Background: A crucial prerequisite for designing and reviewing phase I/II trials is sufficient knowledge about what preclinical studies are needed to demonstrate efficacy and safety. The relevant preclinical questions to be answered depend strongly on the studied disease, the drug target, pathophysiology, and other aspects. However, Good Clinical Practice guidelines such as the ICH E6 address rather general scientific requirements, but they do not help to determine the relevant preclinical efficacy and toxicology studies for a specific disease or therapeutic area. Therapeutic area guidelines (TAG) published by EMA and the FDA define requirements to be fulfilled when launching a trial in a certain indication. TAG could play an important role for improved structure, efficiency, and transparency in translational research, but have not been studied systematically for their utility in this regard.
Objectives: This study aimed to 1) determine the full sample of TAG from EMA and FDA; 2) assess the intersection of TAG topics; and, 3) assess and compare their content for preclinical requirements.
Methods: EMA and FDA websites and databases were systematically searched for TAG. All included TAG were thematically clustered. A mixed-deductive and inductive approach was applied to analyse content on preclinical requirements.
Results: A total of 114 EMA and 120 FDA TAG could be identified, covering 126 distinct topics. Guideline topics are diverse, ranging from common diseases to orphan diseases. Fifty-seven (50%) from 114 EMA and 55 (46%) from 120 FDA TAG do not mention any preclinical requirements. TAG show a strong variation in extent, nature, and level of detail.
Conclusions: Our findings indicate that TAG do not sufficiently inform sponsors or clinical researchers on preclinical requirements for launching early clinical trials in specific therapeutic areas. For the sake of transparency and public accountability, EMA and FDA should set minimum standards in TAG for preclinical requirements. This would facilitate both the assessment of trial applications and limit the conduct of trials with limited prospect of clinical promise or other relevant knowledge gain.