A perspective on the current FDA guidance for diabetes therapies.
It is of paramount importance to a health plan that any therapy result in an improved clinical outcome. In addition, therapy should be priced in a way to keep healthcare and insurance costs as low as possible. Rising medication costs contribute to higher premium costs, making coverage less affordable.1,2
Payers are keenly interested in outcomes data. From their perspective, the goal of treatment for any disease state is not the treatment itself but rather an improvement in the outcome experienced by the member. In this way, the goal of the payer is aligned with the goal of the member. In the case of type 2 diabetes, before 2008 control would result in better outcomes, including cardiovascular outcomes. The recognition that improved glycated hemoglobin did not necessarily lead to a guaranteed improvement in cardiovascular
outcomes resulted in the FDA’s decision to require randomized, adjudicated trials to establish hazard ratios for major adverse cardiovascular events.3
The recent assessment by the FDA questioned the need for continuing the process of requiring cardiovascular outcomes trials for diabetes medications. The FDA Endocrinologic and
Metabolic Drugs Advisory Committee voted 10-9 to continue the current process. This vote affirmed the view that the current requirements assessing the need for cardiovascular safety should remain in place. In the past decade, results from 8 studies have shown no increased risk of adverse cardiovascular events.4 Yet the importance of knowing that the current approach to assess therapy to make sure that these medications would not lead to worse outcomes led to the decision. This logic is aligned with a payer’s concern for improved outcomes. For diabetes and glycemic control, this means making certain that an improvement in glycemic control does not come at the unacceptable cost of worsened cardiovascular outcomes. worsened cardiovascular outcomes.
This decision, however, comes with a downside. The current system requiring cardiovascular outcomes trials increases the cost of drug development. Pharmaceutical companies take the cost of these trials into consideration as they price their drugs. This fact was a consistent theme cited by those who voted to see the current process changed. Questions were raised about alternative ways to provide adequate evidence to assess safety of potential drugs but in a more cost-effective manner. A number of different assessment processes were proposed, but in the end, none proved adequate to convince a majority of the committee.
The impact of this decision is significant. The cost of drug therapy is of major concern and contributes significantly to the ever-increasing cost of healthcare and health insurance. As the cost of bringing a drug to market increases, pharmaceutical companies pass that increase along to the payer. Regardless of whether the payer is a health insurance company or a pharmacy benefit manager, the acquisition price becomes higher. This cost must then be passed along to those buying coverage, leading to higher premiums and greater cost for the patient. Both factors can have significant consequences for care. Higher premiums can result in fewer people being able to afford health insurance.5,6 Higher drug costs for a patient, particularly in the case of diabetes, have been shown to increase the likelihood of nonadherence or nonpersistence.7 Thus, this cost decision does ultimately negatively affect the clinical outcome that was the primary driver of the decision in the first place.
Moving forward, 2 developments will prove crucial to whether the requirement for cardiovascular outcomes trials continues. The first centers on the results of ongoing trials or those required in the future. If the current trend continues and these trials do not uncover new cardiovascular risk findings but rather serve as a very expensive confirmation of the cardiovascular safety evidenced in previous studies, the necessity of these trials becomes less clear. Secondly, the use of big data is becoming more commonplace and
accepted in many aspects of medical care. Future safety studies may well depend on the use of large databases with propensity-matched controls rather than controlled trials. Trials using big data can involve far greater numbers of subjects than do current trials and may prove to be a comparable or potentially superior approach to answering these safety questions. This type of research can also be done at a fraction of the cost of traditional trials.
The cost of drug development in many ways must follow the current trends in all aspects of the delivery of healthcare. New approaches to the provision of care—whether through technology, location, manpower, or research—are rapidly driving change in the healthcare system, with the goal to maintain or improve the quality of care while keeping it affordable.Author Information
Dr Snow is the medical director, Clinical Strategy for Aetna.References
1. Mammoser G. Why rising drug prices may be the biggest risk to your health. Healthline website. healthline.com/health-news/rising-drug-prices-risk-to-your-health#1. Published
July 18, 2018. Accessed December 3, 2018.
2. American Academy of Actuaries. Issue brief: prescription drug spending in the US health care system, an actuarial perspective. actuary.org/files/publications/PrescriptionDrugs.030718.pdf. Published March 2018. Accessed December 3, 2018.
3. FDA Center for Drug Evaluation and Research. Guidance for industry: diabetes mellitus — evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. www.fda.gov/downloads/Drugs/Guidances/ucm071627.pdf. Published December 2008. Accessed December 4, 2018.
4. FDA Center for Drug Evaluation and Research. FDA background document: Endocrinologic and Metabolic Drugs Advisory Committee Meeting, October 24-25, 2018. www.fda.gov/
downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Endocrinologicand-MetabolicDrugsAdvisoryCommittee/UCM623913.pdf. Accessed December 4, 2018.
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7. Fung V, Mangione CM, Huang J, et al. Falling into the coverage gap: Part D drug costs and adherence for Medicare Advantage prescription drug plan beneficiaries with diabetes. Health Serv Res. 2010;45(2):355-375. doi: 10.1111/j.1475-6773.2009.01071.x.