Vascular disease meta analyses
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
Many medical questions about the efficacy and safety of specific treatments cannot be addressed by looking at the results of a single randomized trial, and instead depend on combining the results of many trials that have studied that question. The combination of data from many trials is achieved through the use of meta-analysis. Such meta-analyses are typically done by combining the summary results from each trial in order to achieve an overall summary of the effects of a treatment. Our group specialises, however, in obtaining detailed and complete data from each individual participant included in each of the relevant trials, and then analysing the resulting dataset (which is generally very large) to obtain more comprehensive analyses of how treatment efficacy and safety varies in different clinical circumstances.
We are now using this method to study the effects of: statin therapy on various conditions (such as muscle pain) that have been linked to treatment (but where the link is unproven); alteplase (a ‘clot-busting’ drug) after stroke; low-dose aspirin to prevent a first heart attack or stroke in apparently healthy people, and angiotensin-receptor blockers in Marfan Syndrome (a condition that causes the main artery leaving the heart to expand dangerously).
We are now using this method to study the effects of: statin therapy on various conditions (such as muscle pain) that have been linked to treatment (but where the link is unproven); alteplase (a ‘clot-busting’ drug) after stroke; low-dose aspirin to prevent a first heart attack or stroke in apparently healthy people, and angiotensin-receptor blockers in Marfan Syndrome (a condition that causes the main artery leaving the heart to expand dangerously).
Technical Summary
The aim of this programme of meta-analyses is to determine in detail, for a wide range of individuals, the benefits and risks of several of the most important drugs used for the treatment and prevention of cardiovascular disease. In each meta-analysis, after identifying randomized trials relevant to the particular question of interest, we set up a collaboration among the principal investigators and trial sponsors, and a secretariat in PHRU then coordinates the collection of individual participant data (IPD), data checking, analysis and publication. In each case, new trial evidence is incorporated as it is published, and new analyses are published as the data mature. This approach differs from most other meta-analyses of individual patient data in the subject area of cardiovascular disease, which are generally set up to answer a specific question and are not maintained long-term. Our approach allows us to maintain up-to-date summaries of present knowledge, to respond to requests for new analyses (eg, in response to safety concerns from regulatory authorities), and to influence the formulation of new trial proposals to address gaps or uncertainties in the evidence highlighted by our meta-analyses.
We generally limit our attention to topics for which IPD are likely to be available. Although this approach is very labour intensive, the advantages of achieving access to IPD are that they often provide a more accurate understanding of treatment effects and disease mechanisms. In particular, they allow assessment of the effects of a drug: (i) on particular outcomes (eg, distinguishing between atherosclerotic and non-atherosclerotic cardiac events, or vascular and non-vascular causes of death) defined similarly in each trial, where possible, or if not with a good understanding of how phenotyping of events differs between trials; (ii) on particular types of trial participants, and (iii) over time, which often allows the net effects of treatment to be understood in terms of benefits and hazards occurring on different timescales.
We are coordinating meta-analyses of randomized trials in 4 main areas: (1) the Cholesterol Treatment Trialists’ (CTT) Collaboration, which is undertaking an additional cycle of data collection in order to examine the effects of statin regimens on adverse events such as muscle pain, new-onset diabetes mellitus, haemorrhagic stroke, and other conditions that have been reported – in non-randomized studies – to be associated with statin therapy; (2) the Stroke Thrombolysis Trialists’ (STT) Collaboration, which is currently examining how the results of CT (or MR) scans taken prior to randomization to alteplase vs placebo (or open control) influence functional outcomes; (3) the Antithrombotic Treatment Trialists’ (ATT) Collaboration, which is conducting an updated meta-analysis of data from trials of aspirin vs placebo (or open control) for the primary prevention of cardiovascular disease; and (4) the Marfan Treatment Trialists’ (MTT) Collaboration, which is examining the effects of angiotensin receptor blockers on aortic root size within 10 randomized trials.
We generally limit our attention to topics for which IPD are likely to be available. Although this approach is very labour intensive, the advantages of achieving access to IPD are that they often provide a more accurate understanding of treatment effects and disease mechanisms. In particular, they allow assessment of the effects of a drug: (i) on particular outcomes (eg, distinguishing between atherosclerotic and non-atherosclerotic cardiac events, or vascular and non-vascular causes of death) defined similarly in each trial, where possible, or if not with a good understanding of how phenotyping of events differs between trials; (ii) on particular types of trial participants, and (iii) over time, which often allows the net effects of treatment to be understood in terms of benefits and hazards occurring on different timescales.
We are coordinating meta-analyses of randomized trials in 4 main areas: (1) the Cholesterol Treatment Trialists’ (CTT) Collaboration, which is undertaking an additional cycle of data collection in order to examine the effects of statin regimens on adverse events such as muscle pain, new-onset diabetes mellitus, haemorrhagic stroke, and other conditions that have been reported – in non-randomized studies – to be associated with statin therapy; (2) the Stroke Thrombolysis Trialists’ (STT) Collaboration, which is currently examining how the results of CT (or MR) scans taken prior to randomization to alteplase vs placebo (or open control) influence functional outcomes; (3) the Antithrombotic Treatment Trialists’ (ATT) Collaboration, which is conducting an updated meta-analysis of data from trials of aspirin vs placebo (or open control) for the primary prevention of cardiovascular disease; and (4) the Marfan Treatment Trialists’ (MTT) Collaboration, which is examining the effects of angiotensin receptor blockers on aortic root size within 10 randomized trials.
