Inês Ribeiro-Vaz

Promoting Spontaneous Adverse Drug Reaction Reporting in Hospitals Using a Hyperlink to the Online Reporting Form

AbstractBackground: Spontaneous adverse drug reaction (ADR) reporting has been described as an efficient method to detect drug safety signals. However, under-reporting is a major issue undermining the effectiveness of spontaneous reports. Among hospitalized patients, ADRs are a particularly serious problem because these patients are often treated with more than one drug, and these drugs are often new and aggressive. Objective: To promote spontaneous ADR reporting by healthcare professionals working in hospitals in the northern regions of Portugal, we propose the inclusion of a hyperlink to an online ADR reporting form on hospitals’ electronic patient records (EPRs). The main aim of this study was to evaluate the impact of these hyperlinks on the number of spontaneous ADR reports to the Northern Pharmacovigilance Centre (UFN — Unidade de Farm-acovigilância do Norte). We also assess the number of daily UFN website visits before and after the inclusion of the hyperlinks. Methods: An ecological study was performed in northern Portuguese hospitals from 2006 to 2010. The hyperlinks were included in either EPRs or on computer desktops. The median of spontaneous ADR reports (total and online) per month and the respective ranges were presented before and after the intervention in all hospitals in this study. The comparisons were performed using the Mann-Whitney U-test. Results: Sixteen hospital centres were involved in the study (27 hospitals). Eleven centres (18 hospitals) included the hyperlinks. Considering the hospitals with hyperlink access to the EPRs, the median ADR reports per month significantly increased, from two (range 0–12) to five reports (range 1–17). The median of ADR reports per month using the online form also increased significantly, from one (range 0–5) before the intervention to four (range 1–17) after it. Moreover, serious ADRs increased 3-fold, and non-previously described ADRs increased 4.5-fold. None of these significant increases were observed in the hospitals where the hyperlink was not installed. We also found a significant increase in daily UFN website visits, from ten before the intervention to 27 after it (p<0.001). Conclusion: The increase in ADR reporting shows that the inclusion of hyperlinks to online ADR reporting forms is an easy and cost-effective way to change health professional behaviours with regard to spontaneous ADR reports.

Strategies to increase the sensitivity of pharmacovigilance in Portugal

OBJECTIVE To evaluate the results of an intervention to improve the number and relevance of reports of adverse drug reactions. METHODS A cluster-randomized controlled trial was conducted with pharmacists working in Northern Portugal, in 2007. After randomization, 364 individuals were placed into the intervention group (261 in telephone interviews and 103 in workshops), while the control group was comprised of 1,103 pharmacists. The following were approached in the educational intervention: the problem of adverse drug reaction, the impact on public health and spontaneous reporting. With regard to relevance, adverse reactions were classified into severe and unexpected. Statistical analysis was performed, based on the intention-to-treat principle; generalized linear mixed models were applied, using the penalized quasi-likelihood method. The pharmacists studied were followed during a period of 20 months. RESULTS The intervention increased the rate of spontaneous reporting of adverse reactions three times (RR = 3.22; 95% CI 1.33;7.80), when compared to the control group. The relevance of reporting rose, with an increase in severe adverse reactions by approximately four times (RR = 3.87; 95% CI 1.29;11.61) and in unexpected adverse reactions by five times (RR = 5.02; 95% CI 1.33;18.93), compared to the control group. CONCLUSIONS During a period of up to four months, educational interventions significantly increased the number and relevance of spontaneous reporting of adverse drug reactions by pharmacists in Northern Portugal.OBJETIVO: Evaluar los resultados de intervencion para mejoria de la cantidad y relevancia de las notificaciones de reacciones adversas a medicamentos. METODOS: Fue implementado un estudio controlado aleatorio, por agrupaciones de farmaceuticos que ejercen actividad profesional en la region norte de Portugal, en 2007. Posterior a la aleatoriedad, 364 individuos fueron distribuidos en el grupo de intervencion (261 en la intervencion telefonica y 103 en los workshops); el grupo control fue constituido por 1.103 farmaceuticos. En la intervencion educativa fueron abordados la problematica de las reacciones adversas a medicamentos, el impacto en la salud publica y la notificacion espontanea. Con relacion a la relevancia, las reacciones adversas fueron clasificadas en graves e inesperadas. El analisis estadistico fue efectuado con base en el principio intention-to-treat; se aplicaron modelos lineares generalizados mixtos, utilizando el metodo penalized quasi-likelihood. Los farmaceuticos estudiados fueron seguidos durante un periodo de 20 meses. RESULTADOS: La intervencion aumento tres veces la tasa de notificacion espontanea de las reacciones adversas (RR=3,22; IC95%:1,33;7,80) con relacion al grupo control. Hubo un incremento en la relevancia de las notificaciones con aumento de las reacciones adversas graves en cerca de cuatro veces (RR=3,87; IC95%:1,29;11,61) e inesperadas en cinco veces (RR=5,02; IC 95%: 1,33;18,93), con relacion al grupo control. CONCLUSIONES: Las intervenciones educativas aumentan significativamente, en hasta cuatro meses, la cantidad y la relevancia de las notificaciones espontaneas de reacciones adversas a medicamentos por parte de los farmaceuticos de la region Norte de Portugal.

