Zhongguo Fei Ai Za Zhi. 2022 Jul 20;25(7):443-447. doi: 10.3779/j.issn.1009-3419.2022.101.26.

ABSTRACT

In recent years, China's anti-tumor drugs has shown a continuous growth trend, and the activity of anti-tumor research and development in China accounts for a higher proportion in the world. However, further analysis of research and development hotspots show that the research and development of anti-tumor drugs is uneven among different tumor types. Due to the small number of the patients, it is difficult to conduct clinical trials, resulting in less drug development in the field of rare tumors. However, patients' treatment needs will also bring potential opportunities for pharmaceutical companies. The development of basic research and the discovery of new molecular tumor typing make "rare tumors" a dynamic concept. The scope of "rare tumors" may gradually expand with the precise development of treatment; or as the knowledge of tumors gradually develops from histocytology to the molecular level, It is possible that certain tumors with specific mutations can be combined into a group of non-rare "pan-tumors". Rare tumors are characterized by both rare diseases and tumors. Its drug research and development should not only meet the requirements of tumor drug research and development, but also adapt to the characteristics of rare diseases. Therefore, in the drug research and development, we can refer to the research and development principle of rare disease drugs, combine with the characteristics of tumor diseases, make full use of non-rare tumor clinical trials, make full use of scientific tools and exquisite trial design, and realize the promotion of the research and development of rare tumor drugs. This paper will summarize the thoughts in the review of new drugs in the field of rare tumors, in order to provide guidance for the industry. .

PMID:35899439 | DOI:10.3779/j.issn.1009-3419.2022.101.26

Orphanet J Rare Dis. 2022 Jul 27;17(1):294. doi: 10.1186/s13023-022-02440-4.

ABSTRACT

BACKGROUND: Rare diseases have been increasingly recognized as unmet medical and health needs worldwide; a growing demand for the development of orphan drugs emerges subsequently. Therefore, it is of great interest for both the Chinese regulatory agency and pharmaceutical companies to keep tract on the clinical development of orphan drugs in China.

OBJECTIVE AND METHOD: This study aims to reveal the current situation and trend of the clinical development of orphan drugs in China, based on the data collected from the Chinese official platform, dating from January 1, 2013 to December 31, 2021.

RESULTS: A total of 331 clinical trials for orphan drugs were extracted from the platform, covering 31 rare diseases and 124 drugs. Increases were seen in the annual number of clinical trials and drugs being tested, with a sharp increase after 2018. About the disease types of the 331 trials, Parkinson disease (young-onset, early-onset) (86, 26%), hemophilia (70, 21%), homozygote hypercholesterolemia (60, 18%) were the most common. Furthermore, it was also observed that the largest number of clinical trial units for rare disease in east China (90, 41%) and the smallest number located in northwest China (18, 6%) and northeast China (18, 6%).

CONCLUSIONS: The growth trends illustrate the progress in clinical trial and drug development of rare diseases from 2013 to 2021. However, promoting orphan drugs development still is an important issue in China; at the same time, further efforts should be made for meet the unmet needs of disease types and balance the uneven distribution of medical resources for clinical trial on rare diseases.

PMID:35897012 | DOI:10.1186/s13023-022-02440-4

Genes (Basel). 2022 Jul 22;13(8):1293. doi: 10.3390/genes13081293.

ABSTRACT

Mucopolysaccharidosis type I (MPS I) is a rare inherited lysosomal disorder caused by deficiency of the α-L-iduronidase enzyme, resulting in the progressive accumulation of glycosaminoglycans (GAGs), which interfere with the normal function of multiple tissues and organs. The clinical phenotype includes characteristic facial features, hepatosplenomegaly, dysostosis multiplex, umbilical and inguinal hernias, progressive cognitive deficits with corresponding hydrocephalus, and neuropathology. Untreated children do not survive into the second decade. The common cardiac phenotype seen in MPS I and other MPS types includes valve thickening and dysfunction, conduction abnormalities, coronary artery disease, and cardiomyopathy-usually seen later in the disease course. A 15-month-old ex-35-weeker who presented with cardiomyopathy and left ventricular failure at the age of three weeks is presented here. Early evaluation and diagnosis with the help of newborn screening (NBS), followed by treatment with enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), resulted in improvement of his cardiopulmonary status. In MPS I, an early cardiac phenotype is uncommon. Based on the evidence from the literature review for early neonatal cardiac phenotype, we propose that all infants with abnormal newborn screening for MPS I should receive cardiac screening with echocardiogram and NT-proB-type natriuretic peptide (BNP) during the initial evaluation.

