Responsible PrecliniX

We welcome projects from all career stages from PhD projects to larger European consortia. Write an email to natascha-ingrid.drude@bih-charite.de with a short description of your project. You may include a proposal (draft), publication(s), a thesis, or simply bullet points about a potential new project. Importantly, as we are providing this service within Charité, we are bound by a confidentiality and corporate nondisclosure agreement. We treat all projects with the strictest confidentiality as a matter of course.

PhD students, Postdocs, Principal investigators, or research groups can approach Responsible PrecliniX already at the early stages or at the stage of proposal writing, and subsequently, we accompany projects from the basic idea to translation through a series of Go/No-Go decision points. A funded project can receive counseling for improvements in experimental design, how to design a replication study (sample size, additional drug concentrations, etc.), or best practices for engaging other labs to conduct external replications.

Currently, we operate on a first-come-first-serve basis. However, it is possible to prioritize projects in case of e.g., deadlines for grant applications.

You are the expert in your specific research field. Consequently, we do not interfere with the scientific question and do not provide a scientific review. Instead, we aim at complementing your academic expertise with expertise in statistics (including sample size calculation), experimental design, experimental models (including potential alternatives), robustness, and the role or need of replication studies (within a laboratory or between laboratory) and meta-research (e.g., systematic review methodology).

To assess your project, we use a question catalog to assess the robustness of your project.

Based on this first assessment, we schedule a meeting with you. In this meeting, we will deepen our understanding of your needs and collaboratively identify action items. The evaluation can be helpful

• to improve and strengthen the validity and reliability of the study,
• to find collaborators, and
• to identify and defining go/no-go decision points including preclinical endpoints.

The continuation of the support beyond this first meeting, including the articulation of the contact with Core Facilities or regulatory affairs representatives, will be planned and personalized for each project.

Our counseling sessions are focused on four aspects of the study design: internal validity (e.g., risk of bias), reliability (e.g., general statistical aspects, consistency), external validity (e.g., generalizability across preclinical settings), and translational validity (e.g., the similarity of the preclinical model to human population). In addition, we ask basic questions regarding regulatory affairs and quality assurance to connect projects with other units (e.g., Core Facilities, Regulatory Affairs), depending on specific needs. We can also assist you with the animal permit and/or pre-registration.

We provide counseling and support for all basic and preclinical research projects that aim at clinical translation i.e., the pathway from biomedical discovery to patient benefit. We support in vitro, ex vivo as well as in vivo models. The support available is not restricted to pharmacological interventions or drug development, but also covers surgical procedures, medical devices or studies that focus on gaining mechanistic understanding and/or target validation.

We welcome projects of all types and sizes – from basic discovery research (if the long-term goal is translation) to applied translational research, from PhD projects to EU consortia. Depending on the specific needs of the project and overall demands from the unit, we will scale our contributions accordingly always ensuring that support is given to every project.

The metric was initially developed based on our experience with a pioneering BMBF Call for confirmatory preclinical trials and use cases within BIH programs, such as SPARK and (Junior) Clinician Scientist Program. The metric (=question catalog) and consultation are under continuous evaluation and are constantly refined based on meta-research projects and feedback from researchers like yourselves.

References

(1) Drude, N. I.; Martinez-Gamboa, L.; Danziger, M.; Collazo, A.; Kniffert, S.; Wiebach, J.; Nilsonne, G.; Konietschke, F.; Piper, S. K.; Pawel, S.; Micheloud, C.; Held, L.; Frommlet, F.; Segelcke, D.; Pogatzki-Zahn, E. M.; Voelkl, B.; Friede, T.; Brunner, E.; Dempfle, A.; Haller, B.; Jung, M. J.; Riecken, L. B.; Kuhn, H.-G.; Tenbusch, M.; Higuita, L. M. S.; Remarque, E. J.; Grüninger-Egli, S. L.; Manske, K.; Kobold, S.; Rivalan, M.; Wedekind, L.; Wilcke, J. C.; Boulesteix, A.-L.; Meinhardt, M. W.; Spanagel, R.; Hettmer, S.; von Lüttichau, I.; Regina, C.; Dirnagl, U.; Toelch, U. Planning Preclinical Confirmatory Multicenter Trials to Strengthen Translation from Basic to Clinical Research – a Multi-Stakeholder Workshop Report. Translational Medicine Communications 2022, 7 (1), 24. https://doi.org/10.1186/s41231-022-00130-8.

(2) Drude, N.; Martinez-Gamboa, L.; Haven, T.; Holman, C.; Holst, M.; Kniffert, S.; McCann, S.; Rackoll, T.; Schulz, R.; Weschke, S. Finding the Best Fit for Improving Reproducibility: Reflections from the QUEST Center for Responsible Research. BMC Research Notes 2022, 15 (1), 270. https://doi.org/10.1186/s13104-022-06108-x.

(3) Hülsemann, M.; Wiebach, J.; Drude, N. I.; Kniffert, S.; Behm, L.; Hönzke, K.; Baumgardt, M.; Hippenstiel, S.; Hocke, A. C.; Dirnagl, U.; Tölch, U. Introducing Quality Measures in an Academic Research Consortium. EMBO reports 2022, 23 (8), e55095. https://doi.org/10.15252/embr.202255095.

(4) Drude, N. I.; Gamboa, L. M.; Danziger, M.; Dirnagl, U.; Toelch, U. Science Forum: Improving Preclinical Studies through Replications. Elife 2021, 10, https://doi.org/10.7554/eLife.62101.

(5) Drude, N. I. Voices of the New Generation: My Unconventional Way to Stay in Academia. Nature Reviews Molecular Cell Biology 2022. https://doi.org/10.1038/s41580-022-00554-y.

Responsible PrecliniX is implemented into the BIH strategy and resulted in a permanent position to safeguard its continued existence. To further ensure sustainability, the first evaluation and counseling session will remain free to use at the point of access.

However, to ensure additional funding we apply for (third-party funded) projects that focus on conducting research on research. Responsible PrecliniX is recognized by local organizations like Charité 3R. In this context, Charité 3R appoints Responsible PrecliniX to provide methodological support and accompany projects of an upcoming funding scheme. In addition, to secure funding, we can be acknowledged by you as a cooperation partner and/or co-applicant in funding schemes to promote high quality standards and enable research on research.

We do not provide guidance toward the implementation of a quality management system. However, we can identify needs and connect you with our collaborators from PREMIER and/or EQIPD. Do not hesitate to contact us for further information.