healing wounds in their clinics. The commenter also recommended several amniotic products be offered with varying thicknesses for different wounds and to consider other grafts.

Thank you for your comments. No literature was submitted with this comment. Microlyte Matrix is appropriately non-covered in the proposed LCD as it lacks sufficient evidence to support its use for wound healing in the context of DFUs or VLUs. If this changes, we recommend filing a reconsideration request with supporting literature.

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 the use of real-world data/evidence. 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 RCTs for coverage and elaborate on challenges and concerns of the RCT design. Many commenters feel that the proposed LCD is overly restrictive of qualifying clinical evidence to support coverage decisions. The comments suggested that CMS and the MACs often rely on data from RCTs to inform coverage decisions, though as defined in CMS guidance, the MACs are responsible for reviewing and considering multiple other forms of evidence. CMS noted that “observational studies can be more representative of actual clinical practice and may answer questions that RCTs cannot answer.”

Some commenters indicated that limiting the evidence to RCTs only goes against CMS principles and will unnecessarily limit patients’ and providers’ access to established, well-proven products. Further, they feel it is inconsistent with the FDA’s increasing reliance on RWE pursuant to the 21st Century Cures Act. The comments note that RWE addresses health disparities, as it demonstrates efficacy and patient outcomes in populations that often are underrepresented in RCTs.

One commenter indicated that they do not believe that the statement “quality supporting evidence” provides clear direction as to what is or is not acceptable evidence for the contractor. The commenter goes on to say that the contractor points to Snyder et al and Eriksson et al as examples of “quality supporting evidence.” However, the commenter notes that section 12 of the Snyder document includes clinical trial design recommendations, but the Eriksson document does not. The commenter recommends that the contractor replace the Snyder document with FDA’s Guidance for Industry, Chronic Cutaneous Ulcer and Burn Wounds — Developing Products for Treatment, dated June 2006. Finally, the commenter believes that Level 1 clinical trial evidence in the treated patient population should be prioritized first for coverage.

Many commenters feel that the proposed LCD is overly restrictive of qualifying clinical evidence to support coverage decisions. Multiple comments were received supporting the use of GRADE methodology in the evidence review. It was also commented that many product trials are industry sponsored and that in the United States there is limited mechanism for such trials to be conducted; the commenter does not want this factor to be used as a limitation or to exclude potentially valuable studies.

Thank you for your comments. For acceptable evidence and guidance, please see response to comment #10. The LCD aims to provide Medicare beneficiaries with access to scientifically supported skin substitute grafts and 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 R&N, as stipulated by the Social Security Act, while investigational services are deemed non-covered. Products without supporting evidence are not considered R&N and delay of implementation is not appropriate as there are commercially available products that meet the R&N requirements.

While RCTs are often considered the gold standard in research, the LCD does not mandate that studies must be RCTs to be considered. Various types of evidence were reviewed, not limited to RCTs, and the Risk of Bias 2 analysis was used for this evidence along with the team of medical directors, research experts, and nurses to determine strength, certainty, and validity. This flexibility is intentional, allowing for a broader range of study designs and accommodating future research avenues. 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 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. The MACs use the Risk of Bias 2 (RoB2) tool in evidence 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.

Many comments were received by providers attesting to increased wound healing with the use of Kerecis in their patients. Literature was submitted including 3 studies. The most frequently submitted paper was one by Lantis et al, 2023. Commenters state that the Lantis study was excused from the analysis and addresses the concerns reviewed for Kerecis in the evidence review. Some provided an analysis of the literature in the LCD and how the literature of the products on the covered list compares to Kerecis. Commenters requested that the MAC review the literature as it includes several methodological strengths that are in line with the studies reviewed for proposed covered products. They also expressed concerns about access to care explaining Kerecis addresses populations that are unable to use human derived skin substitute products and increases access to rural beneficiaries because it does not need to be specially stored or refrigerated.

Thank you for your comments. The literature submitted for Kerecis Omega3 has been reviewed and added to the LCD. After review, we agree that the evidence supports coverage, and the product has been added to the covered list. We appreciate the summaries of the evidence and agree that the studies submitted address our concerns.

Many commenters requested clarification on the use of the terms ‘measurable’ and ‘substantial’ related to signs of wound healing stated in the LCD. Comments indicated that these terms were vague and required more detail of what was considered acceptable documentation of the wound(s). Multiple commenters feel that the word “measurable” was not ideal as wounds have too many variables that change such as shape, length, width, depth, granulation, exudate, and inflammation.

A comment was submitted with concerns that under Evidence-Based Guidelines for Skin Substitute Grafts/CTP, the draft LCD states: "For VLU, if substantial ulcer improvement is not demonstrated after a minimum of 4 weeks of standard therapy, skin substitute grafts or CTP may be considered in addition to compression therapy." However, “Substantial ulcer improvement” is never further defined, and the commenter fears this ambiguity may lead to unintended consequences if providers feel constrained in moving to advanced therapies. The DFU literature refers to a 50% reduction in size after 4 weeks of conservative therapy. American Podiatric Medical Association (APMA) recommends including a similar measurable criterion for VLU to help avoid ambiguity.

Comments were submitted with concerns related to the pre and post measurements. Commenters feel that pre and post measurements are only relevant if debridement is performed. While the commenters agree that measuring an ulcer makes sense on each visit, they are concerned about denials when medical reviews are performed if the size is no different and the documentation states post size is same as pre size. The commenters contend that the way the LCD reads, they would have to duplicate the dimensions if there was no change in size and they feel this is not necessary.

Thank you for your comments. We agree with the suggested clarification in terms throughout the LCD and these changes have been made based on this feedback, specifically replacing ‘substantial’ with ‘greater than or equal to 50%.’ The word measurable has been removed as suggested and the language clarifies that the application is appropriate for failed or stalled wounds as defined in the LCD. The requirement in the LCD regarding measurements is to support the response of the ulcer to SOC treatment. It needs to be clear in the medical documentation that the ulcer failed to heal or stalled prior to the skin substitute graft/CTP application. Updates have been made to the Billing and Coding article that address requests for documentation clarification.

A comment was received stating that defining skin substitute grafts/CTP as ‘grafts’ should limit the applications to 2 or less and if not considered dressings, there is no reason for more than 2 of these to ever be applied.

We appreciate your comments. Regarding applications and the flexibility afforded beneficiaries and providers based upon the literature-based evidence, please see response to comments #10, #20, and #56.

A comment was received with concerns that these products do not work and that providers who use them may have conflicts of interest and bias towards certain products. This commenter feels that there is not sufficient evidence for coverage of any skin substitute graft/CTP.

Thank you for your comments. See Comment #17 as to why only skin substitute grafts with literature-based evidence are covered in the proposed LCD. 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.

A comment submitted a general concern about safety and efficacy of covered products and appropriate indications for use of the products. The commenter states they have reviewed claims where these products are used for a variety of indications that are inappropriate. They also expressed concern about products receiving “provisional coverage.” The commenter feels that no product should be “provisionally covered” without safety and efficacy.

Thank you for your comments. The LCD provides that the covered skin substitute grafts are based upon peer-reviewed evidence-based literature as required by Medicare, while those products without such evidence are not covered for DFUs and VLUs. This policy provides coverage guidance for DFUs and VLUs only. The evidence-based approach is congruent with Medicare’s reasonable and necessary requirement for products designed to improve outcomes and enhance wound healing.

A commenter recommended that a definition for “scaffold” be added to the list of definitions for clarity. They suggest using the ASTM Standard 2312-11, Standard Terminology Relating to Tissue Engineered Medical Products includes a definition for scaffold: 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. The comment points out that the ASTM definition is recognized by the FDA and will provide additional information regarding the function of scaffolds in wound healing.

Thank you for your comments. Thank you for submitting a definition of scaffolding. We have added this language to the LCD.

Multiple comments were submitted suggesting that the MACs provide clarification on a process that will apply for moving products from non-covered to covered when new evidence is presented. The concern is that a full reconsideration for each product will be required which would restrict patient access to innovative care. It is recommended that the MACs develop a single, shared process for transitioning products from uncovered to covered. Other commenters suggested that the MAC should only require a review of the evidence and should update the billing and coding article if evidence is sufficient for a product to move to the Group 2 covered product list or in the alternative, place language in the LCD which states than an approved technology assessment completed by the CAC is sufficient for the MAC to include the product in the LCA Group 2 covered product list.

Commenters recommend that the MACs provide clarification and direction regarding the process and timeline to address how products that were granted new HCPCS codes will gain coverage.

It was recommended that the MACs include a process for reviewing (as a group) newly published evidence every quarter.

Alternatively, it was commented that the MAC should consider using the final LCD to establish the broadly applicable analytical framework for assessing evidence supporting coverage of skin substitute grafts/CTP, rather than including product-specific evidence analyses, enabling it to establish product coverage through billing and coding articles without the need for an LCD reconsideration.

Thank you for your comments. Transition of a product from non-covered to covered status occurs through the LCD reconsideration process. Once there is substantial evidence published in peer-reviewed literature, any product can be submitted for LCD reconsideration. This process is governed by IOM 100-08, Medicare Program Integrity Manual, Chapter 13. 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, to facilitate this process. Mechanisms are in place to expedite the process when necessary, such as opening an LCD to comments for a new section only. The MACs intend to work together to streamline this process and provide timely responses within the constraints of the requirements for LCDs. However, despite these efforts, the LCD reconsideration process takes approximately 6 months.

