Supporting evidence in phase 2 cancer trial protocols: a content analysis

Area of Science:

• Oncology
• Clinical Trial Design
• Translational Science

Background:

• Phase 2 trials are critical for advancing cancer drug candidates towards efficacy trials or accelerated approval.
• High attrition rates in phase 2 trials suggest potential deficiencies in the supporting evidence base.
• Evaluating the robustness of evidence is crucial for optimizing clinical trial design and resource allocation.

Purpose of the Study:

• To develop a typology and assessment framework for supporting evidence in phase 2 cancer trials.
• To analyze the content and strength of supporting evidence presented in phase 2 cancer monotherapy trial protocols.
• To identify gaps in evidence presentation that impede critical evaluation.

Main Methods:

• A typology of supporting evidence for phase 2 cancer trials was created.
• A scheme was devised to assess the strength of supporting evidence.
• Content analysis was performed on 50 randomly sampled phase 2 cancer monotherapy trial protocols (Jan 2014-Jan 2019) from ClinicalTrials.gov.

Main Results:

• Most supporting evidence came from trials in different cancers (56%) or preclinical studies (96%), not the target drug-indication (46%).
• Translational relevance was rarely explained (2%); translatability was implied through shared molecular/pathophysiological processes.
• Information for assessing magnitude, precision, and bias was often available for clinical trials but lacking for preclinical studies.

Conclusions:

• Robust supporting evidence is essential for justifying clinical trial commitments.
• Protocols for phase 2 monotherapy cancer trials frequently lack elements needed for critical evidence assessment.
• Structured approaches for presenting supporting evidence are needed to improve trial justification and design.