Percutaneous Image-guided Lumbar Decompression for Lumbar Spinal Stenosis

On January 9, 2014, CMS posted its final decision memorandum for the National Coverage Determination (NCD 150.13) covering PILD for beneficiaries with LSS when provided in a prospective, randomized, controlled clinical study meeting certain conditions under the Coverage with Evidence Development (CED) determination. We received a request to reconsider this NCD based in part on evidence developed in those studies.

We believe that the new evidence supports  broader coverage under CED, therefore the Centers for Medicare & Medicaid Services (CMS) proposes to modify the existing NCD to cover percutaneous image-guided lumbar decompression (PILD) when provided in a clinical study under §1862(a)(1)(E) of the Social Security Act through Coverage with Evidence Development (CED) for Medicare beneficiaries with lumbar spinal stenosis (LSS) who are enrolled in an approved clinical study that meets the broader criteria set forth below. 

The CMS-approved protocol must answer all of the following questions:

For investigators that have completed a CMS-approved randomized controlled clinical trial as specified in the NCD manual (150.13), Medicare proposes to continue to cover PILD under CED for new patients with LSS enrolled and followed in a CMS-approved prospective cohort study.  The new prospective cohort study protocol must specify a statistical analysis and a minimum length of patient follow-up time that evaluates the effect of beneficiary characteristics on patient health outcomes as well as the duration of the benefit.  Outcomes of interest include 6-month, 12-month, and 24-month beneficiary function, quality of life, reduction in pain, change in pain medication use, and change in the overall clinical management of LSS and decision making. This prospective cohort study must also have the following characteristics:

1. The study is conducted by the same study sponsors that conducted a CMS-approved prospective, randomized, controlled trial of PILD for LSS under CED. 
2. The eligibility requirements, both inclusion and exclusion criteria that were specified in the CMS-approved RCT protocol, must be maintained in the new prospective cohort study.
3. The same outcome measures as were used in the CMS-approved RCT must be used in the new prospective cohort study compared to other treatments.
4. Changes in the use of any pain medication for LSS must be tracked in the new prospective cohort study. 
5. All study sites must be listed in the ClinicalTrials.gov database.

All CMS-approved clinical research studies must adhere to the following standards of scientific integrity and relevance to the Medicare population:

Consistent with section 1142 of the Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that CMS determines meet the above-listed standards and address the above-listed research questions.

See Appendix B for the proposed manual language.

CMS is seeking comments on our proposed decision.  We will respond to public comments in a final decision memorandum, as required by §1862(l)(3) of the Social Security Act (the Act).

TO:		Administrative File:  CAG-00433R 
 
FROM:	Tamara Syrek Jensen, JD 
		Director, Coverage and Analysis Group 
		 
		Joseph Chin, MD, MS 
		Deputy Director, Coverage and Analysis Group 
 
		James Rollins, MD, PhD 
		Director, Division of Items and Devices 
		Lead Medical Officer 
		 
		Xiufen Sui, MD, MS 
		Biostatistician 
		 
		Rosemarie Hakim, PhD 
		Epidemiologist 
		 
		Cheryl Gilbreath, PharmD, MBA, RPh 
		Lead Analyst 
		 
		Tara Hall, LGSW 
		Analyst 
		 
SUBJECT:	Proposed National Coverage Determination for Percutaneous Image-guided Lumbar Decompression (PILD) for Lumbar Spinal Stenosis (LSS) 
 
DATE:		September 8, 2016

I. Proposed Decision

On January 9, 2014, CMS posted its final decision memorandum for the National Coverage Determination (NCD 150.13) covering PILD for beneficiaries with LSS when provided in a prospective, randomized, controlled clinical study meeting certain conditions under the Coverage with Evidence Development (CED) determination. We received a request to reconsider this NCD based in part on evidence developed in those studies.

We believe that the new evidence supports  broader coverage under CED, therefore the Centers for Medicare & Medicaid Services (CMS) proposes to modify the existing NCD to cover percutaneous image-guided lumbar decompression (PILD) when provided in a clinical study under §1862(a)(1)(E) of the Social Security Act through Coverage with Evidence Development (CED) for Medicare beneficiaries with lumbar spinal stenosis (LSS) who are enrolled in an approved clinical study that meets the broader criteria set forth below.

The CMS-approved protocol must answer all of the following questions:

For investigators that have completed a CMS-approved randomized controlled clinical trial as specified in the NCD manual (150.13), Medicare proposes to continue to cover PILD under CED for new patients with LSS enrolled and followed in a CMS-approved prospective cohort study.  The new prospective cohort study protocol must specify a statistical analysis and a minimum length of patient follow-up time that evaluates the effect of beneficiary characteristics on patient health outcomes as well as the duration of the benefit.  Outcomes of interest include 6-month, 12-month, and 24-month beneficiary function, quality of life, reduction in pain, change in pain medication use, and change in the overall clinical management of LSS and decision making. This prospective cohort study must also have the following characteristics:

1. The study is conducted by the same study sponsors that conducted a CMS-approved prospective, randomized, controlled trial of PILD for LSS under CED. 
2. The eligibility requirements, both inclusion and exclusion criteria that were specified in the CMS-approved RCT protocol, must be maintained in the new prospective cohort study.
3. The same outcome measures as were used in the CMS-approved RCT must be used in the new prospective cohort study compared to other treatments.
4. Changes in the use of any pain medication for LSS must be tracked in the new prospective cohort study. 
5. All study sites must be listed in the ClinicalTrials.gov database.

All CMS-approved clinical research studies must adhere to the following standards of scientific integrity and relevance to the Medicare population:

Consistent with section 1142 of the Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that CMS determines meet the above-listed standards and address the above-listed research questions.

See Appendix B for the proposed manual language.

CMS is seeking comments on our proposed decision.  We will respond to public comments in a final decision memorandum, as required by §1862(l)(3) of the Social Security Act (the Act).

II. Background

Throughout this document we use numerous acronyms, some of which are not defined as they are presented in direct quotations.  Please find below a list of these acronyms and corresponding full terminology:

AAOS - American Association of Orthopaedic Surgeons
ASA - American Society of Anesthesiologists
BMI - body mass index
CED - Coverage with Evidence Development
CI - confidence interval
CMS - Centers for Medicare & Medicaid Services
CT - computed tomography
ECRI - Emergency Care Research Institute
ESI - epidural steroid injection
FDA - Food and Drug Administration
LF - ligamentum flavum
LSS- lumbar spinal stenosis
MIC - minimal important change
MILD - minimally invasive lumbar decompression
MRI - magnetic resonance imaging
NASS - North American Spine Society
NC - neurogenic claudication
NCA - National Coverage Analysis
NCD - National Coverage Determination
NIH - National Institutes of Health
NPRS - numeric pain rating scale
NRS - numeric rating scale
ODI - Oswestry Disability Index
PDI - Pain Disability Index
PE - pulmonary embolism
PILD - percutaneous image-guided lumbar decompression
PROMIS - Patient-Reported Outcomes Measurement Information System
RCT - randomized controlled trial
US - United States
VAS - visual analog scale
ZCQ - Zurich Claudication Questionnaire

The scope of this national coverage analysis (NCA) includes a review of the evidence on whether PILD improves health outcomes in Medicare beneficiaries with LSS.

Most people will experience low back pain at some point in their lives. Pain complaints are the leading reason for medical visits. The most common pain complaints are musculoskeletal, and back pain is the most common of these, and the prevalence and impact of back pain have led to an expanding array of tests and treatments, including injections, surgical procedures, implantable devices, and medications. (Deyo et al. 2009)

Spinal stenosis is the most common reason for lumbar spine surgery in adults over the age of 65 years.  (Weinstein et al. 2008) Spinal stenosis often results from the aging process. Surgery for spinal stenosis was reported to be the fastest-growing type of lumbar surgery in the United States from 1980 to 2000. Rates of surgery for lumbar stenosis declined slightly from 2002-2007, but use of more complex procedures has increased substantially. (Deyo et al. 2010)

A 1995 population study in Sweden reported spinal stenosis incidence of 50 per 100,000; an incidence of 25 per 100,000 inhabitants for spinal stenosis associated claudication; and, an incidence of 1 per 100,000 for cauda equina syndrome. (ECRI Health Technology Assessment Group 2001)

Lumbar spinal stenosis (LSS) is defined as the reduction of the cross sectional area, i.e. narrowing, of the lumbar spinal canal. It is usually caused by spinal degenerative conditions and is commonly found to be asymptomatic. (Kovacs et al. 2011) LSS is sub-classified into three broad categories, specifically central stenosis, lateral stenosis, and spondylolisthesis. Central stenosis refers to a narrowing of the spinal canal across the anterioposterior diameter, the transverse diameter, or both". (ECRI 2001)