PMID:35893030 | DOI:10.3390/genes13081293

Medicina (Kaunas). 2022 Jul 15;58(7):938. doi: 10.3390/medicina58070938.

ABSTRACT

Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic injuries, tumors, or vascular impairments of the head. Symptoms of HS can also occur in some autoimmune disorders, ophthalmic disorders, sleep disorders, and with certain organic lesions. In this context, a thorough review of the pathophysiology of HS in relation to neurological, ophthalmological, and dermatological conditions is necessary. In this mini-review, we aim to review the pathophysiological changes and underlying mechanisms in primary and secondary HS. Additionally, we discuss possible management approaches for patients with HS in light of the discussed pathological mechanisms. The main symptoms of HS that are correlated with autonomic nervous system impairments include sudden unilateral flushing of the face, neck, chest, and rarely arm, with concurrent contralateral anhidrosis. Despite reported co-occurring syndromes (such as cluster headaches), several studies have shown that HS could frequently overlap with other syndromes that are disruptive to the idiopathic nerve pathways. HS usually does not require any medical treatment. In some severe cases, symptomatic treatments could be needed. However, total symptomatic relief may not be achieved in many cases of HS. We therefore suggest an approach to comprehensive management of HS, which may lead to better long-term control of HS.

PMID:35888657 | DOI:10.3390/medicina58070938

Medicina (Kaunas). 2022 Jul 10;58(7):915. doi: 10.3390/medicina58070915.

ABSTRACT

Background and Objectives: Achenbach's syndrome is usually a benign, self-limiting clinical condition presented with finger discoloration, pain, and edema. Etiology, pathogenesis, and incidence remain unknown due to the variety of clinical features and the diversity of disease states leading to digital ischemia. COVID-19 primarily affects microcirculation, causing endothelial damage and disseminated microthrombosis. Materials and Methods: We reviewed two cases of Caucasian women with Achenbach's syndrome after COVID-19 infection recovery between April and May 2021. Results: Here are presented two extremely rare cases of paroxysmal finger hematoma in two female patients after COVID-19 infection recovery. Conclusions: The exact etiology and pathophysiology of Achenbach's syndrome remain unclear. It is assumed that SARS-CoV-2 infection could be the triggering factor in the pathophysiological mechanism of paroxysmal finger hematoma. We highly recommend the implication of the synthetic prostacyclin receptor agonist (Iloprost) as a first-line conservative treatment in patients with Achenbach's syndrome and COVID-19 infection recovery.

PMID:35888634 | DOI:10.3390/medicina58070915

Int J Environ Res Public Health. 2022 Jul 21;19(14):8874. doi: 10.3390/ijerph19148874.

ABSTRACT

BACKGROUND: Most rare diseases are chronic conditions with variable impairment of functionality, which can result in a need for rehabilitation. To our knowledge, there are no systematic studies on the rehabilitation needs of patients in centres for rare diseases in the literature. Our hypothesis is that participation of these patients is so limited that there is an increased need for rehabilitation. For this reason, a survey on the need for rehabilitation was carried out in all patients presenting to the centre for rare diseases, in order to assess the need for rehabilitative measures to counteract disturbances in activity and participation.

METHODS: A cross-sectional study was performed to collect data using a written questionnaire from December 2020 to June 2021, including patients presenting personally in the center for rare diseases.

RESULTS: Nearly 70% of the participants assessed their own ability to work as critical. Of those surveyed, n = 30 (44.9%) had PDI total ≥ 33 points and, thus, a clear pain-related impairment.

CONCLUSION: The results show functional restrictions in the areas of mental well-being and activity. As expected, the health-related quality of life is reduced as compared to healthy people. Almost half of the participants reported significant pain-related impairments, however, only 9% of all respondents stated that they had received appropriate pain therapy. The results show the need for rehabilitation-specific skills in the care and counseling of patients with rare diseases.

