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Physicians, patients should ‘reflectively reject’ coverage, treatment recommendations based on ICER myeloma report
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The Institute for Clinical and Economic Review, a nonprofit organization that assesses evidence on the value of medical treatments and tests, held its inaugural Midwest Comparative Effectiveness Public Advisory Council meeting on May 26. ICER’s goal was to create a value assessment of various treatment options for relapsed multiple myeloma. I, along with others, have been concerned with the inappropriate application of such analysis to make decisions about insurance coverage of medications.
The purpose of such a meeting and report was to create an “independent” framework that would establish clinical usefulness — ie, “comparative effectiveness” or net health benefit — and a consequent medical economic analysis, or “care value,” in support of one of various therapeutic approaches for multiple myeloma. To more accurately describe the proceedings that led to the final report, I reviewed the full video of the event. My primary concern is that reports like this could be used by payers to deny coverage for lifesaving pharmaceuticals.
Background assumptions and methodology
There are several things to consider:
• Assumptions and intrinsic bias — One must examine assumptions and premises used in the creation of value frameworks such as ICER’s — and, by extension, those of other entities, such as ASCO. One can postulate that the end product of these efforts will be reflective of a number of factors that will lead to its conclusions, including the intent of its creators. Some of these assumptions are — by nature — subjective, and some of the goals of these reports may even be philosophical. These factors may include the implicit or explicit agenda of a group creating such a report; divergent economic and philosophical perspectives on how to improve access to medications or proper spending on medical care; and composition of the expertise of the group generating such reports.
Assuming that all of this possible variation and divergence is acknowledged, it logically follows that the recommendations made will be, by nature, based on the soundness of the medical data being analyzed. This includes the applicability of such data to clinical practice, their relevance to today’s therapeutics, and how these data may have changed with additional knowledge that refines, expands or rebuts the information presented in such original trials. In other words, to be relevant, the applicability of decisions made by ICER or other such panels needs to align with the real world to prevent hypothetical discussions guiding reality.
• Methodology and absence of rebates — ICER’s methodology centers on the fundamental question: Is it worth it for payers to cover a given treatment approach for a patient with multiple myeloma? The methodology is based on a ceiling concept where a maximum amount is accepted for an individual treatment — ie, dollars per quality-adjusted life year — or to a society at large, meaning budget impact or dollars per year per indication. Given these figures are prespecified, and not necessarily by ICER, the final vote is primarily based on whether paying for a combination seems appealing. So if the methodology ultimately will create a computation, why not use real-world data? To presuppose that a patient or a payer pays the wholesale acquisition price for a drug is not descriptive of reality. Omission of rebates and discounts limits the accuracy of the conclusions of the “care value” votes.
• Inclusiveness — ICER’s reports do not seek to expand treatment option recommendations; rather, they evaluate the worth of paying for treatments. Some of the pharmaceutical companies and patient support organizations complained about ICER calling them stakeholders, absent tangible dialogue. Some, such as the Multiple Myeloma Research Foundation, asked for clarification of this nomenclature. Others, like Celgene, requested their names be removed from the report because they felt they did not have substantial input in the process.
Panel composition
Is the ICER panel, or council, ideally positioned to provide an expert opinion on the clinical benefit and the “care value” of the voting questions being presented? Overall, the council has limited expertise in the field of multiple myeloma. With a field so complex, it was unrealistic to expect them to grasp the nuanced implications of what was being discussed. It was evident the team had ample expertise in the field of pharmacoeconomics, epidemiology and evidence-based medicine. But was this sufficient?
To be fair, and despite this limitation, the voting pattern of the council acknowledged the clinical benefit of combinations, even if their recommendations were often clouded by doubts arising from the fact that most of them are not users of such drugs in the clinic. The council also had to vote on the “care value” of treatment combinations that had been previously deemed to be of clinical benefit. The council would universally vote that these combinations were of “low” to “intermediate” value, with no votes to “high” with the exception of panobinostat (Farydak, Novartis). I know many long-term survivors of multiple myeloma who would think their medicines should be “high.”
The voting patterns were consistent with the data presented, but detached from the actual knowledge of the disease and the clinical benefit we observe. In some ways, this is a predetermined outcome of the established process in which valuation of these interventions would be placed against parameters used in other health care valuations. In short, the panelists decided the treatments proposed were good, but that their price points exceeded a monetary amount that could be supported.