Symptomatic patients typically present with symptoms of radicular leg pain or with neurogenic claudication (pain in the buttocks or legs on walking or standing that resolves with sitting down or lumbar flexion). Indications for surgery appear to vary widely, and rates of procedures vary five-fold or more across geographic areas. (Weinstein et al. 2008)

The geographic variation in treatment of LSS, the lack of a definitive diagnostic tool, and the absence of reliable evidence about the natural history of the condition bring up issues on how to best approach the treatment of LSS. The North American Spine Society (NASS) evidence-based clinical guideline identified an absence of reliable evidence about the natural history of degenerative lumbar stenosis. (NASS 2011) The ECRI technology assessment reported, "…the presence of apparent stenosis in the asymptomatic population raises a question about whether stenosis per se causes symptoms, those with more severe symptoms are more likely to have stenosis. …The presence of stenosis and slippage in spinal images of asymptomatic people indicates that treatment must be based on the convergence of symptoms and image evidence rather than on either type of evidence alone." (ECRI 2001)

Haig reported, "Some clinicians use the term stenosis to describe statistical deviation from average size of the spinal canal or neural foramen regardless of the symptoms, while others use it to describe a clinical syndrome that presents classically with neurogenic claudication-pain in the back or legs with ambulation." (Haig et al. 2006) There are no standard criteria for the clinical diagnosis of stenosis. Anatomic measures can be obtained via imaging tests such as magnetic resonance imaging (MRI), which have become a standard for diagnosis. However no clear relation between the severity of symptoms and the extent of stenosis on imaging exists; and surgical outcomes do not clearly relate to the results of imaging measures. In addition, no cutoff for canal size measurement to diagnose the clinical syndrome has been widely accepted. (Haig et al. 2006)

Little is known about the diagnostic accuracy of the different tests available in detecting LSS. (de Graaf et al. 2006) De Graaf talked about an ideal situation with a "clear diagnostic entity with an agreed gold standard to prove its existence as well as knowledge about the natural course and effectiveness of treatments." However, there is no consensus about the gold standard. After a systematic review of the accuracy of diagnostic tests for the diagnosis of LSS, de Graaf could not "draw any firm conclusions about the diagnostic accuracy of imaging, clinical, and other tests in diagnosing lumbar spinal stenosis." (de Graaf et al. 2006)

It appears consensus concerning the definition of spinal stenosis has not been reached among experts. There is no "gold standard" for diagnosis and treatment of stenosis because of variable signs and symptoms, physicians’ history-taking and physical methods and diagnostic tests. (Sandella et al. 2013)

LSS is a pathological condition causing a compression of the contents of the canal, particularly the neural structures. In 2003, Gunzburg and Szpalski opined that if compression does not occur, the canal should be described as narrow but not stenotic. Degenerative disc disease is the most common cause of LSS. A bulging degenerated intervertebral disc anteriorly, combined with thickened infolding of ligamenta flava and hypertrophy of the facet joints posteriorly result in narrowing of the spinal canal. The site of compression may be central, lateral or a combination of the two. "When a canal size is too narrow for the dural sac size that it contains, stenosis occurs. An identical canal size can therefore be stenotic for one person while not being stenotic for another who happens to have a smaller dural sac size. LSS is therefore a clinical condition and not a radiological finding or diagnosis." (Gunzburg and Szpalski 2003)

The utility of diagnostic imaging studies should be to confirm the information gathered from a thorough history and physical exam. In 1996, Boden warned, "Excessive reliance on diagnostic studies without precise clinical correlation can lead to erroneous or unindicated treatment of degenerative disorders of the lumbar spine." (Boden 1996) The clinical syndrome for stenosis does not always present with classic complaints on examination, and similar symptoms occur in a wide variety of disorders ranging from vascular disease to polyneuropathy to mechanical back pain. According to Haig (2006), further confusion can come into play when a radiologist’s report of stenosis influences the clinician’s impression.

Unfortunately, there remains a lack of consensus among clinicians about the indications for surgical intervention for LSS. (Kurd et al. 2012) Non-surgical or conservative care for LSS may include physical therapy, epidural injections, chiropractic manipulation, acupuncture, lumbar corset, the use of anti-inflammatory drugs, and the use of opioid analgesics.

Treatment options for LSS, historically, have varied from conservative management on the one hand and invasive surgical decompression on the other hand. There is a gap for patients failing the former but not severe enough or not ready for the latter. (Mekhail et al. 2012) "While conservative measures, such as physical therapy with/without epidural steroid injections, may be adequate for mild cases, they fail to provide long-term relief to the moderate-to-severe LSS patient and, thus the progression to the next treatment option of surgery. The goal of surgical treatment for symptomatic lumbar canal stenosis is to achieve relief of symptoms by adequate neural decompression while preserving as much of the anatomy and not disrupting the biomechanics of the lumbar spine as possible." (Mekhail et al. 2012)

The AAOS website provided the following information about surgical options for LSS.

The focus of this national coverage analysis is on a newer technique - percutaneous image-guided lumbar decompression (PILD) which is a posterior decompression of the lumbar spine performed under indirect image guidance without any direct visualization of the surgical area. The use of a cannula and trocar provides a portal that allows access to the anatomic area for instruments used for resection. This is a procedure proposed as a treatment for symptomatic LSS unresponsive to conservative therapy. This procedure is generally described as a relatively non-invasive (compared to open surgery) procedure using specially designed instruments to percutaneously remove a portion of the lamina and debulk the ligamentum flavum. (The terms non-invasive, minimally invasive and percutaneous are used interchangeably in the literature.) The procedure is performed under x-ray guidance (e.g., fluoroscopic, CT) with the assistance of contrast media to identify and monitor the compressed area via epiduragram. The procedure that most closely falls under this description is commercially known as the mild® procedure. (Vertos Medical) "The mild® procedure offers a minimally invasive alternative to a standard laminotomy-laminectomy." (Deer et al. 2011)

Endoscopically assisted laminotomy/laminectomy, which requires open and direct visualization, as well as other open lumbar decompression procedures for LSS are not within the scope of this NCA.

III. History of Medicare Coverage

On January 9, 2014, CMS posted its final decision memorandum for National Coverage Determination (NCD 150.13), (https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=269), covering PILD for beneficiaries with LSS when provided in a randomized controlled clinical trial (RCT)  meeting certain conditions under section 1862(a)(1)(E) through Coverage with Evidence Development (CED).  The RCTs must be designed using current validated and reliable measurement instruments and clinically appropriate comparator treatments, including appropriate medical or surgical interventions or a sham controlled arm, for patients randomized to the non-PILD group.

Two studies have been approved:

Study Title: MILD® Percutaneous Image-Guided Lumbar Decompression versus Epidural Steroid Injections in Patients Diagnosed with Lumbar Spinal Stenosis Exhibiting Neurogenic Claudication.
Sponsor: Vertos Medical
Clinicaltrials.gov Number: NCT02093520
CMS Approval Date: 05/06/2014

Study Title: A Prospective, Multi-center, Randomized Controlled Double-Blind Trial Evaluating the VertiFlex® Totalis™ Direct Decompression System versus a Sham Surgical Procedure in Patients with Lumbar Spinal Stenosis
Sponsor: VertiFlex®, Inc.
Clinicaltrials.gov Number: NCT02079038
CMS Approval Date: 05/22/2014

CMS received a complete formal request for a reconsideration of the January 9, 2014, NCD which limits coverage of PILD for LSS to RCTs.  The formal request letter can be viewed via the tracking sheet for this NCA on the CMS website at https://www.cms.gov/medicare-coverage-database/details/nca-tracking-sheet.aspx?NCAId=284.

Medicare is a defined benefit program.  For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in the Social Security Act.  PILD may be considered to be within the benefits described under sections;

• 1861(b) as an inpatient hospital service,
• 1861(s)(2)(B) as a hospital service incident to physicians’ services rendered to outpatients, and
• 1861(s)(1) as a physician service.

Note: This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service.

IV. Timeline of Recent Activities 

V. Food and Drug Administration (FDA) Status

Various devices implanted during spine surgery may fall under FDA regulatory oversight. The focus of our review is for the PILD procedure and no devices are implanted during this procedure, however there are specialized instruments that are used which are under the oversight of the FDA.

