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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - EQIPD (European Quality In Preclinical Data)

Teaser

Summary

The pharmaceutical industry in particular, as well as the advance of biomedical science in general, depend on robust data and scientific rigor as essential for efficient decision making, patent strength and reducing time-to-market/deployment, which in turn determines knowledge gain and availability of new treatments to patients. Recent publications report challenges with the robustness, rigor, and validity of research data, which may misinform decisions about whether to proceed to further preclinical or clinical testing as well as questioning the predictability of preclinical models. There is a need for simple, sustainable solutions that facilitate data quality.
We will propose simple, sustainable solutions to facilitate data quality without impacting innovation and freedom of research. Our consortium is pooling resources from academia and industry to pilot this action in Neuroscience and Safety, but with applicability beyond these R&D areas.
The European Quality In Preclinical Data (EQIPD) consortium is
(i) defining those variables in study design and data analysis that influence outcome in pre-clinical neuroscience (focus on Alzheimerâ€™s disease and psychosis) and (neuro-)safety studies conducted in industry; and establish whether these are the same variables which influence outcome in academia;
(ii) defining the components of the EQIPD quality management system;
(iii) defining consensus quality management recommendations for non-regulated R&D;
(iv) validating the feasibility of the quality management system in prospective studies;
(v) delivering an online educational platform providing certified education and training in the principles and application of quality and rigour.
We are conducting systematic reviews and meta-analysis of historical data sets from industry and academia to identify features of study design which influence outcome in preclinical studies. Informed by the outcome of these analyses, we have used a Delphi approach to reach consensus around core principles for preclinical robustness, and will validate these approaches in cross site experiments and establish ring testing experiments in non-regulated research. We are developing a quality system framework to allow researchers to demonstrate best practice and a governance system to ensure sustainability and relevance.
We are also developing an educational platform to ensure research community-wide expansion of knowledge on criteria and principles necessary to address robustness and quality.
Junior researchers are involved in many of the tasks and are enrolled in an academia/industry joint exchange scheme.

Work performed

We are making good progress across Work Packages: WP1 has established an effective project management structure and is overseeing implementation, communication and dissemination, and has established a Dissemination Approval Committee. WP2 has made 70% progress in converting identified datasets for analysis. Systematic reviews of published data in AD are progressing, with 230,000 identified citations and good performance of the machine learning algorithm. WP3 has completed the review of existing recommendations and identified the key principles of preclinical research quality; the draft framework is now with other WPs for testing. In WP4 the young researchers joint exchange scheme has been established; they have defined minimal requirements for 3 testing paradigms (Irwin, Open Field and EEG) and the first â€œlocalisation stageâ€ is underway. WP5 has defined the scope of the new quality system, and the development of that system is almost complete: testing of the tools and mechanisms to support the implementation and performance monitoring of the new quality system is underway. WP6 have made good progress in developing a monitoring and assessment system for the new quality system, as well as developing a dynamic and efficient governance system. WP7 has hosted a summer school for young researchers, made good progress in establishing the exposure section of the learning environment and some progress in establishing the education section of the learning environment. WP8 have formulated a transparent protocol for unbiased inclusion of experimental paradigms and datasets, developed the EQIPD Data Warehouse, making good progress in implementing a reproducible data pre-processing process and is on track for the provision of a persisting data sharing platform. WP9 has extended its scope and has created an animal care and use questionnaire that has been completed by most consortium partners. Answers are currently analysed and results will be provided to the other WPs.

Final results

The systematic review and meta-analysis of a large volume of historical industry data is unprecedented, and will allow us to establish whether the problems with rigour identified in the published literature also apply to industry data. Preclinical safety data (we focus on the Irwin test) are rarely published so the systematic review and meta-analysis of historical industry safety data will again be unprecedented. Our results will inform the extent to which strategies to improve rigour should be targeted to areas of specific weakness or should be generalised.
The development of tools to improve research rigour will allow involvement of research providers at different stages of improvement. Researchers will be able to shape their improvement strategy in the light of their current performance. Involvement of key external stakeholders will facilitate dissemination and implementation. Finally, the development of standard approaches to ring testing (through which novel experimental approaches and measures of outcome may be validated) and the demonstration of the feasibility of a strategic and organised approach to multicentre efficacy studies represents a major advance.
EQIPD will have expected impacts on (1) improved European citizensâ€™ health and well-being, (2) improved data quality of pre-clinical studies, (3) contribution to animal welfare: 3Rs + robustness, (4) enhanced intellectual property protection and regulatory success, (5) a cultural change in the implementation of quality principles in preclinical science, (6) building confidence between research partners, and (7) facilitation of collaborations through common quality standards.
In particular, we have increased the potential impact on animal welfare and the 3Rs by establishing an additional working group specifically charged with exploiting opportunities to enhance the ethical position of animal research. While the systematic review of guidelines was not targeted at guidelines relating to animal welfare, the search terms used allow re-use for this purpose, and this is something we hope to return to in later stages of the project.
The systematic review of guidelines for research conduct has already had unforeseen beneficial impacts; we have shared these with the US NIH (Shai Silberberg, an Associate Partner) and with a group established by the Australian NHMRC (Glenn Begley, a member of our Scientific Advisory Board). Both agencies are considering training requirements for in vivo researchers and considered our review to provide a basis in evidence for the choice of components of a core curriculum. We are hopeful that they and others may endorse our guidelines, so that there is a globally agreed core curriculum. This would allow training providers (including SMEs) to develop materials secure in the knowledge that there would be substantial demand for their product.