Reporting of comorbidities and health status of participants in clinical trials testing amyloid- and tau-targeting monoclonal antibodies for Alzheimer's disease: A systematic review

Abstract

Background: Controversies exist around the external validity of clinical trials on disease-modifying treatments for Alzheimer's disease (AD). Detailed information on the clinical characteristics of research participants is lacking, hampering the understanding of their representativeness.

Objective: This study aimed to systematically review the baseline comorbidities and health status of patients with AD enrolled in clinical trials.

Methods: A systematic review of scientific and gray literature was conducted. Randomized controlled trials, enrolling participants in the AD continuum, and testing amyloid- and tau-targeting monoclonal antibodies were selected. Data on the type of study and intervention and the baseline clinical characteristics of participants were extracted. The proportion of studies reporting information on comorbidities, integrative measures of health (e.g., number of chronic diseases and multimorbidity, frailty, and gait speed), and non-neurological concomitant therapies of participants was calculated.

Results: Thirty-six articles, referring to 41 studies (21,952 participants) were included. None of the retained trials provided information on the comorbidities or other integrative measures reflecting the baseline health status of participants. Only three studies reported data on non-neurological concomitant therapies. Five documents providing relevant information were identified through gray literature searches covering the websites of regulatory agencies and pharmaceutical manufacturers.

Conclusions: The health characteristics of patients with AD included in randomized controlled trials are poorly reported. Therefore, the external validity of the study findings cannot be fully appreciated.

Keywords: Alzheimer's disease; clinical trials; evidence-based medicine; external validity; monoclonal antibodies.