Comments were submitted expressing concern with the MACs collectively issuing uniform LCDs. The commenter believes that MACs are not permitted to collectively issue uniform final LCDs that effectively establish a nationwide coverage policy. The comments suggest that there are strong indications that such an outcome would be inconsistent with Congress’s intent in creating distinct paths and statutory processes for LCDs versus NCDs.

Thank you for your comments. 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. This LCD was developed according to the process required by the Medicare Program (IOM 100-08, Medicare Program Integrity Manual Chapter 13). As compared to the NCD process, each MAC must conduct their own open meeting, followed by a comment period, and consider unique needs of their jurisdictions in the development of an LCD. The MACs have held open meetings for this proposed LCD and have properly responded to the comments submitted during the appropriate timeframe.

Comments were submitted with concerns regarding the specificity and inclusivity of ICD-10-CM codes. Several comments were related to the treatment of diabetic ulcers, particularly in the context of billing and insurance coverage for skin substitute grafts in limb salvage therapy. There is concern that the codes only include below the ankle (EXX.621, L97.4X, L97.5X), potentially omitting important coverage for other affected areas that might require similar treatments. The comments request that the list of covered ICD-10-CM codes be expanded to encompass diabetic ulcers not just on the heel and midfoot, but also other regions of the lower limb such as the ankles and above. Another commenter requested clarity on coding in relation to dual diagnosis and the order of codes on the claim. Commenters also noted that the non-pressure chronic ulcer codes included in the billing and coding article only allow the shallowest ulcers. The commenters indicated that there are L97.XXX codes that represent ulcers that are deeper, yet do not involve necrosis that they feel should be covered.

A commenter requests to remove any reference to unlimited diagnosis to procedure code limitations with respect to only pertaining to diabetic foot ulcers and venous leg ulcers per the policy language. Only apply ICD-10-CM codes applicable to those two clinical conditions. There were many comments requesting clarity on the grouping of codes including DFU and VLU codes in the same group. The concern was regarding products that do not have sufficient evidence for coverage for DFU and VLU and how the codes should be grouped.

Thank you for your comments. The policy is limited to DFUs and VLUs so diabetic ulcers above the ankle, like other locations that are not DFUs or VLUs, are to be left to the individual MAC’s discretion. Billing and Coding questions have been clarified after additional input and comments received during the open comment period. This also provides further instructions on the use of modifiers and documentation requirements. The HCPCS/CPT and ICD-10-CM codes have been separated into separate groups for DFUs and VLUs as not all products or codes are applicable for both DFUs and VLUs. To prevent confusion, any ICD-10-CM code that is not specific to DFU or VLU that is to be used as a dual diagnosis requirement has been moved to the dual diagnosis asterisk explanation section.

A comment was submitted expressing concern that the LCD will eliminate their ability to treat patients. The commenter explained that in their experience, skin substitute products (including many products in the proposed non-covered category) are critical for effective treatment of chronic wounds that do not heal with SOC treatment, including diabetic foot ulcers, venous leg ulcers, and pressure wounds. The commenter stated that they use these products regularly to treat their patients with significant results.

Thank you for your comments. Medicare Administrative Contractors are required to base their coverage determinations on scientific evidence. The proposed LCD provides a summary of evidence and analysis of evidence to support coverage decisions.

Many commenters requested clarification on documentation requirements for covered indications. The topics for clarification include management of comorbidities, acceptable assessment, documentation for wounds and patient status, satisfactory blood glucose levels, acceptable Hgb A1C, what is meant by nutritional status, acceptable offloading devices, appropriate footwear, SOC, provider clarification, and application number and frequency. One commenter asked what is specifically meant by “assessment.” The commenter wondered if the contractor was looking for specific ICD-10-CM codes to satisfy this and if so, which ones. Commenters further asked what physical exam characteristics would be required for the skin assessment and what level of edema is expected to be present in order to proceed with CTPs.

Thank you for your comments. We agree that accurate documentation is important to ensure appropriate use of these products. We understand auditors may utilize the LCD for their reviews, but this use is beyond the scope of the MACs, especially for auditors outside of the Medicare program. We strive to provide clear language and measures without being overly prescriptive as to not interfere with provider judgment or add additional burden. Documentation in the medical record should clearly support the services rendered. Language to clarify that the treatment is expected to be continued throughout the treatment has been added to the LCD to ensure clarity. The documentation requirements align with what would be expected in the care of a patient with chronic non-healing ulcers. Documentation requirements and instructions, including wastage, are explained in the B&C Article, and not contained within the LCD. The individual MACs will provide education and can develop tools if necessary to aid in compliance with documentation requirements.

For information on application limitations such as number and frequency, please see response to comment #12. Please see response to comment #15 for provider qualification concerns.

A comment was submitted suggesting that “Implemented treatment plan” should be retitled to “implemented treatment plan during the 4 weeks prior to CTP use.” The commenter is also seeking clarification regarding the statement “Infection control with removal of foreign body or nidus of infection.” They request that the contractor specify whether the physician/wound care provider statement that no infection is present will suffice or whether it is necessary to produce some test or study to verify that infection has been managed, and if so, what that test would be.

Thank you for your comments. Language has been added to the LCD to clarify that the SOC treatment plan is to be continued throughout the episode of care. We believe appropriate documentation could include physician or provider observations considering the expertise such individuals have in wound care in describing the status of the wound. Assessment of infection is left to provider discretion, clinical practice standards, and individual patient needs. Additionally, a provider can certainly describe in detail in the medical record that infection control with removal of foreign body or nidus of infection has occurred as set forth in this requirement.

A comment was received concerning specific documentation requirements including “review of pertinent medical information” if there are no changes, reviewing and documenting the procedure risks and complications, and adding documentation for explanation of the planned skin replacement and choice of skin substitute graft/CTP.

Thank you for your comment. Please refer to comment #31 addressing documentation requirement clarification. The medical record should support the service and align with the requirements of the LCD. These noted requirements listed in this comment represent basic documentation that should be found in any history and progress note when describing any medical condition. Typically, such a note would contain pertinent positive and negative findings to describe a medical condition, including wounds. Such a medical record would also include appropriate documentation of a contemplated procedure as well as confirmation of the informed consent process. In situations where there has been no change, the record should indicate no change. It would be reasonable that the provider would review with patients what interventions have been successful or unsuccessful.

A comment was received from a provider who has used the product Helicoll with success in treating a variety of wounds. They state the product has helped patient wounds heal more quickly.

The commenter relayed that they have found that patients suffering with long-term wounds saw improved healing after treatment with this product. No literature was submitted with the comment.

Thank you for your comments. Medicare Administrative Contractors are required to base their coverage determinations on scientific evidence. The coverage decisions for this LCD were made based on the best evidence available at the time. 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. The LCD provides a summary of evidence and analysis of evidence to support coverage decisions.

A commenter submitted a comment indicating that the Draft LCD notes a “promising trend within the literature towards outcome improvement” and states that “coverage will be provided for skin substitute grafts/CTP with peer-reviewed, published evidence supporting their use for chronic ulcers that have failed standard methods.” However, the commenter is concerned that MatriDerm was omitted. The comment indicated that Medicare recently proposed a new HCPCS Level II Code for MatriDerm (A2027) and that their clinical experience with MatriDerm shows improved outcomes, consistent with a randomized controlled trial by Jeon et al. This study found MatriDerm had a 33.5% reduction in time to full healing and a 16.6% improvement in patients healed at 12 weeks. Other literature provided by this commenter in support of MatriDerm includes Buzea et al, 2020, Cervelli et al, 2010, and De Angelis et al, 2013.

Thank you for comments and providing supporting literature. We have reviewed the literature and determined it is of low certainty. MatriDerm will remain on the non-covered list. Three case reports and one prospective randomized trial were reviewed. The 2013 prospective study included 60 patients with chronic DFUs who had MatriDerm and a split-thickness skin graft or split-thickness graft alone applied to wounds. The study investigated the time to complete wound closure and whether there was a higher rate of wound closure in the MatriDerm with split-thickness graft group. However, in this study, MatriDerm was used to aid in healing alongside the split-thickness graft and therefore does not meet the definition of a skin substitute graft as per the LCD.

The three case reports had extremely small sample sizes, minimal follow-up, and lacked controls. In combination, these studies did not provide confidence or a sufficient level of certainty that MatriDerm can be used as an effective skin substitute graft for the treatment of DFUs or VLUs.

Comments were submitted recommending that the contractor provide a Disclaimer for the “Standard of Care” language to avoid the LCD from Becoming Evidence in Medical Malpractice Lawsuits. The commenter recommended a statement such as: “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 diabetic foot ulcers or venous leg ulcers.”

Another comment suggested that the LCD should encourage the best practice in offloading in conjunction with Skin Substitutes grafts/CTP. The commenter suggested that the LCD encourage optimal offloading not only before, but during the grafting period and they specify that based on the evidence, the best practice for offloading plantar foot ulcers is the total contact cast or knee-high RCW rendered-irremovable, in appropriate patients. It is recommended that offloading methods such as casting or equivalent methods should be reimbursed on the same date as the skin substitute application in an effort to improve outcomes. Clarification was requested regarding counseling for smoking cessation and the documentation of this counseling. Another commenter requested that the MACs provide specific tests or methods that will represent an adequate nutritional assessment since auditors are applying their own non-evidence-based standards.

