RESUMO
PURPOSE: To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. METHODS: We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. RESULTS: The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was -1.80 million LYs, attributable to delayed access to diabetes therapies (-0 .18 million LYs) and fewer drugs (-1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. CONCLUSION: The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or for gone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result.