PMID:35886725 | DOI:10.3390/ijerph19148874

Int J Environ Res Public Health. 2022 Jul 19;19(14):8788. doi: 10.3390/ijerph19148788.

ABSTRACT

Assessing public and patients' expectations and concerns about genomic data sharing is essential to promote adequate data governance and engagement in rare diseases genomics research. This cross-sectional study compared the views of 159 rare disease patients, 478 informal carers and 63 healthcare professionals in Northern Portugal about the benefits and risks of sharing genomic data for research, and its associated factors. The three participant groups expressed significantly different views. The majority of patients (84.3%) and informal carers (87.4%) selected the discovery of a cure for untreatable diseases as the most important benefit. In contrast, most healthcare professionals revealed a preference for the development of new drugs and treatments (71.4%), which was the second most selected benefit by carers (48.3%), especially by the more educated (OR (95% CI): 1.58 (1.07-2.34)). Lack of security and control over information access and the extraction of information exceeding research objectives were the two most often selected risks by patients (72.6% and 50.3%, respectively) and carers (60.0% and 60.6%, respectively). Conversely, professionals were concerned with genomic data being used to discriminate citizens (68.3%), followed by the extraction of information exceeding research objectives (54.0%). The latter risk was more frequently expressed by more educated carers (OR (95% CI): 1.60 (1.06-2.41)) and less by those with blue-collar (OR (95% CI): 0.44 (0.25-0.77) and other occupations (OR (95% CI): 0.44 (0.26-0.74)). Developing communication strategies and consent approaches tailored to participants' expectations and needs can benefit the inclusiveness of genomics research that is key for patient-centred care.

PMID:35886636 | DOI:10.3390/ijerph19148788

Int J Environ Res Public Health. 2022 Jul 17;19(14):8694. doi: 10.3390/ijerph19148694.

ABSTRACT

This study described two companies' financial compensation programs for semiconductor workers with suspected work-related diseases (WRDs) and discussed the major related issues. The key contents of the programs found on the websites opened by two semiconductor companies (Samsung and SK Hynix) were cited. In order to select the suspected WRDs for the FSC, all available epidemiologic studies related to health problems conducted in the semiconductor industry were reviewed. Most program contents are similar, although the amount of financial compensation and a few types of disease available for compensation differ between the companies. The group of cancer, rare disease, childhood rare disease among children born to semiconductor workers (hereafter selected diseases among offspring), and fetal loss, including spontaneous abortion (SAB) and stillbirth, were considered for compensation. An employment duration of longer than one year on a semiconductor production line is required for FSC for cancer or rare disease. The FSC for SAB and offspring disease require a period of employment longer than one month, either before three months prior to conception or between conception and childbirth. The maximum amount of compensation per type of cancer and rare disease was fixed based on the medical treatment fee. The FSC programs of the two companies have been operated successfully to date. These programs are arguably considered to contribute to resolving the conflict between companies and workers with WRDs.

PMID:35886546 | DOI:10.3390/ijerph19148694

Genes (Basel). 2022 Jun 21;13(7):1104. doi: 10.3390/genes13071104.

ABSTRACT

BACKGROUND: The UK 100,000 Genomes Project was a transformational research project which facilitated whole genome sequencing (WGS) diagnostics for rare diseases. We evaluated experiences of introducing WGS in Northern Ireland, providing recommendations for future projects.

METHODS: This formative evaluation included (1) an appraisal of the logistics of implementing and delivering WGS, (2) a survey of participant self-reported views and experiences, (3) semi-structured interviews with healthcare staff as key informants who were involved in the delivery of WGS and (4) a workshop discussion about interprofessional collaboration with respect to molecular diagnostics.

RESULTS: We engaged with >400 participants, with detailed reflections obtained from 74 participants including patients, caregivers, key National Health Service (NHS) informants, and researchers (patient survey n = 42; semi-structured interviews n = 19; attendees of the discussion workshop n = 13). Overarching themes included the need to improve rare disease awareness, education, and support services, as well as interprofessional collaboration being central to an effective, mainstreamed molecular diagnostic service.

CONCLUSIONS: Recommendations for streamlining precision medicine for patients with rare diseases include administrative improvements (e.g., streamlining of the consent process), educational improvements (e.g., rare disease training provided from undergraduate to postgraduate education alongside genomics training for non-genetic specialists) and analytical improvements (e.g., multidisciplinary collaboration and improved computational infrastructure).

PMID:35885887 | DOI:10.3390/genes13071104

Biomolecules. 2022 Jul 21;12(7):1009. doi: 10.3390/biom12071009.

ABSTRACT

The importance of mitochondria in mammalian cells is widely known. Several biochemical reactions and pathways take place within mitochondria: among them, there are those involving the biogenesis of the iron-sulfur (Fe-S) clusters. The latter are evolutionarily conserved, ubiquitous inorganic cofactors, performing a variety of functions, such as electron transport, enzymatic catalysis, DNA maintenance, and gene expression regulation. The synthesis and distribution of Fe-S clusters are strictly controlled cellular processes that involve several mitochondrial proteins that specifically interact each other to form a complex machinery (Iron Sulfur Cluster assembly machinery, ISC machinery hereafter). This machinery ensures the correct assembly of both [2Fe-2S] and [4Fe-4S] clusters and their insertion in the mitochondrial target proteins. The present review provides a structural and molecular overview of the rare diseases associated with the genes encoding for the accessory proteins of the ISC machinery (i.e., GLRX5, ISCA1, ISCA2, IBA57, FDX2, BOLA3, IND1 and NFU1) involved in the assembly and insertion of [4Fe-4S] clusters in mitochondrial proteins. The disease-related missense mutations were mapped on the 3D structures of these accessory proteins or of their protein complexes, and the possible impact that these mutations have on their specific activity/function in the frame of the mitochondrial [4Fe-4S] protein biogenesis is described.

PMID:35883565 | DOI:10.3390/biom12071009

Genome Med. 2022 Jul 26;14(1):79. doi: 10.1186/s13073-022-01087-x.

ABSTRACT

BACKGROUND: Genomic variants which disrupt splicing are a major cause of rare genetic diseases. However, variants which lie outside of the canonical splice sites are difficult to interpret clinically. Improving the clinical interpretation of non-canonical splicing variants offers a major opportunity to uplift diagnostic yields from whole genome sequencing data.

METHODS: Here, we examine the landscape of splicing variants in whole-genome sequencing data from 38,688 individuals in the 100,000 Genomes Project and assess the contribution of non-canonical splicing variants to rare genetic diseases. We use a variant-level constraint metric (the mutability-adjusted proportion of singletons) to identify constrained functional variant classes near exon-intron junctions and at putative splicing branchpoints. To identify new diagnoses for individuals with unsolved rare diseases in the 100,000 Genomes Project, we identified individuals with de novo single-nucleotide variants near exon-intron boundaries and at putative splicing branchpoints in known disease genes. We identified candidate diagnostic variants through manual phenotype matching and confirmed new molecular diagnoses through clinical variant interpretation and functional RNA studies.

RESULTS: We show that near-splice positions and splicing branchpoints are highly constrained by purifying selection and harbour potentially damaging non-coding variants which are amenable to systematic analysis in sequencing data. From 258 de novo splicing variants in known rare disease genes, we identify 35 new likely diagnoses in probands with an unsolved rare disease. To date, we have confirmed a new diagnosis for six individuals, including four in whom RNA studies were performed.

CONCLUSIONS: Overall, we demonstrate the clinical value of examining non-canonical splicing variants in individuals with unsolved rare diseases.

PMID:35883178 | DOI:10.1186/s13073-022-01087-x

J Med Internet Res. 2022 Jul 26;24(7):e36691. doi: 10.2196/36691.

ABSTRACT

BACKGROUND: Mobile apps are becoming increasingly popular, with 5.70 million apps available in early 2021. Smartphones can provide portable and convenient access to health apps. Here, we consider apps for people with one of the estimated 7000 rare conditions, which are defined as having an incidence of <1 in 2000. The needs of people with rare conditions are known to be different from those of people with more common conditions. The former may be socially isolated (not knowing anyone else who has the condition) and may not be able to find reliable information about the disorder.

