USE OF A PROSPECTIVE LEAD-IN STUDY TO ENHANCE ELIGIBILITY AND REDUCE SCREEN FAILURE IN MAJOR DEPRESSIVE DISORDER TRIALS

Introduction (Aims): High screen failure rates (SFR) remain a persistent challenge in psychiatric clinical trials, increasing costs and slowing study timelines (Fogel, 2018). Recruitment enhancement strategies such as site-sponsored pre-screening programs represent potential means of improving screening efficiency. Our present study evaluated the potential for a multi-site observational lead-in study to reduce the SFR in Major Depressive Disorder (MDD) industry trials.

Methods

SFR was analyzed across 14 MDD clinical trials at 4 trial sites in the Adams Clinical Site Network. The included trials enrolled participants who completed a 6-week, site-sponsored prospective lead-in trial (TRAIT) in which all participants received an FDAapproved antidepressant therapy (ADT). Across trials and sites, the sample consisted of 160 TRAIT participants, and 458 non-TRAIT participants. The relationship between TRAIT participation and SFR was examined using a multilevel mixed-effects logistic regression model. The model allowed trial-level random intercepts and site-level random intercepts nested within trial, and controlled for age, sex, race, travel time, self-reported depressive symptoms (PHQ-9), past/current psychotherapy experience, and ADT history. In addition, study-wide SFR was averaged across trials when the data were available (SFR = 57.19% across 5 trials).

Results

The model indicated that trial-level variability (variance = 1.05; SD = 1.02) exceeded site-level variability (variance = 6.7 × 10⁻⁷; SD = 0.0008), which was negligible, indicating relative uniformity across the Adams Clinical Site Network. SFR findings revealed that TRAIT participants had 69% lower odds of screen failure in industry-sponsored trials compared with non-TRAIT participants (β = −1.17, SE = 0.33, z = −3.53, p < 0.001). The 61.79% SFR observed for non-TRAIT participants was comparable to the available studywide SFR average, whereas the SFR for TRAIT participants was markedly lower at 45.62%.

Conclusions

Improving screening efficiency is critical for reducing trial costs, accelerating timelines, and ensuring scientific validity (Desai, 2020). The current findings suggest that although trial-level factors such as trial design and inclusion/exclusion criteria are primary drivers of SFR variability, the use of a prospective lead in study can dramatically reduce SFR for MDD clinical trials, especially if implemented uniformly across sites. These results provide support for the practicality of utilizing pre-trial observational studies such as TRAIT to reduce SFR by optimizing recruitment and ensuring screening quality.