Feedback for patients reporting adverse drug reactions; satisfaction and expectations.

OBJECTIVE: Due to the rising number of patient reports in pharmacovigilance, the manner in which feedback is provided to patients is an element to be considered. The objective is to explore the satisfaction of patients towards personalized and general feedback in response to their reported adverse drug reactions (ADRs). METHODS: Patients who reported an ADR to the Dutch Pharmacovigilance Centre for the first time in the period between October 2012 and April 2013 were included. Reporters received personalized feedback or a general acknowledgement letter. Satisfaction towards the received feedback, expressed on a 5-point Likert scale (1 very good to 5 very poor), was studied using a web-based questionnaire. Data were analyzed using Pearson Chi-square test and linear regression analysis. Statistical significance was based on p < 0.05. RESULTS: A total of 471 patient-reporters were contacted with a total response of 52.5%. Respondents of both groups were satisfied with the received feedback, average score 2 (good). Respondents of the personalized feedback-group were however more satisfied score 2.0 versus 2.5 (p < 0.001) and considered the feedback more clear and useful compared with respondents of the acknowledgement letter-group, respectively score 1.6 versus 1.7 (p = 0.01) and score 2.1 versus 2.5 (p < 0.001). CONCLUSION: Patients reporting ADRs are satisfied with feedback received from the pharmacovigilance centre, whether this is a personalized feedback or a general acknowledgment letter. They find it clear, useful and it meets their expectation. Although differences were found between the two types of feedback, these differences did not indicate dissatisfaction towards the received feedback.

Adverse drug reaction reports of patients and healthcare professionals-differences in reported information.

PURPOSE: 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. METHODS: This retrospective study compared the reported information between 200 ADR reports of patients and HCPs. Reports were rendered anonymous and scored for the presence or absence of predefined elements of information. These elements can be objective (e.g. start date of the ADR) or subjective (e.g. the impact or severity of the ADR). A two-sided Pearson's Chi-square test was used to detect statistically significant differences in the reported information. A Bonferroni correction was used to correct for multiple comparisons. Correlation between the elements of information was explored using categorical principal components analysis (CATPCA). RESULTS: Overall, HCPs had a higher score for the presence of objective and patients for subjective elements of information. Elements that were statistically significant more often reported by patients are the impact of the ADR and the patient's weight and height. HCPs statistically significant more often reported the medical history and the route of administration of the drug. CATPCA showed four clusters of elements of information that have fair correlation. CONCLUSIONS: This study demonstrates the differences in reported information between ADR reports of patients and HCPs. Patient reports are more focused on patient-related information and the impact of the reported ADRs, whereas reports from HCPs provide more clinically related information.

Adjuvanted A/H1N1 (2009) influenza vaccination during pregnancy: description of a prospective cohort and spontaneously reported pregnancy-related adverse reactions in the Netherlands.

BACKGROUND: During influenza pandemics, pregnant women have an increased risk of severe complications. Vaccination can diminish these complications. In the Netherlands, the adjuvanted vaccines Focetria® and Pandemrix® were used during the A/H1N1 (2009) influenza pandemic. The national vaccination scheme included pregnant women, but knowledge concerning the safety of adjuvants during pregnancy was lacking. The aim of the study is to assess safety of adjuvanted influenza vaccines during pregnancy. METHODS: The Dutch Teratology Information Service, part of the Netherlands Pharmacovigilance Centre Lareb, recruited 295 A/H1N1 (2009) vaccinated pregnant women through health care providers. Questionnaires were sent during the pregnancy to their health care providers and a second one 6 weeks after the estimated date of birth. Reported complications and adverse outcomes were compared with background rates. Additionally, the spontaneously reported pregnancy-related adverse reactions in the database of the Netherlands Pharmacovigilance Centre Lareb are described. RESULTS: Compared with the background rate, no increased risk of spontaneous abortions or congenital malformations was observed. There were three spontaneous abortions among 23 first trimester exposures. In the cohort of 281 pregnancies with known outcomes, three major malformations were observed after exposure at any time during pregnancy. In these cases exposure occurred once periconceptional, and twice in the second trimester. Furthermore, no increased risk of adverse pregnancy outcomes or neonatal problems were observed. The spontaneously reported pregnancy-related adverse events showed no unexpected pattern. CONCLUSION: The present study adds further reassurance for the safe use of adjuvanted vaccines during pregnancy and facilitates decision making in future pandemics.

