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Introduction Healthcare professionals (HCPs) are informed about new drug safety issues through Direct Healthcare Professional Communications (DHPCs). The influence of DHPC content on the impact of the communication is unclear. Objectives The aim of this study was to assess the effect of content elements 'frequency of the safety issue', 'seriousness of the safety issue', 'need to take action', 'life span of drug involved' and 'type of evidence supporting the safety issue' on hospital-based HCPs' preferences and responses towards DHPCs. Methods A survey study including a conjoint experiment was performed among hospital-based HCPs in the Netherlands. Hypothetical DHPCs varying on the five content elements were constructed. Each respondent received eight out of 16 hypothetical DHPCs and was asked about (1) importance to be informed (fixed-point scale), (2) preferred communication timing (multiple options) and (3) their stated actions (multiple options). Associations were tested using generalized linear mixed models. Results In total, 178 HCPs participated. DHPCs concerning more frequent or serious safety issues, or requiring action, were associated with a higher perceived importance to be informed and a preference for immediate communication. Periodic communication was preferred for DPHCs concerning less frequent or serious safety issues. The most commonly stated action was to discuss the DHPC with colleagues. Monitoring was common when this was recommended. High frequency and seriousness were associated with more prescribing-related actions. Conclusion Frequency and seriousness of the safety issue and the recommended action are likely to influence the impact of DHPCs. The timing of communication could be tailored depending on the content, where less urgent safety issues might be communicated periodically.

INTRODUCTION: The implementation of new drug safety information and Direct Healthcare Professional Communications (DHPCs) in hospitals is important for patient safety.OBJECTIVES: The aim of this study was to gain insight into which procedures and practices are in place to handle new drug safety information and particularly DHPCs in the Dutch hospital setting.METHODS: We first conducted focus groups including medical specialists and hospital pharmacists, focusing on handling of drug safety information at the individual and organisational level. A survey was then developed and distributed among hospital pharmacists in all Dutch hospitals to quantify the existence of specific procedures and committees to handle drug safety information and DHPCs.RESULTS: Eleven specialists and 14 pharmacists from six hospitals participated in focus groups. Drug safety information was usually considered before drugs were included in formularies or treatment protocols. Furthermore, drug safety information was consulted in response to patients experiencing adverse events. DHPCs were mostly dealt with by individual professionals. DHPCs could lead to actions but this was very uncommon. Completed surveys were received from 40 (53%) of the hospitals. In 32 (80%), the hospital pharmacy had procedures to deal with new drug safety information, whereas in 11 (28%) a hospital-wide procedure was in place. Drug safety was considered in committees concerning drug formulary decisions (69%) and antibiotic policies (63%). DHPCs were assessed by a hospital pharmacist in 50% of the hospitals.CONCLUSIONS: Drug safety information was used for evaluation of new treatments and in response to adverse events. Assessment of whether a DHPC requires action was primarily an individual task.

Introduction Healthcare professionals (HCPs) and patients have various motives to report adverse drug reactions (ADRs) to their national agency. These motives may differ between countries. Objective The aim of this study was to assess to what extent motives of HCPs and patients to report ADRs differ between countries. Methods HCPs and patients from Croatia (HR), The Netherlands (NL), and the UK were asked to complete a web-based survey containing questions regarding demographics and ADR reporting. HCPs and patients could select all motives for reporting that applied to them, with a total of 23 and 24 motives, respectively. Descriptive statistics are presented and Chi-square tests were used to test for differences across the countries, with effect sizes calculated using Cramer’s V. Results In total, 296 HCPs and 423 patients were included (60% and 32% from Croatia, 19% and 44% from NL, and 21% and 24% from the UK, respectively). For most of the motives to report or not to report an ADR, there were no differences between countries. Most HCPs from all countries would be motivated to report an ADR if there was a strong suspicion of causality (89%), if it concerned a severe/serious ADR (86%), and if it concerned an ADR for a new, recently marketed drug (77%). Most patients from all countries agreed that they would report an ADR if it concerned a severe ADR (96%), if the ADR influenced their daily activities (91%), and if they were worried about their own situation (90%). Differences across the countries (p

