Mapping the Rare Disease Diagnostic Odyssey of Today: An Adapted Targeted Literature Review (ATLR)

Author(s)

Stefano Tagliabue, MSc1, Perrine Le Calvé, MSc1, Mauricio Castillo Morales, MD, MSc2, Roseline Favresse, MA3, Tim Irfan, MBA4, Nivantha Subiron-Naidoo, MPH, MSc, MD1.
1Oracle Life Sciences, Paris, France, 2Abbott Products Operations AG, Allschwil, Switzerland, 3EURORDIS - Rare Diseases Europe, Nice, France, 4Oracle Life Sciences, Munich, Germany.
OBJECTIVES: Patients with rare diseases often face a prolonged and complex “diagnostic odyssey” before receiving an accurate diagnosis impacting health-related outcomes and quality of life. This ATLR represents the first phase of a broader research initiative aimed at identifying and mapping key barriers to timely and accurate rare disease diagnoses. Evidence was synthesized from peer-reviewed literature and credible online sources. In the second phase, identified barriers will be validated by experts and used to inform the development of an accelerated diagnostic pathway.
METHODS: Searches were conducted in Medline, CINAHL, and PsycINFO for English-language, full-text, peer-reviewed articles published from 2020 onward. A targeted search strategy combined indexing terms and free-text keywords related to rare diseases, diagnosis, and reported barriers. Relevant websites of professional societies and organizations were also reviewed for supplemental data.
RESULTS: Of 136 eligible publications, 40 were selected for full data extraction. Additional insights were gathered from targeted web sources. Thematic analysis and synthesis identified six key milestones in the diagnostic odyssey: Prevention/Screening, Symptom Onset, Health-Seeking Behaviors, Testing, Diagnosis, and Treatment. Across sources, 27 recurring barriers and 9 enablers were identified. The five most frequently reported barriers were: prolonged referral and wait times (52%, n=21), low GP awareness (45%, n=18), misdiagnosis (45%, n=18), fragmented knowledge (45%, n=18), and emotional burden (42%, n=17). Milestones with highest proportion of barriers were: Health-Seeking Behaviors, Screening, and Treatment. The most frequently reported enablers included advancements in DNA sequencing, centers of expertise, and integrated clinics (each 30%, n=12), followed by patient networks and awareness (27%, n=11).
CONCLUSIONS: The rare disease diagnostic odyssey remains impeded by a myriad of barriers. Mapping these barriers along the journey milestones highlights the imperative for the planned second phase to harness the collective intelligence of experts towards consensus for actionable and sustainable solutions to accelerate the diagnostic journey.

Conference/Value in Health Info

2025-11, ISPOR Europe 2025, Glasgow, Scotland

Value in Health, Volume 28, Issue S2

Code

PCR152

Topic

Patient-Centered Research

Disease

Rare & Orphan Diseases

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