Recommendations

In the ABPI’s 2019 Clinical Trials Report, we outlined how the UK can build an ecosystem fit for the future of clinical research. This report builds on those recommendations and outlines industry’s priorities.

In addition, the ABPI and industry recognise that the role of the NHS is critical here.

As clinical research is delivered in the NHS, the UK must work towards embedding a research culture across our healthcare system. A plan must be developed for how funding, resources, facilities and workforce will be made available for research, to ensure the NHS has the capacity and resilience to deliver world-class clinical research throughout the UK. We also need to redefine our prioritisation and support the NHS in resuming healthcare services and research in order to address the unmet needs of all patients, including COVID-19 patients.

1. Restarting and restoring research across the UK and across all disease areas

There is increasing concern amongst industry and charity sponsors around the UK’s progress on the restart of non-COVID-19 clinical research, which is a critical first step in delivering the changes needed to transform our clinical research environment. Many challenges remain across all parts of our healthcare system, following the COVID-19 pandemic, with threats of a second wave and further disruption.

The ABPI and industry appreciate the efforts of NIHR to restart research and the ongoing support from other organisations, such as HRA, MHRA, UKRD and the R&D Forum. However, in order to overcome these challenges, leadership and cross-organisational solutions are required, with support from industry, charity, academia, Government and crucially, the NHS.

2. Transforming the UK clinical research environment with investment to increase levels of research beyond pre-COVID levels

Commitments from the UK Government, in the Life Sciences Industrial Strategy Sector Deals commit funding and infrastructure investment to enhance the UK’s clinical research environment.

Furthermore, the R&D Roadmap published in July 2020, sets out the ambition to be a global leader in research and innovation infrastructure, with commitments to develop a long-term investment plan and increase public investment in R&D to £22bn by 2024/2025. The role of the sector is central to delivering on this ambition, with the sector investing more in R&D than any other sector of the UK economy ⁽⁹⁾.

To enable the NHS to become the best platform in the world for clinical research and an attractive destination for commercial sponsors, the UK Government must deliver on these commitments, working with industry to ensure they have maximum impact on improving the commercial clinical research environment.

In addition, the nation’s largest funder of health and care research, the NIHR, works in partnership with the NHS and the wider life sciences sector, to deliver clinical research in England, including commercial funded research. In 2018/2019, the NIHR centres and facilities supported over 3,500 commercial studies, with over £100m in funding leveraged from industry ⁽³²⁾.

Despite the NIHR’s critical role in the UK clinical research environment and the ongoing COVID-19 R&D effort, the NIHR’s total spend on infrastructure, research programmes and supporting systems has remained unchanged for the past five years, with an annual budget of around £1bn, which has also included its annual contribution to Genomics England ^{(33, 34, 35, 36)}.

Parallel to restarting and restoring research across the UK and across all disease areas, increased investment in the UK’s clinical research environment is required to support the transformational changes needed to increase research activity beyond pre-COVID-19 levels. Investment should be directed by:

a. Optimising the processes for setting up and running clinical trials

Central to the ability of the UK to become a more attractive destination for medical research, is the ability to improve efficiency in approving and setting up trials. Commercial sponsors often experience variable approval timelines, with slow and arduous negotiations around costing and contracting. The UK must be able to offer fast and accurate feasibility, streamlined approvals, globally competitive and harmonised costing and contracting, successful recruitment to time and target, and efficient trial conduct.

For streamlined approvals, much progress has been made with the Combined Ways of Working (CWoW) pilot between HRA and MHRA, set up in April 2018. This initiative brings together a single Clinical Trials of Investigational Medicinal Products (CTIMPs) application for both MHRA’s clinical trial authorisation and HRA’s research ethics committee (REC) opinion and has succeeded in reducing timelines for regulatory and ethics approval ^{(37, 38)}. Work to develop the IT infrastructure to support CWoW has, however, slowed during the COVID-19 pandemic ⁽³⁹⁾. Approval timelines have continued to improve during the COVID-19 pandemic, with unprecedented speed seen for both MHRA and HRA.

For costings, the National Directive on Commercial Contract Research Studies ⁽⁴⁰⁾ commits to harmonising the cost of commercial research, with the National Contract Value Review pilot established to develop a standardised and national approach to costing and contracting for commercial contract research. The process aimed to improve consistency and timelines for study set-up was paused, however, due to the COVID-19 pandemic ⁽⁴¹⁾.

With regard to innovative design, the Life Sciences Industrial Strategy and Sector Deals have committed to funding the research infrastructure to support delivery of a range of complex innovative design (CID) clinical trials, with a cross-sector consensus paper describing how the UK can effectively deliver these types of trials ⁽⁴²⁾. The NIHR, HRA and ECMC have also jointly developed tools and resources to help train and upskill RECs, researchers and the wider community on CID trials ^{(43, 44)}.

As well as innovative design, the COVID-19 pandemic has led to innovative approaches in trial delivery, including medicines and treatments being delivered direct to patients’ homes and remote approaches to patient consultations, patient consent and safety monitoring. With such approaches welcomed and supported by both regulators and sponsors, the question now remains as to whether these flexibilities will be adopted into business-as-usual.

