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Edition of 31 October 2018

International News

USA: 5 Additions to the Undiagnosed Diseases Network

The Undiagnosed Diseases Network (UDN) is a research study, funded by the National Institutes of Health Common Fund, aimed at bringing together clinical and research experts from across the United States to solve medical mysteries using advanced technologies. It was formed in 2015 and has since then been able to diagnose about 200 cases.

The UDN is currently expanding, with the integration of Children’s Hospital of Philadelphia and the Hospital of University of Pennsylvania, University of Miami School of Medicine, University of Utah, University of Washington School of Medicine and Seattle Children’s Hospital, and Washington University in St. Louis. This brings the clinical sites, where UDN participants are evaluated, to 12 US cities.

The UDN also recently published a paper in the New England Journal of Medicine. The study entitled “Effect of genetic diagnosis on patients with previously undiagnosed disease” evaluated patients referred to the UDN to infer the rate of diagnosis and the effect of the diagnosis on medical care. The authors report that, although one third of the accepted patients had previously undergone exome sequencing, the UDN established a clinical diagnosis at a rate of 35%. A specific therapy was recommended for 21% of the patients who received a diagnosis. As a result of these efforts, 31 new syndromes were identified. These results indicate that the approach used by the UDN is successful in increasing the rate of diagnosis.

Press release
Visit the UDN website

USA: Introduction of Rare Disease Fund Act

US Representatives Juan Vargas, Scott Peters and Tom Rooney introduced on 13 September 2018 H.R. 6801, the Rare Disease (RaD) Fund Act. This legislation presented in the House of Representatives is aimed at establishing “a Rare Disease Therapeutics Corporation to encourage the development of high-risk, high-return therapies for rare diseases, and for other purposes”. Back by peer-reviewed simulations conducted at MIT, the bill suggests the use of a megafund model, to create large diversified portfolios, thereby reducing risk, and to structure the financing for these portfolios as combinations of equity and securitised debt. The plan is to attract pension funds, insurance companies, and other large institutional investors, while minimising governmental exposure and lowering drug prices for patients and the healthcare system.

Read the press release from Rep. Vargas
Read the bill

USA: Food and Drug Administration (FDA) awards 12 new grants for the development of rare disease medical products

The US Food and Drug Administration (FDA) announced at the end of September the attribution of 12 new clinical trial research grants through the Orphan Products Clinical Trials Grants Program, totaling more than $18 million over the next four years for the development of medicinal products in the field of rare diseases.

The grant recipients will carry forward clinical research for the treatment of Stargardt disease, primary sclerosing cholangitis, Cushing disease, advanced pancreatic cancer, head and neck squamous cell carcinoma, dystrophic epidermolysis bullosa, myelodysplastic syndrome or acute myeloid leukemia, graft versus host disease, congenital ichthyosis, dopamine agonist intolerant hyperprolactinemia, congenital adrenal hyperplasia, and bronchopulmonary dysplasia.

Read the press release

Cases of acute flaccid paralysis in the United States

The Centers for Disease Control and Prevention (CDC) published a report on 16 October 2018 concerning cases of acute flaccid paralysis (AFP), a disease resembling poliomyelitis. Even though AFP remains rare, the fact that its origin is still unknown and that it has affected a few dozen cases in 2018, mainly children, has proved worrying enough for the health authorities to put in place an update on this disease.

Consult the CDC note

India’s first centre for children with neuromuscular diseases

Bangalore Baptist Hospital in association with ORDI (Organization For Rare Diseases, India) inaugurated mid-September India’s first Paediatric Neuromuscular Service called “The Muscle and Nerve Clinic”. The centre has a range of specialists covering rare diseases affecting the neuromuscular system.

Read the press release

5-year collaboration planned between St. Jude Children’s Research Hospital and World Health Organization

St. Jude Children’s Research Hospital, Memphis, USA, announced at the end of September a five-year collaboration with World Health Organization aimed at transforming cancer care worldwide to cure at least 60 percent of children with six of the most common types of cancer by 2030. This collaboration will bring together stakeholders in childhood cancer from around the world to increase access to care for children with cancer, enhance quality of care by developing national centers of excellence and regional satellites, and influence the integration of childhood cancer into national policies to ensure the greatest chance of survival for all affected children.

Read the press release

Australia: Extension of the Fair for Rare campaign

Rare Voices Australia advocates for an Australian rare disease policy through its Fair for Rare campaign, which enables users to send letters to local MPs to strengthen a collective call for a National Rare Disease Framework. Originally foreseen to end in September, the call is extended until further notice.

Visit the website

Shire opens $1 billion plasma fractionation plant

Shire is a global biotechnology company focused on serving people with rare diseases. The company recently held a kickoff ceremony for its 1 million-square-foot plasma fractionation facility in Georgia, USA. There, the company will manufacture immunoglobulin products to help patients with primary immune deficiency disorders.

Read the press article

European News

Report of the 2018 annual face-to-face meeting of Enpr-EMA members and the Enpr-EMA Coordinating Group

The Coordinating Group (CG) is the operational centre of the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA). Its tasks include:

Facilitating access of the pharmaceutical industry to pediatric clinical study centres and experts;
Identifying new networks to include in Enpr-EMA;
Developing common educational tools for children and parents, to increase their willingness to take part in clinical trials.

