Kees van Grootheest

Adverse drug reaction-related hospitalisations: a nationwide study in The Netherlands.

AbstractBackground: The incidence of adverse drug reaction (ADR)-related hospitalisations has usually been assessed within hospitals. Because of the variability in results and methodology, it is difficult to extrapolate these results to a national level. Objectives: To evaluate the incidence and characteristics of ADR-related hospitalisations in The Netherlands in 2001. Methods: We conducted a nationwide study of all hospital admissions in 2001. Data were retrieved from a nationwide computer database for hospital discharge records. All acute, non-planned admissions to all Dutch academic and general hospitals in 2001 were included in the study (n = 668 714). From these admissions we selected all hospitalisations that were coded as drug-related, but intended forms of overdose, errors in administration and therapeutic failures were excluded. Hence, we extracted all ADR-related hospitalisations. We compared age, sex and the risk of a fatal outcome between patients admitted with ADRs and patients admitted for other reasons, as well as the most frequent main diagnoses in ADR-related hospitalisations and which drugs most frequently caused the ADRs. In addition, we evaluated to what extent these ADRs were reported to the Netherlands Pharmacovigilance Centre Lareb for spontaneous ADR reporting. Results: In 2001, 12 249 hospitalisations were coded as ADR related. This was 1.83% of all acute hospital admissions in The Netherlands (95% CI 1.80, 1.86). The proportion increased with age from 0.8% (95% CI 0.75, 0.85) in the <18 years group to 3.2% in the ≥80 years group (95% CI 3.08, 3.32). The most frequent ADR-related diagnoses of hospitalisations were bleeding (n = 1048), non-specified ‘unintended effect of drug’ (n = 438), hypoglycaemia (n = 375) and fever (n = 347). The drugs most commonly associated with ADR-related hospitalisations were anticoagulants (n = 2185), cytostatics and immunosuppressives (n = 1809) and diuretics (n = 979). Six percent of the ADR-related hospitalisations had a fatal outcome (n = 734). Older age and female gender were associated with ADR-related hospitalisations. Only approximately 1% of the coded ADRs causing hospitalisation were reported to our national centre for spontaneous ADR reporting. Conclusion: The proportion of ADR-related hospitalisations is substantial, especially considering the fact that not all ADRs may be recognised or mentioned in discharge letters. Under-reporting of ADRs that result in hospital admission to our national centre for spontaneous ADR reporting was considerable.

Adverse Drug Reaction Reporting by Patients in the Netherlands Three Years of Experience

AbstractBackground: There has been discussion about the acceptance of adverse drug reactions (ADRs) reported by patients to spontaneous reporting systems. Lack of experience with patient reporting in real life was one of the main drawbacks in this debate. This study covers 3 years of experience with patient reporting in daily practice. We compared patient reports with reports from healthcare professionals. Although patients have the opportunity to report ADRs in several countries, little is published in the literature about the contribution that patient reports have in practice. To our knowledge, this paper is the first to describe long-term experiences with patient reporting as part of a spontaneous reporting system. Methods: The number of reports received, age and sex of the reporters, characteristics of the most frequently reported drugs and characteristics of the ADRs (most frequently reported ADRs, seriousness, outcome) in a 3-year period (April 2004–April 2007) were compared between patient reports and reports from healthcare professionals. Findings: During this 3-year period, the Netherlands Pharmacovigilance Centre Lareb received 2522 reports directly from patients, concerning 5401 ADRs. In the same period, healthcare professionals submitted 10 635 reports, concerning 16 722 ADRs. Differences were found in the categories of seriousness and outcome of the reported ADRs between patients and healthcare professionals. Conversely, similarities between patient reports and reports from healthcare professionals were found in age, sex, most frequently reported ADRs and most frequently reported drugs. Interpretation: Our study highlights clearly that valuable differences between ADR reports from patients and reports from healthcare professionals exist. Differences in interpretation by patients and healthcare professionals may cause the observed disparities in seriousness and outcome of reported ADRs. However, the similarities between patient reports and reports from healthcare professionals in most frequently reported ADRs and most frequently reported drugs are striking. After 3 years of experience with patient reporting, we conclude that patient reporting in spontaneous reporting systems is feasible and that it contributes significantly to a reliable pharmacovigilance.

