RESUMO
PURPOSE: The European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) launched a strategy to examine the public health impact of major regulatory interventions aimed at minimising risks of medicinal products. We conducted a lessons learnt analysis of impact studies completed between 2015 and 2023. METHODS: We surveyed PRAC Sponsors and (Co-)Rapporteurs involved in the evaluation of 12 impact studies (10 commissioned by EMA and 2 conducted collaboratively by Member States) to explore how these support regulatory decision-making. Questions covered achievement of study objectives, risk minimisation effectiveness, added value for regulatory decision-making, and recommendations for future impact studies. Themes were generated using thematic content analysis. RESULTS: Survey responses from 15 PRAC Sponsors and (Co-)Rapporteurs from 10 European Union Member States were included in the analysis. Among four cross-sectional surveys and eight drug utilisation studies, 50% achieved all objectives, the other studies partially due to limitations. Two studies concluded that risk minimisation measures were overall effective, two were effective with variation across countries, two were partially effective and four studies showed limited effectiveness. Two studies were deemed inconclusive due to limitations. The reasons for the limited effectiveness of risk minimisation may be explored using mixed-method approaches. Assessment of study feasibility and a priori discussion of effectiveness measurements is important. CONCLUSION: Despite limitations, impact research adds value to regulatory decision-making by addressing knowledge gaps and providing additional information on unintended consequences of regulatory interventions. Our recommendations will help to improve planning, conducting and interpretating future impact studies.
Assuntos
União Europeia , Farmacovigilância , Humanos , Medição de Risco , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Tomada de Decisões , Inquéritos e Questionários , Estudos Transversais , Saúde PúblicaRESUMO
PURPOSE: The ENCePP Code of Conduct provides a framework for scientifically independent and transparent pharmacoepidemiological research. Despite becoming a landmark reference, practical implementation of key provisions was still limited. The fourth revision defines scientific independence and clarifies uncertainties on the applicability to postauthorisation safety studies requested by regulators. To separate the influence of the funder from the investigator's scientific responsibility, the Code now requires that the lead investigator is not employed by the funding institution. METHOD: To assess how the revised Code fits the ecosystem of noninterventional pharmacoepidemiology research in Europe, we first mapped key recommendations of the revised Code against ISPE Good Pharmacoepidemiology Practices and the ADVANCE Code of Conduct. We surveyed stakeholders to understand perceptions on its value and practical applicability. Representatives from the different stakeholders' groups described their experience and expectations. RESULTS: Unmet needs in pharmacoepidemiological research are fulfilled by providing unique guidance on roles and responsibilities to support scientific independence. The principles of scientific independence and transparency are well understood and reinforce trust in study results; however, around 70% of survey respondents still found some provisions difficult to apply. Representatives from stakeholders' groups found the new version promising, although limitations still exist. CONCLUSION: By clarifying definitions and roles, the latest revision of the Code sets a new standard in the relationship between investigators and funders to support scientific independence of pharmacoepidemiological research. Disseminating and training on the provisions of the Code would help stakeholders to better understand its advantages and promote its adoption in noninterventional research.
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Projetos de Pesquisa Epidemiológica , Farmacoepidemiologia/normas , Farmacovigilância , Guias de Prática Clínica como Assunto , Conflito de Interesses/economia , Conflito de Interesses/legislação & jurisprudência , Europa (Continente) , Humanos , Farmacoepidemiologia/economia , Farmacoepidemiologia/ética , Farmacoepidemiologia/legislação & jurisprudência , Pesquisadores/economia , Pesquisadores/ética , Pesquisadores/normasRESUMO
Florbetapir (18F) for brain amyloid positron emission tomography (PET) imaging has been recently approved in Europe to estimate ß-amyloid neuritic plaque density in the brain when the subject is still alive. Such density is one of the key issues for the definitive diagnosis of Alzheimer's disease (AD) at autopsy. This capability of florbetapir (18F) is regarded as a significant improvement in the diagnostic procedures for adult patients with cognitive impairment who are being evaluated for AD and other causes of cognitive impairment. The current paper highlights the specific characteristics of the European marketing authorization of florbetapir (18F).
