Linda Härmark

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.

ADR Reporting by the General Public: Lessons Learnt from the Dutch and Swedish Systems

Consumer reporting of adverse drug reactions (ADRs) has existed in several countries for decades, but throughout Europe the role of consumers as a source of information on ADRs has not been fully accepted until recently. In Europe, The Netherlands and Sweden were among the first countries to implement consumer reporting well before it was mandated by law throughout the EU. Consumer reporting is an integral part of the spontaneous reporting systems in both The Netherlands and Sweden, with yearly numbers of reports constantly increasing. Consumer reporting forms and handling procedures are essentially the same as for healthcare professional reporting; the message in the reports, not the type of messenger, is what is of importance. Studies have established the significant contribution of consumer reporting to ADR signal detection. Combining all reports regardless of reporter type is recommended since it yields the largest critical mass of reports for signal detection. Examples of signals where consumer reports have been of crucial importance for signal detection are electric shock-like sensations associated with the use of duloxetine, and persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. An example of consumer reporting significantly strengthening a detected signal is Pandemrix® (influenza H1N1 vaccine)-induced narcolepsy. Raising public awareness of ADR reporting is important, but time- and resource-consuming. The minimum effort taken should be to passively inform consumers, e.g. via stakeholders’ homepages and via drug product information leaflets. Another possibility of reaching out to this target group could be through co-operation with other (non-government) organizations. Information from consumer reports may give a new perspective on ADRs via the consumers’ unfiltered experiences. Consumers’ views may change the way the benefit–harm balance of drugs is perceived and assessed today, and, being the ultimate users of drugs, consumers could have a relevant influence in the regulatory decision-making processes for drugs. All stakeholders in pharmacovigilance should embrace this new valuable source of information.

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.

Longitudinal monitoring of the safety of drugs by using a web-based system: the case of pregabalin

Information about the time course of adverse drug reactions (ADRs) is often lacking. If this information would be available, it could help increase patients adherence to drugs when experiencing an ADR. The aim of this study was to demonstrate how a web‐based intensive monitoring system using the patient as a source of information can be used to gather longitudinal safety data of a drug. In this study, pregabalin was used as an example.

Monitoring the safety of influenza A (H1N1) vaccine using web-based intensive monitoring.

BACKGROUND When adjuvant vaccines against the pandemic influenza A (H1N1) virus became available after an accelerated registration process, safety issues dominated the public debate. As part of the immunisation campaign, the Dutch government installed an active monitoring of possible adverse events following immunisation (AEFIs). As part of the monitoring we conducted an anonymous prospective cohort study to identify and quantify the occurrence of AEFIs related to pandemic vaccination among the population immunised in general practice. METHOD Adults aged 60 years and older or persons with a risk-elevating medical condition recommended for vaccination in general practice were eligible for participation. After receipt of the first pandemic vaccine the administrator handed over an information flyer of the web-based monitoring program. The patient could sign up for study participation online. Within one week, three weeks and three months after the first immunisation questions were asked about demographics and health, immunisations, injections site reactions and labeled reactions as well as other possible new AEFIs. RESULTS In all, 3569 participants filled in the first questionnaire. Corresponding figures for the second and third questionnaires were 3395 (95.1%) and 3162 (88.6%). Mean age was 58 years (SD 15) and 50.1% was female. Main indication was 60 years or older followed by presence of pulmonary or cardiovascular disease. Of all participants, 1311 (37%) reported an AEFI. Unexpected serious reactions were not reported nor were there signals of possible new AEFIs. The occurrence of an AEFI was determined by gender, age and type of co-morbidity. CONCLUSION The web-based intensive monitoring system among patients immunised in general practice revealed AEFIs due to pandemic vaccination in one-third of participants. There were no unexpected serious adverse events in this population. This advanced methodology can be further developed to monitor real-time use and AEFIs of vaccines.

