The Journal of Pediatrics
Volume 149, Issue 1, Supplement , Pages S20-S24 , July 2006

Phase I research and the meaning of direct benefit

  • Lainie Ross, MD, PhD

      Affiliations

    • Corresponding Author InformationReprint requests: Dr Lainie Friedman Ross, University of Chicago, Department of Pediatrics, 5841 S. Maryland Ave., MC 6082, Chicago, IL 60637.

References 

  1. US Department of Health and Human Services . (45 CFR 46, Subpart D). Protections for children involved as subjects in research . Federal Register . 1983;48:9814–9820 March 8 revised Federal Register . 1991;56:28032; June 18
  2. American Society of Clinical Oncology . Critical role of Phase I clinical trials in cancer treatment . J Clin Oncol . 1997;15:853–859
  3. Kodish E . Pediatric ethics and early-phase childhood cancer research (conflicted goals and the prospect of benefit) . Accountability Res . 2003;10:17–25
  4. Ratain MJ , Mick R , Schilsky RL , Siegler M . Statistical and ethical issues in the design and conduct of Phase I and Phase II clinical trials of new anticancer agents . JNCI . 1993;85:1637–1643
  5. Estey E , Hoth D , Simon R , Marsoni S , Leyland-Jones B , Wittes R . Therapeutic response in Phase I trials of antineoplastic agents . Cancer Treatment Reports . 1986;70:1105–1115
  6. Decoster G , Stein G , Holdner E . Responses and toxic deaths in Phase I clinical trials . Ann Oncol . 1990;1:175–181
  7. Von Hoff DD , Turner J . Response rates, duration of response, and dose response effects in Phase I studies of antineoplastics . Invest New Drugs . 1991;9:115–122
  8. National Commission for the Protection of Human Subjects . Report and Recommendations (Research Involving Children) . Washington, DC: US Government Printing Office; 1977; DHEW Publication No. (OS) 77-0004.
  9. Smith M , Bernstein M , Bleyer W , Borsi J , Ho P , Lewis IJ , et al.   Conduct of Phase I trials in children with cancer . J Clin Oncol . 1998;16:966–978
  10. Shah S , Weitman S , Langevin AM , Bernstein M , Furman W , Pratt C . Phase I therapy trials in children with cancer . J Pediatr Hematol/Oncol . 1998;20:431–438
  11. Furman WL , Pratt CB , Rivera GK . Mortality in pediatric Phase I clinical trials . JNCI . 1989;81:1193–1194
  12. Estlin EJ , Cotterill S , Pratt CB , Pearson ADJ , Bernstein M . Phase I trials in pediatric oncology (perceptions of pediatricians from the United Kingdom Children’s Cancer Study Group and the Pediatric Oncology Group) . J Clin Oncol . 2000;18:1900–1905
  13. Agrawal M , Emanuel EJ . Ethics of Phase 1 oncology studies (reexamining the arguments and data) . JAMA . 2003;290:1075–1082
  14. King NMP . Defining and describing benefit appropriately in clinical trials . J Law Med Ethics . 2000;28:332–343
  15. Lantos JD . The “Inclusion Benefit” in clinical trials . J Pediatr . 1999;134:130–131
  16. Moreno J , Caplan AL , Wolpe PR . Updating protections for human subjects involved in Research . JAMA . 1998;280:1951–1958
  17. Brody BA . The ethics of biomedical research (an international perspective) . New York: Oxford University Press; 1998;
  18. Horng S , Emanuel E , Wilfond B , Rackoff J , Martz K , Grady C . Descriptions of benefits and risks in consent forms for Phase 1 oncology trials . N Engl J Med . 2002;347:2134–2140
  19. US Department of Health and Human Services . (45 CFR 46, Subpart A). Final regulations amending basic HHS policy for the protection of human research subjects . Federal Register . 1981;46:8366–8391 January 26 revised Federal Register . 1991;56:28003–28018 June 18
  20. Ackerman TF . Phase I pediatric oncology trials . J Pediatr Oncol Nurs . 1995;12:143–145
  21. Appelbaum PS , Roth LH , Lidz CW , Benson P , Winslade W . False hopes and best data (consent to research and the therapeutic misconception) . Hastings Center Report . 1987;17:20–24
  22. Daugherty C , Ratain MJ , Grochowski E , Stocking C , Kodish E , Mick R , et al.   Perceptions of cancer patients and their physicians involved in Phase I trials . J Clin Oncol . 1995;13:1062–1072
  23. Hutchison C . Phase I trials in cancer patients (participants’ perceptions) . European J Cancer Care . 1998;7:15–22
  24. Ulrich C , Grady C , Wendler D . Palliative care (a supportive adjunct to pediatric Phase I clinical trials for anticancer agents) . Pediatrics . 2004;114:852–855
  25. Levetown M . Ethical aspects of pediatric palliative care . J Palliative Care . 1996;12:35–39
  26. Ackerman TF . The ethics of Phase I pediatric oncology trials . IRB (A Review of Human Subjects Research) . 1995;17:1–5
  27. Kreicbergs U , Valdimarsdottir U , Onelov E , Henter J-I , Steineck G . Talking about death with children who have severe malignant disease . N Engl J Med . 2004;351:1175–1186
  28. Oberman M , Frader J . Dying children and medical research (access to clinical trials as benefit and burden) . Am J Law Med . 2003;29:301–317
  29. Moore S . A need to try everything (patient participation in Phase 1 trials) . J Advanced Nurs . 2001;33:738–747
  30. Cox K . Assessing the quality of life of patients in Phase I and II anti-cancer drug trials (interviews versus questionnaires) . Social Science Med . 2003;56:921–934
  31. Bernstein ML , Reaman GH , Hirschfeld S . Developmental therapeutics in childhood cancer (a perspective from the Children’s Oncology Group and the US Food and Drug Administration) . Hematol/Oncol Clin North Am . 2001;15:631–655
  32. Weijer C . The ethical analysis of risks and potential benefits in human subjects research (history, theory, and implications for US regulation) . In: National Bioethics Advisory Commission (NBAC). Ethical and Policy Issues in Research Involving Human Participants . Vol. 2: 2001; Commissioned Papers. August Available online at: http://www.georgetown.edu/research/nrcbl/nbac/human/overvol2.pdf, P-1-P-29

PII: S0022-3476(06)00372-6

doi: 10.1016/j.jpeds.2006.04.046

The Journal of Pediatrics
Volume 149, Issue 1, Supplement , Pages S20-S24 , July 2006

Article Tools