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- Egunsola, Oluwaseun, et al.
(författare)
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Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
- 2017
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Ingår i: BMJ Paediatrics Open. - : BMJ Publishing Group Ltd. - 2399-9772. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aims to characterise paediatric reports with lamotrigine (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and to explore whether potential risk factors can be identified.Design This is a retrospective review of suspected adverse drug reaction (ADR) reports. Reported time from LTG start to SJS/TEN onset, indication for use and dose was explored. To identify potential risk groups, report features (eg, ages, patient sex, co-reported drugs) for LTG and SJS/TEN were contrasted with two reference groups in the same database, using shrinkage logOR.Setting Reports were retrieved from VigiBase, the WHO global database of individual case safety reports, in January 2015.Patients Data for patients aged ≤17 years old were extracted.Results There were 486 reports of SJS/TEN in LTG-treated paediatric patients. Ninety-seven per cent of the cases with complete information on time to onset of SJS/TEN occurred within 8 weeks of initiation of LTG therapy. The median time to onset was 15 days (IQR: 10–22 days). The proportion of SJS/TEN with LTG and valproic acid (VPA) co-reporting was significantly more than non-cutaneous ADRs (43% vs 19%, (logOR: 1.60 (99% CI: 1.33 to 1.84)).Conclusions The results suggest that VPA co-medication with LTG therapy is a risk factor for SJS/TEN in the paediatric population. Although this relationship has been identified from individual case reports, this is the first supportive study from a large compilation of cases. SJS/TEN risk is highest in first 8 weeks of treatment with LTG in children and clinicians should be aware of this risk during this period.
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| 2. |
- Juhlin, Kristina, et al.
(författare)
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A method for data-driven exploration to pinpoint key features in medical data and facilitate expert review
- 2017
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 26:10, s. 1256-1265
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo develop a method for data‐driven exploration in pharmacovigilance and illustrate its use by identifying the key features of individual case safety reports related to medication errors.MethodsWe propose vigiPoint, a method that contrasts the relative frequency of covariate values in a data subset of interest to those within one or more comparators, utilizing odds ratios with adaptive statistical shrinkage. Nested analyses identify higher order patterns, and permutation analysis is employed to protect against chance findings. For illustration, a total of 164 000 adverse event reports related to medication errors were characterized and contrasted to the other 7 833 000 reports in VigiBase, the WHO global database of individual case safety reports, as of May 2013. The initial scope included 2000 features, such as patient age groups, reporter qualifications, and countries of origin.ResultsvigiPoint highlighted 109 key features of medication error reports. The most prominent were that the vast majority of medication error reports were from the United States (89% compared with 49% for other reports in VigiBase); that the majority of reports were sent by consumers (53% vs 17% for other reports); that pharmacists (12% vs 5.3%) and lawyers (2.9% vs 1.5%) were overrepresented; and that there were more medication error reports than expected for patients aged 2‐11 years (10% vs 5.7%), particularly in Germany (16%).ConclusionsvigiPoint effectively identified key features of medication error reports in VigiBase. More generally, it reduces lead times for analysis and ensures reproducibility and transparency. An important next step is to evaluate its use in other data.
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| 4. |
- Juhlin, Kristina, et al.
(författare)
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Outlier removal to uncover patterns in adverse drug reaction surveillance - a simple unmasking strategy
- 2013
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 22:10, s. 1119-1129
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThis study aimed to develop an algorithm for uncovering associations masked by extreme reporting rates, characterize the occurrence of masking by influential outliers in two spontaneous reporting databases and evaluate the impact of outlier removal on disproportionality analysis. MethodsWe propose an algorithm that identifies influential outliers and carries out parallel analysis after their omission. It considers masking of drugs as well as of adverse drug reactions (ADRs), uses a direct measure of the masking effect and makes no assumptions regarding the number of outliers per drug or ADR. The occurrence of masking is characterized in the WHO Global Individual Case Safety Report database, VigiBase and a regional collection of reports from Shanghai, China. ResultsFor WHO-ART critical terms such as myocardial infarction, rhabdomyolysis and hypoglycaemia outlier removal led to a 25-50% increase in the number of Statistics of Disproportionate Reporting (SDR) and gains in time to detection of 1-2years, while keeping the rate of spurious SDRs from the parallel analysis at 1%. Twenty-three per cent of VigiBase and 18% of Shanghai SRS reports listed an influential outlier. Twenty-seven per cent of the ADRs and 5% of the drugs in VigiBase, and 2% of the ADRs and 3% of the drugs in Shanghai SRS were involved in an outlier. The overall increase in the number of SDRs for both datasets was 3%. ConclusionMasking by outliers has substantial impact on specific ADRs including, in VigiBase, rhabdomyolysis, myocardial infarction and hypoglycaemia. It is a local phenomenon involving a fair number of reports but yielding a limited number of additional SDRs.
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| 5. |
- Bouquet, Emilie, et al.
(författare)
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Pharmacovigilance in pediatrics
- 2018
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Ingår i: Therapie (Paris). - : ELSEVIER SCIENCE BV. - 0040-5957 .- 1958-5578. ; 73:2, s. 171-180
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Tidskriftsartikel (refereegranskat)abstract
- The characteristics of pharmacology and drug evaluation in the pediatric age group highlight the necessity for the pharmacovigilance community to adjust to the specific features of children. At the time of marketing a medicinal product intended for children, the product's safety profile is sometimes less well known than for adults due to fewer or small sample clinical trials. Furthermore, the frequent off-labeled drug use, the use of unsuitable dosage forms and the need for continuous dose adjustments increase the risk of medication errors and thus lead to avoidable adverse drug reactions (ADRs). The occurrence of child-specific ADRs (such as growth disorders) or ADRs more commonly occurring in children than in adults make it necessary to monitor the safety of child-specific drugs. Pediatric pharmacovigilance includes also the consequences of in utero exposure, whether manifestations are present from birth or occur in early childhood (such as neurodevelopmental disorders). The incidence of ADRs varies with age, setting of medical care (in- or out-patients, pediatric specialties) and by country in which the study was carried out. The drugs most frequently reported with ADRs are those most commonly used in the pediatric age group, i.e. antibiotics and vaccines. The ADRs most often reported are skin, neurological and general disorders. As in adults, spontaneous notification is essential to generate alerts and child-specific pharmacoepidemiological studies are necessary and should be developed. (C) 2018 Societe francaise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.
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| 6. |
- Cavadino, Alana, et al.
(författare)
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Signal Detection in EUROmediCAT : Identification and Evaluation of Medication-Congenital Anomaly Associations and Use of VigiBase as a Complementary Source of Reference
- 2021
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Ingår i: Drug Safety. - : ADIS INT LTD. - 0114-5916 .- 1179-1942. ; 44:7, s. 765-785
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications. Aims This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals. Methods Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation. Results EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly. Conclusion EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.
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| 9. |
- Karimi, Ghazaleh, et al.
(författare)
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The Impact of Duration of Treatment on Reported Time-to-Onset in Spontaneous Reporting Systems for Pharmacovigilance
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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