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Causality Assessment (causality + assessment)
Terms modified by Causality Assessment Selected AbstractsEvaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug-induced liver injuryALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2008M. GARCÍA-CORTÉS Summary Background, Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. Aim, To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Methods, Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (,w) test. Results, A total of 249 ratings were generated. Between-observer agreement was 45% with a ,w value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, ,w: 0.71). Concordance between the two scales was 24% (,w: 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. Conclusion, The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity. [source] Telithromycin-associated hepatotoxicity: Clinical spectrum and causality assessment of 42 cases,HEPATOLOGY, Issue 1 2009Allen D. Brinker Telithromycin is the first of a new class of ketolide antibiotics with increased activity against penicillin-resistant and erythromycin-resistant pneumococci. This agent received approval by the United States Food and Drug Administration (FDA) in 2004 for treatment of upper and lower respiratory infections. Following market introduction, spontaneous reports of telithromycin-associated hepatotoxicity, including frank liver failure, were received. To address these reports, an ad hoc group with expertise in spontaneous adverse events reporting and experience in evaluating drug-induced liver injury was formed, including members of the FDA, other federal agencies, and academia. The primary objective of this group was to adjudicate case reports of hepatic toxicity for causal attribution to telithromycin. After an initial screening of all cases of liver injury associated with telithromycin reported to FDA as of April 2006 by one of the authors, 42 cases were comprehensively reviewed and adjudicated. Five cases included a severe outcome of either death (n = 4) or liver transplantation (n = 1); more than half were considered highly likely or probable in their causal association with telithromycin. Typical clinical features were: short latency (median, 10 days) and abrupt onset of fever, abdominal pain, and jaundice, sometimes with the presence of ascites even in cases that resolved. Concurrence in assignment of causality increased after agreement on definitions of categories and interactive discussions. Conclusion: Telithromycin is a rare cause of drug-induced liver injury that may have a distinctive clinical signature and associated high mortality rate. Consensus for attribution of liver injury to a selected drug exposure by individual experts can be aided by careful definition of terminology and discussion. (HEPATOLOGY 2009;49:250-257.) [source] Unusual hypersensitivity to warfarin in a critically ill patientJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2004H. Konishi PhD Summary A patient was admitted to the intensive care unit because of respiratory failure, and warfarin therapy was started at 2 mg/day for the treatment of pulmonary embolism, together with other medications. Despite the low dosage of warfarin, international normalized ratio (INR) was markedly elevated from 1·15 to 11·28 for only 4 days, and bleeding symptoms concurrently developed. Vitamin K2 was infused along with discontinuation of warfarin. One day later, the INR was found to have decreased, and bleeding was also improved. An objective causality assessment indicated a probable relationship between clotting abnormality and warfarin administration, although the degree of elevation of the INR was unusual in the light of the daily warfarin dose and duration of its exposure. Based on the clinical status of the patient, it was suspected that several conditions contributed to the abnormal hypersensitivity to warfarin. Contributory factors probably included pharmacokinetic interactions with co-administrated drugs, vitamin K deficiency caused by decreased dietary intake, reduced gut bacterial production, impaired intestinal absorption and hepatic synthetic capacity, and increased consumption of clotting factors. In view of our experience in the present case, it should be stressed that close monitoring of coagulation capacity is necessary in critically ill patients in order to avoid fatal haemorrhage after initiating warfarin therapy regardless of the dosage. [source] Veterinary pharmacovigilance: between regulation and scienceJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001G. Keck Veterinary pharmacovigilance has shown a remarkable development in recent years. After presenting briefly the regulatory context, this paper considers the scope of veterinary pharmacovigilance, causality assessment of suspected adverse drug reactions (ADRs), the systems existing in different countries and the evolution for the coming years. The involvement of veterinary research and teaching institutions should certainly become more important in this cross-road