A systematic review assessing the under-representation of elderly adults in COVID-19 trials

Abstract

BackgroundCoronavirus disease (COVID-19) has caused a pandemic threatening millions of people worldwide. Yet studies specifically assessing the geriatric population are scarce. We aimed to examine the participation of elderly patients in therapeutic or prophylactic trials on COVID-19.MethodsIn this review, randomized controlled trials (RCTs; n=12) comparing therapeutic or prophylactic interventions registered on preprint repositories and/or published since December 2019 were analyzed. We searched in PubMed, leading journals websites, and preprint repositories for RCTs and large observational studies. We aimed to describe the age of included patients, the presence of an upper age limit and of adjusted analyses on age, any exclusion criteria that could limit participation of elderly adults such as comorbidities, cognitive impairment, limitation of life expectancy; and the assessment of long-term outcomes such as the need of rehabilitation or institutionalization. Mean participant ages were reported and compared with observational studies.ResultsTwelve RCTs assessing drug therapy for COVID-19 were included. Mean age of patients included in RCTs was 56.3 years. An upper age limit was applied in three published trials (25%) and in 200/650 (31%) trials registered at clinicaltrials.gov. One trial reported a subgroup analysis in patients ≥65. Patients were excluded for liver-function abnormalities in eight trials, renal disease in six, cardiac disease or risk of torsade de pointes in five, and four for cognitive or mental criteria, which are frequent comorbidities in the oldest patients. Only three trials allowed a family member to provide consent. Patients enrolled in RCTs were on average 20 years younger than those included in large (n≥1000) observational studies. Seven studies had as their primary outcome a clinical endpoint, but none reported cognitive, functional or quality of life outcomes or need for rehabilitation or long-term care facility placement.ConclusionsElderly patients are clearly underrepresented in RCTs, although they comprise the population hardest hit by the COVID-19 pandemic. Long-term outcomes such as the need of rehabilitation or institutionalization were not reported. Future investigations should target specifically this vulnerable population.

Direct and indirect effectiveness of mRNA vaccination against SARS-CoV-2 infection in long-term care facilities in Spain

“…The copyright holder for this preprint this version posted April 15, 2021. ; https://doi.org/10.1101/2021.04.08.21255055 doi: medRxiv preprint Immunesenescence and factors related to chronic conditions, together with malnutrition, are known to impair immunity required for an effective vaccine response [13], and lower neutralizing antibodies response to Pfizer/BioNTech vaccine in people ≥65 years has been reported [6,14]. However, our estimates resulted fairly similar to those of observational studies in younger adult population and are consistent with other studies showing high VE in the elderly from the general population.…”

“…The Pfizer/BioNTech vaccine has shown an efficacy of 95% in preventing Covid-19 in randomized clinical trials [5]. However, elderly persons in general, and those institutionalized in particular, are not represented in randomized studies [6]. Therefore there is great interest in estimating vaccine effectiveness (VE) in this population following its widespread vaccination.…”

An Update on Medication Use in Older Adults: a Narrative Review

“…Furthermore, the outcomes from trials which are underrepresentative of older people may not be generalisable to the older population [45]; the importance of outcomes is discussed later in this review. Over the past year, it has become evident that older adults are even under-represented in COVID-19 trials, despite being one of the populations most affected by and at risk from COVID-19 infection [46][47][48]. Studies have taken a siloed approach as to how comorbidities and age affect outcomes from COVID-19 infection [46,49], and there have been calls for COVID-19 research to be more inclusive of older people with frailty, cognitive impairment, and multimorbidity [46,50].…”

Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study

“…Vaccine efficacy data from frail, older adults requiring long-term care are scarce because these individuals are routinely excluded from clinical studies and vaccine trials. 6 Consequently, trial estimates of vaccine efficacy might not be generalisable to long-term care facility residents because of age-related differences in vaccine-induced immune responses. [7][8][9] Observational data from post-licensure studies in older adults are emerging, [10][11][12] and although a small number of preprint articles have reported on populations in long-term care facilities, [13][14][15][16] the study populations were exclusively vaccinated with BNT162b2 at the manufacturer-recommended dosing interval, and regular asymptomatic screening was rarely done.…”