AGENDA

Wednesday, February 16, 2005
10:00 a.m.–1:45 p.m.
Wohlstetter Conference Center, Twelfth Floor, AEI
1150 Seventeenth Street, N.W., Washington, D.C. 20036

9:45 a.m.	Registration
10:00 a.m.	Welcome
	ROBERT W. HAHN, AEI-Brookings Joint Center for Regulatory Studies
	Presentation
	ERNST R. BERNDT, MIT
	ADRIAN H. B. GOTTSCHALK, BiogenIdec
	Discussants
	SCOTT GOTTLIEB, AEI
	RANDALL LUTTER, FDA
12:00 p.m.	Luncheon
12:30 p.m.	Keynote
	AMIT SACHDEV, FDA
1:45 p.m.	Adjournment

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CONFERENCE SUMMARY

Introduction

On February 16, the AEI-Brookings Joint Center hosted a conference on drug approval times and the impact of legislation. The conference focused on the 1992 Prescription Drug User Fee Act (PDUFA) and two subsequent PDUFA renewals by Congress. Amit Sachdev, Senior Associate Commissioner for Legislative Affairs at the Food and Drug Administration delivered the keynote address.

The conference opened with a presentation by Professor Ernie Berndt, MIT Sloan School of Management and Adrian H. B. Gottschalk, senior manager at Biogen Idec’s corporate strategy group, of a recent study they had conducted. Scott Gottlieb, of the American Enterprise Institute, and Randall Lutter, Chief Economist in the Office of Planning at the Food and Drug Administration, discussed the study’s findings. Following a question and answer session, Mr. Sachdev spoke and then fielded questions.

Presentation

Adrian H. B. Gottschalk
BiogenIdec
Mr. Gottschalk began by describing the “lengthy and risky” drug approval process. He presented graphs to demonstrate that drug approval times increased steadily until the early nineties and then “dramatically decreased” from 1992 to 2001. This drop corresponds with the passage of PDUFA, which required the FDA to review new drug applications within six or ten months and generated increased funds to cover the costs of complying with the legislation. Next, Mr. Gottschalk described how he and Mr. Berndt analyzed the review times for 662 New Molecular Entities to explore the effects of PDUFA. Their study found that PDUFA has significantly shortened drug approval times

Ernst R. Berndt
Massachusetts Institute of Technology
Mr. Berndt explained in more detail their multivariate least squares regression model, the results of which produced additional evidence that PDUFA decreased drug approval times.

Mr. Berndt then discussed whether reduced review times from PDUFA have reduced safety. Three studies tracked drug withdrawals from the market due to safety concerns, Mr. Berndt noted, and none of them found a significant increase in withdrawals as a result of PDUFA. Mr. Berndt cautioned, however, that these studies have a variety of problems, including sample size due to the fact that from 1970-2002 only 22 drugs have been withdrawn for safety reasons.

Discussants

Scott Gottlieb
American Enterprise Institute
Mr. Gottlieb discussed how PDUFA has affected the culture and behavior of the FDA and suggested several reforms. He noted that only FDA managers, and not the “rank and file medical reviewers,” have much awareness of PDUFA. He said that the effects of PDUFA can be observed in the form of 1) increased funding for more reviewers and infrastructure and 2) management reforms. However, he said, Congress often demands that the FDA undertake additional tasks, but does not provide extra funding. In addition, some of the FDA’s work becomes more costly as technologies (like nanotechnology) become more sophisticated. Consequently, a significant share of the PDUFA revenues have not been used to hire new medical reviewers, but instead to keep up with the increasing demands of the FDA mission.

Mr. Gottlieb also explained that research and development is becoming more expensive. The number of trials per new drug is increasing, trial sizes are increasing, and success rates are dropping. Drug companies try to squeeze more revenues out of products already on the market and to acquire other companies with late-stage candidates, leading to consolidation of the industry. Mr. Gottlieb suggested several reforms including reforming the Investigational New Drugs requirement, incorporating more biomarkers in the review process (e.g. approving a drug as effective at reducing cardiovascular disease if it is able to demonstrate that it lowers cholesterol levels), and using information technology to improve efficiency.

