Operational Protocol Models in the Drug Development Process

Abstract

Why do clinical trials that appear to be straightforward yield lower data quality and have longer timelines and higher costs than expected? Why do clinical development programs have difficulty combining studies when creating an integrated regulatory submission? Although the way these problems manifest themselves varies greatly, evidence continually points to the clinical trial protocol(s) as the root cause of operational errors, missed milestones, sponsor-site miscommunications, and incorrect data. Therefore, an up-front investment in analyzing the design features of a protocol for operational clarity and completeness could result in a substantial return from improved trial execution and regulatory reporting.

A protocol design methodology, based on an innovative concept called the ‘operational protocol model’, has been developed to address operational problems. The operational protocol model replaces the current unstructured protocol document with a highly structured formal protocol model. A wide range of automated computer-based protocol quality analysis programs can utilize the operational protocol model to provide insight into protocol design from various perspectives. The operational protocol model is independent of the scientific, clinical, or statistical details of a study. Therefore, the operational protocol modeling methodology can be applied to markedly different protocol designs in widely differing clinical domains.

Based on an empirical analysis of operational errors across a wide range of therapeutic areas, we have defined the following five key goals of a successful protocol design: coherency, completeness, consistency, comparability, and collaboration. The use of an operational protocol model can ensure that every clinical trial protocol designed within the operational protocol model meets all five protocol design quality goals.