Original article
Ethical management in the constitution of a European database for leukodystrophies rare diseases

https://doi.org/10.1016/j.ejpn.2014.04.002Get rights and content

Abstract

Background

The EU LeukoTreat program aims to connect, enlarge and improve existing national databases for leukodystrophies (LDs) and other genetic diseases affecting the white matter of the brain. Ethical issues have been placed high on the agenda by pairing the participating LD expert research teams with experts in medical ethics and LD patient families and associations. The overarching goal is to apply core ethics principles to specific project needs and ensure patient rights and protection in research addressing the context of these rare diseases.

Aim

This paper looks at how ethical issues were identified and handled at project management level when setting up an ethics committee.

Methods

Through a work performed as a co-construction between health professionals, ethics experts, and patient representatives, we expose the major ethical issues identified.

Results

The committee acts as the forum for tackling specific issues tied to data sharing and patient participation: the thin line between care and research, the need for a charter establishing the commitments binding health professionals and the information items to be delivered. Ongoing feedback on the database, including delivering global results in a broad-audience format, emerged as a key recommendation. Information should be available to all patients in the partner countries developing the database and should be scaled to different patient profiles.

Conclusion

This work led to a number of recommendations for ensuring transparency and optimizing the partnership between scientists and patients.

Introduction

Patient registries and databases are key tools for the development of biomedical and clinical research – particularly in the field of rare diseases which faces specific challenges tied to small patient populations and variations among disease sub-types. Gathering information on a large scale has considerable potential for helping to improve diagnosis and treatment, promote the development of clinical trials, and facilitate recruitment.1, 2

One aim of the EU LeukoTreat program (www.leukotreat.eu) is to develop a supranational database geared specifically to leukodystrophy (LD) – the LeukoDataBase (LeukoDB). Collecting clinical data on LD patients will improve understanding of the natural history, epidemiology and genotype–phenotype correlations of these disorders. The challenge is to connect, enlarge and improve pan-European databases on LDs and other genetic diseases affecting the white matter of the brain. Addressing this challenge entails organizing the collection and management of clinical and biological data, including genetic information. The objective is to foster the emergence of innovative therapeutic strategies as part of translational research designed to accelerate the clinical application of fundamental research results.

LDs are a group of rare genetically inherited neurodegenerative diseases of the white matter and its main component, myelin. LDs predominantly affect young children but can also hit adults, causing cognitive deficits and potential loss of autonomy. The overall prevalence of LDs is approximately 1 in 10,000 of the population, with around 1000 new cases every year in Europe. Despite great strides forward made over the past decade in terms of advance in each individual LD, there is currently still no curative therapy (see, Ref. 3, 4 for review).

LeukoTreat has placed ethics issues high up the agenda by pairing the participating LD expert research teams with experts in medical ethics and LD patient families and associations. The overarching goal is to apply core ethics principles to specific project needs and ensure patient rights and protection in research addressing the context of these rare diseases. The ethical approach was integrated right from the project's outset to handle the sharing of medical information at a European level in the context of LD patients, which are a heterogeneous population characterized by variable clinical expression and age of appearance. This approach also considers the harmonization of information and consent on existing practices in national databases.

This paper looks at how ethical issues were identified and handled at project management level during the project lifetime.

Section snippets

Synergy between an ethics committee and an ethics research group

Before starting LeukoTreat, the proposal first received approval from the EC ethics review board, which is an integral component of the research evaluation procedure under FP7.5 The EU report singled out the plan to form a project-long ethics committee as a positive. Indeed, a stand-out feature of LeukoTreat was that it attached a LeukoTreat Ethics Committee (LEC) to the ethics research group involved in the project.

The LEC is composed of two categories of members: project members (clinicians

Data sharing in LeukoDB

The primary concern of the LEC was to establish ethical rules governing the sharing of data. The database gathers socio-demographic and medical data extracted from patient records, including biological, radiological, electrophysiological data, genetic studies and cognitive evaluations. The data are collected and processed in LeukoDB by the referent Clinical Centers in charge of the patients. In the context of biomedical research, the aim of building a European database is to gather data for the

A lack of frontier between care and research: what impact?

The ethical framework governing biomedical research revolves around the dichotomy between care and research. However, in rare diseases like LDs, research and care are very often intertwined, as diagnostics or therapies are often only available at the research stage. Furthermore, the sense of urgency in diseases with no effective therapies is particularly conducive to therapeutic misconception.12 With the focus on implementing the European database on LDs in LeukoTreat (LeukoDB), the lack of a

Experiences in other consortia

Registries and databases gathering trans-national patient data are recognized as high priority tools in the field of rare diseases. However, their regulation is considered to be in its early stages in most European countries where legal requirements are not always the same.23 Most publications reporting on database management tend to focus on technical aspects, the way data are collected, data quality and use. The way ethical aspects tied to patients' rights and information are handled is

Conclusion

This paper reports on experience shared by healthcare professionals, ethics experts and patient representatives on ethical issues management in the setting of a European database on leukodystrophies. The LeukoTreat Ethics Committee established at the outset of the 3-year project acted as a forum for optimizing ethical procedures geared to the rights and expectations of participants.

In this context of a database on rare diseases, patients and families are most often committed by conviction,

Competing interests

None.

Funding

This work was funded by the EU Program FP7 under the LeukoTreat grant agreement no. 241622.

Acknowledgments

LeukoTreat Ethics Committee (LEC) members: Lazare Benaroyo (University of Lausanne, Switzerland); Marie-Claude Blondeau (Leuko Reference Center, AP-HP, Bicêtre Hospital, France); Odile Boesflug-Tanguy (Paris Diderot University, Robert Debré Hospital, France); Ingrid Callies (Paris Descartes University, France); Jean-Christophe Coffin (Paris Descartes University, France); Diane d'Audiffret (Paris Descartes University, France); Nathalie Duchange (Paris Descartes University, France); Gaël de

References (31)

  • Council of Europe

    Convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine: convention on human rights and biomedicine

    (1997)
  • Council of Europe

    Additional protocol to the convention on human rights and biomedicine, concerning biomedical research

    (2005)
  • OECD

    OECD guidelines on the protection of privacy and transborder flows of personal data

    (1980)
  • UNESCO

    International declaration on human genetic data

    (16 October 2003)
  • P. McCormack et al.

    Guidance in social and ethical issues related to clinical, diagnostic care and novel therapies for hereditary neuromuscular rare diseases: “translating” the translational

    PLoS Curr

    (2013)
    • 1

    Present address: Equipe Management des organsiations de santé (MOS), PRES Sorbonne Paris Cité/EHESP, France.

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