Roberta Biegel

(WOMENSENEWS)–As research continues to emerge showing women respond differently and sometimes more adversely than men to widely used medications including antihistamines, antibiotics and painkillers, women’s health advocates are pressing Congress to fund a permanent database to track gender, race and age differences in clinical drug trial results.

Congress created such a program last year on a one-year trial basis following two U.S. General Accounting Office reports critical of the Food and Drug Administration’s oversight of drug research. One of the reports found that eight of 10 drugs the agency pulled off the market over a four-year period caused increased harm in women.

"Most physicians and patients are still not aware that sex matters when prescribing medications," says Sherry Marts, scientific director of the Society for Women’s Health Research, a Washington nonprofit group campaigning for the database, which is scheduled to expire on Oct. 1 at the start of the new federal fiscal year.

The program’s researchers studied how best to standardize incoming drug-trial information on safety and efficacy and designed a database to track and compare drug responses by gender, race and age. If the program is made permanent, the database will compile gender, race and age differences from drug trials in a way that can be shared–after drug approval–with other federal agencies such as the National Institutes of Health.

"We would like to see there’s money set aside to get the database up and running and continue. This is not a one-shot, one-year thing. We want to see it grow," says Roberta Biegel, director of government relations for the Society for Women’s Health Research.

FDA Supports Push for Database

The 2001 General Accounting Office report on the 10 drugs removed from the market from Jan. 1, 1997 through Dec. 31, 2000 by the FDA found that the agency failed to analyze gender differences in drug-safety data from clinical trials, even when drug companies included it in their reports, as required by law. It also found that while the drug makers reported to the FDA that their late-stage drug trials included 55 percent women, only 22 percent of subjects in the companies’ early safety and tolerability trials were female.

Margaret Miller of the FDA’s Office of Women’s Health says a permanent database, stocked with the newly standardized drug-trial information, would avoid the need to remove a drug from the market by highlighting patterns of adverse reactions among women, African Americans and other groups before it reaches the public.

"The analysis you could do with it would be incredible. You could look at adverse events by age group and across drugs, and hopefully have a good public health impact from that data," Miller says. "We like practical at the FDA."

"We would like to see the information incorporated into product labels," Miller adds, so that doctors and patients could adjust dosages by gender, ethnic group or age, based on drug-trial results reported to FDA.

Safety and Efficacy of Many Drugs Vary by Gender

Miller says the new database would also allow the FDA to make sure statistically sufficient numbers of women, minorities and age groups are included in drug trials.

Research on many widely used drugs indicates safety and efficacy can vary according to gender. Studies published in 1997 and 1999 indicated women wake up faster from general anesthesia and suffer more of its side effects than men. A 1999 study led by Dr. Jon Levine found pain drugs called kappa-opioids bring greater relief to women than men. Researchers say they don’t yet know why women respond differently.

"Drug companies still refuse to study women very early in a drug’s development," says Dr. Raymond Woosley, vice president of health science at the Arizona Health Sciences Center in Tucson and a researcher on gender, drugs and heart arrhythmias. "I think they are beginning to look at this but it’s not uniform. I think it should be part of any analysis of a drug’s action. I think it’s just good biology and it’s good business for them to do that."

Yet some drug companies resist gender testing, he says.

"They’ve said in the past: ‘If we have to study drugs in men and women, then we’ve got to double the number of people we study.’ That’s not correct," Woosley says.

"They need to use modern statistical methodology and they can do it with very little change in the way or cost of developing a drug," Woosley says. "Statistical methodology will allow you to tell the difference–if there is one–between men and women without a large increase in the amount of work that has to be done."

Irregular Heart Rhythms Is Common Side Effect Influenced by Sex

Two common reasons drugs get taken off the market are because they harm the liver or cause irregular heart rhythms. In both instances, there’s evidence that women are harmed more than men, Woosley says.

Woosley researched 40 drugs known to sometimes cause irregular heart rhythms and found that nearly a quarter of them posed greater risk to women than men of developing potentially life-threatening arrhythmias. He has made this research available on a Web site for the Arizona Center for Education and Research on Therapeutics.

Pharmacia Corporation’s Norpace, a medication prescribed to remedy abnormal heart rhythms, is listed on Woosley’s site as causing more heart rhythm abnormalities in women than in men. Pharmacia spokesman Mark Kranack did not return several calls requesting comment on the drug’s listing.

Abbott Pharmaceuticals, whose antibiotic Erythrocin is listed on the registry as causing greater heart rhythm abnormalities in women, would not comment on the drug’s inclusion on Woosley’s site. PCE, Abbott’s latest erythromycin product, does warn in its package insert of such potential rhythm abnormalities.

PCE’s package insert, however, does not mention that women are more likely to suffer the potentially fatal heart arrhythmias. Abbott spokeswoman Cindy Resman said women are known to be at higher risk than men for such arrhythmias with or without drugs.

Erythrocin is no longer sold by Abbott in the United States. In July, the FDA posted additional label warnings for the drug of increased danger to elderly patients of heart irregularities and hearing loss.

Abbott would not comment on the decision to stop selling Erythrocin.

Suzanne Batchelor has written for the national science series "Earth and Sky" and on health and medicine for Medscape Health, Web MD and the Texas Medical Association’s "Healthline Texas."



For more information:

Society for Women’s Health Research:

Arizona’s Center for Education and Research on Therapeutics:

International Registry for Drug-induced Arrhythmias: