Older Adults Still Underrepresented in Clinical Trials, International Experts Note During AGS' Annual Scientific Meeting Symposium

Older adults, particularly the frail and those with multiple health problems, are still underrepresented in clinical trials, according to experts participating in a symposium on the subject during AGS' Annual Scientific Meeting in May. Ensuring that a representative sample of older people is included in trials is critical since they often respond differently to medications and other interventions than younger adults, the experts noted.

The symposium, "Fighting Against Age Discrimination in Clinical Trials," was developed by the European Union Geriatric Medicine Society (EUGMS) and co-sponsored by the group and the American Geriatrics Society (AGS). It brought together geriatricians and medical regulatory agency representatives from both the U.S. and the EU. AGS Board Chair Todd P. Semla, PharmD, Clinical Pharmacy Specialist with the Department of Veterans Affairs, and Associate Professor at the Feinberg School of Medicine at Northwestern University, and Jean-Pierre Michel, MD, of the University of Geneva, co-moderated the symposium.

While some clinical trials are including older patients, these trials typically include older adults who are significantly healthier than the patients who geriatricians see, noted panelist Joseph G. Ouslander, MD, Director of the Boca Institute for Quality Aging at Boca Raton Community Hospital and Professor at the University of Miami Miller School of Medicine and the Christine E. Lynn College of Nursing at Florida Atlantic University.

Many patients seen in a geriatrics practice is 80 or older, has multiple health problems, is taking multiple mediations, needs assistance with activities of daily living, has some degree of cognitive impairment, and depends on others for transportation to the practice, Dr. Ouslander noted. By contrast, the typical older subject in a clinical trial is 75 or younger, has minimal co-morbidity, is taking few medications, is cognitively intact and can manage activities of daily living independently and drive or take public transportation.

"Clinical trials must include older patients who are similar to those we treat in practice in order for drugs and other interventions to be effective and safe," he said. "But there are challenges."

Recruiting, screening, getting informed consent from and providing transportation for more complex elderly patients can be extremely challenging, Dr. Ouslander noted. So can addressing complications due to co-morbidity and multiple medication use -- including acute illness during a trial and medication interactions and side effects. The selection of outcomes in trials enrolling the frail elderly is also more complex. Increased attrition and selective attrition among frail older subjects create additional challenges. Clinical heterogeneity, which, among other things, makes adjusting for co-morbidity and illness during trials difficult, adds to these challenges.

Despite these challenges, it's imperative that trials of treatments for common conditions that impair function and quality of life among older patients include the frail elderly, he said. Among other things ask participants questions relevant to the aging, including: Did this treatment benefit you? Would you recommend it to a friend or relative? How much risk and cost are you willing to undertake for the degree of benefit you receive? Dr. Ouslander added.

Efforts to establish multi-center networks of high quality long-term care facilities and programs with leaders interested in participating in age-inclusive trials would facilitate such research. "AMDA (The American Medical Directors Association) has done this somewhat through its research network, but we still have a long way to go," Dr. Ouslander suggested.

The importance, and difficulty, of including older adults in clinical trials, have been issues "for quite some time," said Antonio Cherubini, MD, PhD, of the University of Perugia Medical School, noting that it was two decades ago that the US Food and Drug Administration (FDA) issued guidelines calling for the inclusion of older adults in trials. These guidelines led to a US- European-Japanese conference aimed at addressing the issue. But not much came of it, he said.

When the EU adopted new regulations to enhance clinical trials involving children in 2006, however, members of the recently formed EUGMS wrote the Vice President of the European Commission to both voice support for the new pediatric regulations and note that the rationale behind the new policies applied to clinical trials involving the elderly as well. Commission Vice President Günter Verheugen agreed, and encouraged EUGMS to pursue avenues toward more inclusive trials.

"And this symposium is part of that," Dr. Cherubini noted.

To highlight the importance of including a truly representative sample of older adults in clinical trials, he described the results of trials investigating the treatment of hypertension in the elderly. One trial, which included older adults who were primarily in their mid 60s, found treating hypertension very effective in reducing heart failure. Another study, of a population that included the very old, found that treating hypertension was associated with higher morbidity and mortality.

To step up efforts to ensure that clinical trials are more inclusive, the EU launched the five-stage Increasing the Participation of Elderly in Clinical Trials (PREDICT) project. The project, now in its initial stages, calls for a systematic review of the literature concerning the inclusion of older adults in trials, a review of ongoing trials, evaluations of professional and patient perceptions of trial participation, and the creation of a "charter of rights" for the elderly in trials.

The EUGMS, AGS and other interested parties should continue to work together, and with regulatory agencies, Dr. Cherubini advised, to help shape recommendations concerning clinical trial design.

"Older people can't afford to be left out of clinical trials," he noted.

The FDA shares the view that there is no reason to exclude patients from trials on the basis of advanced age alone, Jeffrey Shuren, MD, JD, the agency's Associate Commissioner for Policy and Planning, explained. Because ensuring that pre-market clinical trials include a representative sample of the aging can be challenging, however, alternative approaches may be necessary. One possibility, Dr. Shuren noted, would be making greater use of Phase IV, post-marketing studies, if appropriate. Another would be making greater use of clinical practice-generated data concerning safety.

Other steps are also needed, added Susanna De. Signore, MD, of the European Medicines Agency. Among these are reaching consensus on how to define frailty, and how to define unique strata of the elderly population.

To view a Web cast of "Fighting Against Age Discrimination in Clinical Trials," visit the American Geriatrics Society's Virtual 2008 Annual Meeting.