PERsonalised MedicIne Trials

Project Information

PERMIT

Grant agreement ID: 874825

DOI

10.3030/874825

Project closed

EC signature date 26 November 2019

Start date 1 January 2020

End date 30 June 2022

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 2 000 000,00

EU contribution

€ 2 000 000,00

Coordinated by

ECRIN EUROPEAN CLINICAL RESEARCH INFRASTRUCTURE NETWORK
France

Periodic Reporting for period 2 - PERMIT (PERsonalised MedicIne Trials)

Reporting period: 2021-01-01 to 2022-06-30

Summary of the context and overall objectives of the project

Personalised medicine (PM) aims at delivering each patient (or subgroup of patients) healthcare strategies best adapted to their individual characteristics. PM requires novel methodological approaches made possible due to high throughput data generation technology and subsequent stratification of patients into homogenous clusters through conventional or machine learning stratification. However, scientific excellence and the validation by health authorities of results from clinical research are essential for those results to be integrated into routine care in a safe and reliable way. Guidelines and best practices that can help to ensure results from research in this field can be accepted as valid and reproducible are needed, so that all stakeholders (regulators, researchers, scientific journals, clinicians, funders, patients, HTAs and more) can safely adopt and integrate results from PM research into healthcare practice.

The objective of the PERMIT Consortium was to provide, in collaboration with all the relevant stakeholders, recommendations on research methods to ensure that PM research programmes (from stratification cohorts to clinical trials) are robust and that they produce reliable results.

The project began by analysing the existing scientific and grey literature to identify and assess the existing methodologies that are used in PM research. Then, the gaps and areas where recommendations would be needed were identified. In the second year of the project a series of workshops, with consortium members and field experts took place. They addressed the gaps and through discussion and consensus developed a series of 71 recommendations. These recommendations cover the full PM research pipeline and can help all stakeholders involved in this pipeline when they design, execute, evaluate, finance, or publish PM research. These recommendations are subdivided into four sets, corresponding to the four stages of the pipeline detailed below. Finally, the project mobilized efforts to disseminate the recommendations and to facilitate their implementation.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the first year of the project, a mapping of the literature identified the currently used methods in the various steps of personalised medicine programmes and identifed gaps and needs for guidelines and recommendations. A series of four scoping reviews was carried out, covering the following stages: the design of the stratification and validation cohorts including the issue of the statistical power and the quality of data; the use of machine learning methods for patient stratification; the translational development step needed to select treatments; and the designs of randomized clinical trials for testing treatments in each cluster as well as the designs of trials that compare the personalised vs. non-personalised approach to assess the value of personalized approach for the public health. The main gaps that exist at each of these stages were identified and corresponded to a lack of clear regulatory requirements, of harmonization in the use of methods, and/or of technical means.

In the second year of the project over 14 working sessions and workshops, with consortium members and field experts, took place. In these meetings the gaps were addressed and through discussion and consensus and a total of 71 recommendations were developed. The recommendations provide guidance through every stage of the personalised medicine research pipeline, highlighting potential pitfalls and methodological challenges that can arise at every stage. They can help all stakeholders of the research pipeline to better design, implement, and assess personalised medicine research programs.

The final six months of the PERMIT project focused on communication, dissemination and implementation. Following a consultation with all key stakeholders on the most adequate dissemination and implementation strategies, scientific publications, lay summaries and training material were prepared. These cater to different stakeholder groups so that all key players of personalised medicine research can adopt and implement the PERMIT recommendations.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The PERMIT recommendations are expected to have a significant impact on all the parties involved in funding, planning, conducting, overseeing, reviewing and publishing PM research. The recommendations will aid all key stakeholders in producing reproducible and valid research results, and to adopt and implement the results of PM. The following impact can be expected:
- The implementation of the PERMIT recommendations by the regulators could facilitate the acceptability of clinical trials and preclinical studies with innovative methodologies, boosting innovation and enhancing access to market of PM therapeutics and diagnostics.
- Academic sponsors can use the recommendations to ensure that the clinical studies or trials that they will sponsor are built from sound methodological research, and will implement robust methodologies.
- They recommendations provide guidance for investigators working on every stage of the PM research programmes, allowing them to better plan and design their studies. Furthermore, they allow investigators involved in multi-stage multidisciplinary endeavours to better understand and assess the stages that come before or after their own.
- The PERMIT recommendations will allow funding bodies to better assess the methods included in research grant proposals.
- National competent authorities and ethics committees will be able to use the recommendations in their assessment of PM clinical studies. The recommendations highlight areas where further regulatory research could be performed to improve clarity and boost innovation in PM.
- Several recommendations highlight the importance of involving patients in the co-design of PM research programs from early to late stages. The communication and training tools can help to raise awareness among the patient communities and can contribute to boosting co-design and engagement.
- Regulators will be able to refer to the PERMIT recommendations in their assessment of PM clinical trials or in future potential guidelines on this subject. The recommendations are also a useful resource for the assessment of the methods used to produce evidence in the stages prior to trial, helping to assess if the full pipeline was designed in the best possible way.
- The implementation of these recommendations can contribute to more robust and more comparable clinical trials, which can in turn help to ensure that HTAs have sufficient quality evidence to perform assessments that can feed into reimbursement policies.
- The recommendations can serve as guidance for journal editors and reviewers who assess PM research findings for publication. The recommendations pinpoint the methodological approaches that should be favoured, and the evidence and justifications that must be reported on.
- PERMIT has also identified a list of future research questions that could be addressed through targeted methodological and regulatory research to further advance the field of PM research.

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