Workshop- and Telephone-Based Interventions to Improve Adverse Drug Reaction Reporting

AbstractBackground: Spontaneous reporting of adverse drug reactions (ADRs) is the method most widely used by pharmacovigilance systems, with the principal limitation being the physician’s underreporting. Objective: This study sought to evaluate the results of workshop and telephone-interview interventions designed to improve the quantity and relevance of ADR reporting by physicians. Methods: A cluster-randomized controlled trial was conducted on 6579 physicians in northern Portugal in 2008. Following randomization, we allocated 1034 physicians to a telephone-interview intervention, 438 to a workshop intervention and the remaining 5107 to the control group. At the workshop, a real clinical case was presented and participants were then asked to report on it by completing the relevant form. In the telephone intervention, participants were asked (i) whether they had ever had any suspicion of ADRs; (ii) whether they had experienced any difficulties in reporting; (iii) whether they remembered the different methods that could be used for reporting purposes; and (iv) whether they attached importance to the individual physician’s role in reporting. We followed up physicians to assess ADR reporting rates to the Northern Pharmacovigilance Centre. In terms of relevance, adverse reactions were classified as serious or unexpected. Statistical analysis was performed on an intention-to-treat basis, and generalized linear mixed models were applied using the penalized quasi-likelihood method. The physicians studied were followed up over a period of 20 months. Results: Two hundred physicians underwent the educational intervention. Comparison with the control group showed that the workshop intervention increased the spontaneous ADR reporting rate by an average of 4-fold (relative risk [RR] 3.97; 95% CI 3.86, 4.08; p < 0.001) across the 20 months post-intervention. Telephone interviews, in contrast, proved less efficient since they led to no significant difference (p = 0.052) vis-à-vis the control group in ADR reporting (RR 1.02; 95% CI 1.00, 1.04). The effects of the interventions on the reporting rate of serious and high-causality ADRs indicated that the RRs associated with workshops were 6.84 (95% CI 6.69, 6.98; p<0.001) for serious ADRs and 3.58 (95% CI 3.51, 3.66; p<0.001) for high-causality ADRs. Conclusions: Whereas telephone interventions only increased spontaneous reporting in the first 4 months of follow-up, workshops significantly increased both the quantity and relevance of spontaneous ADR reporting for more than 1 year.