The MILD® tool kit (Vertos Medical) initially received 510(k) clearance as the X-Sten MILD Tool KIT (X-Stern Corp.) in 2006. The indications for use are identified as, "The X-Sten MILD Tool Kit is a set of specialized surgical instruments intended to be used to perform percutaneous lumbar decompressive procedures for the treatment of various spinal conditions." (http://www.accessdata.fda.gov/cdrh_docs/pdf6/K062038.pdf)

The VertiFlex® Totalis ™ Direct Decompression System received 510(k) clearance in 2012. The indications for use are identified as, "The VertiFlex® Direct Decompression System is a set of specialized surgical instruments intended to be used to perform lumbar decompressive procedures for the treatment of various spinal conditions." (http://www.accessdata.fda.gov/cdrh_docs/pdf12/K122662.pdf)

VI. General Methodological Principles

When making national coverage determinations, CMS generally evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within a benefit category is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.  The critical appraisal of the evidence enables us to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for beneficiaries.  An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary.

A detailed account of the methodological principles of study design that the Agency utilizes to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix A.

Public comments sometimes cite published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination. Public comments that contain personal health information will not be made available to the public. CMS responds in detail to the public comments on a proposed national coverage determination when issuing the final national coverage determination.

VII. Evidence

Neurogenic claudication and various back and leg pains are symptoms of LSS.  Sustained improvement in these symptoms of pain perception and a reduction in the pain-related functional restrictions are appropriate outcomes of clinical trials.  It is challenging to attribute symptom changes to treatment because the natural history of degenerative lumbar spinal stenosis is unclear.  (Issack 2012)  Additionally, pain perception is subject to regression to the mean and placebo effect.  Therefore, clinical trials with appropriate controls utilizing independently assessed validated instruments are most heavily weighted.

Patient reported outcomes reflecting symptoms and function are often used to measure the effects of treatment for symptomatic degenerative lumbar spinal stenosis.  Standardizing the measures facilitates study comparison.  The most commonly used instruments are the Oswestry Disability Index (LDI) and the visual analog scale (VAS).  The ODI is used to measure a patient’s functional disability on a scale of 1 to 100.  VAS measures pain intensity on a scale of 0 to 10.  The Zurich Claudication Questionnaire (ZCQ) is a less commonly used assessment tool for patient function and has several domains.  The Pain Disability Index (PDI) and the Roland-Morris Disability Questionnaire (RMQ) are also tools for measuring disability.  The SF-36 and shorter version, SF-12, are measures of general health status.  A recent study in patients with LSS revealed that subjective measures of pain and disability had little correlation to actual patient activity, calling into question the current use of these measures without other performance or non-pathology specific outcomes.  (Pryce, et al. 2012)  CMS attributes more evidentiary weight to those studies reporting reliable, validated outcomes that reflect true patient activity and quality of life.

With the use of any of these instruments, consideration must be given to the clinical meaning of a change in the reported score.  How well, if at all, does a score change of some increment reflect a meaningful change in symptom or function experienced by the patient?  Other considerations include the error of measurement of the instrument used and the clinical importance of a statistically significant score change.  In a 2003 study by Hagg of 29 patients treated surgically or non-surgically in a randomized controlled trial, the standard error of measurement of the ODI was four units, with a 95% tolerance interval of 10, and the minimum difference that appeared clinically important was 10 units.  The minimal clinically important difference of VAS back pain was 18-19 units [on a 100 point scale] with a 95% tolerance interval of 1.5. (Hagg, et al. 2003)  These recommendations are similar to those by Ostelo who also noted that when baseline was taking into account, a 30% improvement when comparing before and after measures for individual patients—should be the guide for the minimal important change (MIC).  (Ostelo, et al. 2008)  Ostelo, in an aim towards international consensus regarding minimal important change, noted that workshop participants (during the Low Back Pain Forum VII) stressed that proposed MIC values were for individual rather than group changes.  (Ostelo, et al. 2008)  The clinically important change is based on an individual, but is often misused to compare the difference in mean scores between two groups, but this is not a clinically important difference.  (MEDCAC 2006)

Determining the true clinical impact of interventions that treat pain and improve pain-related functional difficulties is challenging.  Well-designed clinical trials can provide the strongest evidence for treatment effect.  Well-constructed randomization protects against bias and inclusion of an appropriate comparator facilitates study interpretation.  In pain treatment trials, the natural history of the disease, regression toward the mean and the placebo response are important considerations.  For these reasons, an appropriate comparator is necessary for accurate interpretation.  Accurate interpretation of pain treatment trials also necessitates reporting of concomitant pain treatments, most importantly analgesic use.  In the case of research in the area of pain treatment, more evidentiary weight is accorded to studies designed to mitigate the bias of placebo response and that account for the natural history of the disease and regression toward the mean.

The 2014 PILD NCD final decision memorandum considered literature published before November 29, 2013.  Section VII, the Evidence Section, of the 2014 decision memorandum includes an explanation of the evidence we considered. We are incorporating the entirety of the previous NCD record as part of this reconsideration record. We performed a literature search utilizing PubMed for randomized controlled trials (RCTs) and nonrandomized controlled trials, cohort or case-control studies, case series studies, and systemic reviews for "percutaneous image-guided lumbar decompression for lumbar spinal stenosis."  CMS limited the search to English language articles specific to the human population. But CMS considered English-language studies conducted outside—as well as inside—the United States.

In this proposed decision memorandum, CMS discusses all new human, English language articles related to PILD that have been published since November 29, 2013. We use a number of sources to identify articles in the medical literature that addressed the use of PILD in patients with LSS. These sources included PubMed, Embase, and Cochrane Collaborative Library. 

We searched the above mentioned three databases for the following terms:

• Lumbar Stenosis
• Lumbar Spinal Stenosis (LSS)
• Minimally Invasive Lumbar Decompression (MILD)
• Percutaneous Decompression
• Percutaneous Image-Guided Lumbar Decompression (PILD)

After performing these searches, CMS then excluded non-English language articles, studies with fewer than ten (10 patients), and those not including human subjects.

We found six articles that met the above criteria. They include the following:

1. One systematic review (Kreiner et al. 2013)
2. Two articles evaluating the same randomized controlled trial (Peter 2016 and Ramsin 2016)
3. One single-site prospective study (Basu 2012)
4. One retrospective observation cohort study (Durkin et al. 2013)
5. One case-series study (Wang et al. 2013)

The questions of interest for this NCA are:

Is the evidence sufficient to conclude that PILD improves health outcomes in Medicare beneficiaries with LSS?

CMS did not request an external technology assessment (TA) on this issue.

Basu S. Mild Procedure Single-Site Prospective IRB Study. Clin Journal of Pain. 2012;28:254-258.

The objective of this study was to describe the six (6) month safety and efficacy results of the MILD procedure in patients treated in a single center. Twenty-seven (27) patients were treated in two (2) study phases from November 2009 through June 2010.

All 27 patients had neurogenic claudication with radiographic confirmation of hypertrophy of ligmentum flavum. They previously had failed conservative treatment. Endpoints of the study included:

1. VAS—to provide a measure of the patient’s back and leg pain;
2. ODI –to measure functional disability; and
3. ZCQ—to measure physical function, symptom severity, and patient satisfaction

The study participants included 14 females and 13 males with a mean age of 63.3 years (range 37 to 83). A total of 44 levels were decompressed; one was unilateral, the rest were bilateral.

No significant intraoperative or postoperative complications were reported. Also, no subsequent surgical decompression procedures were performed during the six (6)-month follow-up period.

Subjects experienced a statistically significant improvement in VAS pain scores (9.1 at baseline to an average of 3.9 at six months; P < 0.001). The baseline average ODI score of 55.1 showed statistically significant improve at six months with a score of 31.1 (P < 0.004). At the six (6)-month follow up, all ZCQ domains, including physical function, symptom severity, and patient satisfaction, showed statistically significant improvements. Based on these findings, the authors conclude that the MILD procedure was safe and effective.

Durkin B, Romeiser J, Shroyer L. et al. Report from a Quality Assurance Program on Patients Undergoing the MILD Procedure. Pain Med. 2013 May;14(5):650-6.

Durkin and associates performed a retrospective observational cohort study to characterize trends in pain and functional outcomes.  They looked to identify risk factors in patients with LSS and neurogenic claudication who underwent the MILD procedure.

In 2010, the Stony Brook Medical Center for Pain Management established a program that offered the MILD procedure to LSS patients.  The Medical Center included a quality assurance registry (Surgical Quality Improvement Program) as part of the program. The registry prospectively gathered safety and outcomes data on all MILD patients. It collected information on preoperative medical characteristics, MRI and CT evidence of lumbar stenosis and LF hypertrophy, intraoperative course, postoperative pain status, and functional outcomes.