Important information regarding reporting of adverse drug reactions: a qualitative study.

OBJECTIVE: To give an overview of the views of different types of reporters (patients and healthcare professionals (HCPs)) and assessors of adverse drug reactions (ADRs) on what they consider important information regarding an ADR report. METHODS: A semi-structured interview was conducted among reporters and assessors of ADRs in the Netherlands. All interviews were audiotaped and transcribed verbatim. Content analysis was used on the data. All transcripts were coded individually by two researchers. A list was drafted of all elements of information mentioned during the interviews. KEY FINDINGS: In total 16 interviews were conducted. Elements of information that were explicitly brought up during the interviews were the impact of the ADR on the patient's daily life and information regarding causality. Furthermore, the correctness of reported information was found important by assessors of ADRs. Generally, patient reporting was seen as a very positive development for pharmacovigilance. CONCLUSION: Patients reported that the severity of ADRs and their impact on daily life were important subjects. In the interviews with HCPs, either reporters or assessors, the focus was mainly on causality. The correctness of the given information is considered by ADR assessors to be very important. Regarding patient reporting the overall view was positive. Because HCPs and patients have different views regarding ADR reporting, in daily practice it is important to receive reports from both groups to assess the true nature of the ADR.

Representativeness of diabetes patients participating in a web-based adverse drug reaction monitoring system.

PURPOSE: Lareb Intensive Monitoring, LIM, is a non-interventional observational cohort method which follows first-time users of certain drugs during a certain period of time and collects information about adverse drug reactions, ADRs. In order for LIM to be a useful pharmacovigilance tool, it is important to know whether the LIM population is comparable to the whole population using the drug. The aim of this study is to compare the LIM diabetes population with an external diabetes reference population on characteristics that may influence the patient's susceptibility for ADRs. METHODS: In this study, a LIM diabetes population was compared to a reference diabetes population derived from The Groningen Initiative to ANalyse Type 2 diabetes Treatment project. Comparisons were made regarding age, gender, body mass index and polypharmacy, as well as diabetes medication used and disease/treatment duration. RESULTS: LIM patients were more often men (58.5% vs 50.8%) and in general younger (59.1 vs 64.7 years) and healthier, by that meaning they had a higher percentage of de novo treated patients (55.5% vs 53.2%), a shorter diabetes treatment duration (3.7 vs 5.5 years) and used less co-medication than patients in the reference population. CONCLUSIONS: This study shows that diabetes patients participating in a web-based intensive monitoring system differ from a reference population. The observed differences might lead to an underestimation of ADRs, but it is not clear whether this would also influence the type or time-course of the reported ADRs. When interpreting results from LIM studies, one should take these differences into account.

Patients' motives for participating in active post-marketing surveillance.

PURPOSE: 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. METHOD: A mixed model approach combining qualitative and quantitative research methods was used. For both parts, patients participating in a web-based intensive monitoring study about the safety of anti-diabetic drugs (excluding insulins) were used. A questionnaire was developed based on the results from qualitative interviews. The data collected through the questionnaires was analysed with descriptive statistics. Relations between patient characteristics and motives were analysed using a t-test or a Chi-squared test. RESULTS: 1332 (54.6%) patients responded to the questionnaire. The main motive for participation was altruism. Often experiencing ADRs or negative experiences with drugs were not important motives. The patient's gender played a role in the different motives for participation. For men, potential future personal benefit from the results was more important than for women. The overall opinion about the system was positive. CONCLUSION: The knowledge that patients participate in this kind of research from an altruistic point of view may strengthen patient involvement in pharmacovigilance.

Intensive monitoring of duloxetine: results of a web-based intensive monitoring study.

