Withdrawing from the treatment does not mean from the study

Letters CBulletin of the World Health Organization | October 2008, 86 (10) Cheung10. YB, Zaman SM, Ruopuro ML, Enwere G, Adegbola RA, Greenwood B, et al. C-reactive protein and procalcitonin in the evaluation of the efficacy of a pneumococcal conjugate vaccine in Gambian children. Trop Med Int Health 2008;13:603-11. PMID:18331385 Direct11. and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease — United States, 1998-2003. MMWR Morb Mortal Wkly Rep 2005;54:893-7. PMID:16163262 Grijalva12. CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet 2007; 369:1179-86. PMID:17416262 doi:10.1016/ S0140-6736(07)60564-9 Black13. SB, Shinefield HR, Ling S, Hansen J, Fireman B, Spring D, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect Dis J 2002;21:810-5. PMID:12352800 doi:10.1097/00006454-200209000-00005 Cutts14. FT, Zaman SM, Enwere G, Jaffar S, Levine OS, Okoko JB, et al. Efficacy of nine- valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet 2005; 365:1139-46. PMID:15794968 doi:10.1016/ S0140-6736(05)71876-6 Klugman15. KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 2003;349:1341-8. PMID:14523142 doi:10.1056/NEJMoa035060 Pneumococcal conjugate vaccine for 16. childhood immunization – WHO position paper. Wkly Epidemiol Rec 2007;82:93-104. PMID:17380597 Withdrawing from the treatment does not mean from the study Having read the recently published pa- per by Williams on the ethical conflict between individual rights and public health rights when conducting research on humans,1 we would like to call attention to a common misconception that occurs in clinical trials: withdrawal from treatment under study necessar- ily implies withdrawal from the study. Failure to continue to study patients who have withdrawn from treatment can severely hinder research, as critical information is lost.2 While there will always be some patients who do not complete the treatment protocol, their data may and should still be used to complete the study protocol, wherever it is practical and where consent can be obtained.3,4 If the reason for stop- ping treatment is due to patient denial of the previously agreed consent, a conflict arises between the rights of the individual and those of the population since the latter might benefit from this lost patient information. As Eriksson & Helgesson5 explain, there are various reasons why patients may choose to ask for their data to be removed from studies. These are le- gitimate concerns and should never be taken lightly. However, every patient who has received medical treatment has reaped the benefits of previous studies, that is to say, from individu- als who have voluntarily allowed their data to be used for the benefit of humanity. It could be argued that it is the duty of every patient to repay this debt. We think that, once informed consent has been given, data belong to the protocol and may be used within the context that was previously agreed: report, publication and oral presenta- tion. Some have argued that “once consent has been given, participants should not necessarily have uncondi- tional or absolute rights to withdraw”.6 This discrepancy hindered our own research recently when one of us tried to distinguish between withdrawing from treatment and withdrawing from the study. The Independent Review Board referred him to item 22 of the Declara- tion of Helsinki,7 which states that: “The subject should be informed of the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal.” But the World Medical Association’s International Code of Medical Ethics8 divides these patient’s rights into two parts. Under this code, item 2 of “Duties of physicians in general” states that: “A physician shall respect a com- petent patient’s right to accept or re- fuse treatment” and item 4 of “Duties of physicians to patients” states that: “A physician shall respect a patient’s right to confidentiality. It is ethical to disclose confidential information when the patient consents to it or when there is a real and imminent threat of harm to the patient or to others and this threat can be only removed by a breach of confidentiality.” Therefore, when volunteering to participate in a random- ized clinical trial, a patient effectively agrees to two different requirements: on the one hand, to random alloca- tion to treatment, and on the other, to measurement and use of aggregated data that is made suitably anonymous. The current wording of the Declaration of Helsinki fails to distinguish between consent to treatment and consent to data. Therefore, when the World Medi- cal Association meets in Seoul, Republic of Korea, in October 2008, we feel that it should deliberate on how to avoid such confusion. ■ Erik Cobo,a Stephen Senn b & Matthew Elmore a References Williams JR. The Declaration of Helsinki 1. and public health. Bull World Health Organ 2008;86:650-1. doi:10.2471/BLT.08.050955 Porta2. N, Bonet C, Cobo E. Discordance between reported intention-to-treat and per protocol analyses. J Clin Epidemiol 2007;60:663-9. PMID:17573981 doi:10.1016/j. jclinepi.2006.09.013 Lachin3. JM. Statistical considerations in the intent-to-treat principle. Control Clin Trials 2000;21:167-89. PMID:10822117 doi:10.1016/ S0197-2456(00)00046-5 Cobo4. E. Diseño y análisis de un ensayo clínico: el aspecto más crítico. Med Clin (Barc) 2004;122:184-9. PMID:14998455 doi:10.1157/13057825 Eriksson5. S, Helgesson G. Potential harms, anonymization, and the right to withdraw consent to biobank research. Eur J Hum Genet 2005;13:1071-6. PMID:15986039 doi:10.1038/sj.ejhg.5201458 Edwards6. SJL. Research participation and the right to withdraw. Bioethics 2005;19:112-30. PMID:15943021 doi:10.1111/j.1467- 8519.2005.00429.x Declaration7. of Helsinki 2004. Available from: http://www.wma.net/e/policy/b3.htm [accessed on 1 September 2008]. World Medical Association International Code of 8. Medical Ethics. Available from: http://www.wma. net/e/policy/c8.htm [accessed on 1 September 2008]. a Department of Statistics and Operations Research, Technical University of Catalonia, Barcelona, Spain. b Department of Statistics, University of Glasgow, Glasgow, Scotland. Correspondence to Erik Cobo (e-mail: erik.cobo@upc.edu).