Opportunities for Improving the Drug Development Process: Results from a Survey of Industry and the FDA

In the United States, the Food and Drug Administration (FDA) agency is responsible for regulating the safety and efficacy of biopharmaceutical drug products. Furthermore, the FDA is tasked with speeding new medical innovations to market. These two missions create an inherent tension within the agency and between the agency and key stakeholders. Oftentimes, communications and interactions between regulated companies and the FDA suffer. The focus of this research is on the interactions between the FDA and the biopharmaceutical companies that perform drug R&D. To assess the current issues and state of communication and interaction between the FDA and industry, we carried out a survey of industry leadership in R&D and regulatory positions as well as senior leadership at the FDA who have responsibility for drug evaluation and oversight. Based on forty-nine industry and eight FDA interviews we conducted, we found that industry seeks additional structured and informal interactions with the FDA, especially during Phase II of development. Overall, industry placed greater value on additional communication than did the FDA. Furthermore, industry interviewees indicated that they were willing to pay PDUFA-like fees during clinical development to ensure that the FDA could hire additional, well-qualified staff to assist with protocol reviews and decision-making. Based on our survey and discussions, we uncovered several thematic opportunities to improve interactions between the FDA and industry and to reduce clinical development times: 1) develop metrics and goals at the FDA for clinical development times in exchange for PDUFA like fees; 2) establish an oversight board consisting of industry, agency officials, and premier external scientists (possibly at NIH or CDC) to evaluate and audit retrospectively completed and terminated drug projects; and 3) construct a knowledge database that can simultaneously protect proprietary data while allowing sponsor companies to understand safety issues and problems of previously developed/failed drug programs. While profound scientific and medical challenges face the FDA and industry, the first step to reducing development times and associated costs and facilitating innovation is to provide an efficient regulatory process that reduces unnecessary uncertainty and delays due to lack of communication and interaction.

Assessing the Safety and Efficacy of the FDA: The Case of the Prescription Drug User Fee Acts

The US Food and drug Administration (FDA) is estimated to regulate markets accounting for about 20% of consumer spending in the US. This paper proposes a general methodology to evaluate FDA policies, in general, and the central speed-safety tradeoff it faces, in particular. We apply this methodology to estimate the welfare effects of a major piece of legislation affecting this tradeoff, the Prescription Drug User Fee Acts (PDUFA). We find that PDUFA raised the private surplus of producers, and thus innovative returns, by about $11 to$13 billion. Dependent on the market power assumed of producers while having patent protection, we find that PDUFA raised consumer welfare between $5 to$19 billion; thus the combined social surplus was raised between $18 to$31 billions. Converting these economic gains into equivalent health benefits, we find that the more rapid access of drugs on the market enabled by PDUFA saved the equivalent of 180 to 310 thousand life-years. Additionally, we estimate an upper bound on the adverse effects of PDUFA based on drugs submitted during PDUFA I/II and subsequently withdrawn for safety reasons, and find that an extreme upper bound of about 56 thousand life-years were lost. We discuss how our general methodology could be used to perform a quantitative and evidence-based evaluation of the desirability of other FDA policies in the future, particularly those affecting the speed-safety tradeoff.

Assessing the Impacts of the Prescription Drug User Fee Acts (PDUFA) on the FDA Approval Process

Congress enacted and renewed the Prescription Drug User Fee Acts (PDUFA) in 1992, and renewed it in 1997 and 2002, mandating FDA performance goals in reviewing and acting on drug applications within specified time periods. In turn, the FDA was permitted to levy user fees on drug sponsors submitting applications to the FDA. While PDUFA mandated action or review times, its ultimate impacts on actual final drug approval times are unknown. We model and quantify the impact of PDUFA-I and II on drug approval times, since these approval dates are the ones most directly related to new medicines becoming available to benefit patients. In assessing the impacts of PDUFA on drug approval times, it is noteworthy that approval times were trending downwards at 1.7% percent per year prior to implementation of PDUFA. Assuming continuation of that time trend, approval times post-PDUFA would have fallen even in the absence of PDUFA. Our principal finding is that PDUFA accelerated this downward trend so that instead of a counterfactual 6% reduction in approval times from 24.2 to 20.4 months in absence of these acts between 1991 and 2002, there was an observed decline of about 42%, from 24.2 to 14.2 months, following implementation of PDUFA. Thus, of the total observed decline in approval times between 1991 and 2002, approximately two-thirds can be attributed to PDUFA. However, much of this impact occurred in the initial years between 1992 and 1997 (PDUFA-I) rather than during the subsequent 1997-2002 time frame (PDUFA-II). We discuss implications of these findings and how future research might quantify the social value of the observed acceleration in the FDA drug approvals.

Genetic survey of caribou populations using microsatellite DNA

Microsatellite loci are highly variable regions of eukaryotic DNA that consist of tandemly repeated sequences of one to six nucleotides in length. The use of microsatellites and the Polymerase Chain Reaction (PCR) are powerful tools for quantifying genetic variation within and among individual populations. Recently, we have developed primers for caribou that amplify 4 microsatellite loci. These microsatellite loci were used to survey the genetic variation in populations of Barren-ground caribou (Rangifer tarandus groenlandicus), Peary caribou (R.t. pearyi) and Woodland caribou (R.t. caribou) of Canada. The four loci examined were all polymorphic, revealing high levels of heterozygosity (> 0.74) in all of the study populations

Monozygotic Twin Wolves with Divergent Life Histories

Genetic evidence for monozygotic (identical) twinning in mammalian species is rare in the literature. Here we report what may be the first pair of monozygotic twins identified in a wild caniform carnivore, the grey wolf (Canis lupus). One of these individuals remained in its natal population of Banks Island, Northwest Territories, Canada, while its twin migrated across the polar sea ice to the mainland. This suggests divergent life history strategies in genetically identical individuals, making this incidence of twinning particularly interesting.Il est rare que la documentation fasse état de preuves génétiques à l’égard de jumeaux monozygotes (identiques) chez les espèces de mammifères. Ici, nous faisons mention de ce qui pourrait être la première paire de jumeaux monozygotes identifiée chez un carnivore caniforme sauvage, le loup gris (Canis lupus). Un de ces individus est resté au sein de sa population natale de l’île Banks, dans les Territoires du Nord-Ouest, au Canada, tandis que son jumeau a migré jusqu’à la terre ferme au moyen de la glace polaire. Cela laisse entrevoir des stratégies de cycle biologique différentes chez des individus génétiquement identiques, ce qui rend cette gémellité particulièrement intéressante

Genetic relationships of three Yukon caribou herds determined by DNA typing

In this paper we examine genetic relationships of caribou (Rangifer tarandus caribou) in the Aishihik, Chisana, and Wolf Lake herds in the Yukon using DNA fingerprinting. The assignment test used in this analysis showed that the caribou herds were distinct. This finding is consistent with movement data from radio-collared caribou which demonstrates home range fidelity. We found a high level of heterozygosity and a genetic basis for population boundaries. DNA fingerprinting may provide an effective means to compare ecological and genetic relationships