PURPOSE: Duloxetine (Cymbalta(®)) is a serotonin (5-HT) and norepinephrine (NE) re-uptake inhibitor indicated for the treatment of depression, diabetic peripheral neuropathic pain and general anxiety disorder. The aim of this study is to gain insight in the user and safety profile of duloxetine in daily practice, reported by patients via a web-based intensive monitoring system during their first 6 months of use. METHODS: First-time users of duloxetine were identified through the first dispensing signal in the pharmacy. Patient demographics and information about drug use and adverse drug reactions, ADRs, were collected through electronic questionnaires sent 2 and 6 weeks, 3 and 6 months after the start of duloxetine administration. ADRs were quantified and signal detection was performed on a case by case basis. RESULTS: Three hundred and ninety-eight patients registered for the study; 69.1 % were female. Depression was the main indication. Three hundred and three patients (76.1 %) filled in at least one questionnaire and 78.9 % of these reported an ADR. Serious ADRs were reported by 4 patients. Three new signals were identified, amenorrhea, shock-like paraesthesias and micturition problems. CONCLUSIONS: Web-based intensive monitoring is an observational prospective cohort study mirroring the use and ADRs of duloxetine in daily practice. This study indicates that duloxetine is a relatively safe drug as used by patients for six months in daily practice, but the aforementioned signals need to be evaluated in more detail.

Adverse drug reaction-related admissions in paediatrics, a prospective single-centre study.

OBJECTIVE: To investigate the incidence and characteristics of hospital admissions related to adverse drug events in the paediatric setting. DESIGN: Prospective single-centre study. SETTING: A secondary and tertiary paediatric care centre. PARTICIPANTS: A total of 683 acutely admitted patients, aged 0-18 year. All acutely admitted patients, using medication before admission, were prospectively screened for possible Adverse Drug Reactions (ADR)-related admission with a trigger list. Included cases were analysed with the Naranjo score for the assessment of causality. MAIN OUTCOME MEASURES: This research explored the incidence of ADR-related admissions and investigated the relation between ADR and the licensing status of the medicines, as well as the severity and potential to prevent the ADRs. RESULTS: A total of 683 patients were admitted acutely during the study period, 47 of them were exposed to cancer chemotherapy. Fifteen patients not exposed to chemotherapy (2.4%) were admitted due to an ADR. Five of these 15 ADRs (33%) were caused by unlicensed or off-label used drugs. Thirty-two patients exposed to chemotherapy (68.1%) were admitted due to an ADR; 27 of these (84%) were caused by unlicensed or off-label used drugs. CONCLUSIONS: In conclusion, this study shows that ADR-related hospital admissions occur more frequently in the paediatric population compared with adults, and more frequently in patients exposed to cancer chemotherapy. No relation was found between the unlicensed and off-label used drugs and the incidence of ADRs.

The rosiglitazone decision process at FDA and EMA. What should we learn?

In September 2010 the EMA decided to suspend the market authorisation of rosiglitazone, while the FDA decided to restrict the use of rosiglitazone. These actions were taken approximately 10 years after the introduction of rosiglitazone, because rosiglitazone might be associated with an increased risk of ischemic heart disease. It is often stated that the first signs of an increased risk of ischemic heart disease were noticed in 2004, however already in 2001 the FDA concluded, based on data available to the EMA at the time of initial approval, that rosiglitazone should not be used in combination with insulin, because this combination therapy was associated with an increased risk of cardiac failure and ischemic heart disease. Remarkably, in 2007, when the evidence against this combination therapy had increased, the EMA made a decision that encouraged the use of insulin in combination with rosiglitazone, while the FDA tried to restrict this combination therapy. Despite the publication of several studies, including a large randomized controlled study, the cardiovascular risk of rosiglitazone still has not been definitively established. The weight given to the benefits and the risks seems mainly a subjective decision. To prevent new cases like rosiglitazone, more attention should be given to evaluation of study protocols of safety trials prior to their starts. This paper gives a critical overview of the decision making process at the FDA and the EMA on the basis of public available information.

Epistaxis and other haemorrhagic events associated with the smoking cessation medicine varenicline: a case series from two national pharmacovigilance centres.