Fifty patients undergoing the MILD procedure from October 2010 to May 2012 were included in the study.  Follow-up visits extended for an additional six (6)-month period. Clinical information was collected prospectively prior to and during follow-up visits at one (1), three (3), and six (6) months following surgery. Specific inclusion and exclusion criteria were established, and all patients underwent the MILD procedure on one (1) to three (3) lumbar regions.

Durkin and associates collected information on: age, gender, body mass index (BMI), preoperative usage of opioid medications, and lumbar spine pathology defined by MRI or CT. The authors looked at severity of canal stenosis and LF hypertrophy [>4 mm] prior to the procedure.

Durkin and associates looked at the data to see if a potential subgroup of MILD patients had improvement in outcomes.  To do this, they compared the change in pre-MILD patient data with follow-up outcomes.

They assessed clinical outcomes using a variety of metrics including:

1. Adverse events (e.g., bleeding, nerve injury, dural tears);
2. Improvement, no change, or worsening based on psychometric tools (11-point numerical rating scale [NRS];
3. Pain interference scores from the National Institutes of Health [NIH] Patient-Reported Outcomes Measurement Information System [PROMIS]; and
4. Patient-completed freehand drawings of their pain distribution patterns related to lower back and/or lower extremities); and
5. Change in functional status as evaluated by the ODI, ZCQ, and NIH PROMIS.

Pain and functional data were collected by a trained clinical team member at baseline prior to the procedure and at one (1), three (3), and six (6) months post-op.

Frequency tables and basic descriptive statistics were generated for all categorical variables, and continuous variables, respectively. Pre and post-procedure change scores were calculated for each pain and functional status measurement instrument. For the univariable analyses, chi-square, Fisher's exact, paired t, and Wilcoxon Signed Rank tests were performed to assess for statistically significant differences. Given the small sample size of 50 patients, the authors could not evaluate the impact of risk factors on postoperative outcomes using multivariable analytical approaches.

In the study, 50 patients underwent MILD procedures (the average age of participants was 73.3 ± 9.4 years; 52.0% of subjects were female patients; mean BMI of 31.2 ± 7.0 and 48% were obese  with BMI ≥ 30). Based on the physical status classification system of the American Society of Anesthesiologists (ASA), 68% of patients had a class 3 grade (severe systemic disease), while 24% and 8% were graded as class 2 (mild systemic disease) and class 4 (life threatening systemic disease), respectively.

Only 30% of the patients were on opioid therapy for pain prior to the MILD procedure. All of the patients had previously undergone low back pain interventions such as epidural lumbar blockade (74%), medial nerve branch blockade (24%), and/or radio-frequency ablation of medial nerve branches (30%). All patients complained of neurogenic claudication with varying degree of pain distribution patterns (buttocks and/or legs) elicited by walking or standing, and the most common lower extremity dermatomes affected were S1 and S2. Almost all patients indicated "low back" pain corresponding to truncal dermatomes L3-L5. Gait instability was present in 68% of the patients; 55.1% of the patients used a walking assistance device.

Psychometric testing revealed that the average pre-operative NRS pain score averaged 7.5 (95% confidence interval [CI] 7.0, 8.0).  Pain on to the ZCQ symptom severity scale averaged 3.2 (95% CI 3.0, 3.4). Pain interference score by the NIH PROMIS (N = 39) at baseline was 63.5 ± 7.7 indicating worse than average impact of pain on daily living compared with the general U.S. population (NRS pain scores and corresponding NIH PROMIS pain interference scores captured different aspects of the patient's pain experience). Functional status by the ODI at baseline averaged 40.6 (95% CI 36.1, 45.1).  The NIH PROMIS physical function scores averaged 34.1 ± 7.2, which indicated a moderate-to-severe impact on daily life in comparison with the general U.S. population norms matched by age and gender.

During the study, none of the MILD participants incurred any procedure-related complications. NRS scores decreased post-operatively; 64.3% of patient reported less pain after 3 months.  One quarter of the patients reported clinically meaningful improvements in functional ODI scores at 6 months.

The authors concluded that overall, pain was reduced and functional status improved in LSS patients following the MILD procedure at 3 months and 6 months. And given the small sample size, it was not yet possible to identify patient subgroups at risk for "no improvement." They also noted that continued follow-up of longer-term outcomes appears warranted to develop evidence-based patient selection criteria.

Kreiner and associates performed a systematic review of the medical literature to determine if the minimally invasive lumbar decompression (MILD) procedure reduces pain in patients suffering with symptomatic LSS. The authors retrieved articles from PubMed, Embase, and the Cochrane Library. Search terms included lumbar stenosis, percutaneous decompression and MILD procedure. They reviewed full length articles written in any language up through May 2013.

The authors only considered articles that met the following criteria:

1. Study participants had lower extremity claudication—confirmed with CT or MRI due to LSS
2. Participants had to be older than 18 years
3. Patients assigned to treatment with MILD
4. Patients were assessed for lower extremity pain relief by using the visual analog scale (VAS)

Secondary outcome measures included ODI—to measure functional benefit—and ZCQ—to measure pain and patient satisfaction. Kreiner and associates monitored complications, adverse events, and co-interventions.

The authors serially assessed intervals of 30 days, 6 weeks, 3 months, 6 months, and 1 year and longer. The study did not specify how long beyond 1 year.  Study quality was assessed using an instrument developed by the International Spine Intervention Society Standards Division.

Three of the authors reviewed all of the articles that met the inclusion criteria and resolved disagreements through discussion. GradePro software (GRADE Working Group) was used to consolidate the data from the different studies into workable follow-up periods of short (4–6 weeks), medium (3–6 months), and long term (1 year and more).

The investigators identified one (1) randomized controlled trial (RCT) (Brown et al. 2012), seven (7) prospective cohort studies (Basu 2012; Chopko 2011; Chopko 2013; Chopko and Caraway 2010; Deer et al. 2012; Mekhail et al. 2012; Wilkinson and Fourney 2012), four (4) retrospective cohort studies (Deer and Kapura 2010; Durkin et al. 2013; Lingreen and Grider 2010; Wang et al. 2013), and one (1) case series (Wong 2012). 

Each of the reviewed articles showed statistically significant improvement in pain relief post-MILD procedure than pre-procedure. Patients had statistically significant pain relief in the short, medium, and long terms. Functional outcome measures similarly showed statistically significant improvement from the MILD procedure. 

While all the studies considered met the inclusion criteria, a few of them had notable deficiencies. Two (2) of the articles considered in the review Wilkinson and Fourney 2012 and Brown, et al 2012—had missing data.  In one study (Mekhail et al. 2012), thirteen (13) patients were not available for follow-up and at least two (2) proceeded to lumbar surgery after one (1) year. No substantial direct procedure-related complications were identified in any of the studies.

In the five (5) studies that evaluated patient satisfaction, ZCQ scores ranged from 1.86 to 2.20 (95% CI ± 0.26). The satisfaction scale ranged from 1.0 to 4.0, with values of less than 2.5 indicating some degree of satisfaction, although a score of 2.0 or lower is typically considered "satisfied." Three (3) studies evaluated medication usage among patients receiving MILD. The results are mixed. The Chopko study showed that half of the patients were able to decrease or stop opioid medication use post-procedure, but the study by Wilkinson and Fourney reported a small post-procedure increase in opioid analgesic usage.

The authors concluded that the MILD procedure was a relatively safe procedure for the treatment of symptomatic LSS. They also noted that outcome data suggest that the MILD procedure provides statistically significant reductions in pain intensity and statistically significant intermediate improvements in function.

Peter S, Ramsin M. MiDAS ENCORE: Randomized Controlled Clinical Trial Report of 6-Month Results. Pain Physician 2016; 19:25-37.

Ramsin M, Peter S. MILD® is an Effective Treatment for Lumbar Spinal Stenosis with Neurogenic Claudication: MiDAS ENCORE Randomized Controlled Trial. Pain Physician 2016; 19:229-242.

Peter and Ramsin conducted a prospective, randomized controlled trial on the use of PILD in patients with LSS. They looked at both six (6)-month and twelve (12)-month clinical endpoints. A total of 302 patients were enrolled in the study from 26 US international pain management centers.

