A systematic literature review of evidence-based clinical practice for rare diseases: what are the perceived and real barriers for improving the evidence and how can they be overcome?

Abstract

BackgroundEvidence-based clinical practice is challenging in all fields, but poses special barriers in the field of rare diseases. The present paper summarises the main barriers faced by clinical research in rare diseases, and highlights opportunities for improvement.MethodsSystematic literature searches without meta-analyses and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.ResultsBarriers specific to rare diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes.ConclusionsEvidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic fields in which multi-stakeholder engagement, especially from patients, is needed for success. Clinical research infrastructures and expertise networks offer opportunities for establishing evidence-based clinical practice within rare diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2287-7) contains supplementary material, which is available to authorized users.

Pachyonychia congenita, a paradigm for rare skin disorders

“…However, in more recent times, there has been a growing recognition of their impact. Many countries have now adopted strategies specifically aimed at improving care standards, such as the U.K. Strategy for Rare Disease, and legislation passed to incentivize drug development has led to the approval of hundreds of new treatments . Rare disorders have also been included in the remit of important genomic studies, such as the U.K.'s 100 000 Genomes Project and the U.S. National Institutes of Health All of Us project.…”

“…The authors detail the clinical features of PC by age and genotype, as well as its significant impact on quality of life and mental health. The results offer a valuable insight into the variability and needs of the patient population, as well as excitement about soon overcoming the traditional barriers to investigating rare disorders, such as small cohorts and poor understanding of their natural history …”

“…Through identifying large patient cohorts, rare disorder registries may permit comparative studies that more rigorously assess these treatments, utilizing novel trial designs to overcome the challenges unique to rare conditions such as the global dispersion of cases . Registries also encourage interest from academic researchers and pharmaceutical companies .…”

“…Many countries have now adopted strategies specifically aimed at improving care standards, 3 such as the U.K. Strategy for Rare Disease, 2 and legislation passed to incentivize drug development has led to the approval of hundreds of new treatments. 4 Rare disorders have also been included in the remit of important genomic studies, such as the U.K.'s 100 000 Genomes Project and the U.S. National Institutes of Health All of Us project. Progress is being made particularly in genetic characterization but there is a long way to go, with the overwhelming majority of these rare disorders remaining without effective treatment.…”

“…The results offer a valuable insight into the variability and needs of the patient population, as well as excitement about soon overcoming the traditional barriers to investigating rare disorders, such as small cohorts and poor understanding of their natural history. 4 Evaluative research assessing outcomes that matter the most to patients is important. In the IPCRR, plantar pain had the biggest impact upon quality of life.…”