Individual patient data meta‐analysis assessing the adverse event profile of Alzheimer dementia randomized clinical trials

Abstract

AbstractBackgroundRegular reporting and monitoring of Adverse Events (AE) and Serious Adverse Event (SAE) are a crucial part of all randomized, controlled clinical trials, providing an assessment of the intervention’s safety profile. This process of adverse event surveillance is critical for participant’s safety and data quality. Knowledge and previous experience from Alzheimer’s disease (AD) trials is necessary in order to assess whether an AE/SAE is currently observed in a trial can occur (and at what frequency) in the placebo arm of the study or may be unique to the test agent. The overarching aim of this project is to evaluate the AE profile observed in the placebo arms in AD randomized clinical trials through a systematic review and meta‐analysis.MethodWe evaluated the safety profiles in placebo‐arm AD trials, we combined Individual Patient Data (IPD) using AE and SAE data from completed randomized clinical trials (RCT) AD trials conducted by the Alzheimer’s Disease Cooperative Study (ADCS). We used descriptive statistics, summarizing baseline participant demographics and AE patient level outcomes at the study level. Meta‐analyses using a Negative‐Binomial model were undertaken to determine the pooled risk ratios (RR) of AE and SAE rates.ResultThe placebo arms of five 18‐month RCTs were included in this meta‐analysis with a pooled sample size of 749 participants. The estimated number of adverse events per participant across the five studies ranged from 1.93 events to 7.05 events per participant. Meta‐analysis of the total number of AEs a participant experiences for the duration of an 18‐month trial was estimated to be 3.85 events (95% confidence interval: (1.54, 9.32)). Similar analyses on the number of SAEs a participant is expected to experience was 0.18 events (0.04, 0.94) per participant.ConclusionThe IPD meta‐analysis models give an indication of the AE profiles we can expect to observe in the placebo arm of future AD trials. We will extend this work by looking at AE classification types and what common types of AEs occur across trials.