Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Randomized controlled trials are the gold standard of drug efficacy assessment, but have limited power to assess adverse drug reactions. • Observational data derived from larger populations of patients are often affected by confounding variables, many of which are difficult to measure or simply not known. WHAT THIS STUDY ADDS • This study demonstrates the utility of the self-controlled case-series method of analysing the safety profile of drugs, which reduces confounding because comparisons are intraperson. • Although such data should not be viewed in isolation, the efficiency and versatility of this method suggest that it could become a future standard in drug safety assessment. AIMS Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population. METHODS We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates. RESULTS Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens–Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found. CONCLUSIONS Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs. [ABSTRACT FROM AUTHOR]