WASHINGTON _ In one of the most sophisticatedanalyses yet published, the General Accounting Office(GAO) has absolved the FDA of that deadly sin it is mostoften accused of committing _ sloth.
A new GAO report, requested by Sen. Nancy Kassebaum(R-Kan.) and released on Tuesday, concludes that theagency cut drug review times almost in half between1987 and 1992. Further, it found that regulatory reviewtimes were shorter in the U.S. than in the U.K., not theother way around as many FDA critics have argued.
"With respect to time, new drug applications [NDA] aremoving more quickly through the drug review andapproval process," stated the report. "Further, themagnitude of the reduction [in review time] _ more than40 percent _ should be considered in the ongoingdiscussions of the need to change the NDA reviewprocess or the agency itself in order to speed theavailability of drugs to patients."
The GAO rejected the argument offered by some groupsthat the British counterpart to the FDA, the MedicinesControl Agency, performs reviews of equivalent qualitysignificantly faster than the FDA. The limited comparabledata available "paint a more ambiguous picture than thatpresented in many recent reports," concluded the GAO."In fact, the latest data published by the regulatory agencyin the U.K. show that it does not have faster approvaltimes than the FDA."
With its report, the non-partisan GAO, a congressionalwatchdog organization, has entered the increasinglypartisan fray over FDA reform. Last November, newlyelected Republicans, led by House Speaker NewtGingrich (Ga.), vowed to overhaul the agency. OnTuesday, Kassebaum, chairman of the Senate Labor andHuman Resources Committee, offered muted praise forthe FDA.
"It appears that improved FDA management andimproved applications by manufacturers were the maincauses of this reduction [in review times]," Kassebaumsaid in a statement about the GAO report. "I believe that[review] time can be shortened considerably more,however, if Congress makes changes now in the way theFDA operates." Kassebaum plans to introduce FDAreform legislation later this month. Currently, at leastthree major FDA reform plans are pending beforeCongress.
But FDA supporters were crowing on Tuesday. "TheGAO's timely analysis is a persuasive case against thosewho claim that Congress should scrap the current systemof FDA review and replace it with a radically differentapproach," said Sen. Edward Kennedy (D-Mass.). "As theGAO report makes clear, the FDA is moving in the rightdirection and Congress should not yield to special interestpressure." Kennedy added that he supports "responsibleFDA reform" and still wants to address "the specialproblems facing biotech products."
The Pharmaceutical Research and Manufacturers ofAmerica (PhRMA) called the GAO report "misleading"because it focuses on drug review times as the onlyrelevant factor of FDA performance. Total drugdevelopment time _ the time required for a new cure toreach the patient from the laboratory _ takes 15 years,according to the Center for Drug Development at TuftsUniversity. "FDA regulatory authority extends overnearly all this process," a PhRMA press release stated."Fundamental FDA reform is needed to reduce thislengthy development period."
GAO Study Breaks New Ground
At Kassebaum's request, the GAO studied the period oftime that begins with the submission to the FDA of anNDA and that ends when a final decision is made on thatapplication. The 700 NDAs submitted to the FDA'sCenter for Drug Evaluation and Research (CDER)between 1987 and 1992 formed the basis of the GAO'sanalysis of overall review times. Because the GAO hadaccess to the FDA's proprietary records, it was able toinclude all NDAs _ both those approved and those notapproved _ in its data base. Most studies of FDAperformance cover only approved drugs, since that's theonly public information.
In addition, the GAO calculated review times from thedate of the initial NDA submission, even if the FDArefused to file it, to the date of the FDA's final action. Incontrast, the FDA calculates its own review times fromthe date it formally "accepts" an NDA. Anotherdifference: the GAO used mean (or average) reviewtimes, rather than median review times, which the FDAemploys to assess its own performance. Key findings ofthe GAO report include:
* NDAs submitted in 1987 took an average of 33 monthsto be approved while NDAs submitted in 1992 wereapproved in an average of 19 months. That represents a42 percent decrease. The reduction in time was observedfor all NDAs and not just for those which were approved;
* Nearly half (44 percent) of the NDAs submitted to theFDA between 1987 and 1992 were not approved formarketing, either because the FDA judged the drugsunsafe or ineffective or because the sponsor withdrew theapplication;
* Only 17 percent of NDAs submitted between 1987 and1992 were given priority status by the FDA. Prioritystatus is reserved for drugs representing a significanttherapeutic advance;
* GAO data on drug review and approval show thatapproximately one-fifth of the time in that processcomprises activities for which sponsors are responsible,such as time taken to respond to FDA inquiries;
* An NDA's priority status (or lack thereof) is astatistically significant predictor of outcome in the FDAreview process. The GAO found that priority NDAs werefour times more likely to be approved than standardNDAs. That means priority NDAs were approved 10months faster than standard NDAs;
* The experience of an NDA's sponsor also is astatistically significant predictor of outcome in the FDAreview process. Applications submitted by the mostexperienced companies (those that submitted nine ormore NDAs between 1987 and 1992) were three timesmore likely to be approved than those submitted by lessexperienced sponsors. That means applications fromexperienced sponsors were approved four months fasterthan those from less experienced sponsors.
In addition, 25 percent of NDAs submitted by the leastexperienced companies (companies that submitted four orfewer NDAs) were deemed "not approvable" by the FDA,while the FDA refused to file another 15 percent of thesesubmissions. In contrast, only 9 percent of NDAs fromexperienced sponsors were ruled "not approvable" andthe agency refused to file only 3 percent of these NDAs. n
-- Lisa Piercey Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.