The next step in translational research: lessons learned from the first preclinical randomized controlled trial

J Neurochem. 2016 Oct;139 Suppl 2:271-279. doi: 10.1111/jnc.13516. Epub 2016 Mar 10.


For years, low reproducibility of preclinical trials and poor translation of promising preclinical therapies to the clinic have posed major challenges to translational research in most biomedical fields. To overcome the limitations that stand between experimental and clinical research, international consortia have attempted to establish standardized guidelines for study design and for reporting the resulting data. In addition, multicenter preclinical randomized controlled trials (pRCTs) have been proposed as a suitable tool for 'bridging the gap' between experimental research and clinical trials. We recently reported the design and results of the first such pRCT in which we confirmed the feasibility of using a coordinated approach with standardized protocols in collaboration with independent multinational research centers. However, despite its successes, this first pRCT also had several difficulties, particularly with respect to following the protocols established in the study design and analyzing the data. Here, we review our experiences performing the study, and we analyze and discuss the lessons learned from performing the first pRCT. Moreover, we provide suggestions regarding how obstacles can be overcome to improve the performance and outcome of future pRCT studies. Translational research is hampered by low reproducibility of preclinical studies and countless failed clinical trials. International consortia have proposed preclinical multicenter trials as an intermediate step to overcome this 'translational roadblock'. We have recently performed the first such preclinical randomized controlled trial (pRCT) by adopting key elements of clinical study design to preclinical research. In this review, we discuss the lessons learned from this trial and provide suggestions how to optimize future pRCTs. This article is part of the 60th Anniversary special issue.

Keywords: randomized controlled trial; replication crisis; stroke; study design; translational research.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical / standards
  • Drug Evaluation, Preclinical / trends*
  • Humans
  • Learning
  • Randomized Controlled Trials as Topic* / methods
  • Randomized Controlled Trials as Topic* / standards
  • Reproducibility of Results
  • Translational Medical Research / methods
  • Translational Medical Research / standards
  • Translational Medical Research / trends*