The invited new members to take part in the annual face-to-face meeting that was held on 15 August 2018 were NETSTAP, a network of pediatricians for clinical studies in children in ambulant treatment, TREAT-NMD, a global organisation bringing together specialists, patient groups and industry representatives in the neuromuscular field and HunPedNet research network.

At this meeting were presented the questions and a summary of the results of the European Reference Network (ERN)-wide survey on the status quo of ERNs and their clinical research activities related to pediatrics, the presentation of which can be consulted here. The results had been presented at the 2018 annual workshop of the Enpr-EMA.

At this meeting also, Luca Sangiorgi, coordinator of ERN-Bond and of the ERNs Working group on research, was endorsed as observing member of the CG to represent ERNs.

Consult the report

A call to protect the European Reference Networks

On 29 March 2019, the United Kingdom must leave the European Union (EU). At present, the UK government and the European Union have not agreed on a withdrawal procedure to protect the UK's ability to continue to participate in the European Reference Networks (ERNs).

Genetic Alliance UK has written, together with a number of experts working in the field of rare diseases, a statement on the importance of UK participation in ERNs.

The declaration and the #ProtectERNs campaign call on the UK government and the European Union to ensure the UK's continued participation in the ERNs.

Patients and their families can participate in the campaign by signing a petition here.

Learn more

Brexit addressed in the European Parliament

Around 20 European health organisations met in the European Parliament on 27 September 2018. This community expressed its concern about the slow pace of negotiations, notably concerning the availability of medicines for European and British patients, the preservation of partnerships in medical research and potential impacts on patient safety.

To find out more

Four additional European countries to sign the Genomics Declaration

Greece, Austria, Croatia and the Netherlands sign the European Declaration "Towards access to at least 1 million sequenced genomes in the EU by 2022", which was launched on 10 April 2018 during Digital Day 2 , which had already been signed by Bulgaria, the Czech Republic, Cyprus, Estonia, Finland, Italy, Lithuania, Luxembourg, Malta, Portugal, Slovenia, Spain, Sweden and UK. This statement was designed to change the game for health research and clinical practice in Europe: sharing more genomic data will improve understanding and prevention of disease, allowing more personalised treatments (and targeted prescription of drugs), especially for rare diseases, cancer and brain-related diseases.

Read the press release on the Netherlands signing the genomics declaration

Open consultation on the investigation of medicinal products in the term and preterm neonate

The directive on the investigation of medicinal products in the term and preterm neonates was prepared during the 2007-2009 period implemented in 2010.

A revision of the directive is now being prepared, to consider new clinical developments, to improve the quality and consistency of neonatal research, while avoiding unnecessary studies in this area of highly vulnerable population.

The public consultation is open until 16 December 2018. Comments should be provided using this template. The completed comments form should be sent to paediatrics@ema.europa.eu.

New Chair for the Committee for Medicinal Products for Human Use (CHMP)

The CHMP is a committee of the European Medicines Agency, charged with the scientific evaluation of new medicines. Dr Harald Enzmann will be its new Chair for three years, and he will replace Dr. Tomas Salmonson. Dr Enzmann is a medical doctor. He works for the Federal Institute for Drugs and Medical Devices (BfArM) in Germany, where he is Head of European and International Affairs. Dr Enzmann has been a member of the CHMP since 2005 and its vice-chair since October 2016.

New version of the website of the European Medicines Agency (EMA)

The EMA launched a new version of its website on September 27, 2018. It has a better search system, a clearer display on mobile, simpler URLs and an updated design.

Visit the website

Update on EMA progress concerning preparations for Brexit

The European Medicines Agency (EMA) has entered the third phase of its continuity plan following Brexit, on 1 October 2018. This plan, announced in early August, aims to reduce some of the EMA's activities to focus on the main functions of the Agency, while preparing the physical move to the Netherlands.

Read the press release

European Commission and EMA joint action plan for the development of medicines for children in Europe

The European Union (EU) Pediatric Regulation entered into force in 2007. In 2017, the European Commission (EC) published its 10-year report on the implementation of the Regulation, which showed that the number of medicines developed for children had increased during this period. However, it also revealed specific challenges, such as the development of drugs for diseases that affect only children or for diseases that manifest differently in adults and children. The report also pointed out that the development and availability of pediatric treatments was often delayed compared to adult treatments.

During a workshop organised on 20 March 2018 by the European Medicines Agency (EMA) and the European Commission, an action plan for the development of pediatric treatments, which includes five pillars, was thought out:

Identify pediatric medical needs;
Strengthen the cooperation of decision-makers;
Ensure completion of Pediatric Investigation Plans (PIPs);
Improve the processing of PIP applications Increase transparency around pediatric medicines;

The implementation of these actions should increase the efficiency of pediatric regulatory processes in the current legal framework and increase the availability of medicines for children.

The plan was originally to be completed within two years. However, due to the impact of Brexit and the relocation of the EMA to the Netherlands, some actions are not expected to be completed by the end of 2020, as indicated in the plan. The plan will be updated over time, based on priorities and availability of resources.