Thank you for your comments. The suggested ‘Standard of Care’ disclaimer has been added to the policy. We agree with the importance of offloading. The LCD requires offloading as indicated in Covered Indications #3 as part of the implemented treatment plan. Language to clarify that the treatment is expected to be continued throughout the episode of care has been added to the LCD to ensure clarity. The billing and coding instructions regarding a contact cast is beyond the scope of this LCD. The comprehensive patient assessment now includes vascular assessments as part of the implemented treatment plan. As always, this requires documentation of what evaluation was done and eliminates the ABI index as a requirement. The LCD specifies that the use of a firm strength compression garment (>20 mmHg) or multi-layered compressive dressings is an essential component of SOC for venous stasis ulcers. These options give flexibility when ordering such compression and the documentation in the medical record provides the rationale for the decision made. The documentation of smoking cessation and counseling is clear from the plain meaning of the language found in the LCD. Nutritional status is addressed in the LCD in the indications section for DFUs and in the Evidence-Based Guidelines for SOC.

A comment was received requesting the use of skin substitute grafts/CTP used in an inpatient setting not be applied toward the total number of grafts considered reasonable and necessary.

Thank you for your comment. Please see comment #12 for information regarding application number and frequency limitations. The goal of using skin substitute grafts/CTP is wound healing regardless of the location of the procedure.

Comment was received requesting the LCD include indications related to peripheral arterial disease and neuropathy in non-diabetic patients. Literature was mentioned in the comment; however, no full-text literature was submitted.

Thank you for your comments. Implementation of this LCD will not restrict use of these products for conditions other than diabetic foot ulcers and venous leg ulcers. Services outside the scope of the LCD must adhere to Medicare’s reasonable and necessary criteria. There was no full-text literature submitted to support the addition of these indications or products. If this is developed in the future, it can be considered via the LCD reconsideration process.

Multiple comments were received discussing the topic of recurrence of both DFUs and VLUs. The commenters feel that it is inappropriate to restrict the use of skin substitute grafts/CTP for recurrent wounds within 12 months as the LCD limitation currently does.

Thank you for your review of the LCD and feedback. We appreciate your expertise in advising on recurrence and that it is medically appropriate to proceed with repeat application for recurrence if previously successful. This has been removed from the LCD as an unsuccessful treatment based on this input and that the limitation was not supported by evidence.

Comment received suggesting the language in the LCD related to chronic conditions be changed from ‘corrected’ to ‘optimized’ as many times chronic conditions cannot be ‘corrected.’

Thank you for your comment. We agree with the suggested clarification in the LCD and these changes have been made based on this feedback specifically changing ‘correcting’ to ‘optimizing.’

A comment was received from a provider advocating for PuraPly’s continued use. They state the product has reduced days-to-heal averages within their practice.

Thank you for your comment. No literature was submitted with this comment. Medicare Administrative Contractors are required to base their coverage determinations on scientific evidence. The proposed LCD provides a summary of evidence and analysis of evidence to support our coverage decisions. The contractor welcomes submission of full-text articles following our reconsideration process once the LCD becomes effective.

A comment was received concerned about indications outside of DFUs and VLUs such as pressure sores and traumatic wounds. The commenter also expressed concerns regarding limiting the number of products and supply issues.

Thank you for your comments. No literature was submitted with this comment. Implementation of this LCD will not restrict use of these products for conditions other than DFUs and VLUs. Services outside the scope of the LCD must adhere to Medicare’s reasonable and necessary criteria and will be reviewed on a case-by-case basis. The LCD is limited to DFUs and VLUs because this is the most seen indications and locations for the use of these products. 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. Suppliers of the covered products have not expressed concern regarding supply chain during the comment period. Several of these organizations have noted that they are confident in their ability to meet this demand and recommend avoidance of delays due to supply chain concerns. Further, the LCD will drive the utilization of products that foster wound healing, not those that fail to do so. Thus, eliminating the time and resources wasted upon products that do not work in the setting of ulcer treatment.

Many comments were received supporting the use of Neox graft products. The commenters explain that Neox graft products for DFUs and VLUs are most effective when left alone on the wound bed to resorb versus weekly application and can remain visible for 3-4 weeks. Commenter, BioTissue, instructs providers to only replace if there is no graft visible on the wound surface. They stated that none of the covered products had evidence to support 3+ week intervals. They noted 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 was submitted. They conclude “Neox 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.” They request that 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. A request was made to revise the table in the LCD to correct the name of the product and align the evidence with each product.

Multiple providers commented expressing support for the use of these products sharing clinical experiences of their own and discussing clinical efficacy, cost-effectiveness, and improving patient quality of life.

Thank you for your comments. 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 outcome to 1 year. However, the very small sample size of 32 subjects and lack of blinding, randomization, and controls does not provide high certainty that the improvement seen in the study population is due to the product and not other factors. Therefore, this study is not sufficient for coverage. Additional literature does not meet the evidentiary bar 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. Please review the response to comments #10 and #20 which addresses literature-based evidence and methodology for the LCD. The product name and citations have been corrected in the tables.

Many comments were received regarding concerns that the LCD would cause market disruption and lack of access to care for beneficiaries. One commenter stated that according to Medicare Claims data, 67% of patients treated with a skin substitute in 2023 received a product on the non-covered list. The commenter is concerned about the implications this LCD will have on patient outcomes and market supply disruptions.

Another commenter believes that the LCD will result in product shortages, high prices, and patients being denied effective treatments. There is concern that the clinical options available to patients and providers will be drastically reduced and risk the creation of a supply and demand crisis. There were requests for a transition period to allow beneficiaries and providers to switch products over time as to not interrupt patient care. It was also mentioned that the reduction in covered products with the LCD would create an increase in amputations and not allow providers the flexibility to tailor treatments to their patients’ unique needs.

Thank you for your comments. Please see comments #42 regarding supply issues, and #72 relating to transitions and interruptions in care. Please review our statement on health equities and disparities in the LCD which underscores our acknowledgment that future studies should be more representative of the diverse population of patients suffering from these conditions as well as including Medicare age beneficiaries. 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.

A comment was received regarding the use of the statement “wound dressings or products” in the LCD. The commenter states that any wording in the LCD that describes the HCPCS codes Q4XXX and A2XXX as a ‘dressing’ is inaccurate and should be removed from the LCD. HCPCS Level II has already made a clear distinction between wound dressings and skin substitute grafts/CTP (A6XXX vs A2XXX/Q4XXX).

he commenter also has concerns about claims that are not for DFUs or VLUs and how they will be handled.

Thank you for your comments. The LCD only applies to VLUs and DFUs. Neither the indications nor limitations would apply to any other types of wounds or products. The LCD defines wound dressing or covering as ‘Applications applied to wounds as a selective barrier to clean, cover, and protect wounds from the surrounding environment to promote optimal wound healing.’ The terms ‘wound dressings or products’ is defined in the LCD and used only in specific product summaries as described in the studies themselves. DME supplies are not addressed in this LCD.

A comment was received requesting clarity on graft size used to fit the wound and billing of these products. The commenter also wanted to let us know that Artacent Wound and Artacent AC have begun a clinical study.

Thank you for your comments. No literature was submitted with this request. Medicare Administrative Contractors are required to base their coverage determinations on published scientific evidence. The proposed LCD provides a summary of evidence and analysis of evidence to support our coverage decisions. Artacent products were reviewed and found to have insufficient evidence to support coverage for DFUs or VLUs. Stakeholders may submit peer reviewed full-text articles to support coverage for skin substitute grafts/CTP via the reconsideration process outlined on our website once the LCD is finalized. With respect to the graft size, such a determination would be based upon the size of the wound and type of graft used. Those decisions are left up to the provider. The billing and coding article contains instructions for billing wastage.

A beneficiary’s son wrote in on behalf of his father. They are concerned with the limited number of products that will be available with the proposed LCD as the commenter’s father has long suffered from diabetes and chronic leg wounds. They are concerned that he will not have access to the products that could work for him should he need them in the future which may result in amputation. They feel that the patient’s provider should be allowed to choose what is best.

Thank you for your comments. We are very sensitive to the medical needs of our beneficiaries. However, we are tasked with covering only those products that have published medical literature-based evidence to support their use as skin substitute grafts for DFUs and VLUs. This LCD is focused only on those type of wounds and products with evidence to support wound healing in this regard. Without such evidence, other non-covered products such as those listed in the LCD do not have the scientific certainty to bolster their use for healing these wounds in the Medicare population.

A request was received to consider Biovance and Biovance 3L for coverage under the proposed LCD and article. Two studies were submitted for review. The commenter states that these studies satisfy the LCD evidence coverage criteria.

Thank you for your comments. Please see response to comments #10 and #20 for a description of appropriate evidence to be considered for LCD coverage. The submitted papers on total ankle replacement and tendon tears are not within the scope of the LCD and we do not consider review papers or product labels for coverage determinations. The Smiell 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. It cannot adequately be determined 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 reviewed in the LCD. Finally, there is a high risk of bias in the absence of randomization or blinding. Therefore, this literature is not considered appropriate for coverage.

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 on the industry and jobs. They feel the LCD inappropriately restricts access to clinically effective treatment and sets forth a coverage policy that is contrary to both clinical evidence and clinical practice. 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 feel there should be more input from providers, researchers, scientists, patients, and producers of the products.