Inclusion criteria included all of the following:

1. Medicare beneficiaries 65 years and older;
2. Patients experiencing neurogenic claudication symptoms for at least three (3) months that  had failed to respond or poorly responded to physical therapy, home exercise programs, and oral analgesics;
3. Patients that had LSS with neurogenic claudication diagnosed via symptomatic diagnosis and radiologic evidence of LSS.  Radiological criteria required unilateral or bilateral ligamentum flavum > 2.5 mm confirmed by a pre-operative MRI or CT performed within twelve (12) months of the baseline visit;
4. Patients with comorbid conditions commonly associated with spinal stenosis; and
5. Patients willing to complete six (6)-month and one (1)-year follow-up visits

Exclusion criteria included:

1. ODI Score < 31 (0-100 ODI Scale)
2. NPRS Score < 5 (0-10 NPRS Scale)
3. Prior surgery at any treatment level
4. History of spinal fractures with current related pain symptoms
5. Grade III or higher spondylolisthesis
6. Motor deficit or disabling back and/or leg pain from causes other than LSS with neurogenic claudication
7. Inability to walk ≥ 10 feet unaided before being limited by pain
8. Previously randomized and/or treated in this clinical study
9. Previously received the MILD procedure
10. Received epidural steroid injections (ESI) eight (8) weeks prior to study enrollment
11. Epidural lipomatosis (if deemed to be a significant contributor of canal narrowing by the physician)
12. Being on (or pending) Workman’s Compensation or known to be considering litigation associated with back pain

Patients were randomized in an allocation ratio of 1-to-1 to the MILD procedure or epidural ESI study cohorts (149 patients were randomized to the MILD and 153 patients were randomized to ESI as active control).  Neither the investigators nor the patients were blinded.  Following randomization, six (6) MILD patients and 22 ESI patients voluntarily withdrew prior to the study treatment, leaving 143 and 131 patients in the MILD and ESI cohorts, respectively. Of these, two (2) ESI patients missed their six (6)-month follow-up visit.  Accordingly, the six (6)-month data analysis included 143 MILD patients and 129 ESI patients.

Between the six (6)-month and one (1)-year follow-ups, two (2) patients in the MILD cohort died of unrelated causes (one cardiopulmonary arrest and one cardiac arrest). Two (2) patients in the ESI arm withdrew for unrelated health reasons. Per the statistical plan, these four (4) patients were included in the one (1)-year analysis using their six (6)-month follow-up data that was carried forward. Two (2) additional patients in the ESI arm missed both the six (6)-month and one (1)-year follow-ups and were not included in this analysis. Therefore, outcomes for 143 patients who received MILD and 129 patients who received ESI were included in the one (1)-year report.

The mean age in the MILD group was 75.6 years, while the mean age of the ESI group was 75.0 years. There was a significant difference in gender between the two groups. When considering males, a larger proportion was in the MILD group (49.7%) compared to the ESI group (37.9%).

Both groups presented with similar adverse events. For the most part, patients reported the same rate and type of adverse events in both groups. The ESI group, however, had significantly more patients presenting with facet arthropathy than found in the MILD group.

Baseline values for ODI, NPRS, and ZCQ domains showed no significant differences between the groups. The ESI group had a significantly higher pre-operative rate of aquatic therapy than the ESI group. Procedure times, procedure settings, and anesthesia type were all significantly different due to the nature of the two (2) treatments.  ESI patients received an average of 1.7 ESI treatments during the first six (6) months with a range of one (1) to four (4) and a median of one (1).  At baseline, 90.6% of MILD patients and 83.0% of ESI patients reported using medication for their neurogenic claudication, and there were no statistical significant differences between the groups. At six (6) months and one (1) year, the percent of patients using these medications in the MILD arm was 89.5% and 88.2%, respectively and in the ESI arm was 85.3% and 84.2%, respectively. Both groups had high non-responder rates. For primary efficacy, at six months, the proportion of ODI responders in the MILD group (62.2%) was statistically significantly higher than for the ESI group (35.7%).  At one (1) year, the 58.0% ODI responder rate in the MILD group was statistically significantly higher than the 27.1% responder rate in the ESI group.

The studies looked at ODI, NPRS, and ZCQ. The primary efficacy measure is the proportion of ODI responders. The study defined ODI responders as patients achieving the validated Minimal Important Change (MIC) of ≥10 point improvement in ODI from baseline to follow-up. Secondary efficacy measures include the proportion of NPRS and ZCQ responders using validated MIC thresholds. The primary safety measure was the incidence of device or procedure-related adverse events in each group.  At both six (6)-month and one (1)-year follow-ups, all primary and secondary efficacy results provided statistically significant evidence that MILD is superior to the active control. Further, all secondary efficacy parameters demonstrated statistical superiority of MILD versus the active control. The primary safety endpoint was achieved, demonstrating that there was no difference in safety measures between MILD and ESIs for both six (6) months and 12 months.

The authors concluded that both six (6)-month and one (1)-year results demonstrate that MILD is statistically superior to ESIs in the treatment of LSS patients with neurogenic claudication and verified central stenosis due to ligamentum flavum hypertrophy. The authors also point out that patients status post the MILD procedure showed statistically significantly improvement in function even after one (1) year.

Wang J, MD, Bowden K, Pang G, Cipta A. Decrease in Health Care Resource Utilization with MILD. Pain Medicine 2013; 14: 657–661.

Wang and associates evaluated how the MILD procedure changed health care resource utilization in their facility.  Health care resource utilization was defined as the need for specialty care and its associated interventional procedures. It was measured by the duration of outpatient care and the number of procedures performed during that time.

All study patients pre-operatively presented with symptoms consistent with LSS. They also had radiographic evidence of central canal stenosis caused by ligamentum flavum hypertrophy by either lumbar computed tomography or magnetic resonance imaging. A cross-sectional view of the patients’ current status was performed, and an independent template was created to extract and compare data. Demographic information, including gender and age, were included. Health care resource utilization was defined as the need for specialty care and its associated interventional procedures. It was measured by the number of month’s duration of outpatient care, as well as the number of procedures performed during that time. A comparison of this usage was performed before and after the MILD procedure.  

Wang and associates determined the number of pre-operative care days by counting from the date of the initial clinic consultation to the MILD procedure date. They also recorded the number of interventional pain procedures performed during that time span that could have been attributed to confounding diagnoses that produce lower back pain or lower extremity symptoms.  The authors defined the post-MILD duration as the day of the MILD procedure to the day of discharge from the chronic pain or spine surgery clinic. They used the post-MILD duration to calculate the amount of time each patient spent in specialty care after the MILD procedure.

Wang and associates monitored the efficacy of the MILD procedure by recording and comparing pre- and post-MILD visual analog scores (VAS).  To calculate the VAS, patients were asked at their first post-operative appointment whether they had functional improvement.  

Over a 13-month period (July 2011 to August 2012) 22 patients underwent the MILD procedure. The majority of subjects were male (95.5%) and their ages ranged from 51 to 91 years of age (mean of 74.2 years and a median of 73.5 years). Though a number of subjects dropped out during the study or were lost to follow-up (n=3), they were still included in the data analysis.

At the time of the chart review, each participant had at least two (2) months of post-MILD follow-up. When looking at pre-MILD chronic pain management resource usage, there was a mean of 9.33 and median of 5.625 months between initial consultation and receiving MILD. During that time, each patient received an average of 3.68 and a median of two (2) chronic pain procedures.  Three (3) patients (13.6%), however, did not receive any interventional pain procedures before MILD.

The entire study cohort received an average of 0.395 pain procedures per month. After the MILD procedure, the patients received a mean of 5.11 and median of 3.0 months of specialty care.  They received an overall mean of 9.55 and median of 9.5 months of post-MILD care.  The researchers then divided the post-MILD specialty care months by total post-MILD months, which yielded 53.6% and represents the percent of post-MILD care that requires specialty management. Further evaluation of these numbers reveals that twelve (12) out of 22 patients (54.5%), including the patients lost to follow-up, were discharged from the chronic pain clinic after the MILD procedure. The other ten (10) patients continued their care with chronic pain management for their LSS, and three of those patients were eventually referred to spine surgery for surgical decompression.

Wang and associates’ assessment revealed that after the MILD procedure, there was a 45% reduction in time spent in specialty care (from 9.55 to 5.11 months) and an almost fourfold decrease in the number of interventional pain procedures performed on patients with LSS. The average VAS score before MILD was 7.0, and 4.82 after, with an average reduction of 2.27 per patient. The authors note that over half the patients no longer required chronic pain management to treat their LSS symptoms.

The authors concluded that MILD is a reliable method to treat LSS, and it also appears to reduce the consumption of limited health care resources.

A MEDCAC meeting was not convened on this issue.

No evidence-based guidelines were found.

No professional society recommendations were found.  We received comments from State and National societies. All comments were reviewed.  

Public comments sometimes cite the published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination.

CMS uses the initial public comments to inform its proposed decision. CMS responds in detail to the public comments on a proposed decision when issuing the final decision memorandum. All comments that were submitted without personal health information may be viewed in their entirety by using the following link - https://www.cms.gov/medicare-coverage-database/details/nca-view-public-comments.aspx?NCAId=284.

Initial Comment Period: 04/13/2016 – 05/13/2016

During the initial 30-day public comment period, CMS received a total of 36 comments. Five (5) comments (13.9%) had to be redacted because they contained personal health information. Medical doctors (24/66.7%) and Directors/Presidents (12/33.3%) of medical centers submitted the majority of comments.  Other commenters included universities or medical colleges (5/13.9%), pain management centers or specialists (10/27.8%), and pain societies (7/19.4%). One manufacturing company (2.8%) submitted a comment.

Three comments (8.3%) were neutral.  They sought assistance in locating study sites participating in the approved CED studies and shared their perspective of various study techniques. Three (8.3 %) commenters were against Medicare coverage for the PILD procedure due to skepticism about the associated health outcomes or benefits.  

Thirty (83.3%) commenters were in favor of expanding Medicare coverage to include PILD.  Five (13.9 %) of these favorable commenters belong to different sectors of the Society of Interventional Pain Physicians. All of the favorable commenters believed PILD to be cost effective, safe and essential in relieving pain and improving quality of life.  We reviewed the comments in their entirety, including reviewing all referenced literature submitted in part as comments from professional organizations.

VIII. CMS Analysis

National coverage determinations are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally by Medicare (§1869(f)(1)(B) of the Act).  In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B, and must not be otherwise excluded from coverage.  Moreover, with limited exceptions, the expenses incurred for items or services must be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. See § 1862(a)(1)(A)of the Social Security Act).

In addition to § 1862(a)(1)(A) of the Act, a second statutory provision may permit Medicare payment for items and services in some circumstances.  That statute, section 1862(a)(1)(E) of the Act, provides, in pertinent part, that:

Section 1142 of the Act describes the authority of the Agency for Healthcare Research and Quality (AHRQ) to conduct and support research on outcomes, effectiveness, and appropriateness of services and procedures to identify the most effective and appropriate means to prevent, diagnose, treat, and manage diseases, disorders, and other health conditions. That section includes a requirement that the Secretary assure that AHRQ research priorities under Section 1142 appropriately reflect the needs and priorities of the Medicare program.

CED is a paradigm whereby Medicare covers items and services on the condition that they are furnished in the context of approved clinical studies or with the collection of additional clinical data.  In making coverage decisions involving CED, CMS decides after a formal review of the medical literature to cover an item or service only in the context of an approved clinical study or when additional clinical data are collected to assess the appropriateness of an item or service for use with a particular beneficiary.

The 2014 CED Guidance Document is available at https://www.cms.gov/medicare-coverage-database/details/medicare-coverage-document-details.aspx?MCDId=27

In our analysis we seek answers to the below questions.  We note that these questions are the same as set forth in the 2014 Decision Memo.

Is the evidence sufficient to conclude that PILD improves health outcomes in Medicare beneficiaries with LSS?

Outcomes of interest include 6-month, 12-month, and 24-month beneficiary function, quality of life, reduction in pain, change in pain medication use, and change in the overall clinical management of LSS and decision making.

In our 2014 PILD NCD Decision Memorandum, we set forth CED criteria that required a randomized controlled trial (RCT). Since that time (January 2014), we have received published, peer-reviewed data from one trial (MILD®).  Two publications resulted from the same study (Peter 2016 and Ramsin 2016).

Peter and Ramsin concluded that MILD® is statistically superior to ESIs in the treatment of LSS patients with neurogenic claudication and central stenosis due to ligamentum flavum hypertrophy. The authors also found that the MILD® procedure showed statistically significantly improvement in function even after one (1) year.

Peter and Ramsin’s papers describe improvements from PILD, but the small sample size and short duration may limit quality and broader applicability of the study results.  Further, the study had a high non-responder rate, and we do not know whether the missing post-operative information would have altered the study results. After reviewing the results of this trial it was noted that there was not any significant changes in the use of medication post-operatively.  We believe this may be a potential confounder and therefore we are interested in whether the patients decreased their pain medication intake during the post-operative six (6)-month and one (1)-year periods.

As explained above, we also reviewed non-RCT articles published after November 2013.  These articles include: a retrospective study by Durkin, Basu’s prospective study, and Wang’s case review article.  These studies supported the findings from the RCT articles, although with lower strength study designs.  Durkin’s study showed that some patients had improved outcomes following the PILD procedure.  But it did not explicitly answer whether patients had a decrease in pain medication usage in the post-operative period.  While the Basu study (2012) showed a statistically significant decrease in pain following the PILD procedure, the sample size was small (n=27); there was no comparison group; and the follow-up was short (6 months).

Kreiner and associates performed a systematic review (Kreiner et. al. 2014). Though the studies revealed statistically significant improvement in pain and function, some studies were only of 6-month duration, and the authors noted that these improvements do not meet some definitions. Lastly, Wang and associates (2013) reviewed health care resource utilization. They conclude that the PILD procedure decreases health care utilization in the post-operative period. But they note a number of limitations in their study design. The limitations include no control group, small number of participants in the study (n=22), and a short duration (6 months).  Moreover, because Wang and associates self-selected the cases, some MILD cases may not have been included in the report.  Therefore, the study may not be representative of the universe of MILD cases.

Overall, the results of the studies are promising.  In our 2014 NCD, we established CED for PILD in beneficiaries with LSS and supported two RCTs.  We commend investigators for participating in CED and completing the procedures in the RCTs and await publication of the 24-month results of the MILD® trial and the results of VertiFlex® trial.  The studies reviewed were promising but had small sample sizes, varied in follow-up, from several weeks to one year, and did not fully address our initial CED questions. Longer term data on endpoints including chronic use of pain medications are needed.  In addition, it is unclear if the observed short term improvements will be maintained when these technologies and procedures are more broadly used in the general Medicare population outside the structured, controlled trial settings. For these reasons, we believe it is important to continue to support translational science and propose to continue CED for those technologies that have reported positive CED RCT findings in study designs and settings that more closely resemble real world practice.

Coverage with Evidence Development

CMS continues to recognize that LSS is a real and important source of pain and functional limitation for Medicare beneficiaries.  We believe that effective minimally invasive procedures could have a potential place in the treatment armamentarium.  But more evidence is needed to show which minimally invasive procedures would improve Medicare beneficiary health outcomes.  Consistent with a translational science framework, as new technologies are developed, a randomized controlled trial as required in NCD (150.13) is needed to determine improvements in health outcomes using the most rigorous study design.  As evidence from controlled settings (e.g., RCTs) is developed, evidence in broader studies in less controlled settings that are more similar to real world practice is needed to show that improvements are maintained when implemented widely over time.  We propose to cover PILD for beneficiaries with LSS under CED to evaluate the durability of the short term improvements seen in the CED RCTs.  We believe to the best to maintain consistency and have confidence in the results that the study sponsor and the inclusion/exclusion criteria should be maintained in this second CED phase.  Further, we remind the study sponsors that under CED the results must be made public within 12 months after the studies primary completion date.  In addition, we propose that these results must be published in a peer-reviewed publication within 24 months of the end of the study. CMS will use these published results to reconsider this decision. 

Using the CED paradigm, we propose to cover a prospective cohort study that have the following characteristics:  

1. The study is conducted by the same study sponsors that conducted prospective, randomized, controlled trial of PILD for LSS that was approved by CMS under CED. 
2. The eligibility requirements, both inclusion and exclusion criteria that were specified in the CMS-approved RCT protocol, must be maintained in the new prospective cohort study.
3. The same outcome measures as were used in the CMS-approved RCT must be used in the new prospective cohort study compared to other treatments.
4. Changes in the use of any pain medication for LSS must be tracked in the new prospective cohort study. 
5. All study sites must be listed in the ClinicalTrials.gov database.

We propose these study characteristics because we are encouraged by the short term meaningful improvement of function, clinical meaningful reduction in pain and improved QoL in the studies we reviewed.

We believe that Medicare beneficiaries will benefit from a better understanding as to which minimally invasive procedures improve long term health outcomes.  We therefore propose continuing coverage of PILD for beneficiaries with LSS under the CED paradigm with the CED criteria outlined above.

