| Summary: | <p><strong>Background:</strong> Meta-analyses of individual-level data from randomized trials are often required to detect clinically worthwhile effects. The Cholesterol Treatment Trialists’
Collaboration, which includes data from numerous large long-term statin trials, is
conducting a review of the effects of statin therapy on all adverse events collected in
those trials. This paper describes the approaches used and challenges faced to
systematically capture and categorise the data.</p>
<p><strong>Methods:</strong> Protocols, statistical analysis plans, case report forms, clinical study reports and data sets were obtained, reviewed and checked. Relevant baseline and
follow-up data from each trial was then reorganised into standardised formats based
upon the Clinical Data Interchange Standards Consortium Study Data Tabulation
Model (CDISC SDTM). Adverse event data were organised and coded (automatically
or, where necessary, manually) according to a common medical dictionary based
upon the Medical Dictionary for Regulatory Activities (MedDRA).</p>
<p><strong>Results:</strong> Data from 23 double-blind statin trials and 5 open-label statin trials were provided, either through direct data transfer or through online access portals.
Together, these trials provided 845 datasets containing over 38 million records
relating to 30,495 study variables and 181,973 randomized patients. Of the 46
CDISC SDTM domains that could potentially have been used to organise the data,
the 13 most relevant to the project were identified and utilised, including 6 domains
related to post-randomization adverse events. Nearly 1.2 million adverse events
were extracted and mapped to over 45,000 unique adverse event terms. Of these
adverse events, 99% were coded to a MedDRA ‘lower level term’, with the remainder
coded to a ‘higher level term’ or, very rarely, only a ‘higher level group term’.</p>
<p><strong>Conclusions:</strong> In this meta-analysis of adverse event data from the large randomized trials of statins, approaches based on common standards for data organisation and
classification have provided a resource capable of allowing reliable and rapid
evaluation of any previously-unknown benefits or hazards of statin therapy.</p>
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