Estratégias para aumentar a sensibilidade da farmacovigilância em Portugal

OBJECTIVE To evaluate the results of an intervention to improve the number and relevance of reports of adverse drug reactions. METHODS A cluster-randomized controlled trial was conducted with pharmacists working in Northern Portugal, in 2007. After randomization, 364 individuals were placed into the intervention group (261 in telephone interviews and 103 in workshops), while the control group was comprised of 1,103 pharmacists. The following were approached in the educational intervention: the problem of adverse drug reaction, the impact on public health and spontaneous reporting. With regard to relevance, adverse reactions were classified into severe and unexpected. Statistical analysis was performed, based on the intention-to-treat principle; generalized linear mixed models were applied, using the penalized quasi-likelihood method. The pharmacists studied were followed during a period of 20 months. RESULTS The intervention increased the rate of spontaneous reporting of adverse reactions three times (RR = 3.22; 95% CI 1.33;7.80), when compared to the control group. The relevance of reporting rose, with an increase in severe adverse reactions by approximately four times (RR = 3.87; 95% CI 1.29;11.61) and in unexpected adverse reactions by five times (RR = 5.02; 95% CI 1.33;18.93), compared to the control group. CONCLUSIONS During a period of up to four months, educational interventions significantly increased the number and relevance of spontaneous reporting of adverse drug reactions by pharmacists in Northern Portugal.OBJETIVO: Evaluar los resultados de intervencion para mejoria de la cantidad y relevancia de las notificaciones de reacciones adversas a medicamentos. METODOS: Fue implementado un estudio controlado aleatorio, por agrupaciones de farmaceuticos que ejercen actividad profesional en la region norte de Portugal, en 2007. Posterior a la aleatoriedad, 364 individuos fueron distribuidos en el grupo de intervencion (261 en la intervencion telefonica y 103 en los workshops); el grupo control fue constituido por 1.103 farmaceuticos. En la intervencion educativa fueron abordados la problematica de las reacciones adversas a medicamentos, el impacto en la salud publica y la notificacion espontanea. Con relacion a la relevancia, las reacciones adversas fueron clasificadas en graves e inesperadas. El analisis estadistico fue efectuado con base en el principio intention-to-treat; se aplicaron modelos lineares generalizados mixtos, utilizando el metodo penalized quasi-likelihood. Los farmaceuticos estudiados fueron seguidos durante un periodo de 20 meses. RESULTADOS: La intervencion aumento tres veces la tasa de notificacion espontanea de las reacciones adversas (RR=3,22; IC95%:1,33;7,80) con relacion al grupo control. Hubo un incremento en la relevancia de las notificaciones con aumento de las reacciones adversas graves en cerca de cuatro veces (RR=3,87; IC95%:1,29;11,61) e inesperadas en cinco veces (RR=5,02; IC 95%: 1,33;18,93), con relacion al grupo control. CONCLUSIONES: Las intervenciones educativas aumentan significativamente, en hasta cuatro meses, la cantidad y la relevancia de las notificaciones espontaneas de reacciones adversas a medicamentos por parte de los farmaceuticos de la region Norte de Portugal.

Workshop- and Telephone-Based Interventions to Improve Adverse Drug Reaction Reporting A Cluster-Randomized Trial in Portugal

BACKGROUND Spontaneous reporting of adverse drug reactions (ADRs) is the method most widely used by pharmacovigilance systems, with the principal limitation being the physicians underreporting. OBJECTIVE This study sought to evaluate the results of workshop and telephone-interview interventions designed to improve the quantity and relevance of ADR reporting by physicians. METHODS A cluster-randomized controlled trial was conducted on 6579 physicians in northern Portugal in 2008. Following randomization, we allocated 1034 physicians to a telephone-interview intervention, 438 to a workshop intervention and the remaining 5107 to the control group. At the workshop, a real clinical case was presented and participants were then asked to report on it by completing the relevant form. In the telephone intervention, participants were asked (i) whether they had ever had any suspicion of ADRs; (ii) whether they had experienced any difficulties in reporting; (iii) whether they remembered the different methods that could be used for reporting purposes; and (iv) whether they attached importance to the individual physicians role in reporting. We followed up physicians to assess ADR reporting rates to the Northern Pharmacovigilance Centre. In terms of relevance, adverse reactions were classified as serious or unexpected. Statistical analysis was performed on an intention-to-treat basis, and generalized linear mixed models were applied using the penalized quasi-likelihood method. The physicians studied were followed up over a period of 20 months. RESULTS Two hundred physicians underwent the educational intervention. Comparison with the control group showed that the workshop intervention increased the spontaneous ADR reporting rate by an average of 4-fold (relative risk [RR] 3.97; 95% CI 3.86, 4.08; p < 0.001) across the 20 months post-intervention. Telephone interviews, in contrast, proved less efficient since they led to no significant difference (p = 0.052) vis-à-vis the control group in ADR reporting (RR 1.02; 95% CI 1.00, 1.04). The effects of the interventions on the reporting rate of serious and high-causality ADRs indicated that the RRs associated with workshops were 6.84 (95% CI 6.69, 6.98; p < 0.001) for serious ADRs and 3.58 (95% CI 3.51, 3.66; p < 0.001) for high-causality ADRs. CONCLUSIONS Whereas telephone interventions only increased spontaneous reporting in the first 4 months of follow-up, workshops significantly increased both the quantity and relevance of spontaneous ADR reporting for more than 1 year.

