1. Javier Júdez Chair of the IIER- Ethics Committee ETHICS, Rare Diseases’ REGISTRIES & BIOBANKS Madrid, 4th-5th march 2013

2. Role of the Ethics Committee - IIER  Advisory Body for the IIER  Interdisciplinary membership  Specially focused in research in RD from a broad perspective: research projects; research policy; research education & promotion; research issues specially related with RD  Long-term commitment (more than 10 years)  Relationship with other regulatory EC (required by law with Clinical Trials or Research project approval) 2

3. Role of Ethics Committee within SpainRDR  Advisory Body for the consortium  For design, deliberation (“preventive ethics role”)  For implementation (“facilitating ethics role”)  For assessment & accountability (“sense-making ethics role”)  Consultation  Low pace – regular meetings Within Consortium milestones and products  Fast pace – urgent issues Extraordinary meetings Expert’s consultation 3

4. Ethical Guidelines (background work) RECOMMENDATIONS ON THE ETHICAL ASPECTS OF COLLECTIONS OF SAMPLES AND HUMAN TISSUE BANKS FOR BIOMEDICAL RESEARCH PURPOSES (february, 2007) ETHICAL GUIDELINES GOVERNING THE CREATION AND USE OF REGISTRIES FOR BIOMEDICAL RESEARCH PURPOSES (november, 2009)

5. Ethical Guidelines (background work) RECOMMENDATIONS ON THE ETHICAL ASPECTS OF COLLECTIONS OF SAMPLES AND HUMAN TISSUE BANKS FOR BIOMEDICAL RESEARCH PURPOSES (february, 2007) ETHICAL GUIDELINES GOVERNING THE CREATION AND USE OF REGISTRIES FOR BIOMEDICAL RESEARCH PURPOSES (november, 2009) 24 recommendations

6. RD policies and networks blossoming: new challenges and need for deliberation and assessment Biospecimens/Biorepositories: Rare Disease Hub (RD-HUB) Global RD Patient Registry and Data Repository (GRDR) Genetic and Rare Diseases Information Center (GARD)

7. Ethical Guidelines – on-going review under the practicalities of SpainRDR RECOMMENDATIONS ON THE ETHICAL ASPECTS OF COLLECTIONS OF SAMPLES AND HUMAN TISSUE BANKS FOR BIOMEDICAL RESEARCH PURPOSES (february, 2007) ETHICAL GUIDELINES GOVERNING THE CREATION AND USE OF REGISTRIES FOR BIOMEDICAL RESEARCH PURPOSES (november, 2009) ON-GOING REVIEW - Population registries vs. Patient registries (networks of registries) -Intertwining of registries, biorepositories & clinical data Informed consent Confidentiality & data protection Benefits, harms in individuals & communities

8. Some of the issues to be discussed include:  Navigating the data-sharing component of the registries  Risk-benefit assessment  Maintenance of identifiers  Information to be released to investigators  Lessons from existing data-sharing models  Approaches to informed consent  Clinical vs. research samples and data  Content, scope, and limits  Appropriateness of waivers  Assent and surrogate permission for pediatric and incapacitated adult subjects  Role of patient and public attitudes in shaping informed consent Some ethical issues to be discussed

9. Some of the issues to be discussed include (cont.):  Return of research results to subjects  Likelihood of clinically useful (valid, actionable) results  Whether, how, by whom to disclose  Resources for recontact and counseling  Patient expectations  Establishing ongoing registry oversight and governance  Maximizing the value of collaborative partnerships between patient advocacy groups, government, and private industry  Benefits-sharing models  Minimizing potential conflicts of interest  Proprietary considerations Some ethical issues to be discussed

10. (i)call attention to the fact that current ethical conversation and regulatory approaches presume a straightforward analogy between biobanking and other forms of nontherapeutic research, without acknowledging that analogical reasoning is at play, (ii)elaborate the conceptual inadequacies of the presumed analogy between research and biobanking, particularly drawbacks of the informed consent model, (iii)invite a broadening of analytic scope to include other possible analogies, specifically considering an analogy between biobanking and clinical surrogacy, (iv)propose several ways that the surrogacy analogy better fits aspects of biobanking than the informed consent model, (v)suggest that multiple ethical analogies should illuminate the development of regulatory oversight. Volume 14 | Number 2 | February 2012 | 183-188 Some future directions? An example

11. -Analogy of biobank with non-therapeutic research Similarities: * the goal of collective benefits, * the intrinsic conflict of interest that goal generates regarding the necessary instrumental use of human subjects, * and the need for ethical protections of human subjects to ensure they are treated as “ends in themselves” and not merely means to an end. Volume 14 | Number 2 | February 2012 | 183-188 Some future directions? An example Review in progress (45 Cfr 46) reaffirm the equation of biobanking with research while modifying review processes by perceived risk.

12. Volume 14 | Number 2 | February 2012 | 183-188 Some future directions? An example Individualized tiered consent may be a concept that is elegant in theory but difficult to translate to effective practice. -Analogy of biobank with non-therapeutic research Differences / disanalogies: The potential risks and benefits of the biobank’s undetermined future research cannot be speculated. Four other major differences between informed consent for research and informed consent for biobanking: (i) The difference between participating in an activity versus participating in an institution; (ii) The difference between one-time versus ongoing decision-making; (iii) The difference between unidirectional versus multidirectional information flows; and (iv) the difference between active versus detached research participation.

13. Volume 14 | Number 2 | February 2012 | 183-188 Some future directions? An example -Where to go from here? Forego potential beneficial research without consent? Waive obligation of consent (balancing interest individual donors vs. perceived social good by EC and communities)? -Role of new analogies to think it through: SURROGACY What potential biobank donors genuinely can be asked for is not consent for research but rather permission for the biobank to make future research decisions on their behalf. Such permission is based more on trust of those who will use the resource than on necessarily limited information about how the resource will be used. Clinical medicine offers one model based on trust: the designation of surrogate decision makers for incapacitated patients, informed by advance directives expressing patients’ basic values. From legal - transactional To communications model

14. Volume 14 | Number 2 | February 2012 | 183-188 Some future directions? An example (i) The informed consent model presupposes known research goals with predictable potential benefits and risks. Alternatively, the surrogacy model facilitates decision-making about unknown future scenarios. (ii) Unlike the unidirectional information flow in informed consent in research, the surrogacy model stresses two-way dialogue between patient and the surrogate designee, clarifying patient values relevant to future unknowns. (iii) The informed consent model envisions a one-time consent process. The surrogacy model incorporates the evolution of patient values over time in response to changing circumstances over time. Conclusion: a more “honest” process. A matter of TRUST more than (only) of CHOICE

15. 15 Thank you! ¡Muchas gracias! javier.judez@ffis.es Acknowledgements: To Dr. Manuel Posada, IIER Director, Spain RDR IP To the IIIER Ethics Committee members