Methodological innovation in large-scale epidemiology

Lead Research Organisation: University of Oxford

Abstract

Advances in medical research and improvements in public health depend on being able to produce reliable studies. The emerging field of so-called ‘Big Data’ offers the potential for changes in the scale and efficiency of those studies. We are now entering an exciting time when new technical developments in the way that we can handle very large datasets are set to transform the way we study health in populations of people.
We aim to maximise the potential of these new methods through a programme of work that expands our existing expertise in recruiting large numbers of people, making measurements of their health and then following them for many years. This programme will be coordinated from the new Big Data Institute at Oxford University, which will provide tremendous opportunities for collaboration with other scientists who are expert in the study of genetics, images (eg CT scans), computers and statistics.

We are also working to improve the regulation of health research to try to remove some of the bureaucratic delays that are currently preventing efficient research. By doing so, we believe that researchers will be able to address a much wider range of important health-related questions more rapidly and cost-effectively, which will benefit the treatment of patients and public health more generally.

Technical Summary

Advances in biomedical and healthcare data science offer the potential of dramatic changes in the scale (size, breadth, depth and duration) and efficiency (data accumulation, storage, processing and dissemination) of clinical trials and observational studies. However, in order to maximise the scientific and public health returns from these new opportunities, it will be important to design systems and approaches that are focused on the key drivers of study quality and essential to ensure that their appropriate use is unencumbered by disproportionate regulatory or bureaucratic obstacles.

Our programme comprises three, overlapping elements:

Streamlining the design, conduct and analysis of population-based studies:
We are developing and evaluating new methods for efficient recruitment (including use of routine clinical data), data collection (e.g. electronic case report forms, scalable approaches to assessment of cognitive function and physical activity), trial management (e.g. to maximise adherence to treatment, completeness of follow-up), quality assurance and trial oversight (including central statistical monitoring and rational pharmacovigilance), adjudication and clinical phenotyping (including theoretical and empirical research on the impact of different approaches on study results), data analysis (e.g. modular tools, test suites, ontological tools, and use of CDISC standards), and data sharing (e.g. clinical trial adverse events, controlled approaches for observational studies).

Big Data for Population Health Research:
This work centres on the collection, analysis and interpretation of population scale biomedical data. In conjunction with the University of Oxford Big Data Institute (www.bdi.ox.ac.uk) and using the streamlined approaches to building and managing large cohorts outlined above, this work focuses on new approaches to the measurement of health and disease. Examples include the use of genomics and immune profiling, imaging (e.g. morphology, digital pathology, radiology), mobile sensors and cameras (e.g. to assess activity and behavioural factors), and patient-oriented applications (e.g. to assess cognitive function, mood, quality of life, diet). Where appropriate, machine learning and other novel statistical approaches are used to analyse these complex, heterogeneous datasets and draw inferences about the causes and consequences, prevention and treatment of disease.

Proportionate regulation of large-scale clinical trials and observational studies:
This work seeks to promote the development and adoption of regulatory approaches that facilitate high quality clinical research. This work is founded on the key principles of protecting the rights, safety and well-being of study participants and ensuring the reliability of the study results (which influence the clinical care of future patients). For example, most clinical trial regulations and guidelines were written many years before the widespread use of information technology and the internet, and are no longer fit for purpose. We work with regulators, industry, academia and patient advocates to identify issues, develop recommendations, make the case for change, and encourage the adoption of more appropriate regulatory approaches in areas such as clinical trials, access to clinical data, and sharing of research data.
 
Description International Committee of Medical Journal editors (ICJME) consultation on guidelines for the re-analysis of randomised trials
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
 
Description International Council on Harmonisation (ICH) consultation E17 draft guideline "Multi-Regional Clinical Trials"
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
 
Description MRC HTMR Response to Consultation on National Standards for Public Involvement in Research developed by NIHR/INVOLVE
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description UKCRC Network Response to Framework for Health and Social Care Research Consultation
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description UKCRC Patient and Public Involvement and Engagement Survey
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description Capital Award
Amount £800,000 (GBP)
Organisation Health Data Research UK 
Start  
 
Description Centre for Research Excellence
Amount £6,000,000 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Digital Innovation Hub Sprint Exemplar
Amount £300,000 (GBP)
Organisation Health Data Research UK 
Start  
 
Description EMPA-KIDNEY trial
Amount £78,800,000 (GBP)
Organisation Boehringer Ingelheim 
Sector Private
Country Germany
Start  
 