OBJECTIVE: The aim of this review is to search for apps developed specifically for people diagnosed with a rare disease and to assess them for quality using the Mobile App Rating Scale (MARS). We examine features that address 6 identified needs of people with a rare disorder and make recommendations for future developers.

METHODS: Google Play Store (Android) and Apple App Store (iOS) were searched for relevant health-related apps specifically for rare diseases. The search included the names of 10 rare disease groups. App quality was determined using MARS, assessing app engagement, functionality, aesthetics, and information.

RESULTS: We found 29 relevant apps (from a total of 2272) addressing 14 rare diseases or disease groups. The most common rare conditions addressed were cystic fibrosis (n=6), hemophilia (n=5), and thalassemia (n=5). The most common app features were web-based information and symptom trackers. The mean MARS score was 3.44 (SD 0.84). Lowest scores were for engagement.

CONCLUSIONS: Most apps provided factual and visual information, providing tools for self-monitoring and resources to help improve interactions during health consultations. App origin and quality varied greatly. Developers are recommended to consider ways to make appropriate apps more easily identifiable to consumers, to always include high-quality information, improve engagement, provide qualitative evaluations of the app, and include consumers and clinicians in the design.

PMID:35881435 | DOI:10.2196/36691

Ther Innov Regul Sci. 2022 Jul 25. doi: 10.1007/s43441-022-00433-w. Online ahead of print.

ABSTRACT

The exclusion of pregnant populations, women of reproductive age, and the fetus from clinical trials of therapeutics is a major global public health issue. It is also a problem of inequity in medicines development, as pregnancy is a protected characteristic. The current regulatory requirements for drugs in pregnancy are being analyzed by a number of agencies worldwide. There has been considerable investment in developing expertise in pregnancy clinical trials (for the pregnant person and the fetus) such as the Obstetric-Fetal Pharmacology Research Centers funded by the National Institute of Child Health and Human Development. Progress has also been made in how to define and grade clinical trial safety in pregnant women, the fetus, and neonate. Innovative methods to model human pregnancy physiology and pharmacology using computer simulations are also gaining interest. Novel ways to assess fetal well-being and placental function using magnetic resonance imaging, computerized cardiotocography, serum circulating fetoplacental proteins, and mRNA may permit better assessment of the safety and efficacy of interventions in the mother and fetus. The core outcomes in women's and newborn health initiative is facilitating the consistent reporting of data from pregnancy trials. Electronic medical records integrated with pharmacy services should improve the strength of pharmacoepidemiologic and pharmacovigilance studies. Incentives such as investigational plans and orphan disease designation have been taken up for obstetric, fetal, and neonatal diseases. This review describes the progress that is being made to better understand the extent of the problem and to develop applicable solutions.

PMID:35881237 | DOI:10.1007/s43441-022-00433-w

Indian Pediatr. 2022 Jul 15;59(7):587.

NO ABSTRACT

PMID:35869882

Am J Nurs. 2022 Aug 1;122(8):22-23. doi: 10.1097/01.NAJ.0000854968.37305.7a.

ABSTRACT

The Food and Drug Administration has approved alpelisib (Vijoice) to treat a rare noninherited genetic disorder called PIK3CA-related overgrowth spectrum.

PMID:35862598 | DOI:10.1097/01.NAJ.0000854968.37305.7a

Cad Saude Publica. 2022 Jul 15;38(6):e00167721. doi: 10.1590/0102-311XPT167721. eCollection 2022.

ABSTRACT

Public policies that serve the Brazilian population with rare diseases are increasingly discussed, either regarding access to medicines, multidisciplinary care, therapeutic alternatives, or representativeness. Although the Brazilian Ministry of Health published in 2014 the Ordinance n. 199, which instituted the Brazilian National Policy of Integral Care for People with Rare Diseases and approving the Guidelines for Integral Care to People with Rare Diseases under the Brazilian Unified National Health System (SUS), this population remains unaided regarding the peculiarities of their treatments. In this scenario, patient associations began to seek spaces for political representation, increasingly provoking legislative initiatives in the Brazilian National Congress, seeking for alternatives for the millions of Brazilians living with rare diseases. By using a qualitative documentary research, the study considers all projects presented until August 2020 on this topic, identifying the main parliamentarians involved, their biographical characteristics, and at which stage of the public policy cycle this topic is in the Brazilian National Congress; thus, identifying a possible path for the consolidation of a policy. We observed that the actions regarding rare diseases are independent of any political party alignment, being an agenda shared by antagonistic groups. This agenda, however, faces the challenge of having only 18 parliamentarians responsible for 50% of all the legislative matters already presented. Furthermore, we also observed that parliamentarians prefer to boost the debate and give visibility to the subject than to invest in new attempts at legal and regulatory changes.

PMID:35857920 | DOI:10.1590/0102-311XPT167721

Mol Genet Metab. 2022 Aug;136(4):289-295. doi: 10.1016/j.ymgme.2022.07.006. Epub 2022 Jul 8.

ABSTRACT

RNA-based therapies are a new, rapidly growing class of drugs that until a few years ago were being used mainly in research in rare diseases. However, the clinical efficacy of recently approved oligonucleotide drugs and the massive success of COVID-19 RNA vaccines has boosted the interest in this type of molecules of both scientists and industry, as wells as of the lay public. RNA drugs are easy to design and cost effective, with greatly improved pharmacokinetic properties thanks to progress in oligonucleotide chemistry over the years. Depending on the type of strategy employed, RNA therapies offer the versatility to replace, supplement, correct, suppress, or eliminate the expression of a targeted gene. Currently, there are more than a dozen RNA-based drugs approved for clinical use, including some for specific inborn errors of metabolism (IEM), and many other in different stages of development. New initiatives in n-of-1 RNA drug development offer new hope for patients with rare diseases and/or ultra-rare mutations. RNA-based therapeutics include antisense oligonucleotides, aptamers, small interfering RNAs, small activating RNAs, microRNAs, lncRNAs and messenger RNAs. Further research and collaborations in the fields of chemistry, biology and medicine will help to overcome major challenges in their delivery to target tissues. Herein, we review the mechanism of action of the different therapeutic approaches using RNA drugs, focusing on those approved or in clinical trials to treat IEM.

PMID:35849888 | PMC:PMC9264812 | DOI:10.1016/j.ymgme.2022.07.006

Orphanet J Rare Dis. 2022 Jul 19;17(1):281. doi: 10.1186/s13023-022-02426-2.

ABSTRACT

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) disease is a rare genetic disorder with symptoms and complications that can significantly affect patients' daily lives. To date, no scale has been validated to assess the specific symptoms of this disease on the quality of life (QOL) of HHT patients. This makes it difficult for clinicians to accurately measure the quality of life of patients with HHT. The present study aims to develop and validate a QOL measurement tool specific to HHT disease: the QOL questionnaire in HHT (QoL-HHT).

METHODS: A quantitative, non-interventional, multi-center study involving HHT patients in twenty French HHT expert centers was conducted. A calibration sample of 415 HHT patients and a validation sample of 228 HHT patients voluntarily participated in the study. Data were analyzed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), Exploratory Structural Equation Modeling (ESEM) analyses, reliability analyses, and correlational analyses.

RESULTS: The EFA, CFA and ESEM results allowed us to provide evidence of the factorial structure of a questionnaire composed of 24 items measuring 6 domains of QOL: Physical limitations, social relationships, concern about bleeding, relationship with the medical profession, experience of symptoms, and concern about the evolution of the disease. Cronbach's alpha coefficients (> 0.70) demonstrated reliable internal consistency of all the QoL-HHT scores (dimensions). The results of the test-retest provided further evidence of the reliability of the QOL-HHT scores over time. Correlational analyses provided evidence for the convergent validity of the QoL-HHT scores.

CONCLUSIONS: We developed a simple and quick self-assessment tool to measure quality of life specific to HHT disease. This study demonstrated reliability and validity of our QoL-HHT scores. It is a very promising tool to evaluate the impact of HHT disease on all aspects of the quality of life of HHT patients in order to offer them individualized medico-psycho-social support.

TRIAL REGISTRATION: ClinicalTrials, NCT03695874. Registered 04 October 2018, https://www.

