Older Americans, Most at Risk from Covid-19, Were Often Excluded from Mandated Clinical Trials of Therapies and Vaccines

Mandating randomized double-blind clinical trials for Covid-19 candidate therapies or vaccines slowed down the ability of citizens to choose those therapies or vaccines in 2020. Arguably those most hurt by the delay were older Americans age 65 and older, who had the greatest risk of death from Covid-19. The mandated trials slowed availability, but did they at least provide older Americans more and better information about the safety and efficacy of the therapies and vaccines? Not as much as you might suppose. The clinical trials often excluded older Americans because their participation would make the trials more expensive, slower, and less likely to prove safety and efficacy at levels that would result in FDA approval.

(p. D3) “Ideally, the patients enrolled in a randomized clinical trial reflect the demographics of the disease,” said Dr. Mark Sloan, a hematologist leading a Covid-19 drug study at Boston Medical Center, in an email. “Unfortunately, this is seldom the case.”

Now, Dr. Sharon K. Inouye, a geriatrician at Harvard Medical School and Hebrew SeniorLife, is sounding an alarm. She points out that in the race to find drugs and vaccines to fight the pandemic — in which 80 percent of American deaths have occurred in people over age 65 — a substantial proportion of studies may be excluding older subjects, purposely or inadvertently.

“A year from now, when these trials are published, I don’t want to see that there’s no one in them over 75,” she said. “If they create a drug that works really well in healthy 50- and 60-year-olds, they’ve missed the boat.”

She and her team have reviewed 241 interventional Covid-19 studies undertaken in the United States and listed on clinicaltrials.gov, a site maintained by a division of the National Institutes of Health.

They found that 37 of these trials — testing drugs, vaccines and devices — set specific age limits and would not enroll participants older than 75, 80 or 85. A few even excluded those over 65.

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Overall, when Dr. Inouye compiled preliminary results, which have not yet been published, she found that about one-quarter of interventional trials in the United States could exclude or underrepresent older adults.

“To have them be this gravely impacted and not include them is immoral,” said Dr. Louise Aronson, the author of the best-selling book “Elderhood” and a geriatrician at the University of California, San Francisco. “It seems crazy.”

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In clinical trials, “you want to control as many factors as possible,” Dr. Aronson said. Most older adults have other illnesses and take multiple medications, so-called confounding variables that make it difficult to distinguish the effects of the drug or vaccine being studied.

Older people also suffer more side effects. “Nearly all drugs are less toxic when given to younger, healthier people,” Dr. Sloan said in an email. Focusing on them produces fewer adverse effects that must be reported, “and thereby improves chances for F.D.A. approval.”

Physical disabilities, which make it harder for seniors to reach study sites, or hearing and vision impairments requiring large-print forms or audio amplification, can further decrease participation. Investigators may need to take the extra step of obtaining family consent if a patient is incapacitated.