Background Some drug safety issues communicated through direct healthcare professional communications (DHPCs) receive substantial media coverage, while others do not. Objectives The objective of this study was to assess the extent of coverage of drug safety issues that have been communicated through DHPCs in newspapers and social media. A secondary aim was to explore which determinants may be associated with media coverage. Methods Newspaper articles covering drug safety issues communicated through 387 DHPCs published between 2001 and 2015 were retrieved from LexisNexis Academic™. Social media postings were retrieved from Coosto™ for drugs included in 220 DHPCs published between 2010 and 2015. Coverage of DHPCs by newspapers and social media was assessed during the 2-month and 14-day time periods following issuance of the DHPC, respectively. Multivariate logistic regression was used to assess potential DHPC- and drug-related determinants of media coverage. Results 41 (10.6%) DHPC safety issues were covered in newspaper articles. Newspaper coverage was associated with drugs without a specialist indication [adjusted odds ratio 5.32; 95% confidence interval (2.64–10.73)]. Negative associations were seen for time since market approval [3–5 years 0.30; (0.11–0.82), 6–11 years 0.18; (0.06–0.58)] and year of the DHPC [0.88; (0.81–0.96)]. In the social media, 180 (81.8%) drugs mentioned in 220 DHPCs were covered. Social media coverage was associated with drugs without a specialist indication [6.92; (1.56–30.64)], and for DHPCs communicating clinical safety issues [5.46; (2.03–14.66)]. Conclusions Newspapers covered a small proportion of DHPC safety issues only. Most drugs mentioned in DHPCs were covered in social media. Coverage in both media were higher for drugs without a specialist indication. Electronic supplementary material The online version of this article (10.1007/s40264-020-00922-7) contains supplementary material, which is available to authorized users.

National competent authorities (NCAs) use Direct Healthcare Professional Communications (DHPCs) to communicate new drug safety issues to healthcare professionals (HCPs). More knowledge is needed about the effectiveness of DHPCs and the extent to which they raise awareness of new safety issues among HCPs.The objective was to assess and compare general practitioners' (GPs'), cardiologists', and pharmacists' familiarity with DHPCs as communication tools, their awareness of specific drug safety issues, and the sources through which they had become aware of the specific issues.GPs, cardiologists, and pharmacists from nine European countries (Croatia, Denmark, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the UK) completed a web-based survey. The survey was conducted in the context of the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. Respondents were asked about their familiarity with DHPCs in general and their awareness of safety issues that had recently been communicated and involved the following drugs: combined hormonal contraceptives, diclofenac, valproate, and ivabradine. Those HCPs who were aware of the specific safety issues were subsequently asked to indicate the source through which they had become aware of them. Differences between professions in familiarity with DHPCs and awareness were tested using a Pearson χOf the 3288 included respondents, 54% were GPs, 40% were pharmacists, and 7% were cardiologists. The number of respondents ranged from 67 in Denmark to 916 in Spain. Most respondents (92%) were familiar with DHPCs, with one significant difference between the professions: pharmacists were more familiar than GPs in Italy (99 vs 90%, P = 0.004). GPs' awareness ranged from 96% for the diclofenac issue to 70% for the ivabradine issue. A similar pattern was shown for pharmacists (91% aware of the diclofenac issue to 66% of the ivabradine issue). Cardiologists' awareness ranged from 91% for the ivabradine issue to 34% for the valproate issue. Overall, DHPCs were a common source through which GPs (range: 45% of those aware of the contraceptives issue to 60% of those aware of the valproate issue), cardiologists (range: 33% for the contraceptives issue to 61% for the valproate issue), and pharmacists (range: 41% for the contraceptives issue to 51% for the ivabradine issue) had become aware of the specific safety issues, followed by information on websites or in newsletters.GPs, cardiologists, and pharmacists were to a similar extent (highly) familiar with DHPCs, but they differed in awareness levels of specific safety issues. Cardiologists were less aware of safety issues associated with non-cardiology drugs even if these had cardiovascular safety concerns. This implies that additional strategies may be needed to reach specialists when communicating safety issues regarding drugs outside their therapeutic area but with risks related to their field of specialisation. DHPCs were an important source for the different professions to become aware of specific safety issues, but other sources were also often used. NCAs should consider the use of a range of sources when communicating important safety issues to HCPs.

