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In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance., (© 2024. The Author(s).)

Background and Aim: Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality analyses. We here describe the development of a guideline (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance [READUS-PV]) for reporting the results of disproportionality analyses in articles and abstracts., Methods: We established a group of 34 international experts from universities, the pharmaceutical industry, and regulatory agencies, with expertise in pharmacovigilance, disproportionality analyses, and assessment of safety signals. We followed a three-step process to develop the checklist: (1) an open-text survey to generate a first list of items; (2) an online Delphi method to select and rephrase the most important items; (3) a final online consensus meeting., Results: Among the panel members, 33 experts responded to round 1 and 30 to round 2 of the Delphi and 25 participated to the consensus meeting. Overall, 60 recommendations for the main body of the manuscript and 13 recommendations for the abstracts were retained by participants after the Delphi method. After merging of some items together and the online consensus meeting, the READUS-PV guidelines comprise a checklist of 32 recommendations, in 14 items, for the reporting of disproportionality analyses in the main body text and four items, comprising 12 recommendations, for abstracts., Conclusions: The READUS-PV guidelines will support authors, editors, peer-reviewers, and users of disproportionality analyses using individual case safety report databases. Adopting these guidelines will lead to more transparent, comprehensive, and accurate reporting and interpretation of disproportionality analyses, facilitating the integration with other sources of evidence., (© 2024. The Author(s).)

Background: The yellow-card scheme continues to be one of the principal methods for signal generation in pharmacovigilance. Nevertheless, under-reporting, one of its disadvantages, delays alert signals and has a negative influence on public health. Educational interventions in pharmacovigilance may have a positive impact on the spontaneous reporting of adverse drug reactions (ADRs)., Objectives: To assess the duration of the effect and effectiveness of an educational intervention in pharmacovigilance designed to improve ADR reporting in a robust pharmacovigilance system., Methods: A spatial, cluster randomized controlled trial was conducted covering all National Health System physicians in the northwest of Spain and targeting those who were actively engaged in clinical practice (n = 7,498). Of these, 2,120 were assigned in three spatial clusters to the intervention group (six hospitals and 138 primary care centers) and 3,614 in four clusters to the control group (seven hospitals and 267 primary care centers). The educational intervention consisted of two complementary approaches--one active (group sessions), the other passive (educational material, reporting form)-implemented from November 2007 to December 2008, with a follow-up period of 8 months., Results: Intervention participation was 53.7 % in a hospital setting and 60.5 % in primary care settings. ADR reporting in the intervention group increased by 65.4 % (95 % confidence interval [CI]: 8.2-153.4) across the follow-up. The ADR reporting rate per 1,000 physicians/year in the intervention group rose from 28.1 to 39.6 following the intervention (51.7 and 27.4 in the first and second 4-month period, respectively). For the intervention group, relative risk (RR) was 2.31 (95 % CI: 1.46-3.68) and 1.04 (95 % CI: 0.61-1.77) in the first and second 4-month period, respectively adjusted to baseline values. There was an increase in unexpected ADR reporting (RR 2.06, 95 % CI 1.19-3.55)., Conclusions: Pharmacovigilance educational interventions that have proved effective can be successfully applied in different geographical areas. A high baseline notification rate could account for the educational program having a moderate effect.

Background: Underreporting is the major limitation of a voluntary adverse drug reaction (ADR) reporting system. Many studies have assessed the effectiveness of different interventions designed to reduce underreporting., Objective: We aimed to conduct a critical review of papers that assessed the effectiveness of different strategies to increase ADR reporting, regardless of the health professionals or patients included., Data Sources: Scientific papers were selected after a search of the MEDLINE-PubMed and EMBASE scientific databases up to 7 December 2010., Study Selection: We included papers in English, French or Spanish that analysed an intervention aimed at increasing the number of reported ADRs, and quantify the results of the intervention in terms of number of reports., Data Extraction: The abstracts retrieved in both computerized searches were reviewed independently by two of the authors. Initially selected papers were thoroughly read to evaluate if they met inclusion and exclusion criteria. Data in finally selected papers were independently extracted by both authors and set in pre-designed tables. A third author took the final decision in case of disagreement. For each study, we analysed study design, type of intervention, assessment period, and results of the intervention., Results: Of the 4,221 papers located that fulfilled the search criteria, 43 met the selection criteria. With the exception of one study, the interventions assessed were deemed to be effective. The vast majority of papers displayed methodological and formal limitations that lowered the grade of evidence. Multiple interventions seem to have had more impact than did single interventions. There were very few cases in which interventions were designed on the basis of inappropriate attitudes and mistaken beliefs about ADRs., Conclusions: In general, there is a need for studies of better methodological quality in this topic, so that more evidence of the effectiveness of the respective strategies can be collected for the purpose of improving ADR reporting by health professionals. It is probable that multiple interventions cause greater increases in the ADR reporting rates than single.

