Whole areas of medicine are underdeveloped.

VI. CONCLUSION The problem explored in this Article is the paradoxical relationship between drug innovation and its reward. The reward shrinks (or, at best, stays flat) when premarket innovation takes longer. On the whole this should lead to post-invention efficiency, minimizing the impact of any endogenous factors contributing to the premarket program length.285 It also means that companies are unlikely to make choices specifically to delay market entry. With the clock ticking on post-approval market exclusivity, there is no benefit to doing so.286 The historical and empirical work in this Article leads to three important insights about the paradoxical relationship between drug innovation and its reward. First, the length of any particular drug’s premarket research and development program may depend heavily on factors like the disease and its therapeutic category, our current understanding of the causal pathways of the disease, the proposed therapeutic outcome, the chemical structure of the active ingredient, its mechanism of action, its physiological effect, and FDA’s innate conservatism. These exogenous factors are beyond the sponsor’s control in the sense that any seasoned firm with qualified personnel picking one premarket program instead of another would face the same issues.287 Second, certain drugs are simply going to take longer to develop. These will include some drugs for some early stage cancers that have a longer time to progression and mortality, for instance, as well as drugs for use in the earliest stages of neurodegenerative diseases if the therapeutic goal is delay or prevention of the ultimate outcome. They will include drugs for long-term use for conditions (such as diabetes mellitus) that significantly precede clinical events of interest (such as heart disease, stroke, and kidney damage). They will include drugs intended for less well understood body systems, like the central nervous system, where even novel surrogate markers may be years off. Third, the choices faced by a company in the new drug paradigm are generally not choices among more and less efficient routes to the same end result. A new drug in the federal drug scheme is a particular combination of active ingredient, product features, and the labeling (disease and outcome). The research performed by a drug’s sponsor thus defines the product approved by FDA at the end of the day. This means the sponsor’s choices during the research and development period are tantamount to choices about the product to be pursued. The Paraplatin example illustrates why it may generally be more rational to select a short runway with a limited approval than a long runway with a broader approval. This decision may be due to the time value of money, but the innovation paradox suggests that it may also result from the price paid in lost effective patent life when clinical programs run longer. As a matter of public policy we may prefer that companies facing this choice select the product with the shorter runway. But in some cases a company will not have that option. If a company must choose between a long runway and a different product altogether, the innovation paradox may mean whole areas of medicine remain underdeveloped. The implication for social welfare is that we may have a profound interest in breaking the paradox – in ensuring that longer research programs no longer lead to shorter rewards.