FP7 Health: Ethics Review & What to Do : Point by Point Dr. Joana Namorado Ethics, Gender Issues Directorate Health- DG RTD – European Commission September 2008 Malta 2008

The purpose of ethical review to ensure that FP7 ethical rules are complied with and that the European Union is not supporting research which would be contrary to the fundamental ethical principles of FP7 to raise researchers’ awareness about ethical issues in research and ensure that these are properly addressed

Proposals for ER/year: Increase in number of proposals…

Relative percentage of Health Proposals ER The Highest is: Health

In 2006, 48% proposals undergoing ethics reviews were from Health ( 134 Health out of 280 )

Number of proposals for ethical review FP Thematic priority 1: Life sciences, genomics and biotechnology for health, Calls Lifehealth 2005 – 6 and 7 Total proposals received: = 815 Total proposals Ethical review: 134 (+ ressub)  134/815 proposals (16% of all received proposals) for ethical review  134/279 proposals (i.e.48,0% of all ranked proposals) genomics and biotechnology for health”: = 64 Combating major diseases: = 69 …First call FP7, deadline 19 April 2007

Legal Basis for Ethical Reviews in FP7 ■ Seventh Framework Programme (Decision N° 1982/2006/EC), Article 6 (1§): All the research activities carried out under the Seventh Framework Programme shall be carried out in compliance with fundamental ethical principles. » ■ Rules for Participation, Article 10: A proposal […] which contravenes fundamental ethical principles […] shall not be selected. Such a proposal may be excluded from the evaluation and selection procedures at any time. » Areas excluded from funding under FP 7, Art. 6 (2§):

Legal Basis for Ethical Reviews in FP7 – Areas excluded from funding under FP 7, Art. 6 (2§): Research activity aiming at human cloning for reproductive purposes B) Research activity intended to modify the genetic heritage of human beings which could make such changes heritable (Research related to cancer treatment of the gonads can be financed) C) Research activities intended to create human embryos solely for the purpose of research or for the purpose of stem cell procurement, including by means of somatic cell nuclear transfer

Ethical Reviews in Practice: The Project Evaluation Process Scientific Evaluation  All proposals submitted to the Commission for funding following a call for proposals are evaluated on their scientific merit.  Scientific evaluators identify the proposals raising ethical issues and needing ethical reviews. ■ Ethical Review (if required) All proposals for funding involving a research intervention on humans, the use of hESC and/or fœtal issues, and non-human primates will be automatically submitted to an ethical review panel.

Proposal Individual evaluation Consensus Panel review Consultation of programme committee (if required) Commission funding and/or rejection decision with hearing (optional) Thresholds Eligibility Negotiation Commission ranking Commission rejection decision Ethical Review (if needed) Ethical Scrutiny (if needed) Applicants informed of results of expert evaluation* invitation to submit second-stage proposal, when applicable Submission and evaluation in FP7 Applicants informed of Commission decision

The Proposal includes a section dedicated to ETHICS. The applicant fills out a table of ethics issues in the proposal Scientific evaluators are asked to signal any ethical issues that arise in a proposal including those which have not been highlighted by the applicant. Ethics: Panorama for FP7 The Proposal

The Ethical Review is organised and carried out by Ethics Review Unit either Remotely or Centrally Automatic ethical review - Proposals involving interventions on human beings, non-human primates, hEmbryos/embryonic stem cells. Where necessary ethical safeguards should be in place i.e. in cases of international co-operation,in third countries. Based on the screening report may consider that no further ethics scrutiny is necessary and the project can be followed by PO who may follow-up indications in the screening report. Ethical review

Applicants are first expected to identify key ethical issues raised by their proposals and explain how they address them. They are: Informed Consent Research on Human Embryos/Foetuses Data Protection and Privacy Research on Animals Research involving Developing Countries Dual Use (research that could have a military application) Ethics: Panorama for FP7 Ethical Review Process Evolving

Under FP7 Art 6 Some areas are excluded from funding: Run it by your ethics expert Human reproductive cloning Germ line gene therapy (except cancer treatment of the gonads) Creation of human embryos solely for the purpose of research (or for the purpose of stem cell procurement, including by means of somatic cell nuclear transfer).

Areas of Special Sensitivity Examples of Important ethical issues : Research involving intervention on human beings, human biological samples, human embryonic stem cells, Personal data or genetic information Animal research esp. non-human primates or non-typical laboratory animals (e.g. dogs, pigs) Developing countries.