Application of Quantitative Signal Detection in the Dutch Spontaneous Reporting System for Adverse Drug Reactions

The primary aim of spontaneous reporting systems (SRSs) is the timely detection of unknown adverse drug reactions (ADRs), or signal detection. Generally this is carried out by a systematic manual review of every report sent to an SRS. Statistical analysis of the data sets of an SRS, or quantitative signal detection, can provide additional information concerning a possible relationship between a drug and an ADR. We describe the role of quantitative signal detection and the way it is applied at the Netherlands Pharmacovigilance Centre Lareb. Results of the statistical analysis are implemented in the traditional case-by-case analysis. In addition, for data-mining purposes, a list of associations of ADRs and suspected drugs that are disproportionally present in the database is periodically generated. Finally, quantitative signal generation can be used to study more complex relationships, such as drug-drug interactions and syndromes. The results of quantitative signal detection should be considered as an additional source of information, complementary to the traditional analysis. Techniques for the detection of drug interactions and syndromes offer a new challenge for pharmacovigilance in the near future.

Consumer Adverse Drug Reaction Reporting A New Step in Pharmacovigilance

The direct reporting of adverse drug reactions by patients is becoming an increasingly important topic for discussion in the world of pharmacovigilance. At this time, few countries accept consumer reports.We present an overview of experiences with consumer reporting in various countries of the world. The potential contribution of patient reports of adverse drug reactions is discussed, both in terms of their qualitative and quantitative contribution. The crucial question is one of whether patient reports will increase the number and quality of the reports submitted and/or lead to a more timely detection of signals of possible adverse reactions, thus contributing to an enhancement of the existing methods of drug safety monitoring. To date, the data available are insufficient to establish such added value.

Experiences with Adverse Drug Reaction Reporting by Patients An 11-Country Survey

AbstractBackground: Patients are important stakeholders in pharmacovigilance; however, little formal evaluation has been undertaken of existing patient reporting schemes within and outside Europe. If patient reporting is to be recognized as beneficial for pharmacovigilance and further optimized, methodology and best practice must be internationally shared and promoted. Objective: This study aims to review the methods of patient reporting of adverse drug reactions (ADRs) in 11 countries worldwide and to compare different aspects of their experiences. Methods: A survey based on telephone interviews, e-mail discussions and field visits of existing practices in consumer and patient reporting of ADRs was performed in the second half of 2010. Results: The start dates of the patient reporting schemes vary from 1964 (Australia) to 2010 (Norway). The number of patient reports per country varies widely. Most countries would ideally spend more resources on making the public aware of the possibility that patients can report ADRs.

Patients’ role in reporting adverse drug reactions

This review discusses the involvement of patients in the reporting of adverse drug reactions (ADRs). Patients benefit from drugs but also experience their adverse effects. Since concerns about the safety of drugs are also patients’ concerns, the patient could also play a part in decreasing the risks of drug therapy. Patient interest in the safety aspects of drugs is evident. At an international level, the merits of patient reports are being considered. To date, the literature does not yet provide any actual results in relation to the detection of ADRs by patients. Different considerations regarding ADR reporting by patients are discussed. The authors conclude that we should positively value patients’ involvement in drug therapy and their concern regarding possible adverse effects. As a consequence, patients’ reports on ADRs should be accepted.This review discusses the involvement of patients in the reporting of adverse drug reactions (ADRs). Patients benefit from drugs but also experience their adverse effects. Since concerns about the safety of drugs are also patients’ concerns, the patient could also play a part in decreasing the risks of drug therapy. Patient interest in the safety aspects of drugs is evident. At an international level, the merits of patient reports are being considered. To date, the literature does not yet provide any actual results in relation to the detection of ADRs by patients. Different considerations regarding ADR reporting by patients are discussed. The authors conclude that we should positively value patients’ involvement in drug therapy and their concern regarding possible adverse effects. As a consequence, patients’ reports on ADRs should be accepted.

Motives for reporting adverse drug reactions by patient-reporters in the Netherlands

AimThe aim of this study was to quantify the reasons and opinions of patients who reported adverse drug reactions (ADRs) in the Netherlands to a pharmacovigilance centre.MethodA web-based questionnaire was sent to 1370 patients who had previously reported an ADR to a pharmacovigilance centre. The data were analysed using descriptive statistics, χ2 tests and Spearman’s correlation coefficients.ResultsThe response rate was 76.5% after one reminder. The main reasons for patients to report ADRs were to share their experiences (89% agreed or strongly agreed), the severity of the reaction (86% agreed or strongly agreed to the statement), worries about their own situation (63.2% agreed or strongly agreed) and the fact the ADR was not mentioned in the patient information leaflet (57.6% agreed or strongly agreed). Of the patient-responders, 93.8% shared the opinion that reporting an ADR can prevent harm to other people, 97.9% believed that reporting contributes to research and knowledge, 90.7% stated that they felt responsible for reporting an ADR and 92.5% stated that they will report a possible ADR once again in the future.ConclusionThe main motives for patients to report their ADRs to a pharmacovigilance centre were the severity of the ADR and their need to share experiences. The high level of response to the questionnaire shows that patients are involved when it comes to ADRs and that they are also willing to share their motivations for and opinions about the reporting of ADRs with a pharmacovigilance centre.

