Evaluation of the Effectiveness of the Risk Minimization Measures of Sodium Oxybate in the European Union.
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ABSTRACT:
SUBMITTER: Iranzo A
PROVIDER: S-EPMC7581670 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Evaluation of the Effectiveness of the Risk Minimization Measures of Sodium Oxybate in the European Union.
Iranzo Alex A Serralheiro Pedro P Schuller Jan-Christof JC Schlit Anne-Françoise AF Bentz Jürgen W G JWG
Drugs - real world outcomes 20201201 4
<h4>Background</h4>Sodium oxybate (Xyrem<sup>®</sup>), approved by the European Medicines Agency (EMA) for narcolepsy with cataplexy, is only available through risk mitigation programs due to potential adverse effects including respiratory and central nervous system depression, neuropsychiatric events, and misuse.<h4>Objective</h4>We report findings from a survey evaluating effectiveness of the European Union Xyrem<sup>®</sup> Risk Management Plan (RMP).<h4>Patients and methods</h4>A cross-secti ...[more]
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Project description:BackgroundA Guide for Healthcare Professionals (HCP Guide) and patient alert card (PAC) for atezolizumab as additional risk minimization measures for physicians were distributed to raise awareness and help in the detection and management of immune-related adverse drug reactions.ObjectivesThe main objective of this study was to assess the receipt, knowledge, and behaviors of physicians regarding the atezolizumab HCP Guide and PAC.MethodsA multi-country, one-wave, observational, cross-sectional, web-based, self-reported physician survey was conducted to assess the level of knowledge of key messages related to immune-related adverse drug reactions summarized in the atezolizumab HCP Guide and PAC among physicians (oncologists, pulmonologists, and urologists) prescribing atezolizumab in six European countries (Denmark, Germany, Italy, Spain, Sweden, and the UK). Responses regarding the receipt, understanding and use of the materials, and knowledge and behavior related to the HCP Guide and PAC are presented as percentages and continuous scores scaled out of 100 points, with corresponding 95% confidence intervals (CIs).ResultsAmong 313 physicians (255 oncologists, 30 pulmonologists, and 28 urologists), 77.4% received the HCP Guide and 74.2% the PAC. The HCP Guide was read by 71.3% of the 267 physicians who received the materials, and the mean usage score was 69.5 (95% CI 66.0-72.9), and 57.1% of physicians had scores ≥ 70. The HCP Guide was completely understood by 85.4% of physicians who had read it. Mean knowledge scores were 63.9 (95% CI 62.1-65.7) and 39.4% of physicians had correct knowledge scores ≥ 70. Mean knowledge scores were 66.8 (95% CI 64.9-68.7) for receipt of both the HCP Guide and PAC, 59.4 (95% CI 55.5-63.4) for one of the materials, and 60.8 (95% CI 55.4-66.2) for having received none of the materials. Mean behavior scores were 78.9 (95% CI 76.8-81.0), and 74.8% of physicians had behavior scores ≥ 70. The mean behavior score was 79.0 (95% CI 76.5-81.5) for those who received both the HCP Guide and PAC, 76.9 (95% CI 72.2-81.5) for receipt of one of the materials, and 81.5 (95% CI 75.0-88.0) for those who received none of the materials.ConclusionsThe study assessed the effectiveness of the atezolizumab additional risk minimization educational materials among physicians in six European countries, using process indicators. The educational materials reached over 70% of target physicians, 57.1% of whom reported using them. Knowledge and behavior related to immune-related adverse drug reactions for atezolizumab were no better in those who received the additional risk minimization educational materials. The results support the safe use of atezolizumab by these physician groups and contributed to the European Medicines Agency permitting removal of the HCP Guide.