Read the press release
Consult the plan

Ten years of European action against rare cancers

EU action on rare cancers has grown considerably over the last decade, thanks to a unique collaborative approach and a multi-stakeholder approach. This was one of the key messages of a recent European Parliament event on rare cancers, jointly organised by Rare Cancers Europe (RCE), the European Society of Medical Oncology (ESMO) and The Parliament Magazine, on 25 September 2018. The debate focused on the challenges facing the 24 European Reference Networks (ERNs) for rare diseases, including rare cancers, the implementation of the cross-border healthcare directive, the problems related to the generation and exploitation of evidence on rare cancers, and the potential impact of the draft EU Regulation on Health Technology Assessment (HTA).

RCE was created by ESMO in 2008 to improve the care of rare cancer patients and focuses on integrating rare cancer into the European political agenda. Its activities have improved the diagnosis and care of rare cancers, including the creation of Joint Action on Rare Cancer (JARC) and support for ERN training, and helped to bring together scattered expertise.

Read the press release

Huge Big Data programme launched by UK National Health System

In March 2017, the NHS England Board of Directors (National Health Service) defined its strategic approach for the creation of a National Genomic Medicine Service, building on the NHS contribution to the "100,000 Genomes" project. This approach includes five key elements:

A national genomic laboratory service through a network of Genomic Laboratory Hubs
A new National Genomic Test Directory to underpin the genomic laboratory network
A national Whole Genomic Sequencing provision and supporting informatics infrastructure developed in partnership with Genomics England
A clinical genomics medicine services and an evolved Genomic Medicine Centre service
A national co-ordinating and oversight function within NHS England (Genomics Unit)

Starting in October, NHS England began regularly performing a standard set of genomic tests for certain cancers and rare diseases, thus completing the uneven use of such tests. MP Matt Hancock, Secretary of State for Social Affairs and Health, confirmed that whole genome sequencing will be offered to adults with rare diseases or difficult-to-treat cancers, an offer that will be extended from 2019 onwards to all critically ill children, including those with possible genetic disorders and cancers. Crucially, for patients who consent, the data from these tests will be kept in a national research center together with their health records. The size of the NHS, universal coverage and lifelong health records promise to make this database particularly useful.

Read the briefing note from Genetic Alliance UK

AEGLE project reports on the process of health data after the adoption of the GDPR

EU rules on data protection have changed since the implementation of the General Data Protection Regulation (GDPR). In the framework of the AEGLE project, data were collected in four different Member States of the European Union. The original question was whether it is possible in this new regulatory context to process personal data, particularly health data, for research purposes. The answer was different for each country, despite the GDPR directive. While this instrument provided for a certain degree of harmonisation of the data protection legal frameworks throughout the European Union, divergent legal rules remained in particular concerning the re-use of personal data without the informed consent of the data subjects. Another issue was to know whether the implementation of the GDPR would affect this state of play and harmonise the rules applicable to data processing for scientific research in the European Union. The legal assessment by time.lex addressing these issues was prepared for the AEGLE project based on country reports from all the countries of the European Union, plus Norway and Switzerland, comparing the situation under the previous regime and the GDPR, while applying the new rules specifically to the AEGLE platform. The reports for the different countries were published at the end of August.

Read the press release
Consult country by country reports

Bioinformatics

Medical image synthesis for data augmentation and anonymisation using Generative Adversarial Networks

Researchers from the Nvidia Corporation, MGH and BWH Center for Clinical Data Science and the Mayo Clinic published recently in Simulation and Synthesis in Medical Imaging and on the arXiv platform their work on the generation of synthetic images for medical purposes. They illustrated improved performance on tumour segmentation by leveraging the synthetic images as a form of data augmentation as well as the value of generative models as an anonymisation tool. Useful for all medical uses, this technology might prove to be especially useful in the field of rare diseases to generate synthetic data.

arXiv:1807.10225

Consult the article

matchbox: An open-source tool for patient matching via the Matchmaker Exchange

matchbox is an open-source, platform-independent, portable bridge between any given rare disease genomic centre and the Matchmaker Exchange (MME) network, which was launched in 2013 and allows investigators searching for novel genetic causes of rare diseases to find individual patients with the same candidate gene and overlapping phenotypic features. This tool thus allows to search for additional cases by making it possible to query across institutional boundaries. The history and results were published in Human Mutation.

Hum Mutat. 2018 Sep 21

Consult the PubMed abstract

HerGePred: Heterogeneous network embedding representation for disease gene prediction

The identification of genes involved in rare and genetic diseases is a first step in revealing the underlying mechanisms of disease and potentially find treatments. Computational methods have been developed for the identification of such genes. However, disease-gene prediction is still an issue that could be solved by making full use of disease-related and gene-related (Gene Ontology) information. A team of researchers have developed an approach for disease gene prediction called HerGePred and validated their framework. Results were accepted for publication in IEEE Journal of Biomedical and Health Informatics.

