BackgroundSubstandard medicines, whether the result of intentional manipulation or lack of compliance with good manufacturing practice (GMP) or good distribution practice (GDP), pose a significant potential threat to patient safety. Spontaneous adverse drug reaction reporting systems can contribute to identification of quality problems that cause unwanted and/or harmful effects, and to identification of clusters of lack of efficacy. In 2011, the Uppsala Monitoring Centre (UMC) constructed a novel algorithm to identify reporting patterns suggestive of substandard medicines in spontaneous reporting, and applied it to VigiBase®, the World Health Organization’s global individual case safety report database. The algorithm identified some historical clusters related to substandard products, which were later able to be confirmed in the literature or by contact with national centres (NCs). As relevant and detailed information is often lacking in the VigiBase reports but might be available at the reporting NC, further evaluation of the algorithm was undertaken with involvement from NCs.ObjectiveTo evaluate the effectiveness of an algorithm that identifies clusters of potentially substandard medicines, when these are assessed directly at the NC concerned.MethodsThe algorithm identifies countries and time periods with disproportionately high reporting of product inadequacy. NCs with at least 20 clusters were eligible to participate in the study, and six NCs—those in the Republic of Korea, Malaysia, Singapore, South Africa, the UK and the USA—were selected, taking into account the geographical spread and prevalence of recent clusters. The clusters were systematically assessed at the NCs, following a standardized protocol, and then compiled centrally at the UMC. The clusters were classified as ‘confirmed’, ‘potential’ or ‘unlikely’ substandard products; or as ‘confirmed not substandard’ when confirmed by an investigation; or as ‘indecisive’ when the information available did not allow a sound assessment even at the NC.ResultsThe assessment of a total of 147 clusters resulted in 8 confirmed, 12 potential and 51 unlikely substandard products, and a further 19 clusters were confirmed as not substandard. Reflecting the difficulty of evaluating suspected substandard products retrospectively when additional information from the primary reporter, as well as samples, are no longer available, 57 clusters were classified as indecisive.ConclusionWhile application of the algorithm to VigiBase allowed identification of some substandard medicines, some key prerequisites have been identified that need to be fulfilled at the national level for the algorithm to be useful in practice. Such key factors are fast handling and transfer of incoming reports into VigiBase, detailed information on the product and its distribution channels, the possibility of contacting primary reporters for further information, availability of samples of suspected products and laboratory capacity to analyse suspected products.Electronic supplementary materialThe onlin...

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Within pharmacovigilance, knowledge of time-to-onset (time from start of drug administration to onset of reaction) is important in causality assessment of drugs and suspected adverse drug reactions (ADRs) and may indicate pharmacological mechanisms involved. It has been suggested that time-to-onset from individual case reports can be used for detection of safety signals. However, some ADRs only occur during treatment, while those that do occur later are less likely to be reported. The aim of this study was to investigate the impact of treatment duration on the reported time-to-onset. Case reports from the WHO Global ICSR database, VigiBase, up until February 5th 2010 were the basis of this study. To examine the effect of duration of treatment on reported time-to-onset, angioedema and hepatitis were selected to represent short and long latency ADRs, respectively. The reported time-to-onset for each of these ADRs was contrasted for a set of drugs expected to be used short- or long-term, respectively. The study included 2,980 unique reports for angioedema and 1,159 for hepatitis. Median reported time-to-onset for angioedema in short-term treatments ranged 0-1 days (median 0.5), for angioedema in long-term treatments 0-26 days (median 8), for hepatitis in short-term treatments 4-12 days (median 7.5) and for hepatitis in long term treatments 19-73 days (median 28). Short-term treatments presented significantly shorter reported time-to-onset than long-term treatments. Of note is that reported time-to-onset for angioedema for long-term treatments (median value of medians being 8 days) was very similar to that of hepatitis for short-term treatments (median value of medians equal 7.5 days). The expected duration of treatment needs to be considered in the interpretation of reported time-to-onset and should be accounted for in signal detection method development and case evaluation.

Letters not directly related to articles published in Clinical Medicine and presenting unpublished original data should be submitted for publication in this section. Clinical and scientifi c letters should not exceed 500 words and may include one table and up to fi ve references. Clinical stories are necessary for drug safetyPost-marketing reports of suspected adverse drug reactions (ADRs) are key elements to prevent patients being harmed by drugs. In addition to the data collected on pre-specifi ed fi elds, descriptive free-text case stories (narratives) might be crucial when interpreting these reports, which can add to the knowledge of adverse effects and are the basis for regulatory decisions.Narratives occur in only 11% of the reports in VigiBase, 1 the WHO Global Individual Case Safety Report database. 2 Usually only minimum information about the drugs and ADRs are listed in the structured data fi elds. The citation below is a fragment from a published case report for a 13-year-old boy with olanzapine-induced rhabdomyolysis with concomitant lithium-induced electrocardiogram changes.