RESUMO
Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Custos de Cuidados de Saúde/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/economia , Estudos de Casos e Controles , Consenso , Tomada de Decisões , Humanos , Análise de Intenção de Tratamento/estatística & dados numéricos , Adesão à Medicação/psicologia , Médicos/organização & administração , Placebos/administração & dosagem , Medição de Risco , Segurança , Sociedades Científicas/organização & administração , Espanha/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , United States Food and Drug Administration/organização & administraçãoRESUMO
OBJECTIVES: This study sought to assess whether transradial access (TRA) compared with transfemoral access (TFA) is associated with consistent outcomes in male and female patients with acute coronary syndrome undergoing invasive management. BACKGROUND: There are limited and contrasting data about sex disparities for the safety and efficacy of TRA versus TFA for coronary intervention. METHODS: In the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) program, 8,404 patients were randomized to TRA or TFA. The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACCE or major bleeding. RESULTS: Among 8,404 patients, 2,232 (26.6%) were women and 6,172 (73.4%) were men. MACCE and NACE were not significantly different between men and women after adjustment, but women had higher risk of access site bleeding (male vs. female rate ratio [RR]: 0.64; p = 0.0016), severe bleeding (RR: 0.17; p = 0.0012), and transfusion (RR: 0.56; p = 0.0089). When comparing radial versus femoral, there was no significant interaction for MACCE and NACE stratified by sex (pint = 0.15 and 0.18, respectively), although for both coprimary endpoints the benefit with TRA was relatively greater in women (RR: 0.73; p = 0.019; and RR: 0.73; p = 0.012, respectively). Similarly, there was no significant interaction between male and female patients for the individual endpoints of all-cause death (pint = 0.79), myocardial infarction (pint = 0.25), stroke (pint = 0.18), and Bleeding Academic Research Consortium type 3 or 5 (pint = 0.45). CONCLUSIONS: Women showed a higher risk of severe bleeding and access site complications, and radial access was an effective method to reduce these complications as well as composite ischemic and ischemic or bleeding endpoints.
Assuntos
Síndrome Coronariana Aguda/cirurgia , Cateterismo Periférico/métodos , Artéria Femoral , Intervenção Coronária Percutânea/métodos , Artéria Radial , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/mortalidade , Angiografia Coronária , Europa (Continente) , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Complicações Pós-Operatórias/epidemiologia , Punções , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
The present report describes the quality of care, including in hospital mortality for more than 22.000 STEMI patients admitted in 60 Belgian hospitals for the period 2008-2016. We found a strong increase in the use of primary PCI over time, particularly for patients that were admitted first in a non-PCI capable hospital, reaching a penetration rate of >95%. The transition of thrombolysis to transfer for pPCI in the setting of a STEMI network was, however, associated with an increase of the proportion of patients with prolonged (>120 min) diagnosis-to-balloon time (from 16 to 22%), suggesting still suboptimal interhospital transfer. The in-hospital mortality of the total study population was 6.5%. For non-cardiac arrest patients in-hospital mortality decreased from 5.1% to 3.7%, while it increased for cardiac arrest patients from 29 to 37%. The observation that quality indicators (QI's), such as modalities and timing of reperfusion therapy, were associated with lower levels of mortality, underscores the potential of QIs for STEMI to improve care and reduce unwarranted variation and premature death from STEMI.
RESUMO
This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled "The Role of Endpoint Adjudication in Medical Device Clinical Trials". The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence.