A Comparison of the Quality of Informed Consent for Clinical Trials of an Experimental Hookworm Vaccine Conducted in Developed and Developing Countries

Abstract

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed consent process of a series of clinical trials of an investigational hookworm vaccine that were performed in Brazil and the United States. A standardized questionnaire was used to assess the ethical quality of the informed consent process in a series of Phase 1 clinical trials of the Na-GST-1/Alhydrogel hookworm vaccine that were conducted in healthy adults in Brazil and the United States. In Brazil, the trial was conducted at two sites, one in the hookworm non-endemic urban area of Belo Horizonte, Minas, and one in the rural, resource-limited town of Americaninhas, both in the state of Minas Gerais; the American trial was conducted in Washington, DC. A 32-question survey was administered after the informed consent document was signed at each of the three trial sites; it assessed participants’ understanding of information about the study presented in the document as well as the voluntariness of their decision to participate. 105 participants completed the questionnaire: 63 in Americaninhas, 18 in Belo Horizonte, and 24 in Washington, DC. Overall knowledge about the trial was suboptimal: the mean number of correct answers to questions about study objectives, methods, duration, rights, and potential risks and benefits, was 45.6% in Americaninhas, 65.2% in Belo Horizonte, and 59.1% in Washington, DC. Although there was no difference in the rate of correct answers between participants in Belo Horizonte and Washington, DC, there was a significant gap between participants at these two locations compared to Americaninhas (p = 0.0002 and p = 0.0001, respectively), which had a lower percentage of correct answers. Attitudes towards participating in the clinical trial also differed by site: while approximately 40% had doubts about participating in Washington, DC and Belo Horizonte, only 1.5% had concerns in Americaninhas. Finally, in Belo Horizonte and Washington, high percentages cited a desire to help others as motivation for participating, whereas in Americaninhas, the most common reason for participating was personal interest (p = 0.001). Understanding of information about a Phase 1 clinical trial of an experimental hookworm vaccine following informed consent was suboptimal, regardless of study site. Although overall there were no differences in knowledge between Brazil and the US, a lower level of understanding about the trial was seen in participants at the rural, resource-limited Brazilian site. These findings demonstrate the need for educational interventions directed at potential clinical trial participants, both in developing and developed countries, in order to improve understanding of the informed consent document.

Author Summary

Informed consent is an essential element of the ethical conduct of clinical trials of new vaccines, regardless of the study setting. However, the quality of informed consent is often suboptimal. Some research has suggested that the quality of the informed consent process may be reduced in resource-limited areas compared to developed country settings. To test this, we conducted a study of the quality of the informed consent process in two similar Phase 1 clinical trials of the Na-GST-1/Alhydrogel hookworm vaccine that were conducted in healthy adult volunteers in Brazil and in the United States. In Brazil, the trial was conducted at two sites, one a large urban area (Belo Horizonte), and the other a rural, resource-limited region of the state of Minas Gerais; in the United States, the trial was conducted in Washington, DC. A structured questionnaire was administered after the informed consent document was signed at each of the three clinical trial sites, which tested understanding about the information contained in the document and attitudes toward the volunteers’ participation in the clinical trial. The results indicate that there were no substantial differences between the overall quality of the informed consent obtained from participants in the United States and in Brazil. However, a significant association was found between the particular site where the trial was conducted and the quality of the informed consent process, with residents of the site in rural Brazil having the lowest percentage of correct answers on the informed consent questionnaire. The informed consent process should therefore take into account the specific characteristics of the population in which the trial is being conducted.