Trials Methodology Research Partnership

Lead Research Organisation: University of Liverpool
Department Name: Biostatistics

Abstract

Clinical trials are vital for testing whether a new treatment provides benefit to patients. There are tens of thousands of new clinical trials started each year, funded by both public and private sector. Trials are very expensive, both in terms of money but also burden on patient and healthcare systems. It is therefore important that clinical trials are done as efficiently as possible.

In the UK and Ireland there are several different groups of researchers who work on clinical trials. These groups have substantial expertise in particular areas of how to do more efficient and informative trials. This grant has the objective of bringing these researchers together as the Trials Methodology Research Partnership. This new partnership will focus on major areas where clinical trials need to be improved to help increase the health of society.

The partnership will consist of an executive committee that will oversee eight working groups. These groups will each tackle a major area for improving trials. Each working group will consist of experts across the UK who will identify what new work is needed in the area, and how to ensure the best methods can be used in real clinical trials. The working groups will put together new funding proposals for focused projects.

The groups making up the partnership have each committed funding for a research student who will work on a PhD in clinical trials methodology. These students will contribute towards the goals of the partnership.

This grant will provide funding to establish and coordinate the partnership and its working groups. It will also provide funding for three smaller research projects, which are linked with major priorities of the partnership.

The first focus is stratified medicine. This is about improving knowledge about which patients a new treatment works well for, allowing them to receive the best treatment for them. The typical way of doing clinical trials may not be suitable when a treatment works differently in different types of patient. A pilot project to be funded by this partnership will review what future trials research is needed to help stratify patients better. This pilot project will lead to a larger project for which a separate grant application will be made.

The second focus is health informatics. This is the use of new digital technology to improve trials. Health informatics has a huge potential to reduce the cost of and increase the amount of information available from trials. Linked with the first focus, more high-quality information may lead to better stratification of patients. The Health Informatics working group will hold a workshop to bring together expertise in this area. This will lead to identification of methodological issues that can be tested within future trials that make use of digital technology.

The third focus is global health trials. Many diseases are becoming more frequent in Low and Medium Income Countries (LMICs). Clinical trials conducted solely in LMICs are common but are often difficult to do. The global health working group will develop research projects to address these difficulties. It will help deliver this by making small grants available to encourage international cooperation between LMIC researchers and those based in UK and Ireland.

The partnership will also help support successful initiatives that have benefited UK trials methodology research such as the COMET Initiative, the International Clinical Trials Methodology Conference and the online guidance packs for best trial practice.

The partnership will support the development of further specific project grants. This will develop a new sustainable portfolio of trials research that will ensure the UK and Ireland is at the forefront of trials methodology research. The resulting research will make trials more efficient and improve healthcare worldwide.

Technical Summary

Clinical trials provide the highest quality of information about new health interventions. They require large financial, patient and healthcare system resources to be successful. It is a priority for medical research that methodology for increasing the efficiency of clinical trials is developed.

In this Trials Methodology Research Partnership we propose to bring together several networks and institutions that have strong expertise in particular areas of trials research. The partnership will consist of an executive committee that will oversee eight working groups, each working in a distinct priority area for trials. Funding will be used to coordinate the partnership and its working groups. The partnership will also provide funding for several smaller research projects, which are linked with three priority areas for future trials research: stratified medicine, health informatics and global health.

The initial projects are: 1) a review of methodology gaps for which future trials research is needed to help stratify patients better; 2) collation of ongoing studies followed by a workshop to bring together expertise in health informatics; a prioritization exercise to design Studies Within A Trial (SWATs) that could be embedded within future trials to build an evidence base for best use of digital technology in trials; 3) a pump-priming funding stream to enable international collaboration between researchers from resource-poor countries and those based in UK and Ireland, to encourage methodology research for global health trials.

The partnership will also create a national cohort of PhD students who will work on clinical trials methodology, and continue support for successful initiatives such as the International Clinical Trials Methodology Conference and online guidance packs for best trial practice.

The initial investment in this Partnership will lead to future proposals for larger, focused research projects that will make future trials more efficient.

Planned Impact

Who will benefit from this research?

The cross-disciplinary nature of the Partnership's research portfolio and networks will ensure that a wide range of users will benefit from this research, including clinical trial practitioners, systematic reviewers, patients and the public, regulators, research funders, journal editors, policymakers, and methodologists.

How will they benefit from this research?

The Trials Methodology Research Partnership (TMRP) will facilitate the advancement of clinical trials methodology which will lead to improvements in, and increased efficiency of, clinical trials, leading to improvements in health care. Direct and indirect impacts for users include:
(1) Clinical trial practitioners: Our research will generate new knowledge and innovative methodologies which will be deliberately developed to be of relevance to clinical trial practitioners who will also benefit from our related training activities. Through our PhD student cohort, the TMRP will deliver highly skilled researchers in priority areas such as health informatics, medical statistics and health economics, who will directly benefit clinical trial practitioners through the TMRP advisory service, and by developing this workforce for future clinical trials. This area of activity will be facilitated and enhanced by our TMRP Clinical Engagement Lead.
(2) Systematic reviewers: The TMRP research and training programme that focusses on improving the conduct, analysis and reporting of clinical trials has the potential to directly improve the systematic review process (e.g. disseminating recommendations on outcome reporting to clinical trialists will reduce the important problem of outcome reporting bias in systematic reviews). Our research will also contribute to recommendations about how best to use systematic reviews to inform clinical trial design and conduct through, for example, opportunities afforded by HRB TMRN's recent award for capacity development in evidence synthesis.
(3) Patients and the public: We aim to generate research that will directly impact upon participants of clinical trials, as well as the wider patient groups for which those trial results apply. Use of innovative, more appropriate, evidence-based methods in clinical trials will lead to trial results that are more applicable (e.g. using outcomes that are relevant to patients), which will improve clinical decisions and impact on patients' quality of life, health and well-being.
(4) Research Funders: MRC- and HRB-funded partners have already achieved some impact with trial funders. TMRP will allow shared knowledge of what works in stakeholder engagement to achieve direct impact. TMRP will engage with the international effort to improve efficiency of clinical trials and reducing 'research waste', targeting global funders with NIHR's help.
(5) Journal editors: Activities within TMRP that focus on research to improve the reporting of clinical trials will be of direct benefit to journal editors. Partners are involved with international groups such as the EQUATOR Network and CONSORT, and these links will be exploited to aid dissemination.
(6) Policymakers: Through COMET we are learning how to engage with influential policymakers such as PCORI (USA), NICE (UK), and the Guidelines International Network.
(7) Methodologists: We will develop and apply new and innovative clinical trial methodologies which will directly benefit other clinical trial methodology researchers and aid future advancement of methodological research. Our training courses will allow methodologists to gain knowledge in cross-disciplinary clinical trials research methods.
(8) Regulators: Strategic connections with the regulatory authorities will be developed as appropriate to an initiative or project. Examples to date are the work with the FDA through the Clinical Trials Transformation Initiative, MHRA in the development of a risk-based monitoring tool, and EMA regarding core outcome sets.

Publications

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