How many zebras are there, and where are they hiding in medical literature? A literature review of publications on rare diseases

ABSTRACT Background: Reliable and accurate medical literature is essential for patients with rare diseases (affecting ~400 million people globally), their advocates, and caregivers (PACs), and health-care professionals (HCPs). Methods: We quantified the number of English-language publications on rare diseases in PubMed from 2009 to 2018. To test our search strategy, we evaluated inclusion of articles on 20 randomly selected rare diseases. We further examined 100 randomly selected articles from 2009 to 2013 and from 2014 to 2018 for journal type, article access, and PAC involvement. Results: Of the 10,882,681 articles published, 14,202 (0.13%) mentioned the MeSH term ‘rare disease’ in the title or abstract. Nineteen of 20 randomly selected diseases were included in our search results; an independent search for the ‘missing’ disease yielded no articles. Despite a numerical increase over time, there was little change in the proportion of rare disease articles. Most articles were in specialty journals, and ~2/3 were behind paywalls. The majority of rare disease manuscripts were case reports; almost no articles included PACs as authors. Conclusions: The number of high-quality medical publications on rare diseases is not commensurate with their overall prevalence and there are access barriers, highlighting an unmet need in medical literature that would benefit all stakeholders.