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Ethics of Hematopoietic Stem Cell Transplantation in Type 1 Diabetes MellitusEthics of Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

JAMA. 2007;298(3):285-286. doi:10.1001/jama.298.3.285-a
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AUTHOR INFORMATION

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

ETHICS OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN TYPE 1 DIABETES MELLITUS

To the Editor: We believe that the study of autologous hematopoietic stem cell transplantation for treatment of newly diagnosed type 1 diabetes mellitus (DM) by Dr Voltarelli and colleagues1 raises serious ethical concerns regarding participant selection and study design.

Although the researchers were able to get research ethics approval in Brazil, the participant selection fails international standards of research ethics. Virtually every country in the world, including Brazil, is a signatory to the Declaration of Helsinki, international research ethics standards written by the World Medical Association. According to the Declaration of Helsinki, “For a research subject who is . . . a legally incompetent minor, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law. These groups should not be included in research unless the research is necessary to promote the health of the population represented and this research cannot instead be performed on legally competent persons.”2 Research involving pediatric participants is ethical if it will promote the health of children and the research cannot be performed on adults. Although the majority of individuals with type 1 DM present in childhood, a significant number present in young adulthood. Thus, it is possible to have performed this research first on adults instead of enrolling 8 minors (<18 years) among the first 15 participants.

One justification for including children might be that type 1 DM is more aggressive in children. This may justify not waiting for long-term results; however, it does not justify the inclusion of children in the first phase of this research. The first participant presented with diabetic ketoacidosis and his response was quite poor, leading to a change in study design and inclusion criteria. It was not known a priori whether this would happen in other patients, which is why such research should be performed first on competent adults.

Even if the only participants had been adults, it is not clear that the study as designed would have been ethical. Age-matched controls are needed to determine the extent of benefits and short-term and long-term harms. To what extent this protocol will lead to long-term insulin independence is unknown and requires long-term follow-up. The follow-up period in the protocol overlaps with the known and variable honeymoon period observed in individuals with type 1 DM,3 particularly those who have received immunosuppresive therapy.4 5

These ethical concerns are particularly relevant given that the evolving standard of care for treatment of type 1 DM is reasonably effective, if highly demanding and imperfect.

Financial Disclosures: None reported.

References
Voltarelli JC, Couri CE, Stracieri AB.  et al.  Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus.  JAMA. 2007;297(14):1568-1576
PubMed
World Medical Association Declaration of Helsinki.  World Medical Association Web site. http://www.wma.net/e/policy/b3.htm. Published October 9, 2004. Accessed April 11, 2007
Knip M, Sakkinen A, Huttunen NP.  et al.  Postinitial remission in diabetic children: an analysis of 178 cases.  Acta Paediatr Scand. 1982;71(6):901-908
PubMed
Yilmaz MT, Devrim AS, Biyal F.  et al.  Immunoprotection in spontaneous remission of type 1 diabetes: long-term follow-up results.  Diabetes Res Clin Pract. 1993;19(2):151-162
PubMed
Bougneres PF, Carel JC, Castano L.  et al.  Factors associated with early remission of type I diabetes in children treated with cyclosporine.  N Engl J Med. 1988;318(11):663-670
PubMed

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Voltarelli JC, Couri CE, Stracieri AB.  et al.  Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus.  JAMA. 2007;297(14):1568-1576
PubMed
World Medical Association Declaration of Helsinki.  World Medical Association Web site. http://www.wma.net/e/policy/b3.htm. Published October 9, 2004. Accessed April 11, 2007
Knip M, Sakkinen A, Huttunen NP.  et al.  Postinitial remission in diabetic children: an analysis of 178 cases.  Acta Paediatr Scand. 1982;71(6):901-908
PubMed
Yilmaz MT, Devrim AS, Biyal F.  et al.  Immunoprotection in spontaneous remission of type 1 diabetes: long-term follow-up results.  Diabetes Res Clin Pract. 1993;19(2):151-162
PubMed
Bougneres PF, Carel JC, Castano L.  et al.  Factors associated with early remission of type I diabetes in children treated with cyclosporine.  N Engl J Med. 1988;318(11):663-670
PubMed
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