Advancing UK Regulatory Science Strategy in the Context of Global Regulation: a Stakeholder Survey

Background The UK’s transition from the European Union creates both an urgent need and key opportunity for the UK and its global collaborators to consider new approaches to the regulation of emerging technologies, underpinned by regulatory science. This survey aimed to identify the most accurate definition of regulatory science, to define strategic areas of the regulation of healthcare innovation which can be informed through regulatory science and to explore the training and infrastructure needed to advance UK and international regulatory science. Methods A survey was distributed to UK healthcare professionals, academics, patients, health technology assessment agencies, ethicists and trade associations, as well as international regulators, pharmaceutical companies and small or medium enterprises which have expertise in regulatory science and in developing or applying regulation in healthcare. Subsequently, a descriptive quantitative analyses of survey results and directed thematic analysis of free-text comments were applied. Results Priority areas for UK regulatory science identified by 145 participants included the following: flexibility: the capability of regulations to adapt to novel products and target patient outcomes; co-development: collaboration across sectors, e.g. patients, manufacturers, regulators, and educators working together to develop appropriate training for novel product deployment; responsiveness: the preparation of frameworks which enable timely innovation required by emerging events; speed: the rate at which new products can reach the market; reimbursement: developing effective tools to track and evaluate outcomes for “pay for performance” products; and education and professional development. Conclusions The UK has a time-critical opportunity to establish its national and international strategy for regulatory science leadership by harnessing broader academic input, developing strategic cross-sector collaborations, incorporating patients’ experiences and perspectives, and investing in a skilled workforce. Supplementary Information The online version of this article (10.1007/s43441-021-00263-2) contains supplementary material, which is available to authorised users.

"Regulatory Science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all FDA-regulated products." (FDA, 2010) https://app.smartsurvey.co.uk/survey/print/id/722319?t=1&dst=false&dsl=true&dpt=true&dpb=false&dpn=true&dqn=true&dqb=false&st=473078 3/13 "Regulatory Science can be described as a range of scientific disciplines that are applied to the quality, safety and efficacy assessment of medicinal products that inform regulatory decision-making throughout the lifecycle of a medicine. It encompasses basic and applied medicinal science and social sciences and contributes to the development of regulatory standards and tools" (EMA, 2018) "The acquisition and analysis of data sufficient to inform decision making pertinent to the approval of safe and effective therapeutics, devices and cosmetics and ensuring the safety and nutritional value of the food supply." (FitzGerald, 2010) "The science of developing methods to quantitatively and/or qualitatively analyze and understand the causal relations and mechanisms of the substances and the phenomena around us, and measuring their positive and negative effects. Their efficacy and safety are appropriately predicted, evaluated and judged using the methods developed and the results obtained in the [regulatory science], contributing to public health." (The Pharmaceutical Society of Japan, 2016) "The application of the biological, medical and sociological sciences to enhance the development and regulation of medicines and devices in order to meet the appropriate standards of quality, safety and efficacy." (CASMI, 2013) Other (please specify):

Current challenges and opportunities in regulatory science
5. What are the most important features of future regulation for UK healthcare innovation, which regulatory sciences needs to more effectively enable. Select all that apply *

Data sharing
Open access Costs associated to data sharing (e.g. the costs of anonymising data) Cooperation between agencies (e.g. MHRA, EMA and FDA) Dialogue/cooperation across stakeholders e.g. between academia -industry (including biopharma and med tech) -regulatory agencies -patients Remaining aligned with EU following the UK's exit from the European Union Faster approval of medical products Development of a framework to make regulatory decisions about risks and benefits of products that increasingly involve new technology (e.g. -digitally-based products/AI and product development, production processes and novel supply chains) and target patient outcomes. Technological and scientific challenges -genomics and increased personalisation/specialisation of products Developing effective tools to track and evaluate outcomes for reimbursement Professional development (i.e. workshops or courses to supplement knowledge base) Workforce retention rates Other (please specify):

Please rank (drag and drop the question boxes) the most important features of future regulation for UK healthcare innovation, which regulatory sciences needs to more effectively enable: *
Co-development: collaboration across sectors, e.g. patients, manufacturers, regulators and educators working together to develop appropriate training for novel product deployment Responsiveness: the preparation of frameworks which enable timely innovation required by emerging events Speed: the rate at which new products can reach the market Flexibility: the capability of regulations to adapt to novel products and target patient outcomes Reimbursement: developing effective tools to track and evaluate outcomes for "pay for performance" products Education and professional development Reinforce patient relevance in evidence generation, increased patient involvement in regulatory activities, including patient representatives as additional experts in Scientific Advisory Groups, as well as patient contribution to scientific advice and protocol assistance.

Strategic areas for development
Enhance understanding and appropriate use of methods to capture information on patient preferences and the potential acceptability of tradeoffs between treatment benefit and risk outcomes.
Increase use and transparency of patient input as evidence in regulatory science decision-making.
Expand patient centered outcomes research by compiling datasets converted to standardized format across critical classes of drugs that are entered into the clinical trials repository.
Identification and use of approaches and best practices to facilitate patient enrollment and minimizing the burden of patient participation in clinical trials.
Other ( Explore innovative ways of using real world data to assess clinical effectiveness in routine clinical settings Explore developing more agile regulatory approvals processes for novel and generic products Explore developing standards for new areas e.g. digital health, artificial intelligence, machine learning Explore supporting opportunities in vaccines, combination products, software algorithms, remote site reporting and additives Other (please specify):

Develop systems and processes for integrated medicines and devices surveillance
Optimise signal and and risk assessment functions to respond to risks in real time Develop professional expertise and systems to improve market surveillance of medical devices using the new regulations and its new data sets Develop and expand use of medical device electronic data standards with partners Encourage reporting of adverse incidents from patients and health care professionals

Systematically evaluate effectiveness of risk minimisation and impact
Work closely with key source countries to assure safe production and supply

Strategic areas for development
10. Thinking about your stakeholder group, which of the actions below are most important for the development of UK regulatory science. Select all that apply Organisational excellence/efficiency * Identify future capability needs and ensure the right skill mix is available to support innovation and deliver priority programmes and core functions Identify opportunities to recruit, retain and develop staff; including new training opportunities Invest in scientific capabilities to meet emerging needs. Invest in staffs specialist skill sets, and in facilities to deliver state of the art regulation and services.
Focus on identifying and developing talent and on the importance of leadership, in the context of organisational development in an environment of scientific advance and environmental change Explore new methodologies for detecting data integrity issues associated with regulatory studies Explore opportunities to develop collaborations and information sharing with key global regulators, international partnerships with WHO and other key players Other (please specify):

Current training and future needs
Regulatory science encompasses a wide range of subjects, including not only disciplines associated with regulation, such as statistics, engineering and clinical research, but also disciplines outside the biomedical sciences such as informatics, economics, risk communication, and sociology.
Please state whether you agree with the following statements: 11. Due to its breadth and dynamism, regulatory sciences require life-long learning* and development. *Life-long learning: Voluntary and self-motivated education or learning, beyond formal education, to improve personal or professional development. *