IEEE J Biomed Health Inform. 2018 Sept

Consult the article

Epilepsyecosystem.org: crowd-sourcing reproducible seizure prediction with long-term human intracranial EEG

Crowd-sourcing ecosystems leverage quality data to enable cost-effective, rapid development of predictive algorithms to warn patients of epilepsy seizures. The work presented in Brain involved an international competition, a follow-up held-out data evaluation, and online platform, Epilepsyecosystem.org. Long-term continuous intracranial electroencephalography from prediction-resistant patients were analysed. The results of the study indicated that seizure prediction was possible in a wider range of patient than anticipated and that different algorithms were sometimes more appropriate for different patients.

Brain. 2018 Sep 1;141(9):2619-2630

Consult the PubMed abstract

Creating datasets and cleaning existing data identifiers in a cystic fibrosis registry using probabilistic approach from astronomy

A research article published in PLOS One bridges the gap between biomedical and astronomy research. The researchers applied astronomical statistical matching techniques to link individual patient records so they can be used where identifiers are absent or to validate uncertain identifiers. They applied it to a subset of data held in the European Cystic Fibrosis Society Patient Registry. They found that their framework could create longitudinal samples where none existed and validate pre-existing patient identifiers.

PLoS One. 2018 Jul 9;13(7):e0199815

Consult the PubMed abstract

Registries & Biobanks

USA: NORD receives grant from Anthem Foundation for expansion of Rare Disease Database

A $95,000 grant was awarded from the Anthem Foundation to the National Organization for Rare Diseases (NORD) to improve the effectiveness of the Rare Disease Database and upgrade the website’s functionality and platform. The more user-friendly interface will in turn benefit researchers, medical professionals, public policy officials and members of the media who wish to seek information on rare diseases.

Read the press release

A practical guide from the Medical Research Charities Group to set up a rare disease patient registry

The Medical Research Charities Group organised a workshop, entitled “The Nuts and Bolts of Patient Registries”, for their member charities and other guests in April 2018. A guide emerged from this workshop and is now available online.

Italy: 6-year experience from the hospital-based Italian Mastocytosis Registry

The Italian Mastocytosis Registry was set up in 2009 to collect data of mastocytosis patients at a multidisciplinary and national level, to investigate major differences in disease-related features, symptoms and clinical course when comparing different age groups, to understand the basis of different diagnosis and therapeutic algorithms and to explore whether disease outcomes in Italian patient could confirm data from available resources. Analysis over 6 years on 600 patients revealed some centre-specific approaches for diagnosis and therapy. Authors of the resulting paper published in Future Oncology highlighted the importance of a multicentre database for rare diseases like mastocytosis.

Future Oncol. 2018 Nov;14(26):2713-2723

Consult the PubMed abstract

The Glomerular Disease Study and Trial Consortium: A grassroots initiative to foster collaboration and innovation

A paper published in Kidney International Reports described the creation of a platform in which nephrologists, nephropathologists, and scientists come together to share experiences, participate in medical education, and conduct translational research activities in the field of glomerular kidney disorders, through an international initiative called the Glomerular Disease Study and Trial Consortium.

Kidney Int. 2018 Sep

Consult the abstract

Health Economics

Estimated costs of pivotal trials for novel therapeutic agents approved by the FDA from 2015 to 2016

The global clinical trial cost assessment was evaluated for 59 novel therapeutic agents approved by the US Food and Drug Administration (FDA) from 2015 to 2016. The estimates costs ranged from less than $5 million for trials without a control group to $346.8 million for a noninferiority trial with endpoints assessing clinical benefit. Costs also varied by trial end point, treatment duration, patient enrollment, and therapeutic area. The central cluster of trials had estimated costs of $12.2 million to $33.1 million. This article published in JAMA Internal Medicine highlights the fact that contrary to popular belief, pivotal trials for novel drugs with substantial clinical effects can be conducted at a lower cost than what the widely held assumption indicates.

JAMA Intern Med. 2018 Sep 24

Consult the PubMed abstract

Direct healthcare costs for children diagnosed with genetic diseases are significantly higher than for children with other chronic diseases

A Canadian group of researchers led a retrospective cohort study using population-based provincial health administrative data for children with genetic diseases compared with three matched cohorts of children with asthma, diabetes, or from the general population. The results, published in Genetics in Medicine, indicated that direct healthcare costs for children with genetic diseases were significantly higher than that of the others cohorts. The researchers postulate that these findings will have important implications for resource allocation and funding prioritisation concerning this particular population.

Genet Med. 2018 Sep 24

Consult the PubMed abstract

Disease and economic burden for rare diseases in Taiwan: a longitudinal study using Taiwan’s National Health Insurance Research Database

A study published in PloS One examined the national trends in the prevalence of rare diseases and their health-related economic burden in Taiwan, using the National Health Insurance Research Database claim from 2003 to 2014. The researchers found that prevalence of rare diseases and their related economic burden have grown substantially over the past twelve years and they postulate that these trends are likely to continue. These results provide an empirical basis for future studies on rare diseases and orphan drugs.

