Research Article: Clinical Practice Guidelines for Rare Diseases: The Orphanet Database

Date Published: January 18, 2017

Publisher: Public Library of Science

Author(s): Sonia Pavan, Kathrin Rommel, María Elena Mateo Marquina, Sophie Höhn, Valérie Lanneau, Ana Rath, Alanna M Chamberlain.


Clinical practice guidelines (CPGs) for rare diseases (RDs) are scarce, may be difficult to identify through Internet searches and may vary in quality depending on the source and methodology used. In order to contribute to the improvement of the diagnosis, treatment and care of patients, Orphanet ( has set up a procedure for the selection, quality evaluation and dissemination of CPGs, with the aim to provide easy access to relevant, accurate and specific recommendations for the management of RDs. This article provides an analysis of selected CPGs by medical domain coverage, prevalence of diseases, languages and type of producer, and addresses the variability in CPG quality and availability. CPGs are identified via bibliographic databases, websites of research networks, expert centres or medical societies. They are assessed according to quality criteria derived from the Appraisal of Guidelines, REsearch and Evaluation (AGREE II) Instrument. Only open access CPGs and documents for which permission from the copyright holders has been obtained are disseminated on the Orphanet website. From January 2012 to July 2015, 277 CPGs were disseminated, representing coverage of 1,122 groups of diseases, diseases or subtypes in the Orphanet database. No language restriction is applied, and so far 10 languages are represented, with a predominance of CPGs in English, French and German (92% of all CPGs). A large proportion of diseases with identified CPGs belong to rare oncologic, neurologic, hematologic diseases or developmental anomalies. The Orphanet project on CPG collection, evaluation and dissemination is a continuous process, with regular addition of new guidelines, and updates. CPGs meeting the quality criteria are integrated to the Orphanet database of rare diseases, together with other types of textual information and the appropriate services for patients, researchers and healthcare professionals in 40 countries.

Partial Text

Clinical practice guidelines (CPGs) are “systematically developed statements to assist practitioners and patient decisions about appropriate health care for specific circumstances” [1]. Many CPGs have been developed in the last 25 years, as depicted in a recent review [2]. However most of them are aimed at common diseases and recommendations dedicated to rare diseases (RDs) remain scarce. In the European Union, a disease is considered as rare when it affects not more than 5 per 10,000 persons [3]. The rarity of randomised controlled trials puts a brake on the development of high quality guidelines for RDs, as well as the high development costs for funders who consider more prevalent diseases to be priority investment targets. In spite of these hurdles, over the last few years the development and dissemination of CPGs for RDs has garnered increasing attention [4–6]. The contribution of CPGs to shortening the time to diagnosis and improvement of the quality of care is now widely acknowledged, and several European countries have included CPG development as a priority in their respective national plans on RDs [7].

The difficulty to retrieve RD guidelines from the abundance of recommendations available for non-rare diseases is well known [13, 20]. As an additional challenge, the Orphanet database comprises more than 7,800 diseases/groups of diseases (excluding disorder subtypes) that represent potential targets for guideline retrieval, and to which only a global literature survey for guidelines and RDs can be applied, yielding very few appropriate results. Some medical societies and health organisations with websites gathering guidelines for a large variety of diseases, including RDs, were useful sources. In all cases, the retrieval of a potentially interesting document through this global survey was followed by specific disease guideline search to determine whether it was the most relevant CPG. Due to the diversity of publication media, it is clear that case-by-case approaches should be applied rather than a single retrieval strategy. Moreover, different search engines may be complementary to each other (e.g. Pubmed and Google Scholar) and may help in retrieving different documents. This is likely due to differences in the search algorithms rather than in differences in content coverage [29, 30].

Access to information on RDs is one of the priorities adopted in most national plans in Europe [46]. Initiated in 2011, the Orphanet guideline dissemination project responds to this objective. In addition, it corresponds to a real need from both professionals and patients, as observed from our annual surveys [47] and from direct users’ feedback who have expressed their interest in accessing more clinical guidelines in more languages. CPG collection, evaluation and dissemination is a continuous process, with regular addition of new guidelines. Documents included in the Orphanet database may also be replaced by updates released by a guideline development group (providing they fulfil the quality criteria), old documents may be removed when they are obviously not up-to-date or according to the expiry date set by the development group, and finally, older guidelines may be replaced by more recent ones when appropriate, e.g. when a new document is of higher quality or when it is of similar quality but contains additional/more recent information useful for clinical practice. Compared to general guideline databases such as G-I-N [9], besides free access and quality assessment, CPGs disseminated via Orphanet are part of an information network gathered around the disease entity: each CPG can be accessed from the specific disease page where other types of information can be found, among which the ORPHA code, epidemiological and genetic data, disease summary, classification, health care resources, data on research activities and available drugs, links to other websites, guides for patients and families, etc. Therefore, the guideline database is included into a more global project that establishes a link between diseases, the existing textual information concerning RD and the appropriate services for patients, researchers and healthcare professionals. This integrative dimension is a unique feature of the Orphanet database that can serve various stakeholders and purposes. It can be used to identify medical areas for which CPGs are totally lacking but for which clinical research is active and/or drug development is ongoing.




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