PURPOSE: To present a case series of haemorrhagic events associated with varenicline identified from the New Zealand (NZ) and Netherlands national pharmacovigilance centres and propose a possible mechanism for these adverse events. METHODS: Reports of epistaxis and other haemorrhagic events (in all system organ classes excluding gynaecological) associated with varenicline were identified and assessed in both the NZ Intensive Medicines Monitoring Programme (IMMP) and the Netherlands Pharmacovigilance Centre Lareb (Lareb). Additional reports were identified from the World Health Organisation Uppsala Monitoring Centre (WHO-UMC) datasets, and these also underwent causality assessment. RESULTS: A total of 30 reports of haemorrhagic events were identified by the NZ IMMP (16 reports) and Lareb (14 reports). Six cases of epistaxis were identified, and four patients had a positive dechallenge on withdrawal of varenicline, suggesting a causal association. Another five reports of gingival bleeding were identified, with three patients having a positive dechallenge. Another patient who experienced haemoptysis while taking varenicline had a positive dechallenge and a positive rechallenge. In the WHO datasets, a further 49 reports of epistaxis, 39 reports of haemoptysis and 21 reports of thrombocytopenia were identified. A plausible mechanism for haemorrhagic events associated with varenicline may be a result of interaction with the serotonin (5-HT) receptor system and transporter. CONCLUSIONS: This is the first specific investigation of haemorrhagic events associated with varenicline. The results of our assessment of reports identified by two national pharmacovigilance centres suggest that there may be causal relationship between varenicline and these adverse events.

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.

Experiences with adverse drug reaction reporting by patients: an 11-country survey.

BACKGROUND: 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. Most countries have three different ways for patients to report ADRs - a paper form, an electronic form on a website or by telephone. The level of sophistication of the electronic forms varies. The route of handling of patients' and healthcare professionals' ADR reports is the same for most countries. Personalized feedback on the reported association for each report is only given by four organizations. All countries have guidelines for the identification of patients in the database and most undertake checks for duplicate reports. In all countries, with the exception of Norway, it is possible to ask patients for follow-up. None of the organizations seek medical confirmation for each patient report. There is a difference between countries that do a causality assessment for each incoming ADR report and countries that only do a causality assessment of reports when they are looking at a potential signal. All countries assess the seriousness of reports, mostly by using the criteria of the CIOMS committee. In all countries, patient reports are used for signal detection purposes and in publications about ADRs. The Netherlands and the UK are actively evaluating their patient reporting schemes. None of the organizations hired additional staff when they started with patient reporting. CONCLUSIONS: This study provides a comprehensive review on the methods used in patient reporting of ADRs. Although there are some differences in the way various countries handle patient reports of ADRs, the importance of giving the public the opportunity to report and the additional scientific value of the collected data is widely recognized by the countries who participated in this survey.

[Adverse drug reactions of a slimming product contaminated with sibutramine]. / Bijwerkingen afslankmiddel, vervuild met sibutramine.

BACKGROUND: On the internet numerous diet pills and weight loss courses are advertised. These products may contain active ingredients or contaminants that are not mentioned on the pack or in the patient information leaflet. CASE STUDY: The Netherlands Pharmacovigilance Centre Lareb received two reports of undesirable effects associated with the unregistered slimming product 'Green Coffee 800'. A 33-year-old woman reported hypomania and a 44-year-old woman reported abnormal hepatic enzyme levels after the use of this product. Research by the Food and Consumer Product Safety Authority revealed that samples of the slimming coffee Green Coffee 800 contained sibutramine. The Dutch Healthcare Inspectorate issued a warning about this product in August 2010. It is plausible that the Green Coffee 800 in the reports sent to Lareb also contained sibutramine. CONCLUSION: The slimming product Green Coffee 800 may contain sibutramine and may cause severe adverse reactions. This product is still advertised on the Internet.

Effectiveness of pharmacovigilance training of general practitioners: a retrospective cohort study in the Netherlands comparing two methods.

BACKGROUND: Spontaneous reporting is a cornerstone of pharmacovigilance. Unfamiliarity with the reporting of suspected adverse drug reactions (ADRs) is a major factor leading to not reporting these events. Medical education may promote more effective reporting. Numerous changes have been implemented in medical education over the last decade, with a shift in training methods from those aimed predominantly at the transfer of knowledge towards those that are more practice based and skill oriented. It is conceivable that these changes have an impact on pharmacovigilance training in vocational training programmes. Therefore, this study compares the effectiveness of a skill-oriented, practice-based pharmacovigilance training method, with a traditional, lecture-based pharmacovigilance training method in the vocational training of general practitioners (GPs). The traditional, lecture-based method is common practice in the Netherlands. OBJECTIVE: The purpose of this study was to establish whether the use of a practice-based, skill-oriented method in pharmacovigilance training during GP traineeship leads to an increase of reported ADRs after completion of this traineeship, compared with a lecture-based method. We also investigated whether the applied training method has an impact on the documentation level of the reports and on the number of unlabelled events reported. STUDY DESIGN: A retrospective cohort study. The number of ADR reports submitted to the Netherlands Pharmacovigilance Centre Lareb (between January 2006 and October 2010) after completion of GP vocational training was compared between the two groups. Documentation level of the reports and the number of labelled/unlabelled events reported were also compared. RESULTS: The practice-based cohort reported 32 times after completion of training (124 subjects, 6.8 reports per 1000 months of follow-up; total follow-up of 4704 months). The lecture-based cohort reported 12 times after training (135 subjects, 2.1 reports per 1000 months of follow-up; total follow-up of 5824 months) [odds ratio 2.9; 95% CI 1.4, 6.1]. Reports from GPs with practice-based training had a better documentation grade than those from GPs with lecture-based training, and more often concerned unlabelled events. CONCLUSIONS: The practice-based method resulted in significantly more and better-documented reports and more often concerned unlabelled events than the lecture-based method. This effect persisted and did not appear to diminish over time.

