Objective: To identify risk factors for premature withdrawal from a large, multi-center Parkinson’s disease clinical trial of possible neuroprotection.

Background: Premature withdrawal (PW) of subjects can be a significant complicating factor for clinical trials. The problem of PW is particularly important in long-term studies, such as those designed to study potentially neuroprotective medications. Identifying and characterizing causes of PW can be helpful in both interpreting clinical trial results and in design of future trials. The recently completed LS1 study comparing creatine versus placebo was the largest disease modification trial performed to date in PD. There were 586 subjects who were unable to complete participation thus providing an opportunity to study the issue of PW in a post-hoc analysis.

Methods: We performed an analysis of demographic and disease-specific severity items at baseline with a Cox-proportional hazard model, treating site as a random variable, to identify baseline risk factors for premature withdrawal or study medication discontinuation. We then performed a longitudinal analysis of risk factors for PW per year of study participation.

Results: Risk factors for PW overall were rate of worsening in activities of daily (Schwab & England) score, gender, number of adverse events, rate of worsening in PD-related quality of life (PDQ-39) score, and randomization to active creatine. Risk factors for PW after completing the first year of the study included adverse events and randomization to creatine, suggesting that PW occurring later in the study was more driven by study medication-related factors as opposed to demographics.

Conclusions: These results indicate that women were more likely than men to withdraw from the LS1 study, and subjects with worse disability or more adverse events were also more likely to quit the study. Female gender remained a risk factor for PW even after one year of participation in the study. Future clinical trials in this study population may need to recruit more women in order to avoid skewing results toward men. Pilot studies should be done over a longer period of time to provide an assessment of adverse event frequency.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/risk-factors-for-premature-withdraw-from-the-ls-1-pd-study/