Thank you for your comments. The intent of the LCD is to prioritize patient care and ensure Medicare beneficiaries have access to scientifically supported skin substitute grafts and CTPs that have proven effective in accelerating ulcer healing, thereby enhancing healthcare outcomes. Medicare Administrative Contractors are required to base their coverage determinations on scientific evidence. The coverage decisions for this LCD were made based on the best evidence available at the time. Local Coverage Determinations should clearly identify what services are covered and what services are non-covered. Furthermore, we held numerous open meetings (4 total) over a 3-year period with stakeholders, with 2 of the meetings occurring this year for First Coast for this proposed LCD. Many listening sessions were also conducted with other MACs and stakeholders over the last couple of years. Providers may submit peer reviewed full-text articles related to any skin substitute grafts/cellular and tissue-based products via the reconsideration process outlined on our website once the LCD is finalized. Please refer to response to comments #10, #20, and #56 for information on the evidence process and methodology used in developing this LCD.

A comment was received from a beneficiary asking to not limit these products and the ability of physicians to adequately treat people.

Thank you for your comment. Please review response to comments #10, #20, and #56 that address the evidence needed to ensure appropriate coverage for products in this LCD. The products covered in the LCD have literature-based evidence supporting their utilization to heal DFUs and VLUs. Medicare Administrative Contractors are required to base their coverage determinations on published scientific evidence. The LCD provides a summary of evidence and analysis of evidence to support our coverage decisions. Stakeholders may submit peer reviewed full-text articles to support coverage for skin substitute grafts/CTP products via the reconsideration process outlined on our website once the LCD is finalized.

A comment was received requesting coverage for the product ActiGraft. The comment also included a request for more transparent requirements to determine eligibility for coverage which will help guide manufacturers and stakeholders to generate the necessary evidence to support coverage in the future. The commenter includes a list of clinical study characteristics they feel should be included in the LCD to provide guidance.

Thank you for your comments. Please review response to comments #10, #20, and #56 that address the evidence needed to ensure appropriate coverage for products in this LCD. No literature was submitted with this comment. The products covered in the LCD have literature-based evidence supporting their utilization to heal DFUs and VLUs. Medicare Administrative Contractors are required to base their coverage determinations on published scientific evidence. The LCD provides a summary of evidence and analysis of evidence to support our coverage decisions. Providers may submit peer reviewed full-text articles to support coverage for skin substitute grafts/CTP via the reconsideration process outlined on our website once the LCD is finalized.

A comment was received opposing the proposed LCD. They feel it is wrong to eliminate coverage for many skin substitutes and limit applications to 4 per 12-week episode of care.

Thank you for your comments. Please review response to comments #10, #20, and #56 that address the evidence needed to ensure appropriate coverage for products in this LCD. The application number has been changed. Please see response to comment #12 which discusses the application frequency and treatment episode timeframe.

A comment was received requesting coverage for Derma-Gide. Considering the level one prospective, randomized clinical evidence supporting the use of Derma-Gide in the treatment of DFUs, the commenter is requesting reconsideration for the inclusion of Derma-Gide as covered for the treatment of DFUs in the proposed LCD.

Thank you for your comment. After review of the literature, it was determined that the evidence is sufficient for coverage of Derma-Gide. It has been added to the covered list of products for DFUs in the LCD and article.

A comment was received requesting specific clinical scenarios in which the use of these products is supported by robust evidence. The commenter also had concerns about the use of rebate programs encouraging excessive use of skin substitute grafts/CTP leading to unnecessary spending. They proposed guidelines related to clinical indications, rebate program transparency, utilization monitoring, and education for providers.

Thank you for your comments. The LCD sets forth clear indications and limitations for skin substitute grafts/CTP for DFUs and VLUs. Rebate program transparency is not within the purview of the MACs and beyond the scope of the LCD. However, MACs are engaged in provider education and monitoring of claims for overutilization. Please review response to comments #10, #20, and #56 that address the evidence needed to ensure appropriate coverage for products in this LCD.

The policy's focus on evidence-based methodology 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 DFUs and VLUs are left to the discretion of the individual MACs, who must also adhere to the reasonable and necessary standard. This approach ensures that all products are evaluated fairly, without bias towards any product or group.

Many comments were received requesting to remove the exclusion or revise limitations for those with comorbidities, specifically diabetes that is not controlled. Commenters recognize the importance of addressing underlying comorbidities, however, feel the word ‘correcting’ is misleading as many systematic pathologies cannot be ‘corrected.’

Thank you for your comments. We agree with the suggested clarification in the LCD and these changes have been made based on this feedback specifically changing ‘correcting’ to ‘optimizing.’ Uncontrolled diabetes has been removed from the exclusion criteria. Blood glucose and Hemoglobin A1c are still important to evaluate diabetic patients and will remain in the LCD.

A comment was received requesting coverage for product Bio-Connekt which is listed in the non-covered section of the proposed LCD and states ‘no literature found’. The commenter feels that it is unfair to only consider literature located in the public domain for evidence. They provided a summary of data of pre-clinical testing which was reviewed by experts at the FDA. The commenter feels that the proposed LCD dismisses significant case studies and real-world evidence that would be useful in determining coverage for products.

Thank you for your comment. No literature was submitted with this comment. 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. This 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.

Unpublished literature is not considered in the LCD process. The outcomes of investigations cannot be assumed without scrutiny by the peer-reviewed process. For evidence requirements, see response to comments #10 and #20.

A comment was received requesting coverage for Symphony and concerns about the pathway for adding products to the covered list in a timely manner as new evidence develops. The commenter states that Symphony has a pending RCT. They are concerned that requiring a full LCD reconsideration to add products to the list of covered skin substitute grafts/CTP will delay patients’ access to innovative wound care products. There was also concern related to the 45-day notice period and requesting additional time prior to implementation of the policy.

Thank you for your comments. 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 and covering a service without sufficient (and published) evidence does not meet the definition of R&N which is a requirement for the MACs.

For evidentiary requirements see response to comments #10, #20, and #56 for access to care and supply issues, see response to comments #42 and #44, for the reconsideration process, see response to comment #27.

The LCD aims to provide Medicare beneficiaries with access to scientifically supported skin substitute grafts and 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 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 delay of implementation is not appropriate as there are commercially available products that meet the R&N requirements.

We acknowledge concerns raised by stakeholders regarding potential treatment disruptions for patients within a 12-week care episode, 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.

A commenter sent in recommendations of moving lists of non-covered and covered products to a policy article so that the article can be revised without a full LCD reconsideration and using a case-by-case adjudication of skin substitute grafts with registered RCTs underway.

Thank you for your comments. For the reconsideration process see response to comment #27. For unpublished literature see response to comment #57. The LCD process requires a listing of the covered products as well as explication of the evidence that supports these products. It is not appropriate to place this information in the related policy article.

A comment was received requesting clarification on how the MAC intends to implement the LCD noting that the draft policy article contains a list of diagnosis codes ‘supporting’ medical necessity. They request the MAC confirm that it is using these diagnosis codes as a proxy for DFU and VLU treatment and apply the coverage restrictions in the LCD exclusively where these diagnosis codes are billed. They request clarification on how cases billed with codes outside of this LCD and article will be handled and if coverage will be restricted based on specific study parameters for DFUs and VLUs.

Thank you for your comments. The LCD sets forth clear indications and limitations for skin substitute grafts/CTP for DFUs and VLUs. Therefore, the LCD will be implemented consistent with the covered indications and limitations for those conditions. Other uses of the products are not addressed, nor will they be limited by the LCD. The MACs are responsible for ensuring that all services meet the R&N criteria for coverage as established by Medicare.

A comment was received noting the omission of Matriderm from the covered products list. The commenter states they have used this product, and it has demonstrated improved outcomes for their patients. Data with positive outcomes for this product were mentioned.

Thank you for your comment. See response to comment #35 as well. There was no literature submitted with this comment; however, other commenters submitted literature in support of Matriderm and this literature was reviewed. 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 reduced 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 did not meet the definition of a skin substitute graft/CTP as it was used in this study. Additional literature includes a case study in DFUs, VLUs, and mixed leg ulcers. Due to the lack of sufficient evidence, this product will remain on the non-covered list.

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 and there is no evidence they function in this capacity. If such evidence is developed it can be submitted through the LCD reconsideration process.

A comment was received asking that the MAC move all products from group 3 (non-covered) to group 2 (covered).

Thank you for your comments. The LCD is based upon published peer-reviewed evidence that supports use of these covered products for use in DFU and VLU wound healing. The non-covered products do not have such evidence and will not be redistributed to the Group 2 covered products. This is mandated by IOM 100-08, Chapter 13. See response to comments #10 and #20 for the methodology used in LCD development. For the type of literature supporting the LCD process, see response to comments #10, #20, and #56. For the reconsideration process designed to add other products that have new evidence supporting their coverage, see response to comment #27.

A comment was received requesting the MAC review evidence and provide coverage for the following: TheraSkin, DermACELL, Theragenesis, and Matrion. Literature was submitted for review. The commenter also requested clarification on use of products outside of the indications in the LCD and how the claims will be handled.