Web-based intensive monitoring: from passive to active drug surveillance

Introduction: Recently, the European pharmacovigilance legislative framework changed. Post-authorisation safety studies (PASS) and additional monitoring of drugs will be important tools in ensuring the safety of drugs. Methods that can facilitate gathering of the requested information are essential. In this article, web-based intensive monitoring is described and future applications of this method are discussed. Areas covered: Web-based intensive monitoring is a non-interventional observational cohort study using patients as a source of information. Eligible patients are identified in the pharmacy, and information about drug use and adverse events is collected through web-based questionnaires. An overview of the results as well as the pros and cons of this method is given. A discussion on how this methodology can be expanded to other settings and how it can be used in the future is included. Expert opinion: The main idea with web-based intensive monitoring, using a specific inclusion point, letting patients be the source of information and following the patients over time via web questionnaires, can be a useful tool in post-marketing surveillance. Aspects other than adverse drug reactions, such as information about indication for use and off-label use, dosage and compliance can also be collected.

Patients’ motives for participating in active post-marketing surveillance

Web‐based intensive monitoring is a method to actively collect information about adverse drug reactions (ADRs) using patients as a source of information. To date, little is known about patients’ motivation to participate in this kind of active post‐marketing surveillance (PMS). Increased insight in this matter can help us to better understand and interpret patient reported information, and it can be used for developing and improving patient‐based pharmacovigilance tools. The aim of this study is to gain insight into patients’ motives for participating in active PMS and investigate their experiences with such a system.

Patient-Reported Safety Information: A Renaissance of Pharmacovigilance?

The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years have passed since the legislation was introduced and the key question is: does pharmacovigilance yet make optimal use of patient-reported safety information? Independent research has shown beyond doubt that patients make an important contribution to pharmacovigilance signal detection. Patient reports provide first-hand information about the suspected ADR and the circumstances under which it occurred, including medication errors, quality failures, and ‘near misses’. Patient-reported safety information leads to a better understanding of the patient’s experiences of the ADR. Patients are better at explaining the nature, personal significance and consequences of ADRs than healthcare professionals’ reports on similar associations and they give more detailed information regarding quality of life including psychological effects and effects on everyday tasks. Current methods used in pharmacovigilance need to optimise use of the information reported from patients. To make the most of information from patients, the systems we use for collecting, coding and recording patient-reported information and the methodologies applied for signal detection and assessment need to be further developed, such as a patient-specific form, development of a severity grading and evolution of the database structure and the signal detection methods applied. It is time for a renaissance of pharmacovigilance.

The contribution of direct patient reported ADRs to drug safety signals in the Netherlands from 2010 to 2015

The purpose of this study was to investigate the contribution of patient reports to signals sent by the Netherlands Pharmacovigilance Centre Lareb to the Dutch Medicines Evaluation Board and to determine if there are certain types of signals where patient report add a distinct contribution.

Safety Concerns Reported by Patients Identified in a Collaborative Signal Detection Workshop using VigiBase: Results and Reflections from Lareb and Uppsala Monitoring Centre

IntroductionPatient reporting in pharmacovigilance is important and contributes to signal detection. However, descriptions of methodologies for using patient reports in signal detection are scarce, and published experiences of how patient reports are used in pharmacovigilance are limited to a few individual countries.ObjectiveOur objective was to explore the contribution of patient reports to global signal detection in VigiBase.MethodsData were retrieved from VigiBase in September 2016. Drug–event-combination series were restricted to those with >50% patient reports, defined as reporter type “Consumer/non-health professional” per E2B reporting standard. vigiRank was applied to patient reports to prioritize combinations for assessment. Product information for healthcare professionals (HCPs) as well as patient information leaflets (PILs) were used as reference for information on adverse drug reactions (ADRs). Staff from the Uppsala Monitoring Centre and the Netherlands Pharmacovigilance Centre Lareb categorized the combinations. Potential signals proceeded to a more in-depth clinical review to determine whether the safety concern should be communicated as a “signal.”ResultsOf the 212 combinations assessed, 20 (9%) resulted in eight signals communicated within the World Health Organization (WHO) programme for international drug monitoring. Review of PILs revealed insufficient ADR descriptions for patients and examples of poor consistency with product information for HCPs. Patient narratives provided details regarding the experience and impact of ADRs and evidence that patients make causality and personal risk assessments.ConclusionsSafety concerns described in patient reports can be identified in a global database including previously unknown ADRs as well as new aspects of known ADRs. Patient reports provide unique information valuable in signal assessment and should be included in signal detection. Novel approaches to highlighting patient reports in statistical signal detection can further improve the contribution of patient reports to pharmacovigilance.