Correspondence

Bone Marrow Transplantation for Sickle Cell Disease

N Engl J Med 1996; 335:1845-1846December 12, 1996

Article

To the Editor:

The report by Walters et al. on successful eradication of sickle cell disease through bone marrow transplantation (Aug. 8 issue)1 raises some ethical issues. Although this multicenter study was conducted under the supervision of a Data Safety and Monitoring Board of the National Institutes of Health and had the approval of each center's institutional review board, the article raises questions about the issues of informed consent. The following statement from the methods section is confusing: “All the patients or their parents or guardians gave written informed consent for their participation.” The study involved only children under 16 years of age; the actual range of age was 3.3 to 13.9 years, with a median of 10.4. All the patients were underage and hence could not have given informed consent. Which patients — other than the parents or guardians who gave their own consent — are being referred to in the article?

Khalid L. Rehman, M.D.
St. Vincent's Medical Center, Staten Island, NY 10310

1 References

1. 1

   Walters MC, Patience M, Leisenring W, et al. Bone marrow transplantation for sickle cell disease. N Engl J Med 1996;335:369-376
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Dr. Rehman asks how patients less than 16 years of age could give informed consent to participate in a multicenter study of bone marrow transplantation for sickle cell disease. In our study, parents or legal guardians gave their written informed consent for patients less than 18 years of age. Verbal assent (the patient's agreement to participate in research) accompanied parental written consent for children 7 to 11 years of age, and detailed informed consent was obtained from patients 12 years of age and older. These procedures were in accord with institutional-review-board guidelines from the federal government's Office of Protection from Research Risks and guidelines for informed consent from the American Academy of Pediatrics.1

The ability of children and adolescents to consent to participate in research studies is facilitated by dealing with concrete items rather than abstract concepts.2 By the age of 11, a child's reasoning ability has become advanced, and by the age of 14, adolescents can weigh alternatives as well as adults.3 Individual institutional review boards vary in their interpretations of federal regulations governing consent for adolescent minors. Nearly 70 percent of responding institutional review boards required parental consent for all research on minors, but this proportion decreased if boards reviewed 10 or more adolescent protocols per year.4

Without question, parents' attitudes and values are critical in decisions about consent for procedures such as bone marrow transplantation. Among the families of patients who fulfilled our study's eligibility requirements, only 10 percent declined to proceed with HLA typing, and among those with a suitable marrow donor, only 16 percent refused transplantation.5 The willingness of families to participate in this investigation underscores the importance of pediatric participation in well-designed treatment studies aimed at improving outcomes in children and adolescents.

Keith M. Sullivan, M.D.
Mark C. Walters, M.D.
Fred Hutchinson Cancer Research Center, Seattle, WA 98104

Kwaku Ohene-Frempong, M.D.
University of Pennsylvania, Philadelphia, PA 19104

5 References

1. 1

   American Academy of Pediatrics, Committee on Drugs. Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics 1995;95:286-294
   Web of Science | Medline

2. 2

   Susman EJ, Dorn LD, Fletcher JC. Participation in biomedical research: the consent process as viewed by children, adolescents, young adults, and physicians. J Pediatr 1992;121:547-552
   CrossRef | Web of Science | Medline

3. 3

   Weithorn L, Campbell SB. The competency of children and adolescents to make informed treatment decisions. Child Dev 1982;53:1589-1598
   CrossRef | Web of Science | Medline

4. 4

   Mammel KA, Kaplan DW. Research consent by adolescent minors and institutional review boards. J Adolesc Health 1995;17:323-330
   CrossRef | Web of Science | Medline

5. 5

   Walters MC, Patience M, Leisenring W, et al. Barriers to bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 1996;2:100-104
   Medline