Ethical, legal, and social issues (ELSI) in rare diseases: a landscape analysis from funders


Recent interest in personalized medicine has highlighted the importance of research in ethical, legal, and social issues (ELSI). Issues in ELSI research may be magnified in the rare diseases population (i.e., small numbers of affected individuals, challenges in maintaining confidentiality, and paucity of treatments for diseases where natural history information may be limited). More than other areas of research, potential barriers include the lack of funding opportunities and appropriate review processes for applications to funding agencies. The ELSI Working Group of the International Rare Diseases Research Consortium (IRDiRC) performed an informal survey on ELSI funding initiatives to learn more about different funding mechanisms and to identify potential gaps in funding opportunities. The Working Group discusses these challenges and highlights the role of funding agencies and partners such as patient advocacy groups, specialists in social sciences and humanities, and clinicians to advance ELSI research in rare diseases.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    National Research Council. Mapping and sequencing the human genome. Washington, DC: The National Academies Press; 1988. Accessed 13 Jan 2019.

    Google Scholar 

  2. 2.

    McEwen JE, Boyer JT, Sun KY, Rothenberg KH, Lockhart NC, Guyer MS. The Ethical, Legal, and Social Implications Program of the National Human Genome Research Institute: reflections on an ongoing experiment. Annu Rev Genomics Hum Genet. 2014;15:481–505.

    CAS  Article  Google Scholar 

  3. 3.

    Meslin EM, Thomson EJ, Boyer JT. The Ethical, Legal, and Social Implications Research Program at the National Human Genome Research Institute. Kennedy Inst Ethics J. 1997;7:291–8.

    Article  Google Scholar 

  4. 4.

    US Government Publishing Office. Genetic Information Nondiscrimination Act of 2008. 2008. Accessed 27 Jan 2019.

  5. 5.

    US Government Publishing Office. Revised Common Rule. 2017. Accessed 27 Jan 2019.

  6. 6.

    Gainotti S, Mascalzoni D, Bros-Facer V, Petrini C, Floridia G, Roos M, et al. Meeting patients’ right to the correct diagnosis: ongoing international initiatives on undiagnosed rare diseases and ethical and social issues. Int J Environ Res Public Health. 2018;15:10.

    Article  Google Scholar 

  7. 7.

    McCormack P, Kole A, Gainotti S, Mascalzoni D, Molster C, Lochmüller H, et al. ‘You should at least ask’. The expectations, hopes and fears of rare disease patients on large-scale data and biomaterial sharing for genomics research. Eur J Hum Genet. 2016;24:1403–8.

    CAS  Article  Google Scholar 

  8. 8.

    Bereza E. The use of clinical databases in disease outcomes research: Is the ethics of IRB review keeping up? Mult Scler. 2017;23:1325–7.

    Article  Google Scholar 

  9. 9.

    Polisena J, Burgess M, Mitton C, Lynd LD. Engaging the Canadian public on reimbursement decision-making for drugs for rare diseases: a national online survey. BMC Health Serv Res. 2017;17:372.

    Article  Google Scholar 

  10. 10.

    Hallowell N, Parker M, Nellåker C. Big data phenotyping in rare diseases: some ethical issues. Genet Med. 2019;21:272–4.

    Article  Google Scholar 

  11. 11.

    Parker LS, Sankar PL, Boyer J, Jean McEwen JD, Kaufman D. Normative and conceptual ELSI research: what it is, and why it’s important. Genet Med J Am Coll Med Genet. 2019;21:505–9.

    Google Scholar 

  12. 12.

    Knoppers BM. Framework for responsible sharing of genomic and health-related data. HUGO J. 2014;8:3.

    Article  Google Scholar 

  13. 13.

    Mascalzoni D, Dove ES, Rubinstein Y, Dawkins HJ, Kole A, McCormack P, et al. International charter of principles for sharing bio-specimens and data. Eur J Hum Genet. 2015;23:721–8.

    Article  Google Scholar 

  14. 14.

    Gainotti S, Turner C, Woods S, Kole A, McCormack P, Lochmuller H, et al. Improving the informed consent process in international collaborative rare disease research: effective consent for effective research. Eur J Hum Genet. 2016;24:1248–54.

    CAS  Article  Google Scholar 

  15. 15.

    Schieppati A, Henter J-I, Daina E, Aperia A. Why rare diseases are an important medical and social issue. Lancet. 2008;371:2039–41.

    Article  Google Scholar 

  16. 16.

    Cannizzo S, Lorenzoni V, Palla I, Pirri S, Trieste L, Triulzi L, et al. Rare diseases under different levels of economic analysis: current activities, challenges and perspectives. RMD Open. 2018;4:e000794.

    Article  Google Scholar 

  17. 17.

    Lander ES, Baylis F, Zhang F, Charpentier E, Berg P, Bourgain C, et al. Adopt a moratorium on heritable genome editing. Nature. 2019;567:165.

    CAS  Article  Google Scholar 

  18. 18.

    Baker D, Knoppers BM, Phillips M, van Enckevort D, Kaufmann P, Lochmuller H, et al. Privacy-preserving linkage of genomic and clinical data sets. IEEE/ACM Trans Comput Biol Bioinform. 2019;16:1342–8.

