The Institute of Medicine (IOM) on Thursday released a reporturging that pregnant women not be routinely excluded fromexperimental drug trials.

The IOM report was commissioned to study ethical and legalissues surrounding women and clinical research. A committeeof 13 experts concluded, among other things, that pregnantwomen and women of reproductive potential should not bebarred from partaking of the risks and benefits of clinicalresearch.

The report said a pregnant woman should be "treated as anindividual, not only as a carrier of a fetus" and should beallowed to make up her own mind about the risks ofparticipating in a clinical trial of a drug offering significantpotential benefit to her health. However, in cases where anexperimental drug offers no possibility of benefit andsignificant risk, the panel concluded that excluding pregnantwomen was appropriate.

"Pregnant women need and take drugs," said Sheldon Segal, anIOM committee member from The Population Council in NewYork. "Yet doctors don't know what to expect or whether toalter dosages when treating a pregnant woman because thereare no data."

The report's conclusions on allowing pregnant women in drugtrials is bound to generate controversy in the researchcommunity. Since the 1950s and '60s, when two notoriousdrugs, thalidomide and DES (diethylstilbestrol), werediscovered to cause severe birth defects, the federalgovernment has observed strict laws to protect fetuses. "Thiselement of the report is going to be quite dicey," said one FDAofficial, who asked not to be identified.

The IOM report noted that 75 percent of women use betweenthree and 10 different drugs while pregnant, yet most of thesedrugs were never tested on pregnant women, so their effectsaren't known. "We must fill gaps in knowledge about how tomanage disease and illness in pregnant women," said IOMcommittee co-chair Ruth Faden, director of the program in law,ethics and health at Johns Hopkins University in Baltimore."Federal regulations must be revised for this to happen."

Although the IOM report focused on clinical studies sponsoredby the government, Faden said she hopes the drug industrywill adopt the principles of inclusion for pregnant women andothers outlined in the IOM report because there is no "morallyrelevant" difference between government-funded clinical trialsand those sponsored by private industry.

But the drug industry is unlikely to be enthusiastic aboutincluding pregnant women in clinical trials. The threat oflawsuits from pregnant women or their grown childrenclaiming damage from the use of experimental drugs loomslarge.

Anita Allen, a professor of law at Georgetown University LawCenter in Washington, D.C., and an IOM committee member,conceded that there are no clear legal precedents in the area ofliability and compensation for pregnant women (and theirfetuses) who participate in clinical trials of experimental drugs."We don't know what the courts will hold," she said. "Inclusionhas risks, but exclusion also has risks." Allen argued that thereis a countervailing set of liabilities companies could face --liability for marketing a product to the general population,including pregnant women, when it's only been tested in asmall slice of that population.

Other Issues

The IOM report also concluded that more attention should bepaid to studying gender-specific responses to drugs in clinicaltrials and to recruiting more diverse patient populations,including women, minorities and people from differentsocioeconomic backgrounds. It further stated that thesevariables should be considered carefully when trial data isanalyzed.

But the panel members said there is not enough evidence tosupport claims made by some activist groups that women ingeneral have been systematically excluded from drug trials.

In fact, the FDA published a Government Accounting Office(GAO) survey in the Federal Register last July that showed thatin clinical trials submitted to FDA under new drug applications(NDAs), women were fairly represented. In drug trials for anti-inflammatory agents, 60-65 percent of the patients werewomen; for anti-infective agents, about 40 percent werewomen; and for central nervous system (CNS) drugs andanesthetics, 40-50 percent were women. For trials ofcardiovascular disease drugs, only 20 percent of the patientswere women, but this corresponds roughly to the incidence ofheart disease seen in the female population in the age groupsstudied.

"The idea that women are left out of drug development trials isjust wrong," said Robert Temple, director of the FDA's Office ofDrug Evaluation I. "Exclusion is not the issue; analysis is theissue." He said that while companies collect data such asinformation on pharmacokinetics and event rates for adversereactions, they rarely analyze that data for gender-baseddifferences.

The IOM is a private, non-profit organization chartered by theNational Academy of Sciences to advise the federal governmenton public health matters. The report took 14 months tocomplete at a cost of $328,000. It was funded by the Office ofResearch on Women's Health (ORWH) of the National Institutesof Health (NIH), with additional support from The FordFoundation, Syntex and the IOM.

-- Lisa Piercey Washington Editor

(c) 1997 American Health Consultants. All rights reserved.