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Medicare’s Coverage Of Colorectal Cancer Drugs: A Case Study In Evidence Development And Policy
Payers point to the lack of unbiased evidence for making coverage decisions for new and often costly technologies. This paper provides a case study of a new approach to developing information to meet the needs of a payer: Medicare’s coverage with evidence development (CED) policy. Medicare’s decision to condition coverage of cancer therapies on clinical trial participation is an early application of CED and signals Medicare’s interest in developing evidence on new technologies for beneficiaries. This paper reviews the rationale and challenges Medicare faces in applying its CED policy and discusses the implications of payers’ using and generating evidence.
AS THE PRINCIPLES OF EVIDENCE-BASED MEDICINE (EBM) become standard for all levels of health care decision making, policymakers, purchasers, and payers began investing in new approaches to create and use clinical research. In early 2000 the Institute of Medicine (IOM) convened a wide range of health care stakeholders to discuss challenges facing clinical research. Many criticized the inadequacy of current public and private investments in clinical research to produce "an adequate volume or quality of information to support policy decision-making."1 Purchasers and payers specifically pointed to limited unbiased evidence on which to base coverage decisions for new and often costly drugs. A challenged clinical research enterprise. Evidentiary requirements defined by regulatory agencies such as the Food and Drug Administration (FDA) drive drug manufacturers’ investments in clinical research on drugs. The goal of most FDA-focused studies is to ensure the safety and efficacy of a drug, rather than to evaluate its effectiveness in the clinical setting.2 However, rising health care costs and continued concerns about safety and quality have resulted in payers’ demanding additional evidence, beyond that required by the FDA, to justify the benefit of a medical technology before paying for it. Payers often seek answers to other questions not typically addressed, such as the comparative effectiveness of a new drug with the market leader, evidence of effectiveness in populations not studied as part of FDA trials, and evidence of the safety and effectiveness of off-label uses. Medical product manufacturers’ research investments are shaped by the FDA’s regulatory requirements and, to a lesser extent, by payers’ requests for additional evidence on clinical effectiveness. And despite payers’ unanswered questions, they have not historically served as research sponsors and have limited means to directly fund research. This paper provides a case study of a new approach to developing evidence to meet the needs of payers: the Centers for Medicare and Medicaid Services’ (CMS’s) coverage with evidence development (CED) policy.3 This emerging policy should be viewed in the context of rapid innovation of costly therapies coupled with widespread demand for use of these new therapies in new and expanding indications. Medicare’s evolution from payer to purchaser. As the country’s largest health care payer, the CMS must continually balance the tension between providing access to medical innovations and controlling costs. By law, the CMS has the authority to review whether specific medical procedures, technologies, and services are "reasonable and necessary" and should be paid for by Medicare.4 These determinations typically are made locally by Medicare contractors, who issue local coverage determinations (LCDs). However, these determinations can also be made nationally through the CMS’s national coverage determination (NCD) process. Generally, Medicare defers to the prevailing practices of providers in determining the "reasonableness" and "necessity" of a particular item or service. However, Medicare is exploring ways to move from being a payer to becoming a more prudent purchaser. In the past few years, the CMS has diverged from its historical tendency to provide unconditional coverage for most FDA-approved medical products, particularly drugs. Instead, the CMS has increasingly chosen to limit or condition coverage for certain technologies and services by subpopulations, facilities, and specific indications.5 These determinations are based on the CMS’s review of available evidence, including published and unpublished studies, technology assessments, clinical guidelines, and discussions with experts in relevant clinical or methodological areas. Perhaps the most dramatic example of Medicare’s evolution toward more prudent purchasing is the program’s recently adopted alternative to the traditional binary "yes-or-no" coverage determination: the CED policy.6 The CED policy is a means by which Medicare coverage is conditioned on the acquisition of additional data. However, to some, the CED policy is viewed as a barrier to appropriate diffusion of a technology.