National competent authorities (NCAs) use Direct Healthcare Professional Communications (DHPCs) to communicate new drug safety issues to healthcare professionals (HCPs). More knowledge is needed about the effectiveness of DHPCs and the extent to which they raise awareness of new safety issues among HCPs.The objective was to assess and compare general practitioners' (GPs'), cardiologists', and pharmacists' familiarity with DHPCs as communication tools, their awareness of specific drug safety issues, and the sources through which they had become aware of the specific issues.GPs, cardiologists, and pharmacists from nine European countries (Croatia, Denmark, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the UK) completed a web-based survey. The survey was conducted in the context of the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. Respondents were asked about their familiarity with DHPCs in general and their awareness of safety issues that had recently been communicated and involved the following drugs: combined hormonal contraceptives, diclofenac, valproate, and ivabradine. Those HCPs who were aware of the specific safety issues were subsequently asked to indicate the source through which they had become aware of them. Differences between professions in familiarity with DHPCs and awareness were tested using a Pearson chi (2) test per country and post hoc Pearson chi (2) tests in the case of statistically significant differences.Of the 3288 included respondents, 54% were GPs, 40% were pharmacists, and 7% were cardiologists. The number of respondents ranged from 67 in Denmark to 916 in Spain. Most respondents (92%) were familiar with DHPCs, with one significant difference between the professions: pharmacists were more familiar than GPs in Italy (99 vs 90%, P = 0.004). GPs' awareness ranged from 96% for the diclofenac issue to 70% for the ivabradine issue. A similar pattern was shown for pharmacists (91% aware of the diclofenac issue to 66% of the ivabradine issue). Cardiologists' awareness ranged from 91% for the ivabradine issue to 34% for the valproate issue. Overall, DHPCs were a common source through which GPs (range: 45% of those aware of the contraceptives issue to 60% of those aware of the valproate issue), cardiologists (range: 33% for the contraceptives issue to 61% for the valproate issue), and pharmacists (range: 41% for the contraceptives issue to 51% for the ivabradine issue) had become aware of the specific safety issues, followed by information on websites or in newsletters.GPs, cardiologists, and pharmacists were to a similar extent (highly) familiar with DHPCs, but they differed in awareness levels of specific safety issues. Cardiologists were less aware of safety issues associated with non-cardiology drugs even if these had cardiovascular safety concerns. This implies that additional strategies may be needed to reach specialists when communicating safety issues regarding drugs outside their therapeutic area but with risks related to their field of specialisation. DHPCs were an important source for the different professions to become aware of specific safety issues, but other sources were also often used. NCAs should consider the use of a range of sources when communicating important safety issues to HCPs.

Introduction National competent authorities (NCAs) for medicines coordinate communication relating to the safety of medicines in Europe. The effectiveness of current communication practices has been questioned, particularly with regard to reaching general practitioners (GPs). Objective The aim of this study was to assess current European NCA safety communication practices and to investigate European GPs’ awareness of and preferences for safety communications on medicines. Methods Web-based surveys were distributed among European NCAs and healthcare professionals (HCPs). The survey among regulators was emailed to a representative of each of the 27 European countries participating in the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. HCPs from nine European countries (Denmark, Spain, Croatia, Ireland, Italy, The Netherlands, Norway, Sweden, and the UK) were asked about their preferences through a link to the survey on websites, in newsletters, and/or in a direct email. From this survey, data from GPs were used and descriptive analyses were conducted. Results Current NCA practices were reported for 26 countries. In 23 countries (88%), NCAs published direct healthcare professional communications (DHPCs, i.e. urgent communication letters for serious safety issues) on their website in addition to distribution to individual HCPs. Educational materials were available on the NCA’s website in 10 countries (40%), and 21 NCAs (81%) indicated they had their own bulletin/newsletter, which is often presented on the NCA’s website (15 countries; 60%). More than 90% of the 1766 GPs who completed the survey were aware of DHPCs. The most preferred senders of safety information were NCAs and professional bodies, while the preferred channels for keeping up to date with safety information were medicines reference books and clinical guidelines. GPs found the repetition of safety issues useful (range of 80% in the UK to 97% in Italy). Preference for an electronic copy rather than a hardcopy varied per country (36% in Sweden to 72% in Spain). Conclusions NCAs use similar methods for safety communications on medicines. Most GPs were aware of urgent communications and preferred similar senders of safety communications; however, their preferences towards the format differed per country. Electronic supplementary material The online version of this article (doi:10.1007/s40264-017-0535-0) contains supplementary material, which is available to authorized users.

Introduction In general, women more often experience metformin-associated adverse drug reactions (ADRs) than men. Objectives We aimed to assess whether sex differences in reported ADRs for metformin are observed at different times after initiation, and to explore their concurrence with sex differences in the dose of metformin over time. This may guide future studies in assessing the involved mechanisms of sex differences in metformin-associated ADRs and may guide sex-specific management of ADRs in clinical practice. Methods This study has a longitudinal design using data about patients initiating metformin collected by the Dutch National Pharmacovigilance Center Lareb through their Intensive Monitoring program. Patients were asked to complete a web-based questionnaire six times after initiation (i.e., at 2 weeks, 6 weeks and at 3, 6, 9, and 12 months). The outcome variables were the proportion of patients reporting any ADR (primary) and the dose of metformin (secondary). Sex differences in the proportions of ADRs and in the dose were tested at each assessment using Pearson Chi-Squared tests and Wilcoxon rank-sum tests, respectively. Using Bonferroni adjustment for multiple testing, a p value