| S-EPMC8668858 | biostudies-literature
Project description:INTRODUCTION:Two risk minimization (RM) tools-a healthcare professional frequently asked questions (HCP-FAQs) brochure and a patient/caregiver information brochure (PCIB)-were developed for HCPs and for adolescents (aged???13 years) receiving aripiprazole for bipolar I mania and their caregivers. OBJECTIVES:This study evaluated the effectiveness of these RM tools in improving the awareness and education of HCPs and patients/caregivers. METHOD:The RM tools were distributed to HCPs (identified in agreement with the marketing authorization holder [MAH] and local regulatory authorities), who in turn distributed the PCIBs to patients/caregivers. A web-based survey was then conducted targeting HCPs and patients/caregivers. RESULTS:The response rate was low: 118 of 23,282 invited HCPs and 16 patients/caregivers completed the survey. Overall, 42% (49/118) of HCP respondents were aware of aripiprazole RM tools; of these, 59% (29/49) of HCPs read them at least once and 66% (19/29) of these used the RM tools while discussing the benefit-risk profile of aripiprazole with patients/caregivers. In total, 30 of the 118 HCPs (25%) were aware of the PCIB, and 26 distributed it to their patients/caregivers, whereas seven HCPs advised them to read the brochure. Overall, 15 of the 16 patients/caregivers were aware of the PCIB, and 13 read/referred to it. Of these, 12 found the PCIB useful, and five monitored their weight while receiving aripiprazole and reported potential risks immediately to their HCP. CONCLUSION:The response rate to the survey was low, and the tools displayed limited utility and effectiveness in improving awareness and education in a small number of responders. Therefore, the aripiprazole risk management plan was amended, and the tools were discontinued.
| S-EPMC6061424 | biostudies-literature
Project description:An important element of risk management is the planning and implementation of risk minimisation measures (RMMs) and the evaluation of their effectiveness by process or outcome indicators. The aim of this review is to summarize the characteristics of risk minimisation (RM) effectiveness studies in Europe and provide an overview of RMMs and their effectiveness.This was a qualitative review of RM effectiveness studies in the European Union electronic Register of Post-Authorization Studies (EU PAS Register); data extracted included study design, population, sample size, data sources, drug information, RMMs, study period, indicators, and their reported effectiveness.Of the 872 records in the EU PAS Register, 19 studies evaluating the effectiveness of RMMs were included. Eleven were cross-sectional surveys and 8 used secondary data sources. Eighty-nine percent (17/19) evaluated additional RMMs (used when routine RMMs are considered insufficient), and 36% (7/19) evaluated changes in routine RMMs (applicable to all medicinal products). A total of 42 effectiveness indicators were identified: 18 process and 24 outcomes. Half of the indicators (21/42) were successful; 2% (1/42) indicators were partially successful; 17% (7/42) indicators were inconclusive. Effectiveness of the remaining 31% (13/42) indicators could not be determined owing to limited information. The United Kingdom was the most frequent country for the conduct of RM effectiveness studies.Most of the included studies evaluated additional RMMs. Half of the effectiveness indicators (process and/or outcome) were reported as successful. This review provides evidence to support the development of future guidance on the effectiveness of RM in Europe.
| S-EPMC6055865 | biostudies-other
Project description:INTRODUCTION:Studies measuring the effectiveness of risk minimization measures (RMMs) submitted by pharmaceutical companies to the European Medicines Agency are part of the post-authorization regulatory requirements and represent an important source of data covering a range of medicinal products and safety-related issues. Their objectives, design, and the associated regulatory outcomes were reviewed, and conclusions were drawn that may support future progress in risk minimization evaluation. METHODS:Information was obtained from risk management plans, study protocols, clinical study reports, and assessment reports of 157 medicinal products authorized for cardiovascular, endocrinology, and metabolic indications. We selected observational studies measuring, as outcomes of interest, the relationship between the RMMs in place and (1) implementation measures, such as clinical knowledge or physicians` compliance to recommendations contained in the RMMs; and (2) occurrence or reduced severity of the adverse drug reactions for which the RMMs were required. RESULTS:Of 59 eligible studies (24 completed, 35 ongoing), 44 assessed implementation measures, whereas only 15 assessed safety outcomes (1 study as a single endpoint and 14 studies with other endpoints). Fifty-one studies used non-experimental designs and 25 studies employed electronic healthcare databases for analysis. Of the 24 completed studies, 17 were considered satisfactory and supported immediate regulatory decision making, 6 were considered inconclusive and required new evaluations, and 1 was terminated early because new safety restrictions were required, thereby necessitating a new evaluation. Compliance with agreed deadlines was considered acceptable in 21 of 24 completed studies; the average time for a submission was 37 months (standard deviation ± 17), with differences observed by type of data source employed. CONCLUSIONS:Three important gaps in the evaluation plans of RMMs were identified: lack of early feedback on implementation, limited evaluation of safety outcomes, and inability to provide information on the effectiveness from an integrated measurement of different elements of a set of risk minimization tools. More robust evidence is needed to advance regulatory science and support more rapid adjustment of risk minimization strategies as needed.
