Edition of 23 May 2024

International News

European News

European Parliament votes to adopt EU Disability Card

During the European Parliament’s plenary session on 24^th April, MEPs voted to approve the provisional agreement on the European Disability Card, which aims to enhance mobility for people with disabilities across the EU. This is a positive development for Europeans living with a rare disease, many of whom are affected by a related disability.

The proposed legislation represents a mutual recognition between Member States of a person’s disability status. As such, it hopes to ensure equitable access to a range of services for persons affected by a disability while living or travelling in the EU. Once implemented, holders of a Disability Card will be able to use it as proof of their disability, thus granting them access to preferential conditions in services such as public transport and leisure activities. As outlined in the adopted text, individuals participating in mobility programmes such as Erasmus+ and third-country nationals.

Responding to the parliamentary vote, EURORDIS praised the move towards more normalized accessibility standards. However, they reiterated their previous concerns that a reliance on national-level eligibility criteria could cause inequitable implementation between Member States, leaving individuals with less common, less severe, or less visible disabilities by the wayside. To address this gap, EURORDIS is urging Member States to adopt broad and inclusive eligibility criteria.

The next step towards implementation of the Disability Card will come following the European elections in June, when it will need to be formally adopted by the Council of Europe and published in the Official Journal of the European Union. After this step is taken, the legislation will enter into force and the next step will be taken towards making Europe a more accessible region for persons with disabilities.

Rare Disease Moonshot recommendations on translational research needs

The Rare Disease Moonshot project has published a new set of recommendations on how public-private partnerships (PPPs) can be leveraged to accelerate translational research for rare diseases. These recommendations provide a collaborative framework for PPPs to optimally leverage the strengths of various stakeholders to close the gap between scientific discovery and clinical application. These gaps are particularly important in rare diseases, where limited clinical experience and scientific knowledge give rise to a high level of unmet research needs for many disorders.

The new report first discusses the major challenges to conducting effective translational research for rare diseases. These include a lack of incentives, the need to understand the complex pathobiology of specific RDs, the cost of development, and a complex regulatory landscape. In order to overcome these challenges, the report then presents practical recommendations for targeted PPPs. These are:

Develop a shared vision along the value chain with a patient-focused translational research approach;
Ensure structural access to expertise from the entire value chain;
Invest in innovative methods as well as standardisation and awareness;
Accelerate translation through PPPs by creating cross-sectoral accelerators and strengthening existing innovation hubs;
Enhance and utilize Technology Transfer Offices (TTOs).

Implementation of these recommendations is expected to lead to significant improvements in patient outcomes, as well as a more effective navigation of the transitional research landscape. To further support PPPs engaging in translational rare disease research, the report suggests some specific actions, along with the respective implicated stakeholders, to further the implementation of the recommendations (see below).

Suggested actions for the implementation of the recommendations (via Rare Disease Moonshot)

Rare Disease Moonshot is a European PPP launched in December 2022 to boost research and development into rare and paediatric diseases. It was established in response to the European Commission’s call to address unmet medical needs, and brings together the Critical Path Institute, EATRIS, ECRIN, EFPIA, EUCOPE, EUROPABio and EURORDIS to discover new therapies for conditions which lack an approved treatment.

Health Economics

Economic evaluation of orphan drugs: Challenges and opportunities

A review was recently published in PharmacoEconomics exploring the issues, challenges, and opportunities when generating evidence for health technology assessments (HTAs) in rare diseases (RD). In the article, the authors identify the main challenges facing economic evaluation of orphan drugs for RD, and provide recommendations for researchers conducting health economic studies in RD.

HTA is a process undertaken following regulatory approval of medicines which determines the level of reimbursement to be provided by the relevant government or private sector payer(s). It uses a cost-benefit analysis approach to determine the value of the treatment based on its effectiveness. Applying this strategy to RD drugs can be challenging due to small patient populations and a resulting lack of robust clinical evidence.

In this study, researchers conducted an umbrella review of systematic reviews of economic studies concerned with orphan and ultra-orphan drugs published from 2010-2023. They found a scarcity of evidence on health economic parameters such as clinical effectiveness, costs, quality of life, and natural history of disease.

Evaluations such as cost-effectiveness and budget-impact analyses were also rare, and typically of low-to-moderate quality. Causes for this gap were identified to be the aforementioned limited health economic parameters, combined with publication bias (particularly in the case of cost-effectiveness analyses).

In order to overcome the challenges uncovered by their review, the authors made several recommendations to make economic evaluations of orphan drugs in RD more sustainable:

Adopt comprehensive, transparent and flexible cost-effectiveness models
Conduct further research on the effect of publication bias on the ability to meet cost-effectiveness thresholds
Take advantage of underutilized opportunities to combat data scarcity, such as disease registries, collaboration with patient organisations, early economic evaluation of phase II data, and risk-sharing agreements

By considering these recommendations, researchers can design more, higher-quality economic evaluation studies. This will allow for increased evidence generation, thereby leading to a higher likelihood of favourable pricing and reimbursement decisions.

