608,538 research outputs found
Reporting rare paediatric progressive genetic conditions: a step towards international classification
Get PDFCreating a multi-center rare disease consortium – the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)
Get PDFThe Promise of Priority Review Vouchers as a Legislative Tool to Encourage Drugs for Neglected Diseases
Get PDFDespite the intellectual property system’s success in promoting the economic well-being of the United States, this system has not achieved all socially valuable ends. Insufficient treatments are applied both to diseases endemic in developing countries, such as malaria, and rare diseases, such as rare childhood cancers. Several legislative tools aim to promote socially valuable drugs and biologics through market incentives. The priority review voucher (PRV) program is the latest and most unique of these legislative tools aimed at encouraging the development of drugs for neglected diseases without burdening taxpayers. The Creating Hope Act—recently signed into law as part of the Food & Drug Administration Safety & Innovation Act—extends the PRV program to rare pediatric diseases. This Issue Brief argues that some provisions in this new legislation may result in undesirable collateral effects that could prevent the legislation from fulfilling its objective of encouraging investment in treatments for rare pediatric diseases
Orphan drugs and the NHS: Should we value rarity
Get PDFCost effectiveness plays an important part in current decisions about the funding of health technologies. Drugs for rare disease (orphan drugs) are often expensive to produce and, by definition, will benefit only small numbers of patients. Several countries have put measures in place to safeguard research and development of orphan drugs, but few get close to meeting the cost effectiveness criteria for funding by healthcare providers. We examine the justifications for special status for rare diseases and ask whether the cost effectiveness of drugs for rare or very rare diseases should be treated differently from that of other drugs and interventions
Regulating Rare Disease: Safely Facilitating Access to Orphan Drugs
Get PDFWhile approximately one in ten Americans suffers from a rare disease, only 5 percent of rare diseases have a U.S. Food and Drug Administration (FDA) approved treatment. Congressional and regulatory efforts to stimulate the development of rare-disease treatments, while laudable, have not resolved the fundamental issues surrounding rare-disease treatment development. Indeed, small patient populations, incomplete scientific understanding of rare diseases, and high development costs continually limit the availability of rare-disease treatments. To illustrate the struggle of developing and approving safe rare-disease treatments, this Note begins by discussing the approval of Eteplirsen, the first drug approved for treating a rare disease called Duchenne muscular dystrophy. After exploring the current drug regulation system and how this impacts the availability of rare-disease treatments, this Note examines the 21st Century Cures Act’s patient experience data provisions and the currently pending Trickett Wendler Right to Try Act. Ultimately, the unmet therapeutic needs of rare-disease patients can be met while protecting patient safety, this Note reasons that, if carefully implemented, the 21st Century Cures Act and the Trickett Wendler Right to Try Act could work in tandem to safely facilitate patient access to rare-disease treatments
Population Genetics of Rare Variants and Complex Diseases
Get PDFIdentifying drivers of complex traits from the noisy signals of genetic
variation obtained from high throughput genome sequencing technologies is a
central challenge faced by human geneticists today. We hypothesize that the
variants involved in complex diseases are likely to exhibit non-neutral
evolutionary signatures. Uncovering the evolutionary history of all variants is
therefore of intrinsic interest for complex disease research. However, doing so
necessitates the simultaneous elucidation of the targets of natural selection
and population-specific demographic history. Here we characterize the action of
natural selection operating across complex disease categories, and use
population genetic simulations to evaluate the expected patterns of genetic
variation in large samples. We focus on populations that have experienced
historical bottlenecks followed by explosive growth (consistent with most human
populations), and describe the differences between evolutionarily deleterious
mutations and those that are neutral. Genes associated with several complex
disease categories exhibit stronger signatures of purifying selection than
non-disease genes. In addition, loci identified through genome-wide association
studies of complex traits also exhibit signatures consistent with being in
regions recurrently targeted by purifying selection. Through simulations, we
show that population bottlenecks and rapid growth enables deleterious rare
variants to persist at low frequencies just as long as neutral variants, but
low frequency and common variants tend to be much younger than neutral
variants. This has resulted in a large proportion of modern-day rare alleles
that have a deleterious effect on function, and that potentially contribute to
disease susceptibility.Comment: 36 pages, 7 figure
Improving translational studies: lessons from rare neuromuscular diseases
Get PDFAnimal models play a key role in the development of novel treatments for human disease. This is particularly true for rare diseases – defined as disorders that affect less than 1 in 2000 people in the human population – for which, very often, there are no effective methods of treatment. Pharmaceutical companies are increasingly focussing on the development of therapies for the more than 7000 rare diseases. Because the majority of these are the result of single gene disorders, the exceptional ability to manipulate the mouse genome means that many such studies will take place in the laboratory mouse. But how good are the mouse models and how useful are they in assessing the potential for translational medicine? In this Editorial, I will discuss current difficulties in translational research as well as examples of good laboratory practice and guidelines that are being implemented to improve the translational potential of animal studies in the field of neuromuscular rare diseases. This could represent a potentially useful approach for adoption by other disease fields to achieve a greater success rate in translational studies
Generating health technology assessment evidence for rare diseases
Get PDFObjectives: Rare diseases are often heterogeneous in their progression and response to treatment, with only a small population for study. This provides challenges for evidence generation to support HTA, so novel research methods are required.
Methods: Discussion with an expert panel was augmented with references and case studies to explore robust approaches for HTA evidence generation for rare disease treatments.
Results: Traditional RCTs can be modified using sequential, three-stage or adaptive designs to gain more power from a small patient population or to focus trial design. However, such designs need to maintain important design aspects such as randomization and blinding and be analyzed to take account of the multiple analyses performed. N-of-1 trials use within-patient randomization to test repeat periods of treatment and control until a response is clear. Such trials could be particularly valuable for rare diseases and when prospectively planned across several patients and analyzed using Bayesian techniques, a population effect can be estimated that might be of value to HTA. When the optimal outcome is unclear in a rare disease, disease specific patient reported outcomes can elucidate impacts on patients’ functioning and wellbeing. Likewise, qualitative research can be used to elicit patients’ perspectives, with just a small number of patients.
Conclusions: International consensus is needed on ways to improve evidence collection and assessment of technologies for rare diseases, which recognize the value of novel study designs and analyses in a setting where the outcomes and effects of importance are yet to be agreed.</p
The Italian National Rare Diseases Registry.
Get PDFINTRODUCTION:Rare disease registries are a priority at European level and specific actions are being implemented by the European Commission to support their development.In Italy, a National Registry of rare diseases has been established in 2001 as a network of regional registries. The latter have gradually been established and the full coverage of the Italian territory was attained during 2011. METHODS:Here we describe the basic features of the National Registry of rare diseases; the activities carried out to promote consistent operations in the regional registries; and the overall quality and composition of the records collected. RESULTS:After a validation process, including removal of duplicate records, 110,841 records of patients with rare diseases, single and with group denominations, are stored in the National Registry of rare diseases. They correspond to the overall diagnoses communicated to national registry by regional registries up to 30 June 2012.The quality of the data collected by the the National Registry of rare diseases has been assessed with respect to completeness and consistency of procedures. Variables characterising case and diagnosis showed a very limited number of missing values. Records reported at least one case of 485 rare conditions. DISCUSSION:To date, the National Registry of rare diseases is a surveillance system with the main objective of producing epidemiologic evidence on rare diseases in Italy, and of supporting policy making and health services planning.Data quality still represents a limitation for any sound epidemiological estimate of rare diseases in Italy. However, improvements of the quality of collected data and the completeness of case notifications should be strengthened.
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