| S-EPMC5808048 | biostudies-literature
Project description:PurposeThe purpose of the study is to evaluate the effectiveness of risk minimization measures-labeling changes and communication to health care professionals-recommended by the European Medicines Agency for use of cilostazol for the treatment of intermittent claudication in Europe.MethodsObservational study of cilostazol in The Health Improvement Network (United Kingdom), EpiChron Cohort (Spain), SIDIAP (Spain), Swedish National Databases, and GePaRD (Germany). Among new users of cilostazol, we compared the prevalence of conditions targeted by the risk minimization measures in the periods before (2002-2012) and after (2014) implementation. Conditions evaluated were prevalence of smoking, cardiovascular conditions, concurrent use of ?2 antiplatelet agents, concurrent use of potent CYP3A4/CYP2C19 inhibitors and high-dose cilostazol, early monitoring of all users, and continuous monitoring of users at high cardiovascular risk.ResultsWe included 22 593 and 1821 new users of cilostazol before and after implementation of risk minimization measures, respectively. After implementation, the frequency of several conditions related to the labeling changes improved in all the study populations: prevalence of use decreased between 13% (EpiChron) and 57% (SIDIAP), frequency of cardiovascular contraindications decreased between 8% (GePaRD) and 84% (EpiChron), and concurrent use of high-dose cilostazol and potent CYP3A4/CYP2C19 inhibitors decreased between 6% (Sweden) and 100% (EpiChron). The frequency of other conditions improved in most study populations, except smoking, which decreased only in EpiChron (48% reduction).ConclusionsThis study indicates that the risk minimization measures implemented by the EMA for the use of cilostazol have been effective in all European countries studied, except for smoking cessation before initiating cilostazol, which remains an area of improvement.
| S-EPMC6175151 | biostudies-literature
Project description:IntroductionSevere hypersensitivity reactions (HSRs) such as anaphylaxis are of great clinical concern because of their life-threatening potential. The adverse events attributable to intravenous iron products include HSRs. An investigation by the European Medicines Agency presented in late 2013 resulted in the implementation of risk minimization measures (RMMs).ObjectiveThis study evaluated the number of severe HSRs reported for intravenous iron substances related to exposure for the 4-year periods before and after this implementation.MethodsThis was a retrospective pharmacoepidemiologic study with a case-population design. We obtained information from the safety surveillance database EudraVigilance on spontaneously reported severe HSRs using the Medical Dictionary for Regulatory Activities preferred terms "anaphylactic reaction/shock" and "anaphylactoid reaction/shock". Exposure was estimated using IQVIA MIDAS sales data in European economic area countries.ResultsReporting rates for individual products were heterogenous, and the implementation of RMMs appeared to have no clear impact. Reporting rates remained low for the full study period for iron sucrose (0.03-0.20) and ferric gluconate (0.02-0.14) and were higher at the beginning and lower at the end of the study period for ferric carboxymaltose (1.47-0.18). No clear trend was detected for iron dextran (range 0.22-2.80) and iron (III) isomaltoside 1000 (range 0-7.94).ConclusionsFuture research is needed to investigate whether the wide variability in reporting rates for severe HSRs associated with these intravenous iron products are due to potential differences in the safety profiles of these substances.
| S-EPMC6965341 | biostudies-literature
Project description:Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed.Open-label study.We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration.Sodium oxybate significantly improved voice symptoms (P = .001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium oxybate further showed a trend for improving VT symptoms (P = .03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug's effects were observed approximately 30 to 40 minutes after its intake and lasted about 3.5 to 4 hours.Our study demonstrated that sodium oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of sodium oxybate in SD and SD/VT may be linked to that of alcohol, and as such, sodium oxybate might be beneficial for alcohol-responsive SD and SD/VT patients.4 Laryngoscope, 127:1402-1407, 2017.
