Flaws in the U.S. Food and Drug Administration's rationale for supporting the development and approval of BiDil as a treatment for heart failure only in black patients

The U.S. Food and Drug Administration's (FDA) rationale for supporting the development and approval of BiDil (a combination of hydralazine hydrochloride and isosorbide dinitrate; H-I) for heart failure specifically in black patients was based on under-powered, post hoc subgroup analyses of two relatively old trials (V-HeFT I and II), which were further complicated by substantial covariate imbalances between racial groups. Indeed, the only statistically significant difference observed between black and white patients was found without any adjustment for potential confounders in samples that were unlikely to have been adequately randomized. Meanwhile, because the accepted baseline therapy for heart failure has substantially improved since these trials took place, their results cannot be combined with data from the more recent trial (A-HeFT) amongst black patients alone. There is therefore little scientific evidence to support the approval of BiDil only for use in black patients, and the FDA's rationale fails to consider the ethical consequences of recognizing racial categories as valid markers of innate biological difference, and permitting the development of group-specific therapies that are subject to commercial incentives rather than scientific evidence or therapeutic imperatives. This paper reviews the limitations in the scientific evidence used to support the approval of BiDil only for use in black patients; calls for further analysis of the V-HeFT I and II data which might clarify whether responses to H-I vary by race; and evaluates the consequences of commercial incentives to develop racialized medicines. We recommend that the FDA revise the procedures they use to examine applications for race-based therapies to ensure that these are based on robust scientific claims and do not undermine the aims of the 1992 Revitalization Act.     

Asymmetric contests with liquidity constraints

We consider two bidders with asymmetric valuations competing to win an exogenous prize. Capital markets are imperfect, such that the contestants possibly face a liquidity constraint. We show that aggregate investments are lower if at least one bidder has a liquidity constraint, even if the low-valuation bidder possibly increases his/her investments. Furthermore, the effect of the high-valuation bidder’s liquidity constraint on competitive balance is ambiguous. However, if the low-valuation bidder is constrained, greater wealth unambiguously increases competitive balance. Surprisingly, if the low-valuation bidder has a constraint, a tighter constraint can increase his/her profit.     

Cardiac Sudden Death as a Result of Acute Coronary Artery Thrombosis During Chemotherapy for Testicular Carcinoma

Abstract: We report the first acute coronary fibrin thrombus arising upon atherosclerosis detected at autopsy in a man receiving chemotherapy for testicular carcinoma. The decedent was a smoker with no other known atherosclerotic risk factors. Histology revealed superficial atherosclerotic plaque erosion with endothelial necrosis and no intraplaque hemorrhage. A focus of intimal lymphoid infiltrates was noted away from the plaque. These findings raise the possibility of chemotherapy‐induced vascular damage as a factor in thrombogenesis. A review of Pubmed was performed which documented clinical reports of an association of chemotherapy with acute cardiac ischemia but no well described autopsy findings. Our case highlights the need for careful assessment of the coronary system in chemotherapy patients dying suddenly, particularly in the absence of significant atherosclerotic risk factors. Such postmortem examination will ensure thorough death investigation and may elucidate the pathogenesis of thrombosis with potential reduction in cardiac ischemic risks of chemotherapy patients.