The randomized clinical trial, long the gold standard of medical research, supposedly provides the most reliable data regarding which drugs, devices and procedures prove effective on real patients and which don’t. But when the people enrolled in the trial are quite different from those who will actually use the drug or device or undergo the procedure, the data are far less reliable.
Yet it happens, startlingly often, with old people. They’re not well presented in clinical trials, a fact that undermines their doctors’ best efforts at providing treatment.
“In taking care of older patients, we’re often guessing the best therapy on insufficient data,” said a frustrated Dr. Ken Covinsky, a geriatrician at the University of California, San Francisco. For any given treatment, “the risks and benefits may be very different for older patients, but we have no evidence to use.”
Why not? In last month’s Journal of General Internal Medicine, a University of Michigan team pointed to some systemic problems. Analyzing more than 100 studies published during 2007 in prestigious medical journals, the researchers found that more than 20 percent excluded participants above a particular age. That actually represented considerable progress; a previous study of trials published from 1994 to 2006 found that 39 percent had excluded people over age 65.
More disturbingly, even when older people aren’t barred by age, they get left out for other reasons. More than 45 percent of the trials that didn’t have age limits excluded people for having other illnesses or cognitive impairment, for having a reduced life expectancy or physical disabilities or functional limitations, even for living in a nursing home or senior residence – all restrictions that tend to remove the elderly from the mix. Simply requiring study participants to show up at an office or clinic for regular monitoring may prevent frail elders or those who lack transportation from participating.
Dr. Donna Zulman, an internist and the study’s lead author (she’s now teaching at Stanford University), empathizes with her fellow researchers. “It’s really hard to do clinical trials, and when patients are complicated, with multiple health problems, it can be even more difficult,” she told me in an interview. “It makes for a cleaner trial if certain patients are excluded.”
Nevertheless, “the study population should reflect the population that will be treated in the real world,” she said, “particularly if it’s studying a drug that will be used by older and frailer adults.”
Locating a group of perfectly healthy 85-year-olds for a drug trial — people who have no “co-morbidities” (doctorspeak for other illnesses) that might confound the experiment — is tough, agrees Dr. John Sloan, a family physician in Vancouver, British Columbia, whose book “A Bitter Pill” criticizes the prevailing treatment of older patients. But even if investigators manage to find enough of those sturdy subjects, the trial’s results won’t be very useful in his practice. Most of Dr. Sloan’s elderly patients aren’t perfectly healthy; they have multiple chronic diseases, often including dementia; they take lots of drugs and are physically fragile.
So the study’s authors call on regulators and investigators to include older adults in clinical trials and to analyze whether treatments affect them differently from younger participants. “Huge amounts of money flow into these trials,” Dr. Zulman said. “If we’re not getting results that help us take care of these most complex and expensive patients, we’re not getting much value from them.”