CLINICALTRIALS: gov/ct2/show/NCT03695874.

PMID:35854330 | DOI:10.1186/s13023-022-02426-2

Recenti Prog Med. 2022 Jul-Aug;113(7):451-459. doi: 10.1701/3850.38340.

ABSTRACT

INTRODUCTION: Rare diseases have a high social and health impact. Since 2005, AIFA has been funding independent clinical research. The objective of this paper is to describe data on independent research on rare diseases financed by the Agency.

METHODS: With reference to studies financed by AIFA between 2005-2018 the following data have been collected: financial characteristics, study design, therapeutic area, population included, completion status, availability of study results publications, publication characteristics and conclusions. Data have been analyzed in order to provide information on characteristics and scientific productivity of clinical studies on rare diseases.

RESULTS: Between 2005 and 2018, AIFA published 9 Calls for Funding of Independent Research and financed 282 clinical studies, 111 (about 40%) of which were on a rare disease and/or a rare tumor for a total of € 43,455,438. Studies were interventistic in 93.6% (mainly phase II or III). The most represented therapeutic area was oncology (19.9%), followed by neurology (17.1%), and onco-hematology (16.2%). 28.8% of clinical studies enrolled fragile population (children, elderly, pregnant women). Fourty eight studies (43.2%) completed according to protocol, 8 (7.2%) completed with reduced sample size, 18 (16.2%) were prematurely terminated, while 37 of them are still ongoing. In the subgroup of 74 closed studies at least a scientific publication is available for 49 of them. A total of 81 papers are available including two publications related to ongoing studies (range 1-8; mean 1.5; median 1). Cumulative Impact Factor is 619.269 (range for single paper 0.17-34.492).

DISCUSSION: A good percentage of clinical studies financed by AIFA were on rare diseases and/or rare tumors. Clinical trials were less likely to complete according to protocol than observational ones, in agreement with literature data; on the other hand once completed, clinical trials were more likely to publish research findings. Overall, 66.2% of closed studies has at least one publication; this percentage is higher if we consider the subgroup of clinical trials and if we consider clinical trials completed according to study protocol (95.3%).

PMID:35852081 | DOI:10.1701/3850.38340

Recenti Prog Med. 2022 Jul-Aug;113(7):440-450. doi: 10.1701/3850.38339.

ABSTRACT

INTRODUCTION: Rare disease (RD) patients present complex therapeutic needs. When there are therapeutic options available, orphan drugs (OD) represent only a limited proportion of prescribed treatments. This study aims at investigating the real-world use of treatments considered not replaceable and essential for the care of RD patients, besides their reimbursement status, using data from a RD population-based registry.

METHODS: The study is based on data derived from the Veneto region RD registry. For the period 2019-2020, we have analyzed the prescriptions of treatments defined as essential and not replaceable, besides their reimbursement status, included in therapeutic plans issued by RD expert Centres for patients resident in the Veneto region (north-east of Italy, 4.9 million inh.). The correspondent pharmaceutical costs have been estimated as well.

RESULTS: In the study period there have been 22.186 prescriptions, included in 9,197 therapeutic plans issued for RD patients resident in the monitored area. The plans present a high level of complexity in terms of number and type of prescribed treatments, with 11% of the plans containing 5 or more prescriptions. 3,041 medicinal products have been prescribed in the study period, of whom 41% are drugs. Although these prescriptions are distributed among all the groups of RD patients, only a limited proportion of products (n=10) is responsible of the 50% of all the costs attributable to these treatments. Overall, the annual cost attributable to essential treatments not directly reimbursed by the national health system is quantifiable in 1 million euros per million inhabitants.

CONCLUSIONS: This real-world study offers a snapshot of the complexity of treatments defined as essential, besides their reimbursement status, in therapeutic plans issued by RD expert Centres for a consistent group of RD patients monitored by a population-based registry. It highlights the complexity of the therapeutic approaches put in place for the care of RD patients, including drugs and a variety of other treatments. Population-based registries collecting data on prescribed treatments can contribute to understand the therapeutic needs of RD patients, treatments' accessibility and the impact of prescriptions on the global pharmaceutical costs.

PMID:35852080 | DOI:10.1701/3850.38339