ODAC Agenda Includes Comments, Data, Debate, Vote

ABSTRACT: This is part 2 of a two-part article that provides a behind the scenes look at the workings of the FDA Oncologic Drugs Advisory Committee. Part 1, which appeared last month, described the committees' duties and how members are selected. This article outlines a typical meeting and tells how the FDA uses the recommendations.

By Margot Fromer

WASHINGTON-The 11 member Oncologic Drugs Advisory Committee (ODAC)was established in 1978 to offer scientific and technical adviceto the FDA about the safety and effectiveness of cancer drugs,including new drugs and new indications for already approved agents,Adele Seifried, MS, ODAC administrator, told ONCOLOGY NEWS INTERNATIONAL.

Except in rare circumstances, all ODAC meetings, which take placeat FDA headquarters in Rockville, Md, are open to the public.They are announced in the Federal Register at least 2 weeks inadvance. A meeting usually lasts 2 days during which two to fournew drug applications are considered.

The FDA sets an agenda for each meeting and prepares a set ofquestions for the committee's consideration.

Time for Public Comments

An hour is set aside at the beginning of each meeting so thatmembers of the public can make comments in person or have lettersread into the record.

"This is an extremely important part of the process,"said Paul Bunn, MD, a 3-year member of ODAC and its new chairman."Also, because the meetings are open, drug companies cansee how they are run and how ODAC works," added Dr. Bunn,director of the University of Colorado Cancer Center. "Ithink the quality of the sponsors' presentations has improvedbecause of this," he said.

Charles A. Schiffer, MD, ODAC's immediate past chairman, alsolikes open meetings and the opportunity for public comment. "TakeAIDS for example. In the beginning, activists were clamoring fornew treatments. They didn't care how bad the side effects werebecause they felt that nothing could be worse than the onslaughtof AIDS."

But as time went on, he said, the activists learned how drugsare tested and approved, and they began to realize how importantit is in the long run to have good studies done by reliable anddisciplined researchers.

"The people concerned about AIDS who came to our meetingsrapidly learned some of the ins and outs of pharmaceutical researchand could then serve as informed and responsible advocates fortheir constituents," said Dr. Schiffer, professor of medicineand oncology, University of Maryland Cancer Center.

The Presentations

After public comments, the new drug's sponsor is given time tomake its presentation. An FDA medical reviewer then summarizesthe agency's evaluation of the sponsor data (the culmination ofmany months of work prior to the ODAC meeting). The FDA then asksODAC for its advice about safety and efficacy, labeling and specialwarnings, and additional studies needed.

The Debate

After fortifying themselves with coffee and snacks, ODAC membersbuckle down to serious discussion. They ask questions of boththe FDA medical reviewer and the drug's sponsor, and they debatewith one another.

This is the part that ODAC members seem to enjoy most. Dr. Schifferdescribed it as "intellectual fun." He said that thecommittee wants to maintain a collegial atmosphere with both theFDA reviewer and the drug company representatives.

"For a very few drugs, the decision on approval is easy,"he said. "If there's a striking new compound that obviouslycures people, it's going to be approved. But most new drugs fallinto a gray area."

He noted that in these cases, both the FDA and ODAC try to beliberal. "If it looks like it's going to have a dramaticlong-term benefit in even a small percentage of patients withan otherwise untreatable disease, and if the side effects aretolerable, we often recommend approval," he said.

During the final discussions, interpretations of data are discussed,and the ultimate issues of safety and efficacy are weighed. Whenall members have had their say, when all questions have been answered,a vote is taken.

What the Vote Means

A vote in favor of approval means only that ODAC, a committeeof private individuals, recommends that FDA take action. "Ittakes a few months for the agency to officially give its stampof approval," Ms. Seifried said.

The Division of Oncologic Drug Products reviews the committee'sdiscussion (which is both audio- and videotaped), especially ifthe vote was close or tied. Chemical and manufacturing issuesmust also be ironed out with the sponsor.

"The division takes our advice very seriously, but it isnot obligated to do what the committee recommends," she noted.Dr. Bunn was asked if he ever feels frustrated if the FDA doesnot follow ODAC's recommendations on approval.

"Not really," he replied. "First of all, it's thelaw and we all understand that. Second, now that we have acceleratedapproval, things aren't as black and white as they used to be.We can recommend approval with some caveats [further clinicaltrials or more or different data on studies already completed],and that seems to work well."

He spoke positively about accelerated approval, which has beenused more frequently in the past decade as a result of consumeractivism.

"It's reasonable to try new things," Dr. Bunn said."Time will tell if accelerated approval works well in thelong run. I think that if a drug is safe and has some positiveeffect but more clinical work still needs to be done, I say giveit a try."

Current ODAC Members

Paul Bunn, MD, Chairman
University of Colorado Cancer Center

Adele S. Seifried, MS, Executive Secretary
Food and Drug Administration

Janice Dutcher, MD
Montefiore Medical Center, New York

Arlene Forastiere, MD
The Johns Hopkins Oncology Center

Richard Gelber, PhD
Dana-Farber Cancer Institute

James Ingle, MD
Mayo Medical School, Mayo Clinic

James Krook, MD
The Duluth Clinic Limited

Judith Ochs, MD
Arkansas Children's Hospital, Little Rock

Robert Ozols, MD, PhD
Fox Chase Cancer Center, Philadelphia

Albert Siu, MD, Consumer Rep
Mt. Sinai Medical Center, New York

Sandra Swain, MD
Salick Health Care Inc., Bethesda, Maryland