PLoS One. 2018 Sep 21;13(9):e0204206

Consult the PubMed abstract

Leveraging EUnetHTA’s conceptual framework to compare HTA decision drivers in France, Italy, and Germany from a pharmaceutical manufacturer’s point of view

Health Technology Assessment (HTA) procedures largely differ across European countries. Researchers reviewed recent appraisals of a pharmaceutical manufacturer in three major European markets (France, Italy, and Germany) and identified and categorised related decision driver. In conclusion of this study, they found that the focus of these three countries on the clinical domains within the EUnetHTA (a joint action, established to create an effective and sustainable network for health technology assessment (HTA) across Europe) framework is a suitable starting point for the development of a joint HTA view on clinical evidence. They found that differences also still had to be addressed before such a collaboration can emerge.

Health Econ Rev. 2018 Sep 21;8(1):24

Consult the PubMed abstract

Screening

Service provision of non-invasive prenatal testing for Down syndrome in public and private healthcare sectors

Researchers from Hong Kong, Singapore and Leeds led a study using in-depth interviews with twenty obstetric providers offering non-invasive prenatal testing (NIPT) in Hong Kong. The surveys indicated that although the providers had good knowledge of clinical advantages of NIPT, they were uncertain as to how to introduce the procedure to women. Authors of this paper published in BMC Health Services Research indicate that these results uncover the need for guidelines to enable better coordination of public and private sector services to enable women to make informed choices regarding prenatal testing.

BMC Health Serv Res. 2018 Sep 21;18(1):731

Consult the PubMed abstract

Attitudes to prenatal screening among Norwegian citizens: liberality, ambivalence and sensitivity

An electronic questionnaire was completed by Norwegian adults, regarding prenatal screening and diagnosis. In this country, access to screening for fetal abnormalities is still restricted. The results, published in BMC Medical Ethics, indicated that the majority of respondents supported increased access to prenatal screening with ultrasound and/or full genome sequencing of fetal DNA, although the concerns about the specific diagnosis of Down syndrome concerned significant minorities.

BMC Med Ethics. 2018 Sep 18;19(1):80

Consult the PubMed abstract

Ethical / Legal / Social

Mining Facebook data of people living with rare diseases

A content-based and temporal analysis of Facebook engagement and the decalogue of the Spanish Federation of Rare Diseases datasets was recently published in International Journal of Environmental Research and Public Health. The research groups analysed wereare public (which means that they belong to Facebook pages openly available to the public), users’ anonymity and privacy were preserved in the study, and information was only displayed in an aggregated way, removing names and email addresses. The analysis had two objectives: to help users interested in rare diseases, enabling them to maximise the engagement of their posts, and to help organisations to align their priorities with the interests of people expressed in social networks. The researchers observed that the following words have a large presence in the decalogue and are little-used on Facebook: disability, professionals and diseases. Similarly, the following are the words most present on Facebook with little representation in the decalogue: help, life, people and children. This article is helpful in aligning rare disease organisations with the interests of rare disease patients, that often concern quality of life.

Int J Environ Res Public Health. 2018 Sep; 15(9): 1877

Consult the PubMed abstract

Experience with the use of an online community on Facebook for Brazilian patients with gestational trophoblastic disease

A Facebook page headed by Brazilian specialised physicians in gestational trophoblastic disease (GTD) was created in 2013 to provide online support for patients. A cross-sectional study published in Journal of Medical Internet Research aimed to describe the netnography (an online research method which is applied to understanding social interaction in contemporary digital communications contexts) of Brazilian patients with GTD on Facebook. The survey indicated that the resource was particularly valuable for women being cared for outside of established reference centres.

J Med Internet Res. 2018 Sep 24;20(9):e10897

Consult the PubMed abstract

Perceptions of telemedicine for patient education among online support group patients with chronic or rare conditions

Cogent Medicine recently made available a study based on the cross-sectional survey of 274 patients with rare or chronic conditions recruited from an international online health community. The survey’s purpose was to test patient perceptions of the Community of Inquiry (CoI) framework for telemedecine for patient education (TPE). The CoI framework aims to provide successful online education and is comprised of three factors: cognitive presence, social presence and teaching presence. The authors suggest that a standardised TPE framework, similar to CoI, could remedy a divide between patients who are eager to use online education, and providers reluctant to support these services for fear of spreading inaccurate information.

Cogent Medicine. 2018;5(1):1525148

Consult the abstract

Health-related quality of life in children with PFAPA syndrome

Conventionally, Periodic Fever, Aphtous stomatitis, Pharyngitis and Adenitis (PFAPA) is considered a benign form of recurrent fever. However, according to the clinical practice of the authors of a study published in Orphanet Journal of Rare Diseases, fever episodes do have a huge impact on daily activities. The observational cohort study demonstrated that the wellbeing of PFAPA children was poor, with a major impact on psychosocial functioning and increased fatigue.

Orphanet J Rare Dis. 2018 Aug 29;13:132

Consult the article

Impact of myeloproliferative neoplasms on employment status and work productivity

The American Journal of Managed Care recently published a cross-sectional survey-based study on the association between myeloproliferative neoplasms and employment outcomes. The authors found that patients experienced symptom burden that negatively impacted their quality of life and ability to perform daily activities, which impacted also work productivity and career potential. The authors also argue to conclude that comprehensive supportive care may improve work productivity.