Description NIHR Oxford Biomedical Research Centre
Amount £4,000,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2017 
 
Description ORION-4
Amount £52,000,000 (GBP)
Organisation The Medicines Company 
Sector Private
Country Global
Start 12/2017 
 
Description ORION-4 trial
Amount £51,600,000 (GBP)
Organisation The Medicines Company 
Sector Private
Country Global
Start  
 
Description Oxford Substantive Site
Amount £3,800,000 (GBP)
Organisation Health Data Research UK 
Start  
 
Description Population Health Research Unit: Big Data & Computing Innovation
Amount £2,200,000 (GBP)
Funding ID MC_UU_00017/5 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description Trials Methodology Research Partnership
Amount £400,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description MoreTrials Campaign 
Organisation James Lind Alliance
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution PHRU set up and leads this campaign in partnership with the charity, Sense About Science, London. The aim is to remove regulatory and other barriers to the conduct of high-quality randomised trials. Currently, more than 200 trialists from 30 countries along with 12 research organisations have signed up to support the campaign.
Collaborator Contribution Collaborations are helping to promote the campaign and helping to write new guidelines for the conduct of high-quality randomised trials.
Impact For the first time, ICH has engaged with academic trialists and acknowledged the need to involve key outside stakeholders in future guideline development. The recent update to ICH (E6) GCP included the proposals for improvement recommended by the MoreTrials collaboration.
Start Year 2015
 
Description MoreTrials Campaign 
Organisation Sense about Science
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution PHRU set up and leads this campaign in partnership with the charity, Sense About Science, London. The aim is to remove regulatory and other barriers to the conduct of high-quality randomised trials. Currently, more than 200 trialists from 30 countries along with 12 research organisations have signed up to support the campaign.
Collaborator Contribution Collaborations are helping to promote the campaign and helping to write new guidelines for the conduct of high-quality randomised trials.
Impact For the first time, ICH has engaged with academic trialists and acknowledged the need to involve key outside stakeholders in future guideline development. The recent update to ICH (E6) GCP included the proposals for improvement recommended by the MoreTrials collaboration.
Start Year 2015
 
Description NHS Digital Research Advisory Group 
Organisation National Health Service
PI Contribution Accessed NHS data for research
Collaborator Contribution data provision
Impact n/a
Start Year 2016
 
Description CTSU Participant Panel Meetings 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact NDPH (Nuffield Department of Population Health) Participant Panel was established in 2013 to involve trial participants (who live locally) in the design, running and dissemination of our studies as well as providing a forum to develop new research ideas.

None.
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017
 
Description Clinical Trial Operation Strategy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact In June 2017, facilitated a group debate on risk-based monitoring to clinical trial directors and project managers
Year(s) Of Engagement Activity 2017
 
Description Designing and running streamlined randomized trials 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact In January 2018, ran an awareness presentation on talk approaches to risk-based monitoring methods
Year(s) Of Engagement Activity 2018
 
Description Engaging Tricky Research Sites 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact In May and September 2017 delivered presentations and workshops to UK trial managers to improve knowledge of trial coordination methodology. The result was an increased awareness of site selection and retention methods
Year(s) Of Engagement Activity 2017
 
Description Invited workshop participant, Cancer Research UK / School of International Futures "Future of Clinical Trials after Brexit" report 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited workshop participant, Cancer Research UK / School of International Futures "Future of Clinical Trials after Brexit" report
Year(s) Of Engagement Activity 2018
 
Description Office for Life Sciences 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Life Sciences Strategy Workshop, Office for Life Sciences (Dept for Health/BEIS)
Year(s) Of Engagement Activity 2017
 
Description Organizing committee, NIHR HTA / CPRD / HDR UK Frontiers Meeting: Digitally-enabled randomized clinical trials 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Organizing committee, NIHR HTA / CPRD / HDR UK Frontiers Meeting: Digitally-enabled randomized clinical trials
Year(s) Of Engagement Activity 2018
 
Description St Hugh's School visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact School visit, (year 8) St Hugh's School, Oxfordshire. June 2018.
Year(s) Of Engagement Activity 2018
 
Description When trials go global 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact In November 2017, presented 'methods of efficiency when running trials with international papers' to clinical trial managers, project managers and monitors to increase knowledge of streamlining by using Quality by Design principles.
Year(s) Of Engagement Activity 2017