The current literature does not address general disparities, though gender, age, and some demographic information are reported in some studies. The studies fail to discuss matters related to race or ethnicity, socio-economic status, disability, geographic location or religious beliefs. In general, there is significant information in the literature regarding disparities in pain management, however, in the more recent studies reviewed in this analysis, CMS found no discussion regarding such disparities. Future studies involving the use of PILD in patients with LSS are encouraged to incorporate health disparity measures so that the findings may be more generalizable to the Medicare population.  

IX. Conclusion

On January 9, 2014, CMS posted its final decision memorandum for the National Coverage Determination (NCD 150.13) covering PILD for beneficiaries with LSS when provided in a prospective, randomized, controlled clinical study meeting certain conditions under the Coverage with Evidence Development (CED) determination. We received a request to reconsider this NCD based in part on evidence developed in those studies.

We believe that the new evidence supports  broader coverage under CED, therefore the Centers for Medicare & Medicaid Services (CMS) proposes to modify the existing NCD to cover percutaneous image-guided lumbar decompression (PILD) when provided in a clinical study under §1862(a)(1)(E) of the Social Security Act through Coverage with Evidence Development (CED) for Medicare beneficiaries with lumbar spinal stenosis (LSS) who are enrolled in an approved clinical study that meets the broader criteria set forth below. 

The CMS-approved protocol must answer all of the following questions:

For investigators that have completed a CMS-approved randomized controlled clinical trial as specified in the NCD manual (150.13), Medicare proposes to continue to cover PILD under CED for new patients with LSS enrolled and followed in a CMS-approved prospective cohort study.  The new prospective cohort study protocol must specify a statistical analysis and a minimum length of patient follow-up time that evaluates the effect of beneficiary characteristics on patient health outcomes as well as the duration of the benefit.  Outcomes of interest include 6-month, 12-month, and 24-month beneficiary function, quality of life, reduction in pain, change in pain medication use, and change in the overall clinical management of LSS and decision making. This prospective cohort study must also have the following characteristics:

1. The study is conducted by the same study sponsors that conducted a CMS-approved prospective, randomized, controlled trial of PILD for LSS under CED. 
2. The eligibility requirements, both inclusion and exclusion criteria that were specified in the CMS-approved RCT protocol, must be maintained in the new prospective cohort study.
3. The same outcome measures as were used in the CMS-approved RCT must be used in the new prospective cohort study compared to other treatments.
4. Changes in the use of any pain medication for LSS must be tracked in the new prospective cohort study. 
5. All study sites must be listed in the ClinicalTrials.gov database.

All CMS-approved clinical research studies must adhere to the following standards of scientific integrity and relevance to the Medicare population:

Consistent with section 1142 of the Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that CMS determines meet the above-listed standards and address the above-listed research questions.

See Appendix B for the proposed manual language.

CMS is seeking comments on our proposed decision.  We will respond to public comments in a final decision memorandum, as required by §1862(l)(3) of the Social Security Act (the Act).

When making national coverage determinations, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service is reasonable and necessary.  The overall objective for the critical appraisal of the evidence is to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for patients.

We divide the assessment of clinical evidence into three stages: 1) the quality of the individual studies; 2) the generalizability of findings from individual studies to the Medicare population; and 3) overarching conclusions that can be drawn from the body of the evidence on the direction and magnitude of the intervention’s potential risks and benefits.

The methodological principles described below represent a broad discussion of the issues we consider when reviewing clinical evidence.  However, it should be noted that each coverage determination has its unique methodological aspects.

Assessing Individual Studies

Methodologists have developed criteria to determine weaknesses and strengths of clinical research.  Strength of evidence generally refers to: 1) the scientific validity underlying study findings regarding causal relationships between health care interventions and health outcomes; and 2) the reduction of bias.  In general, some of the methodological attributes associated with stronger evidence include those listed below:

1. Use of randomization (allocation of patients to either intervention or control group) in order to minimize bias.
2. Use of contemporaneous control groups (rather than historical controls) in order to ensure comparability between the intervention and control groups.
3. Prospective (rather than retrospective) studies to ensure a more thorough and systematical assessment of factors related to outcomes.
4. Larger sample sizes in studies to demonstrate both statistically significant as well as clinically significant outcomes that can be extrapolated to the Medicare population.  Sample size should be large enough to make chance an unlikely explanation for what was found.
5. Masking (blinding) to ensure patients and investigators do not know to that group patients were assigned (intervention or control).  This is important especially in subjective outcomes, such as pain or quality of life, where enthusiasm and psychological factors may lead to an improved perceived outcome by either the patient or assessor.

Regardless of whether the design of a study is a randomized controlled trial, a non-randomized controlled trial, a cohort study or a case-control study, the primary criterion for methodological strength or quality is to the extent that differences between intervention and control groups can be attributed to the intervention studied.  This is known as internal validity.  Various types of bias can undermine internal validity. These include:

• Different characteristics between patients participating and those theoretically eligible for study but not participating (selection bias).
• Co-interventions or provision of care apart from the intervention under evaluation (performance bias).
• Differential assessment of outcome (detection bias).
• Occurrence and reporting of patients who do not complete the study (attrition bias).

In principle, rankings of research design have been based on the ability of each study design category to minimize these biases.  A randomized controlled trial minimizes systematic bias (in theory) by selecting a sample of participants from a particular population and allocating them randomly to the intervention and control groups.  Thus, in general, randomized controlled studies have been typically assigned the greatest strength, followed by non-randomized clinical trials and controlled observational studies.  The design, conduct and analysis of trials are important factors as well.  For example, a well-designed and conducted observational study with a large sample size may provide stronger evidence than a poorly designed and conducted randomized controlled trial with a small sample size.  The following is a representative list of study designs (some of that have alternative names) ranked from most to least methodologically rigorous in their potential ability to minimize systematic bias:

Randomized controlled trials
Non-randomized controlled trials
Prospective cohort studies
Retrospective case control studies
Cross-sectional studies
Surveillance studies (e. g. , using registries or surveys)
Consecutive case series
Single case reports

When there are merely associations but not causal relationships between a study’s variables and outcomes, it is important not to draw causal inferences.  Confounding refers to independent variables that systematically vary with the causal variable.  This distorts measurement of the outcome of interest because its effect size is mixed with the effects of other extraneous factors.  For observational, and in some cases randomized controlled trials, the method in that confounding factors are handled (either through stratification or appropriate statistical modeling) are of particular concern.  For example, in order to interpret and generalize conclusions to our population of Medicare patients, it may be necessary for studies to match or stratify their intervention and control groups by patient age or co-morbidities.

Methodological strength is, therefore, a multidimensional concept that relates to the design, implementation and analysis of a clinical study.  In addition, thorough documentation of the conduct of the research, particularly study selection criteria, rate of attrition and process for data collection, is essential for CMS to adequately assess and consider the evidence.

Generalizability of Clinical Evidence to the Medicare Population

The applicability of the results of a study to other populations, settings, treatment regimens and outcomes assessed is known as external validity.  Even well-designed and well-conducted trials may not supply the evidence needed if the results of a study are not applicable to the Medicare population.  Evidence that provides accurate information about a population or setting not well represented in the Medicare program would be considered but would suffer from limited generalizability.

The extent to that the results of a trial are applicable to other circumstances is often a matter of judgment that depends on specific study characteristics, primarily the patient population studied (age, sex, severity of disease and presence of co-morbidities) and the care setting (primary to tertiary level of care, as well as the experience and specialization of the care provider).  Additional relevant variables are treatment regimens (dosage, timing and route of administration), co-interventions or concomitant therapies, and type of outcome and length of follow-up.

The level of care and the experience of the providers in the study are other crucial elements in assessing a study’s external validity.  Trial participants in an academic medical center may receive more or different attention than is typically available in non-tertiary settings.  For example, an investigator’s lengthy and detailed explanations of the potential benefits of the intervention and/or the use of new equipment provided to the academic center by the study sponsor may raise doubts about the applicability of study findings to community practice.

Given the evidence available in the research literature, some degree of generalization about an intervention’s potential benefits and harms is invariably required in making coverage determinations for the Medicare population.  Conditions that assist us in making reasonable generalizations are biologic plausibility, similarities between the populations studied and Medicare patients (age, sex, ethnicity and clinical presentation) and similarities of the intervention studied to those that would be routinely available in community practice.

A study’s selected outcomes are an important consideration in generalizing available clinical evidence to Medicare coverage determinations.  One of the goals of our determination process is to assess health outcomes.  These outcomes include resultant risks and benefits such as increased or decreased morbidity and mortality.  In order to make this determination, it is often necessary to evaluate whether the strength of the evidence is adequate to draw conclusions about the direction and magnitude of each individual outcome relevant to the intervention under study.  In addition, it is important that an intervention’s benefits are clinically significant and durable, rather than marginal or short-lived.  Generally, an intervention is not reasonable and necessary if its risks outweigh its benefits.