Randall Lutter
Food and Drug Administration
Mr. Lutter outlined some of the limitations of the Berndt, et al. study and suggested several next steps in the evaluation of PDUFA. He noted that the U.S. used to approve only 5% of new active substances before any other country in the world and now approves 47% before any other country. It is unclear, he noted, whether PDUFA is responsible for this decline since approval times were declining before the act was passed. The key finding in the Berndt et al. study, therefore, is that PDUFA accelerated the decline in approval times.

Mr. Lutter expressed skepticism with studies that use FDA safety withdrawals as a measure of the degree of caution the FDA employs when approving new substances. Safety withdrawals are rare events that vary significantly depending on the choice of cohorts (start and end points of time periods studied). Furthermore, do more withdrawals indicate that more drugs are unsafe or that the FDA is more effective or cautious? Mr. Lutter said an analysis of the use of black box safety warnings on prescription drugs, rather than safety withdrawals, is a better measure of safety. Using this measure, he finds that PDUFA has no significant effect.

Question and Answer Session

The questions following the morning session of the conference focused on explaining why drug approval time decreased and the goals of the FDA. One audience member asked what part of PDUFA is most responsible for the decreased approval time. Mr. Gottlieb responded that the greatest improvements in efficiency come from management structural changes because PDUFA is process-oriented. He also said that setting goals and increasing funding must be done in concert to be effective. Another audience member noted that safety has always seemed to be the FDA’s top goal and asked how likely it is that approval speed might become more of a priority in the future. Mr. Gottschalk replied that because of the negative public outcry resulting from incidents like the Vioxx case, he does not anticipate any diminishing emphasis on safety. Mr. Berndt also mentioned that he would be contributing to a study on the costs and benefits of the PDUFA legislation, expected to be published by this summer.

Keynote

Amit Sachdev
Food and Drug Administration
Mr. Sachdev began by explaining the challenges faced by the FDA because of a mission that grows increasingly complex while resources remain constant. He said that the FDA should place a priority on restoring the public trust in the FDA and the promise of the medical technology it regulates. Mr. Sachdev praised PDUFA as an outstanding government innovation. He said empirical evidence has shown that PDUFA has increased access to more and better medicines, enhanced agency resources, and maintained the same level of safety standards. In Mr. Sachdev’s opinion, the FDA and other agencies need to continue to innovate with legislation like PDUFA in order to continue this success. The key to such innovation in the near term is successful collaboration with industry to improve scientific understanding, leverage limited resources, and enhance predictability and reliability. Mr. Sachdev emphasized his opinion that that enhanced isolation and separation will not lead to great FDA success, despite that suggestion from some of PDUFA’s critics.

Question and Answer Session

Questions following Mr. Sachdev’s talk focused on the positive and negative effects of industry ties to the government as well as public perception of risk and drug approval delays. One audience member asked if the FDA should report the number of lives lost due to limited access to medicine as a result of delayed drug approvals. Mr. Sachdev commented that although the idea is a good one, it probably would not be best undertaken by the FDA because the FDA is tasked with issuing statements of public confidence. He suggested that other organizations might be more appropriate to issue such a report. Another audience member asked whether the government should attempt to improve public understanding of risk. Mr. Sachdev said that this is an important task, and that the FDA should start by educating doctors. Mr. Sachdev was also asked to what extent the FDA is afraid of anti-competitive behavior on the part of the pharmaceutical firms meeting with government. He said that there are well-established pathways for the government to interact with industry to improve policy and that he is not suggesting any change to current anti-competitive laws and processes. He also said that many groups would be involved in this process in addition to government and manufacturers.

Jordan Connors, a researcher at the AEI-Brookings Joint Center for Regulatory Studies, prepared this conference summary.