During the COVID-19 pandemic, studies such as the Oxford RECOVERY platform trial tested a range of repurposed medicines as possible COVID-19 treatments in large patient numbers with a simple endpoint ⁽⁴⁵⁾. This demonstrated how innovative design and delivery approaches can support recruitment of large patient cohorts and quickly produce robust results to support healthcare delivery decision-making. Support for innovative design and delivery must also span across the full range of trials, including for more complex trials, needed to develop novel treatments.

In developing novel medicines, patient safety is paramount in early-phase trials, where tolerability is routinely explored initially in small patient numbers. Early efficacy studies usually examine a variety of measures and endpoints, again in fairly small numbers and with stringent safety monitoring. Only when there is confidence that the balance between efficacy and safety looks promising is the novel medicine tested in larger numbers, usually comparing several measures with the current standard of care. With the evolving ability to stratify patients into smaller specific sub-groups using biomarkers and through genomic analyses, more complex innovative design trials are needed to generate robust data on a variety of endpoints to support the trend towards precision and personalised medicines.

In the UK, we have the patients, the medical expertise and the research capability to conduct all types of trials and to lead innovation, but we need the system to support efficient set-up, recruitment and conduct of these trials.

Through support and investment, the NIHR, HRA, MHRA and other organisations which drive and facilitate clinical research, can deliver on rolling out the CWoW pilot further and developing their IT infrastructure, establishing a national costing review process, and supporting new ways of designing and delivering clinical trials.

b. Building a workforce fit for the future with opportunities for all to be involved in research

The successful set-up and delivery of research relies on research culture being embedded locally and nationally across the NHS, with supporting infrastructure, capacity and workforce.

To date, the life sciences sector and Government have highlighted the need to enhance the clinical research workforce, with proposals aimed at protecting time for researchers ⁽⁴⁶⁾, combating the clinical pharmacology skills shortages ⁽⁴⁷⁾ and upskilling clinical and non-clinical staff in research ⁽⁴⁸⁾. In addition to existing initiatives, transformative solutions are needed to ensure a successful recovery from the COVID-19 pandemic.

Industry welcomes the NHS People Plan ⁽⁴⁹⁾, published in July 2020, which highlights how the NHS workforce responded during the COVID-19 pandemic. In particular, NHS staff were able to provide an around-the-clock recruitment service, which patients directly benefited from, with enhanced opportunities to participate in research. The NHS People Plan commits to making the most of the skills across the workforce, including pharmacists, nurses and clinicians, ensuring educational and training programmes are available to support the development of their research skills and understanding.

To secure the step-change needed to build a workforce fit for the future and deliver on the commitments in the NHS People Plan, clinical research needs to be integrated in routine healthcare with opportunities provided for every healthcare professional to take part in research delivery. The Government’s Life Science Council’s Clinical Research Working Group and other cross-sector groups must continue to work together to provide the driving force needed for this transformative change.

c. Harnessing the UK’s health data to support the efficient design, feasibility, recruitment and conduct of the full range of clinical trials

Key aspects of enhancing the UK’s clinical research environment are data and digital capability. We must be collecting the right data needed to help answer research questions and help identify the right patients, across all disease areas. This data must also be discoverable and useable, in a well governed and safe environment, with fair value contracting frameworks for researcher access.

Industry recognises that the UK is taking important and positive steps to help digitise and link the UK’s health datasets to achieve this goal. One such example is the launch of NHS DigiTrials ⁽⁵⁰⁾, the Health Data Research Hub for clinical trials, developed to improve efficiency and effectiveness of clinical trials in the UK. During COVID-19, NHS DigiTrials has continued to support the identification of potential sites and patients and expanded its services to include outcome data, to help understand the dose response of a drug in development.

Communicating the impact and progress of such initiatives and articulating the UK clinical trials data offer, are also both important. The Government’s Life Science Council’s Clinical Research Working Group is developing a framework to support data custodians in articulating the data offer and services that they provide, to help global industry’s understanding and discoverability of UK assets.

As health data is collected from patients and members of the public, and in order for it to be used to support the development of new treatments, patients and members of the public must have trust and confidence that their personal information will be used only in the way that they choose, that it is securely protected when it is used, and that its use will be carefully governed. Industry is committed to working with Government and the wider research community to ensure that consistently high standards of governance are established and maintained, in order to generate and maintain the trust of patients, the public and other stakeholders, in the use of health data for research.

d. Driving continuing high standards for transparency

Clinical research conducted for the benefit of the public and patients globally, must be available, accessible and understandable. Over the past 10 years, there has been significant progress in registration and reporting of clinical trials, with many pharmaceutical companies leading the way and setting the standard for best practice ⁽⁵¹⁾.

