​Running an IPD project: from developing the protocol to preparing data for meta-analysis

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• Collecting, checking and managing IPD is more involved and complex than extracting or collecting existing aggregate data, but is fundamental for ensuring subsequent IPD meta-analyses are robust and comprehensive.

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• An IPD meta-analysis protocol should be registered or published, and include details about the:

- objectives

- inclusion and exclusion criteria (for trials and participants)

- main and additional outcomes to be evaluated

- particular participant-level covariates to be included or examined;

- processes for data transfer, collection, coding and checking;

- risk of bias assessments 

- statistical methods

• A separate comprehensive statistical analysis plan may also be necessary.

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• The project should aim to maximise the quantity of high quality IPD collected in order to limit bias and uncertainty of results, and to complete the planned analyses reliably.

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• Negotiating and maintaining collaboration with trial investigators can take considerable time and effort but is critical to the success of most IPD projects.

• IPD should be transferred and stored securely, and used carefully and appropriately, in order to respect participant confidentiality, whilst also adhering to the data use or other contractual agreements put in place with those providing their IPD.

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• Variables contained in the supplied IPD will often need to be re-coded, re-defined or derived in a format that is common to all trials, to enable subsequent meta-analysis of the IPD.

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• Data checking make take considerable time but is essential to help identify and rectify any major errors, inconsistencies or biases in the IPD, as well as promoting better understanding of individual trials.

• Data checking and scrutiny may also afford credibility, which may be particularly important for controversial or high-profile topics.

• A detailed log of all changes and transformations made to the IPD from each trial should be maintained, to enable transparency and reproducibility, and allow independent examination of the process used.

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• Assessment of risk of bias for each trial and its IPD is a continual process:

- initially it is based on information from trial publications or protocols

- supplemented by any information provided by the original trial investigator

- then refined or updated once IPD have been received, checked and cleaned.

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• Some risk of bias concerns may be alleviated by actually having the IPD (e.g. inclusion of participants originally excluded by the trial investigators); conversely, some risk of bias concerns may only become apparent from checking the IPD (e.g. noticeable baseline imbalance indicative of flawed randomisation).

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• Regular contact with the project advisory group is recommended, to provide an open forum for discussion of objectives, methods, clinical and practical issues; ultimately, all collaborators will have input into the interpretation and dissemination of results.

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• It can be helpful to incorporate patient and public involvement and engagement throughout the whole project, for example to provide input into the development of the research questions and the interpretation and dissemination of results.