Clinical Trials: Our Relationship With the Payor Goes Beyond Mere Reimbursements
By Michael Wininger, PhD
Introduction Clinicians are reimbursed for their services when they provide approved treatments for patients with covered indications, i.e., symptoms or diagnoses that are recognized by the payor as valid reasons for prescription. Payor policy is determined by panel review of the best available information regarding treatment efficacy. There are five main sources of information on which policy is written: clinical science, meta-analyses, professional guidelines, expert guidance, and stakeholder opinion. Stakeholder opinion is expected to be experiential in nature: a forum for the patient, the family member, the nonprofit, etc., to speak to the human element of medicine.
The four remaining forms of information are mostly or entirely empirical. And these branches of information all share a common root: the clinical trial.
A View From the Outside As a case study, consider the implantable cardioverter defibrillator (ICD), a biomedical device with a long history of coverage determination review by CMS. The ICD was first approved for implantation by the U.S. Food and Drug Administration (FDA) in 1985, and the first CMS coverage determination letter was published in 1986, with several reviews to the national coverage determination (NCD) over the subsequent 30 years.
Table 1 A Brief History of CMS Coverage Determinations for the Implantable Cardioverter Defibrillator
1985 FDA approval of first implantable defibrillator1986 Coverage for life-threatening ventricular tachyarrhythmias1991 Ventricular fibrillation not due to transient or reversible cause1999 Demonstrated or risk of developing ventricular tachyarrhythmia
Clarification of device investigational device exemption Category B
Expansion of device-eligible patient categories
Clarification of eligibilities, exceptions to waiting periods, ending registry requirement
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In the late 1980s and 1990s, a series of large-scale, multicenter randomized clinical trials was designed in order to test the safety and efficacy of the ICD in various subpopulations. As these trials completed in the late 1990s and 2000s, CMS reviewed its coverage determination, which included specification of the ICD’s investigational device exemption (IDE). As this wave of clinical trials ebbed, the ensuing 15 years brought guidelines development by professional societies, additional clinical trials, and meta-analyses.
The trend is obvious: In a period when clinical trials are abundant, national coverage determinations undergo regular review and revision; once the clinical trials have subsided, experts are able to establish consensus practice guidelines, integrate plural data pools through reflective meta-analyses, and carry out more focal clinical trials to refine the knowledge base.
Connection to O&P There are 345 national coverage determinations listed by CMS; only two (Prosthetic Shoe, 280.10; and Durable Medical Equipment, 280.1) pertain to prosthetics and/or orthotics (it is noted that 280.1 points to a more detailed Chapter 20 of the Medicare Claims Processing Manual “Durable Medical Equipment, Prosthetics, Orthotics, and Supplies, DMEPOS”).
By contrast, there are 45 NCDs for the cardiovascular system (plus many additional heart-related therapies listed in other categories), and 19 NCDs for the renal system (plus many additional items in other categories). Per clinicaltrials.gov, there are nearly 14,000 clinical trials registered matching to “heart OR cardiac” as condition or disease, and nearly 7,500 trials registered matching to “kidney OR renal.” There are fewer than 500 trials matching to “prosthetic OR prosthesis NOT valve NOT eye NOT dental,” and most of these appear to pertain to prevention or management of
Table 2: Field Developments Cited in the CMS National Coverage Determinations (NCDs)
surgical joint replacement, not artificial limbs. Here we see further demonstration of the association between clinical trials and Medicare footprint.
What Can We Do? In order to get the attention of CMS, a clinical trials framework is needed within the orthotics and prosthetics community. CMS explicitly references the canonical Levels of Evidence in its own decision memos, expressly prioritizing multisite clinical trials in its review, itemizing the design aspects that they feel strengthen or weaken studies.
By using these principles as a guide, we will position ourselves to be maximally relevant and impactful with CMS and the broader scientific community. By promoting well-designed and wellexecuted studies, we will demonstrate the worthiness of our innovations as part of the formulary of treatment options.
