What happens when the research is over? Researcher and funder perspectives J Whitworth Head of International Activities Wellcome Trust Global Forum on Bioethics in Research Blantyre March 2005

Basic premise: To leave a study population better off after a research study than it was before Widespread agreement with this in principle, the difficulty is in the implementation

Two aspects: Collateral benefits (standard of care) Access to established or successful trial interventions

Collateral benefits By–products of conducting research May or may not be necessary for study design Examples:  Provision of health care benefits to community  Strengthening local research capacity  Provision of technical or clinical equipment

Collateral benefits Basic premise: Aim to ratchet up general standard of care with each and every trial  Needs to be sustainable once research is over  Best done in collaboration with local health services  Minimise gulf between service provision for study participants and community

Collateral benefits Wellcome Trust will consider funding collateral benefits if:  They are sustainable once research is over  They do not adversely affect local research environment eg by raising unrealistic expectations for future trials  They do not amount to coercive or undue pressure to participate

Provision of proven interventions May be successful research interventions, or previously established interventions Widespread agreement with this in principle, ensures local applicability, avoids exploitation Funders often require application to include plan for after trial access to care

Provision of proven interventions To whom? Study participants, study community, national citizens For how long? Some interventions are life long Whose responsibility? Researchers, funders, sponsors, national governments

Whose responsibility? Researchers Usually assumed to be responsible. But team may leave after research. May not have power. Funders Usually consider health care outside remit eg NIAID, Wellcome Trust, MRC.

Whose responsibility? Sponsors May be appropriate to assist researchers engage with government ministries or pharmaceutical companies. Do they have the expertise? Governments Ultimately responsible for provision of health care. Proper authority to determine ‘best practice’. Policy makers unlikely to agree to provision of intervention before results of trial known.

Examples DART Multicentre trial of ART regimen and monitoring (Uganda and Zimbabwe) Funders made clear would not pay for ART even during trial Drug companies made clear would not pay for ART after trial Local ethics committees felt trial was on balance beneficial to participants with 4 yrs ART Researchers obtained letter from relevant Ministers of Health accepting responsibility for appropriate continuing care of trial participants including ART No sense of a ‘team’ of researchers, funders and sponsors

Observational study of non-communicable disease Cross-sectional prevalence study of obesity, diabetes, hypertension East African country Who is responsible for health care for those individuals found with treatable conditions? Diabetes, hypertension require skilled treatment for life. Researchers/sponsors? Able to commit for decades? National government? Struggle to provide single dose vaccines. Is such a trial ethical? Case study 2

Practicalities of post-trial access Intervention may be long-term, eg insulin Intervention may not be needed for several years, eg ART in HIV seroconverters Untested mechanisms, eg ‘escrow accounts’ Mechanisms for systems where the patient pays Should payments be waived for study participants? For what? How to organise?

Wellcome Trust position statement on research involving people in developing countries Launched today Ethical framework underlying funding decisions Guidance and practical advice Covers relevance of research, selecting participants, consent, ethical review, collateral benefits, standards of care for control groups, post-research access.

Wellcome Trust position statement on research involving people in developing countries Will consider supporting processes to address post-research access ideally before starting research. Assistance – letter of support Funding – meetings and discussions with health authorities, governments, pharmaceutical companies, NGOs.

These are not controversial principles. But they are difficult to apply in practice. As usual, the devil is in the detail.