A survey of spontaneous reporting of adverse drug reactions in 10 years of activity in a pharmacovigilance centre in Portugal

Reporting of adverse drug reactions (ADRs) may differ between countries.

Promoting adverse drug reaction reporting: comparison of different approaches

ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report.

Adverse drug reactions in children: a ten-year review of reporting to the Portuguese Pharmacovigilance System

Objective: Adverse drug reactions (ADR) are a public health problem. They cause significant morbidity, mortality and health costs. Less is known about pediatric ADR. Our goal was to characterize a pediatric case series of ADR reported to the Portuguese Pharmacovigilance System (PPS) during the past 10 years. Research design and methods: Retrospective analysis of ADR reports concerning patients till 17 years old received by the PPS between 2003 and 2012. We evaluated patients’ demographic data and involved drugs, as well as characteristics and seriousness of reactions, stratified by age groups. Results: We found 1742 reports (50% females) corresponding to 9.7% of the total received. The age of the patients varied from 0 to 17 years (median: 5 years, interquartile range: 10.6), with 566 cases (32%) occurring in patients younger than 2y. Among the 1195 serious cases, 31% (370) episodes led to hospitalization. In 32 cases (2%) there was a fatal outcome. Most of the ADR reported referred to general disorders and administration site conditions, followed by skin and subcutaneous tissue reactions. Vaccines were the most represented group (42%) followed by antibacterials for systemic use (17%). Conclusions: Pediatric ADR represents about 10% of the reports received by the PPS. Most ADR were considered serious. Major findings varied according to age groups.

Causality assessment of adverse drug reaction reports using an expert-defined Bayesian network

In pharmacovigilance, reported cases are considered suspected adverse drug reactions (ADR). Health authorities have thus adopted structured causality assessment methods, allowing the evaluation of the likelihood that a drug was the causal agent of an adverse reaction. The aim of this work was to develop and validate a new causality assessment support system used in a regional pharmacovigilance centre. A Bayesian network was developed, for which the structure was defined by experts while the parameters were learnt from 593 completely filled ADR reports evaluated by the Portuguese Northern Pharmacovigilance Centre medical expert between 2000 and 2012. Precision, recall and time to causality assessment (TTA) was evaluated, according to the WHO causality assessment guidelines, in a retrospective cohort of 466 reports (April-September 2014) and a prospective cohort of 1041 reports (January-December 2015). Additionally, a simplified assessment matrix was derived from the model, enabling its preliminary direct use by notifiers. Results show that the network was able to easily identify the higher levels of causality (recall above 80%), although struggling to assess reports with a lower level of causality. Nonetheless, the median (Q1:Q3) TTA was 4 (2:8) days using the network and 8 (5:14) days using global introspection, meaning the network allowed a faster time to assessment, which has a procedural deadline of 30 days, improving daily activities in the centre. The matrix expressed similar validity, allowing an immediate feedback to the notifiers, which may result in better future engagement of patients and health professionals in the pharmacovigilance system.

Implementing Guidelines for Causality Assessment of Adverse Drug Reaction Reports: A Bayesian Network Approach

In pharmacovigilance, reported cases are considered suspected adverse drug reactions (ADR). Health authorities have thus adopted structured causality assessment methods, allowing the evaluation of the likelihood that a medicine was the causal agent of an adverse reaction. The aim of this work was to develop and validate a new causality assessment support system used in a regional pharmacovigilance centre. A Bayesian network was developed, for which the structure was defined by an expert, aiming at implementing the current guidelines for causality assessment, while the parameters were learnt from 593 completely-filled ADR reports evaluated by the Portuguese Northern Pharmacovigilance Centre expert between 2000 and 2012. Precision, recall and time to causality assessment (TTA) was evaluated, according to the WHO causality assessment guidelines, in a retrospective cohort of 466 reports (April to September 2014) and a prospective cohort of 1041 reports (January to December 2015). Results show that the network was able to easily identify the higher levels of causality (recall above 80%), although strugling to assess reports with a lower level of causality. Nonetheless, the median (Q1:Q3) TTA was 4 (2:8) days using the network and 8 (5:14) days using global introspection, meaning the network allowed a faster time to assessment, which has a procedural deadline of 30 days, improving daily activities in the centre.