CORRESPONDENCE

Re: Views of American Oncologists About the Purposes of Clinical Trials

Barry D. Anderson, Malcolm A. Smith, Gregory H. Reaman, Eric D. Kodish

Affiliations of authors: B. D. Anderson, M. A. Smith, Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD; G. H. Reaman, Children’s Oncology Group, Bethesda, MD; E. D. Kodish, Children’s Oncology Group Bioethics Committee, Rainbow Babies and Children’s Hospital, Cleveland, OH.

Correspondence to: Barry D. Anderson, M.D., Ph.D., NCI-CTEP, 6130 Executive Blvd., EPN 7025, Rockville, MD 20852 (e-mail: andersonb{at}ctep.nci.nih.gov).

In a recent article in the Journal, Joffe and Weeks (1) reported that most pediatric oncologists offered their patients the opportunity to enroll in trials to ensure that their patients received "state-of-the-art" therapy and that nearly 40% of responding pediatricians "reported that trials exist primarily to ensure state-of-the-art therapy for the participants themselves." In an accompanying editorial, Miller (2) worried that a substantial proportion of pediatric oncologists might misconceive the purpose of clinical trials, thereby creating a "therapeutic misconception" for the children and families who agree to trial participation, as well as for the oncology teams treating those children.

Pediatric cancer specialists in North America have cooperatively designed and conducted sequential, randomized phase III clinical trials for more than four decades to use evidence-based information to refine the treatment of children with cancer. The state-of-the-art treatment for a child with cancer derives from the best therapy identified in prior clinical trials, and this best-available treatment serves as the standard arm of subsequent phase III clinical trials. Thus, the standard arms of clinical research protocols serve as de facto practice guidelines, and newly diagnosed children can receive this state-of-the-art standard therapy whether or not they enroll in a clinical research trial.

The national pediatric phase III cancer therapy studies are reviewed by multiple panels of childhood cancer experts to ensure that all treatment arms comply with current best-available therapy. Once a trial is initiated, data monitoring committees are charged with stopping the study if sufficient evidence develops to demonstrate that treatment outcome or toxicity no longer conform to best-available therapy. By investigating incremental modifications of best-available therapy in sequential phase III studies, pediatric oncology specialists have learned to employ radiotherapy, surgery, and a limited number of common chemotherapy agents in a risk-based manner, thereby generating steady improvements in patient outcome. For example, 5-year survival for children with acute lymphoblastic leukemia, which was less than 5% in the early 1960s, increased to approximately 50% in the mid-1970s and to 85% by the mid-1990s.

The academic environment in which most pediatric oncologists practice allows physician–investigators to pursue clinical research as a means to improve treatments. However, this pursuit sets up a potential conflict between the practitioner’s dual roles as clinician and investigator. In recognition of this potential conflict, the Children’s Oncology Group has studied the informed-consent process (3,4) and is working to clarify and improve both the decision-making process that families encounter and the information provided by the pediatric oncology team. Efforts to discriminate between the experimental and the standard treatment components of a protocol’s diagnostic and therapy requirements have been augmented. The goal of these efforts is to help families and their physicians better understand how research questions affect potential study participants and better determine whether study enrollment is the most appropriate choice for a particular child.

Pediatric cancer specialists are committed to clinical research because they understand that well-designed clinical trials with appropriate safeguards are the best path to identifying and delivering more effective therapies, while at the same time providing treatment that is consistent with current best-available therapy. Society, and especially children diagnosed with cancer, continues to be well served by the dedicated clinical care and clinical research efforts of the health care professionals specializing in pediatric oncology.

REFERENCES

1 Joffe S, Weeks, JC. Views of American oncologists about the purposes of clinical trials. J Natl Cancer Inst 2002;94:1847–53.[Abstract/Free Full Text]

2 Miller FG. Ethical significance of ethics-related empirical research. J Natl Cancer Inst 2002;94:821–2.

3 Kodish ED, Pentz RD, Noll RB, Ruccione K, Buckley J, Lange, BJ. Informed consent in the Childrens Cancer Group: results of preliminary research. Cancer 1998;82:2467–81.[CrossRef][Medline]

4 Levi RB, Marsick R, Drotar D, Kodish, ED. Diagnosis, disclosure, and informed consent: learning from parents of children with cancer. J Pediatr Hematol Oncol 2000;22:3–12.[CrossRef][Medline]



             
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