| S-EPMC5415435 | biostudies-literature
Project description:BackgroundThe European Commission requires tobacco products sold in the European Union to display standardized text health warnings. This article examines the effectiveness of the text health warnings among daily cigarette smokers in four Member States.MethodsData were drawn from nationally representative samples of smokers from the International Tobacco Control Policy Evaluation Project surveys in France (2007), Germany (2007), the Netherlands (2008) and the UK (2006). We examined: (i) smokers' ratings of the health warnings on warning salience, thoughts of harm and quitting and forgoing of cigarettes; (ii) impact of the warnings using a Labels Impact Index (LII), with higher scores signifying greater impact; and (iii) differences on the LII by demographic characteristics and smoking behaviour.ResultsScores on the LII differed significantly across countries. Scores were highest in France, lower in the UK, and lowest in Germany and the Netherlands. Across all countries, scores were significantly higher among low-income smokers, smokers who had made a quit attempt in the past year and smokers who smoked fewer cigarettes per day.ConclusionThe impact of the health warnings varies greatly across countries. Impact tended to be highest in countries with more comprehensive tobacco control programmes. Because the impact of the warnings was highest among smokers with the lowest socioeconomic status (SES), this research suggests that health warnings could be more effective among smokers from lower SES groups. Differences in warning label impact by SES should be further investigated.
| S-EPMC3457002 | biostudies-literature
Project description:Farmland birds are among the most threatened bird species in Europe, largely as a result of agricultural intensification which has driven widespread biodiversity losses. Breeding waders associated with grassland and arable habitats are particularly vulnerable and a frequent focus of agri-environment schemes (AES) designed to halt and reverse population declines. We review existing literature, providing a quantitative assessment of the effectiveness of policy and management interventions used throughout Europe to improve population and demographic metrics of grassland-breeding waders. Targeted AES and site protection measures were more likely to be effective than less targeted AES and were ten times more likely to be effective than would be expected by chance, particularly for population trend and productivity metrics. Positive effects of AES and site protection did not appear synergistic. Management interventions which had the greatest chance of increasing population growth or productivity included modification of mowing regimes, increasing wet conditions, and the use of nest protection. Success rates varied according to the species and metric being evaluated. None of the policy or management interventions we evaluated were associated with a significant risk of negative impacts on breeding waders. Our findings support the use of agri-environment schemes, site protection, and management measures for grassland-breeding wader conservation in Europe. Due to publication bias, our findings are most applicable to intensively managed agricultural landscapes. More studies are needed to identify measures that increase chick survival. Despite broadly effective conservation measures already in use, grassland-breeding waders in Europe continue to decline. More research is needed to improve the likelihood and magnitude of positive outcomes, coupled with wider implementation of effective measures to substantially increase favorable land management for these species.
| S-EPMC6238142 | biostudies-literature
Project description:BACKGROUND:Several publications describe HIV-1 RNA false-negative results or viral load underquantitation associated with Communauté Européenne(CE)-marked qualitative or quantitative nucleic acid amplification technique (NAT) assays. 6 cases occurred during blood screening in Germany, with 2 of them causing HIV-1 transmissions to recipients of blood components. The implicated NAT assays were mono-target assays amplifying in different viral genome regions (gag or long terminal repeat). METHODS:Specimens characterized by HIV-1 NAT underquantitation or false-negative NAT results were comparatively investigated in CE-marked HIV-1 NAT systems of different design to identify potential reasons. The target regions of the viral nucleic acids were sequenced and these sequences compared to primers and probes of the assays. Potential risk minimization measures were considered for quantitative and blood-screening HIV-1 NAT systems. RESULTS:Nucleotide sequencing of the viral target region in cases of HIV-1 RNA underquantitation or false-negative test results revealed new HIV-1 variants that were mismatched with primers and probes used in some mono-target assays. So far, dualtarget NAT assays have not been associated with mismatch-based false-negative test results. From 2015, the Paul Ehrlich Institute will request HIV-1 NAT assays of dual-target design or an analogous solution for further reducing the risk in blood screening. CONCLUSION:HIV differs from other blood-borne viruses with regard to its fast evolution of new viral variants. The evolution of new sequences is hardly predictable; therefore, NAT assays with only 1 target region appear to be more vulnerable to sequence variations than dual-target assays. The associated risk may be higher for HIV-1 NAT assays used for blood screening compared to quantitative assays used for monitoring HIV-1-infected patients. In HIV-1 screening NAT assays of dual-target design may adequately address the risk imposed by new HIV-1 variants.
| S-EPMC3949608 | biostudies-literature