to make their data available for meta‐analysis. Also, whilst collection of IPD may be at the top of the IPD meta‐analysis research team's agenda, it will not necessarily be a priority for the trial investigators, so perseverance, patience, tact and diplomacy must all be brought to bear.
Invitations to participate may need to be issued several times before receiving a reply. If no response is forthcoming from the first or corresponding author of the trial publication, it is worth seeking contact with other authors, or the data centre that hosts the trial (e.g. a trials unit or cooperative group) to trace an appropriate trial contact, particularly for older trials. In this context, careful logs of contact and the status of agreements should be maintained, especially if many studies are eligible for inclusion in the IPD meta‐analysis project.
An initial correspondence can help prime trial investigators, letting them know at an early stage about the IPD project, and inviting their in principle support and agreement to collaborate. This may even take place during the planning phase, to provide an early opportunity to assess the feasibility of the approach (Section 3.4), to support a funding application (Section 3.9), or to inform a power calculation (Chapter 12). As the project moves forward, these early contacts can be repeated, particularly if some time has elapsed between initial contact, the award of funding and project start‐up. Correspondence may be via a simple email or letter describing the nature of the collaboration they are being invited to join, with or without a project scope that outlines the project objectives and high‐level methods (Section 3.3). This is a good time to seek key design features from trial investigators (Section 4.2.4), and thereby clarify understanding of each trial, and if need be, verify eligibility.
Subsequently, a more formal invitation to collaborate is usually accompanied by a draft protocol (Section 4.2.2), which may also include information on timelines, any funds available, the dissemination strategy and authorship policy for subsequent papers. Also, it can be useful to supply trial investigators with a provisional list of the variables required, or to provide them with the detailed data dictionary (Section 4.2.7), so that they might check which data items they will be able to share. If it transpires that certain key variables of interest (e.g. those that are hypothesised to modify treatment effect) have been collected in very few trials, then it may be necessary to document this and discuss how it impacts upon the IPD meta‐analysis protocol and statistical analysis plan. The availability of data may even influence the decision to proceed with the project (e.g. if the potential power is considered very low; Chapter 12), or at least highlight whether the meta‐analysis results will likely be better suited to informing the rationale and design of a new trial rather than influencing clinical practice.
At this stage, it may be worth giving trial investigators the opportunity to provide feedback on the draft protocol, and flag any important issues that may need further exploration and development in a subsequent version. This process also serves to emphasise to trial investigators that they are active members of the collaborative group, rather than being just passive providers of IPD, which may be important in securing their agreement to share data. That said, and as noted in Section 3.2.1, it is important that the central research team remain as independent and autonomous as possible, retaining the responsibility for deciding which methods and analytic approaches are appropriate to the project. Feedback on the protocol should also be sought from the project advisory group, including any patients or public representatives, which requires that a good lay summary of the project is available, and that additional explanatory material is provided, as required.
A data‐sharing agreement outlining the nature of the collaboration, the responsibilities and obligations of each party, and intellectual property arrangements (Section 3.11) will usually be supplied with the finalised protocol. Normally this should be signed by both data provider and recipient before any trial IPD can be transferred. It is also useful to include a data transfer guide (Section 4.4.2), outlining the steps that should be taken to protect participant confidentiality and transfer data securely, as well as the detailed data dictionary, which describes the preferred format and coding for the IPD meta‐analysis project (Section 4.2.7).
Usually, further communication back and forth between the IPD meta‐analysis research team and trial personnel is required, to ensure appropriate understanding of the supplied IPD, and to resolve any queries arising from data harmonisation, checking (Section 4.5) or risk of bias assessment (Section 4.6). As the project will take place over a prolonged period, it is also good practice to give trial investigators regular updates on progress, for example, letting them know how many groups have agreed to collaborate, the status of data collection, and any deviations from the project timetable or protocol. This can be achieved via regular short newsletters, email updates or a project website (e.g. Figure 4.4). If trial investigators are unable to provide their IPD, or respond to queries in a timely manner, this can place extra time pressure on those undertaking data checking, harmonisation and analysis. Therefore, it is important to keep communicating key deadline dates for the project. Although it is wise to include some flexibility and contingency when setting these, any trials that fail to meet final deadlines may ultimately need to be excluded, so as not to jeopardise the successful delivery of the IPD meta‐analysis results.
4.4 Obtaining IPD
Given that IPD meta‐analyses are typically collaborative projects, trial investigators and their host institutes need to ensure that trial IPD are suitably de‐identified, then transferred and stored securely, so as to preserve participant privacy, and that any unauthorised use is prohibited, as set out in the data‐sharing agreement (Section 3.11).
4.4.1 Ensuring That IPD Are De‐identified
It is important to request that data providers take steps to de‐identify participants in their IPD, before transferring it to the meta‐analysis research team, so as to minimise the risk of participants being re‐identified and their confidentiality being breached.98 De‐identification generally involves the removal of all identifiers that could directly identify individuals, such as participant names and medical or hospital numbers. In an IPD meta‐analysis project, this small degree of de‐identification is the usual process followed by data providers, because the data recipients (i.e. the IPD project’s central research team) will not have access to the full, original (identifying) data. However, the data protection legislation of the country from which the trial originates, or institutional requirements, may necessitate more stringent de‐identification measures, for example, the removal or recoding of indirect or quasi‐identifiers such as dates of birth, and the removal or redaction of free‐text verbatim terms. Direct identifiers may be replaced with new pseudonyms, and quasi‐identifying dates may be removed or generalised to, for example, just the month and year so as to limit the risk of identification.99 As the link between the shared IPD and original trial data is preserved, it remains feasible to consult with trial investigators on any issues that arise at the participant