The promise of innovation. Colorectal cancer accounts for about 10 percent of all U.S. cancer deaths and is the country’s second leading cause of cancer death. The American Cancer Society (ACS) estimates that in 2005 there were 145,290 new cases (71,820 men and 73,470 women) and 56,290 deaths from colorectal cancer.7 Treatment for colorectal cancer depends on the stage of the cancer as well as other factors and can include surgery, chemotherapy, and radiation therapy. Until the past decade there were limited treatment regimens for colorectal cancer following the failure of surgical treatments.8 Since 1996 there has been rapid innovation in chemotherapy treatments for colorectal cancer, with the FDA approving four new therapies: the cytotoxic drugs irinotecan (Camptosar) in 1996 and oxaliplatin (Eloxatin) in 2002, as well as the targeted biologics cetuximab (Erbitux) and bevacizumab (Avastin) in 2004 (Exhibit 1  ).
A mixed blessing for Medicare. Each of these new therapies is considered to be an advance, offering patients a major improvement in quality of life or life expectancy, or both. However, they are also widely recognized as expensive agents.9 In the case of colorectal cancer, a disease of the elderly among whom the median age at diagnosis is seventy-two, balancing costs with access is done mainly by the Medicare program, the primary insurer of Americans age sixty-five and older.10 Despite the large responsibility borne by the CMS in paying for expensive cancer therapies, Medicare’s use of the NCD process for cancer therapies has been limited, because of several unique attributes of clinical cancer practice and statute. Medicare covers most physician-administered drugs or biologics for their FDA-labeled indications and has the authority to cover medically accepted off-label uses at the CMS’s discretion.11 Increasingly, cancer care requires physicians to apply past experiences in making treatment decisions for individual patients; as a result, treatment regimens often include off-label uses of agents. Medicare is required by law to cover off-label uses of cancer agents that have either been captured in an approved compendia or published in a recognized journal. For all other off-label uses of cancer drugs, local CMS contractors have the discretion to provide coverage. Because of these avenues for Medicare coverage, cancer drugs have rarely become the subject of an NCD. Although the on-label indications of the new colorectal cancer therapies (oxaliplatin, irinotecan, cetuximab, and bevacizumab) may be relatively narrow, sensitivities around their potential off-label use in other cancer indications and the potential high cost of these therapies have raised concerns about their potential impact on Medicare. Although cost is not an explicit factor in Medicare coverage decisions, it has increasingly become an important factor in choosing which technologies undergo a national coverage review.12 In addition, the effectiveness of an off-label use of a therapy may be less well understood and is often not subjected to the same level of scrutiny as its on-label uses. A rare NCD for cancer drugs. The confluence of increased scrutiny of off-label uses, the potential for high costs to Medicare, and the CMS’s increased ability to engage in evidence-based clinical reviews led to the 12 February 2003 NCD to evaluate whether the use of oxaliplatin was "reasonable and necessary" for Medicare beneficiaries with colorectal cancer. At that time, the only FDA-approved use of oxaliplatin was for treating colorectal cancer that recurred following initial treatment.13 In May 2003 the CMS added irinotecan to the open oxaliplatin NCD because of a perceived lack of available evidence supporting adjuvant uses of irinotecan when compared to first- and second-line therapies. Once cetuximab and bevacizumab were approved by the FDA as treatments for colorectal cancer, they were included in the NCD as well. After a preliminary review of clinical studies and receipt of public comments, the CMS revised the focus of the NCD to consider only off-label uses not already statutorily protected.14 In considering this NCD, the CMS staff reviewed various sources of evidence—peer-reviewed medical literature, manufacturers’ data, and clinical practice guidelines—and consulted clinical experts, the FDA, the National Cancer Institute (NCI), and the American Society of Clinical Oncology (ASCO). At the time of the CMS review, there was no evidence identified for the adjuvant use of irinotecan, the adjuvant and first-line uses of cetuximab, and the adjuvant and second-line uses of bevacizumab. The CMS examined and reported on how each of the four agents had received either accelerated or expedited approval from the FDA and that for some of the agents, known safety issues or a lack of survival data had been recognized at the time of their FDA approval. Ultimately, the CMS found that the quality of the studies supporting off-label uses varied widely. As a result, on 15 September 2004 the CMS met with the NCI to identify "high priority clinical questions" regarding the use of the four anticancer agents under consideration in this NCD. In January 2005, nearly two years following the initiation of the NCD, the CMS released the final decision, which stated that Medicare would cover the off-label uses of oxaliplatin, irinotecan, cetuximab, or bevacizumab nationally in nine NCI clinical trials identified by the NCI and the CMS. In addition, the final decision reinforced local Medicare contractors’ authority to continue to cover other medically accepted off-label indications of the four agents at their discretion, including the indications being studied in the nine NCI trials.
