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Progress in genetic diagnosis and orphan drug legislation has opened doors to new therapies in rare neurogenetic diseases (RNDs). Innovative therapies such as gene therapy can improve patients' quality of life but come with academic, regulatory, and financial challenges. Registries can play a pivotal role in generating evidence to tackle these, but their development requires multidisciplinary knowledge and expertise. This study aims to develop a practical framework for creating and implementing patient registries addressing common challenges and maximizing their impact on care, research, drug development, and regulatory decision making with a focus on RNDs. A comprehensive 3-step literature and qualitative research approach was used to develop the framework. A qualitative systematic literature review was conducted, extracting guidance and practices leading to the draft framework. Subsequently, we interviewed representatives of 5 established international RND registries to add learnings from hands-on experiences to the framework. Expert input on the draft framework was sought in digital multistakeholder focus groups to refine the framework. The literature search; interviews with 5 registries; and focus groups with patient representatives (n = 4), clinicians (n = 6), regulators, health technology assessment (HTA) bodies and payers (n = 7), industry representatives (n = 7), and data/information technology (IT) specialists (n = 5) informed development of the framework. It covers the interests of different stakeholders, purposes for data utilization, data aspects, IT infrastructure, governance, and financing of rare disease registries. Key principles include that data should be rapidly accessible, independent, and trustworthy. Governance should involve multiple stakeholders. In addition, data should be highly descriptive, machine-readable, and accessible through a shared infrastructure and not spread over multiple isolated repositories. Sustainable and independent financing of registries is deemed important but remains challenging because of a lack of widely supported funding models. The proposed framework will guide stakeholders in establishing or improving rare disease registries that fulfill requirements of academics and patients as well as regulators, HTA bodies, and commercial parties. There is a need for more clarity regarding quality requirements for registries in regulatory and HTA context. In addition, independent financing models for registries should be developed, as well as well-defined policies on technical uniformity in health data.
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Enfermedades Raras , Sistema de Registros , Humanos , Enfermedades Raras/terapia , Enfermedades del Sistema Nervioso/terapiaRESUMEN
CONTEXT: Heart failure is a complex syndrome that arises when the heart is incapable of pumping enough blood to respond to the metabolic needs of the body. Heart failure is often caused by defective contraction and relaxation of the myocardium, accompanied by elevated cardiac filling pressure. It represents the final stage of a number of cardiovascular diseases. Characterized by limitation in activities of daily living and progressive exhaustion at rest, heart failure is a disabling and life-threatening condition. Severe heart failure, defined as class IV using the functional classification scheme of the New York Heart Association (NYHA), is associated with a 1-year mortality of about 50%. Heart failure is a major public health problem, associated with high rates of morbidity and mortality. It is estimated that more than 80,000 people are affected in Quebec, and the incidence of heart failure is expected to increase as a result of ageing of the population. More than 75% of patients suffering from heart failure in
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Humanos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/cirugía , Corazón Auxiliar , Medicina Basada en la Evidencia , Insuficiencia Cardíaca/complicaciones , Evaluación de la Tecnología BiomédicaRESUMEN
CONTEXT: Aortic valvular stenosis, or narrowing of the valve orifice, is a progressive disease that generally affects patients over the age of 65 years in Western countries and is usually caused by degenerative calcification. Aortic stenosis causes increasing resistance against the ejection of blood from the left ventricle towards the aorta. After symptoms appear (dyspnea, angina, syncope), the disease rapidly progresses causing severe limitation of physical capacity, heart failure, and high risk of mortality. Aortic stenosis represents the third most common cardiovascular disease among adults and the most frequent cardiac valve illness among elderly persons in the industrialized world. Its prevalence is estimated at at 2.8% in the population aged 75 and older in the United States. In Quebec, the number of octogenarians will double to about 780,000 persons by 2035, representing about 9% of the total population. Aortic stenosis will thus become more frequent and is expected to have an increasingly important impact on the Quebec health care system. Until recently, the only effective therapy for severe or symptomatic aortic stenosis was surgical valve replacement, but about a third of elderly patients can be refused this procedure due to their health status or aortic anatomy, which renders surgery too risky. In 2002, a percutaneous technique for implanting an aortic valve was developed, allowing the delivery by catheter and deployment of an aortic valve bioprosthesis, without recourse to open-heart surgery. Since then, the number of transcatheter aortic valve implantations (TAVIs) carried out worldwide has increased at a rapid rate. However, there are no Canadian clinical practice guidelines specific to TAVI, and the criteria for selection of patients raise important questions. Currently in Quebec, several institutions either have already set up a TAVI program or are in the process of doing so. A narrative review of the literature up to 2009 and an analysis of the Quebec experience was published in 2010 by a working group of the Réseau québécois de cardiologie tertiaire (RQCT). Following the release of this document, the ministère de la Santé et des Services sociaux (MSSS) recommended that this procedure be used only for patients who cannot be treated by traditional surgical methods due to an excessive risk of complications and be offered only by university hospitals or institutes with experienced multidisciplinary teams (performing a minimum of 30 procedures a year). Also, the MSSS gave the Institut national d'excellence en santé et en services sociaux (INESSS) the mandate to perform an evaluation of TAVI. OBJECTIVES OF THIS EVALUATION: 1. Synthesize, via a systematic review, the recent evidence on effectiveness, safety and economic issues related to TAVI using the Cribier-Edwards / Edwards SAPIEN or CoreValve bioprostheses for adult patients with severe, symptomatic aortic stenosis, with an emphasis on clinical results at 1 year; and to 2. Synthesize, via a narrative review, the principal organizational aspects of delivering this procedure, including the selection of patients before implantation and key considerations concerning ethics and the patient's perspective. METHODS: A systematic search of the scientific literature published between January 2008 and January 2011 was carried out using bibliographic databases, 2008 being the year when clinical results on mortality at 1 year began to become available. Given the relative lack of publications from registries, on quality of life and regarding economic issues, we also selected several oral presentations from scientific conferences. Using primary research articles and registry reports that provided survival data at 1 year as the main source of information, we examined clinical results for TAVI patients at 30 days and at 1 year. In order to summarize issues pertaining to organizational aspects and patient eligibility, we retrieved relevant information from the following sources: 1) the most recent expert consensus documents from North America and Europe; 2) health technology assessment (HTA) reports published between 2008 and 2010, and the 2011 update of a report by the National Institute for Health and Clinical Excellence (NICE); 3) relevant articles retrieved from our literature search; and 4) a key research article and accompanying editorial, published in June 2011, concerning cohort A of the PARTNER randomized controlled trial. RESULTS: In the systematic review of clinical results, 17 studies met our selection criteria: 13 were research studies (1 randomized controlled trial, 4 controlled cohort studies, 8 case series), and 4 were analyses of registries (2 national, 2 from industry), which can be considered as case series. Most studies were from outside North America. In the clinical trial (PARTNER B cohort), 179 patients were randomized to transfemoral TAVI, and 179 were randomized to medical treatment (most of the patients in this group also underwent balloon aortic valvuloplasty (BAV) for aggravation of their aortic stenosis). We also retained 3 HTA reports and 2 systematic review. In each of the 17 studies, the patients eligible for TAVI were considered either inoperable, not suitable for surgery or at high surgical risk. In almost every study, it was indicated that patient selection was based on the consensus decision of a multidisciplinary team. In general, TAVI patients were elderly (with a mean age of at least 81 years) and the majority were in New York Heart Association (NYHA) class 3 or 4, but the extent of surgical risk varied greatly across studies.