Test Patterns

Older people take the majority of prescription drugs, yet they are frequently excluded from the studies that test drugs' safety and effectiveness. Scientists and doctors are examining why they're left out and devising ways to include them.

As anyone who s shopped for clothing knows, one-size-fits-all usually means one-size-fits-none. But that s the approach researchers have traditionally taken when testing drugs for treating human diseases, at least as far as age is concerned. Clinical trials, the controlled studies that determine whether a drug is safe and effective, often lump together volunteers of all ages--and exclude older individuals (see "Seniors Can Find Standard Meds Hard to Swallow").

Although some observers might view the omission of older people as a form of discrimination, those involved in the research describe it as an unfortunate side effect of setting up successful trials. "It s not a form of ageism," contends Lodovico Balducci, a geriatric oncologist at the H. Lee Moffitt Cancer Center in Tampa, Florida. Multiple health problems and difficulty in fulfilling a trial s demands frequently keep seniors out of studies. And doctors anticipation of these problems can deter them from enrolling older patients. Now some researchers are challenging these biases and trying to find ways to encourage the elderly to participate in studies that could provide them with medications that are tailored to their needs.

Underrepresentation of seniors is perhaps most pronounced in studies of anticancer therapies. "Cancer is a disease of the aged," says Balducci. "Sixty percent of cancer cases occur in people age 65 and older," yet by some estimates, people over 65 account for only 25% of subjects in cancer trials.

In the early days of cancer therapy, when most patients died, such exclusion made sense: Researchers favored testing therapies on otherwise healthy individuals because they were most likely to survive the treatment and respond to it. Such a focused effort is crucial in the initial stages of drug trials, when a negative outcome can quash enthusiasm for a promising treatment. "But once you have found that a treatment works, you need to try to see how beneficial it is in people who are not that perfect," says Balducci. Jason Karlawish, a bioethicist and Alzheimer s disease (AD) researcher at the University of Pennsylvania in Philadelphia, agrees: "You want clean data. But you [also] want a reasonable sense" of how the drugs will work in the kinds of people who will take them. And now that treatments have become safer and some cancers have become curable, Balducci says "it s a rather different ball game. Now is the time to look at older persons."

Doing so might profoundly influence health care. With little information about how seniors respond to drugs, doctors don t know whether the elderly should receive different doses than their younger counterparts do or different medications altogether. As a result, seniors might not receive the optimal therapy or, worse, could be exposed to dangerous side effects or drug interactions that are exacerbated by age. The problem is significant because as people grow older, they re more likely to need prescription drugs to control medical problems: Among seniors over 70, two-thirds are on a regimen of multiple pills.

But studying a drug s effects in elderly patients presents unique challenges. For instance, researchers design trials to produce the cleanest data possible so that if a therapy works, the numbers will show it. As a result, clinicians prefer to study people with only the particular disease they re trying to treat--and seniors frequently suffer multiple maladies. A cancer therapy study, for example, might exclude people with liver problems or heart disease, afflictions associated with old age. Such restrictions improve the quality of resulting data; for instance, they reduce individual differences in drug metabolism and minimize the risk that participants will die during the trial.

The biggest barrier to enlisting the elderly in drug studies might be the biases of the doctors running the trials. Many physicians perceive that elderly patients are uninterested in participating in drug studies or unable to handle the burden of clinic visits. But new research is challenging that view. For instance, in a study published last year in the Journal of Clinical Oncology, scientists interviewed breast cancer patients at hospitals that had conducted trials. Among the patients who were eligible, doctors had asked twice as many individuals under 65 to join clinical trials as they did those over 65, believing that the older patients were likely to refuse the invitation. Questioning the patients revealed that this was not the case, a finding that led Harvey Cohen of Duke University in Durham, North Carolina, to conclude that when it comes to physicians including the elderly in clinical trials, "we have seen the enemy and it is us." Cohen says he hopes that hard data about why the elderly do or do not participate in clinical trials will persuade clinicians to actively recruit them.

Even if clinicians encourage the elderly to enroll, they still face challenges in working with them, especially when studying diseases that precipitate mental decline. For instance, researchers must carefully assess whether a patient is sufficiently cognizant of the risks assumed by participating in a study. If an individual is not competent, researchers can, in some states, enlist a caregiver or family member to provide consent.

Once a trial on cognitive decline begins, researchers rely not only on the subject but, as the disease progresses, also the caregiver to fulfill the tasks required in a trial: taking medication on schedule and getting into the clinic when necessary, for example. Such requirements often overburden patients whose mental faculties are waning, as well as their caregivers; thus, scientists can experience difficulty finding the volunteers they need. To overcome this barrier, AD researcher Leon Thal of the University of California, San Diego, is examining the effectiveness of memory tests and other assessments that can be carried out at home, obviating the need for patients to travel to a clinic and potentially removing a barrier to their participation. Karlawish is also pursuing this avenue and is currently surveying patients to determine whether those changes would encourage trial participation. "The presumption is that they would, but we don t know for sure," he says.

Researchers say they hope that such studies will entice investigators to give seniors a fair shake. "We re doing that in our trials," says Thal, who has started recruiting people with severe cases of AD, who tend to be older. If that approach spreads, doctors might soon be able to provide the custom-tailored treatments that the elderly deserve.

R. John Davenport is a science writer based in Santa Cruz, California, and an associate editor of SAGE Crossroads sister site, SAGE KE. He thinks retirement is the perfect time to experiment with drugs.