Intensive Monitoring of Pregabalin Results from an Observational, Web-Based, Prospective Cohort Study in the Netherlands Using Patients as a Source of Information

Background: Pregabalin is one of the first drugs registered for the treatment of neuropathic pain. It is also indicated as adjuvant therapy in the treatment of epilepsy and for generalized anxiety disorder. Pregabalin is a GABA analogue and exerts its effect by binding to the α2-δ subunit of voltage-gated calcium channels, leading to a decreased synaptic release of neurotransmitters.Objective: To gain insight into the safety and user profile of pregabalin in daily practice, reported by patients via a web-based intensive monitoring system based at the Netherlands Pharmacovigilance Centre Lareb.Methods: Lareb Intensive Monitoring is an observational prospective cohort study with no limiting inclusion or exclusion criteria compared with clinical trials. First-time users of pregabalin were identified through the first prescription signal in intensive monitoring participating pharmacies between 1 August 2006 and 31 January 2008. Eligible patients received information about the pregabalin study in the pharmacy. When registering online, patient characteristics and information about pregabalin and other concomitant drug use were collected. After registration, the patient received questionnaires by e-mail 2 weeks, 6 weeks, 3 months and 6 months after the start of pregabalin. In these questionnaires, possible adverse drug reactions (ADRs) were addressed. Reactions not labelled in the Summary of Product Characteristics of pregabalin, and reactions that were labelled but were interesting for other reasons, were analysed on a case-by-case basis.Results: In total, 1373 patients filled in the online registration form. The average age of participants was 54.5 years (range 11–89), with 58.0% being female. The indication for pregabalin use was neuropathic pain in 85.9% of participants. The average daily dose was 201 mg, and 80.5% of all users used pregabalin capsule 75 mg. All patients who registered for the study were sent a questionnaire; 1051 (76.5%) patients filled in at least one questionnaire. There were no statistically significant differences found regarding sex, age or daily dosage between this latter group compared with the patients who registered for the study but did not fill in a questionnaire. At least one possible ADR was reported by 69.3% of patients and serious ADRs were reported by 11 patients. The five most frequently reported possible ADRs were dizziness, somnolence, feeling drunk, fatigue and increased weight. Four associations were further analysed. Headache was analysed because of its high frequency. The time to onset ranged from a few hours to 5 months, with a median time to onset of 2 days. In 15 reports the headache passed without withdrawing the drug, and in ten cases the headache disappeared after drug withdrawal. Upper abdominal pain, a possible drug interaction between pregabalin and blood glucose-lowering agents, and suicidal ideation were considered to be signals.Conclusions: Web-based intensive monitoring is an observational prospective cohort study. It will therefore provide a picture of the use of pregabalin and its ADRs in daily practice. This study indicates that pregabalin is a relatively safe drug. Eleven patients (<1.0%) experienced a serious ADR while using the drug. The most frequently reported possible ADRs correspond with the reactions most frequently reported during clinical trials. The study demonstrates that a web-based intensive monitoring system can contribute to greater knowledge about a reaction, such as headache, with quantification and information about latencies and time course of the reaction. It can also detect signals worth further investigation, such as abdominal pain and possible interaction with oral antidiabetics.

Reporting of adverse drug reactions by general practitioners : a questionnaire-based study in the Netherlands

AbstractBackground: There has been a gradual decline over the years in the number of spontaneous reports of potential adverse drug reactions (ADRs) from general practitioners (GPs) in the Netherlands. Objective: To reveal aspects of knowledge, attitudes and behaviour that can stimulate GPs to submit (more) ADRs. Methods: Dutch GPs were divided into the following two groups based on their reporting behaviour during the period 2004–6: (i) active reporters; and (ii) non-reporters. A random selection from each group was sent a questionnaire, based on the Ajzen and Fishbein model, focussed on their reporting behaviour. The questions were subdivided into knowledge-related questions, attitude-related questions and questions about the influence of the professional environment. Results: 700 questionnaires were completed, corresponding with an overall response of 47%. GPs who actively reported ADRs differed from their non-reporting colleagues: they had more knowledge on ADR reporting, were more interested in pharmacotherapy and more often had a positive example in their professional environment. Both reporting and non-reporting GPs considered it very important to comply with their professional environment. Conclusion: Specific education and training of GPs on pharmacotherapy, preferably with extra attention to ADR reporting, is expected to improve ADR reporting. Improved communication of GPs with their fellow GPs and pharmacists as well as with their patients may further stimulate ADR reporting.

Adverse drug reaction reports of patients and healthcare professionals—differences in reported information†

This study aims to explore the differences in reported information between adverse drug reaction (ADR) reports of patient and healthcare professionals (HCPs), and, in addition, to explore possible correlation between the reported elements of information.