Knowledge creation about ADRs--turning the perspective from the rear mirror to the projector?

UNLABELLED: What is already known about this subject? Serious and unexpected adverse drug reactions (ADRs) have been reported shortly after marketing of a number of drugs. Review of ADR cases by the regulatory authorities has resulted in suspension of drugs or restrictions in product information. What this study adds? Information about serious and unexpected ADRs of three drugs with reported serious ADRs was already present in the registration files. Observations of these ADRs were not investigated further before marketing. A more active utilization of the ADR information in premarketing studies could probably prevent the appearance of unexpected and serious ADR cases after marketing. AIMS: Spontaneous reports of adverse drug reactions (ADRs) are often the only documentation used to justify the recall of drugs from the market. The purpose of this study was to investigate whether it would have been possible to foresee serious ADR cases based on available information on ADRs reported in Phase II and III clinical trials before marketing. METHODS: We conducted a retrospective analysis of reported ADR data in Phase II/III clinical trials in the registration material for three different ADR scenarios: (i) trovafloxacin/alatrofloxacin and hepatotoxicity; (ii) tolcapone and hepatotoxicity and neuroleptic malignant syndrome; and (iii) rituximab and cytokine release syndrome. We chose the scenarios because they were of serious character and caused great damage to the patients and because of different outcomes of the scientific discussions in the regulatory agencies. RESULTS: In all three cases, the registration material contained observations of ADRs, but there had been no follow-up on these observations. ADRs were mentioned in the summary of product information (SPC) purely as information, to some extent accompanied by recommendations. The information was not converted into new knowledge and remained tacit knowledge embedded in the SPCs disseminated to health professionals/prescribers. CONCLUSIONS: The registration material analysed contained information about ADRs that were reported later, meaning that it would have been possible to foresee the occurrence of the ADRs at the time of licensing. More active utilization of the information from Phase II/III clinical trials is recommended to prevent the appearance of unexpected ADRs and further emphasis in SPC warnings to doctors about possible serious ADRs.

Creating knowledge about adverse drug reactions: a critical analysis of the Danish reporting system from 1968 to 2005.

Data on adverse drug reactions (ADRs) have been collected in Denmark since 1968 and the process is ongoing. This article explores knowledge created by the system, including how the collected data have been used to monitor the safety of licensed drugs. Nonaka's theory of knowledge creation was used to discriminate between tacit and explicit knowledge. A total of 56,802 ADR case reports were received from 1968 to 2005. The analysis shows a rather stable number of ADR cases from 1980, with about 2000 reports per year. The distribution of cases into serious and non-serious ADRs has been one to four throughout the period under study, but with large variations. Analysis of selected ADR cases shows that the system lacked the potential to capture available knowledge. Consequently the ADR reports have had limited value and significance in the process of creating scientific knowledge. Thus, the analysis questions the way available data can become explicit as a basis for regulatory decisions and whether all data can become knowledge, including who decides what knowledge is.

Drug-related problems in general practice: results from a development project in Denmark.

OBJECTIVE: The objective of the study is identify and document drug-related problems and other possible quality problems in primary care through a pharmacist-run medication review and screening service. GPs' acceptance and implementation rates of the pharmacist's recommendations are evaluated. METHOD: A community pharmacist worked 20 h per week for 18 months in a GP practice with three GPs. RESULTS: The pharmacist completed 40 reviews and identified 103 drug-related problems. GPs had a high rate of acceptance of the pharmacist's suggested interventions (83%), and 77% of the recommendations had been implemented. 765 (12.5%) possible quality problems were identified after screening 6094 medical records. The physicians accepted 86% of the recommendations to initiate low dosage ASA and treatment was implemented for 63% of the patients. 76% of the recommendations to initiate Statin treatment were agreed on and 56% were implemented. CONCLUSIONS: The pharmacist was able to identify drug-related problems and other possible quality problems with regard to quality assurance of individual patient's drug treatment. The GPs accepted and implemented the pharmacist's recommendations. It was feasible to implement the services and to establish well-functioning co-operation between the pharmacist and the GPs.