Recruitment and Retention in a Long-Term Prospective Observational Investigation of Pregnant Women with Epilepsy
Ippolito, D.; Meador, K.; Pennell, P.; Moore, E.; Browning, N.
NIH Workshop on Enrollment and Retention of Participants in NIH-funded Clinical Trials
Location: Bethesda, MD
Background/Rationale: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (previously called the NEAD study) is an NIH-funded prospective observational multi-center investigation of pregnancy outcomes for both the mother and child. The study has been conducted for over a decade providing a rich experience in recruitment and retention techniques. The NEAD component enrolled 305 pregnant women with epilepsy, from 1999 to 2004. The MONEAD study began in 12/2012 enrolling 550 women (350 pregnant women with epilepsy, 100 pregnant women without epilepsy, and 100 non-pregnant women with epilepsy). Goals/Objectives: To review the approaches, problems and solutions identified from the NEAD/MONEAD Study regarding successful recruitment and retention. Strategy/Methodology: Factors affecting recruitment and retention were considered in the original design and then monitored during the study in order to make changes in response to observed problems. Factors considered included design complexity, inclusion/exclusion criteria, recruitment sources, patient "load" (e.g., visits and tests), incentives to patients, multiple contact points for patients, frequency of patient interactions, feedback to patients, individual center performance, and reimbursements to centers linked to performance. Examples are given in the Outcomes section. Outcomes: The NEAD study ultimately met its recruitment and retention goals, but faced multiple problems. It began with 17 centers, deleted 5 centers due to poor performance, and added 14 new centers to meet enrollment goals. Two deleted centers were expected to enroll over 40% of the patients based on pre-study estimates, and several other centers performed poorly. Ultimately, over 78% of subjects enrolled came from only 34% of the centers. The original design included carbamazepine, phenobarbital, and phenytoin based on pre-study surveys. However, when initiated in 1999, very few patients were taking phenobarbital, so it was deleted and two AEDs that were commonly prescribed were added (i.e., lamotrigine and valproate). Conclusions/Future Directions: Lessons from NEAD were applied to the MONEAD study. Poor performance centers were deleted, new centers were added, design factors were altered prior to the initiation of MONEAD, and an updated survey of the centers was performed to identify the most commonly prescribed AEDs to women with epilepsy of childbearing age. MONEAD enrollment is on track to meet its goals, having enrolled over half of the subjects in each of the three study groups. No MONEAD centers have been dropped for lack of enrollment and all sites are actively enrolling subjects. Critical factors in successful recruitment and retention include a practical design, recruitment sources, sharing of successful recruitment materials/strategies among centers, maintaining patient contact, feedback and incentive for participation, ongoing monitoring of center performance, and a reimbursement mechanism linked to recruitment and retention.