The positive ratio of potential benefits and risks of a clinical trials is a fundamental ethical principle and a crucial prerequisite for the approval of authorities and ethics committees. The transition from the preclinical to the clinical research phase is a particularly important step in the development of new medical treatments and evaluation of risks and benefits at this stage is subject to particularly difficult challenges.
Preclinical studies are the basis for the planning and approval of early human research (clinical trials phase I/II), including the risk-benefit-assessment. Besides data on safety and toxicology of the new product, preclinical data on efficacy is needed to justify the testing on human (“clinical promise”).
Recently, several studies have shed a light on weaknesses in the practice of translational research. These weaknesses are especially related to the quality of preclinical studies.
STRUCTURES aims to improve quality, structure and transparency in translational research by providing evidence from several empirical research studies. Relevant stakeholders (e.g. animal researchers, competent bodies etc.) will be engaged to develop practice-oriented approaches and governance tools.
Further, in the course of STRUCTURES two PhD-projects will be conducted:
PhD Sören Sievers (Medizinische Hochschule Hannover)
Object of the study is the current justification practice for clinical studies. It investigates the quality of evidence from preclinical studies, which are submitted to research ethics committees in the form of an Investigator’s Brochure (IB). Main focus is the extent, to which the reported studies and their quality features enable a risk-/benefit-assessment of a further study in human subjects. After the recent examination of the benefit aspect through reported preclinical efficacy studies this work addresses the risk part represented by reported preclinical safety studies.
PhD Johannes Schwietering (Medizinische Hochschule Hannover)
Before a clinical study can be conducted on humans, a research ethics committee has to perform a risk-benefit analysis. Therefore, the research ethics committee receives an Investigator’s Brochure from the research institution in which all existing evidence regarding the efficacy, safety and pharmacokinetics of the compound under investigation is presented. The current research project primarily investigates if the reporting quality of early phase clinical trials in Investigator’s Brochures enables a risk-benefit analysis. This work is closely linked to other projects which investigate the conditions for a Good Justification Practice for clinical trials.
- Langhof, Holger; Chin, William; Wieschowski, Susanne; Federico, Carole; Kimmelman, Jonathan; Strech, Daniel (2018): Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross-sectional study. British Journal of Pharmacology 175, 4229–4238, doi: 10.1111/bph.14485.
- Strech, Daniel (2018): Präklinische Wirksamkeit? Wen schert´s? Laborjournal online 7-8/2018, 26-29
- Wieschowski, Susanne; Chin, William; Federico, Carole; Sievers, Sören; Kimmelman, Jonathan; Strech, Daniel (2018): Preclinical efficacy studies in investigator brochures: Do they enablerisk-benefit assessment? PLoS Biol. 2018 Apr 5;16(4):e2004879. doi: 10.1371/journal.pbio.2004879
- Wieschowski, Susanne; Silva, Diego; Strech, Daniel (2016): Animal Study Registries: Results from a Stakeholder Analysis on Potential Strengths, Weaknesses, Facilitators, and Barriers. PLoS Biol. 2016 Nov 10;14(11):e2000391. doi: 10.1371/journal.pbio.2000391