Background

Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer's disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants' study partner type, with participants enrolling with non-spouse study partners being at greater risk.

Methods

We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia. Cox's proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout.

Results

Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p value = 0.027 for test of differences by partner type), but in models adjusting for potential confounding factors, the differences were not statistically significant (p value = 0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model.

Conclusions

After adjustment for age, no differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.

Reluctance to undergo lumbar puncture (LP) is a barrier to neurological disease biomarker research. We assessed whether an educational intervention increased willingness to consider research LP and whether message framing modified intervention effectiveness. We randomly assigned 851 recruitment registry enrollees who had previously indicated they were unwilling to be contacted about studies requiring LP to gain or loss framed video educational interventions describing the procedure and the probability of experiencing adverse events. The gain framed intervention emphasized the proportion of individuals free of adverse events; the loss frame emphasized the proportion experiencing adverse events. The primary outcome for the study was the participant's post-intervention agreement to be contacted about studies requiring LP. Participants were mean (SD) age 60.1 years (15.7), 69% female (n = 591), and mostly college educated and white. Among the 699 participants who completed the study, 43% (95% CI: 0.39, 0.47; n = 301) changed their response to agree to be contacted about studies requiring LP. We estimated that participants randomized to the gain framed intervention had 67% higher odds of changing their response compared to those randomized to the loss frame (Odds Ratio = 1.67; 95% CI: 1.24, 2.26; p < 0.001). A classification and regression tree model identified participants' pre-intervention willingness as the strongest predictor of changing response. Education, in particular education that alerts participants to the probability of not experiencing adverse events, may be an effective tool to increase participation rates in research requiring LP.