Questions still remain regarding the impact of the NCD for Anticancer Chemotherapy for Colorectal Cancer. Here we compare the CMS’s stated intentions in using a CED approach to the NCD with the outcome during the first year of implementation. These findings are preliminary, since the magnitude and scope of the CED-NCD approach to these four therapies are unprecedented in the CMS’s history, and one year’s experience is likely too short a period from which to draw any sustaining conclusions. Nonetheless, it is important to examine this initiative, since it is likely to serve as an exemplar for subsequent efforts to couple evidence generation with Medicare coverage. The CMS asserts that the final NCD provides beneficiaries with consistent access to promising uses of four cancer drugs in the context of the NCI clinical trials, while preserving local contractors’ discretion to further cover any off-label uses of these four drugs. In addition, the CMS felt that the NCD would assure the accelerated development of new evidence of the effectiveness of the off-label uses of these four drugs and views this NCD as a potential model for extending coverage to other promising cancer therapies in the specific clinical trials. Finally, the CMS acknowledges that the final outcome of the NCD may "encourage industry to invest in studies that will expand [the] knowledge base for patient and doctor discussions."15 Recent changes to Medicare’s NCD process have made the process more open, participatory, and accountable to stakeholders. The CMS received comments from twenty-seven individuals and groups representing professional associations, national associations of cancer centers, manufacturers, and patient advocates. The majority of commenters generally supported the draft NCD. However, many of them raised issues with the specific NCD as well as with the CMS’s general approach of conditioning Medicare coverage to the collection of additional data.
Sufficiency of the data.
First, objections were raised over whether the additional data collection would ultimately result in high-quality evidence of the effectiveness of the off-label uses of these agents for the Medicare population. None of the nine trials chosen was specifically designed to determine appropriate use or effectiveness of these therapies in the Medicare population; indeed, all are open to all adults age eighteen and older (Exhibit 2
Access to the four cancer drugs. Second, questions remain as to whether linking Medicare coverage to the NCI trials would ultimately restrict Medicare beneficiaries’ access to the four cancer drugs, despite local contractors’ discretion to continue to cover these agents. Many raised concerns that the CMS should ensure access for beneficiaries and their health care providers who do not desire to enroll in or are not eligible for the NCI clinical trials. In addition, some feared that the NCD would yield a de facto restriction of off-label coverage determinations by local contractors. However, a detailed search of the Medicare Coverage Database revealed that no local contractor maintains a single broad policy including all four drugs. Only two local contractors have revised their LCDs to reflect changes in the final NCD. And despite the feared effects of inconsistent local coverage policies, several contractors continue to provide broad coverage for uses of the four drugs beyond those studied in the NCI trials. Coverage expansions. Third, commenters questioned whether the final NCD resulted in an expansion of coverage. For instance, many pharmaceutical companies typically provide investigational drugs free of charge.16 However, the final NCD unquestionably guarantees the coverage of the drugs in the trials. Rationale for chosen trials. Fourth, public commenters felt that the agency failed to provide a transparent rationale for why it chose the specified trials. They felt that the CMS did not adequately involve the public or affected stakeholders in the selection process. The CMS, in response, committed to developing a process with stakeholders to select future trials for inclusion in this NCD. CED and existing policies. Fifth, the CED policy raises questions regarding its relationship with existing policies, such as the CMS’s clinical trials NCD, which provides Medicare coverage for the routine costs of beneficiaries enrolled in "qualified" clinical trials.17 The availability of the clinical trials policy raises questions regarding whether the CED policy plays a unique role in encouraging Medicare beneficiaries’ enrollment in clinical trials and the development of new knowledge. Lastly, many questioned the CMS’s general authority to link coverage with additional data collection.
