DECIDE - Phase II

Background / Rationale

Preclinical research explores potential novel therapies with the ultimate goal of bringing these therapies to patients. This is known as translation of scientific knowledge from basic to applied clinical research. However, before entering the clinical trial phase, where the treatment is tested in patients, efficacy of potential treatments needs to be confirmed through careful hypothesis testing and experimentation in preclinical model systems. Unfortunately, translational failures are frequent. Here, clinical trials cannot hold up to promising preclinical results, creating a translational gap. This has implications not only on a medical, but also on an economic, social, and ethical scale. 

Objectives

To better understand evidence generation in preclinical development pathways, theGerman Federal Ministry of Research, Technology and Space (BMFTR) started funding several preclinical confirmatory studies (1^st call, 2^nd call). As an accompanying project within this consortium, the DECIDE team supports and counsels the preclinical study groups throughout the funding period. After finishing the first phase of DECIDE, DECIDE - Phase II aims to identify success factors and to develop a best practice guideline for confirmatory studies from a meta-research perspective. Subsequently to the first cohort of studies accompanied by DECIDE, run between 2020 – 2024, the DECIDE – Phase II project has started in 2024. 

Methodology

In collaboration with Responsible PrecliniX, DECIDE – Phase II provides counselling to a set of multi-laboratory confirmatory preclinical trials to assess their experimental design regarding reliability as well as internal, external and translational validity (Drude et al., 2021). A counselling tool (Responsible PrecliniX, Carneiro et al. 2023) is used to guide meetings with the research groups to map out how they can improve their experimental design and thus generate evidence that is decision-enabling regarding translation. 

Additionally, the DECIDE team will host educational workshops and lectures to both inform and develop best practice frameworks for planning, conducting, and analyzing multi-lab preclinical research (Drude et al., 2022). Furthermore, the project aims to expand on the previously conducted meta-research during the first phase of DECIDE with a special focus on the implementation of multicenter-specific experimental approaches. A joint analysis of confirmatory results and the protocol evolution in the light of initial exploratory findings will be conducted. DECIDE – Phase II further aims at developing an evidence synthesis framework adopted for decision-making in preclinical settings.

Expected Results / Implications / Perspectives

Along with other resources*, outcomes of the first phase of DECIDE have been used to inform the 2^nd call from the BMFTR for funding confirmatory multi-laboratory preclinical studies demonstrating the project’s sustainability.  

DECIDE – Phase II aims to identify, document and address potential improvements of confirmatory multicenter preclinical studies through counseling, educational lectures, and workshops with and for funded project teams, addressing e.g. robust experimental design or regulatory affairs. 

Based on the previously funded research projects accompanied during the first phase of DECIDE, a joint analysis of the completed confirmatory projects will be conducted to assess replication success, to develop a framework for evidence synthesis, and to further map strategies and goals of confirmatory studies. In addition, it is expected that meta-research outputs will also inform the development of experimental protocols with increased validity and feasibility under particular consideration of the multi-laboratory context.  

The openly accessible DECIDE repository on the Open Science Framework provides additional details on the analysis plan for the upcoming meta-analysis, along with publications, preprints, and materials from the Preclinical Rethinking webinar.

* Glossary Preclinical Confirmatory Studies and Systematic Reviews and Guidance for planning and conducting confirmatory preclinical studies and systematic reviews