EU-PEARL: Co-production of knowledge to advance drug development. Re: Co-production of knowledge: the future
On behalf of the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project (1), we welcome the BMJ´s recent collection on Increasing the Impact of Health Research through Co-production of Knowledge (2). Redman, et al (3) and others (4) highlight the benefits and challenges to establishing collaborative research approaches, in comparison to traditional siloed approaches, to improve, accelerate and generalize the knowledge created to be implemented faster and safer. We would like to add to this, by sharing our experience within a clinical trial research setting.
EU-PEARL is a multi-stakeholder, multi-sector collaborative research project (2019-2023), funded by the Innovative Medicines Initiative 2 Joint Undertaking, which aims to build capacity and support the transformation of the classical trial approach into a cross-company collaborative, multi-compound, patient-centred integrated research platform (IRP) i.e., a common enabling framework for platform trials, including also a research clinical network and federated patient data (1,5). Why is this new approach needed? Instead of evaluating only one or a small number of investigational drugs via classical clinical trials, innovative platform trials enable the concurrent evaluation of multiple treatments, from potentially multiple sources, for a disease or condition. As such, they have the potential to revolutionize the clinical research landscape and are foreseen to bring additional benefits to multiple stakeholders (6); recent examples are the platform trials being conducted for COVID-19 (7,8) and Acute Myeloid Leukaemia (9).
The EU-PEARL consortium consists of 36 partners from academic hospitals, pharmaceutical companies, Non-Governmental Organizations, Patient Representative Groups, and small and medium-sized enterprises, who are working together to co-produce the knowledge required to develop a disease-agnostic IRP, and four disease-specific IRPs for major depressive disorder, tuberculosis, non-alcoholic steatohepatitis and neurofibromatosis (10). In addition, due to the novelty of this work, regulatory, legal, methodological and data guidance is being developed, as well as new materials on how to facilitate meaningful and effectively engage patients in the co-design of platform trials. Once completed, these outputs will be shared widely to engage stakeholders and encourage their utilization for future platform trials. Furthermore, we are developing sustainability business plans for the four disease-specific IRPs, and for a trusted sustainability entity ready to set-up and coordinate the operation of the IRP for any disease. The overall intention is to enable this new approach to become more widespread, and for future trials to be more adaptive, patient-centred, efficient, collaborative and cost-effective, to accelerate drug development.
As Redman, et al (3) mention, and based on our experiences so far, to facilitate the effective working of these types of collaborations, multiple components need be in place, such as financial, human and technical resources, as well as incentives for multi-stakeholders. In addition, solidarity, trust, open communication and standardized terminology must be fostered, alongside power sharing, clear commitment, and mutual respect for the diverse stakeholders’ perspectives (3,11). Lastly, evaluations of such efforts are key to establishing when, where and how to best co-design and co-implement them in the future (3,4); EU-PEARL intends to contribute to this learning in the clinical trials arena, with on-going evaluations of our efforts.
Lucinda Cash-Gibson (1); Juan M Pericàs (1, 2); Edwin van de Ketterij (3); Dipak Kalra (4); Francesco Patalano (5); Joan Genescà (1, 2)
1. Vall d'Hebron Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain.
2. Liver Unit, Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.
3. European Infrastructure for Translational Medicine (EATRIS), Amsterdam, Netherlands.
4. The European Institute for Innovation through Health Data (i~HD), Gent, Belgium.
5. Novartis Pharma AG, Basel. Switzerland.
1. EU-PEARL project website. Available: https://eu-pearl.eu/. Accessed 28/05/2021.
2. BMJ collection on co-production of knowledge (www.bmj.com/co-producing-knowledge)
3. Redman S, Greenhalgh T, Adedokun L, Staniszewska S, Denegri S, et al. Co-production of knowledge: the future BMJ 2021; 372 :n434 doi:10.1136/bmj.n434
4. Oliver, K., Kothari, A. & Mays, N. The dark side of coproduction: do the costs outweigh the benefits for health research? Health Res Policy Sys 17, 33 (2019). https://doi.org/10.1186/s12961-019-0432-3
5. Parke T, et al. 2020. EU-PEARL. D2.1 Report on Terminology, References and Scenarios for Platform Trials and Master protocols. Available: https://eu-pearl.eu/wp-content/uploads/2020/06/EU-PEARL_D2.1_Report-on-T....
6. Meyer EL, Mesenbrink P, Dunger-Baldauf C, Fülle HJ, Glimm E, Li Y, Posch M, König F. The Evolution of Master Protocol Clinical Trial Designs: A Systematic Literature Review. Clin Ther. 2020 Jul;42(7):1330-1360. doi: 10.1016/j.clinthera.2020.05.010. Epub 2020 Jul 1. PMID: 32622783.
7. Park JJH, Mogg R, Smith GE, et al. How COVID-19 fundamentally has changed clinical research in global health. Lancet Glob Health 2021; 9: e711–20
8. Collignon O, Burman CF, Posch M, Schiel A. Collaborative Platform Trials to Fight COVID-19: Methodological and Regulatory Considerations for a Better Societal Outcome. Clin Pharmacol Ther. 2021 Jan 28:10.1002/cpt.2183. doi: 10.1002/cpt.2183. Epub ahead of print. PMID: 33506495; PMCID: PMC8014457
9. Rosenberg, L., Levaux, H., Levine, R.L. et al. Streamlined Operational Approaches and Use of e-Technologies in Clinical Trials: Beat Acute Myeloid Leukemia Master Trial. Ther Innov Regul Sci (2021). https://doi.org/10.1007/s43441-021-00277-w
10. Dhaenens BAE, Ferner RE, Bakker A, Nievo M, Evans DG, Wolkenstein P, Potratz C, Plotkin SR, Heimann G, Legius E, Oostenbrink R. Identifying challenges in neurofibromatosis: a modified Delphi procedure. Eur J Hum Genet. 2021 Apr 26:1–9. doi: 10.1038/s41431-021-00892-z. Epub ahead of print. PMID: 33903738; PMCID: PMC8071842
11. Rycroft-Malone, Jo et al. Collaboration and Co-Production of Knowledge in Healthcare: Opportunities and Challenges.International journal of health policy and management vol. 5,4 221-3. 28 Jan. 2016, doi:10.15171/ijhpm.2016.08
Competing interests: All authors are members of the EU-PEARL Consortium. The EU-PEARL (EU Patient-cEntric clinicAl tRial pLatforms) project has received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking (JU) under grant agreement No 853966. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and Children’s Tumor Foundation, Global Alliance for TB Drug Development non-proﬁt organization, Springworks Therapeutics Inc. This publication reﬂects the authors’ views. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein. LC-G, JMP, JG: Vall d´Hebron Institute for Research (VHIR) is the Coordinator of the EU-PEARL (EU Patient-cEntric clinicAl tRial pLatforms) project that has received funding from the Innovative Medicines Initiative (IMI). EvdK is employed by the European Infrastructure for Translational Medicine (EATRIS), Amsterdam, Netherlands. EATRIS is a partner of the EU-PEARL (EU Patient-cEntric clinicAl tRial pLatforms) project that has received funding from the Innovative Medicines Initiative (IMI). DK: None declared. FP is an employee and a shareholder of Novartis Pharma AG