Correspondence
Informed Consent for a Clinical Trial in Thailand
N Engl J Med 1998; 339:1331-1332October 29, 1998
- Article
To the Editor:
With respect to the recent controversy over clinical trials in developing countries, Lurie and Wolfe1 criticized the ethics of study design, whereas Varmus and Satcher2 asserted the validity and necessity of such studies. The issue of informed consent has been overshadowed in this debate. Although consent may have been given in a placebo-controlled trial conducted in Thailand of zidovudine to reduce vertical transmission of the human immunodeficiency virus (HIV),3 we believe that the consent may not have been informed.
We compared the revised consent form (Thai and English versions) to ensure that the Thai version was an accurate translation and understandable by both lay Thai speakers and Thai academics. Each component is essential to meaningful informed consent. We found that the Thai and English versions differed in their description of the study design.
The Thai version states that “half of the participants will receive zidovudine, whereas the other half will receive a comparison drug that does not contain zidovudine. This drug has no effect on your health or your baby's health. Using the drug that does not contain zidovudine will help determine the advantages and disadvantages of zidovudine.” The English version states that “half [of the women] will be given zidovudine, and half will be given an inactive substance called placebo. Placebo is like a sugar pill which has no effect on your health or your baby's health. The reason why some women will get the placebo is to allow the study investigators to determine as clearly as possible if a short oral dosage of zidovudine is effective and safe compared to taking no drug.”
Nowhere in the Thai version do the words “inactive substance,” “placebo,” or “sugar pill” (for which Thai words or concepts exist) appear, whereas all are included in the English version. Researchers used the phrase “comparison drug that does not contain zidovudine” in the Thai version. Why was this phrase not clarified with the use of Thai terms for “inactive substance” or “sugar pill” — terms that can be understood by laypersons?
The second sentence in the Thai excerpt suggests that the comparison “drug” has no side effects, rather than clarifying what a placebo is, as in the English version. In addition, unlike the English version, the Thai version does not make it explicit that the study is a comparison of zidovudine and placebo. Thus, the subjects' understanding may unintentionally have been compromised.
Obtaining informed consent is difficult, requiring precise translations of descriptions of complicated procedures and sensitivity to diverse cultural perceptions. Since researchers are often not involved in the actual consent process, a reliable system must be established that ensures that subjects fully comprehend their role in the study.
3 ReferencesAbinash Achrekar, M.P.H.
Rajesh Gupta, B.S.
Yale University School of Medicine, New Haven, CT 065201
Lurie P ,Wolfe SM . Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries. N Engl J Med 1997;337:853-856
Full Text | Web of Science | Medline2
Varmus H ,Satcher D . Ethical complexities of conducting research in developing countries. N Engl J Med 1997;337:1003-1005
Full Text | Web of Science | Medline3
Shaffer N, Limpakarnjanarat K, Chuachoowong R, Mastro T, Young N. Phase III randomized placebo-controlled trial to evaluate the safety and efficacy of short course oral antenatal zidovudine (ZDV) to reduce perinatal HIV transmission, Bangkok, Thailand. Atlanta: Centers for Disease Control and Prevention, January 15, 1996. (Revised consent form, April 7, 1997.)
Author/Editor Response
The above letter was referred to the Thai Ministry of Public Health and to the authors of the study in question, who offer the following replies:
To the Editor: In reference to the study by Shaffer et al., both the English and Thai versions of the consent form were carefully reviewed by the Ethical Review Committee of the Thai Ministry of Public Health.1 The Thai members of the committee found the Thai language in the consent form to be appropriate and clear and understandable in its description of the concept of an inactive comparison pill, or placebo.
1 ReferencesChart Pichayangkura, M.D.
Vichai Chokewiwat, M.D., M.P.H.
