1. African perspective on ethical guidelines Salim S Abdool Karim
CAPRISA: Center for the AIDS Program
of Research in South Africa,
University of Natal and Columbia University,
October 15-17, Santiago, Chile

2. Overview of Presentation
Global Context
Ethical Oversight
Choice of appropriate controls in trials
(Guideline 11)
Case Study of exclusive breastfeeding

3. Global Context World population: wealthiest 20% vs poorest 20%
Start of 20th century : 9X
: 30X
: 60X
: >70X
Life Expectancy:
Industrialized countries : >70 years
Poor countries : <50 years

4. Global Context Annual per capita health expenditure
US : $ African countries: <$5
Patterns of diseases
52 million deaths per year
18 million : infectious and parasitic diseases
10 million: diseases of circulatory system
6 million : malignant tumors
Poor countries : 80% of global burden of diseases in DALYs

5. Global Context Early 21st century
World characterized by widening economic and health disparities between rich and poor countries
Increase in absolute poverty - >50% of world population live on <$2/day
Emergence of new diseases afflicting those predominantly marginalized by poverty

7. Research Ethics Committees
Evaluate research proposals with special attention to:
Equity in distribution of benefits and burdens
Risk/Benefit ratios
Conflicts of interests
Adequacy of information provided for participants
Protection of freedom – within consent freedom; for subjects to withdraw without prejudice to care; investigators to publish
Educate and assist researchers and community in understanding and appreciating ethics of research
Monitor and audit research and provide public accountability

8. Research Ethics Committees -
Developing countries
Ethics receives patchy attention
Little uniformity in structure and function
Some instances – self-appointed private ethics committees
Little accountability
Conflict of interest – eg. Drug company payments, carers vs researchers

9. of scientific evidence
Trials - Benchmark
of scientific evidence
Need for more clinical trials to find solutions to the many problems in developing countries
Care in Africa is so under-developed that even slight improvements will raise standards substantially
Choice of control group in trials: If developed country Standard of Care is applied, will the study results be useful?

10. Exclusive Breastfeeding vs
Formula feeding
Perinatal transmission rate in Africa: 25-30% of babies are HIV+
Best proven therapeutic method = ACTG 076 (AZT + formula feeding) = 64% lower
Current standard of care is Nevirapine + mixed feeding – 52% lower
In South Africa: NVP + mixed feeding = 14-18% of babies are HIV+

11. Exclusive Breastfeeding vs
Formula feeding
Vitamin A trial found that exclusive b/feeding lowers HIV infection rate in baby
Is it ethical to do a trial on exclusive b/feeding with control as
NVP + mixed feeding?
NVP + formula feeding?
AZT + formula feeding (ACTG 076)?

12. Case study: Breastfeeding
At issue is that formula theoretically protects fully from breastfeeding transmission
Formula Feeding : possible 0% HIV Risk
Breastfeeding : up to 14% HIV Risk
Is a trial to assess efficacy of exclusive breastfeeding ethical?
Exclusive b/f is unlikely to be as good as f/f
Exclusive b/f is likely to be worse than f/f
Exclusive b/f may or may not be better mixed feeding

13. Case study: Scenarios
A) Exclusive b/feeding vs Exclusive formula feeding
12% vs % = 50% worse
B) Exclusive breastfeeding vs Current mixed feeding
12% vs % = 50% better
Some argue that A is unethical as the study intervention is not thought a priori to be equivalent to formula feeding, which is best proven therapeutic method
Some argue that only A is ethical, this will prevent the discovery of a cheap practical solution to reduce HIV infection in those babies who cannot be formula fed?

14. Should potential low efficacy HIV vaccines be tested in high
HIV prevalence countries?
Based on mathematical models it is unlikely that low efficacy vaccines will be useful in low prevalence countries
Is it ethical to do phase III efficacy trials of low efficacy vaccines only in high risk countries when it may not be ethical to conduct these trials in low risk countries?

15. Conclusion
Research in developing countries depends on local ethics committees to serve as custodians to determine if the research is warranted and whether it is exploiting the poor and vulnerable (ala Capron)
Capacity building for ethics committees
Ethically important to encourage research aimed at finding low efficacy but feasible solutions for the developing world

16. Acknowledgements Solly Benatar, University of Cape Town, South Africa
Cynthia Woodsong, Family Health International, North Carolina
Cheryl Baxter, CAPRISA