Two significant steps towards improved codification for rare diseases
Currently, only a small fraction of rare diseases have codes in international nomenclatures, making it a challenge to trace patients with rare diseases in health information systems on a national and international level. Having codes for each rare disease would help European and national health authorities obtain a better knowledge of healthcare pathways and of their impact on specialised health care services (centres of expertise for instance) as well as on a country’s budget planning for health and social service.
Although much headway has been made to ensure that the rarest diseases will appear in the next version of the International Classification of Diseases (ICD11) currently available in a beta version, the release date of this classification is not scheduled until 2017, and implementation may be much later. In order to ensure that rare diseases can be traced in health information systems as soon as possible, Orpha codes, which are linked with ICD11, are proposed as a complementary coding system when a code does not exist for a rare disease. Two steps were recently made to improve the codification of rare diseases in the form of the adoption of the Commission Expert Group on Rare Diseases’ first recommendation on ways to improve codification for rare diseases (Read the coding recommendation), and an expert workshop aimed at sharing experiences and approaches to the use of Orpha codes as a complementary coding system.
A first recommendation for the Commission Expert Group on Rare Disease focuses on improving codification
The European Commission Expert Group on Rare Diseases adopted its first recommendation on codification for rare diseases at their third meeting last month. Addressed to the MS and the European Commission, it outlines the state of play in the field, and provides the rationale for the use of Orpha codes as a complementary coding system when no specific code exists for a rare disease.
Six recommendations are proposed to improve the codification of rare diseases in health information systems. These include the need to consider a complementary approach whilst rare diseases are incorporated into ICD and SNOMED-CT; the importance of exchanging experiences on the use of Orphacodes at national level through a working group to be established in a future EU Joint Action on rare diseases ; and the further promotion of Orphacodes within the ICD11 revision process taking place at the World Health Organization. Member States are encouraged to consider and explore the feasibility of the use of Orphacodes at national level and to include the codification of rare diseases as an area of their national plans/strategies for rare diseases. The recommendation concludes with a strong encouragement for EU Member States and the European Commission to seek possibilities to support the implementation of identified solutions.
Exchanging experiences and approaches to coding rare diseases
On 1-2 October 2014, the European Commission's Joint Research Centre (JRC) hosted a workshop to explore the best ways in which to improve the codification of rare diseases in health information systems through the complementary use of Orphacodes. Orphacodes are the codes attributed to all rare diseases within the Orphanet classification. Experts from the fields of coding and registries joined Member State representatives to discuss the possible models for implementation of the additional Orphacodes at national level alongside the terminologies currently in use, as well as the possible areas of European collaboration to facilitate the use of data for rare diseases research in the future.
Participants agreed that coding systems, tools and practices around Europe are highly heterogenous and that a sole solution adapted to all countries' needs is unrealistic. However, a majority of European countries are interested in making rare disease patients visible in their health information systems using an Orphacode as a complementary code when one does not exist in the terminology they currently use. It was decided to promote further exchange between the countries interested in using Orphacodes and those that do so already so as to help countries define the best strategy, notably through the development of an alignment of Orphacodes and the versions of the International Classification of Diseases (ICD) used in each country. Although all efforts to implement Orphacodes will be carried out at national level due to national specificities, a common approach for data exploitation will be needed at European level in the future.
Consult the report from the workshop on Orphacodes in Health Information Systems.
These two steps bring the rare disease community a little further forward towards the goal of making rare diseases visible in health information systems. Once an effective system is in place, a wealth of information will be made available to help improve our knowledge of healthcare pathways, which will hopefully lead to improved planning of health and social services.