Thank you for your comment and literature submitted. In the current proposed LCD, DermACELL is listed as a covered product for DFUs only, TheraSkin is listed as covered for DFUs only, Theragenesis is non-covered due to insufficient evidence, and Matrion is non-covered due to no literature found. The submitted literature has been reviewed and forms the basis for non-coverage/coverage under the LCD. If literature to support coverage becomes available in the future, please submit it for the reconsideration process. Please see response to comment #27 for reconsideration. This LCD will not limit the use of these products for indications outside of DFUs and VLUs. How the MAC responds to claims outside of the scope of the LCD is addressed by the individual MAC.

A comment was received requesting there not be any delay in implementation once the standard 45-day public notice period has ended. The commenter also stated concern that studies of covered products took place only in outpatient settings and on small wounds.

Thank you for your comment. Please see response to comment #57 regarding implementation. Please see response to comments #10, #20, and #56 regarding evidence and methodology for the LCD.

A comment was received concerning potential conflicts of interest within the MACs, specifically those with Medicare Advantage plans. They are concerned with who is benefiting from the policy.

Thank you for your comments. The beneficiaries are the Medicare population. The commitment to transparency is evident throughout the policy's development, including an open comment period which allowed for diverse input from stakeholders. This is instrumental in refining and improving the policy to better serve the needs of the healthcare community and the beneficiaries.

Please see response to comments #28, which details MAC collaboration, and #10, #20, and #56 regarding evidence, methodology for the LCD, and the process that MACs use to create an LCD.

A comment was received in support of the use of skin substitute grafts/CTP noting faster healing times, reduced amputation rates, and more. The main concern of the comment was related to the application frequency and duration of treatment using the products.

Thank you for your comments. See response to comment #12 regarding application frequency. We have changed these limitations in the LCD to better reflect the evidence.

A comment was received in support of product InnovaMatrix which is currently listed in the LCD as non-covered due to insufficient evidence. The commenter states there are at least 6 clinical trials that attest to the effectiveness of InnovaMatrix’s predicate device. They stated that in their clinical experience, this product has improved wound healing and reduced healing times.

Thank you for your comments. No literature was submitted with this comment. There is insufficient evidence to support InnovaMatrix for treatment of DFUs/VLUs. The fact that InnovaMatrix’s predicate device was supported by 6 clinical trials is not sufficient for coverage in this LCD. This policy is based entirely on evidence and not on FDA pathways. For FDA requirements, see response to comment #5. While the Premarket Approval (PMA) requirement from the FDA might be useful, 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. Predicate devices are not sufficient for coverage. It is noted 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 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.

A comment was received regarding skin substitute options available for those with religious, cultural, and ethical objections to human or animal-based products. They are requesting coverage for Microlyte Matrix.

Thank you for your comments. Please see comment #19 about the lack of sufficient evidence for the use of this product in DFUs and VLUs. Utilizing an evidence-based approach ensures there is no favoritism or discrimination against any specific company, populations, religious, cultural, or ethnic group or regulatory pathways. All products being utilized as skin substitute grafts/CTPs, as defined in the LCD, are equally considered under this policy, including synthetics. 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. Please refer to response to comments #10, #20, and #56 for information on the evidence process.

A comment was received discussing that the products are inaccurately grouped, implying they should be grouped by product type. Specifically mentioned is Microlyte Matrix which is a fully synthetic product. They also state there is a ‘shift’ in the definition of skin substitute grafts and this change introduces the requirement of quality supporting evidence for product classification. They understand this requirement may improve standard of evidence for coverage decisions; however, it also adds complexity to an already intricate system. Another concern is that of provider autonomy to use products depending on the patient need.

Thank you for your comments. Please see response to comments #19 and #67 for MicroLyte Matrix, and #10, #20, and #56 for evidence required for coverage of products in the LCD.

Utilizing an evidence-based approach ensures there is no favoritism or discrimination against any specific company, populations, or regulatory pathways. All products being utilized as skin substitute grafts/CTPs, as defined in the LCD, are equally considered under this policy, including synthetics.

The LCD section on “Product classification” explains the rationale as to why the LCD looks at products individually rather than as a class and does not consider the products within the same class “interchangeable and 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/CTPs 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 explain why 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. They 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 conclude that due to processing variations, each product must be studied in a “properly conducted clinical trial”. A 2024 systematic review/meta-analysis (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 the 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.”

There was a comment received concerning the impact of this LCD on medical device companies and innovation related to favoritism of large companies over smaller start-ups. The commenter believes the MACs should create and support a competitive marketplace that fosters the growth of smaller companies. They also urge reconsideration of evidentiary standards and the differences between 510K clearances, PMA, and HCT/P approvals. They feel that excluding 510K-based products undermines smaller companies’ contributions.

Thank you for your comments. The existence of a HCPCS code or approval via an FDA regulatory pathway, including the PMA requirement, does not translate to Medicare coverage. The MACS do not control any FDA process or have input therein. The item or service must satisfy the R & N standards for coverage. This policy proposal emphasizes an evidentiary review for each product, aligning with the 21st Century Cures Act's mandate for peer-reviewed 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. Please refer to response to comments #10, #20, and #56 for information on the evidence process.

A comment was received discussing the definitions used within the proposed LCD. They feel the definitions used are inconsistent, unnecessary, and inappropriate. The commenter suggests deferring to CMS’s definitions instead of the HCPCS Level II Coding definitions.

They request coverage for ProgenaMatrix which they state has quality evidence demonstrating safety, effectiveness, and positive clinical outcomes. An unpublished study, poster presentation, and limited case series were submitted. The commenter also requests clarity on coverage for wound types other than DFUs and VLUs.

Thank you for your comment. The proposed policy only applies to DFUs and VLUs. Wounds outside the scope of the LCD will be handled per the individual MACs. While we appreciate the summary of literature on ProgenaMatrix we cannot consider unpublished literature and the 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.

Regardless of the definition of skin substitute grafts/CTP, coverage is based on evidence that demonstrates effectiveness and clinical benefit for coverage. The LCD aims to provide Medicare beneficiaries with access to scientifically supported skin substitute grafts and 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 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 delay of implantation is not appropriate as there are commercially available products that meet the R&N requirements. See response to comments #10, #20, and #56 regarding evidence and methodology for the LCD.

A commenter submitted concerns regarding device companies and lobbyists and potential conflicts of interest, financial gain, and the interest of the beneficiaries. They believe a previous change request (CR) which designated companies as stakeholders was a mistake.

Thank you for your comments. We agree that there are various influences in the market which is why it is so important that the products selected for coverage have the evidence to support their use for wound healing in DFUs and VLUs as in the LCD. The previous CR mentioned in the comment is outside the scope of the LCD and outside of the MAC’s control. See response to comments #10, #20, and #56 regarding evidence and methodology for the LCD.

A commenter submitted concerns regarding production of the covered products under the current proposed LCD. They are concerned that supply will not be enough to meet demands once the LCD goes into effect and are requesting additional time to increase production. They also state that providers and their staff will require training and education on the covered products which will take time. They request the MAC be mindful of this when implementing the final LCD.

We acknowledge concerns raised by stakeholders regarding potential treatment disruptions for patients within a care episode. We also acknowledge concerns related to supply and demand. Therefore, the notice period for this policy 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, ensure continuity of care for Medicare beneficiaries, and allow time for increased production should the manufacturers feel it necessary during this transition. See response to comment #42 for a discussion of supply chain issues.

A comment was received requesting SnapshotNIR, a non-contact, portable, near-infrared spectroscopy (NIRS) device, be added to the LCD for evaluating perfusion and tissue viability and help with decision making regarding the use of skin substitute grafts/CTP.

Thank you for your comment. No literature was submitted with this comment. Regarding the proposed technology in the comment, the modality to perform these measurements is out of the scope of the LCD which involves only skin substitute grafts/CTP for DFUs and VLUs. An LCD request can be made with included peer-reviewed published literature to address this specific area of wound care. Based on comments received during the comment period, ABI has been replaced in the LCD with “vascular assessments.”

A comment was received requesting more time for manufacturers to submit clinical trial or real- world data for product coverage prior to limiting A or Q code products. They also requested clarification on adding products in the future without having to reopen the LCD each time.

Thank you for your comments. See response to comment #57 regarding implementation delay. Medicare Administrative Contractors are required to base their coverage determinations on scientific evidence. The LCD provides a summary of evidence and analysis of evidence to support our coverage decisions. Providers may submit peer reviewed full-text articles to support coverage for skin substitute grafts/CTP via the reconsideration process outlined on our website once the LCD is finalized. See response to comment #27 for addition or transition of products to the covered list via reconsideration.

A comment was received regarding the combination drug/device product Omeza OCM. The commenter believes the product does not meet the definitions utilized in the proposed LCD and therefore, should not be included. CMS wrote in the 2023 OPPS rule in the Federal Register: “Regarding Omeza collagen matrix, an amorphous solid is not a graft skin substitute product even if the product forms a sheet-like layer after application. Therefore, we cannot assign the product to either the high-cost skin or the low-cost skin substitute group.” Omeza agreed with this assessment and therefore submitted in April 2024 a request for transitional pass-through designation as a new category of product in the outpatient setting (OPPS) in addition to its positive current reimbursement status in the office-based setting based upon the evidence of clinical utility. The commenter states Omeza OCM has been inappropriately included in the LCD and therefore should be explicitly removed as a product governed by the proposed LCD.

