Med Pediatr Oncol 2002;39:207–209

ETHICAL ISSUESMedical Research: Why Trouble the Patient for

Informed Consent?

Sheila M. Farnell, PhD*

INTRODUCTION

Many children, who less than a decade ago wouldprobably have died of cancer, can now be cured. Thisimprovement in survival is a result of clinical research,most in the context of Randomized Controlled Trials(RCT). As such research becomes increasingly intensive,invasive and complex a high degree of moral uncertaintyconcerning informed consent is coming to the fore.

This article is based on the author’s research conduc-ted at three of the largest pediatric oncology centers in theUK and one in the USA in conjunction with a PhD thesis[1]. The primary concern of the thesis was the ethicalimplications of experimental therapies in pediatric onco-logy conducted through RCT. These concerns, however,can also be extrapolated to adult patients.

ARGUMENT AGAINST OBTAININGINFORMED CONSENT FOR ENTRY INTO RCT

The argument is that if full disclosure is made, thenpatients will be caused needless anxiety, the physician–patient relationship will suffer and ‘‘much needed trialswill fail through lack of willing participants’’ [2]. AsTobias and Souhami put it, ‘‘the issue of informed consenthas [thus] become a major barrier to the successfulconduct of randomized clinical trials in cancer. The manypractical difficulties have led to low levels of recruitment,especially where there is a substantial difference betweenthe treatment policies being compared’’.

‘‘It does not take many such consultations’’, writeTobias and Souhami ‘‘to change a well intentioned andcommitted trialist into a disgruntled clinician who nolonger feels that the game is worth the candle. It can beextremely difficult to sustain the physician–patientrelationship through such a harrowing discussion andparticularly unfortunate for the patients . . .’’ [3].

One can sympathize with investigators in theirbeneficent wish to offer the best treatment available andtheir paternalistic desire to protect the patient and/orproxy from potentially hurtful information. Communica-

tions often take place in a highly emotive atmosphere.The patient and/or proxy is usually frightened, and thereis often difficulty in understanding what is being saidconcerning the disease and especially when the patientand/or proxy first hears of the concept of RCT. They aretold that the investigator does not know which treatmentis best, and that, if randomization is agreed to, theultimate decision concerning treatment will be made bythe computer. Confidence and trust in the investigator areeasily undermined.

Since they see thousands of such patients someinvestigators believe they can ‘‘make a much more accu-rate judgement of the utilitarian outcomes than theindividual patients facing up to disease’’ [4]. This situa-tion was clearly evident during my own empiricalresearch, and was usually motivated by a desire toprotect the parents.

An individual may prefer not to be fully informed, i.e.,may prefer to abnegate the freedom and allow theinvestigator to make specific treatment choices becausehe (the individual) may feel incompetent to decide forhimself or does not want the responsibility. This holdstrue especially in the case of proxy consent.

IMPLICATIONS OF NOT OBTAININGINFORMED CONSENT

Not obtaining informed consent raises immediatequestions concerning the consequences (both ethicallyand legally) if, at some future time, a patient and/or proxydiscovers that they (or their child) have been subjected toresearch without their knowledge.

Ethically, an individual can exercise his autonomy(freedom of choice) by requesting, i.e., giving authority

Key words: medical ethics; medical research; informed consent; proxy consent;pediatric oncology

——————The Garden House, 32 Mallorie Park Drive, Ripon, HG4 2QF, England

*Correspondence to: Sheila M. Farnell, The Garden House, 32Mallorie Park Drive, Ripon, HG4 2QF, England.

Received 13 June 2001; Accepted 22 January 2002

� 2002 Wiley-Liss, Inc.DOI 10.1002/mpo.10109

to the investigator to make decisions for him. But thedecision to abnegate the freedom to make treatmentchoices, the right to self-determination, can only be madeby the ‘‘person who possesses the right’’—only he can‘‘decide whether he wishes to exercise it’’ [5].

Before relinquishing his authority, the individualpatient/proxy should be clearly informed that he is beingasked to participate in research. Details of the nature andprocess of that research must be presented. Moreover, itmust be made clear that he can refuse to participate and, ifhe does consent that he can withdraw at any time. This isa requirement recognized by most ethical guidelines andparticularly by the Declaration of Helsinki and theNuremberg Code. The former, a code of ethics on humanexperimentation drawn up in 1965 by the World MedicalAssociation, states: ‘‘In any research on human beings,each potential subject must be adequately informed of theaims, methods, anticipated benefits and potential hazardsof the study and the discomfort it may entail. He or sheshould be informed that he or she is at liberty to abstainfrom participation in the study and that he or she is free towithdraw his or her consent to participate at any time.The physician should then obtain the subject’s freelygiven informed consent, preferably in writing’’. It alsostipulates that the interests of the subject must alwaysprevail over the interest of science and society [6]. TheNuremberg Code is the result of a proposal shortly afterWorld War II to publish a Universal Code of ResearchEthics. The first principle of this Code states that in orderto avoid treating a person simply as a means to an end inscientific research, it is absolutely essential to obtain hisvoluntary consent. This requires that the person involvedshould, ‘‘have the legal capacity to give consent; be sosituated as to be able to exercise free power of choicewithout any element of force :: constraint or coercion,’’have ‘‘sufficient knowledge’’ on which to decide andhave ‘‘sufficient comprehension’’ to make an ‘‘enligh-tened decision’’ [7]. This requirement is essential in thecase of third-party decisions (proxy consent) concerninga child or infant who is terminally ill. For the proxy tobe in a position to decide what is in the best interest of thechild, full disclosure concerning the research must bemade by the investigator to the proxy without ‘‘bringingundue pressures to bear on their patients in an effort topersuade them to participate’’ [5]. The investigator mustbe aware that the patient and/or proxy may be saying:‘‘I’ll leave it to you, you know best’’ and will be ‘‘expres-sing not so much genuine consent as an anxious wish tobe compliant and cause as little trouble as possible’’ [5].

