Impact of Protocol Amendments, Personnel Experience and Social Determinants of Health on Study Protocol Adherence in Clinical Trials with Combination Products.

Abstract

Introduction: The amendments to the International Council for Harmonization (ICH) Good Clinical Practice (GCP) E8 guidelines were introduced to enhance clinical trial quality, patient safety, and efficiency through a more patient-centric, risk-based approach. This study investigates the impact of various study risk factors such as protocol amendments, informed consent changes, protocol complexity, and social determinants of health (SDOH) on protocol deviations and patient retention in clinical trials involving combination products.

Methods: A retrospective analysis of 14 clinical trials with 202 enrolled subjects was conducted. Key risk indicators (KRIs) such as protocol amendments, amendments triggering informed consent changes, study staff experience, and clinical trial phase were evaluated for their association with protocol deviations. The analysis also explored the influence of social factors, including age, gender, race, insurance type, and travel distance on protocol adherence.

Results: Study revealed that longer study participation was associated with an increased number of protocol deviations (p = 0.0003), while no significant associations were found between protocol deviations and demographic factors (p = 0.4039 for gender; p = 0.40650 for age), insurance type (p = 0.0640), or complexity scores (p = 0.7798). The findings highlight the importance of effective informed consent processes, study staff training, and risk management strategies to minimize protocol deviations and enhance data integrity in clinical trials.

Conclusion: while larger numbers of participant were associated with more deviations, site preparedness and patient compliance can mitigate these risks, underscoring the need for robust quality management systems in clinical trials.