Thank you for your comment. There is no evidence that Omeza OCM is an exception and should be excluded from the LCD. The 510(k) letter from the FDA was reviewed and the predicate devices for Omeza OCM which the 510(k) clearance was based upon is a product that was being used as a skin substitute graft/CTP for management of chronic ulcers including DFU and 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 DFUs and VLUs, evidence for use must be demonstrated to be considered for coverage. There is not sufficient evidence to cover this product for management of chronic DFUs or VLUs, 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. Please refer to response to comments #10, #20, and #56 for information on the evidence consideration process.

A comment was received stating many concerns regarding the limiting of access to wound care products for beneficiaries, increased costs for the Medicare program, MACs working together to create a policy, the ability to obtain coverage through the reconsideration process, requirements of evidence for coverage, and the need for a CAC meeting on this topic.

Thank you for your comments. Please see response to comments #10, #20, and #56 regarding evidence and methodology for the LCD. See response to comments #5, #11, #24, and #69 for access concerns, and #27 for reconsideration requests.

A comment was received requesting that Resolve Matrix be placed in the covered group of products. The comment letter stated 3 reasons for this change in coverage: the predicate product, Oasis Wound Matrix, has already been identified for coverage in the proposed LCD, there is literature that supports coverage for Oasis Wound Matrix and Resolve Matrix, and the FDA has determined that Resolve Matrix is substantially equivalent to Oasis Wound Matrix, therefore, it is at least as safe and effective as Oasis Wound Matrix.

Thank you for your comments. 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.

The LCD is written with rigorous methodology applied uniformly across all studies with 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 there are no perfect studies and limitations are inherent, the LCD strives to provide coverage for products that demonstrate a high certainty that they enhance wound healing and clinical outcomes. This is done with a level of confidence that the observed benefits are due to the product's efficacy rather than random chance. Further investigation with more robust design, larger sample sizes, and long-term follow-up can refine the understanding of these products, but in the interim ensuring access to those products with supporting evidence is prioritized.

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.

A comment was received requesting coverage for the following: ACAPatch, CaregraFT, AlloPLY, and AmnioTX. The commenter states that each of these products received HCPCS Level II codes in the first quarter of 2024. These products are, by definition and FDA regulation, equivalent to other products listed in the covered group in the proposed LCD (Affinity, Amnioband, and EpiFix). Failure to treat the requested products as equivalent to the covered products mentioned would violate standards under the Administrative Procedure Act (APA) and due process that prohibit ‘arbitrary’ or ‘capricious’ decision making.

Thank you for your comments. No literature was submitted with this comment. For classification of products, see comment #68. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. For FDA regulatory requirements, see response to comment #77. Note, FDA approval or registration is not tantamount to Medicare coverage because the product must meet the reasonable and necessary standard.

The products requested for coverage by the commenter were not issued to the MAC until the 3rd quarter of 2024; therefore, they could not be included in the current policy. 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.

A comment was received requesting that product Talymed be covered in the final LCD due to the FDA’s determination that it is substantially equivalent to Oasis Wound Matrix which is covered. The commenter states there is overwhelming clinical evidence to support this conclusion.

Thank you for your comment. 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. See response to comments #56 and #77.

A comment was received with concerns regarding the transition to a new product if the patient is in a current treatment course with a product that will now be noncovered and what happens if the new product is not as effective in healing the patient’s wound. There is also concern about the 12-week limitation and complex wounds needing more time. The commenter also has concerns about the term ‘scaffolding’ used in the LCD. They state if they put ‘scaffolding’ in their TRG application for 361 HCT/P, the product will not be approved. They believe gel products should be included in the LCD.

The comment also includes concerns on the evidentiary bar required by the LCD. Studies required take many months to complete so they request additional time for studies to finish and more products to become available to avoid a delay in patient care. They also state that new innovations will be stifled as this LCD will drive investment away from wound care technologies.

Thank you for your comments. The LCD aims to provide Medicare beneficiaries with access to scientifically supported skin substitute grafts and 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 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 delay of implantation is not appropriate as there are commercially available products that meet the R&N requirements.

See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

We acknowledge concerns raised by stakeholders regarding potential treatment disruptions for patients within a 12-week care episode, therefore the notice period for this policy 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. In addition, 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 16 weeks allowing providers greater discretion on frequency of applications based on the needs of the individual patient.

A comment was received regarding patients who have multiple wounds requiring treatment with these products stating that it is not uncommon to have a healing wound when another has developed. The commenter also requests additional time for manufacturers to submit clinical trial or real-world data before limiting products via the LCD and a clear pathway on how to add future products without having to open the LCD each time.

Thank you for your comment. Each wound is considered separately and is considered as a distinct episode. However, the LCD only address DFUs and VLUs, so other types of wounds would be handled individually at the discretion of the MACs. See response to comment #57 for delay in implementation and #27 for addition and reconsideration of products.

A comment was received requesting a review of a study from Liden et al published in 2023. This study is a more recent, prospective, randomized, RCT involving Supra SDRM. This study was not included in the proposed LCD summary of evidence. The study compared Supra SDRM to a collagen dressing in the healing of DFUs. The study found that the median time to full healing was reduced by 44% in the Supra SDRM group versus the collagen group.

Thank you for your comments. The LCD basis for coverage decisions is based on evidence for the individual products and does not base this decision on SR/MA which are fraught with heterogeneity making it difficult to draw definitive conclusions. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

Thank you for the submission of the Liden et al 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 is not sufficient evidence for coverage of Supra SDRM. If future evidence is developed it can be submitted through the LCD reconsideration process.

A comment was received with concerns that certain products on the covered list are not supported by adequate data and evidence. The commenter requests that products with the same level of evidence be treated the same. They state that Kerecis Omega3 has the same amount and level of evidence as 3 (FlexHD Allopatch, Grafix Stravis, Oasis Tri-layer) products on the covered list, however, Kerecis Omega3 is not covered. They are requesting that the 4 products all be placed on the noncovered list based on the evidence for each product.

Thank you for your comments. The LCD aims to provide Medicare beneficiaries with access to scientifically supported skin substitute grafts and 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 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 delay of implementation is not appropriate as there are commercially available products that meet the R&N requirements. We have reviewed literature submitted related to Kerecis Omega3 and agree that it meets criteria for coverage and it has been placed in the covered list of products. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received with a provider testimony for the use of skin substitute grafts/CTP. The provider had a patient with an above the knee amputation (AKA) on one side who developed a wound on the other foot. The patient was going to choose hospice if he was facing a below the knee amputation (BKA) on the other foot as the idea of being immobile without any legs was not a life he wanted to live and he could no longer drive to dialysis. Using one of the products not on the covered list we were able to heal this patient's wound and keep it manageable, the patient is still doing well driving himself to dialysis.

Thank you for sharing this story and your comments. See response to comment #80 regarding the LCD development process and the need for literature-based evidence to support use of skin substitute grafts/CTP. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received requesting the coverage of a currently noncovered product, APIS. Two studies were submitted for review in support of this product to demonstrate the product’s safety, effectiveness, and positive clinical outcomes. The commenter also requests that applications be increased from 4 to 8.

Thank you for your comments and submitting literature. We have analyzed the papers but conclude there is insufficient evidence for coverage of the product APIS as explained in the evidence section of the LCD. The additional supporting literature was also referenced. If literature is developed that provides further clarification on the product this can be submitted through the LCD reconsideration process. See response to comment #12 for number of applications and frequency.

A comment was received requesting clarity for the use of skin substitute grafts/CTPs in other indications outside of DFUs and VLUs. They feel that leaving all other indications up to ‘medical necessity’ will create confusion. The commenter also requests that the timeframe of 4 weeks versus 30 days be reconciled throughout the LCD to be consistent.

Thank you for your comments. The policy is limited to only DFUs and VLUs. No other wounds are addressed. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. The B&C article has been corrected to 4 weeks in place of 30 days for consistency.

A comment was submitted requesting coverage for multiple products including Apligraft, Dermagraft, Affinity, NuShield, PuraPly AM, and PuraPly XT. The commenter states that each of these products meets all the criteria for coverage.

Thank you for your comments. Apligraft, Dermagraft, and Affinity are covered in the policy. Please refer to the LCD. The newly published literature for NuShield and PuraPly has been added to the LCD. The literature is not sufficient to support coverage of PuraPly as explained in the LCD section discussing PuraPly. The evidence regarding NuShield was deemed sufficient for coverage and the product has been added to the covered list. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A commenter requested the MACs provide timely recognition of additional products found to meet criteria within 30 days of receiving the new evidence. They request increasing number of applications permitted and clarification on the statement regarding excessive wastage to avoid confusion.

Thank you for your comments. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. For reconsideration requests and timing see response to comment #27. Documentation requirements and instructions, including wastage, are explained in the B&C Article, and not contained within the LCD. Additional guidance for wastage has been added to the B&C Article. The individual MACs will provide education and can develop tools if necessary to aid in compliance with documentation requirements. Steps to minimize wastage are expected to curtail the misuse of products which will in turn reduce demand by eliminating overutilization and improper use.

A comment was received stating that the LCD is a positive first step to curbing the fraud and abuse related to skin substitute grafts/CTPs. The commenter wanted to bring our attention to a CMS rule, “If obvious signs of worsening or lack of treatment response is noted, continuing treatment with the skin substitute would not be considered medically reasonable and necessary without documentation of a reasonable rationale for doing so.” They feel that the finalization will not end all the ongoing fraud and abuse but is a start in correcting it.