1.Applicants identify key ethical issues explain how they address them then list them. 2.Scientific Evaluation 3.Ethics Review at EC level -2 STEPS 1: Ethics Screening-: 2: Ethics Review 4.Ethics (Screening or Review) Report 5.Requirements incorporated in Grant Agreement 6.Possibility of Ethics Audit Ethics: Process for FP7 Novel Ethical Review Process

1.Applicants identify key ethical issues explain how they address them then list them. 2.Scientific Evaluation 3.Ethics Review at EC level -2 STEPS 1: Ethics Screening-: 2: Ethics Review 4.Ethics (Screening or Review) Report 5.Requirements incorporated in Grant Agreement 6.Possibility of Ethics Audit Ethics: Process for FP7 Novel Ethical Review Process

The Proposal includes a section dedicated to ETHICS. Part 4 of Guide for Proposers The applicant fills out a table of ethics issues in the proposal+addresses issues Scientific evaluators signal any ethical issues in a proposal, even those missed by the applicant. Applicants identify key ethical issues explain how they address them then list them

Applicants are expected to identify key ethical issues raised by their proposals and explain how they address them. They are: Intervention on Human beings Informed Consent Research on Human Embryos/Foetuses Data Protection and Privacy Research on Animals Double Standards- research in Developing and Third Countries Dual Use (research that could have a military application) Applicants identify key ethical issues Novel Ethical Review Process

1.Applicants identify key ethical issues explain how they address them then list them. 2.Scientific Evaluation 3.Ethics Review at EC level -2 STEPS 1: Ethics Screening 2:Ethics Review 4.Ethics Result - Screening or Review Report 5.Requirements incorporated in Grant Agreement 6.Possibility of Ethics Audit Ethics: Process for FP7 Novel Ethical Review Process

PHASE 1) Ethics screening Screening by Experts, PO and Sc&S Screening carried out according to the specific requirements of WP The outcome: (i.e. which proposals need full Ethical Review) Screening seeks to divide proposals into three groups: -No ethical review required. This decision is taken by the relevant PO assisted by the screeners experts -Those that require only the approval from the relevant national or local ethics committees (requested before the start of the RTD activities) -Those that require ethical review Directorate L will be provided with the screening report and will decide that the ethics review is completed. Proposals go to ethical screening. This process, is part of the Ethics Process Identifies proposals for ethical review.

PHASE 1) Ethics screening Those adequately treated every issue have a screening report which may include 'REQUIREMENTS' -These will be included in the contract -May be additional info or alteration of the proposal -May be accompanied by info and explanation to ensure good ethical practice. Those requiring automatic ER Directorate L will conduct ethics review. Proposals move from ethical screening to ethical review which is conducted by an independent panel of experts chosen by the Commission These experts may work remotely or in Brussels.. Proposals go to ethical screening. as part of the Ethics Process Identifies proposals for ethical review +

1.Applicants identify key ethical issues explain how they address them then list them. 2.Scientific Evaluation 3.Ethics Review at EC level -2 STEPS 1: Ethics Screening-: 2: Ethics Review 4.Ethics (Screening or Review) Report 5.Requirements incorporated in Grant Agreement 6.Possibility of Ethics Audit Ethics: Process for FP7 Novel Ethical Review Process

The Ethical Review is organised and carried out by Directorate L either Remotely or Centrally Automatic ethical review - Proposals involving interventions on human beings, non-human primates, hEmbryos/embryonic stem cells, developing/third countries, dual use. Where necessary ethical safeguards should be in place i.e. in cases of international co-operation,in third countries. + Ethics Review When screening considers that further ethics scrutiny is necessary 2) Ethical review

Expert reads,writes individual report - Once reports completed, Expert communicates with other experts Experts on line, and work towards a consensus, assisted by the Chair of the panel. If Consensus results An Ethics report is drafted and the requirements will be part of the contract negotiation process If there is NO Consensus A panel will convene in Brussels for face-to-face debate mediated by Commission officials. In all cases: The panel issues an 'Ethical Review Report' The proposal ethics status will be judged 'Sufficient' or 'Insufficient'. - 'Sufficient' means that the proposal identifies and addresses the relevant ethical issues. - 'Insufficient' means that there remain significant weaknesses which should be amended. There may be 'REQUIREMENTS' which will part of the contract negotiation process. These may be: more information or modifications to the proposal itself. They should contain explanation and information to ensure compliance with good ethical practice. Remote Assessment using IT Tool

