Data about the elderly aren’t properly represented in clinical studies, and the aged may be at risk when they take prescription drugs.

That was the upshot of Prescription Drugs: FDA Guidance and Regulations Related to Data on Elderly Persons in Clinical Drug Trials, a recent report by the Government Accountability Office (GAO), the investigative agency of Congress.

According to Marcia Crosse, the GAO’s director of health care, the elderly are participating in drug trials—but sponsors aren’t breaking them out into reports, tables and other analysis so that safety and efficacy data specific to that population can be assessed. The GAO report raises an ill-defined prospect of voluntary changes to trial design practices or additional regulation to add the elderly as a distinct population of formal regulatory interest, along with women, children and minorities.

More Complications

The elderly do consume a huge percentage of the drugs on the market; they experience higher rates of complications from those drugs. Shouldn’t society know exactly how those drugs affect the aged? Shouldn’t the FDA have specific requirements about the number of elderly represented in trials? That’s the stance of Rep. Henry Waxman (R-Calif.) and Sen. Edward M. Kennedy (D-Mass.), who asked the GAO to conduct the study.

In response, the GAO analyzed 36 new drug applications (NDAs) that came in to the FDA between January 1, 2001, and June 30, 2004, for drugs to be used for conditions (cancer, endocrine disorders, circulatory conditions, etc.) found frequently in the elderly, which the GAO defined as 65 years old and over.

Incomplete Documentation

GAO analysts found that about a quarter of NDAs—eight out of 36—had incomplete documentation regarding elderly subjects. 

“One of the concerns we had,” said Crosse, “was that the age ranges used were inconsistent from one study to another and sometimes didn’t allow for any differentiation.”

50 and Older...

For example, she said, one study, in breaking down age groups, only had a category for people “50 and older.” With data like that, Crosse said, there’s no way to tease out how many participants were elderly. Even worse, one study had an age range of 18 to 91, without breaking any participants into groups according to age.

The GAO report pointed out that the FDA has acknowledged that drugs need to be studied for use in elderly persons, and that the agency requires sponsors to report data by age. But the agency is not detailed in that guidance. It doesn’t mandate any specific, standardized age ranges. It only offers suggestions for age categories.

Consistency Lacking

“The concern we have is that the FDA isn’t doing what they could to insure that there is consistency,” Crosse said. “For other groups—pediatric, minority and gender—they have required that the data be identified in certain formats, and they have guidances out requiring that that data be present in certain ways. While they have suggested that that be done for age, they have accepted [the data] however sponsors have chosen to submit it.”

A problem also exists with the FDA medical officers who review NDAs, the report found. Only about a third of the 36 NDAs documented the medical officers’ review of data on elderly study participants. In the rest, it just didn’t come up.

Where’s the Discussion?

“Because [medical officers] weren’t documenting in their reviews what was done to examine this issue, it wasn’t clear how closely they were examining it [for each NDA],” said Crosse. “These are pharmaceuticals that one would expect to be most heavily used by elderly patients, and so we would expect to see some discussion.”

The report also found that one study on an unnamed drug that had the potential to be used by many elderly people didn’t permit any elderly people to be enrolled in the study. Crosse said she was shocked to find this. The FDA doesn’t allow this, but somehow it happened.

Just a Proxy

“It’s fine if there are co-morbidities and the person needs to be excluded from a clinical trial because of that—that’s perfectly reasonable,” said Crosse. “But age in and of itself is just a proxy and doesn’t really tell you much. There’s a huge range in the health and vigor of people.”

The report was the last in a series borne out of the request from Waxman and Kennedy. Previous reports scrutinized issues on the representation of women, minorities and children in clinical trials. In the past, the FDA made changes to accommodate those groups—particularly with regard to women’s participation in trials.

—by