AJMC. 2018 Sep

Consult the abstract

Long‐term clinical outcomes in a cohort of adults with childhood‐onset systemic lupus erythematosus

At the end of August, the long-term clinical outcomes of childhood-onset systemic lupus erythematosus in adults were evaluated and the results published in Arthritis & Rheumatology. Researchers analysed data from the Childhood-onset SLE in the Netherlands (CHILL-NL) study to determine the effect of disease course and damage accrual over time on health-related quality of life. The authors note that the majority of adults with childhood‐onset systemic lupus erythematosus in this cohort developed significant damage at young age and have impaired health-related quality of life without achieving drug free remission, illustrating the great impact of the disease on future life.

Arthritis Rheumatol. 2018

Consult the PubMed abstract

A pilot study on oral health-related quality of life in patients with systemic sclerosis

A study to identify possible association between physician assessment of systemic sclerosis severity and the socioeconomic status with oral health-related quality of life was conducted from Croatia and the results published in Journal of International Medical Research. The data showed that oral health-related quality of life was positively correlated with the severity of general, skin, gastrointestinal, and joint-tendon involvement. Based on these results, the authors argue for a collaboration between rheumatologists and dental professionals which could induce improvement of oral health in systemic sclerosis patients.

J Int Med Res. 2018 Sep 13:300060518791089

Consult the PubMed abstract

Mental well-being in non-ambulant youth with neuromuscular disorders

Research done in Australia analysed, using a cross-sectional survey, non-ambulant youths’ (13-22 year olds) mental wellbeing and relationships with physical health, participation and social factors. The results were collected with a primary outcome measure of the Warwick Edinburgh Mental Wellbeing Scale. Interestingly, non-ambulant youths with neuromuscular disorders rated their mental wellbeing higher than youths in the general population, and authors argue that enabling youth’s educational attainment and attending to social support may optimise youths’ wellbeing.

Neuromuscular dis. 2018 Sep

Consult the abstract

A qualitative study on everyday life and mastocytosis from a patient perspective

Seven qualitative, semi-structured interviews with adult patients living with indolent systemic mastocytosis were conducted to describe everyday life with the disease. Conclusions from this study indicated that patients with this disease were severely affected in their family and social lives. This paper published in Journal of Clinical Nursing highlights the importance to take into account experiences from everyday life when counselling and tailoring treatment to the patient’s needs.

J Clin Nurs. 2018 Sep 19

Consult the PubMed abstract

Challenges in implementing genomic medicine: the 100,000 Genomes Project

The aim of the 100,000 Genomes Project is to create a new genomic medicine service for the UK’s National Health Service (NHS). The project will sequence 100,000 genomes from around 70,000 people. Participants are NHS patients with a rare disease, their families, and patients with cancer. In a paper published in the Journal of Translational Genetics and Genomics, researchers from Leicester give a review of the history of the 100,000 Genomes Project and what has been learned to date (concerning patient engagement, education, consent, legacy, etc). Based on this overview, they provide ten recommendations in ways that other healthcare systems could use similar approaches. This will be especially useful, as we have mentioned in this edition’s editorial that a lot of countries have started to launch similar approaches of mass genome sequencing.

J Transl Genet Genom. 2018;2:13

Consult the abstract

Corporate social responsibility (CSR) of innovative pharmaceutical corporations: the case of BIOGEN

The aim of a paper published in Comparative Economic Research was to discuss the common features and specificity of Corporate Social Responsibility (CSR) practices of innovative transnational corporations acting in the pharmaceutical industry, understood as their ability to make a breakthrough in the treatment of rare, incurable diseases. Traditional CSR practices include corporate philanthropy, community and neighbourhood programmes, volunteerism, etc. The author of the paper argues that the issue of CSR in the innovative pharmaceutical industry is the pricing of orphan and ultra-orphan drugs, while the case study of BIOGEN seems to show that the company is aware of the need to remove barriers to access the medicines. The author also suggests that a stronger international cooperation is needed to ensure equity of medicine access in a more efficient way.

Comparative Economic Research. 2018 Sep;21(3)

Consult the abstract

Study Design

Innovative study designs optimising clinical pharmacology research in infants and children

A supplement article published in The Journal of Clinical Pharmacology indicates that half of recent pediatric trials fail to achieve labeling indications due to inadequate study design. Thus the authors list innovative study designs to optimise the amount of pharmacokinetic data collected from small volumes and with the fewer number of procedures. This includes the use of opportunistic and sparse sampling, collaboration using large research networks, Bayesian adaptive techniques, modeling and simulation, and the collection of de-identified genetic and clinical data.

J Clin Pharmacol. 2018 Oct;58 Suppl 10:S58-S72

Consult the PubMed abstract

The path to perfect pediatric posology: drug development in pediatrics

Extrapolation of results found in adult clinical studies might not work for conditions that do not occur in adults and pharmacokinetic and safety information cannot be extrapolated and must be collected in children of all ages so that clinicians can use medication optimally and avoid severe adverse reactions. A supplement article published in The Journal of Clinical Pharmacology reviews why it is important to conduct pediatric studies and the crucial factors to keep in mind when doing so.