Background: 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.

A voluntary reporting system of adverse drug reactions (ADRs) is fundamental to drug safety surveillance but under-reporting is its major limitation. This bibliographic review sought to assess the influence of personal and professional characteristics on ADR reporting and to identify knowledge and attitudes associated with ADR reporting. A systematic review was conducted using the MEDLINE and EMBASE databases. We included papers that were published in English, French and Spanish, and covered a study population made up of health professionals. In each case, the following data were extracted: study population; workplace; study type; sample size; type of questionnaire; type of scale for measuring knowledge; response rate; personal and professional factors; and knowledge and attitudes (based on Inman's 'seven deadly sins') associated with reporting. Based on a search of computerized databases, we identified a total of 657 papers in MEDLINE and 973 in EMBASE. In all, the review covered 45 papers that fulfilled the inclusion criteria. Medical specialty was the professional characteristic most closely associated with under-reporting in 76% of studies involving physicians. Other factors associated with under-reporting were ignorance (only severe ADRs need to be reported) in 95%; diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 72%; lethargy (an amalgam of procrastination, lack of interest or time to find a report card, and other excuses) in 77%; indifference (the one case that an individual doctor might see could not contribute to medical knowledge) and insecurity (it is nearly impossible to determine whether or not a drug is responsible for a particular adverse reaction) in 67%; and complacency (only safe drugs are allowed on the market) in 47% of studies. While personal and professional factors display a weak influence, the knowledge and attitudes of health professionals appear to be strongly related with reporting in a high proportion of studies. This result may have important implications in terms of public health, if knowledge and attitudes are viewed as potentially modifiable factors.

Background: Adverse drug reaction (ADR) reporting systems are the basic component for comprehensive postmarketing surveillance of the risk of drug-induced adverse effects. The aim of this study was to evaluate the effectiveness of educational outreach visits aimed at improving ADR reporting by pharmacists., Methods: The study population comprised all pharmacists working in a catchment area covered by Portugal's Northern Regional Health Authority. Using unequal randomization, four spatial-clusters were assigned to the intervention group (n = 342) and eleven to the control group (n = 1091). The intervention took the form of 1-hour long educational outreach visits tailored to training needs detected in a previous study, with a 13- to 16-month follow-up period (March-June 2004 through June 2005). This study is registered as an international standard randomized controlled trial, number ISRCTN45894687., Results: At baseline, ADR reporting rates (per 1000 pharmacist-years) did not differ significantly between the intervention and control groups (32.28 vs 29.16). The adjusted increase in ADR reporting attributable to the intervention was 275.63 per 1000 pharmacist-years (95% CI 162.15, 389.12; relative risk [RR] = 5.87, 95% CI 1.98, 17.39). The intervention succeeded in multiplying the reporting rate of: serious ADRs, 10-fold (RR = 9.79; 95% CI 2.24, 42.66); unexpected ADRs, 4-fold (RR = 4.41; 95% CI 1.11, 17.53); high-causality ADRs, 9-fold (RR = 8.67; 95% CI 2.12, 35.42); and new drug-related ADRs, 9-fold (RR = 9.33; 95% CI 2.53, 34.40). While the greatest effect was registered during the first 4 months post-intervention, differences remained statistically significant for 8 months., Conclusions: Educational outreach visits improve ADR reporting by pharmacists in terms of quantity and relevance.