Who Can Do It? Integration of clinical trials into O&P requires evolution, in terms of both culture and infrastructure. The clinical scientists among us will readily embrace a clinical trials enterprise and can adapt easily.
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Table 3: Design Considerations That Increase or Decrease Influence in CMS Review
Prospective design (cf. retrospective)
Masking (“blinding”) of participants or study personnel
Incorporation of a control group
Demonstration of statistical support
Randomized allocation of patients to study arm
But we’ll need to recruit the tinkerers, the gadget geeks, the technicians, the designers, and the purist clinicians among us to add an extra dimension to their mindset: Can you make your invention ruggedized for deployment in a patient trial? Can you refine your technique so that a uniform approach reduces variability in the treatment effect? Can you introduce a research element into your clinic visit in a way that balances both the patient’s need for treatment and also the field’s need to gain evidence of treatment safety and efficacy through empiric means?
We’ll need to attract diverse professionals into the field, including data management specialists, statisticians, regulatory experts, and those with expertise in quality assurance and human rights.
Training Because the clinicians are the drivers of clinical science, the graduate training programs are the most logical venue for instilling the fundamentals of clinical trials. The standards put forth by the National Commission on Orthotic and Prosthetic Education for the MSPO degree require an understanding of the
Differential measurement of outcomes (detection bias)
Differential compliance or reporting rates (attrition bias)
Study population does not generalize
Co-morbidities pose competing risks
Treatment interacts with other interventions
research process and of using research findings to influence clinical practice; as well as formal training in research methods and completion of a research or capstone project. The methodologies associated with a clinical trial are niche, and more commonly taught in the context of an MPH or an MS in biostatistics. But it is conceivable that the basic elements of clinical trial design can be delivered in a brief, but cogent and informative, module as part of a research methodology course. Randomization, stratification, batch effects, survival analysis, interim analysis procedures, and concepts related to conditional power can be introduced to students as introductory material; more sophisticated concepts could be packaged in an elective course.
One particularly intriguing opportunity would be that of the transitional MSPO model. For active clinicians in the field seeking to enhance their education and professional credentials, the transitional master’s provides a unique occasion to engage a class of certified clinicians—typically with many years of experience—together in a research project that takes on the structure of a
multisite clinical trial. The transitional program’s distance learning format actually facilitates the creation of a distributed network of clinician-researchers, executing a uniform protocol, managed centrally through the institution.
The Two-Way Street The U.S. Department of Health and Human Services not only reviews evidence from clinical trials, but maintains policy to promote their completion. Consider 42 CFR 405.201, wherein investigational device exemptions are described. CMS’s National Coverage Determination 310.1 considers IDEs as routine costs in clinical trials; this provision is specifically intended to ensure that clinical trials continue to escalate the level of evidence so that policy can be refined through evidence-based medicine. Clinical trials are considered the essential tool for providing definitive medical evidence of treatment efficacy. At the highest level of regulation and oversight, the clinical trial is the recognized standard.
At ground level, it may be easy to dismiss the clinical trial as an extravagance more suited for other medical disciplines. For that matter, our relationship with the payor can seem narrow: Claim gets filed, claim gets reimbursed. But clinical trials are not only accessible, they are essential. And they are a vehicle by which our relationship with the payor can become bidirectional: Payor creates policy, we change policy through rigorous scientific study. Orthotic and prosthetic devices should join defibrillators at the heart of trials-based medicine.
Michael Wininger, PhD, is a faculty member in the University of Hartford’s Master’s and Transitional Master’s of Science in Prosthetics & Orthotics Program, Yale School of Public Health (Department of Biostatistics), and is a statistician of medicine for the U.S. Department of Veterans Affairs Cooperative Studies Program. He also is lead statistician on the Efficacy and Safety of the Implantable Cardioverter Defibrillator Implantation in the Elderly clinical trial (“the I-70 Study”), NCT02121158.