FDA to Change Drug Research Policy on Women

Responding to growing concerns that medical research into drugs does not take gender differences into account, the Food and Drug Administration intends to reverse a policy that forbids using women of child-bearing age in medical drug research, FDA Commissioner David A. Kessler said Wednesday.

Also, the agency will require that any research submitted by drug manufacturers for new drug approvals include data regarding effects on women, he said.

“In the past, medical research has focused on males and all too frequently women have been included as an afterthought,” Kessler said in an interview. “Eliminating these barriers is the right thing to do.”

The policy of excluding women of child-bearing potential from drug studies, which has been in effect since 1977, arose after a number of medical tragedies involving the use of drugs during pregnancy. Today, generally, medical practice discourages the use of any drugs or alcohol during pregnancy.

Starting in 1958, for example, hundreds of babies with a deformity called phocomelia--literally “seal limbs”--were born in England and Europe of mothers who had taken thalidomide, a sedative that had never gained approval in the United States.

In another case, DES, a drug used from the 1940s well into the early 1970s to prevent miscarriage was found to cause cancer and other serious health problems in the offspring of women who had taken it.

“It’s not surprising that we ended up with guidelines as rigid as the ones we have,” said Dr. Ruth Merkatz, special assistant to the commissioner for women’s health issues.

But the policy of excluding all women of child-bearing potential from drug studies has been too broad and unwarranted, Kessler said.

“In 1993, there are technologies to prevent pregnancy that can be relied upon without this near absolute restriction,” he said. “This change doesn’t diminish our concern for the fetus. But we also have to consider the scientific benefits of inclusion.”

It is an established medical fact that men and women can respond differently to the same prescription drug because of physiological differences, such as body fat, hormones and other factors.

For example, women can metabolize some antihypertensive and cardiovascular drugs at a slower rate than men. Also, drug interactions with women’s hormones and their use of oral contraceptives can result in different responses.

Until recently, drug research rarely, if ever, took these factors into consideration.

“In the end, having this information can increase the safety and efficacy of a drug, and have significant effect on how a patient does,” Kessler said.

“We’re not requiring a lot of additional new studies,” Kessler added. “What we’re saying is that the trials must be designed to have a reasonable number of women so that gender analysis can be performed. We’re looking to screen people in these studies to see whether there are pharmacological differences in the way the drugs work.”

In part, the policy change indicates an increasing willingness by the FDA in recent years to take certain risks so that potentially significant new benefits can be reaped.

“I think the reversal reflects a shift away from a focus on the best interest of the fetus and concerns about liability to really taking women’s health issues very seriously,” said Art Caplan, director of the University of Minnesota center for biomedical ethics.

The rule has prohibited all women of child-bearing potential from participating in Phase I and early Phase II studies of new drugs. Phase I studies are conducted on small numbers of people to determine whether a drug is safe. Phase II studies, which include much larger numbers of individuals, attempt to find out whether a drug is effective.

Women of child-bearing age have been permitted in later Phase II and Phase III studies, which further evaluate a drug’s efficacy on larger numbers of people. Although women are allowed in these later studies, they traditionally have been under-represented.

In fact, several reports, including one issued last fall by the watchdog congressional General Accounting Office, called upon the FDA to ensure that gender differences were studied in prescription drug testing and criticized drug manufacturers for their failure to analyze trial data for such differences.

Dr. Sidney Wolfe, director of the Public Citizen Health Research Group, which has monitored the FDA for many years, said that the expansion of women in medical research “has to be done very carefully,” but he said that he welcomes the change.