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Participation in randomized trials in developing countries
LETTERS
Participation in randomized trials in developing countries To the Editor: We read with interest the report by Caldwell et al1 on factors and risk-benefit assessment of parents in enrolling their children in randomized clinical trials. We would like to share our experience conducting randomized clinical trials in children with human immunodeficiency virus (HIV) in Bangkok, Thailand. In resource-limited settings like Thailand, two important factors appear to affect the parents’ decision: financial concerns and difficulties in accessing care. When the average monthly income is approximately $100 (USD), many families cannot afford even the cheapest triple antiretroviral regimen of $27 USD per month. Moreover, HIV invariably affects more than one family member, further decreasing affordability. Leaving financial issues aside, parents are often reluctant to access care at their local hospitals because of fear of discrimination and lack of confidentiality. These issues are not so important in developed countries, but in developing countries, they can cause parents to enroll their children before truly understanding the risks and benefits of the trial. The ‘‘hope for a miracle cure’’ for children with terminal illnesses in this study is replaced by ‘‘hope for receiving care and treatment’’ in our case. Investigators conducting clinical trials in developing countries have to be vigilant in protecting patients’ rights and ensuring that all safety precautions are taken.2 Parents need to have time to understand and decide about their child’s participation. In this study, the doctors influenced the parents’ decisions. In our culture, parents are not accustomed to questioning doctors; therefore, doctors need to exercise utmost care in providing correct and unbiased facts. We find that having non-MD medical staff members explain the study allows parents to be more comfortable in exploring the issues that would help them decide. Wichitra Apateerapong, RN Jintanat Ananworanich, MD The HIV Netherland Australia Thailand Research Collaboration (HIV-NAT) The Thai Red Cross AIDS Research Center Bangkok, Thailand YMPD540 10.1016/j.jpeds.2003.09.034
REFERENCES 1. Caldwell PH, Butow PN, Craig JC. Parents’ attitudes to children’s participation in randomized controlled trials. J Pediatr 2003;142:554-9. 2. Angell M. Investigators’ responsibilities for human subjects in developing countries. N Engl J Med 2000;342:967-9.
140 Letters
Reply To the Editor: We thank Apateerapong and Ananworanich for their insight on conducting randomized clinical trials in children with human immunodeficiency virus in Bangkok. Although the perceived benefits of access to free medication and treatments not routinely available were identified in our study, we agree that these factors may be more influential in resource-limited settings. The ethics of conducting clinical trials in developing countries has been much debated, because there are concerns that participants may be exploited because of the asymmetry in knowledge and authority between researchers and their subjects.1 For example, the argument that the use of placebo (when effective treatment is available) is justified in trials conducted in developing countries because the standard of care is usually no treatment in these resource limited settings raises ethical issues.2 Although the United States and EC are developing guidelines to address the issue of international research and ethical conduct of trials in developing countries,3,4 the enforcement of these recommendations is often left to the discretion of researchers because local ethics panels are commonly lacking in resource-limited countries.3 We agree with Apateerapong and Ananworanich that nonmedical personnel may help improve patients’ understanding and awareness of clinical trials,5 and doctors need to be aware of their influence on patient participation.1 Patrina H. Y. Caldwell, BMed, FRACP Jonathan C. Craig, MBChB, MM(ClinEpi), DCH, FRACP, PhD Phyllis N. Butow, BA(Hons), MPH, MClinPsych, PhD Centre for Kidney Research NHMRC Centre of Clinical Research Excellence in Renal Medicine and University of Sydney Sydney, Australia YMPD541 10.1016/j.jpeds.2003.09.035
REFERENCES 1. Angell M. The ethics of clinical research in the Third World. N Engl J Med 1997;337:847-9. 2. 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;337:853-5. 3. Bosch X. Improve trials in poor nations, say EC’s ethics advisers. Lancet 2003;361:579. 4. McCarthy M. US ethics guidelines for trials in the developing world. Lancet 2001;357:1506. 5. Aaronson NK, Visser-Pol E, Leenhout GH, Muller MJ, van der Schot AC, van Dam FS, et al. Telephone based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials. J Clin Oncol 1996;14:984-6.