Thank you for your comments. The indications and limitations provide instructions for proper use and limits of skin substitute grafts in DFUs and VLUs. 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.

A comment was received expressing strong support for the proposed LCD. They submitted some recommendations to help strengthen the policy including an increased benchmark for exceptional cases, expanded covered diagnosis list, clarifying any discrepancies between the LCD and article, and providing an alternative to the ABI requirement.

Thank you for your comments. Clarification and additional information on the use of modifiers for exceptional cases have been incorporated into the B&C article. The LCD and B&C article will be revised to align. Please see response to comment #6 regarding the ABI requirement. Please see comment #29 regarding diagnosis codes.

A comment was received requesting a correction for the descriptor for AlloPatch in Table 1 of the LCD. The commenter requests removal of “MatrixHD” as the description now should read “FlexHD or AlloPatch HD, per square centimeter.”

Thank you for your comments. The descriptor for AlloPatch has been corrected.

A comment was received requesting coverage for product DermaPure which is a decellularized dermal allograft. The commenter states the product meets all the requirements included in the LCD. It is mentioned that the product is not a multi-application CTP and does not have a high ASP when used in a physician’s office. Clinical studies published in peer-reviewed journals demonstrate positive outcomes.

Thank you for your comments. The evidence for DermaPure was reviewed in the LCD and found to be insufficient for coverage. The new literature has been added to the LCD bibliography. Cost (ASP) is not a factor in determining coverage. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment requests that AmniPly be included in the LCD and that there is clinical evidence that supports its effectiveness in DFUs and VLUs. AmniPly meets criteria to be regulated under section 361 of the Public Health Service Act as evidenced by a letter from the FDA TRG.

Thank you for your comments. There was insufficient literature found to provide coverage for this product. FDA approval or clearance under Section 361 of the PHS Act is not tantamount to Medicare coverage. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. For reconsideration requests and timing see response to comment #27 once additional evidence becomes available for the product.

A comment was received agreeing with the application limitations but requesting clarification on the approval process for additional applications. The commenter requests product Amnioexcel be granted provisional payment status as there is a trial ongoing currently.

Thank you for your comments. The frequency of applications has been modified pursuant to feedback provided in the comments and new literature available. See response to comment #12. Amnioexcel was reviewed in the LCD and found to have insufficient evidence for coverage. We cannot consider unpublished literature. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. For reconsideration requests and timing see response to comment #27 once additional evidence becomes available for the product.

A comment was received discussing the positive effect skin substitute grafts/CTP have on wound healing and the economic implications of this. They strongly urge CMS to recognize the significance of including coverage of these products in the management of DFUs and VLUs.

Thank you for your comment. This is what this policy aims to do.

A comment was received concerning the MACs overlooking of important data that supports the coverage of Mirragen. One full-text study was submitted with the comment.

Thank you for your comments. 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 as reviewed in the evidence review and tables of the LCD. 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 response to comment #27). See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received stating that the MACs created what they consider to be an NCD by working together. They state the MACs circumvented the formal process required by CMS. They recommend the MACs have a formal consultation process with national clinical experts to opine prior to the LCD being finalized.

Thanks for your comments. MACs are permitted to collaborate. The MACs followed the process required for LCD development according to the PIM (Chapter 13). Stakeholder input was sought throughout the process and changes from previous draft LCDs were made based on this input. Comment letters from the previous open comment period including major societies, and numerous presentations including public listening sessions, and other open meetings 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 during this process. While not required for LCD development a technology brief developed by AHRQ informed the LCD development (see response to comment #27). See response to comment #28 for additional information.

A comment was received requesting changing of term ‘adjunctive treatment’ to ‘advanced therapy.’

Thank you for your comment. The LCD only refers to skin substitute graft/CTPs as advanced therapies. The only time they are referred to adjunctive therapy is in the “Societal Input” section, and this is to be consistent with the wording from the guidelines being referenced.

A comment was received requesting reconciliation of the discrepancy involving 4 weeks versus 30 days found in the LCD and article.

Thank you for your comment. This discrepancy has been reconciled.

A comment was received requesting the MAC write the LCD in such a way that products can be added to the list of covered codes in the LCD without going through the full reconsideration process, so patients have appropriate and timely access to products.

Thank you for your comments. The only way to achieve coverage is via the LCD reconsideration process as reflected in the PIM (Chapter 13). See response to comment #27 for reconsideration requests and timing when additional evidence becomes available for the product.

A comment was received requesting clarity on evidence criteria for coverage. The commenter states the LCD emphasizes RTCs, but it is unclear if other types of studies would qualify including real-world data and evidence which they feel should be considered.

Thank you for your comments. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received stating that the LCDs definition of a skin substitute functioning like ‘scaffolding for skin growth’ is contrary to FDA regulatory framework for 361 HCT/P products. The Proposed LCD requires that, to be eligible for Medicare coverage, skin substitutes must both (1) allow scaffolding for skin growth and remain on the recipient and grow in place or allow the recipient’s cells to grow into the implanted graft material and (2) be used in accordance with their intended use as approved/regulated by FDA. For 361 HCT/P products, however, it is impossible to meet both requirements.

The comment also discusses the use of the AMA CPT codebook. The AMA CPT codebook is simply a coding manual that classifies products and procedures. It is not a compendium of recognized uses of these products and procedures, nor does it purport to analyze any clinical data or evidence supporting their use. Therefore, it cannot be the sole source for Medicare coverage determinations.

Thank you for your comments. Section 361 of the PHS Act is only part of the FDA regulatory scheme, and it does not translate to Medicare coverage under the reasonable and necessary standard. See response to comment #80 for further information. The LCD is based entirely on evidence and not related to the FDA regulatory processes. The existence of an HCT/P does not equate coverage nor does that fact alone satisfy the definition of reasonable and necessary (see response to comments #5). The LCD does not evaluate products for function as scaffolding, but effectiveness in wound healing. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received requesting coverage of products Vendaje and AmnioWrap2. The commenter submitted a copy of the FDA’s TRG letter with the comment. They state these products are reasonable and necessary treatments for the healing of DFUs and VLUs that have failed to respond to conservative wound care measures.

Thank you for your comments. TRG letters do not relate to Medicare coverage of products under the LCD or generally under the reasonable and necessary standard of review. See response to comments #5, #80, and #102. Neither of these products have literature-based evidence to support their use in wound healing pursuant to the LCD. If peer reviewed published literature is available, it can be submitted through the LCD reconsideration process for consideration for coverage. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received with 4 recommendations for strengthening the proposed LCD. These included providing the GRADE criteria or protocols used to evaluate evidence, removing product-by-product evaluations and instead using an Appendix in the B&C article to avoid reopening the LCD each time new evidence is reviewed, providing an efficient timeline and process for new evidence to be reviewed and products covered, and permitting patients on treatment plans to be grandfathered if a product that will be noncovered is currently in use.

Thank you for your comments. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. The only way to achieve coverage is via the LCD reconsideration process as reflected in the PIM (Chapter 13). See response to comments #27 once additional evidence becomes available for the product. See response to comment #57 regarding the extended timeframe to prevent disruption in care.

A comment was received in disagreement with the proposed LCD stating that it is inappropriate and irresponsible. The commenter worries that the use of these products will be dampened instead of appropriately revamping the reimbursement of these products to those who report their ASPs.

Thank you for your comments. See response to comment #97 for information regarding the LCD process. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received with a brief review of studies in support of the use of skin substitute grafts/CTPs. The overview submitted was not related to any specific product, but the use of CTP in general and evidence of improved healing rates when they are used on DFUs. The commenter believes that covered products should not be limited as they have seen patients who respond to a CTP after not responding to a different CTP. Limiting the number of covered products will affect how they are able to treat patients.

Thank you for your comment. No full-text literature was submitted for review with this comment. See response to comment #97 for information regarding the LCD process. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received requesting additional time prior to implementing the LCD to allow for manufacturers to submit clinical trial data or RWE. They also request a clear pathway on how to add products in the future without opening the LCD each time.

Thank you for your comments. See response to comment #97 for information regarding the LCD process. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. The only way to achieve coverage is via the LCD reconsideration process as reflected in the PIM (Chapter 13). See response to comment #27 once additional evidence becomes available for the product.

A comment was received thanking the MAC for doing the work for this proposed LCD.

Thank you for your comment.

A comment was received requesting additional time for implementation and patients on current treatment plans be grandfathered.

Thank you for your comments. See response to comment #97 for information regarding the LCD process. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. See response to comment #57 regarding the extended timeframe to prevent disruption in care and implementation delay.

A comment was received regarding a paper that was referenced in the LCD; however, the paper makes no reference to CTPs. The commenter objects to the implication that the paper discussing tumor regression is even relevant to the LCD. They are requesting it be deleted.

The commenter also requests the term ‘skin replacement therapy’ be changed to ‘skin replacement surgery’ throughout the LCD.

Thank you for your comments. We also feel that skin replacement surgery is the appropriate terminology and consistent with published literature. The Winkler paper was submitted by a stakeholder during the comment period from a prior draft LCD and several CTP have published bench studies demonstrating they interact with the extracellular matrix as part of their mechanism for wound healing, so it is pertinent to the better understanding the 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.

A comment was received requesting an extended notice period to allow clinicians to complete current episodes of care and not interrupt care to switch products. If an extension for implementation is not possible, they request that patients on current treatment plans be grandfathered.

