Carlo Giacomo Leo

RARE-Bestpractices: a platform for sharing best practices for the management of rare diseases

Over the last decade the European Union has been coordinating actions addressing various aspects of rare diseases and has funded several cross-border research projects. Recently has initiated the biggest rare disease international collaborative effort by launching the International Rare Diseases Research Consortium (IRDiRC). RARE-Bestpractices is one of the more than 100 collaborative research projects on rare diseases funded under the Seventh Framework Programme for Research and Technological Development (FP7; 2007-2013) (1). As a wide, open and inclusive network, RARE-Bestpractices will build on the knowledge of the experts in rare disease research area and experts in guideline development and health technology assessment area, brought together, for the first time, from academic institutions, agencies, organizations, patient advocacy groups, governmental bodies. The project aims at building a platform to collect and exchange information on best practices for the management of rare diseases; to identify relevant research needs; to promote the development of high quality guidelines; and to contribute in making patients, health professionals and policy makers “informed guideline users”. Besides, RARE-Bestpractices will intend to define the extent to which conclusions from cost-effectiveness analyses for pharmaceuticals are accounted for and implemented in guidelines across a range of countries.

Congenital anomalies among live births in a polluted area. A ten-year retrospective study

BackgroundCongenital anomalies and their primary prevention are a crucial public health issue. This work aimed to estimate the prevalence of congenital anomalies in Brindisi, a city in southeastern Italy at high risk of environmental crisis.MethodsThis research concerned newborns up to 28 days of age, born between 2001 and 2010 to mothers resident in Brindisi and discharged with a diagnosis of congenital anomaly. We classified cases according to the coding system adopted by the European Network for the Surveillance of Congenital Anomalies (EUROCAT). Prevalence rates of congenital anomalies in Brindisi were compared with those reported by EUROCAT. Logistic regression models were adapted to evaluate the association between congenital anomalies and municipality of residence of the mother during pregnancy.ResultsOut of 8,503 newborns we recorded 194 subjects with congenital anomalies (228.2/10,000 total births), 1.2 times higher than the one reported by the EUROCAT pool of registries. We observed 83 subjects with congenital heart diseases with an excess of 49.1%. Odds Ratios for congenital heart diseases significantly increased for newborns to mothers resident in Brindisi (OR 1.75 CI 95% 1.30-2.35).ConclusionsOur findings indicated an increased prevalence of Congenital Anomalies (especially congenital heart diseases) in the city of Brindisi. More research is needed in order to analyze the role of factors potentially involved in the causation of congenital anomalies.

Developing methodology for the creation of clinical practice guidelines for rare diseases: A report from RARE-Bestpractices

Rare diseases are a global public health priority; they can cause significant morbidity and mortality, can gravely affect quality of life, and can confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by clinicians. Thus, clinical practice guidelines are potentially very helpful in supporting clinical decisions, health policy and resource allocation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system is a structured and transparent approach to developing and presenting summaries of evidence, grading its quality, and then transparently interpreting the available evidence to make recommendations in health care. GRADE has been adopted widely. However, its use in creating guidelines for rare diseases – which are often plagued by a paucity of high quality evidence – has not yet been explored. RARE-Bestpractices is a project to create and populate a platform for sharing best practices for management of rare diseases. A major aim of this project is to ensure that European Union countries have the capacity to produce high quality clinical practice guidelines for rare diseases. On February 12, 2013 at the Istituto Superiore di Sanità, in Rome, Italy, the RARE-Bestpractices group held the first of a series of 2 workshops to discuss methodology for creating clinical practice guidelines, and explore issues specific to rare diseases. This paper summarizes key results of the first workshop, and explores how the current GRADE approach might (or might not) work for rare diseases. Avenues for future research are also identified.

Cost and benefit in cardiovascular imaging: the quest for economic sustainability.