Ministry of Public Health, Nonthaburi 11000, Thailand1
Shaffer N, Limpakarnjanarat K, Chuachoowong R, Mastro T, Young N. Phase III randomized placebo-controlled trial to evaluate the safety and efficacy of short course oral antenatal zidovudine (ZDV) to reduce perinatal HIV transmission, Bangkok, Thailand. Atlanta: Centers for Disease Control and Prevention, January 15, 1996. (Revised consent form, April 7, 1997.)
Author/Editor Response
Ensuring the informed consent of participants in research is the biggest responsibility of investigators and ethics oversight committees. We believe the informed-consent process in our study met extremely high standards.
To ensure that potential participants understood our study design, particularly the use of a placebo, we followed a multistep process. First, the subjects were referred to us by hospital staff members, who explained the placebo-controlled design. Second, the subjects were introduced to the study two or more times by different members of the study staff on different days. Third, flip charts and booklets were used that described the purpose of the study, its design, and procedures, including the use of placebo, in explicit and understandable language and diagrams. Fourth, there was independent certification by two staff members that each woman understood the concept of a placebo. Furthermore, before signing, women were given a copy of the consent form and encouraged to review it at home. When consent was given, a staff member and an investigator again confirmed that each woman understood the study design. During this multistep process, 44 women were considered unable to provide informed consent and were excluded.
Because the Thai language has no literal equivalents for “placebo” or “sugar pill,” we chose, after careful consideration, a Thai phrase that would convey the sense of these words. Although there may be several ways to translate the word “placebo,” we used the term ya priab tiab for “comparison substance.” Although ya can mean drug, it also connotes “substance” in many common phrases, such as ya-see-fun (toothpaste) and ya-kad-rong-tao (shoe polish). To clarify that this substance was inactive, our materials also referred to “placebo” as “an inactive substance used for comparison and without effect on the mother and child.” In our blinded, independent, professional back-translation performed in Thailand, the Thai phrasing in question was translated into English as “placebo.”
The investigators were intimately involved in the consent process and actively took responsibility to ensure the participants' understanding. In addition, our entire protocol, including the Thai-language consent form and the consent process, was reviewed and approved by the Ethical Review Committee of the Thai Ministry of Public Health.
We appreciate the opportunity to clarify for those not familiar with the Thai language or our study procedures how we addressed the important issue of ensuring truly informed consent for participation in a placebo-controlled trial.
Khanchit Limpakarnjanarat, M.D., M.P.H.
Rutt Chuachoowong, M.D., M.P.H.
HIV–AIDS Collaboration, Nonthaburi 11000, ThailandChaiporn Bhadrakom, M.D.
Siriraj Hospital, Bangkok 10700, ThailandWimol Siriwasin, M.D.
Rajavithi Hospital, Bangkok 10400, ThailandSanay Chearskul, M.D.
Siriraj Hospital, Bangkok 10700, ThailandTawee Chotpitayasunondh, M.D.
Queen Sirikit National Institute for Child Health, Bangkok 10400, ThailandNathan Shaffer, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333- Citing Articles (4)
Citing Articles
1
P. A. Marshall, C. A. Adebamowo, A. A. Adeyemo, T. O. Ogundiran, M. Vekich, T. Strenski, J. Zhou, T. E. Prewitt, R. S. Cooper, C. N. Rotimi. (2006) Voluntary Participation and Informed Consent to International Genetic Research. American Journal of Public Health 96:11, 1989-1995
CrossRef2
Patricia A. Marshall. (2006) Informed Consent in International Health Research. Journal of Empirical Research on Human Research Ethics 1:1, 25-42
CrossRef3
Wendy K. Mariner. (2003) Taking Informed Consent Seriously in Global HIV Vaccine Research. JAIDS Journal of Acquired Immune Deficiency Syndromes 32:2, 117-123
CrossRef4
Peter H. Kilmarx, Gita Ramjee, Dwip Kitayaporn, Prayura Kunasol. (2001) Protection of human subjects' rights in HIV-preventive clinical trials in Africa and Asia: experiences and recommendations. AIDS 15, S73-S79
CrossRef