The implementation timeline has been extended to 90-days total to mitigate interruptions in care. See response to comment #57, regarding the extended timeframe to prevent disruption in care and implementation delay.

A comment was received requesting a complete revision of the draft LCD. Other recommendations received from the commenter are removing ‘exceptional cases’ and add examples of demonstrable progression in healing, language should be added that in cases where there may be limited availability for vascular studies every attempt should be made and any obstacles prohibiting it should be documented, remove ‘suggested as’ benchmarks and replace with portable near-infared spectroscopy, allow additional time for manufacturers to submit clinical trial data before policy implementation, and add a clear pathway on how to add future products and evidence without having to open the LCD each time.

Thank you for your comments. See response to comment #57 regarding the extended timeframe to prevent disruption in care and implementation delay. See response to comment #27 once additional evidence becomes available for the product. 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 response to comments #4 and #12). Regarding vascular assessments, we believe the choice of techniques stated in the LCD are supported by sufficient literature.

A comment was received stating that the proposed LCD does not have an acceptable definition of skin substitute graft that is consistent with medical use and considers the diversity of products. The commenter says this is evident by the misuse of the word ‘graft’ in the title of the LCD and this misuse will misinform providers on the intent and purpose of the LCD.

Thank you for your response. Regarding the definition of skin substitute grafts/CTP, the LCD acknowledges lack of clarity and the definition of skin substitute grafts/CTP but determines that the definition that aligns with the CPT code book is most appropriate as these are the codes that are addressed by the LCD. If additional evidence is developed in the future to justify a change to the definition this may be considered through the LCD reconsideration process (see response to comment #27). 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, B&C article, and CPT code book ensure accuracy when billing for the products and services provided. Also, the definition of CAMP has been added to the LCD, but the LCD refers to skin substitute grafts/CTP throughout to be consistent with the current literature and guidelines as this new terminology has not been fully adopted at this time and is not reflected in most literature.

A comment was received disagreeing with the proposed LCD’s requirement for specialty care related to venous/arterial cases and diabetes. They believe this will result in significant delays in care and ensuing malpractice for providers who are not initiating therapy while patients are awaiting specialist care. The commenter also stated that it is not reasonable for medical evaluation of vascular disease to occur within 4 weeks of identification as there are limited vascular surgeons in the US and many beneficiaries do not have access to Vascular Interventional Radiology. They are also concerned that in some markets, the wait time for endocrinology appointments can be 3 months or greater. Another concern they submitted was the deviation from the instructions for use regarding the number of applications on multiple products (specifically mentioning Apligraft, Dermagraft, and Oasis products).

Thank you for your comments. No full text literature was submitted with this comment. The application frequency of these products has been updated as a result of comments received and further review of the literature, see response to comment #12 and the revised LCD. 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.

A comment was received requesting a simplified process that the MACs will follow to add new codes for products to the LCD and B&C article. They recommend a review of the ‘non-covered’ codes on a quarterly basis as new products are granted HCPCS codes.

Thank you for your comments. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. The only way to achieve coverage is via the LCD reconsideration process as reflected in the PIM (Chapter 13). See response to comment #27 once additional evidence becomes available for the product.

A comment was received indicating that the limitation in number of products available with the proposed LCD does not allow providers the freedom to treat their patients with the flexibility to switch products if they find one product is not resulting in improved healing. They are requesting a pathway for exceptional circumstances to use additional products if the patient’s wound is not responding to treatment with the covered products.

Thank you for your comments. The policy covers those products that have evidence to support their use in wound healing in DFUs and VLUs. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. See response to comment #42 for supply chain issues.

A comment was received requesting greater detail in the LCD on the topic of wound assessment and SOC treatment in the 4 weeks prior to skin substitute graft/CTP therapy. They suggest options focused on wound care clinician training, best practices in wound bed preparation, metrics to aid in determining when the wound is best prepared for graft/product placement, and key parameters of wound bed appearance to increase the probability that these products would bring the wound to closure. The commenter also requests transparency in the clinical trial design of high certainty evidence evaluated in the LCD.

Thank you for your comments. Wound bed preparation, training of clinicians, and metrics/parameters to aid in determining wound bed readiness is outside of the scope of this LCD. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received requesting clarification on patients in a current episode of care being treated with a product that will be noncovered with the implementation of the LCD. The commenter suggests a phase in approach to allow to provider training and patient transition to a new product. They are also requesting guidance of evidence requirements for future studies so that they may be considered when published.

Thank you for your comments. See response to comment #57 which details the extension of the effective date of the LCD which will mitigate interruptions in care. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received requesting insight on the appropriate control groups to demonstrate medical necessity when comparing skin substitute grafts. The commenter understands that FDA clearance does not equate to reasonable and necessary, but they are wanting examples of this to help educate providers how to understand for example, well-done studies versus a case series. They feel this is important because often advanced dressings are denied as not reasonable and necessary.

Thank you for your comments. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received suggesting removal of Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification for VLUs as they state it does not have anything to do with outcomes for VLUs. They also request additional applications greater than 4 due to factors such as comorbidities, age, ulcer size, volume, location, etc.

Thank you for your comments. No full-text literature was submitted with this comment. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD. See response to comment #12 regarding changes in number of applications.

A comment was received requesting additional time prior to implementation of the LCD to allow for manufacturers to submit clinical data and possibly add products to the covered list as they feel that there are too few covered in the proposed LCD that nuanced needs of their patients may not be met. They also suggest a streamline pathway for the addition of new products without having to open the LCD up for comment every time.

Thank for your comments. The 45-day notice period has been extended to 90 days. See response to comment #57. Peer reviewed literature-based evidence can be submitted in an LCD reconsideration request for new products. See response to comment #27 which outlines the reconsideration process for additional products to be considered for coverage as well as transition from covered to non-covered status in the LCD.

A comment was received stating skin substitute products are more effective for wounds compared to SOC.

Thank you for your comment.

A comment was received with a provider’s clinical experience and support of the product DermaPure. The provider states they have used this product for many types of wounds including DFUs and VLUs with increased rates of wound healing. They give some personal practice statistics in support of this product.

Thank you for your comments. Please review response to comment #92 for the reason DermaPure is not covered in the LCD. See response to comments #10, #20, and #56 regarding evidence, rationale for the policy, and methodology for the LCD.

A comment was received concerning the implementation of the new policy and patients who are within an episode of treatment. They request information on how patients will be transitioned to new products. They also request clarity on the timelines, requirements for publications, and a clear pathway for tissue companies to move from non-covered to covered status.

Thank you for your comments. See response to comment #57 which describes the 90-day extension for the effective date of the policy that will mitigate interruptions of care or access concerns. See response to comment #27 which outlines the reconsideration process for additional products to be considered for coverage as well as transition from covered to non-covered status in the LCD.

A beneficiary submitted a comment stating how much skin substitute products help them in healing their own wound. They do not feel that critical wound care should be limited by Medicare.

Thank you for your comments. Medicare only covers services or products that have evidence to support the reasonable and necessary standard for care. Thus, this policy is limited to DFUs and VLUs and the products that have evidentiary support for their use in wound healing.

A provider commented that they use Clarix grafts for cases and loves the results. The product can be kept in the freezer which they state has been a ‘game changer’ that helps reduce inflammation and scarring.

Thank you for your comments. This product and supporting literature were reviewed in the LCD and found to lack sufficient evidence for coverage for DFUs and VLUs. See response to comment #27 which outlines the reconsideration process for products to be considered for coverage as well as transition from covered to non-covered status in the LCD.

A comment was received supporting the LCD and requesting coverage for 2 products, Amnioband Membrane and AlloPatch Pliable, to be covered for both DFUs and VLUs.

Thank you for your comments. No literature was submitted. AmnioBand was found to have sufficient evidence for coverage for DFUs and VLUs. AlloPatch was found to have sufficient coverage for DFUs. There is insufficient evidence for further coverage. The LCD provides the explanation. Please see response to comment #27 which outlines the reconsideration process for products to be considered for coverage as well as transition from covered to non-covered status in the LCD.

A Comment was received from a provider concerned that with the implementation of the LCD, their practice will have to undergo the process of sourcing new products and patients who have failed to heal with products on the covered list will continue to suffer due to limited product options. They suggest allowing only products on the ASP pricing file to provide some limitation, but not as strict as the proposed LCD.

Thank you for your comments. The LCD will help Medicare patients as it will drive providers to use products that facilitate healing and have literature-based evidence to support coverage. The LCD will be effective 90 days from final publication, rather than 45 days so there will be a slight delay in implementation. See response to comment #42 regarding supply chain issues. We believe there will be no delay in provision of covered products.

A comment was received requesting clarification on the JZ/JW modifiers as they believe it will create confusion among providers. They suggest that all MACs keep the same general guidance related to the modifiers as to create consistency across the MACs. They also request that the 4 weeks versus 30 days discrepancy be reconciled prior to publication. A suggestion was also made to revise the terminology regarding comorbidities from ‘correcting’ to ‘optimizing’ as in most cases, diabetes cannot be ‘corrected.’

Thank you for your comments. The B&C article has been corrected to 4 weeks (not 30 days) for consistency. We agree with the suggested clarification of terms throughout the LCD and these changes have been made based on this feedback specifically changing ‘correcting’ to ‘optimizing.’ JZ/JW modifier clarification has been added to the B&C article.