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Objective: Better understanding the impact of social determinants of health (SDOH) barriers from the patient perspective is crucial to improve holistic patient support in generalized myasthenia gravis (gMG), a rare autoimmune disorder with high disease and treatment burden. The objective of this study was to identify economic challenges experienced by individuals living with gMG and SDOH barriers to better address current unmet needs. Methods: Adults (18-75 years) living with gMG and experiencing SDOH barriers in the United States were recruited to a mixed-methods study including qualitative interviews and a web-based quantitative survey. Quotas were implemented to include a balanced spread of baseline demographic categories including insurance type, living environment, and employment status among the study sample. Direct and indirect economic challenges were identified by degree of concern. Results: The survey was completed by 38 individuals living with gMG, the majority of whom were enrolled in public insurance and not employed. The most commonly reported major economic concerns were managing funds for emergency care (66%), loss of income (61%), and non-medical expenses (58%), highlighting the diversity of economic challenges. Individuals who were using public insurance plans, living in non-urban environments, and unemployed experienced pronounced challenges around managing non-medical costs and accessing government assistance. Conclusion: Both direct and indirect costs were emphasized as major concerns among individuals living with gMG and SDOH barriers. Increasing access to relevant, personalized, and holistic resources, including care management, should be prioritized to improve disease management and outcomes for individuals living with gMG.
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BACKGROUND: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011. However, study start-up was significantly delayed and recruitment did not start until January 2013. METHOD: The FOR-DMD study is used as an example to identify systematic problems in the set-up of international, multi-centre clinical trials. The full timeline of the FOR-DMD study, from funding approval to site activation, was collated and reviewed. Systematic issues were identified and grouped into (1) study set-up, e.g. drug procurement; (2) country set-up, e.g. competent authority applications; and (3) site set-up, e.g. contracts, to identify the main causes of delay and suggest areas where anticipatory action could overcome these obstacles in future studies. RESULTS: Time from the first contact to site activation across countries ranged from 6 to 24 months. Reasons of delay were universal (sponsor agreement, drug procurement, budgetary constraints), country specific (complexity and diversity of regulatory processes, indemnity requirements) and site specific (contracting and approvals). The main identified obstacles included (1) issues related to drug supply, (2) NIH requirements regarding contracting with non-US sites, (3) differing regulatory requirements in the five participating countries, (4) lack of national harmonisation with contracting and the requirement to negotiate terms and contract individually with each site and (5) diversity of languages needed for study materials. Additionally, as with many academic-led studies, the FOR-DMD study did not have access to the infrastructure and expertise that a contracted research organisation could provide, organisations often employed in pharmaceutical-sponsored studies. This delay impacted recruitment, challenged the clinical relevance of the study outcomes and potentially delayed the delivery of the best treatment to patients. CONCLUSION: Based on the FOR-DMD experience, and as an interim solution, we have devised a checklist of steps to not only anticipate and minimise delays in academic international trial initiation but also identify obstacles that will require a concerted effort on the part of many stakeholders to mitigate.