Two outside consultants and recognized multiple myeloma experts — S. Vincent Rajkumar, MD, of Mayo Clinic in Rochester, Minnesota, and Ravi Vij, MD, MBA, of Washington University School of Medicine in St. Louis — provided comments and context. Interestingly, one of the greatest ironies of the meeting was that Rajkumar — someone who passionately advocates for lower prices for medications — had to defend pharmaceutical companies and the quality of clinical trials and had to educate others in the process of understanding the applicability of clinical trials in multiple myeloma.
A patient-centric report?
Were the meeting and the report patient centric? The meeting had some discussion about the use of quality-adjusted life years. Bioethicists have questioned the use of this metric to deny treatments. The only ethical way to use quality-adjusted life years is to select a treatment among two that are identical — a rarity in medicine — and make a selection solely based on costs.
The organizers stated that, “Patients should be able to make judgments.” Is this possible based on the ICER report? Isn’t it true that ICER’s aims to help the broader needs of society can only be achieved at the expense of the individual? Who decides what is the appropriate ceiling for payment for any medical intervention? Are these metrics based on amounts that are truly universally accepted?
Although the meeting included commentaries from patient-support organizations and patient advocates, the session was not patient centric. The meeting was payer centric. Patients pleaded for continued coverage for drugs that had been lifesaving to them or a loved one. Why plea, even if in anger, to a self-anointed arbiter group seemingly incapable of fully understanding the therapy of such a complex disease? In fact, one of the panel members explicitly stated he would vote on almost all “care value” proposals as low given his personal beliefs that this money could be better used for other purposes in society. That is not patient centric. To this person, spending money on infrastructure, public health and other noble societal aspirations was superior to the idea of focusing on providing access to life-saving medications for patients with cancer.
I have previously criticized the limitations of ICER’s value framework and postulates of clinical benefit. Although the comparative effectiveness votes are primarily based on factual analysis of data presented, voting on the “care value” would seem to require understanding of the potential clinical value of these drugs. It was not clear to me this was within the grasp of the council.
For instance, it was concerning that a disproportionate amount of time was spent discussing panobinostat, a histone deacetylase inhibitor newly approved for the treatment of multiple myeloma. Of all therapies approved, most myeloma experts would agree panobinostat is probably the one that is least likely to have a long-term impact on patients’ survival or long-term outcomes, and yet it consistently appeared as the favorite of the council.
Very little time was spent discussing the benefits and risks of carfilzomib (Kyprolis, Onyx), and almost no time was spent discussing lenalidomide (Revlimid, Celgene) or pomalidomide (Pomalyst, Celgene). Myeloma experts know that bortezomib (Velcade, Millennium/Takeda) is primarily used now in a subcutaneous fashion. Lastly, it was self-evident that the report would be extremely limited given that daratumumab (Darzalex, Janssen) would not be included due to the lack of available clinical trial data comparing the agent to alternative treatment regimens.
Conclusion
So where do we go from here? Regardless of the intentions or potential benefits of an analysis like this, the intrinsic limitations of the panel’s subject matter expertise, plus methodological and data limitations, precludes statements or claims about economic worth of the various treatment options for the disease.
Physicians, patients, patient advocates and patient support organizations should reflectively reject any coverage or treatment recommendations that are associated with this report. The mere thought of calling a peer-to-peer appeal with an insurance company and having the insurance employee cite ICER will only be tolerated by a hefty dose of omeprazole and lorazepam!
References:
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Fonseca R. Comments for the proposal by the Institute for Clinical and Economic Review (ICER) to do an evaluation of treatment options for relapse or refractory multiple myeloma. Available at: liberteriandoc.tumblr.com/post/138874134054/comments-for-the-proposal-by-the-institute-for. Accessed on Aug. 12, 2016.
Goldberg R. ICER: A cancer survivor/marathon runner’s perspective. Available at: drugwonks.com/blog/icer-a-cancer-survivor-marathon-runner-s-perspective. Accessed on Aug. 12, 2016.
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Hinkel J. Having cancer doesn’t make me worth less. Available at: https://medium.com/@jenniferhinkel/having-cancer-doesn-t-make-me-worth-less-2dab642928d9#.wxnzc25uf. Accessed on Aug. 12, 2016.
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Rafael Fonseca, MD, is Getz family professor of cancer, chair of the department of medicine and distinguished Mayo investigator at Mayo Clinic in Phoenix, Arizona. He can be reached at fonseca.rafael@mayo.edu.
Disclosure: Fonseca has received a patent for the prognostication of multiple myeloma based on genetic categorization by fluorescence in situ hybridization. He reports consultant fees from Amgen, Bayer, Bristol-Myers Squibb, Celgene, Janssen, Millennium/Takeda, Novartis and Sanofi. He also is a member of the Scientific Advisory Board of Applied Biosciences.