The US Food and Drug Administration (FDA) could do more to ensure senior citizens are taken into account both in the design and assessment of clinical trials, a new report from the Government Accountability Office (GAO) suggests.

“Seniors use more drugs than any other age group but they are not getting enough attention in the drug approval process,” said Representative Henry Waxman, chairman of the House Committee on Oversight and Government Reform. Waxman asked the GAO to address the issue along with Edward Kennedy, chairman of the Senate Committee on Health, Education, Labor and Pensions.

As the GAO report noted, senior citizens – those aged 65 years and over – are not only heavy users of prescription drugs but are also more likely than younger adults to experience side-effects associated with these drugs. One reason is that deterioration of liver and kidney functions means seniors often cannot eliminate drugs from their system as efficiently as younger people.

In compiling the report, the GAO reviewed FDA guidance on drug studies and on the format and content of new drug applications (NDAs). It also looked at the agency’s requirements on reporting drug safety and effectiveness data by age in NDAs and reporting data relating to elderly patients in drug labelling.

To assess how drug sponsors had responded to these guidelines and requirements, the GAO examined 36 NDAs submitted to the FDA between 1 January 2001 and 30 June 2004 that had been reviewed by the agency and were for drugs targeting diseases determined by the Office to affect senior citizens “with a disproportionately greater frequency compared to younger persons”.

In addition, the GAO examined FDA guidance for its medical officers in reviewing drug data on senior citizens and interviewed agency officials responsible for overseeing the NDA review process to gauge how this guidance related to the wider review function.

Avoid exclusion

As the GAO pointed out, FDA guidance recommends that drug sponsors avoid excluding potential subjects from clinical trials on the basis of advanced aged and makes various suggestions as to how sponsors should report the age of trial participants to help the agency determine how many seniors are included. Moreover, FDA regulations require sponsors to report trial data by age.

In the 36 NDAs reviewed for the GAO report, sponsors generally included senior citizens in clinical trials and reported safety and effectiveness data for this population, the Office found. Specifically, seniors were included in at least one clinical trial supporting each of the NDAs reviewed while with 28 of the NDAs, the GAO was able to determine the number of elderly participants in at least one of the trials.

Furthermore, the Office noted, FDA officials are developing guidance that would combine information currently available in multiple guidance documents on the format sponsors should use when they report safety data in an NDA, including data about age. In the GAO’s NDA review, most sponsors used the age category of 65 years and over when reporting on a drug’s safety and effectiveness by age.

Expectations not conveyed

More problematic was the way these data were handled. The agency’s expectations that medical officers will review safety and effectiveness data for elderly trial participants “are not conveyed in agency guidance”, the GAO report said. Rather, the guidance on evaluating safety and effectiveness data refers to age subgroups only “broadly” – for example, by suggesting that it may be appropriate to examine whether there are differences in the safety and effectiveness of drugs between demographic subgroups such as “old” and “young” participants.

“FDA officials responsible for overseeing the NDA review process told us they believe that the agency’s reviewers understand that FDA guidance calling for an analysis of age, or information on special populations or demographic subgroups, also applied to elderly persons,” the GAO commented. “Agency officials added that age-related differences are almost always part of the team discussions about NDAs held by medical officers when deciding whether to recommend a drug for approval.”

Nonetheless, the GAO found that only about two-thirds of medical officer reviews of the NDAs scrutinised for the report documented the officer’s review of safety or effectiveness data for people aged 65 years and over.

Nor, the GAO added, does FDA guidance suggest that medical officers determine whether sufficient numbers of senior citizens have participated in clinical trials supporting NDAs. It does not suggest either that medical officers document in their clinical review summaries the methods they used to determine whether sufficient numbers of elderly people participated in the relevant trials.

Only about one quarter of the medical officer clinical review summaries examined by the GAO documented the officer’s review of whether senior citizens were adequately represented in the trial. And none of these reviews documented the methods used by the medical officer to make a determination of adequacy. “Nevertheless,” the GAO commented, “FDA officials told us that medical officers routinely make such determinations.”

This was not enough to appease Kennedy and Waxman, who said the GAO report “finds that in several key areas, FDA rules for drug approval fail to guarantee the safety and effectiveness of drugs for seniors”. Oversight would be needed to make sure the FDA responded to the GAO’s observations, Waxman added.