The proportion of women in randomized clinical trials (RCTs) for Alzheimer disease (AD) is higher than the proportion of men but significantly lower than that of the general population, according to a study in JAMA Network Open.
Women make up two-thirds of patients with AD. Sex differences could affect the results in AD RCTs, yet, there’s limited data on the differences in sex reported in these trials. The objective of the current study was to assess the female to male ratio in AD RCT enrollment and the reporting of sex-stratified results in these trials.
Researchers conducted a systematic review and meta-analysis of RCTs on AD to determine their sex distribution of patients. The trials were initially identified using the key word “Alzheimer disease” at ClinicalTrials.gov and then were searched on PubMed, Google Scholar, and Scopus from September 4, 2019, to May 31, 2020.
A total of 77 articles with more than 100 participants that included both sexes were included in the analysis; 64 articles were categorized as primary (56 on AD dementia and 8 on prodromal AD) and 13 as secondary (all on AD dementia).
In the 56 primary articles on AD dementia (mean [SD] age of participants, 73.5 [2.5] years), the overall proportion of women was 59.0% (23,348 of 39 575 total participants). The mean (SD) proportion of women in the trials for approved drugs was 67.3% (6.9%), and in trials for experimental medications the rate was 57.9% (5.9%).
Trials involving approved drugs had a higher probability of including women compared with trials of experimental drugs (odds ratio [OR], 1.26; 95% CI, 1.05-1.52; P =.02). Also, a lower probability of including women was observed in trials with participants who had a higher mean baseline Mini-Mental State Examination score (OR, 0.98; 95% CI, 0.97-1.00; P =.02).
Location was the only factor significantly associated with inclusion of women in AD trials, as location in Europe had a higher probability that the trials included women (OR, 1.26; 95% CI, 1.05-1.52; P =.01), and location in North America was associated with a lower probability (OR, 0.81; 95% CI, 0.71-0.93; P =.002).
The study authors found a statistically significant increasing temporal trend of articles that referenced a sex-specific data analysis in the methods (R, 0.30; 95% CI, 0.05-0.59; P =.03) and a comparable trend for sex stratification (R, 0.26; 95% CI, 0.01-0.55; P =.055).
The researchers noted that because only RCTs in the US are required to register at ClinicalTrials.gov, it is possible that the analysis was skewed toward US trials. Another limitation is that owing to the exclusion of solely pharmacokinetic and safety trials from the analysis, potential sex differences were not obtained for these characteristics.
“Although the findings suggest that current clinical trials for AD enroll more women than men, strategies to increase women’s participation in clinical trials for AD should be discussed and the reporting of trial outcomes by sex should be encouraged,” the researchers concluded.
Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Martinkova J, Quevenco F-C, Karcher H, et al. Proportion of women and reporting of outcomes by sex in clinical trials for Alzheimer disease: a systematic review and meta-analysis. JAMA Netw Open. September 13, 2021. doi: 10.1001/jamanetworkopen.2021.24124