Nearly one quarter of clinical trials for COVID-19 treatments and vaccines may have exclusion criteria that specify an age-cut-off for enrollment, a new study suggests. Researchers examined data on 847 studies registered in the clinicaltrials.gov database between Oct. 1, 2019, and June 1, 2020, involving vaccines and treatments for COVID-19 to see how often people aged 55 and older, and particularly adults 65 to 80 who are most affected by the virus, are excluded from enrollment. Overall, 195 trials (23%) had an age cut-off for enrollment. When researchers added in other exclusion criteria that indirectly created a high risk of excluding older adults from eligibility, they found that 53% of all trials in the analysis—including every vaccine trial—involved age-related direct or indirect exclusions. "The important take-home message for clinicians, older adults, and global societies, is that older adults who are the target population of COVID-19, need to be included in any clinical trials of treatments or vaccines," said senior study author Dr. Sharon Inouye, director of the Aging Brain Center at HebrewSeniorLife and Beth Israel Deaconess Medical Center in Boston, and a professor at Harvard Medical School. "This is essential to develop and test treatments that work in this population, and to assure their safety," Dr. Inouye said by email. "We hope that physicians will encourage their older adult patients to enroll in trials, that they will advocate for their inclusion with trialists and policymakers, and that they will observe the results of the trials in planning their treatment approaches." When researchers examined why older adults were excluded from trials, they found compliance concerns were the most common reason, cited in 213 trials. The next most common reason was what researchers described as "broad, unspecified" concerns (174 trials), followed by comorbidities (68 trials), and technology requirements (21 trials). Of the 232 phase 3 trials in the analysis, a total of 38 (16%) involved age-cutoffs for enrollment and a total of 77 (33%) had exclusion criteria likely to remove many older adults from eligibility, the study found. This made half of all phase 3 trials likely to exclude older adults, the researchers concluded. Among the 18 vaccine trials, 11 (16%) had age-based enrollment criteria and the rest of these trials had exclusion criteria likely to remove older adults from eligibility. This meant that none of the vaccine trials would be likely to include older adults, the researchers concluded in JAMA Internal Medicine. A few phase 2 or phase 3 SARS-CoV-2 vaccine trials launched after the current study period do expressly include adults aged 65 and older in their protocols, including trials of vaccines from Arcturus Therapeutics and Johnson & Johnson. Several more include volunteers aged 60 and over without an upper age limit. The study team notes that excluding some trial participants with severe or uncontrolled comorbidities might be necessary to protect the health and safety of older adults. One limitation of the study, the authors acknowledge, is that researchers didn't do a detailed review of study protocols that would be needed to assess the validity of any exclusion criteria related to comorbidities. "Scientifically, a legitimate concern is that you want to test to see if a therapy works in a highly controlled way where the one condition targeted is the only thing present—then you can find the answer in smaller numbers of people with greater certainty," said Dr. Janice Schwartz, a professor of medicine in the divisions of geriatrics and clinical pharmacy at the University of California, San Francisco. When more trial participants have comorbidities or other factors common in older adults, the studies may become more complex to evaluate, require more participants, take longer to complete, and cost more to conduct, Dr. Schwartz, who wasn't involved in the study, said by email. "But, at some point—preferably before you expose the public to new medical entities—you need to find out if it is safe and effective in people like the patients who will receive it," Dr. Schwartz said. "Unless we alter requirements for enrollment in trials to resemble the patients who will be getting the drugs in the clinical setting, it will be impossible to make informed treatment decisions and provide the best care." Source
