Abstract
Diseases that affect a very small percentage of the population are often neglected in planetary health innovation ecosystems. Large gaps, both in theory and action, continue to exist in early diagnosis and treatment as well as clinical trials of new therapeutic candidates for rare diseases.
A recent systematic review illustrates the inconsistencies and variations in rare disease definitions, for example, by country, geographic region, and regulatory agencies (Abozaid et al., 2025). The disparities in definitions also impact the “orphan drug” clinical trials aimed at rare disease therapeutics global development. In the European Union, both qualitative and quantitative criteria are deployed in rare disease definition as “life-threatening or chronically debilitating illnesses with extremely low prevalence (less than 5 per 10,000)” (Abozaid et al., 2025).
Definitions matter because they determine who is included and excluded in rare disease clinical trials, and since clinical trials offer hope and potential access to emerging drug candidates. Also, there are gaps in knowledge on clinical signs and time course of rare diseases and response to treatments. For patients living in rural communities, access to rare disease diagnostics, treatments, and clinical trials can be further limited.
Can Digital Technologies Be Utilized for Clinical Trials of Rare Diseases?
Over the past decade, digital transformation with artificial intelligence (AI) and related technologies has been changing planetary health practices and clinical trials (Ghadessi et al., 2023; Sato et al., 2022). In this context, the Internet of Things (IoT) is a convergence of digital technologies with sensors, big data, advances in the Internet and digital connectivity, and high-throughput data analysis (Gabbal, 2015). Internet of Medical Things (IoMT) reflects the evolution of IoT to the clinic. Rare diseases clinical trials stand to benefit from IoMT. For example, through IoMT, rural communities may be able to access clinical trials for rare diseases, while the clinical course of rare diseases and their responses to treatments can be characterized in greater detail, thus contributing to the phenomics of rare diseases. In effect, IoMT would have the twin benefit of advancing rare disease diagnostics and therapeutics development.
Recent public and private investments in the Eastern Mediterranean in AI and the rise of academic centers focusing on digital health research and development speak to the potentials for digital transformation in rare disease clinical trials in the region. Additionally, the high prevalence of rare diseases in the Eastern Mediterranean is another context where digital technologies can help inform the design and implementation of rare disease clinical trials regionally and globally.
Finally, AI and digital transformation also present challenges because the same technologies that increase efficiency and throughput can potentially be misused for surveillance of society. Therefore, careful attention has to be paid to responsible use of digital innovations in clinical trials and health care. A recent study on Large Language Models (LLMs) is particularly noteworthy because LLMs are utilized in various contexts, including in science and medicine. Loru et al. point to limitations of LLMs, especially about their role in evaluative processes: “our results suggest that they may rely on lexical associations and statistical priors rather than contextual reasoning or normative criteria. We term this divergence epistemia: the illusion of knowledge emerging when surface plausibility replaces verification.” (Loru et al., 2025).
In summary, this letter calls for innovations not only in rare disease omics but also in the way rare disease clinical trials are designed and implemented. In the current digital age, thinking about the prospects and challenges of digital transformation and attendant innovation for rare disease clinical trials is timely, both in the Eastern Mediterranean region and around the world.
Footnotes
Author Disclosure Statement
A.K. is President & Founder for Ascot Science CRO Sariyer, Istanbul, Türkiye. The views are the personal opinions of the author only and do not necessarily represent those of the affiliated institutions. No funding was received in support of this letter.
Funding Information
No funding was received for this letter article.
Author’s Contributions
A.K.: Article conception, writing, and proofreading of the final version for publication.
Disclaimer
The views are the personal opinions of the author only and do not necessarily represent those of the affiliated institutions.