Journal of Clinical Pharmacology. 2018;58(S10)

Consult the abstract

A case study of an adaptive design for a clinical trial in a rare disease area

A paper published by a Sanofi team in Pharmaceutical Statistics considered the application of a seamless phase II/III design to a clinical trial in a rare disease area, with two arms and two endpoints: two doses of an experimental treatment (low dose and high dose) and one placebo control, one intermediate 6-month phase II endpoint, one primary endpoint later on, and one secondary 12-month phase III endpoint. As it is difficult to recruit patients in rare disease areas, the proposed inferential seamless design is thought to be able to speed up the drug development process.

Pharmaceutical Statistics. 2018 Sep

Consult the abstract

“Quality in, quality out”: a stepwise approach to evidence-based medicine for rare diseases promoted by multiple endocrine neoplasia 1

A paper led by researchers at the University Medical Centre Utrecht and published in Endocrine Connections identifies observational studies within patient cohorts as the most feasible study design regarding disease prevalence. They give a review of strategies to identify sufficient patients, maximise and maintain patient enrollment and standardise the data collection process. With this knowledge, they propose a stepwise approach that can guide others to start a database for rare diseases, including: 1) Formulating research questions; 2) Patient inclusion; 3) Data storage and data collection; 4) Designing a prospective database based on outcomes of the retrospective database and 5) Biobanking.

Endocrine Connections. 2018 Nov

Consult the abstract

Clinical trials in children and adolescents with systemic lupus erythematosus

As in many rare diseases, clinical trials are difficult to set up for systemic lupus erythematosus due to a reduced number of patients. Drawing from a collaboration between the USA and Italy, and on behalf of Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group, researchers published a review in Annals of the Rheumatic Diseases to evaluate the current regulatory framework regarding medication approvals, delineate barriers to clinical trial conduct, and strategies to improve access to new medications for the disease. The authors argue that sufficient numbers of patients are available as well as experienced investigative teams to perform pivotal clinical studies, which should omit traditional parallel-arm placebo designs and extrapolate as much as possible using adults trials and open-label and innovative design studies.

Annals of the rheumatic diseases. 2018

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The POWER-tool: Recommendations for involving patient representatives in choosing relevant outcome measures during rare disease clinical trial design

Researchers have developed a tool to involve patients in the determination of outcome measures and the choice of measurement instruments, developed with a patient think tank and road-test in an ongoing trial. The development and first experiences of the tool were described in an article published in Health Policy.

Health Policy. 2018 Sep 21. pii: S0168-8510(18)30500-1

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Design and endpoints for clinical trials in primary sclerosing cholangitis

A collaboration between the USA and the Netherlands seeded a review published in Hepatology on regulatory information, the available literature on natural history, and potential candidate clinical and surrogate endpoints in primary sclerosing cholangitis.

Hepatology. 2018 Sep;68(3):1174-1188

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Treatment of pustular psoriasis with anakinra: a statistical analysis plan for stage 1 of an adaptive two-staged randomised placebo-controlled trial

The study, published in Trials, aims to test the hypothesis that IL-1 blockade with anakinra will deliver therapeutic benefit in palmoplantar pustular psoriasis. The article describes the important features of the innovative small population trial design used in this case and the pre-specified statistical analysis plan for stage 1.

Trials. 2018 Oct 3;19(1):534

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Special considerations for clinical trials in fibrodysplasia ossificans progressiva (FOP)

The International Clinical Council on FOP (ICC) was established in 2016 to provide consolidated and coordinated advice on the best practices for clinical care and clinical research for individuals who suffer from FOP. The Clinical Trials Committee of the ICC developed a focused list of key considerations that encompass the specific and unique needs of the FOP community – considerations that are endorsed by the entire ICC. These considerations complement established protocols for developing and executing robust clinical trials by providing a foundation for helping ensure the safety of subjects with FOP in clinical research trials. Thus, the authors of a paper published in British Journal of Clinical Pharmacology proposed FOP-specific clinical trial considerations that were agreed upon by international FOP clinical experts.

Br J Clin Pharmacol. 2018 Oct 3

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A systematic review on clinical significance in pediatric oncology randomised controlled treatment trials

Clinical significance in a randomised controlled trial (RCT) can be determined using the minimal clinically important difference (MCID). The aim of a study published in Trials was to assess clinical significance in the pediatric oncology randomised controlled trial treatment literature. The authors found that a minority of RCTs in the pediatric oncology literature reported methodological attributes related to clinical significance and a notable portion of statistically insignificant studies were possibly clinical significance. From the conclusions of this study, the authors proposed several recommendations to promote the incorporation of clinical significance into RCT design and interpretation.

More largely, they postulate that their results raise the question of whether clinical significance is under-utilised and poorly reported in other rare disease contexts wherein obtaining an adequate study sample challenges feasibility. Moreover, research and knowledge translation efforts are required to raise awareness and understanding of the importance of clinical significance.

Trials. 2018;19:539

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Orphan Drugs

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 17-20 September 2018

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended thirteen medicines for approval, including three orphan medicines, at its September 2018 meeting.

The CHMP recommended granting marketing authorisations for:

The gene therapy Luxturna (voretigene neparvovec), for the treatment of adults and children with inherited retinal dystrophy caused by RPE65 gene mutations, a rare genetic disorder which causes vision loss and usually leads to blindness.
Jivi (damoctocog alfa pegol), for the treatment of haemophilia A (congenital factor VIII deficiency)
Poteligeo (mogamulizumab), for the treatment of mycosis fungoides or Sézary syndrome.