But in RCT the investigator does not know what is bestfor the individual patient. Indeed, an ethical prerequisiteis that the relative efficacy of the treatment arms isuncertain.

I believe that current efforts to avoid the uniformrequirement to seek informed consent for RCT are

dangerous. They ultimately betray the patient’s and/orproxy’s ability to exercise his right to self-determination.This is a position I find morally unacceptable.

COMMUNICATION DIFFICULTIES

It is no doubt difficult and stressful to explain theconcept of RCT. Yet, to purport that the solution lies innot informing at all (as Tobias and Souhami advocate), toreduce distress is spurious [8].

There is convincing evidence that most patients(including parents of children) want more not less infor-mation concerning what is happening to them (or theirchild), regardless of the severity of potential risks [9].Moreover, there is a strong association between prefer-ences for information and participation in health care [10]and better outcomes [11].

Central to the issue of communication is the question:‘‘Do you think it is possible to explain the situation (theconcept of RCT) in detail including all the options, to theparent/child?’’ When I put the question to the physiciansin my own study, only one felt that it is not. All the othersthink that, ‘‘given time’’, it is possible.

In RCT this is critically important, since patientsforego their right to treatment, that is, as Wong puts it,‘‘tailored entirely to their needs; hence the treatmentpolicy decided on is not always in the patients bestinterests’ [12].

The equipoise conditions required for RCT cannotjustify paternalism, however well motivated, i.e., decid-ing what is good for that particular person/patient becausethe investigator does not know what is good for or inthe best interests of the individual patient. This holds trueespecially in pediatric oncology. Nonetheless, if a patientand/or proxy is not given a choice of all the treatmentalternatives, then recruitment into a RCT may ‘‘usurp thepatient’s preferences and compromise autonomy’’ [13].

I found that the less information and time that thechildren/proxies were given the more they opted forrandomization (see below)—a conclusion that was sharedby several pediatricians, nursing staff, and patients.

IS FUTURE RESEARCH THREATENED?

A Professor of Pediatric Oncology and Director ofResearch, who is heavily involved in the design andimplementation of trials in the UK informed me that:‘‘The big thrust towards informed consent is alteringrandomization . . . the more information that is given, thenthe more patients opt out. . . . If this trend continues thenresearch in paediatric oncology [in the UK] willbe seriously threatened; indeed it could come to a totalhalt’’ (Bailey CC, 1993, verbal comments).

It has also been claimed that: ‘‘Widespread acceptanceof the prime importance of autonomy is leading to thecollapse of many important trials in the UKand the USA [4].

208 Farnell

Not to seek informed consent based on the fact thatmore patients may refuse to be randomized is clearly notpaternalism because the action is not taken for the good(protection) of the individual patient. Rather, it is takenfor utilitarian purposes even if these are believed to be forthe good of future generations.

Failure to seek one individual’s consent for entry into aRCT can easily be extended to failure to seek the consentof many individuals. The slope then becomes extremelyslippery in that it could become the general policy of anentire society. One need only recall the atrocities of thosemedical experiments during World War II that wereconducted for the ‘‘good’’ of society.

Medical ethics will then have strayed far from thecooperative partnership between subject and investigatorthat can be built only on the basis of respect, loyalty andfidelity [14].

Children with cancer are especially in a precariousposition because research, even though conducted on thegrounds of beneficence, is often an implicit part of thetreatment prescribed in pediatric oncology.

REFERENCES

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3. Tobias JS, Souhami RL. Fully informed consent can be needlesslycruel. Br Med J 1993;307:1119–1201.

4. Baum M. The ethics of clinical research. In: Byrne P, editor. Ethicsand law in health care and research. United Kingdom: Wiley;1990. p 1–7.

5. Anonymous. Informed consent: ethical, legal, and medicalimplications for doctors and patients who participate in rando-mised clinical trials. Br Med J 1983;286:1117–1121.

6. British Medical Association. Philosophy and practice of medicalethics. British Medical association. 3rd edition. United Kingdom:British; 1988. p 101–102.

7. Nuremberg Code. Trials of war criminals before the Nurembergmilitary tribunals under control council law: 1949. No. 10, Vol. 2,p 1891–1892. US Government. In: Levine RJ, editor. Ethics andregulations of clinical research. 2nd edition. USA: Urban &Schwarzenberg; 1986.

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9. Sharp MC, Strauss RP, Lorch SC. Communicating medical badnews: parents’ experiences and preferences. J Pediatr 1992;121:539–546.

10. Cassileth BR, Zupkis RV, Sutton-Smith K, March V. Informationand participation preferences among cancer patients. Ann InternMed 1980;92:832–836.

11. Lidz CW, Appelbaum PS, Meisel A. Two models of implement-ing informed consent. Arch Intern Med 1988;148:1385–1389.

12. Wong JG. Informed consent in clinical trials. Open discussionpromotes trust. [letter; comment on: Br Med J 1993;307:1199–1201]. Br Med J 1993;307:1495.

13. Kodish E, Lantos JD, Siegler M. Ethical considerations inrandomized controlled clinical trials. Cancer [Supplement]1990;65:2400–2404.

14. Bok S. Informed consent in tests of patient reliability. JAMA1992;267:1118–1119.

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