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Resource allocation for high-cost treatments: Current approaches and future directions

A new article has been published in the International Journal of Health Policy and Management exploring different institutional approaches to allocating resources for high-cost therapeutics in rare and paediatric diseases. The authors also discuss the need for standardised, evidence-based decision-making processes to help guide healthcare institutions when choosing which treatments to fund and list on formularies.

Through a systematic literature review, researchers assessed current strategies employed by healthcare institutions when making decisions on off-formulary, high-cost drugs and therapeutics. They identified five themes which were relevant to these processes: institutional strategy, substantive criteria, procedural considerations, guiding principles and frameworks, and operational activities. There was also a sixth theme specific to rare and paediatric diseases, which addressed the various considerations specific to the contexts of such conditions.

This analysis revealed the common factors which impact decision-making processes across different healthcare systems. The authors also identified specific challenges when making funding decisions, many of which relate to ethical considerations. Based on these findings, the article proposes several recommendations to help guide decision-makers. These are:

The importance of incorporating novel forms and sets of data, including RWE and public/patient input, when trial-based data is lacking;
Establishing a documented decision-making process which improves transparency;
Using frameworks or checklists to guide the development of funding decisions/policies that relate to funding;
The importance of ongoing tracking and evaluation of data regarding past decisions to inform future decision-making, as well as the potential for disinvestment.

By implementing these recommendations, the hope is that decision-making processes will become more robust, and best practices can be established to help ensure access to important therapies while allocating resources in a deliberate, cost-effective manner.

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Orphan Drugs

Availability and accessibility of oncologic orphan drugs in Bulgaria

A new study has been published in the journal Cancers investigating the availability and accessibility of orphan drugs for rare cancers in Bulgaria. Researchers compared data from both European and national sources to assess the availability, delays, and budgetary impact of such treatments. Their analysis found that there were significant disparities in accessibility, and highlights the need for more targeted policies to improve equity among this particularly vulnerable patient population.

Generally speaking, people living with a rare cancer experience challenges similar to those of other rare diseases, such as significant health inequities due to diagnostic complexity and delayed access to innovative therapies. These barriers are exacerbated in countries such as Bulgaria, where resource constraints and scarcity of expertise create additional requirements for policy and translational research.

In order to understand the current status of rare cancer treatments in Bulgaria, researchers used data from EU and national sources during the period of 2020-2023 to identify the number of available and accessible orphan drugs for rare cancers, as well as the delay from market authorisation to reimbursement, the dynamics of public expenditures, and regional disparities in access across the country. They also compared this status with that of non-oncological orphan drugs.

The study found that in total, only 15 out of 50 oncological orphan drugs which had been authorised by the EMA were accessible for Bulgarian patients. The median delay between market authorisation and reimbursement via inclusion in the Bulgarian Positive Drug List was 760 days, or about 2 years, which is significantly longer than the reported delay in many Western European countries. These and other findings from the study highlight the specific challenges rare cancer patients face in Bulgaria with regards to accessing treatment, and underscores the need for targeted European and national policies to help address this inequality.

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Quality of Care

Utility of next generation sequencing for diagnosing and managing genetic disease in developing countries

A new article has been published in the European Journal of Human Genetics, discussing the role of next generation sequencing (NGS) as a diagnostic and management tool for critically ill children with a suspected genetic disorder, particularly in developing countries.

As NGS-based techniques continue to be developed and refined, they show promise for diagnosing and evaluating genetic disorders in critically ill infants and children. However, data on its utility in developing countries remains limited. In this study, the authors analysed the use of NGS on children with a suspected genetic disorder requiring critical care at a hospital in Northern India. They assessed the diagnostic rate of these strategies, as well as the clinical impact on patient management.

The study led to a precise molecular diagnosis in 32 patients out of the total cohort of 70. Of these, a significant change in clinical outcome was observed in 13 cases. These changes resulted from various modifications to treatment plans, including a change in medication, specific dietary management, redirection to palliative care, avoidance of a major procedure, and better reproductive counselling.

One of the main limiting factors to using NGS in this and similar contexts observed by the study was the delay in turn-around time for sequencing results. Due to resource constraints, rapid and ultra-rapid sequencing was not available in the study hospital. This is representative of conditions in the majority of healthcare settings in developing countries.

Overall, despite this challenge, the study still found that NGS has great utility for managing critically ill patients with suspected genetic disorders in developing countries. This is largely due to the clinically significant impact of being able to achieve a precise molecular diagnosis.