The Journal of Pediatrics
January 2004
Participation in randomized trials in developing countries To the Editor: We read with interest the report by Caldwell et al1 on factors and risk-benefit assessment of parents in enrolling their children in randomized clinical trials. We would like to share our experience conducting randomized clinical trials in children with human immunodeficiency virus (HIV) in Bangkok, Thailand. In resource-limited settings like Thailand, two important factors appear to affect the parents’ decision: financial concerns and difficulties in accessing care. When the average monthly income is approximately $100 (USD), many families cannot afford even the cheapest triple antiretroviral regimen of $27 USD per month. Moreover, HIV invariably affects more than one family member, further decreasing affordability. Leaving financial issues aside, parents are often reluctant to access care at their local hospitals because of fear of discrimination and lack of confidentiality. These issues are not so important in developed countries, but in developing countries, they can cause parents to enroll their children before truly understanding the risks and benefits of the trial. The ‘‘hope for a miracle cure’’ for children with terminal illnesses in this study is replaced by ‘‘hope for receiving care and treatment’’ in our case. Investigators conducting clinical trials in developing countries have to be vigilant in protecting patients’ rights and ensuring that all safety precautions are taken.2 Parents need to have time to understand and decide about their child’s participation. In this study, the doctors influenced the parents’ decisions. In our culture, parents are not accustomed to questioning doctors; therefore, doctors need to exercise utmost care in providing correct and unbiased facts. We find that having non-MD medical staff members explain the study allows parents to be more comfortable in exploring the issues that would help them decide. Wichitra Apateerapong, RN Jintanat Ananworanich, MD The HIV Netherland Australia Thailand Research Collaboration (HIV-NAT) The Thai Red Cross AIDS Research Center Bangkok, Thailand YMPD540 10.1016/j.jpeds.2003.09.034
REFERENCES 1. Caldwell PH, Butow PN, Craig JC. Parents’ attitudes to children’s participation in randomized controlled trials. J Pediatr 2003;142:554-9. 2. Angell M. Investigators’ responsibilities for human subjects in developing countries. N Engl J Med 2000;342:967-9.
140 Letters
Reply To the Editor: We thank Apateerapong and Ananworanich for their insight on conducting randomized clinical trials in children with human immunodeficiency virus in Bangkok. Although the perceived benefits of access to free medication and treatments not routinely available were identified in our study, we agree that these factors may be more influential in resource-limited settings. The ethics of conducting clinical trials in developing countries has been much debated, because there are concerns that participants may be exploited because of the asymmetry in knowledge and authority between researchers and their subjects.1 For example, the argument that the use of placebo (when effective treatment is available) is justified in trials conducted in developing countries because the standard of care is usually no treatment in these resource limited settings raises ethical issues.2 Although the United States and EC are developing guidelines to address the issue of international research and ethical conduct of trials in developing countries,3,4 the enforcement of these recommendations is often left to the discretion of researchers because local ethics panels are commonly lacking in resource-limited countries.3 We agree with Apateerapong and Ananworanich that nonmedical personnel may help improve patients’ understanding and awareness of clinical trials,5 and doctors need to be aware of their influence on patient participation.1 Patrina H. Y. Caldwell, BMed, FRACP Jonathan C. Craig, MBChB, MM(ClinEpi), DCH, FRACP, PhD Phyllis N. Butow, BA(Hons), MPH, MClinPsych, PhD Centre for Kidney Research NHMRC Centre of Clinical Research Excellence in Renal Medicine and University of Sydney Sydney, Australia YMPD541 10.1016/j.jpeds.2003.09.035
REFERENCES 1. Angell M. The ethics of clinical research in the Third World. N Engl J Med 1997;337:847-9. 2. 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;337:853-5. 3. Bosch X. Improve trials in poor nations, say EC’s ethics advisers. Lancet 2003;361:579. 4. McCarthy M. US ethics guidelines for trials in the developing world. Lancet 2001;357:1506. 5. Aaronson NK, Visser-Pol E, Leenhout GH, Muller MJ, van der Schot AC, van Dam FS, et al. Telephone based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials. J Clin Oncol 1996;14:984-6.
The Journal of Pediatrics
January 2004