Case Study 4: What is a Study's Responsibility to the Community?

Cholera, a watery diarrhea that may have a mortality rate of over 30% in severe untreated cases, is endemic in the Bengal region of the Indian Subcontinent-West Bengal in India and Bangladesh.  Fortunately, there is an effective treatment for cholera based on the principle of re-hydration and fluid maintenance.  Oral re-hydration therapy (ORT) and/or intravenous fluids are very effective in treating the fluid losses in cholera such that mortality from properly treated cases should not exceed 5% (the cost of ORT is 1/50 of IV).  Treatment can be carried out in simple treatment centers that are equipped only with cots, buckets, and fluid.  Tetracycline (or other appropriate antibiotics) reduce the duration of illness in half, but are not essential in treatment.  Re-hydration therapy is equally effective in the treatment of all dehydrating diarrheas.  The Cholera and Diarrheal Research Institute, an Indian medical research center which is based in Calcutta, has just received a grant to study the effectiveness of a new vaccine against the cholera strain Vibrio cholera 0139.  The new strain of Vibrio cholera recently appeared in both Eastern and Western Bengal.  The new vaccine was developed at a large American university and has been through Phase I and II testing. At the present time, the vaccine costs $1.00 per dose, and three doses are required; however, it is estimated that cost will be reduced by 75% in the future.  The Indian government's per capita expenditure on health in this region is $5.00 per year.

The field site, a rural rice-growing area with a population of about 75,000, is 2 hours drive from Calcutta by mainly country roads; even paved roads are not good and often are risky.  A government clinic services the community, but often it finds itself short of the medicines it needs.  It has no cholera cots, and its physician population changes every 12 to 18 months.  In the area are some "unlicensed doctors" and a number of traditional practitioners.  Few of these providers have modern treatments for cholera or other diarrheas.

The vaccine will be given to children less than 5 years of age in a double-blind fashion, with one group receiving the vaccine and the other a booster dose of tetanus toxoid.  As the placebo group is more likely to have cholera, the Institute feels that a treatment facility should be established in the field site to provide state-of-the art care for all patients with cholera and other diarrheas.  The Institute would provide the facility, the personnel, the equipment, and medicine to the community free-of-charge.  Others have suggested that the government clinic be upgraded.  The Institute, however, would have no control over the selection or personnel or quality of care provided.  The Institute does not have an endowment and depends on government grants and research awards to finance its activities.  Some in the research group are concerned that the Institute may take on a long-term commitment to provide treatment that it can ill afford.

A group of public health activists in Calcutta have raised a number of concerts regarding informed consent and some design issues.  The study group dealt with many of these concerns, though two ('research subjects' rights') concerns remain outstanding:
(1) What is the Institute's long-term commitment to providing health care to the community?
Will the Institute leave the area after the study has been completed, or will they provided some ongoing support in the future (and, if so, of what kind)?; and
(2) If the vaccine is effective, will all participants in the study receive free doses of the proven-effective medication?  If so, for how long (can and will this follow-up support be continued)?  Should all the citizens of the nation(s) (or region) benefit from the results of the study?

Comment on the ethical issues raised by the group of concerned public health activists.  You may also wish to consider the following:

• Who will pay for any long-term health care?
• Are there any other messages that should accompany the distribution of vaccines other than (a) to take note of all cases of diarrhea and (b) to immediately report to the treatment facility it the diarrhea become severe?
• At what level of efficacy should the vaccine be considered as a useful preventive measure?
• Who should make this determination (and how and why)?