Heterogeneity between Pharmacoepidemiological Studies Using the Clinical Practice Research Datalink (CPRD)

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The CPRD has been collecting medical data among UK patients since 1987. Many studies on the risk of cancer associated with prescription of antidiabetic drugs have used the CRPD database. The objective was to compare methods and results of studies on the same exposure and outcome combination based on the CPRD.A systematic Pubmed search of articles on diabetes and cancer based on the CPRD was performed. Articles were grouped into common exposure and outcome combinations. Methods and results were compared, especially in case of diverging results between studies, with a focus on study design and statistical methods. Forty-six studies were identified. Five of them studied colorectal cancer (CRC) occurrence in diabetic patients prescribed with metformin. All studies consistently found no significant increased or decreased CRC risk associated with metformin prescription. Five studies examined the risk of bladder cancer in relation to pioglitazone prescription. Two studies found a significantly increased risk of bladder cancer, one based on the analysis of the full dataset and one based on a nested case-control design using conventional matching procedures. The three other studies found no association, all of which used propensity score matched cohort design. Four studies investigated the risk of breast cancer among insulin glargine users. The three studies that included diabetic subjects who were prescribed glargine or another insulin therapy for the first time (i.e., the new user design) found no association. The study that included past and new users of glargine and of another insulin found a significantly increased risk. Despite the use of the same data source, studies on the same exposure and outcome may arrive at markedly different conclusions. Studies using propensity scores for matching subjects or including past users in cohorts may obtain results substantially different than studies using conventional statistical approaches. Disclosure A. Koechlin: None. P. Boyle: Other Relationship; Self; Sanofi. P. Autier: Other Relationship; Self; Sanofi.