Finalizing a plan to guarantee quality in translational research for Neuromuscular diseases

Date: 2017-03-06
Number: 227
City: Heemskerk


227th ENMC International Workshop: Finalizing a plan to guarantee quality in translational research for Neuromuscular diseases

Date: 10 – 11 February 2017                                                Translations of the report: Italian

This workshop was supported by:



High quality translational research data are critical to successfully move new drugs from laboratory bench to patient bedside especially for rare neuromuscular diseases. The development of new medicines for rare diseases mostly starts in an academic lab, where researchers follow an idea or a hypothesis and plan the first experiments to test its validity. Such proof-of-concept studies are studies that investigate the mechanism of action of a drug at the molecular level, or test in cell systems and mice if a drug has an effect on a pathological feature. In a later phase, more detailed studies on animal models of a disease are necessary to see if the drug overall ameliorates the pathology of the animal (efficacy studies). This final pre-clinical stage should be carefully designed to try and closely match the conditions to be used for a potential human clinical trial using this same drug.  If these last animal studies give positive results, the drug may be considered to be applied in a clinical study on patients, to see if the efficacy is shown also in humans. The passage from the preclinical study phase on animals to the clinical phase on persons is called translation.

Academic researchers record the progress made in their research projects in form of articles (papers) that they submit for publication to scientific journals. The number of papers and the journals where these are published mean a lot for the researcher’s career and for the future probability to get their research funded. Journal editors select the quality of submissions by the process of peer reviewing and they are interested in publishing papers that will make an impact, because these will be cited in the future and will increase their visibility. Because of these reasons, titles of papers sometimes suggest amazing results even for early proof of concept studies.

Fortunately, in the last decade the interest in finding cures and medicines for rare diseases has increased considerably. More research projects are funded; more clinical studies are initiated both by academics and by companies. The exchange of know-how between clinicians (expert on the disease), patients (expert on the daily management of the disease), researchers (familiar with experiments and their evaluation), companies (advanced in the development of drugs and organisation of clinical trials) and regulators (experts in the requirements for approval of medicines) becomes important. The need of selecting the most promising treatments prior to starting a costly clinical trial has increased. The failure of many human trials in the past has driven attention to the quality of the published preclinical work: were animal experiments conducted with the rigor of a clinical study? Can they be reproduced by another laboratory? Are results powered enough to make the statement they make?

In this landscape, to more rigorously select strongly justified clinical trials, we identified the following discussion topics, for which we invited representative stakeholders to agree together on measures to improve more efficient and effective translation of preclinical work and collaboration among professionals.:

  • How to increase cross-talk between clinicians, researches, industry and patients

  • How to improve quality of animal studies that aim at showing efficacy of a treatment for a particular disease

  • How to encourage funding and publication of not novel studies that aim at reproducing data observed by others, and publication of negative results.

After a first series of introducing talks and testimonials, the participants divided into discussion groups, and following deliverables were agreed upon:

  1. Workshops will be organized at international meetings to inform stakeholders in the topics they are not familiar with, in order to improve efficiency at all levels of drug development. In particular, it was suggested to make use of the broad expertise represented in the TACT committee, a group created by TREAT-NMD that realistically evaluates the possibility of drug or treatment to translate to humans.

  2. Journal editors agreed to make an effort in requiring some standards in reporting preclinical trials by explicitly stating them in the instructions for authors. This would help also reviewers to search for such criteria in the submitted manuscripts. They suggest that quality requirements by funding agencies, set before a project is funded, may have more impact on quality of the experiments conducted. They recognise that the publication of negative  resultsis not attractive to many journals. However, some journal are addressing this important issue, since it is critical that studies that do NOT support use of a drug are also published, to provide a balanced picture . This group also suggests that small, controlled pilot trials on humans before a big clinical trial would help to predict translatability.

  3. Funding agencies proposed to improve awareness on high quality preclinical research among smaller patient organisations that do not have an expert scientific commission in place to evaluate project quality, and to take a leading role in educating such organisations. Furthermore, they propose to use the leverage they have on industry to require strong preclinical data before engaging in a clinical trial.

Workshop participants were researchers, clinicians, industry representative active in the field on neuromuscular diseases; patient organizations that fund research project and the main journals that publish neuromuscular research. They arrived from Europe, USA and Australia. Parent Project Muscular Dystrophy USA kindly supported the travel costs of all overseas participants.

A full report is published in the Neuromuscular Disorders (pdf)

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