Introduction

The COVID-19 pandemic has led to greater public and government awareness of the importance of the life sciences and regulation of new medical interventions. For such interventions to be delivered effectively, patients and the public need to trust the regulatory processes. The detrimental effects of a lack of trust are apparent in anti-vaccine campaigns.

One way to promote patient and public trust in regulatory processes and ensure that regulations are responsive to their needs is through greater patient and public involvement and engagement (PPIE) in regulatory science initiatives and healthcare regulation. Patients and the public can provide unique insights based on their experiences, which cannot be substituted by expert knowledge from other stakeholders, and may influence the eventual success or failure of new medicines and healthcare technologies1. Furthermore, in line with the principles of biomedical ethics (autonomy, beneficence, non-maleficence and justice), patients and the public should be involved and engaged in regulatory science and processes that may affect them directly or indirectly2.

Here, we highlight key PPIE initiatives by regulatory agencies and regulatory science centres, suggest strategic areas for improvement, and present patient perspectives on PPIE. Supplementary Figure 1 shows the key stakeholders in regulatory science and Supplementary Box 1 provides definitions of key terms.

PPIE initiatives from regulatory agencies

Regulatory agencies have undertaken PPIE initiatives and published strategic documents on PPIE. Here we briefly discuss selected recent initiatives, with further information provided in Supplementary Box 2.

The US Food and Drug Administration (FDA) recently convened a series of public workshops with patients/advocates, researchers, practitioners and drug developers to inform the development of four patient-focused drug development (PFDD) guidance documents. The documents are intended to provide methodological guidance to foster the systematic collection of patient and caregiver input to inform medical product development and regulatory decision-making processes.

Patient and consumer organizations were consulted during the development of the European Medicines Agency (EMA)’s Regulatory Science to 2025 strategy. They provided substantial input that shaped several strategic goals with core recommendations for patient relevance in evidence generation, innovation in clinical trials, benefit–risk assessment and market access.

Following the Independent Medicines and Medical Devices Safety Review, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has made substantial progress in integrating PPIE in its work. Its new delivery plan for 2021–2023, Putting patients first: A new era for our agency, highlights the importance of engagement with patients and their outcomes, which the MHRA have put at the heart of the delivery plan. The Patient and Public Involvement Strategy, published in September 2021, was informed by extensive public consultations, and sets out how the agency will deliver the change across five key workstreams.

Work is underway to develop Health Canada’s Patient Involvement Strategy, with the goal of integrating patient expertise in Health Canada’s policy and regulatory decisions. Key areas of development focus on structural and cultural changes to encourage patient involvement in Health Canada’s regulatory work, potentially including, for example, new patient-focused guidance and increased patient representation on relevant scientific and advisory committees.

PPIE initiatives from public regulatory science centres

Academic/not-for-profit regulatory science centres play an important role in fostering PPIE in regulatory science and healthcare regulation. These organizations are often affiliated with university healthcare centres and interact directly with patients, collating and presenting their findings to regulators or policy makers.

The FDA's Centers of Excellence in Regulatory Science and Innovation (CERSIs) are collaborations between the FDA and academic institutions to advance regulatory science through innovative research, training and scientific exchanges. In Europe, several centres of excellence exist. For example, the Copenhagen Centre for Regulatory Science aims to improve the drug regulatory system and contribute to an improvement in the health of society and sustainable drug innovation. The UK’s Birmingham Health Partners’ Centre for Regulatory Science and Innovation (CRSI) works with multi-stakeholder groups, including patients, in the development of guidelines (Supplementary Box 3).

Areas for development of PPIE in regulatory science

Collaboration. Further international collaboration and sharing of good practice by stakeholders is needed. Organizations such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), as well as public–private partnerships such as the US Critical Path Institute or SISAQOL-IMI, have an important role to play. Continuously sharing best practices at forums such as the FDA/EMA Patient Engagement Cluster will ensure that the quality of PPIE in regulatory science is enhanced, reduce inefficiencies and help optimize approaches.

