Inter-expert agreement of seven criteria in causality assessment of adverse drug reactions

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.     

The importance of direct patient reporting of suspected adverse drug reactions: a patient perspective

AIM

To explore the opinions of patient reporters to the UK Yellow Card Scheme (YCS) on the importance of the scheme.

METHODS

Postal questionnaires were distributed on our behalf to all patient reporters submitting a Yellow Card to the Medicines and Healthcare Regulatory Agency (MHRA) between March and December 2008, with one follow-up reminder to non-responders. Qualitative analysis was undertaken of responses to an open question asking why respondents felt patient reporting was important. This was followed up by telephone interviews with a purposive sample of selected respondents.

RESULTS

There were 1362 evaluable questionnaires returned from 2008 distributed (68%) and 1238 (91%) respondents provided a total of 1802 comments. Twenty-seven interviews were conducted, which supported and expanded the views expressed in the questionnaire. Four main themes emerged, indicating views that the YCS was of importance to pharmacovigilance in general, manufacturers and licensing authorities, patients and the public and health professionals. Reporters viewed the YCS as an important opportunity to describe their experiences for the benefit of others and to contribute to pharmacovigilance. The scheme''s independence from health professionals was regarded as important, in part to provide the patient perspective to manufacturers and regulators, but also because of dismissive attitudes and under-reporting by health professionals.

CONCLUSION

Direct patient reporting through the YCS is viewed as important by those who have used the scheme, in order to provide the patient experience for the benefit of pharmacovigilance, as an independent perspective from those of health professionals.     

Feedback for patients reporting adverse drug reactions; satisfaction and expectations

Objective: Due to the rising number of patient reports in pharmacovigilance, the manner in which feedback is provided to patients is an element to be considered. The objective is to explore the satisfaction of patients towards personalized and general feedback in response to their reported adverse drug reactions (ADRs).

Methods: Patients who reported an ADR to the Dutch Pharmacovigilance Centre for the first time in the period between October 2012 and April 2013 were included. Reporters received personalized feedback or a general acknowledgement letter. Satisfaction towards the received feedback, expressed on a 5-point Likert scale (1 very good to 5 very poor), was studied using a web-based questionnaire. Data were analyzed using Pearson Chi-square test and linear regression analysis. Statistical significance was based on p < 0.05.

Results: A total of 471 patient-reporters were contacted with a total response of 52.5%. Respondents of both groups were satisfied with the received feedback, average score 2 (good). Respondents of the personalized feedback-group were however more satisfied score 2.0 versus 2.5 (p < 0.001) and considered the feedback more clear and useful compared with respondents of the acknowledgement letter-group, respectively score 1.6 versus 1.7 (p = 0.01) and score 2.1 versus 2.5 (p < 0.001).

Conclusion: Patients reporting ADRs are satisfied with feedback received from the pharmacovigilance centre, whether this is a personalized feedback or a general acknowledgment letter. They find it clear, useful and it meets their expectation. Although differences were found between the two types of feedback, these differences did not indicate dissatisfaction towards the received feedback.     

Interpreting adverse drug reaction (ADR) reports as hospital patient safety incidents

AIM

In the UK, the National Patient Safety Agency (NPSA) includes adverse drug reactions as a reporting category, while the MHRA Yellow Card Scheme also collects data regarding adverse drug reactions (ADRs). In this study, we aimed to assess ADRs using NPSA criteria and discuss the resulting implications.

METHODS

ADRs identified in a 6-month prospective study of 3695 inpatient episodes were assessed according to their impact on the patient and on the organization, using tools developed by the NPSA.

RESULTS

Seven hundred and thirty-three (100%) ADRs were assessed. In terms of impact on the patient, 537 (73.3%) were categorized as ‘low’ (minor treatment), 181 (24.7%) as ‘moderate’ (moderate increase in treatment, no permanent harm), 14 (1.91%) as ‘severe’ (permanent harm) and 1 (0.14%) was categorized as ‘catastrophic’ (direct cause of death). In terms of impact on the organization, none was categorized as ‘no harm/ no risk’, 508 (69.3%) as ‘insignificant’, 188 (25.6%) as ‘minor’, 25 (3.4%) as ‘moderate’, 12 (1.6%) as ‘major’ and none was classed as ‘catastrophic’. Less than 2% of ADRs would be eligible for detailed analysis according to the NPSA guidance. The ADRs that cause incidents of greater significance relate to bleeding, renal impairment and Clostridium difficile infection.

CONCLUSIONS

Classification of ADRs according to NPSA guidance offers limited additional value over and above that offered by the Yellow Card System. A consistent message needs to be sent to prospective reporters of ADRs; the availability of more than one system is likely to confuse reporters and does not aid patient safety.     

对家长关于儿童药品不良反应认知和接受宣传、教育态度的问卷调查

目的:调查家长对儿童药品不良反应(adverse drug reactions,ADRs)的认知情况和对接受ADRs宣传和教育的态度,分析影响家长上报儿童ADRs的因素,找出提高家长ADRs上报率的措施.方法:采用发放调查问卷的方式,就儿童ADRs的相关问题,对在上海4家医院就诊儿童的家长进行调查分析.结果:共发放问卷600份,回收有效问卷552份(回收率为92%).结果发现,52%的家长对ADRs的理解不正确,不报告的主要原因是不能判断ADRs.87.8%的家长渴望学习ADRs知识.家长们对发生在神经系统和皮肤黏膜的ADRs比较关注.结论:家长对儿童ADRs的认知和判断能力欠缺,但对接受ADRs宣传和教育的态度比较积极.应针对具体情况,加强对家长关于儿童ADRs的培训工作.     