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 α(2)-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.

The proportion of patient reports of suspected ADRs to signal detection in the Netherlands: case-control study.

AIM: To determine the contribution of patients' adverse drug reaction (ADR) reports to signals detection, through a study of the signals sent by Lareb to the Dutch Medicines Evaluation Board. METHODS: The percentage of patient's ADR reports contributing to generate signals of adverse drug reactions was determined. A case-control design was used to study if the proportion of patient reports in associations that had been selected as 'signals' differed from non-signals. A logistic regression analysis was used to calculate the Odds Ratio with 95%CI for patient reports in the cases and controls. RESULTS: The number of patient reports which contributed to a signal has increased from 0 reports in 2003 to 31 reports in 2008 (9% of total). Since 2005 patient reports have triggered particular associations to be selected as a signal. In 2007, 28% of all trigger reports were reported by a patient. The case-control analysis showed that patient reports were equally present in the reports used in signal formation (cases) as in the controls, reports not contributing to a signal. Odds Ratio (OR) was 1.10 (95%CI 0.81-1.49) and OR = 0.96 (95%CI 0.50-1.87) for the 'trigger reports'. CONCLUSIONS: The proportion of patient reports contributing to generate signals was equal to the proportion of patient reports in the database. Patient's reports of adverse drug reactions can provide a valuable contribution to the detection of signals in addition to healthcare professionals' reports. In the Netherlands, direct patient reports have added to the signals of adverse drug reactions sent to the Medicines Evaluation Board.

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.

Uterine perforation with the levonorgestrel-releasing intrauterine device: analysis of reports from four national pharmacovigilance centres.

BACKGROUND: Levonorgestrel-releasing intrauterine devices (LNG-IUD) are commonly used for contraception and other indications in many countries. National pharmacovigilance centres have been receiving reports from healthcare professionals and patients of uterine perforation associated with the use of these LNG-IUDs. METHODS: National pharmacovigilance centres in the Netherlands, New Zealand, Switzerland and Germany did a search on their adverse drug reaction databases for reports of cases of uterine perforation after insertion of a LNG-IUD received between the introduction of the LNG-IUD onto the market in the late 1990s and 15 July 2007. The number of women affected and patient characteristics such as age, parity and breastfeeding status were examined. In addition, the method of detection of the perforation and the time until discovery of the perforation were analysed. RESULTS: Between the introduction of the LNG-IUD onto the market in each country and 15 July 2007, 701 cases of uterine perforation with a LNG-IUD were reported; 8.5% of the perforations were detected at the time of insertion. Abdominal pain and control/check-up visits were the most common events that lead to the detection of a perforation. Of 462 women known to be parous, 192 (42%) were breastfeeding at the time the perforation was discovered. CONCLUSIONS: Uterine perforations can be asymptomatic and may remain undetected for a long time after IUD insertion. Abdominal pain, control/check-up visits or changes in bleeding patterns are triggers for detection of perforation and should therefore be taken seriously.

Fever following immunization with influenza A (H1N1) vaccine in children: a survey-based study in the Netherlands.