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Compostos de Anilina , Encéfalo/diagnóstico por imagem , Etilenoglicóis , Radioisótopos de Flúor , Placa Amiloide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina/efeitos adversos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/diagnóstico por imagem , Aprovação de Drogas , Etilenoglicóis/efeitos adversos , Europa (Continente) , Radioisótopos de Flúor/efeitos adversos , Humanos , Tomografia por Emissão de Pósitrons/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Risco , Sensibilidade e EspecificidadeRESUMO
The European Medicines Agency (EMA) supervises medicines' safe and effective use throughout the product's life cycle by, for example, monitoring the implementation of risk minimization measures (RMMs). Limited information is available on factors associated with effectiveness of RMMs. This study reviews post-authorization safety studies (PASS) evaluating the effectiveness of RMMs assessed by the Pharmacovigilance Risk Assessment Committee (PRAC) between 2016 and 2021. PASS assessment reports finalized by PRAC between January 1, 2016, and December 31, 2021, were compiled from non-public EMA databases and PASS characteristics were extracted. Of the 93 PASS included, 62.4% aimed to measure healthcare professionals' awareness, knowledge, and behavior regarding RMMs. There were 67.7% of the 93 PASS that used primary data, 24.7% used secondary data sources, and 7.5% used both. A cross-sectional study design was most frequently applied (77.4%), followed by a cohort study design (29.0%). Nearly 40% of the included PASS did not render a conclusion on RMM effectiveness. Of the 60% that did render a conclusion, 82.1% were deemed effective. Only minor differences in characteristics were found when stratified by outcome (i.e., effective RMM, ineffective RMM, and no conclusion on RMM effectiveness). To conclude, 4 out of 10 PASS assessing impact of RMMs did not render a conclusion on RMM effectiveness. No clear differences in PASS characteristics were found in relation to their outcomes, indicating that additional research is needed to understand better the underlying reasons for PASS being inconclusive.
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Pessoal de Saúde , Farmacovigilância , Humanos , Estudos de Coortes , Estudos Transversais , Medição de RiscoRESUMO
INTRODUCTION: As patient registries are not subject to regulatory requirements on the collection of adverse events (AEs) related to medicinal products, they may not have foreseen the collection of such information on a routine basis or as part of specific data collection schemes. OBJECTIVE: The European Medicines Agency conducted a survey among registries to better understand their approach towards the collection, management and reporting of AEs related to medicines. METHOD: An online survey composed of 15 questions was distributed in May 2020 to registries listed in the European Network of Centres in Pharmacoepidemiology and Pharmacovigilance (ENCePP) resources database for completion by August 2020. Aggregated results are presented in this paper. RESULTS: One third of the registries completed the survey (31/85; 36.5%). Most of the respondents routinely collect information on medicines (29/31; 93.5%), out of which 65.5% (19/29) also collect data on AEs and adverse drug reactions (ADRs). Frequencies and timelines for collecting and reporting AEs/ADRs vary widely across registries, as does their level of experience in providing data to third parties for regulatory purposes. CONCLUSIONS: The low response rate may indicate little interest in this topic or that registries were not originally developed for routine data collection on AEs/ADRs and, ultimately, monitoring of the safety of medicines. Results indicate that clear guidance on the collection and use of real-world data in regulatory frameworks and strengthened collaboration between registry holders, academia, regulators and medicines developers are needed to achieve comprehensive and high levels of quality of safety data captured by registries to support regulatory decision making. These will hopefully be enabled by the European Medicines Regulatory Network strategy to 2025.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Farmacoepidemiologia , Sistema de Registros , Inquéritos e QuestionáriosRESUMO
Information derived from routinely collected real-world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real-world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019. For MAAs, 63 of 158 products (39.9%) contained RWE with a total of 117 studies. For 31.7% of these products, the RWE submitted was derived from data collected before the planned authorization. The most common data sources were registries (60.3%) followed by hospital data (31.7%). RWE was mainly included to support safety (87.3%) and efficacy (49.2%) with cohort studies being the most frequently used study design (88.9%). For EOIs, 28 of 153 products (18.3%) contained RWE with a total of 36 studies. For 57.1% of these products, studies were conducted prior to the EOIs. RWE sources were mainly registries (35.6%) and hospital data (27.0%). RWE was typically used to support safety (82.1%) and efficacy (53.6%). Cohort studies were the most commonly used study design (87.6%). We conclude that there is widespread use of RWE to support evaluation of MAAs and EOIs submitted to the EMA and identify areas where further research is required.