    Article  Google Scholar 

  19. 19.

    Kodra Y, Weinbach J, Posada-de-la-Paz M, Coi A, Lemonnier SL, van Enckevort D, et al. Recommendations for improving the quality of rare disease registries. Int J Environ Res Public Health. 2018;15.

    Article  Google Scholar 

  20. 20.

    Monaco L, Crimi M, Wang CM. The challenge for a European network of biobanks for rare diseases taken up by RD-Connect. Pathobiol J Immunopathol Mol Cell Biol. 2014;81:231–6.

    CAS  Article  Google Scholar 

  21. 21.

    FDA. FDA: Orphan Drug Act. 1983. Accessed 27 Jan 2019.

  22. 22.

    European Commission. EC: Regulation No 141/2000 of the European Parliament and of the Council on Orphan Medical Products. 2000. Accessed 27 Jan2019.

  23. 23.

    PMDA. PMDA: The Article 77–2 of the Pharmaceutical Affairs Law. 1985. Accessed 27 Jan 2019.

  24. 24.

    Gericke CA, Riesberg A, Busse R. Ethical issues in funding orphan drug research and development. J Med Ethics. 2005;31:164–8.

    CAS  Article  Google Scholar 

  25. 25.

    Rodriguez-Monguio R, Spargo T, Seoane-Vazquez E. Ethical imperatives of timely access to orphan drugs: is possible to reconcile economic incentives and patients’ health needs? Orphanet J Rare Dis. 2017;12:1.

    CAS  Article  Google Scholar 

  26. 26.

    Heeney C, Hawkins N, de Vries J, Boddington P, Kaye J. Assessing the privacy risks of data sharing in genomics. Public Health Genomics. 2011;14:17–25.

    CAS  Article  Google Scholar 

  27. 27.

    Hardavella G, Bjerg A, Saad N, Jacinto T, Powell P. How to optimise patient and public involvement in your research. Breathe. 2015;11:223–7.

    Article  Google Scholar 

  28. 28.

    PARADIGM. PARADIGM, patients active in research and dialogues for an improved generation of medicines. 2019. Accessed 27 Jan 2019.

  29. 29.

    IRDiRC. International Rare Diseases Research Consortium. IRDiRC. 2019. Accessed 13 Jan 2019.

  30. 30.

    Dawkins HJS, Draghia-Akli R, Lasko P, Lau LPL, Jonker AH, Cutillo CM, et al. Progress in rare diseases research 2010-6: an IRDiRC perspective. Clin Transl Sci. 2018;11:11–20.

    Article  Google Scholar 

  31. 31.

    FFRD. Appel à projets de recherche 2018 «Sciences humaines et sociales & maladies rares». https://www.fondation-Mal.Contentuploads2018022018SHSMR.pdf. Accessed 13 Jan 2019.

  32. 32.

    NIH. PA-17-325: Ethical, Legal, and Social Implications (ELSI) of Genomics Research Project Grant Program (R01). 2017. Accessed 28 Jan 2019.

  33. 33.

    Japan Agency for Medical Research and Development. Awarded Projects under the Research and Development Program for Enhancement of Research Integrity. 2016. Accessed 28 Jan 2019.

  34. 34.

    BMBF-Internetredaktion. Bekanntmachung - BMBF. Bundesminist. Für Bild. Forsch. - BMBF. 2018. Accessed 28 Jan 2019.

  35. 35.

    Horizon 2020—European Commission. Science with and for Society. Horiz. 2020 - Eur. Comm. 2013. Accessed 28 Jan 2019.

  36. 36.

    NIH. The Health of Sexual and Gender Minority (SGM) Populations (R21 Clinical Trial Optional). 2013. Accessed 28 Jan 2019.

  37. 37.

    Berg JS, Agrawal PB, Bailey DB, Beggs AH, Brenner SE, Brower AM, et al. Newborn sequencing in genomic medicine and public health. Pediatrics. 2017;139.

    Article  Google Scholar 

  38. 38.

    E-Rare. ERA-net for research programmes on rare diseases. 2018. Accessed 16 Feb 2019.

  39. 39.

    NIH Administrative Supplement for Research on Bioethical Issues (Admin Supp Clinical Trial Optional) - PA-19-217. 2019.

Download references


Members and contributors of the IRDiRC ELSI Working group included ALH, HD, RI, DJ, NL and MP. In addition, we would like to thank Domenica Taruscio (ISS, Italy) and Manuel Posada (ISCIII, Spain) for their review and feedback on the manuscript.


The IRDiRC Scientific Secretariat was supported by the European FP7 contract “SUPPORT-IRDiRC”(N° 305207). Daria Julkowska received funding from the European Union’s Horizon 2020 Research and Innovation Program under grant agreement EJP RD N°825575.

Author information



Corresponding author

Correspondence to Adam L. Hartman.

Ethics declarations

Conflict of interest

The authors declare no competing interests. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, or the US Government.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hartman, A.L., Hechtelt Jonker, A., Parisi, M.A. et al. Ethical, legal, and social issues (ELSI) in rare diseases: a landscape analysis from funders. Eur J Hum Genet 28, 174–181 (2020).

Download citation

Further reading


Quick links