Introduction: Pharmacists can play a fundamental role in adverse drug reaction (ADR) reporting, although the factors that affect underreporting among these professionals are unknown. The objectives of this study were to identify (i) professional or demographic characteristics; and (ii) attitudes associated with pharmacists' ADR reporting in northern Portugal., Methods: We conducted a case-control study on a population of pharmacists employed in hospital and community pharmacies across Portugal's Northern Regional Health Authority catchment area in 2003. Cases (n=34) comprised pharmacists who had reported at least one ADR to the northern region's drug surveillance unit, and controls (n=280) were randomly sampled from pharmacists who had never reported an ADR. All were interviewed using a mail questionnaire. Most attitudes were based on Inman's 'seven deadly sins' and were measured using a continuous visual analogue scale. Answers were recorded in a range from 0 (total disagreement) to 10 (total agreement). Logistic regression was used to determine the ADR reporting adjusted odds ratio (OR) for a change in exposure corresponding to the interquartile range for each attitude., Results: The response rate was 86.8%. Reporting probability proved higher among hospital versus community pharmacists (adjusted OR 20.0; 95 CI 3.3, 125.0; p<0.001). Attitudes to ADRs were strongly associated with reporting probability. Hence, an interquartile decrease in any of the following attitudes increased the probability of reporting by (i) 223% (95% CI 51, 595; p < 0.05) for "Really serious ADRs are well documented by the time a drug is marketed"; (ii) 240% (95% CI 89, 508; p=0.002) for "I would only report an ADR if I were sure that it was related to the use of a particular drug"; (iii) 316% (95% CI 44, 1104; p=0.010) for "It is only necessary to report serious or unexpected ADRs"; and (iv) 171% (95% CI 13, 549; p=0.020) for "I do not have time to think about the involvement of the drug or other causes in ADRs"., Conclusions: ADR under-reporting is strongly associated with certain attitudes, possibly indicating that under-reporting could be minimised through educational interventions targeted at changing such attitudes. Pharmacists' ADR education must be improved and educational programmes should be focused on altering attitudes identified by the study as being associated with under-reporting. Our data also indicate that community pharmacists must be a priority target for this intervention.

Objectives: Voluntary adverse drug reaction (ADR) reporting is fundamental to medical drug safety surveillance; however, substantial under-reporting exists and is the main limitation of the system. This study sought to identify the knowledge- and attitude-related factors associated with ADR reporting by physicians in Northern Portugal., Methods: Case-control study covering a population of National Health Service medical practitioners. The 88 cases comprised physicians who had reported at least one ADR to the drug surveillance unit from the year 2000 to the date of enrolment in the study. The 771 controls were randomly selected from among the remaining physicians. All interviews were conducted using a self-administered questionnaire. Knowledge and attitudes regarding spontaneous ADR reporting were based on Inman's 'seven deadly sins'. Agreement with the questions included in the questionnaire was measured using a horizontal, continuous visual analogue scale, which was unnumbered. Recorded answers were read in a range from zero (total disagreement) to ten (total agreement). We used logistic regression to determine the ADR reporting adjusted odds ratio (ORadj) for a change in exposure corresponding to the interquartile range for each attitude., Results: A total of 397 questionnaires were received from 731 eligible practitioners (54.3%). Physicians who worked in primary versus hospital care (ORadj 7.74 [95% CI 1.85, 32.30]) and in general medicine (ORadj 1.05 [95% CI 0.30, 3.69]) versus medical specialities were more likely to report ADRs. In contrast, physicians working in the medical-surgical/surgical fields were significantly less likely to report ADRs compared with medical specialists (ORadj 0.10 [95% CI 0.02, 0.46]). Attitudes to ADRs were strongly associated with reporting probability. Hence, an interquartile decrease in any of the following attitudes increased the probability of reporting by: (i) 87% (p < 0.05) for complacency (the belief that really serious ADRs are well documented by the time a drug is marketed); (ii) 109% (p < 0.01) for insecurity (the belief that it is nearly impossible to determine whether a drug is responsible for a particular adverse reaction); (iii) 143% (p < 0.001) for diffidence (the belief that one would only report an ADR if one were sure that it was related to the use of a particular drug); (iv) 220% (p < 0.001) for indifference (the belief that the one case an individual doctor might see could not contribute to medical knowledge); and (v) 71% (p < 0.05) for ignorance (the belief that it is only necessary to report serious or unexpected ADRs)., Conclusion: This study shows that there are attitudes strongly associated with under-reporting. The implementation of purpose-designed educational interventions based on the attitudes identified in this study may serve to improve reporting substantially.