1.Applicants identify key ethical issues explain how they address them then list them. 2.Scientific Evaluation 3.Ethics Review at EC level -2 STEPS 1: Ethics Screening-: 2: Ethics Review 4.Ethics (Screening or Review) Report 5.Requirements incorporated in Grant Agreement 6.Possibility of Ethics Audit Ethics Issues One by One Or, on How TACKLE Ethics issues

The Ethical Review is organised and carried out by Directorate L either Remotely or Centrally Automatic ethical review - Proposals involving interventions on human beings, non-human primates, hEmbryos/embryonic stem cells, developing/third countries, dual use. Where necessary ethical safeguards should be in place i.e. in cases of international cooperation in third countries. + Ethics Review When screening considers that further ethics scrutiny is necessary Mandatory Ethical review

Ethics check list* Informed Consent Does the proposal involve children? Does the proposal involve patients or persons not able to give consent? Does the proposal involve adult healthy volunteers? Does the proposal involve Human Genetic Material? Does the proposal involve Human biological samples? Does the proposal involve Human data collection? Research on Human embryos/foetus Does the proposal involve Human Embryos? Does the proposal involve Human Foetal Tissue/Cells? Does the proposal involve Human Embryonic Stem Cells? Privacy Does the proposal involve processing of genetic information or personal data (eg. health, sexual lifestyle, ethnicity, political opinion, religious or philosophical convinction)? Does the proposal involve tarcking the location or observation of people? Research on Animals Does the proposal involve research on animals? Are those animals transgenic small laboratory animals? Are those animals transgenic farm animals? Are those animals cloning farm animals? Are those animals non-human primates? Research Developing countries Use of local resources (genetic, animal, plant, etc.)? Benefit to local community (capacity building ie access to healthcare, education, etc. ) Dual Use Resarch having potential military/terrorist application * Found in the Science and Society w.page

Informed Consent When is it needed? When children are involved. Healthy volunteers. Human genetic material. Human biological samples. Human data collection Insurance

People : Informed Consent When is it needed? When Children involved Healthy volunteers Human genetic material Human biological samples Human data collection What must be in Consent form ? State + explain That it is research Purpose+duration+description foreseen risks benefits Alternative confidentiality Treatment/compensation +information contact for rights/claims contact for injury to the subject Voluntary participation No penalty or loss on stopping

Informed consent – 2 crucial Issues How can the subjects contribute to science- How will researchers protect their subjects and data. Financial benefit – for researcher, promoter, humanity – What Future use

Privacy and Data Protection Refers to relation between tech and the right to privacy identifiable data collected and stored, Improper or non-existent disclosure control Data affected by privacy issues Health information. Criminal justice. Financial information. Genetic information. Location information. Data privacy / share data while protecting identifiable information. How to Deal with Data Protection and Privacy? describe the procedures for informed consent + confidentiality inform consent for duration + code or anonymised banked biomaterial, security for storage and handling Fairly and lawfully processed limited purposes Adequate, relevant sufficient Accurate Timely storage Processed in due form subject's rights Secure Not transferred abroad unprotected

Research with Animals/NHP Convincing Application of the 3Rs  Reduction, Replacement, Refinement ■ To describe and justify:  Species and Numbers  Humane End Points and Pain Suffering ■ To Check for alternatives (cf. the following websites):   s s

Third Countries 1. Activities open for International Cooperation  International Cooperation Partner Countries (ICPCs) can participate in projects and receive EC funding (as in FP6)  Industrialised countries may be funded if their participation is seen as essential for the project  Minimum number of participants: 3 from MS/AS 2. Specific International Cooperation Actions  Address specific issues that partner countries face or have a global character, on the basis of mutual interest and benefit  Minimum number of participants: 2+2 (2 from MS/AS + 2 from ICPCs) BUT Ethics Requirements MUST BE equivalent to those applied in MS

Research in Developing Countries – No DOUBLE Standards  Does the research project provide benefit to the local community (in terms of access to healthcare, education, allocation of property rights, capacity to assess and use modern technologies while respecting the population 's own choices and needs, etc.)?  Does the research project use local resources (genetic resources, animal, and plants)? Result in their benefit or?