Organizational approaches. PPIE is often conducted ad hoc on a project-by-project basis, limiting its effectiveness. Organizations whose activities are informed by regulatory science need to take a broader perspective, by embedding PPIE within the wider infrastructure of the organization. There is a need for a strategy for systematic PPIE at an organization level, which patient and the public contribute to and regularly review3. Appropriate training needs to be provided for staff, and multidisciplinary collaborative working should be encouraged. Practical considerations to facilitate PPIE are detailed in Supplementary Box 4.

Inclusivity and diversity. The views and input of all groups should be effectively captured and incorporated in regulatory processes to prevent the widening of existing health inequalities or creation of new ones. There is a tendency to focus on patients who are the immediate beneficiaries of medical research. However, the broader ramifications of medical research and drug development may affect everyone in society, and so participation by members of the public should be encouraged. It is essential to engage with individuals from underserved groups; for example, minority ethnic populations, elderly and teenage/young adult populations. As these individuals may be less engaged with PPIE, strategies to facilitate their involvement in PPIE activities should be co-designed with members of these groups.

Communication. Effective continuous communication channels with PPIE group members can help sustain engagement over time. Patients and the public should be regularly informed about how their feedback has been used to inform regulation. Effective communication and transparency could build trust and help demystify the regulatory process and correct patient and public misconceptions. Concerns raised by PPIE members should be addressed promptly.

Measuring impact. There is a need to develop effective methods to record PPIE and capture evidence of its impact. Regularly monitoring and reporting key performance indicators could facilitate the assessment of PPIE impact4. The GRIPP2 checklist, which provides international guidance for reporting of PPI in health and social care research, can be used to document evidence of PPIE.

Patient advocacy perspectives

The key elements of PPIE, proposed by Kathy Oliver, patient advocate and Chair of the International Brain Tumour Alliance, are presented in Supplementary Figure 2 and may be summarized as follows. There should be a clear strategy for sustainable patient engagement and structured interaction; PPIE should be meaningful, not just a tick-box exercise; opportunities for mutual learning should be taken; processes should enhance effective collaboration; and PPIE should be timely, rather than ‘rubber stamping’ at the end. As Elaine Manna, patient partner, notes: “It is vital for patients to be equally involved in their healthcare, to understand how decisions are made and to have agency in the decision-making process. Being informed is empowering and often reassuring for patients and carers.” Overall, PPIE builds trust by enhancing patients’ and the public’s understanding of the activities of regulatory agencies, which could improve the uptake of new therapies and medical technologies.

Acknowledgements

O.L.A. receives funding from the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC), the NIHR Applied Research Collaboration (ARC), NIHR Birmingham-Oxford Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, at the University of Birmingham and University Hospitals Birmingham NHS Foundation, Innovate UK (part of UK Research and Innovation), Gilead Sciences, Merck and Sarcoma UK. S.C.R. receives funding from Merck, UK SPINE, and European Regional Development Fund – Demand Hub. M.J.C. receives funding from NIHR BRC, NIHR BTRU, the NIHR Surgical Reconstruction and Microbiology Research Centre and NIHR ARC West Midlands, UK SPINE, European Regional Development Fund – Demand Hub, Health Data Research UK at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Innovate UK (part of UK Research and Innovation), Macmillan Cancer Support, UCB Pharma, GSK, and Gilead Sciences. The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agencies or organizations with which the authors are employed/affiliated.

Competing Interests

O.L.A. declares personal fees from Gilead Sciences, Merck and GSK outside the submitted work. S.C.R. declares personal fees from Merck. M.J.C. received personal fees from Astellas, Aparito, CIS Oncology, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK and the Patient-Centered Outcomes Research Institute outside the submitted work. In addition, a family member of M.J.C. owns shares in GSK. All other authors declare no competing interests.