Nicholas Moore

Comparison of three methods (consensual expert judgement, algorithmic and probabilistic approaches) of causality assessment of adverse drug reactions: an assessment using reports made to a French pharmacovigilance centre.

AbstractBackground: Different methods have been proposed for assessing a possible causal link between a drug treatment and an adverse event in individual patients. They approximately belong to three main categories: expert judgement, operational algorithms and probabilistic approaches. Objective: To compare, in a set of actual drug adverse event reports, three different methods for assessing drug causality, each belonging to one of the three main categories: expert judgement, the algorithm used by the French pharmacovigilance centres since 1985, and a novel method based on the logistic function. Methods: Fifty drug-event pairs were randomly sampled from the database of the Bordeaux pharmacovigilance centre, France. To serve as the gold standard, the probability for drug causation, from 0 to 1, was first determined for each drug-event pair by a panel of senior experts until consensus was reached. Causality was then assessed by members of the Bordeaux pharmacovigilance centre by using the French algorithm and the logistic method. Results expressed as a probability with the logistic method and as a score from 0 to 4 with the French algorithm were then compared with consensual expert judgement, as were the sensitivity, specificity and positive and negative predictive values. Results: Probabilities ranged from 0.08 to 0.99 (median 0.58; mean 0.60) for experts versus 0.18–0.88 (median 0.73; mean 0.67) for the logistic method. Consensual expert judgement was not discriminant (p = 0.50) in ten cases. For the algorithm, only three of five causality scores were found, doubtful scores being clearly predominant (74%) followed by possible (16%) and probable (10%) scores. Sensitivity and specificity were 0.96 and 0.42, respectively, for the logistic method versus 0.42 and 0.92 for the algorithm. Positive and negative predictive values were 0.78 and 0.83, respectively, for the logistic method versus 0.92 and 0.42 for the algorithm. Conclusions: Agreement between the three approaches was poor, and only satisfactory for drug events judged as drug-induced by consensual expert judgement. The logistic method showed high sensitivity at the expense of poor specificity. Conversely, the algorithm had poor sensitivity but good specificity. The comparatively good sensitivity and positive predictive values of the logistic method suggest that it may be more useful in the routine or automated assessment of case reports of suspected but still unknown adverse drug reactions. With a substantial rate of false positives relative to true negatives (low specificity), the logistic method does not replace, but can be complemented by, critical clinical assessment of individual cases in evaluating drug-related risk.

The Case-Population Study Design An Analysis of its Application in Pharmacovigilance

AbstractBackground: The case-population approach or population-based case-cohort approach is derived from the case-control design and consists of comparing past exposure to a given risk factor in subjects presenting a given disease or symptom (cases) with the exposure rate to this factor in the whole cohort or in the source population of cases. In the same way as the case-control approach, the case-population approach measures the disproportionality of exposure between cases of a given disease and their source population expressed in the form of an odds ratio approximating the ratio of the risks in exposed and notexposed populations (relative risk). Objective: The aim of this study was to (i) present the case-population principle design in a way understandable for non-statisticians; (ii) propose the easiest way of using it for pharmacovigilance purposes (mainly alerting and hypothesis testing); (iii) propose simple formulae for computing an odds ratio and its confidence interval; (iv) apply the approach to several practical and published examples; and (v) discuss its pros and cons in the context of real life. Methods: The approach used is derived from that comparing two rates expressed as person-time denominators. It allows easy computation of an odds ratio and its confidence interval under several hypotheses. Results obtained with the case-population approach were compared with those of case-control studies published in the literature. Results: Relevance and limits of the proposed approach are illustrated by examples taken from published pharmacoepidemiological studies. The odds ratio (OR) reported in a European case-control study on centrally acting appetite suppressants and primary pulmonary hypertension was 23.1 (95% CI 6.9, 77.7) versus 31 (95% CI 16.2, 59.2) using the case-population approach. In the European case-control studies SCAR (Severe Cutaneous Adverse Reactions) and EuroSCAR on the risk of toxic epidermal necrolysis associated with the use of medicines, the OR for cotrimoxazole was 160 and 102, respectively, versus 44.4 using the case-population approach. Similarly, these two case-control studies found ORs of 12 and 72 for carbamazepine versus 24.4 using the case-population approach, 8.7 and 16 for phenobarbital versus 21.9, 12 for piroxicam (analysed in the SCAR study only) versus 14.5, and 5.5 and 18 for allopurinol versus 3.4 using the case-population approach. Conclusions: Being based on the estimate derived from sales statistics of the total exposure time in the source population of cases, the method can be used even when there is no information about the actual number of exposed subjects in this population. Although the case-population approach suffers from limitations stemming from its main advantage, i.e. impossibility to control possible confounders and to quantify the strength of associations due to the absence of an ad hoc control group, it is particularly useful to use in routine practice, mainly for purposes of signal generation and hypothesis testing in drug surveillance.

Choice of the denominator in case population studies: event rates for registration for liver transplantation after exposure to NSAIDs in the SALT study in France

The effect of denominator options on event rates was tested on the French part of the Study of Acute Liver Transplant (SALT).

Administrative complexities for a European observational study despite directives harmonising requirements

For pharmacoepidemiological studies in Europe, accessing data should require only authorisation by the relevant data protections committees, as expected from the 1995 Data Protection Directive (95/46/EC). Our experience from a multinational observational study across seven European countries shows that this is certainly not the case.

