WASHINGTON _ Representatives of largepharmaceutical and biotechnology companies last weekcame away from a discussion of how to rethink the wayAIDS clinical trials are run without a clear sense that anyprogress was made.
Several participants at the three-day conference who wereinterviewed by BioWorld Today said they were guardedlyoptimistic about what transpired at the meeting but saidthey still lacked a signal from the FDA or NationalInstitutes of Health about how they could redesignclinical information and still meet the FDA's regulatoryrequirements.
The discussion took place before a joint meeting of theFDA Antiviral Drugs Advisory Committee and theNational Task Force on AIDS Drug Development.
Suzanne Beckner, vice president of clinical developmentat Viral Technologies Inc., of Alexandria, Va., decried thelack of progress. "Virtually nothing has changed since thelast meeting six months ago on AIDS clinical trials,"Beckner said in an interview with BioWorld Today.
"Manufacturers are under the gun to document safety andefficacy. The only way to show that is to documentclinical benefit and the only way to show clinical benefitis to use end-stage patients. But there is no way they willstay in a protocol," she said.
"We go round and round. The companies wereencouraged by the discussion but are skeptical aboutwhether FDA or NIH will follow-up on what was said,"Beckner said.
She said that the future of innovative clinical trialdevelopment lies with the Intercompany Collaborationbut that group is "winding down." At last week's meting,Waijen Soo, vice president, Hoffman-La Roche Inc.,Nutley, N.J., said that the Intercompany Collaboration, agroup of 16 companies involved in AIDS research, needssome clear answers about how to proceed. (See BioWorldToday, Sept. 8, 1995, p. 1.)
"FDA could throw out the whole notion of clinical trialsbut this would require that the agency craft a reasonablealternative. So far it hasn't taken that step. The industryneeds to feel comfortable that a new creative clinical trialconcept will be accepted. Right now nobody is willing tostep forward," Beckner said.
Dan Odenheimer, a clinical affairs officer withBoehringer Mannheim Pharmaceuticals Corp., ofGaithersburg, Md., offered a more positive reaction to theconference. He said he was convinced that the meetinghad elicited a useful discussion on clinical end points, butwas "not sure that anything was resolved."
Odenheimer said he thought a proposal to use datacomparing those who enrolled in a manufacturer'scompassionate use lottery to those who did not to bepromising. That proposal was made by AIDS activistJules Levin, of ACT UP in Brooklyn, N.Y., at theconference.
One manufacturer may deploy such a data collectionscheme. Abbott Laboratories, Abbott Park, Ill., on Aug.31, 1995 announced a compassionate use program forRitonavir slated to start in January 1996 for its proteaseinhibitor drug for treating AIDS and HIV. The companyis considering "what data we can gather from thecompassionate use program but we are far from a finaldecision," according to Doug Petkus, a spokesman forAbbott.
One clinical trials researcher maintained that AIDSclinical trials won't change much in the foreseeablefuture. "Testing of AIDS drugs will work only when thereis a blockbuster cure," said Don Hoover, a biostatisticianwith Johns Hopkins University's School of Hygiene andPublic Health, of Baltimore. Conducting clinical trials forAIDS drugs will continue to be difficult because patientswill switch treatment arms. AIDS patients are testingthemselves with viral load makers. If their numbers goup, they will switch from the control group to thetreatment arm," Hoover said in an interview withBioWorld Today. The result will be clinical trials "wheresmall differences between the control arms become evensmaller," he added.
Hoover is involved in collecting observation data onclinical trial cohorts but readily admits that that goldstandard of the clinical trial must be not be discarded."We need to evaluate the side effects of a drug regardlessof its benefits, if it extends life or reduces suffering. Onlya pivotal clinical trial can answer these questions," hesaid.
Hoover said the best results that manufacturers canexpect from AIDS clinical trials is one that uses a "short-term end point that studies effects that are not longlasting."
One manufacturer is committed to obtaining results undera traditional, controlled clinical trial. "We've put ournickels down on clinical trials," said Howard Jaffee, vicepresident, Gilead Sciences Inc., of Foster City, Calif.
"Even if FDA grants us accelerated approval, werecognize that the question of utility of the drug is notanswered. We want to prove that the drug really works,"he told BioWorld Today. n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.