Salim S Abdool Karim

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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, 2003. Santiago, Chile

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Overview of Presentation

• Global Context
• Ethical Oversight
• Choice of appropriate controls in trials
• (Guideline 11)
• Case Study of exclusive breastfeeding

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Global Context

• World population wealthiest 20 vs poorest 20
• Start of 20th century 9X
• 1960 30X
• 1990 60X
• 1997 gt70X
• Life Expectancy
• Industrialized countries gt70 years
• Poor countries lt50 years

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Global Context

• Annual per capita health expenditure
• US 4000 African countries lt5
• 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

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Global Context

• Early 21st century
• World characterized by widening economic and
  health disparities between rich and poor
  countries
• Increase in absolute poverty - gt50 of world
  population live on lt2/day
• Emergence of new diseases afflicting those
  predominantly marginalized by poverty

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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

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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

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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?

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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

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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)?

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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

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Case study Scenarios

• A) Exclusive b/feeding vs Exclusive formula
  feeding
• 12 vs 8 50
  worse
• B) Exclusive breastfeeding vs Current mixed
  feeding
• 12 vs 18 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?

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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?

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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

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Acknowledgements

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