Pediatr Blood Cancer 2009;52:437–438

HIGHLIGHTby Stacey L. Berg, MD*

When Too Much Is Just Enough: What Do Oncologists Tell Parents?(Commentary on Ramirez et al., page 497)

T he need to obtain informed consent before a patient receives

medical care, and particularly before a person becomes the

subject of biomedical research, is now widely recognized. It has

been nearly 100 years since Benjamin Cardozo stated that ‘‘Every

human being of adult years and sound mind has a right to

determine what shall be done with his own body’’ [1], and just over

50 since the term ‘‘informed consent’’ was coined to describe a

patient’s decision to permit medical treatment after a physician has

disclosed the pertinent facts related to that treatment [2]. With

respect to research, the Nuremberg Code [3] states that any person

contemplating entering a study ‘‘should have sufficient knowledge

and comprehension of the elements of the subject matter involved

as to enable him to make an understanding and enlightened

decision.’’ For any prospective subject to arrive at such a decision,

he must be informed among other things of the risks he may be

exposed to in the course of participation. Despite many years of

analysis and regulation of informed consent, however, the

adequacy of communication between investigator and subject

remains difficult to assess, and the whether research consent is truly

‘‘informed’’ is frequently questioned [4–9].

The risks of chemotherapy for childhood cancer, whether in or

out of a research setting, are numerous, and many of them are

potentially life-threatening. Further complicating their discussion is

that some adverse events occur frequently but are not usually

serious; some occur rarely but are life-threatening; some, like

alopecia, may be medically insignificant but socially or psycholog-

ically quite important; and some do not even manifest themselves

until months or years after treatment is completed. Most children in

the United States receive their anticancer therapy as part of a clinical

trial. Thus, the risks of treatment are usually included in the

informed consent document, even for the drugs or other parts of

treatment that are not different from standard therapy. The federal

regulations require that a research informed consent include ‘‘any

reasonably foreseeable risks or discomforts to the subject’’ [10]; for

some investigators and IRBs, especially given the current litigious

environment of medicine, ‘‘reasonably foreseeable’’ has tended to

mutate into ‘‘conceivably possible.’’ Written consent forms for

oncology trials average over 10 printed pages and are steadily

lengthening [7,11]. Thus investigators struggle to identify and present

risks in a way that is meaningful to the potential research subject.

In this issue of Pediatric Blood & Cancer, Ramirez et al. quantify

the number of acute and late toxicities presented by oncologists in

initial informed consent conferences with parents of children newly

diagnosed with leukemia. A major strength of the investigative

approach taken is that conferences were audiotaped so that toxicities

could be counted objectively, rather than relying on parent or

investigator recall of what was presented. Of note, the number of

toxicities discussed per conference was large: an average of 24 per

conference, with an upper end of 47. Two particularly interesting

trends emerge from the data: first, most conferences focused on high

probability, acute side effects rather than low probability side effects

even if those potentially might be more serious; and second, there

was a small but statistically significant trend for more experienced

oncologists to present fewer side effects than younger colleagues.

Both of these findings suggest that investigators sought as best as

they could to convey the information they thought was most impor-

tant to the families’ decision making. The authors raise the concern

that late effects are given short shrift in the process, suggesting

perhaps that even more risks should have been included in the

discussions.

This study did not seek to compare the information conveyed

orally in the conference with that given in the written consent form

or other resources. Since, as is often stated, informed consent is a

process not limited to a single conference or printed form, it would

be a mistake to use this study draw broad conclusions about the

comprehensiveness of the risk information made available to

the families before they decided whether to permit their children to

be enrolled in research. Nonetheless, this study makes an important

contribution to our understanding of how risks are enumerated to

potential research subjects. Future studies should build on these data

to evaluate the effects of various methods of presenting risks on

subject comprehension and, ultimately, on the best ways to enhance

the ‘‘informed’’ aspect of research consent.

REFERENCES

1. Schloendorff v. Society of New York Hospital, 211 N.Y. 125, 105

N.E. 92 (1915). 1915.

2. Salgo v. Leland Stanford etc. Bd. Trustees, 154 Cal.App. 2d 560.

1957.

3. Nuremberg Code. 1949.

4. Joffe S, Cook EF, Cleary PD, et al. Quality of informed consent: A

new measure of understanding among research subjects. J Natl

Cancer Inst 2001;93:139–147.

5. Flory J, Emanuel E., Interventions to improve research parti-

cipants’ understanding in informed consent for research: A

systematic review. JAMA 2004;292:1593–1601.

6. Tait AR, Voepel-Lewis T, Malviya S, et al. Improving the

readability and processability of a pediatric informed consent

� 2008 Wiley-Liss, Inc.DOI 10.1002/pbc.21871Published online 4 December 2008 in Wiley InterScience(www.interscience.wiley.com)

——————Texas Children’s Cancer Center, Baylor College of Medicine, Houston,

Texas

*Correspondence to: Stacey L. Berg, Texas Children’s Cancer Center,

Baylor College of Medicine, 6621 Fannin St., MC3-3320, Houston, TX

77030. E-mail: sberg@txccc.org

Received 21 October 2008; Accepted 21 October 2008

document: Effects on parents’ understanding. Arch Pediatr

Adolesc Med 2005;159:347–352.

7. Beardsley E, Jefford M, Mileshkin L. Longer consent forms for

clinical trials compromise patient understanding: So why are they

lengthening? J Clin Oncol 2007;25:e13–e14.

8. Tait AR, Voepel-Lewis T, Malviya S. Do they understand? (part I):

Parental consent for children participating in clinical anesthesia

and surgery research. Anesthesiology 2003;98:603–608.

9. Daugherty CK., Impact of therapeutic research on informed

consent and the ethics of clinical trials: A medical oncology

perspective. J Clin Oncol 1999;17:1601–1617.

10. Title 45, Code of Federal Regulations, Part 46: Health and Welfare,

Protection of Human Subjects. 6/23/05.

11. Sharp SM., Consent documents for oncology trials: Does

anybody read these things? Am J Clin Oncol 2004;27:570–

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Pediatr Blood Cancer DOI 10.1002/pbc

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