de Boissieu Paul, Kanagaratnam Lukshe, Abou Taam Malak, Roux Marie-Paule, Dramé Moustapha, Trenque Thierry
Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Reims University Hospital, Reims, France; University of Reims Champagne-Ardenne, Faculty of Medicine, EA 3797, Reims, France.
Pharmacoepidemiol Drug Saf. 2014 Sep;23(9):989-92. doi: 10.1002/pds.3622. Epub 2014 Apr 15.
The purpose of this study was to identify a notoriety bias in a database of spontaneous reports and its consequences on the calculation of the reporting odds ratio (ROR).
We used the case/noncase methodology to calculate the ROR for bisphosphonates and osteonecrosis of the jaw (ONJ) in the French national pharmacovigilance database (from 1985 to 2013). To evaluate notoriety bias, drug-related risk factors for ONJ [as specified in the summary of product characteristics (SPC) of bisphosphonates] were systematically scanned for notifications of reports of ONJ occurring under bisphosphonate therapy. When a risk factor was present, the ONJ was considered as not due to bisphosphonates, and a second ROR was calculated under the hypothesis of maximum bias.
In total, 148 cases of ONJ were reported (143 with bisphosphonates and five without). The raw ROR was 3448 (95% confidence interval 1413-8417). After analysis of the reports, only 86 had no mention of a risk factor for ONJ. The ROR under the maximum bias hypothesis was 87 (95% confidence interval 63-121). Among ONJ where chemotherapy was being administered simultaneously to bisphosphonates, 27 reports did not consider the chemotherapy to be implicated, despite seven of these occurring in cases where ONJ was mentioned in the summary of product characteristics.
The existence of a notoriety bias has an impact on measures of disproportionality. The detection of pharmacovigilance signals might be delayed. It is advisable to list all drugs being taken when an adverse drug reaction occurs, and not only those known to be associated with the observed reaction.
本研究旨在确定自发报告数据库中的知名度偏差及其对报告比值比（ROR）计算的影响。
我们采用病例/非病例方法，在法国国家药物警戒数据库（1985年至2013年）中计算双膦酸盐与颌骨坏死（ONJ）的ROR。为评估知名度偏差，系统扫描了双膦酸盐产品特性摘要（SPC）中指定的ONJ药物相关风险因素，以查找双膦酸盐治疗下发生的ONJ报告通知。当存在风险因素时，ONJ被视为并非由双膦酸盐引起，并在最大偏差假设下计算第二个ROR。
共报告148例ONJ（143例使用双膦酸盐，5例未使用）。原始ROR为3448（95%置信区间1413 - 8417）。报告分析后，仅86例未提及ONJ风险因素。最大偏差假设下的ROR为87（95%置信区间63 - 121）。在同时接受双膦酸盐和化疗的ONJ病例中，27份报告未考虑化疗有影响，尽管其中7例在产品特性摘要中提及了ONJ。
知名度偏差的存在会影响不均衡性测量。药物警戒信号的检测可能会延迟。发生药物不良反应时，建议列出所有正在服用的药物，而不仅仅是那些已知与观察到的反应相关的药物。