BACKGROUND: In November 2009, all children in the Netherlands from 6 months up to 4 years of age were indicated to receive the Influenza A (H1N1) vaccine. Fever is a common adverse event following immunization in children. Pandemrix®, an inactivated, split-virus influenza A (H1N1) vaccine, was used for this age group. A clinical study mentioned in the Summary of Product Characteristics of Pandemrix® found an increased reactogenicity after the second dose in comparison with the first dose, particularly in the rate of fever. In the Netherlands, this adverse reaction was a point of concern for the parents or caregivers of these children. OBJECTIVE: To investigate the course and height of fever following the first and second dose of Pandemrix® in children aged from 6 months up to 4 years. The secondary aim was to evaluate the use of an online survey during a vaccination campaign. DESIGN: Survey-based descriptive study. SETTING: Adverse drug reaction reporting database of the Netherlands Pharmacovigilance Centre (Lareb). PARTICIPANTS: Parents or caregivers (n = 839) of vaccinated children who reported fever to Lareb following the first immunization with Pandemrix®. Questionnaires were sent by email to parents or caregivers of eligible children following the first and second doses of Pandremix®. MAIN OUTCOME MEASURES: Time between vaccination and the occurrence of fever, the maximum measured temperature, the occurrence of other adverse events after first and second vaccination, the decision to get the second vaccination and the social implication of the fever in terms of absence from work, nursery or school, and hospitalization. RESULTS: Following the first vaccination against Influenza A (H1N1), the height of the fever was between 39.0 and 40.0°C in 359/639 (56.2%) of the children. In most of these children (235/639 [36.8%]), the onset of fever was between 6 and 12 hours following vaccination. 450/639 (70.4%) children recovered within 2 days. Of the 539 responders to the second questionnaire, 380 (70.5%) received the second vaccination against Influenza A (H1N1) and 213 (56.1%) of these children experienced fever again. The height of the fever was significantly lower (t-test; p = 0.001) and the duration was significantly shorter (Pearson's Chi-square; p = 0.002) in comparison with the first vaccination. The height of the fever after the first vaccination was associated with the decision to receive the second vaccination (t-test; p = 0.000). In the studied group, 342 (53.5%) parents or caregivers needed to stay home from work and 405 (63.4%) children stayed home from nursery or school due to fever following the first vaccination. CONCLUSIONS: The results of this study can be used in future vaccination campaigns to be able to inform people in an evidence-based manner about the risks and benefits of the vaccine and to avoid unnecessary concern and negative media attention. This could contribute to improved immunization levels. A web-based survey is demonstrated to be a useful tool to quickly gather information about a current safety concern and consequently inform the public to support an ongoing vaccination campaign.

Monitoring adverse events of the vaccination campaign against influenza A (H1N1) in the Netherlands.

BACKGROUND: In November 2009, a vaccination campaign against Influenza A (H1N1) was started in the Netherlands. The accelerated registration procedure of the vaccines used in this campaign and the use of these vaccines on a large scale indicated a need for real-time safety monitoring. OBJECTIVE: To describe the processing, analysing and performing of signal detection by the Netherlands Pharmacovigilance Centre (Lareb) on reports of adverse events following immunization (AEFI) with respect to the two pandemic influenza vaccines, Focetria® and Pandemrix®, used in the Netherlands. The secondary aim is to provide a summary of the results of the safety monitoring of both vaccines. STUDY DESIGN: Description of the process of collecting information and analysis of the safety monitoring of the pandemic vaccines during the vaccination campaign against H1N1 in the Netherlands. An observational study on adverse events following immunization (AEFIs) associated with vaccines used in this campaign was conducted. RESULTS: The use of a dedicated web form with predefined AEFIs enabled an efficient way of processing and analysing the reports, resulting in a close to real-time monitoring of the safety of the vaccines. From 1 November 2009 until 1 March 2010, 7534 reports concerning one or more AEFIs possibly related to the administration of both vaccines were received. 2788 of the reports related to Focetria® and 4746 of the reports related to Pandemrix®. The total time between receiving the reports and completion was longer for the serious reports (average 2.8 days) compared with the non-serious reports (average 0.8 days). The profile of the reported adverse events is comparable with the information provided in the Summary of Product Characteristics (SPC). Differences in reported AEFIs between both vaccines may be caused by bias and confounding due to the different populations for which these vaccines have been used. No signals of possible batch-related problems were detected for either vaccine. CONCLUSIONS: The method applied allowed for real-time monitoring for AEFIs during the mass vaccination campaign. The use of web-based forms, preferably with information on venue and used batch numbers, enabled an efficient monitoring of possible batch-related problems. No major safety issues occurred with respect to the type of reported AEFIs, or with the batches of either vaccine.