Diagnosing rare diseases is a major challenge. Rare diseases (RD) whose definition is based on a prevalence notion are not only numerous (more than 7000 are described, mostly with a genetic origin) but also extremely diverse in their expression, their cause, their semiology and nosology and, for most, their natural history are not firmly established. Many rare diseases share symptoms with “common” diseases. Despite increasing knowledge and new imaging or biological and molecular technologies, diagnosis remains difficult, even for the best experts.
As a consequence, the long lag time between first symptoms and diagnosis is identified as a key problem to be fixed, especially pointed out by patient organizations (1). A timely diagnosis is a critical step to ensure a proper access to expert clinical management for patients suffering from rare diseases. Currently, this delay is thought to be unacceptably long, and amenable to improvement if appropriate measures are undertaken. The reasons for such a delay are diverse and cumulative.
A delayed diagnosis can occur because the patient did not consult early enough, or because the symptoms are non-specific or uncommon for the disease to be considered. A delay can also occur because scientific knowledge is still limited, or because all investigations have been performed without any conclusive result. These delayed diagnoses are not avoidable at a given time point.
In contrast, the determinants of the healthcare systems contributing to delays could be totally or partially addressed. Those may include health professionals’ lack of awareness and of experience with RD, difficulties in referring patients to expert centers, lack of specialized centers or too distant ones, understaffed expert centers, or limited access to genomic services.
Many initiatives have been taken in the past to address these issues. In Europe, Orphanet was specifically established in 1997 to disseminate the information on RD and expert resources. In 2004, the French government adopted the first Public Health Plan for rare diseases, including the establishment of a network of expert centers in academic hospitals and many other initiatives likely to contribute to a better diagnosis of RD (2). A recommendation of the Council of European Ministries was adopted in 2010, urging all European countries to set up a national plan or strategy for RD before 2014, a recommendation followed by most countries (3; 4). With the progressive availability and affordability of Next-Generation Sequencing (NGS) technologies, the debate around solution for the diagnosis of rare diseases focused on the access to sequencing technologies and on accelerating the identification of disease-causing genes by involving all undiagnosed patients in research protocols (5; 6).
Improving the diagnosis of RD is an enormous challenge for public and private actors, as it is a multifaceted phenomenon, encompassing all aspects of medicine. But, today, the development of digital technologies offers genuine opportunities for progress: for patients and their caregivers, with new tools and options for dealing with their condition; for healthcare professionals with tools supporting their daily administrative, medical and research duties; for healthcare systems, with tools to optimize care. The sector of rare diseases is at urgent needs and the community is organized and dedicated enough to quickly adopt innovations which could improve patients’ quality of life.
In this context, developing eHealth solutions that are specifically suited to RD was identified by Sanofi France, in partnership with Orange Healthcare, as an obvious priority for its open innovation initiative, named UniR. A group of stakeholders, including patients, patient associations, healthcare professionals, researchers, administrators, healthcare and digital specialists, was invited, in 2018, to identify tangible eHealth solutions to reduce diagnostic delay. This open innovation initiative brought together 16 experts in rare diseases along with six representatives from national centers of expertise and four patient associations for rare diseases. After 30 individual interviews and three workshops, the group identified 13 obstacles that are sources of diagnostic delay, and suggested 14 digital-based solutions to reduce such delays. The outcome of this brain storming exercise is published as a white book (7).
During the process of deciding about the potential solutions to be developed in the short term, emerged the idea of defining a subset of rare diseases to focus on, for practical reasons. As testing these solutions would only be possible for a limited number of RD, the most ethical approach would be prioritizing RD for which a delayed diagnosis would be especially detrimental, because an established and effective standard management is already defined (including clinical guidelines and / or specific drug). It is this approach that is now described. This choice does not imply that an absence of diagnosis, or a very late diagnosis, is not detrimental in the context of other diseases. Of course, it is the case for all of them. The current approach just aims at proposing a rational way of choosing rare disease on which pilot projects will be tested, addressing so the most urgent needs.