Background: Non-serious symptomatic adverse drug events (ADEs) affect the real benefit-risk ratio of a drug. Currently, such ADEs are quantified in different ways, often using reports from a healthcare provider or patients, resulting in large variations in estimated rates. Several studies showed that patients report bothersome or symptomatic ADEs more frequently than providers, but no comparisons to an external reference or gold standard have been made. Objective: We conducted a literature review to assess the agreement and concurrent validity of healthcare provider- and patient-oriented methods for quantifying symptomatic ADEs of oral blood glucose-lowering drugs in patients with type 2 diabetes mellitus. Methods: We systematically searched MEDLINE and EMBASE databases for observational studies reporting on rates of ADEs in patients treated for type 2 diabetes that were published between 1999 and 2011. We included nine observational studies reporting absolute rates of symptomatic ADEs in patients receiving monotherapy. We calculated 95% confidence intervals and assessed agreement between rates observed with different methods. We assessed concurrent validity using the range noted in the Summary of Product Characteristics (SPC) as the gold standard. Results: A comparison of rates reported by patients and providers was only possible using three studies of metformin that assessed mainly gastrointestinal (GI) ADEs. Provider-oriented methods by means of medical record review gave lower rates for abdominal pain (0.6–3.7%), dyspepsia (1.3–2.8%) and constipation (0.6–1.0%) than a patient questionnaire method (8.5%, 11.9% and 20.7%, respectively). For diarrhoea, the patient-reported rate (5.2%) was in agreement with the provider-based rates (1.6–7.6%). The majority of the rates reported by providers and patients were not corresponding with the ranges in the SPC. For GI ADEs the rates were all lower, whereas for lactic acidosis and hypoglycaemia the rates were higher. Conclusion: Although it has repeatedly been proposed that patients’ reports on safety should be incorporated with providers’ reports, especially for symptomatic ADEs, the number of observational studies using patient-oriented methods for assessing ADEs other than hypoglycaemia are limited. Provider-based measurement tended to underestimate symptomatic ADEs. Patient-oriented methods seemed to give ADE rates that were closer to the rates reported in the SPC.

Background Direct patient reporting of adverse drug events (ADEs) is relevant for the evaluation of drug safety. To collect such data in clinical trials and postmarketing studies, a valid questionnaire is needed that can measure all possible ADEs experienced by patients.Objective Our aim was to develop and test a generic questionnaire to identify ADEs and quantify their nature and causality as reported by patients.Methods We created a draft list of common ADEs in lay-terms, which were classified in body categories and mapped to the Medical Dictionary for Regulatory Activities (MedDRA (R)) terminology. Questions about the nature and causality were derived from existing questionnaires and causality scales. Content validity was tested through cognitive debriefing, revising the questionnaire in an iterative process. Feasibility and reliability were assessed using a Web-based version of the questionnaire. Patients received the questionnaire twice. Feasibility was assessed by the reported time needed for completion and ease of use. Reliability was calculated using Cohen's kappa and proportion of positive agreement (PPA) on: (1) any AIDE at patient level; (2) similar ADEs at MedDRA (R) System Organ Class level; and (3) the same AIDE at AIDE-specific level.Results In the development phase, 28 patients with type 2 diabetes or asthma/chronic obstructive pulmonary disease (COPD) participated. Questions and answer options were rephrased, layout was improved, and changes were made in the classification of ADEs. The final questionnaire consisted of 252 ADEs organized in 16 body categories, and included 14 questions per reported AIDE. A total of 135 patients using a median of five different drugs completed the Web-based questionnaire twice. The median completion time was 15 mm for patients not reporting any AIDE, and 30 mm for patients reporting at least one AIDE. Three quarters of the patients found the questionnaire easy to use. Test-retest reliability was acceptable at patient level (kappa = 0.50, PPA 0.64) and at MedDRA (R) System Organ Class level (kappa = 0.52, PPA 0.54), but was low at ADE-specific level (kappa = 0.38, PPA 0.38).Conclusion We developed a generic patient-reported AIDE questionnaire and confirmed its content validity. The questionnaire was feasible and reliable for reporting any AIDE and similar ADEs at MedDRA (R) System Organ Class level. Additional work is, however, needed to reliably quantify specific ADEs reported by patients.