activity. [source] Evaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug-induced liver injuryALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2008M. GARCÍA-CORTÉS Summary Background, Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. Aim, To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Methods, Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (,w) test. Results, A total of 249 ratings were generated. Between-observer agreement was 45% with a ,w value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, ,w: 0.71). Concordance between the two scales was 24% (,w: 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. Conclusion, The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity. [source] Adverse effects of neuromuscular blocking agents based on yellow card reporting in the U.K.: are there differences between males and females?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2006FRCA, Karen Patricia Light MBBS Abstract Background Adverse drug reactions (ADRs) are known to occur during anaesthesia; in the U.K. such ADRs may be reported through the Yellow Card Scheme (YCS). Our aim was to determine the demographics of ADRs to neuromuscular blocking drugs without formal causality assessment. Methods A retrospective analysis of ADRs to seven neuromuscular blocking drugs reported via the YCS during a greater than 30-year period was performed. Sex and age were analysed in order to identify at risk groups. Results Of 998 reports, 969 included gender. Non-allergic suspected reactions occurred with almost the same frequency as those with an allergic component. The majority occurred in females 676 (70%), and significant sex differences were measured between drugs. Males were more likely to have suffered an ADR to atracurium (p,=,0.01) whilst females experienced more ADRs to suxamethonium (p,=,0.01). ADRs proved fatal in 81 (9%) of the 950 reports for single drugs. Mortality following suxamethonium was significantly higher in males at 22% compared with 9% females (p,<,0.001). More women than men were reported to have allergic reactions, 73% (362/499) compared with 27% (137/499) respectively. The female:male ratio for ADRs was reversed for subjects <,10 years compared with peak ADR reports during the decade from 31,40 years. Conclusions Sex differences in mortality exist in this analysis. The unexpected high frequency of non-allergic ADRs suggests that morbidity and mortality from reactions to established drugs is twice that expected from allergic reactions alone. Standards and guidance for the reporting of ADRs warrant urgent development. Copyright © 2006 John Wiley & Sons, Ltd. [source] Inter-expert agreement of seven criteria in causality assessment of adverse drug reactionsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2007Yannick Arimone What is already known about this subject ,,In pharmacovigilance, many methods have been proposed for causality assessment of adverse drug reactions. ,,Expert judgement is commonly used to evaluate the causal relationship between a drug treatment and the occurrence of an adverse event. This form of judgement relies either explicitly or implicitly on causality criteria. What this study adds ,,Our study compares the judgements of five senior experts using global introspection about drug causation and seven causality criteria on a random set of putative adverse drug reactions. ,,Even if previous publications have shown poor agreement between experts using global introspection, few have compared judgements of well trained pharmacologists, familiar with using a standardized causality assessment method. Aims To evaluate agreement between five senior experts when assessing seven causality criteria and the probability of drug causation. Methods A sample of 31 adverse event-drug pairs was constituted. For each pair, five experts separately assessed (i) the probability of drug causation, which was secondarily divided into seven causality levels: ruled out (0,0.05), unlikely (0.06,0.25), doubtful (0.26,0.45), indeterminate (0.46,0.55), plausible (0.56,0.75), likely (0.76,0.95), and certain (0.96,1); and (ii) seven causality criteria. To test discrepancies between experts, the kappa index was used. Results The agreement of the five experts was very poor (kappa = 0.05) for the probability of drug causation. Among the seven levels of causality, only ,doubtful' showed a significant rate of agreement (kappa = 0.32, P < 0.001). For all criteria, the kappa index was significant except for the item ,risk(s) factor(s)' (kappa = 0.09). Agreement between experts was good (0.64, P < 0.001) only for the criterion ,reaction at site of application or toxic plasma concentration of the drug or validated test'. However, the rate of agreement with kappa indices of the causality criteria ranged from 0.12 to 0.38. Conclusions This study confirms that in the absence of an operational procedure, agreement between experts is low. This should be considered when designing a causality assessment method. In particular, criteria inducing a low level of agreement should have their weight reduced. [source] | ||||||||||