In response to the article of Otero JH et al., CostEffective Diagnostic Cardiovascular Imaging: When Does it Provide Good Value for Money? [1]. Every year five billion imaging tests are performed worldwide, and about half of these are cardiovascular examinations [2]. According to recent estimates, at least one-third of all examinations are partially or totally inappropriate, i.e. risks and costs outweigh benefits [3]. In a context of scarce resources, and consequently the need to optimize their allocation, economic evaluation could play an important role in establishing a cost-effective health care program and supporting the decisions of policy-makers. In this issue of the journal, after having identifying all original cost-utility analyses in diagnostic cardiovascular imaging, Otero et al. systematically summarize the reported results and characteristics of those technologies reported to be cost-effective [1]. The Authors underline that each test represents a cost and a risk, and that very small individual costs and risks become significant when multiplied by the large number of tests performed worldwide annually. This important concept has farreaching implications. The cost of a medical imaging test has three different components: immediate cost; long-term cost (for instance, due to a new cancer developing decades after testing, as a consequence of the imaging test); and a societal cost due to the possible environmental impact of the imaging procedure.

Evaluating reporting and process quality of publications on UNHS: a systematic review of programmes

BackgroundCongenital hearing loss is one of the most frequent birth defects, and Early Detection and Intervention has been found to improve language outcomes. The American Academy of Pediatrics (AAP) and the Joint Committee on Infant Hearing (JCIH) established quality of care process indicators and benchmarks for Universal Newborn Hearing Screening (UNHS). We have aggregated some of these indicators/benchmarks according to the three pillars of universality, timely detection and overreferral. When dealing with inter-comparison, relying on complete and standardised literature data becomes crucial.The purpose of this paper is to verify whether literature data on UNHS programmes have included sufficient information to allow inter-programme comparisons according to the indicators considered.MethodsWe performed a systematic search identifying UNHS studies and assessing the quality of programmes.ResultsThe identified 12 studies demonstrated heterogeneity in criteria for referring to further examinations during the screening phase and in identifying high-risk neonates, protocols, tests, staff, and testing environments. Our systematic review also highlighted substantial variability in reported performance data. In order to optimise the reporting of screening protocols and process performance, we propose a checklist. Another result is the difficulty in guaranteeing full respect for the criteria of universality, timely detection and overreferral.ConclusionsStandardisation in reporting UNHS experiences may also have a positive impact on inter-program comparisons, hence favouring the emergence of recognised best practices.

The true cost of cardiovascular imaging: focusing on downstream, indirect, and environmental costs

To develop a more realistic assessment of costs, herein named “true” costs, the extra-cancer from medical radiation, environmental damage from imaging paraphernalia and radioactive wastes must be included as long-term costs from imaging examinations. It is urgent to define the “true” costs across imaging modalities as it interferes on physicians’ decision to request an exam and on research projects such as cost-effectiveness analysis. Cardiology is the specialty that most will benefit from the outcome as cardiovascular exams represent almost 30% of the total exams acquired annually worldwide.

Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements

The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the “regulatory capture” effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases.

A conceptual framework for rationalized and standardized Universal Newborn Hearing Screening (UNHS) programs

Congenital hearing loss is the most frequent birth defect. The American Academy of Pediatrics and the Joint Committee on Infant Hearing established quality of care process indicators for Universal Newborn Hearing Screening starting from 1999. In a previous systematic review of Universal Newborn Hearing Screening studies we highlighted substantial variability in program design and in reported performance data. In order to overcome these heterogeneous findings we think it is necessary to optimize the implementation of Universal Newborn Hearing Screening programs with an appropriate application of the planning, executing, and monitoring, verifications and reporting phases. For this reason we propose a conceptual framework that logically integrates these three phases and, consequently, a tool (a check-list) for their rationalization and standardization.Our paper intends to stimulate debate on how to ameliorate the routine application of high quality Universal Newborn Hearing Screening programs. The conceptual framework is proposed to optimize, rationalise and standardise their implementation. The checklist is intended to allow an inter-program comparison by removing heterogeneity in processes description and assessment.