Duke 2008 | ASHE | Equity and Efficiency in Health and Healthcare

Well-publicized withdrawals of otherwise beneficial drugs because of relatively small risks of severe side effects raise the question of how risks and benefits should be compared to maximize the net societal benefit of new pharmaceuticals. The Food and Drug Administration Amendments Act of 2007 requires FDA to evaluate methods for assessing risks and benefits in the drug-approval process. This session includes methodological, industry, and regulatory perspectives on what economists can contribute to improving methods for weighing treatment benefits against treatment risks for new pharmaceuticals. The chair and each of the panelists are participants in FDA’s current risk-benefit initiative.

In all the recent withdrawals, interventions offering potentially significant therapeutic benefits were found to carry increased risks of serious and possibly life-threatening adverse events. Decisions to halt the development or sale of such therapies clearly require a decision regarding the balance between benefits and risks. Despite the importance of establishing consistent and principled criteria for determining when benefits outweigh risks, experts have provided surprisingly little guidance to help decision makers evaluate such tradeoffs.

FDA’s drug-approval decisions are based on very limited scientific evidence beyond the original clinical-trial data on safety and efficacy. Decisions generally are informed by advisory bodies of scientists and clinicians, although balancing benefits and risks involves social judgments for which scientists have no special expertise. Regulatory procedures also include hearing testimony from patients and physicians who have experienced the beneficial or adverse outcomes of a therapy. However, such anecdotal testimony does not provide systematic evidence of the willingness of well-informed stakeholders to accept observed or expected risks to achieve the therapeutic benefits of these products. Furthermore, it is unclear whether those who advocate for less restrictive or more restrictive access to medications are representative of the population for whom the medication is indicated.

Existing federal regulations and guidance documents focus primarily on quantifying clinical evidence of efficacy and safety rather than balancing risks and benefits. Current risk- benefit evaluations do not require quantifying or even formal consideration of the values of patients, physicians, or other stakeholders. A recent Institute of Medicine report notes that “in both the pre-approval and the post-marketing setting, the risk-benefit analysis that currently goes into FDA decisions appears to be ad hoc, informal, and qualitative.”

This panel will provide a structured discussion of FDA’s current initiative to evaluate alternative methods for incorporating quantitative risk-benefit analysis in evaluating new pharmaceuticals. After the chair’s presentation of an overview of the policy context and impetus behind the initiative, panelists will discuss the following questions.

1. Why is FDA now interested in possible solutions to a problem that has existed for many years?
2. What alternative risk-benefit analysis methods are available to decision makers?
3. What are the methodological and institutional advantages and disadvantages of various approaches?
4. What can economists contribute to finding a principled, but pragmatic solution to incorporating risk-benefit analysis in the FDA drug-approval process?