The CHMP adopted a negative opinion refusing a marketing authorisation for:

The applicant for Exondys (eteplirsen) requested a re-examination of the Committee's negative opinion for this medicine adopted at the May 2018 meeting. After considering the grounds for this request, the CHMP re-examined the initial opinion and confirmed its previous recommendation to refuse the granting of a marketing authorisation for this medicine.

The Committee recommended extensions of indications for:

Cabometyx
RoActemra
Venclyxto

Expanded patient access to investigational new devices

The Food and Drug Administration (FDA) has several pathways, similar to drug approval processes, for expanded use of unapproved medical devices in patients for whom no reasonable alternative therapy is available. With the advent of 3D printing and bioprinting, new rules are evolving to address concerns which are explored in a review published in JACC: Basic to Translational Science. The author explores the regulatory pathways involved,the rules as to how and when a device may be modified and future regulatory concerns for personalised devices created in 3D printing processes.

JACC Basic Transl Sci. 2018 Aug; 3(4): 533–544

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Addressing the needs of Canadians with rare diseases: an evaluation of orphan drug incentives

Currently, these is no orphan drug policy in Canada, although policymakers recently reversed their decision in order to follow the footsteps of the US or the EU which have the most extensive orphan drug policies. An article, published in Journal of Law and the Biosciences by Emily Harris from the University of Saskatchewan in Canada, argues that introducing orphan drug incentives in Canada would be a good decision and considers three potential orphan drug incentives in a Canadian context, as well as analyses whether it would be reasonable to expect incentives to have an impact in terms of increasing Canadians’ access to rare disease treatment.

Journal of the Law and the Biosciences. 2018 Aug

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Access to orphan drugs: a cross country comparison of legislative approach among Serbia, Croatia and Macedonia

The objective of an article published in Acta Medica Medianae was to identify differences in patient access to orphan drugs in the three pharmaceutical markets of Serbia, Croatia and Macedonia. The retrospective cross-sectional analysis cross-compared between national drug lists and the List of Orphan Drugs in Europe (LODE) indicated variations between countries in availability and access to orphan drugs. Namely, patients in Croatia had a greater number of registered and refunded drugs, but in Serbia, more than half of registered Orphan Medicinal Products (OMPs) could be refunded through the National Health Insurance Fund.

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Access to orphan drugs is a challenge for sustainable management of cystinosis in China

Once the diagnosis is confirmed, specific treatment with cysteamine, the only specific drug approved by the Food and Drug Administration for cystinosis, should be initiated to preserve renal function and improve growth in affected children. However, cysteamine is difficult to access in China. An opinion piece published in Chinese Medical Journal describes the difficult situation encountered by two young cystinosis patients and calls for a worldwide policy and action regarding the treatment of rare diseases so that medication can be accessed by anyone who need it.

Chin Med J (Engl). 2018 Oct 5; 131(19): 2388–2389

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Rare genetic diseases with defects in DNA repair: opportunities and challenges in orphan drug development for targeted cancer therapy

The journal Cancers recently published a review of the recent advances in the understanding of how many rare disease genes participate in promoting genome stability. The two authors from Cold Spring Harbor Laboratory summarise the latest developments in exploiting rare diseases to uncover new biological mechanisms and identify new synthetic lethal interactions for anticancer drug discovery that are in various stages of clinical studies.

Cancers (Basel). 2018 Sep 1;10(9)

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Retrospective analysis of dose-finding studies among orphan drugs approved in the EU

The high unmet medical need for many rare diseases contributes to a pressure for fast registration of new orphan drugs, that are already difficult to test in a clinical setting due to the limited number of patients, disease heterogeneity, insufficient knowledge of the pathology and lack of appropriate pharmacodynamic measures. For these reasons, the quality of dose-finding studies may be lacking. Authors of a paper published in the Journal of Clinical Pharmacology investigated to what extent were dose-finding studies performed and what were the major difficulties in defining the right dose in orphan drugs, as well as how were these difficulties addressed for the orphan drugs that have reached the EU market. The authors thus found that dose-finding studies were only performed in two thirds of the dossiers of authorised orphan drugs (for metabolic diseases and solid tumours). Furthermore, dose-finding studies performed post-marketing often indicated that registered doses were not optimal, but these were nevertheless not changed post-marketing. They suggest that guidance for such studies in the pre-marketing period, as well as obligations in the post-marketing period, may generate more robust data that would benefit patients and health care providers.

J Clin Pharmacol. 2018 Sep 7

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Orphan drug designations in ophthalmology

A retrospective, observational review of orphan drug designations in ophthalmology was performed for 72 new ophthalmic drugs that were designated since the passage of the Orphan Drug Act in 1983. Of these orphan medicines, four received NDA (New Drug Application) approval. The study published in Journal of Eye Diseases and Disorders therefore concluded to a low rate of commercialisation of new ocular pharmaceutical agents with orphan designation being approved for the original indication.

J Eye Dis Disord 2018;4:1

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Summary of the edition of 31 October 2018

Editorial
Political news
Scientific news
And also...