Older Adults Likely to be Excluded from COVID-19 Vaccine Trials

Older adults are more likely to be excluded from more than 50 percent of COVID-19 clinical trials and 100 percent of COVID-19 vaccine trials, according to a recent JAMA Network Open study.

Researchers conducted 847 clinical trials in which exclusions were identified by viewing all of the eligibility and exclusionary criteria. 

Out of the 847 clinical trials conducted, 195 (23 percent) included an age cut-off. 

The most common age-related exclusion was compliance concerns, with 129 of the exclusions related to consent. Additionally, 252 of these trials (30 percent) did not have an age-based exclusion. 

Age exclusions were identified by viewing all of the eligibility and exclusionary criteria. Specific age exclusions were classified into five-year categories from ages 55 to 80 years of age, which is most affected by COVID-19.

Researchers highlighted that these exclusions will limit the ability to evaluate the efficacy, dosage, and adverse effects of the intended treatments. 

Antibody responses to vaccines could decrease with age and may improve with increasing antigen levels, adjuvants, or repeated dosing. 

“We acknowledge that some exclusions for severe or uncontrolled comorbidities will be essential to protect the health and safety of older adults. However, caution must be taken to avoid excluding otherwise eligible participants for reasons that are not well-justified,” researchers said in the study.

Researchers highlighted that in 232 Phase 3 clinical trials, 16 percent included age cut-offs and 33 percent had exclusions generally affecting older adults. Additionally, 50 percent of these trials were deemed high risk for excluding older adults. 

Of 18 vaccine trials, 61 percent included age cut-offs, while seven trials had broad non-specified exclusions. But 100 percent of vaccine trials were considered high risk for eliminating older adults. 

“If the older age group is excluded from vaccine trials, efforts to ensure effectiveness, titrate dosage or frequency, and assess adverse effects in the group most vulnerable to COVID-19 will not be possible,” researchers said. 

Globally, individuals over 65 years account for the greatest risk of severe disease and death due to COVID-19, making up 30 percent to 40 percent of cases and more than 80 percent of deaths. 

But there is a long history of exclusion of older adults from clinical trials. In response, the National Institutes of Health instituted the Inclusion Across the Lifespan policy.

The Inclusion Across the Lifespan Policy ensures individuals are included in clinical research in a way that is appropriate to the scientific question under study. This way, the knowledge gained from NIH-funded research is applicable to those affected by the researched diseases/conditions. 

Adults 65 years of age and account for the group of patients with certain health conditions, including cancer, cardiovascular disease, arthritis, and Parkinson’s disease.

Unfortunately, these patients are poorly represented in clinical trials. Specifically, up to 35 percent of published trials excluding older people, according to an NIH article. 

For example, although individuals aged 65 years and older account for 61 percent of all new cancer cases and 70 percent of all cancer deaths, in the clinical trials active between 1993 and 1996, these individuals comprised only 25 percent of oncology trial participants. 

Generally, clinical trials conducted in adult population include patients between the ages of 18 and 64 years. But drugs should be studied in all age groups and trial participants should be representative of the patient population receiving the therapy in daily medical practice, NIH researchers noted.

“Aging has a significant effect on the responses to pharmacological interventions,” they said.

“Age-related physiological and pathological changes play a major role in altering pharmacological actions of drugs. Age-related changes in hepatic and renal functions significantly affect the absorption, distribution, metabolism, and excretion of the drugs.”