href="#ulink_cc859420-f158-5d09-b576-8c33dcebb777">Table 4.2). Thus, an unambiguous missing data code such as 99 or, even better, a negative integer such as –9 would have been preferable. Furthermore, it is prudent to discriminate between different types of missing data, such as missing for the participant (e.g. –9 or 9), not applicable to the participant (e.g. –8 or 8) or not collected for the trial (e.g. –7 or 7). For example, in an IPD meta‐analysis of progesterone for pre‐term birth,79 if a baby was stillborn, certain baby outcomes were coded as 8 to signify that they could not be collected, and as 9 to indicate a true missing value. Although this could be inferred from the birth data, coding the IPD in this way made it easier to calculate the proportions of missing data and to cross‐check.
Table 4.2 Excerpt from a data dictionary developed for an IPD meta‐analysis project the effects of anti‐platelets for prevention of pre‐eclampsia in pregnancy97
Source: Lesley Stewart and Lisa Askie, based on the data dictionary used by Askie et al.97
| Variable | Definition | Issue |
|---|---|---|
| Severe maternal morbidity | 1 = none 2 = stroke 3 = renal failure 4 = liver failure 5 = pulmonary oedema 6 = disseminated intravascular coagulation 7 = HELP syndrome 8 = eclampsia 9 = not recorded | Collection as a single variable did not allow for the provision of more than one morbidity for the same women |
| Gestation at randomisation | Gestation in completed weeks9 = unknown | Woman could be randomised at 9 weeks gestation |
4.3 Initiating and Maintaining Collaboration
Negotiating and maintaining collaborations with trial investigators and organisations from different countries, settings and disciplines can take considerable time and effort, and requires careful management,43,44 but is critical to the success of collaborative IPD meta‐analysis projects. In an era where the value of clinical data sharing is more widely appreciated, persuading trial investigators of the value of participating is becoming easier. However, it is worth remembering that not all trial investigators will be obliged by their funders to share their IPD, and it is perfectly reasonable that they may require persuading of the project’s value and rigour before they agree 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,
