Strategies to Minimize Risks and Exploitation in Phase One Trials on Healthy Subjects*

*Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government.

Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors.

*Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government.

Keywords:

• phase one studies
• clinical trials
• ethics
• safety
• exploitation

ACKNOWLEDGMENT

This research is supported in part (to David B. Resnik) by the intramural research program of the National Institute of Environmental Health Sciences, National Institutes of Health. This paper was also supported in part (to Adil E. Shamoo) by a grant from Fogarty International Center/NIH 1R25TW007090-01.

Notes

*Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government.

1. The term “phase one trials” is part of the United States Food and Drug Administration's regulatory lexicon relating to INDs (investigational new drugs). The term is also commonly used to describe the first time a new drug, biologic or medical device is used in a human being. We will use this broader understanding of “phase one trials” in our article. Although our article will focus on phase one trials on new drugs, the points we will make should also apply to biologics and medical devices.

2. Some claim that many phase four studies are unnecessary marketing ploys (Angell 2004).

3. Phase I Clinical Trials Unit, Ltd. (2004), located in Plymouth, England, is a company that specializes in conducting phase one studies for drug companies. The company has a database of about 5,000 regular volunteers and a clinical staff of about 100 employees. It also has 61 beds, 21 monitored beds, a pharmacy, an ethics committee. It advertises that it can recruit many different types of volunteers for drug studies, including older men and women; sterilized men and post-menopausal women; obese subjects; and smokers and non-smokers. Volunteers stay at the company's facilities overnight or longer. The company claims that its facilities are comparable to a quality hotel, with televisions in every bedroom, lounges, landscaped gardens, and catered food.

4. Phase one studies on sick patients have a range of other problems that we will not explore here, notably, the therapeutic misconception: subjects tend to believe that the study will provide them with a medical benefit even when they are informed that the purpose of the study is to develop medical knowledge and that they have a very small chance of deriving some medical benefit from participation (see Miller 2000). The data indicate that disclosure of the risks and benefits of participation in phase one trials is usually adequate, but very ill patients continue to hope that they will receive a direct medical benefit (Agrawal and Emanuel 2003; Daugherty et al. 1995; Horng et al. 2002).

5. Because the subjects in these studies are healthy, not sick, they are less likely to succumb to the therapeutic misconception. See op cit, note 4.

6. A recent study by Bentley and Thacker (2004) shows that money can influence the decision to participate in research but that it does not blind subjects to high risks.