Rationale and planning 

  • IPD meta-analysis offers many potential advantages compared to a conventional meta-analysis of aggregate data.

  • However, IPD meta-analysis projects are a considerable undertaking and so should not be embarked upon lightly.

  • In particular, researchers should take time to:

- understand the rationale for using IPD to answer their research question

- carefully plan the IPD project and the steps involved for its initiation

Rationale for undertaking an IPD meta-analysis projects

  • Compared to using published aggregate data, IPD projects can provide substantial improvements in the extent and quality of data available.

  • They can give greater scope and flexibility in the analyses, for example

- to adjust for prognostic factors

- to examine participant-level associations 

- to examine more complex relationships (e.g. non-proportional hazards, correlated outcomes, multiple time-points, non-linear treatment-covariate interactions, etc ) 

- to examine prognostic factors

- to develop and validate clinical prediction models

  • Important differences can occur between IPD and aggregate data meta-analysis results.

  • But this depends on many aspects including:

- the availability of IPD

- whether IPD leads to improvements in the quality and quantity of data

- how analysis methods planned by the IPD researchers compare with those done by original trial investigators.

  • Given the additional resource requirements, it is important to consider carefully whether an IPD project is needed instead of a conventional systematic review using aggregate data.

  • The decision will depend on the particular research question, and whether IPD would produce a more reliable and comprehensive answer than using the aggregate data already available for eligible trials.

  • Generally, the more nuanced or complex the research question, and the more the focus is on the participant-level (e.g. treatment-covariate interactions, developing risk prediction models, etc), then the more important the IPD approach will be. 

  • It is useful to first undertake a review to identify existing studies and whether they report suitable aggregate data to answer the research question of interest. Where focus is on overall treatment effects, published aggregate data may suffice; however, when going beyond the overall effect, IPD meta-analysis projects are usually required.

  • Even when IPD meta-analysis projects are needed, the available IPD needs to be of sufficient quality, record the required participant-level characteristics and outcomes of interest, and have reasonable statistical power to address the research question(s) reliably.

  • Therefore, careful planning and preparatory work is needed, to ensure it is achievable.

 

Planning & initiating IPD meta-analysis projects

  • IPD meta-analyses are major research projects that typically take upwards of two years to complete.

  • Specific research funding is usually required, and they cannot be done on a volunteer basis or in spare time.

 

  • They require broader skills than conventional systematic reviews and meta-analyses of aggregate data, including greater statistical expertise and experience in managing participant-level data.

  • Many IPD meta-analysis projects are collaborative, involving partnership with trial investigators who contribute IPD from their trials for re-analysis and whose role is acknowledged through membership of a collaborative group and authorship arrangements.

  • An advisory group may be set up to include wider clinical, topic or methodological expertise and to facilitate patient and public involvement.

  • Obtaining IPD from repositories or data-sharing platforms is emerging as a possible alternative or complement to collaboration with trial investigators.

  • Initiating an IPD meta-analysis requires careful planning and detailed preparation.

  • A clear overview of the entire project is needed at the outset, to give the best chance of success.

 

  • Set-up tasks can include developing a project scope, establishing the central research team and advisory group, seeking in principle agreement to collaborate from trial investigators and/or identifying other sources of IPD, developing data-sharing agreements, applying for research funding, and for ethical approval or exemption. 

  • Careful specification of proposed inclusion and exclusion criteria in terms of the PICOS (Population, Intervention, Comparator, Outcomes, Study design) framework at the outset, and reference to them throughout the IPD meta-analysis project, should ensure that the final results are clinically relevant and applicable as intended

  • A competent central research team should include members with experience of successfully completing an IPD meta-analysis project, advanced statistical knowledge, experience in managing and coding IPD, and strong communication skills.

  • The team should be as independent as possible and should not include members with a vested interest or strongly held views on the particular topic under investigation, such as whether a particular intervention is or is not effective.

  • Prospective IPD meta-analysis projects need detailed and specialist planning.