Is paracetamol hepatotoxic at normal doses

We note that the number of registrations for hepatic transplantation for paracetamol overdose found in SALT (Study of Acute Liver Transplantation) in the UK1—63 cases in 2005-07 (5.25 cases per quarter)—was the same as that reported by Hawton and colleagues.2 However, in the UK and …

Self‐medication misuse in the Middle East: a systematic literature review

Regulations usually distinguish between prescription‐only (POM) and over‐the‐counter (OTC) medicines. The former requires medical prescription; the latter are available for SM of common minor or easily treated ailments. However, in the Eastern Mediterranean countries, theoretical prescription medicines can easily be purchased without a prescription, as self‐medication (SM) resulting in potential misuse and unnecessary risk for patients. The magnitude of this activity is uncertain. The aim of this article, therefore, is to undertake a comprehensive review to identify the different types of medicines that can easily be purchased as SM in Middle East and recognized as misused. An extensive review of the published literature (1990–2015) was conducted using Pubmed, web of science, Cochrane, and Google Scholar databases, for OTC medicine misuse in the Middle East. A total of 72 papers were identified. Medicines involved in misuse included: codeine containing products, topical anesthetics, topical corticosteroids, antimalarial, and antibiotics. Self‐medication misuse of medicines seemed widespread. Individual treatment patterns were not clearly identified. Studies were not standardized, limiting the comparability between studies and the estimation of the scale of misuse. Pharmacists, friends, or parents were found to be the main sources of SMs. Knowledge and attitudes are an important contributing factor in the misuse of these medications. Strategies and interventions to limit misuse were rarely identified in literature. In conclusion, a massive problem involving a range of medicines was found in Middle East. Standardization of studies is a prerequisite to the understanding and prevention of misuse of self‐medication.

Ibuprofen is a marker of soft tissue infection

The references cited in Ospina and Salcedo’s letter seem not to support the authors’ affirmation that ibuprofen increases the risk of soft tissue infection in varicella.1 Reference 3—the only methodologically sound study—says that the study data do not support the hypothesis that non-steroidal anti-inflammatory drugs, or ibuprofen in particular, increase the risk …

A few clarifications please

Lapi and colleagues’ paper makes good pharmacological sense but I have a few comments.1 Firstly, the authors state that they adjusted for indication but it seems that they did this for antihypertensive drugs only. Was the indication for the use of non-steroidal anti-inflammatory drugs (NSAIDs) included? NSAIDs are usually …

Evaluation of Self-medication Use of Antibiotics within Lebanese Population: A Prospective Pilot Study

Objective: The aim of this study was to assess the appropriateness of antibiotic used in community based pharmacy setting. Method: It is a cross sectional prospective study in a community-based pharmacy setting in Lebanon. It uses a structured random interview to patients visiting a community pharmacy and seeking for antibiotics. Baseline characteristics and reason for self-medication were collected. Completing the questionnaire after 30 days provided information on adherence and usage pattern. Data were analyzed using descriptive statistics and Chi-square test. A multivariate logistic regression was performed to predict factors affecting appropriateness. Results: 62.7% of 501 participants bought antibiotics without prescription. Amoxicillin/clavulanic acid was the most used antibiotic as self-medication (33.7%). 62.4% of patients used the right antibiotic and 80.1% used it in correct dosage. The duration of treatment was inappropriate in the majority of cases (68.6%). When all of these three factors were summed together, it turned out that 83.6% of antibiotics were utilized inappropriately. Appropriateness in use was seen in 27.6% and 16.4% of the prescribed and non-prescribed antibiotics respectively. Conclusion: Our study shows great misuse of antibiotics and hence there is a need to increase awareness of the health risks related to inappropriate and uncontrolled use of antibiotics.

Community Usage Pattern of Antibiotics within Lebanese Population: A Prospective Study

Introduction: Antibiotic misuse is a worldwide public health problem and a major cause of antibiotic resistance. Objective: The aim of this study therefore was to describe the usage pattern of antibiotics in Lebanon. Method: It is a prospective study in a community-based pharmacy setting in Lebanon. It uses a structured random interview to patients visiting community pharmacy seeking for antibiotics. Baseline characteristics and reason for self-medication were collected. Completing a self-administered questionnaire after 30 days provided information on safety, efficacy and usage pattern. Data were analyzed using descriptive statistics and Chi-square test. Results: 62.7% of 501 participants bought antibiotic without prescription. Pharmacists were the main helpers (34.7%). Amoxicillin/clavulanic acid was the most used antibiotic as self-medication (33.7%). The overall average dispensation was 9.07 DDD for short term use (< 2 weeks). In the follow up, the average DDD consumed by patient was7.07 DDD and 62.5% were consumed between 1 to 7 DDD. The average request per year was 3.35 which was significantly higher in patients without prescription than with prescription (p= .029).Males were dispensed more DDDs than females but the result was not significant. Patients with ages from 25-50 years old had significantly consumed more than 1 DDD per day (61.7%) compared to patients with age above than 50 years old (41%, p=.002). Conclusion: Antibiotic consumption in Lebanon is uncontrolled. Educational programs should be implemented for the public to reduce the usage of antibiotic.