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Screening and Prenatal Diagnosis

Ethical, Legal and Social

Identifying physical and psychosocial "red flags" for rare disease based on patient experiences

A new study published in the Orphanet Journal of Rare Diseases analyses patient group narratives to uncover biopsychosocial warning signs of undiagnosed rare disease (RD).

The diagnostic odyssey is a well-documented phenomenon among people living with an RD. Following the initial onset of symptoms, there is typically a significant delay before a correct diagnosis is made. During this waiting period, patients frequently endure extensive testing and procedures due to the challenges associated with RD diagnosis. There is therefore a need for evidence-based guidance for non-specialist clinicians to help identify when a patient may be presenting with a rare disease, in order to begin the process as soon as possible and minimise diagnostic delay.

In order to identify a set of “red flags” for potential undiagnosed rare disease, Medics for Rare Diseases developed a questionnaire which was shared with UK-based patient groups. Study participants were asked about typical experiences relating to physical and psychosocial manifestations and presentation of disease, patient interactions with healthcare providers, and family history.

Based on the survey responses, the authors identified seven specific red flags of rare disease. They were:

Multi-system involvement (3 or more);
Genetic inheritance pattern;
Continued presentation throughout childhood and adulthood;
Difficulties at school (especially relating to absences, difficulty participating in physical education and experiences of bullying or social isolation);
Multiple specialist referrals;
Extended period with unexplained symptoms;
Misdiagnosis

The identification of these key commonalities experienced by patients with RD across both physical and psychosocial domains, can help non-specialist clinicians identify when a patient presents with signs of a potential undiagnosed RD. In particular, these findings could be used to develop a clinical decision support tool to help improve patient experience and minimise the diagnostic odyssey.

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Overcoming stigma associated with genetic testing for rare diseases

An article has been published in Frontiers in Genetics exploring the stigma associated with genetic testing for rare diseases (RD), including the underlying causes and recommendations for overcoming this stigma.

Of the thousands of rare diseases which have been identified to date, more than 70% are genetic in origin. For families affected by such conditions, the possibility of inheriting or transmitting a genetic disease has a substantial social and psychological impact, including feelings of guilt, blame, and stress about passing the disease on to future generations. This stigma affects all stages of the disease journey for people living with a rare disease (PLWRD) and their families, and adversely impacts their quality of life. In order to better understand its interaction with genetic testing specifically, researchers conducted a literature review of articles on stigma associated with genetic testing for RD from January 2013 to February 2023.

The study found that stigma and genetic discrimination against PLWRD were presented in various forms, including regulatory issues, insurance or employment, and social issues such as exclusion from social activities. Furthermore, this stigma extended beyond just PLWRD, also affecting individuals with positive carrier status. The review identified this stigma as a significant barrier to accessing genetic testing for RD, and also found that it discouraged the implementation of important large-scale detection strategies such as cascade screening and population carrier screening.

In order to improve access to genetic testing and the overall quality of life of PLWRD and their families, the authors emphasise the need for a greater emphasis on recognising and addressing stigma in RD education. They also call for convenient and culturally-appropriate carrier screening initiatives which proactively address potential stigma. Finally, pre- and post-genetic counselling is identified as an important tool for addressing stigma.

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International News

European News

Health Economics

Orphan Drugs

Quality of Care

Screening and Prenatal Diagnosis

Registries and Biobanks

Epidemiology

Summary of the edition of 23 May 2024

Editorial

Political news

Scientific news

And also...

International News

Scotland publishes first Genomic Medicine Strategy

NORD announces 2024 Rare Impact honourees

European News

European Parliament votes to adopt EU Disability Card

Rare Disease Moonshot recommendations on translational research needs

Understanding JARDIN, the new Joint Action to support integration of ERNs

EU4Health targeted consultation

EJP RD Final Conference: Registration deadline extended

Share4Rare: 4th Call4Projects opens

Health Economics

Economic evaluation of orphan drugs: Challenges and opportunities

Resource allocation for high-cost treatments: Current approaches and future directions

Orphan Drugs

Availability and accessibility of oncologic orphan drugs in Bulgaria

Quality of Care

Utility of next generation sequencing for diagnosing and managing genetic disease in developing countries

Screening and Prenatal Diagnosis

Understanding patient preferences in genetic newborn screening: Protocol of a Screen4Care study

Ethical, Legal and Social

Identifying physical and psychosocial "red flags" for rare disease based on patient experiences

Overcoming stigma associated with genetic testing for rare diseases

Registries and Biobanks

Protocol of the Swiss-Ped-IBrainD registry

Epidemiology

Inherited retinal diseases in Portugal: Socioeconomic epidemiology

Summary of the edition of 23 May 2024

Editorial

Political news

Scientific news

And also...