Accelerating new drug development

HOUSTON The US Food and Drug Administration (FDA) system of user fees has accelerated new drug development, but a recent survey suggests difficulties in obtaining volunteers for human clinical trials still slow progress.In 1992, the US Congress authorized a five-year program providing the FDA with additional resources to hire more medical and scientific reviewers to conduct pre-market reviews, as well as support staff and field investigators. This Prescription Drug User Fee Act (PDUFA) was intended to accelerate the application review process for human prescription drugs and biological products. The additional resources came from user fees paid by firms requesting an accelerated review of their products. According to Jane Henney, former FDA Commissioner, "There was not then, and never has been, a guarantee of approval," as a result of payment of fees and accelerated review. The increased funding also enabled the FDA to upgrade the agency's information management system. The success of the PDUFA in decreasing drug application review time without compromising consumer safety resulted in its renewal in 1997. Under the sunset provisions of the Congressional authorisation, further legislative action will be necessary for the FDA to maintain the authority to collect user fees beyond 2002. These fees have become a critical part of FDA funding. Henney has reported, "As we began the user fee program in 1993, 7% of drug review funding came from user fees. This percentage has increased each year. In this fiscal year (2001) drug review funding from user fees will nearly equal the funding received from appropriations." Reviewing the results obtained under the PDUFA in late 2000, Henney noted, "Approval time has dropped from a pre-PDUFA median of 23 months to 12 months. Approval time for priority products has dropped from a median of more than 12 months in the early PDUFA years, to 6 months. The quality of submissions has improved too. Now, approximately 80% of applications submitted are ultimately approved. Before PDUFA, only about 60% were eventually approved." As a result of PDUFA, Henney claimed, "At FDA, drugs and biologics are now being reviewed as fast or faster than anywhere in the world, without compromising the very stringent standards Americans have come to expect." She also said, "Because our reviews are more timely nearly 18 months has been shaved off industry drug development time — resulting in savings of nearly 2 billion dollars per year."Nevertheless, PDUFA is not a panacea. US Senator Ted Kennedy has challenged the drug industry by noting, "Average drug approval times were reduced from 30 to 18 months. The goal now is to achieve comparable reductions in drug development times." According to healthcare policy analyst Michael Cannon of the Citizens for a Sound Economy Foundation, "From a patient's perspective, the most important indicator is overall approval time: the time between a new drug's discovery and FDA approval, not just FDA review time."Average clinical development time is a component of overall drug approval time and has an important influence on how quickly new and improved drug treatments are available to patients. It is the one factor that patients themselves can influence by volunteering to participate in clinical drug trials. Praising the PDUFA, Senator Kennedy has noted, " … the agency has accelerated approval for cancer drugs and expanded access of patients to clinical trials." But access and participation are two different things. "We have a shortage of patients for clinical trials and this slows down the development of effective new treatments," said Ellen Stovall, a two-time cancer survivor and executive director of the National Coalition of Cancer Survivorship. "Most patients simply do not know about clinical trials that could help them," observes Robert Comis, president of the Coalition of National Cancer Cooperative Groups, which conducts clinical trials for the National Cancer Institute (NCI). "Clinical trials represent the very best care we have to offer for many cancer patients, yet many do not take advantage of the opportunity because of lack of awareness or misconceptions of what a clinical trial really is." Last week's release of results of a Harris Interactive survey of 6,000 cancer patients supports Comis' opinion. Roughly 85% of cancer patients were either unaware or unsure that participation in clinical trials was an option and about 75% said they would have been willing to enrol had they known of the option. Misconceptions also reduce patient participation in clinical trials. Of the 16% of cancer patients who were aware of the clinical trial option, three in four turned it down citing four major reasons: about 37% thought the medical treatment they would receive in a clinical trial would be less effective than standard care; roughly 31% worried they would get a placebo; 22% that they would be treated like a 'guinea pig' or that their insurance company would not cover costs (20%). Nevertheless, progress is being made. Recent data from the Tufts Center for the Study of Drug Development indicate that new molecular entities approved 1996–98 required an average of only 5.9 years of clinical research compared with 7.2 years for the preceding 1993–95 interval (4,5). This 15-month saving in overall drug development time coincides with the substantial PDUFA increase in FDA–sponsor interactions regarding the clinical trial process. According to Senator Kennedy, "Patient representation on FDA advisory panels has increased. Clinical research has been strengthened by relieving regulatory burdens. The results of these efforts have been more drugs, faster approvals and better research." But some have criticised the PDUFA. For example, the National Organization for Rare Diseases has noted, "The performance goals of the current PDUFA legislation are measured in time, without adequate safeguards in place to quantify safety and effectiveness. There have been too many recent withdrawals of marketed drugs that have maimed and killed people … We suspect that the large number of market withdrawals since PDUFA was implemented tends to indicate that increased speed of NDA [New Drug Approvals] and PLA reviews may not be the wisest public health policy."PDUFA is still a work in progress. Dr Henney has noted "There are many start-up companies, including orphan drug manufacturers and humanitarian device companies that are not yet profitable, and have limited resources available to them to bring important therapeutic discoveries to market." She has suggested, "Accommodations should be made to waive user fees for the product, facility and application fees for eligible start-up and not-yet-profitable companies under very specific and stringent circumstances." She concludes, "The agency cannot be perceived as favouring some companies and products over others simply because more money changes hands."

Accelerating new drug development

US FDA user fees may have accelerated new drug development but a recent survey suggests difficulties in obtaining volunteers for human clinical trials still slow progress.

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