Read the flash report on the proceedings of the meeting of Commission Expert Group on Rare Diseases held on 12-13 November 2014
On behalf of the Federal Ministry of Health (BMG), the German Institute for Quality and Efficiency in Health Care (IQWiG) analysed the studies on which approval of orphan drugs are based in Europe. Based on their analyses, IQWiG concluded that randomised control trial (RCT) should be the norm and not the exception for studies on rare disease. The report states that clinical trials with low number of participants is not a preferable scenario as the effect on small populations can only be determined if they are studied in sufficiently large samples, and IQWiG believes that this should be possible using disease networks and registries of patients. According to the report, decreasing precision by increasing the significance level is preferred to decreasing sample size and therefore advocate raising the level of significance above 5-10%. IQWiG believes that raising the significance level will allow the estimation of the level of uncertainty. IQWiG also observed that 82 out of the 125 studies for rare disease approvals, submitted to EMA between 2001 and 2013, were RCTs and therefore conclude that it is not necessary to change course and accept drug approvals based on small sample sizes. Although IQWiG qualifies their analysis with the statement “all patients have a right to quality”, it must be noted that demanding RCTs for all orphan drugs may limit access to drugs for rare disease patients, which can be inequitable as well. 
With the advent of prohibitively expensive orphan drugs, the Dutch government introduced a policy whereby they could be financed, with the criteria that the expected cost-effectiveness be incorporated in its reimbursement application. Reimbursement based on expected cost-effectiveness was considered temporary and the drug would be re-evaluated based on data collected for the drug, over a period of four years. Whether this re-evaluation was optimal is analysed in an article published in Health Policy. 
In Denmark, many actions concerning the provision of healthcare for rare diseases were carried out following the recommendations of a report concerning rare diseases issued in 2001. A working group of stakeholders was established in 2012 with the task to elaborate a comprehensive national strategy for rare diseases in Denmark based on the experiences of the implementation of the recommendations the 2001 report and the national designations of centres of expertise in 2010. A Danish Strategy for Rare Diseases was submitted in 2014.The National Strategy of Rare Diseases in Denmark-2014 has made several recommendations aimed towards better care and increased research and development in the area of rare diseases. 
An article published in the Annals of Oncology discusses the endpoints for clinical trials that need to be accepted by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan to approve oncology drugs. The authors inform that even though acceptance of surrogate endpoints is crucial for accelerated approval of drugs, the number of surrogate endpoints has decreased after the revision of guidelines in Japan. Although Japan has many expedited programs in regulatory systems including orphan drug designation, priority review, public knowledge-based application, and a special committee on unapproved drugs, they are lagging behind the US and EU in drug approvals. The authors believe that an accelerated approval program, and a system for discussing surrogate endpoints so far, is called for in order to bring oncology drugs to the needy patients faster. 
In Canada, the Children’s Hospital of Eastern Ontario are challenging patents held by companies on genes in the Federal Court of Canada. The hospital is specifically challenging the patent held on a genetic test for long QT syndrome – a rare inherited genetic disorder, which has fatal consequences. Testing for the gene in people with a family history of the disorder can help doctors prevent incidents in high-risk patients before they happen. Test for long QT syndrome costs CAD 4500 and, when incidentally discovered in a patient, cannot be revealed to that patient and the doctors can be prevented from learning anything further, due to the patents held by a US company –Transgenomic North America. This violation of patient rights and incorrect usage of patenting has been taken to the Federal Court on medical and ethical grounds, citing barriers that gene patents present in providing tests for genetic diseases. 
A review published in Pediatrics and Neonatology introduces the screening and referral network of genetic evaluation for children with developmental delay in Taiwan. According to the article, all cities and counties in Taiwan have an established network for screening, detection, referral, evaluation, and intervention services. The authors believe that Taiwan provides children with developmental delay services from the medical, educational, and social welfare sectors and has an opportunity for increased awareness to improve early detection and intervention. However, they also allude to the lack of resources, due to which there is limited access to advanced genetic testing such as microarray or whole exome testing for these conditions. Despite this, the authors believe that Taiwan works in a gainful manner, which may be an example for countries with limited resources. 
Lebanese children with special needs are usually supported by non-governmental organisations (NGOs) for their education and health. Children with psychomotor or mental impairment, as well as children with rare diseases usually come from a low socio-economic background and hence have difficulty finding qualified professionals to support their oral health.
