Embedding Pragmatic Retention and Safety Strategies in Alzheimer’s Clinical Trials: Lessons from the EHSAN RCT

Background: Alzheimer’s disease (AD) trials face adherence and safety challenges intensified by resource limitations. The EHSAN randomized controlled trial integrated culturally adapted safety and retention mechanisms to maintain data quality and participant well-being. Methods: EHSAN screened ۱۰۵۰ and randomizes ۳۲۱ AD patients (MMSE ۱۲–۲۶) prescribed acetylcholinesterase inhibitor therapy to Hydralazine -HCL or placebo for ۱۲ months. Of these, ۱۱۱ patients discontinued or withdrew from the study. The protocol includes adaptive dose-reduction rules for cardiovascular events, caregiver training modules and logbooks, transport reimbursement, and ۲۴-hour call monitoring (۱). This trial was registered at Clinical Trials.gov (ID: NCT۰۴۸۴۲۵۵۲). Results and Discussion: These pragmatic adjustments improved retention (>۶۵ % at interim analysis) and ensured timely SAE reporting without compromising blinding. Integration with the insurance system facilitated identification of potential participants, real-time adverse-event reimbursement and long-term post-trial surveillance. Compared with high-income-country RCTs, EHSAN demonstrates that context-specific logistics and adaptive safety monitoring strengthen feasibility and external validity in LMICs. Conclusion: Culturally tailored retention, caregiver engagement, and dynamic safety algorithms can enhance both ethical conduct and scientific robustness of dementia trials in limited-resource settings.

کلیدواژه ها:

Alzheimer’s disease ، pragmatic trial design ، safety monitoring ، caregiver support ، retention