发达国家药物不良反应监测概况

药物不良反应(ADRs)是世界医疗界的难题,本文对欧美等发达国家药物不良反应发生现状、监管现状及避免ADRs增进药物安全性的方法等几方面进行综合评述,以助于吸取有效经验。     

Pharmacists' role in reporting adverse drug reactions in an international perspective

INTRODUCTION: The participation of the pharmacist in national spontaneous reporting systems for adverse drug reactions (ADRs) has not always been a matter of course. Even today, there are a number of countries, in particular the Scandinavian countries, where pharmacists are not authorised to report ADRs. In those countries in which they are allowed to report, they do not always use this opportunity. METHODS: We have conducted a review of the literature to investigate the involvement of pharmacists in ADR reporting. In addition, we evaluated the pharmacists' actual contributions in 2001 by means of an international questionnaire-based survey among the countries participating in the WHO Drug Monitoring Programme in September 2002. Apart from the numbers of pharmacists' reports, respondents were asked to indicate their assessment of both the quality and the significance of the contribution. Of the 68 participating countries, 41 responded by returning the questionnaire. RESULTS AND CONCLUSIONS: The appreciation of pharmacists' ADR reports is high in those countries that have more experience with greater numbers of pharmacists' reports. The countries that received fewer reports from pharmacists gave lower scores to their contribution. If the specific contribution pharmacists can make to the quantity and quality of ADR reports were to be exploited to a greater extent, this could lead to a substantial improvement of the international adverse drug reactions reporting system.     

Causality assessment of suspected adverse drug reactions: A transatlantic view

The European Community's (EC) pending requirement for a standard assessment of the causal association between a drug product and a reported drug-associated event prompts a review of this aspect of pharmaceutical safety evaluation. Pharmaceutical manufacturers who use various methods, or no methods, may need to consider these EC definitions and their interpretation for evaluating their current procedures and planning any future changes. This paper first describes the EC classifications and their basis as one statement on the status of causality assessment in Europe. Reflecting the rather different view of causality assessment in North America, this paper then briefly reviews the evolution and uses of causality assessment over the last two decades. The controversies over causality are next discussed, followed by examination of the diverse uses of assessment by a pharmaceutical manufacturer or a regulator. Finally, the paper concludes with thoughts on applying causality concepts as tools for enhancing drug-risk assessment.     

Under-reporting of serious adverse drug reactions in Sweden

INTRODUCTION: Adverse drug reactions (ADR) constitute a major problem, both from a medical point of view and as an economical burden. Spontaneous reporting of ADRs is one of the methods for post marketing surveillance of drug safety. Under-reporting can also provide an important obstacle to rapid and relevant signal detection. AIM: To investigate the rate of under-reporting serious ADRs of selected ICD 10 diagnoses. METHOD: In order to investigate the under-reporting rate we investigated at five hospitals within the county of Norrbotten in Sweden the total number of diagnosed cases during a period of 5 years (1996-2000) with the following diagnoses: cerebral haemorrhage (I 61.0-I 61.9), pulmonary embolism (I 26.0 and I 26.9), embolism or thrombosis (I 74.0-I 74.9), phlebititis, thrombophlebitits or venous thrombosis (I 80.0-I 80.3, I 80.8 and I 80.9) and portal vein thrombosis and other thrombosis or emboli (I 82.0-I 82.3, I 82.8 and I 82.9). The identity of these patients was obtained through a database search. The patients' case records were then scrutinized by a specially trained nurse and the drugs used at the time of the event were noted. An assessment of the possibility of an ADR was performed using standard WHO causality criteria. Later, database search in the Swedish ADR registry was performed in order to investigate whether these suspected ADRs had been reported to the national authority in Sweden or not. RESULTS: In total 1349 case records were found and scrutinized. Of these, 107 patients had received drugs that could have been a probable or possible cause to the diagnoses. Of these 92 cases had not been reported and only 15 patients were found in the database, giving an overall under-reporting rate of all ADRs of 86%.The most commonly occurring diagnoses were cerebral haemorrhage followed by venous thrombosis, 545 and 468 respectively. Among those cases that should have been reported according to the existing rules for spontaneous reporting of suspected ADRs the most frequently occurring diagnosis was cerebral haemorrhage (I 61.0) in connection to treatment with anticoagulants. CONCLUSION: The rate of spontaneous ADR reporting is very low, also for serious and fatal reactions.     

左氧氟沙星的不良反应

左氧氟沙星是临床广泛应用的抗菌药，用药期间可能出现的不良反应涉及消化系统、中枢神经系统、心血管系统、血液及内分泌系统等8大系统，包括恶心、呕吐、头晕、头痛、皮肤过敏反应等症状。本文对左氧氟沙星不良反应进行简要综述，旨在引起临床医生的重视，促进其合理应用。     

Comparison of 500 spontaneous and 500 published reports of adverse drug reactions

The information and case quality of 500 spontaneous and 500 published adverse drug reaction (ADR) reports were compared, including a study of the most common criteria used in different causality assessment methods. The criteria were more often of positive value in the published reports. Nevertheless, spontaneous reports play an important role in the detection of new ADRs.