Organisations
People |
ORCID iD |
Colin Baigent (Principal Investigator) |
Publications
Staplin N
(2021)
Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.
in EClinicalMedicine
Patrono C
(2019)
Role of aspirin in primary prevention of cardiovascular disease.
in Nature reviews. Cardiology
Baigent C
(2019)
Variability in aspirin efficacy: all in the genes?
in European heart journal
Mafham M
(2021)
What is the association of COVID-19 with heart attacks and strokes?
in Lancet (London, England)
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_00017/1 | 01/04/2019 | 31/03/2024 | £5,782,000 | ||
MC_UU_00017/2 | Transfer | MC_UU_00017/1 | 01/04/2019 | 31/03/2024 | £2,644,000 |
MC_UU_00017/3 | Transfer | MC_UU_00017/2 | 01/04/2019 | 31/03/2024 | £3,269,000 |
MC_UU_00017/4 | Transfer | MC_UU_00017/3 | 01/04/2019 | 31/03/2024 | £1,831,000 |
MC_UU_00017/5 | Transfer | MC_UU_00017/4 | 01/04/2019 | 31/03/2024 | £2,183,000 |
Description | CTT muscle NICE |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | CTT muscle results |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | VOG team support to RECOVERY Trial |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | VOG team provides ongoing expertise in doing systematic reviews to RECOVERY team, enabling publishing of RECOVERY research findings re acute treatments for Covid-19 in context. |
Description | Announcement of CTT muscle results at ESC |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A series of interviews undertaken by members of the CTT following the publication of the effectsof muscle pain from statins |
Year(s) Of Engagement Activity | 2022 |
Description | Faculty of Pharmaceutical Medicine Curriculum and Assessment Working Group |
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 | Member of Faculty of Pharmaceutical Medicine Curriculum and Assessment Working Group |
Year(s) Of Engagement Activity | 2019 |
Description | IF Science Oxford |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | The group undertook public engagement activities at the IF Oxford Science Festival |
Year(s) Of Engagement Activity | 2019 |
Description | IF-Oxford 2022 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | 15-16 October 2022 IF-Oxford (Ideas Festival), Science @ the Shops, Templars Square Shopping Centre, Oxford. Organising institution: IF Oxford which is produced by charity Oxfordshire Science Festival (Attended by VOG team members: Heather Halls and Lisa Holland). • Programme introduction: "Help me stay well. Your arteries are amazing. They carry blood loaded with oxygen around your body, but when they become narrowed or blocked, things can go seriously wrong. Find out how to keep your arteries clear and your blood flowing, to protect your heart and brain, with interactive games (Saturday and Sunday). Oxford Population Health, University of Oxford." • The aim of this activity was to provide a lay audience with information about statins, to enable them to understand the risks and benefits of these drugs, learn how to be critical about what they read, determine what is a strong study, and trust and understand the results about statin adverse effects. It was produced in conjunction with the publication of the CTT muscle paper. It was aimed largely at adults, who are more likely to be prescribed statins than children, and older children who will be learning about statins as part of the GCSE Combined Science and GCSE Biology curricula. • 4 activities: o a) 'Don't lose your balls': a team-based game where teams are given 3 possible answers to a question and then have to 'hedge their bets', dividing 10 tennis balls between buckets representing the answers they think are correct. Balls placed in the 'incorrect' buckets are lost, and the winner is the team with the most balls left at the end. o b) 'Make me healthy': the aim was to remove all the 'bad' cholesterol from a life-sized cardboard human body illustrated with major arteries and organs, by correctly answering age-appropriate questions about healthy living. o c) An interactive poster with flaps illustrating the progression from early-phase trials through to meta-analyses, to illustrate the power of large-scale trials and meta-analyses. This also revealed a message as the flaps were being opened, saying 'Statins Are Safe and Work', which could only be read when all the flaps had been opened. o d) Statin muscle video which was scrolling through on a table for less outgoing people to engage in. • An information leaflet was also produced for the public to take away and read at their leisure, and Sophia Wilkinson apparently wrote up an evaluation report for this activity which engaged ~165 people. Data Game activity: Lisa Holland and Heather Halls met with Hannah Freeman to pass on the Data game activity which she is now responsible for developing for teacher use. |
Year(s) Of Engagement Activity | 2022 |
Description | NDPH Participant Panel |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | NDPH Participant Panel CTT overview; 2 hours; 2021-01-29 |
Year(s) Of Engagement Activity | 2020 |
Description | NDPH Participant Panel |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Updated the NDPH Public Advisory Panel (formerly Participany Panel) about the status and progress of meta analyses |
Year(s) Of Engagement Activity | 2019 |
Description | Oxford Open Doors 2019 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Took part in the 2019 Oxford Open Doors public engagement event on Saturday 14 September |
Year(s) Of Engagement Activity | 2019 |
Description | Science Week - Bladon Primary School |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Presentation and engagement around planning experiments during Oxford Science Week |
Year(s) Of Engagement Activity | 2019 |
Description | Science Week - Freeland Primary School |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Used data games to engage with primary school during Oxford Science Week |
Year(s) Of Engagement Activity | 2019 |
Description | Science Week 2020 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | The Science Week; several VOG Research Associates visited to Pegasus School, Blackbird Leys Oxford data game with nearly 150 children; opportunity to enhance the National Curriculum learning objective; 1 day; 2020-03-09 |
Year(s) Of Engagement Activity | 2020 |