Despite the challenges raised to the CMS’s final decision, the Anticancer Chemotherapy for Colorectal Cancer NCD has clearly signaled the CMS’s interest in understanding the effectiveness of medical technologies for its beneficiaries. It is also important to note that the CED policy has precedent in previous Medicare decisions. In the case of lung volume reduction surgery (LVRS), the agency directly sponsored research and limited Medicare coverage to beneficiaries enrolled in the National Emphysema Treatment Trial (NETT), a National Institutes of Health (NIH) trial designed to better understand the risks and benefits of LVRS for the Medicare population.18 The NETT ultimately provided the CMS with the evidence it used to base its final NCD for LVRS. Contribution to data registries. The CMS is already involved in several other applications of CED. In many of these, the CMS has not uniformly conditioned Medicare coverage to clinical trials. In fact, Medicare has more commonly linked Medicare coverage to the development of registries, such as the CMS’s cosponsorship of the American College of Cardiology’s National Cardiovascular Data Registry’s (ACC-NCDR’s) Implantable Cardioverter Defibrillator (ICD) Registry, and the decision to condition coverage of certain fluorodeoxyglucose–positron emission tomography (FDG-PET) on the creation of the National Oncologic PET Registry.19 Generating evidence. The CMS is not limited to using its coverage authority to advance the goal of understanding the effectiveness of a technology for Medicare beneficiaries. Several other initiatives might enable the CMS to fulfill its goal. The announcement of the CMS’s Medicare integrated data strategy to create a comprehensive research resource on prescription drug use and use of medical services and the collaboration of the CMS with the Agency for Healthcare Research and Quality (AHRQ) to implement a comparative effectiveness research agenda are just two recent examples of CMS efforts to generate evidence.20 Collecting quality-of-care evidence. In addition, the CMS has several initiatives in place to collect evidence on the quality of care Medicare beneficiaries receive in the hospital, physician’s office, and nursing home. In particular, the CMS’s 2006 Oncology Demonstration Projects provide physicians with an incentive to report data on the health care experiences of their cancer patients.21 Possible CMS-FDA collaboration. It is also feasible that the CMS could work with the FDA to further help inform Medicare coverage decisions. Despite the differences between the FDA’s "safety and efficacy" and the CMS’s "reasonable and necessary" criteria, the long-discussed parallel FDA-CMS review process now seems more likely given the advent of CED. CED could serve as a bridge to connect the FDA’s regulatory requirements with Medicare’s coverage demands. Several opportunities for collaboration exist in postmarket safety monitoring, where patient registries, Medicare claims analysis, and prospective data collection could help meet the needs of both agencies. IT WILL BE IMPORTANT TO MONITOR HOW the CMS continues to use its influence in the health care system to address questions regarding evidence of benefit and the potential value of medical technologies for Medicare beneficiaries. In particular, it will be important to understand whether the CED policy results in an expansion of coverage, rather than slowing access to promising innovations, and whether it successfully balances the unique health care needs of Medicare beneficiaries, the preferences of their health care providers, and the availability of existing alternatives for accessing the technologies. Finally, the mark of the CED policy will be determined not only by payers and purchasers, but also by providers and patients who use the evidence generated in treatment decision making.
Tanisha Carino (tcarino{at}avalerehealth.net) is a director at Avalere Health LLC in Washington, D.C. Reginald Williams is a senior associate, and Allison Colbert is an associate. Perry Bridger is a vice president. The authors thank Sean Tunis, Mark Clanton, and Ellen Feigal for discussing various concepts and issues found within the paper; and Dan Mendelson, Jon Glaudemans, and Lindsey Spindle for their contributions.
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