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Ethical Use of Human Subjects

1. Globalization of Clinical Trials

2. Case Study

3. Placebos

Globalization of Clinical Trials

 Background:

• Industry- sponsored clinical research has traditionally occurred in North American, Western Europe, and Oceania. In recent years a shift in research occurring in emerging regions such as Latin America, Asia, and Africa has been noted.
•  Reasons for the shift include reduction in operational costs, the ability to recruit large numbers of participants, and the nature of regulatory authorities.
•  Potential benefits: Globalization allows for greater access to high quality medical care and diffusion of medical knowledge.
•  Potential hazards: There may be inadequate regulatory oversight in emerging regions. U.S. based companies may be focused on the needs in the U.S. market, not the needs of the population where the research occurs. Drugs are not as widely available in emerging countries as wealthy countries.

Who benefits from the globalization of clinical trials?

Can results from the study population be generalized to populations in which the treatments will most likely be used?

Should research be based on the local standard of care of the best standard of care?

Case Study

• The drug zidovudine has been shown the cut the rate of vertical transmission of HIV and is recommended in the U.S. for all HIV- infected pregnant women.
• However, in developing countries the drug is not widely used due to it’s exorbitant cost.
• In 1994 the World Health Organization determined that in developing countries, "Placebo-controlled trials offer the best option for a rapid and scientifically valid assessment of alternative antiretroviral drug regimens to prevent [perinatal] transmission of HIV."
• Subsequent placebo-controlled studies occurred in a number developing countries with sponsorship from the FDA

Is this conclusion ethical?

Should research in developing countries be held the to ethical standards of the sponsoring country?

 Would a controlled trial with zidovudine generate scientifically valid results?

 Placebos

 Background:

• Placebos are used to account for the confounding nature of the placebo effect
• FDA considers placebo-controlled studies part of the gold standard of clinical research
• In some cases where a treatment exists a placebo is not used. Instead the new treatment is compared to the old treatment in an active-control study.
• Placebos have confounding effects depending on several factors, so placebos do not entirely remove confounding effects. The form and color of the placebo can have varying placebo responses

 Are placebo-controlled trials necessary for scientifically valid research?

 Are placebo-controlled trials meaningful from the patient’s perspective?

 What is the primary function of clinical research?