Bernard Bégaud

A Potential Event-Competition Bias in Safety Signal Detection: Results from a Spontaneous Reporting Research Database in France

BackgroundIn spontaneous reporting databases, reports of well-established drug-event associations may mask alerts that arise from other drugs (drug competition bias). However, a symmetrical event-competition bias has not yet been explored whereby known events may mask an association with new events for a given drug or drug class.ObjectiveThe objective of this study was to explore the effects of event-competition bias on safety signals generated from spontaneous reporting databases.MethodsThe drug classes tested included statins, oral anticoagulants, antipsychotics and HIV antiretrovirals. For each, a type A reaction was selected, and its potential competitive effect on the generation of other safety signals for the drug was explored. These were rhabdomyolysis/myopathy for statins, haemorrhage for oral anticoagulants, extrapyramidal syndrome for antipsychotics and lipodystrophy for HIV antiretrovirals. Signals of disproportionate reporting (SDRs) were detected using the case/non-case approach in the French research spontaneous reporting database (which contains reports from 1 January 1986 to 31 December 2001), before and after removing all reports concerning these competitor events. SDRs were considered as potential signals if not reported in the literature before 1 January 2002 but confirmed since.ResultsThe whole database included 207,236 reports, 4,355 of which included statins as one of the suspected drugs. The removal of reports of rhabdomyolysis/myopathy concerned 8,425 reports among which 867 involved statins. After this removal, 11 new SDRs appeared for statins that had not been detected initially. Similarly, 15 SDRs were unmasked for oral anticoagulants, six for antipsychotics and nine for HIV antiretrovirals. After literature-based assessment, five of the 41 unmasked SDRs appeared related to potential safety signals confirmed after 2002.ConclusionThis study demonstrated that a masking phenomenon resulting from an event-competition effect could occur when performing signal detection using disproportionality analyses of spontaneous reporting databases. This should be taken into account when routine signal detection is performed.

Who seeks primary care for sleep, anxiety and depressive disorders from physicians prescribing homeopathic and other complementary medicine? Results from the EPI3 population survey

Objectives To describe and compare patients seeking treatment for sleep, anxiety and depressive disorders (SADD) from physicians in general practice (GPs) with three different practice preferences: strictly conventional medicine (GP-CM), mixed complementary and conventional medicine (GP-Mx) and certified homeopathic physicians (GP-Ho). Design and setting The EPI3 survey was a nationwide, observational study of a representative sample of GPs and their patients, conducted in France between March 2007 and July 2008. Participants 1572 patients diagnosed with SADD. Primary and secondary outcomes The patients’ attitude towards complementary and alternative medicine; psychotropic drug utilisation. Results Compared to patients attending GP-CM, GP-Ho patients had healthier lifestyles while GP-Mx patients showed similar profiles. Psychotropic drugs were more likely to be prescribed by GP-CM (64%) than GP-Mx (55.4%) and GP-Ho (31.2%). The three groups of patients shared similar SADD severity. Conclusion Our results showed that patients with SADD, while differing principally in their sociodemographic profiles and conventional psychotropic prescriptions, were actually rather similar regarding the severity of SADD in terms of comorbidities and quality of life. This information may help to better plan resource allocation and management of these common health problems in primary care.

Effects of Cydonia oblonga Miller extracts on blood hemostasis, coagulation and fibrinolysis in mice, and experimental thrombosis in rats.

INTRODUCTION Cydonia oblonga Miller (COM) is traditionally used in Uyghur medicine for the prevention of cardiovascular disease. The present study is designed to explore the effects of COM extracts on models and markers of thrombosis and related biomarkers. MATERIALS AND METHODS 20, 40, 80 mg/kg/day COM aqueous extracts and 5mg/kg/day aspirin, orally for 14 days were compared to untreated controls in mice on bleeding and clotting times, using the tail cutting and glass slide methods and for death rates in collagen-epinephrine pulmonary thrombosis, thrombolysis in vitro and euglobulin lysis time (ELT). In rats, common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6-keto-PGF1α) were measured. RESULTS AND CONCLUSION Compared to controls, COM extracts dose-dependently prolonged bleeding by 2.17, 2.78 and 3.63 times, vs. aspirin 2.58, and the clotting time by 1.44, 2.47 and 2.48 times, vs. aspirin 1.91. COM reduced pulmonary embolus mortality by 27, 40 and 53%, vs. 47% for aspirin. COM dose-dependently increased thrombolysis by 45, 55 and 63%, vs. 56% for aspirin, and shortened ELT to 71, 61 and 43%, vs. 43% for aspirin. In rats, venous occlusion time was prolonged. Arterial and venous thrombus weights were dose-dependently reduced in COM groups. TXB2 decreased and 6-keto-PGF1α increased with COM and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with COM but not for aspirin. CONCLUSION We confirm the experimental effects of COM on hemostasis and thrombosis. Further exploration of putative clinical effects appear justified.

Authors’ reply to Coyle-Gilchrist and colleagues and Bocti and colleagues

Coyle-Gilchrist and colleagues and Bocti and colleagues are directly or indirectly concerned with the possible non-causal nature of the association we found between benzodiazepines and dementia.1 2 3 We emphasise that we never concluded that this association was causal. We designed our study to go further than previously published studies by minimising possible confounding …