Evaluating, adapting and extending individual patient data (IPD) methods of evidence synthesis

Lead Research Organisation: University of York
Department Name: Centre for Reviews and Dissemination

Abstract

Health and healthcare decisions should be informed by robust research evidence of the highest possible standard.

To reach reliable conclusions about the benefits and risks of a particular treatment, it is important to consider results from all relevant clinical trials and to use objective and transparent methods to summarise findings across trials. This is called systematic review. Systematic reviews that collect and re-analyse original ?raw? research data are called IPD (individual patient data) meta-analyses, and are considered to be a gold standard approach. These projects allow more detailed analysis than can be done in systematic reviews that rely on summary data extracted from published trial reports.

The methods used in IPD meta-analysis were developed around projects in cancer and heart disease and usually involve relatively straightforward methods of analysing and combining data. As IPD meta-analyses become used in new clinical areas, and as we need more sophisticated evaluation to guide complex decisions, we need to evaluate, extend and adapt these methods.

We will use (anonymous) data from 32,217 pregnant women enrolled in 31 randomised trials (that we previously collected in an international project exploring whether antiplatelet agents such as aspirin can prevent pre-eclampsia) to explore how we can improve the methods that researchers use in future. We will explore and develop both practical and statistical methods. These will relate to:

(1) issues specific to data from pregnancy and childbirth (e.g. how to best analyse data from twin or other multiple pregnancies)
(2) issues that are general to IPD meta-analysis (e.g. most appropriate statistical approaches to analysis, including how best to find out whether particular types of people do particularly well or badly from a treatment, and how to deal with situations where trials have data missing)
(3) issues relating all types of systematic review (e.g. trying to find out why the first trials of antiplatelet agents for prevention of pre-eclampsia reported the most beneficial results)

We will also try to find out which aspects of analysis are likely to change the findings of a systematic review and which are unlikely to change findings, so that we know where to focus efforts if time and resource are limited.

Findings of this project will be published and shared with the Cochrane Collaboration methods groups feeding into the guidance and advice provided by them. Ultimately, findings should help ensure that healthcare decisions are underpinned by the most reliable evidence synthesis methods.

Technical Summary

Evidence synthesis underpinning health and healthcare decisions should be robust and of the highest possible standard. Individual patient data (IPD) meta-analyses which centrally collect, check, re-analyse and pool the original ?raw? data from relevant studies, are considered to be a gold standard of systematic review. Current approaches to IPD meta-analyses are largely those developed in cancer and cardiovascular disease and usually involve relatively straightforward methods of synthesis. As the IPD approach moves to new areas of healthcare, and we require more sophisticated evaluation to guide complex decisions, there is a need to evaluate, extend and adapt the methodology of IPD meta-analysis.

We will utilise previously collected data from 32,217 pregnant women enrolled in 31 randomised trials of pre-eclampsia primary prevention, to explore and develop the methods used in both IPD and aggregate data systematic reviews. We will explore and develop both practical and statistical methods relating to:

? issues specific to synthesis of data from pregnancy and childbirth research (linkage between mothers and babies and dealing with multiple pregnancies)
? issues that are generally applicable to the conduct of IPD meta-analysis (one or two stage analysis, fixed or random effects, subgroup or modelling based approach to exploring potential effect modifiers/treatment interactions, dealing with sparse and missing data)
? issues relating to all types of systematic review (selective reporting of outcomes, the utility of meta-regression).

Distinguishing between aspects of analysis that materially alter the results of systematic review from those that, whilst theoretically/ statistically valid, are unlikely to impact importantly on results, may also guide where best to focus efforts where time and resource are limited.

In addition to journal publications and conference presentations, findings will be shared with the Cochrane Collaboration IPD Meta-analysis Methods Group and Statistical Methods Group and will feed into the guidance and advice provided by these groups.

Given the likely increased need for, and potential of IPD meta-analysis to influence practice and future research, the proposed work could have far-reaching impact. Ultimately, findings should help to ensure that healthcare decisions are underpinned by the most reliable evidence synthesis methods.

Publications

10 25 50
 
Description Future of IPD meta-analysis within Cochrane: Asked to Chair and establish a working group reporting on future challenges and benefits of increasing IPD meta-analyses to inform Cochrane Content Strategy
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Evaluating progestogen for prevention of preterm birth (EPPPIC): an individual participant data meta-analysis.
Amount $419,696 (USD)
Funding ID PA-1608-5707 
Organisation Patient-Centered Outcomes Research Institute 
Sector Charity/Non Profit
Country United States
Start 03/2017 
End 09/2018
 
Description NIHR HTA: Intensive behavioural interventions based on applied behaviour analysis on young children with autism: systematic review and value of information analysis
Amount £250,024 (GBP)
Funding ID HTA/16/104/15 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2017 
End 12/2018
 
Description NIHR NETSCC Cochrane Programme Grants: Systematic Reviews Programme Grant: Progesterone for preterm birth prevention: how to establish a Cochrane-affiliated individual patient data (IPD) repository
Amount £9,133 (GBP)
Funding ID 16/114/35 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 12/2017 
End 11/2019
 
Description Systematic Review and Meta-Analysis of the Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2).
Amount $307,875 (USD)
Organisation Yale University 
Sector Academic/University
Country United States
Start 09/2012 
End 09/2013
 
Title PRISMA-IPD checklist 
Description Reporting guideline and checklist to improve the reporting of individual participant data (IPD) meta-analyses 
Type Of Material Improvements to research infrastructure 
Year Produced 2015 
Provided To Others? Yes  
Impact Being used by those reporting IPD meta-analyses. Published in JAMA (145 citations, altmetric score 154) and available on the PRISMA website. 
URL http://www.prisma-statement.org/Extensions/IndividualPatientData.aspx