Edition of 15 February 2023

A new commentary published in Healthcare Papers explores the different perspectives of patient advocates engaged in rare disease drug policy. Patient advocacy organisations play a number of different roles, among which is pushing for policy change or reform. These groups can have significant political influence, sometimes being the deciding factor in the decision of whether or not to adopt a specific policy or approve a certain drug. As such, understanding common models of patient advocacy and how actors respond to them can be useful in developing policy that maintains access to life-saving medicines, while also being economically viable.

To further explore the different factors affecting the perspectives and approaches of patient advocates, the article compares two such groups from Canada and their contrasting advocacy efforts concerning a drug intended to treat cystinosis. One group, which was smaller and did not receive any funding from the pharmaceutical industry, was highly critical of the drug’s price and was ultimately successful in having the price lowered. The other, which does receive industry funding, was supportive of the drug’s approval and did not raise any concerns about the pricing.

While this comparison does not demonstrate any concrete connections between industry funding and the position of patient advocacy organisations, it does point to the importance of maintaining transparency with regards to the funding of such groups. Ensuring that patient advocates are free from external political influence would help ensure that lobbying efforts, even when taking different approaches, are being done in the best interests of the rare disease community.

A systematic review recently published in the European Journal of Human Genetics examines the perspectives of different professional stakeholder groups on reproductive genetic carrier screening (RGCS). Despite being a powerful tool for the diagnosis and management of rare genetic disorders, carrier screening has only been incorporated into public health systems for specific at-risk subgroups. Understanding stakeholder attitudes can help inform responsible implementation of expanded carrier screening programs, to support couples in their reproductive decision-making while balancing demands on healthcare systems.

The authors identified two broad themes which emerged in stakeholder views. The first theme, clinical challenges, focuses on the management of offering genetic testing. It includes considerations such as making RGCS available to all couples who request it, before pregnancy, and making clear and reliable information available through genetic counselling. The second theme was program management challenges. It tackles issues associated with prospective policy planning, such as mitigating social pressure, ensuring equitable access, and education of non-genetic clinicians.

Overall, this review provides a set of principles which can be used to guide the ethical integration of more expanded RGCS into public health systems while taking potential resource and infrastructure constraints into account. In particular, the authors highlight the need to draft policies which emphasise voluntary participation, fair access, and information sharing about the complexities and limitations of RGCS.

A new study published in the Orphanet Journal of Rare Diseases investigates the relationship between social support and psychological disorders for patients and family caregivers of rare bone diseases (RBDs). While such support is known to improve well-being for families with rare diseases, its specific effect on disorders such as depression and anxiety has not yet been established.

RBDs are known to often cause high levels of psychological distress. For patients, this can be due to social difficulties and stress caused by their disease. For families and caregivers, it is exacerbated by heavy financial and emotional burdens associated with treatment. More comprehensive social support has been suggested as a mechanism for alleviating distress and improving patient and family social well-being and mental health.

In order to better define the specific relationship between social support and depression and anxiety, researchers analysed survey data collected from both RBD patients and their caregivers. Both groups demonstrated a high prevalence of the disorders, and responses showed that access to social support was relatively poor. However, when such support was available, it was found that anxiety and depressive symptoms of caregivers improved significantly. These findings highlight the need for improved, dedicated social support for RBD patients and families, along with social awareness and strengthened implementation of RBD policy.

A new study published in Nature Genetics presents a new framework for overcoming the sample size challenges associated with the discovery of rare genetic variants associated with complex phenotypes. The framework in question, MetaSTAAR, uses meta-analysis of large-scale whole genome sequencing/whole exome sequencing (WGS/WES) data to analyse traits in a resource-efficient manner.

Meta-analysis of data from multiple studies, where only summary statistics are shared, is a cost-effective, instrumental tool for augmenting sample sizes in the study of rare variants. However, existing methods have a variety of limitations which prevent them from being of use when it comes to extremely large-scale (i.e. biobank-level) data.

To overcome these challenges, MetaSTAAR stores study-specific variant summary statistics in a compact manner and dynamically incorporates functional annotations. This allows for the analysis of large-scale WGS studies and biobank data while requiring less storage space and reduced processing times compared to other methods. MetaSTAAR also maintained accurate rates of type I error in simulation studies.

The MetaSTAAR framework provides researchers with the capacity to perform meta-analysis of extremely large-scale WGS data, including studies using biobank data, in order to detect rare variants associated with both quantitative and dichotomous phenotypic traits. This has broad implications for improving the statistical power of such research, and enabling better diagnostic yields of genetic health services.