If key health outcomes have not been studied or the direction of clinical effect is inconclusive, we may also evaluate the strength and adequacy of indirect evidence linking intermediate or surrogate outcomes to our outcomes of interest.

Assessing the Relative Magnitude of Risks and Benefits

Generally, an intervention is not reasonable and necessary if its risks outweigh its benefits.  Health outcomes are one of several considerations in determining whether an item or service is reasonable and necessary.  CMS places greater emphasis on health outcomes actually experienced by patients, such as quality of life, functional status, duration of disability, morbidity and mortality, and less emphasis on outcomes that patients do not directly experience, such as intermediate outcomes, surrogate outcomes, and laboratory or radiographic responses.  The direction, magnitude, and consistency of the risks and benefits across studies are also important considerations.  Based on the analysis of the strength of the evidence, CMS assesses the relative magnitude of an intervention or technology’s benefits and risk of harm to Medicare beneficiaries.

150.13 – Percutaneous Image-guided Lumbar Decompression (PILD) for Lumbar Spinal Stenosis (LSS)
(Rev.)

A. General

PILD is a posterior decompression of the lumbar spine performed under indirect image guidance without any direct visualization of the surgical area. This is a procedure proposed as a treatment for symptomatic LSS unresponsive to conservative therapy. This procedure is generally described as a non-invasive procedure using specially designed instruments to percutaneously remove a portion of the lamina and debulk the ligamentum flavum. The procedure is performed under x-ray guidance (e.g., fluoroscopic, CT) with the assistance of contrast media to identify and monitor the compressed area via epiduragram.

B. Nationally Covered Indications

Effective for dates of service specified below, the Centers for Medicare & Medicaid Services (CMS) has determined that PILD will be covered by Medicare when provided in a clinical study under section 1862(a)(1)(E) through Coverage with Evidence Development (CED) for beneficiaries with LSS who are enrolled in an approved clinical study that meets the criteria in section I or II below:

1. Effective for services performed on or after January 09, 2014, PILD will be covered by Medicare through CED for beneficiaries with LSS who are enrolled in an approved clinical study that meets the following criteria.  CMS has a particular interest in improved beneficiary function and quality of life, specific characteristics that identify patients who may benefit from the procedure, and the duration of benefit. A clinical study seeking Medicare payment for PILD for LSS must address one or more aspects of the following questions in a prospective, randomized, controlled design using current validated and reliable measurement instruments and clinically appropriate comparator treatments, including appropriate medical or surgical interventions or a sham controlled arm, for patients randomized to the non-PILD group.

The study protocol must specify a statistical analysis and a minimum length of patient follow up time that evaluates the effect of beneficiary characteristics on patient health outcomes as well as the duration of benefit.

1. Does PILD provide a clinically meaningful improvement of function and/or quality of life in Medicare beneficiaries with LSS compared to other treatments?


2. Does PILD provide clinically meaningful reduction in pain in Medicare beneficiaries with LSS compared to other treatments?


3. Does PILD affect the overall clinical management of LSS and decision making, including use of other medical treatments or services, compared to other treatments?

These studies must be designed so that the contribution of treatments in addition to the procedure under study are either controlled for or analyzed in such a way as to determine their impact.

1. The principal purpose of the research study is to test whether a particular intervention potentially improves the participants’ health outcomes.
2. The research study is well supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
3. The research study does not unjustifiably duplicate existing studies.
4. The research study design is appropriate to answer the research question being asked in the study.
5. The research study is sponsored by an organization or individual capable of executing the proposed study successfully.
6. The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found at 45 CFR Part 46. If a study is regulated by the Food and Drug Administration (FDA), it must be in compliance with 21 CFR parts 50 and 56.
7. All aspects of the research study are conducted according to appropriate standards of scientific integrity (see http://www.icmje.org).
8. The research study has a written protocol that clearly addresses, or incorporates by reference, the standards listed here as Medicare requirements for CED coverage.
9. The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Trials of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life threatening as defined in 21 CFR §312.81(a) and the patient has no other viable treatment options.
10. The clinical research study is registered on the ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.
11. The research study protocol specifies the method and timing of public release of all prespecified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors (http://www.icmje.org).
12. The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria effect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial. If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
13. The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

Consistent with section 1142 of the Social Security Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that CMS determines meet the above-listed standards and address the above-listed research questions.

II. Effective for services performed on or after the date of this final decision memo posting, PILD will be covered by Medicare through CED for beneficiaries with LSS who are enrolled in an approved clinical study that meets the broader criteria set forth below: 

The CMS-approved protocol must answer all of the following questions:

For investigators that have completed a CMS-approved randomized controlled clinical trial as specified in section B-I of the NCD manual, Medicare will cover PILD under CED for new patients with LSS enrolled and followed in a CMS-approved prospective cohort study.  The new prospective cohort study protocol must specify a statistical analysis and a minimum length of patient follow-up time that evaluates the effect of beneficiary characteristics on patient health outcomes as well as the duration of the benefit. Outcomes of interest include 6-month, 12-month, and 24-month beneficiary function, quality of life, reduction in pain, change in pain medication use, and change in the overall clinical management of LSS and decision making.  This prospective cohort study must also have the following characteristics:

1. The study is conducted by the same study sponsors that conducted a CMS-approved prospective, randomized, controlled trial of PILD for LSS under CED. 
2. The eligibility requirements, both inclusion and exclusion criteria that were specified in the CMS-approved RCT protocol, must be maintained in the new prospective cohort study.
3. The same outcome measures as were used in the CMS-approved RCT must be used in the new prospective cohort study compared to other treatments.
4. Changes in the use of any pain medication for LSS must be tracked in the new prospective cohort study.
5. All study sites must be listed in the ClinicalTrials.gov database.

All CMS-approved clinical research studies must adhere to the following standards of scientific integrity and relevance to the Medicare population:

1. The principal purpose of the study is to test whether the item or service meaningfully improves health outcomes of affected beneficiaries who are represented by the enrolled subjects. 
2. The rationale for the study is well supported by available scientific and medical evidence.
3. The study results are not anticipated to unjustifiably duplicate existing knowledge. 
4. The study design is methodologically appropriate and the anticipated number of enrolled subjects is sufficient to answer the research question(s) being asked in the National Coverage Determination.  
5. The study is sponsored by an organization or individual capable of completing it successfully.
6. The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found in the Code of Federal Regulations (CFR) at 45 CFR Part 46. If a study is regulated by the Food and Drug Administration (FDA), it is also in compliance with 21 CFR Parts 50 and 56.  In addition, to further enhance the protection of human subjects in studies conducted under CED, the study must provide and obtain meaningful informed consent from patients regarding the risks associated with the study items and/or services, and the use and eventual disposition of the collected data.
7. All aspects of the study are conducted according to appropriate standards of scientific integrity.  
8. The study has a written protocol that clearly demonstrates adherence to the standards listed here as Medicare requirements.  
9. The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Such studies may meet this requirement only if the disease or condition being studied is life threatening as defined in 21 CFR §312.81(a) and the patient has no other viable treatment options.  
10. The clinical research studies and registries are registered on the www.ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.  Registries are also registered in the Agency for Healthcare Research & Quality (AHRQ) Registry of Patient Registries (RoPR).
11. The research study protocol specifies the method and timing of public release of all prespecified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early.  The results must be made public within 12 months of the study’s primary completion date, which is the date the final subject had final data collection for the primary endpoint,   even if the trial does not achieve its primary aim.  The results must include number started/completed, summary results for primary and secondary outcome measures, statistical analyses, and adverse events. Final results must be reported in a publicly accessibly manner; either in a peer-reviewed scientific journal (in print or on-line), in an on-line publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTrials.gov, or in journals willing to publish in abbreviated format (e.g., for studies with negative or incomplete results).
12. The study protocol must explicitly discuss beneficiary subpopulations affected by the item or service under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial.  If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
13. The study protocol explicitly discusses how the results are or are not expected to be generalizable to affected beneficiary subpopulations. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

Consistent with section 1142 of the Social Security Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that CMS determines meet the above-listed standards and address the above-listed research questions.

C. Nationally Non-Covered Indications

Effective for services performed on or after January 09, 2014, CMS has determined that PILD for LSS is not reasonable and necessary under section 1862(a)(1)(A) of the Social Security Act.

D. Other

Endoscopically assisted laminotomy/laminectomy, which requires open and direct visualization, as well as other open lumbar decompression procedures for LSS are not within the scope of this NCD.

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