The COVID-19 pandemic has highlighted the benefit of rapid and robust dissemination of research findings that are widely and easily accessible, such as the results from the RECOVERY trial, regarding dexamethasone and hydroxychloroquine, helping to inform clinical practice ⁽⁵²⁾. This should set the standard for how research in the UK is communicated, ensuring that a shift towards rapid dissemination does not jeopardise robust analysis or the process of peer review.

The UK is now taking strides towards a more open and transparent research environment, with the Government’s International Research and Innovation Strategy highlighting a commitment to greater openness in research ⁽⁵³⁾, and a review underway of UKRI’s open access policy ⁽⁵⁴⁾. The ABPI believes greater openness can support better collaborations between industry and academia, helping speed up the translation of promising discoveries into development in clinical trials.

The HRA also published its Make it Public strategy ⁽⁵⁵⁾, outlining how it is planned to make transparency straightforward and research findings more public. The ABPI and industry welcome this strategy, in particular the commitments around ensuring all clinical trials that take place in the UK are registered and supporting best practice through guidance, support and clear communication. At the end of the UK’s transition period, we must have mechanisms in place to support the registration and reporting of clinical trials for all research, both commercial and non-commercial, conducted in the UK.

e. Creating a regulatory environment which supports innovation in life sciences

The COVID-19 pandemic has highlighted that the UK can deliver clinical research at pace and at scale, with agile and flexible approaches ^{(21, 22)}. The pharmaceutical industry has welcomed this approach, in particular the streamlined approvals and guidance from UK regulators, MHRA and HRA ^{(24, 25)}. These approaches, coupled with the highest standards of patient safety in our regulatory and clinical research environment, are important factors for global pharmaceutical companies when considering investment in clinical research. The Medicines and Medical Devices Bill ⁽⁵⁶⁾ offers the opportunity for secondary legislation to drive changes that could help anchor more clinical research activity in the UK and bring further benefits and opportunities to the NHS and UK patients. Consultation with industry will be essential to identify which changes and flexibilities can have the maximum impact whilst maintaining the highest standards of patient safety. The Government’s R&D Roadmap acknowledges innovative regulation as a key area of opportunity and with other global regulators seeking to modernise regulations post-COVID-19, the UK should seize this short window of opportunity to build upon the UK’s reputation as a global thought leader in innovative regulation.

3. Ensuring that all patients have the opportunity to be involved and engaged with research

COVID-19 has had a significant impact on society, not least on health and medical research and healthcare systems. With the ambition to research and develop new treatments and vaccines for COVID-19, which work for all in society, there is a critical need to ensure patient and public involvement and engagement is embedded across the research environment.

Prior to the pandemic, much progress had been made in the UK and beyond to articulate the value of patient and public involvement and engagement, share best practice and equip the research community with tools and resources to support such activities, including but not limited to, the UK Standards for Public Involvement ⁽⁵⁷⁾, guidance on joint working for industry and charities ^{(58, 59)}, and the EU initiative, PARADIGM ⁽⁶⁰⁾.

In the early stages of the pandemic, a limited number of COVID-19 research applications to the HRA included patient and public involvement and engagement activities in their research plans. This has improved, with HRA providing a new service for those looking to conduct patient and public involvement and engagement activities for COVID-19 research; however, as the UK prepares for a potential second wave of the disease, it remains unclear how embedded the public voice is in planning and recovery.

Furthermore, with a growing body of evidence demonstrating the differential impact COVID-19 has on black, Asian and minority ethnic (BAME) people, it is essential that we support BAME communities in engaging and participating in COVID-19 research. The ABPI and industry welcome NIHR efforts to fund research into understanding the disproportionate impact on BAME communities ⁽⁶¹⁾; however, the life sciences sector and Government must work together to ensure system-wide diversity and inclusion of research participants and contributors.

The Government’s R&D Roadmap ⁽⁶²⁾ commits to levelling up R&D across the UK by lowering barriers to participation and supporting increased collaboration at a local level. This is an opportunity to maximise the opportunities for involvement and participation in research of new medicines and vaccines and deliver the greatest societal benefit for all patients and members of the public, across England and the devolved administrations.

4. Making research and innovation central to the UK’s trade strategy

The COVID-19 pandemic has demonstrated the benefit of collaboration and partnership in science, research and innovation, with academia, charity, industry and Government working together at pace, nationally and internationally, to develop new medicines and vaccines for COVID-19.

In particular, delivery of multi-site and multi-country clinical trials and the sharing of data have been of critical importance to the global COVID-19 R&D effort. As clinical trials are a key part of the global research ecosystem, not just for COVID-19, the UK should continue participating in international clinical trials.

As countries look to recover from COVID-19 and rebuild research environments, especially for other diseases, such as cancer and rare diseases, the UK should build on existing partnerships, growing its collaborative and competitive research base and scoping out opportunities with other leading research hubs, such as the USA and Asia.

Furthermore, to ensure that the UK retains its position as a global hub for life sciences, the movement of high-skilled people is vital. The UK’s intent to develop a new immigration system to allow for the best and brightest scientists from the EU and the rest of the world to travel to and work in the UK, is welcomed.