Developing Countries - No Double Standards? what constitutes the best interest of subjects – with insightful recognition that individual and cultural preferences, and what can be achieved in any particular context, may differ significantly; what distinguishes the truly universal from imperialistic notions; 3) the relevance of contextual issues that can be taken into consideration on moral grounds without resorting to ethical relativism The issues requiring special attention : Unequal burden of diseases/effort to treat the breadth and depth of poverty; and high levels of illiteracy disparities in health and in access to health care imbalance between resources for research and basic health care Poor scientific and ethics infrastructures for reviewing disempowerment in personal and communal lives the cultures’ sense of self versus perceptions the classical western notion to be ill in contexts different from researchers’ experience what to expect from those consult for help

Dual Use Research that can have military application In the case of health, it has to be carefully screened for excesses.

Ethical Review in hESC Research Each research proposal involving the use of hESC, which is supported within FP7, is assessed by at least two independent ethical reviews: in the country itself where the research will be carried out, at the EU level. * No System in the world offers a higher guarantee regarding the respect of fundamental ethical principles. * If the research raising ethical issues is performed in more than one country (i.e. n countries), it implies that more than two ethical reviews will be performed (i.e. in fact n+1 ethical reviews)

Very similar to the panorama in FP6 Revision at mid-term for the 2 nd part of FP7 ( ) hESC: When involving the use of hESC in their research project, researchers should take into account and specify that : The process does not destroy embryos (including to procure stem cells); the consortium has taken into account the legislation, regulations, ethics rules and/or codes of conduct in place in the countries where the research using the hESC will take place, including the procedures for obtaining informed consent; the source of the hESC*; the protection of personal data (genetic data and privacy); the nature of financial inducements, if any; positive opinion from a Committee constituted by Member States representatives; PROGRAMME COMMITTEE assent approval of the relevant national or local ethics committee prior to the start of the research activities. * Please note that hESC lines from commercial providers are also subject to these rules hESC Research in FP7

Must all Ethics Committees permissions be presented ? No, but in the the proposal The issues must be recognised The issues must be enumerated The issues must be addressed The solutions must be pondered The permissions mentioned and planned.

What are ethics reviewers looking for? Was consideration given to ethical issues such as, insurance and incidental problems; how are they dealt with? When people are involved, is the participant aware of the approach taken. Situations leading to conflict of interest – is the researcher carrying out the research should not be the person to inform the subject about the pros and cons of the clinical trial. Full disclosure of incentives, financial and others; money may not be the only incentive. The approach must fit context and nature of the research. You must inform the subject that refusing or abandoning the study will not have adverse consequences.

What are ethics reviewers looking for? Does the researcher realise the ethics implication of his work The involvement of children (and vulnerable people) is sensitive. Identify direct benefit to the child. If individual benefit is not present and children need to be involved ensure that there is a minimum risk and burden to the child. Is the information accurate, complete and coherent If animals are involved, numbers, species and origin of animals must be specified. What happens at the end of the research project. Are there alternatives to animal experimentation?

Main Problems found: Consistency and context  Insurance  Incidental Findings  Incentives (Financial inducements, etc.)  Issues related to Children: Minimum Risk/Burden? Real and Direct Benefit?  Research on Animals: Number; End Points; alternatives?  Developing Countries: Benefit sharing  Conflict of Interest: Treating Doctor; Research Interest

Ethics mirrors the clarity of Science The Ethics of a proposal can be a positive structuring factor of a proposal Like the budget, it quantifies, clarifies and shapes the proposal Clarity of purpose simplifies Transparency Transparency opens the way to accountability Ethics bridges science and application

Thank You Dr. Joana Namorado Directorate Health DG RTD – European Commission FP7 –Cooperation theme

How to deal with informed consent in practice?- Address the issue Who should consent exclude vulnerable persons, prisoners, mentally impaired persons, severely-injured patients, very young children, But avoid lost opportunities for these persons, framework should guarantee their participation (notion of surrogate legal/ therapeutic representative). How to inform is it understood? How do you check the critical part of the process? People rarely able to recall what they have agreed upon by signing an inform consent. The following strategies may be of great help: Translator participation Presentation of the project using technologies (video, power-point, theatre play, etc.) Interviews of the participants to ensure that they understand the issues in the research project

Ethics in the Health theme Key issues  for humans: Informed Consent / Data Protection / Privacy  for animals: the 3Rs (Reduce, Replace, Refine)  for human embryonic stem cells: some restrictions & conditions 3 areas are excluded from funding - Human reproductive cloning - Intentional germ line modification (except research relating to cancer of the gonads which can be funded) - Creation of human embryos for research or stem cell procurement (including by means of somatic cell nuclear transfer) NB: all ethics issues must be recognised and addressed in the proposal. - Guide for Applicants, Annex 4, section 4. - Checklist: