REVISE

In the REVISE project (Reviewing the Supporting Evidence in Investigator’s Brochures), we look into attitudes toward Investigator’s Brochures (IBs), a key document for independent review-procedures in translation.

To make a clinical trial ethical, regulatory agencies and institutional review boards have to judge whether the trial-related benefits outweigh the trial-inherent risks. These risk-benefit assessments are based on evidence from preclinical and clinical studies reported in IBs. They present the collected preclinical and clinical evidence relevant to the study of an investigational product(s) in human subjects and aim to inform clinical investigators, regulatory authorities, and institutional review boards (IRBs).

Three publications resulting from the STRUCTURES project have shown that the reporting of existing preclinical and clinical evidence supporting the study rationale in IBs is suboptimal:

• Wieschowski, Susanne, William Wei Lim Chin, Carole Federico, Sören Sievers, Jonathan Kimmelman, and Daniel Strech. „Preclinical Efficacy Studies in Investigator Brochures: Do They Enable Risk–Benefit Assessment?“ PLOS Biology 16, Nr. 4 (April 2018): e2004879. https://doi.org/10.1371/journal.pbio.2004879.
• Schwietering, Johannes, Daniel Strech, and Merlin Bittlinger. „Reporting of Prior Clinical Studies in Investigator’s Brochures Did Not Adhere to the Basic Principles of Evidence Synthesis: A Cross-Sectional Study“. Journal of Clinical Epidemiology, September 2020, S0895435620311082. https://doi.org/10.1016/j.jclinepi.2020.09.022.
• Sievers, Soeren, Susanne Wieschowski, and Daniel Strech. „Investigator Brochures for Phase I/II Trials Lack Information on the Robustness of Preclinical Safety Studies“. British Journal of Clinical Pharmacology, October 2020, bcp.14615. https://doi.org/10.1111/bcp.14615.

This is worrying for two reasons: First, because incomplete reporting of key study parameters limits any type of critical appraisal as the quality and robustness of the presented evidence cannot be assessed. Second, if studies are reported selectively, most likely favoring positive results, it might bias decision-making on when to launch and approve early-phase clinical trials. If we conduct early-phase clinical trials without the institutions designated to perform critical appraisal of the supporting preclinical evidence underlying the study rationale actually able to perform this task, this contradicts fundamental ethical, even legal, principles.

In an ongoing interview study we research key stakeholders’ attitudes towards this issue and aim to derive according guidance.