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Truly informed consent is a difficult thing to achieve! Patients are not healthy volunteers and their vulnerability challenges their ability to assess the risk/benefit of health choices. In this paper we consider some or the issues surrounding this important aspect of modern practice, and offer some suggestions on how to improve the process,with the goal of increasing participation in clinical research, and enhancing patients’confidence in their medical advisors.
Keywords: Clinical trials, consent, ethics, randomisation
J.R.Coll.Surg.Edinb., 46, April 2001, 100-102
Cancer is the second commonest cause of death in the Western world. After many years of endeavour, mortality rates for some of the common tumours have recently started to decline. Whilst some of this is due to changes in lifestyle, improved treatment is a major factor and research, particularly clinical trials, are an essential component of this continuing effort to improve outcome. The cornerstone of clinical research is the randomised-controlled trial (RCT).
In a RCT a proposed new treatment option, which is considered by experts to be potentially superior, is evaluated against the best standard treatment currently available. Patients have a 50:50 chance of receiving either the standard treatment or the experimental arm. Results of the RCT will decide whether the new treatment is in fact any better than the previous standard therapy, though enrolled patients may expect a benefit regardless of which arm they receive, purely by virtue of being in the study.1,2 Despite this, the level of accrual to trials is generally very low, with less than 5% of patients with solid tumours being entered into clinical trials.3
Possible reasons why more patients are not offered treatment as part of clinical trials include:
In this article we will look at some of the issues relating to informed consent; its origins, what it entails, whether it is always necessary and how it may be improved.
Though commonly regarded as having been introduced in the Nuremberg code, the first use of the term ‘informed consent’was actually in relation to concerns regarding a clinical trial in cancer patients.4 However, the concept, if not the term itself, was extolled in principle 1 of the Nuremberg code, as a human right of research volunteers.5 The subsequent Declaration of Helsinki, focused on the obligations of the investigators to such research subjects. These two documents now form the mainstay of the ethical principles governing human research. Despite the over-whelming support for these principles in general, it later became apparent that they were not always adhered to.
In 1966 Henry Beecher revealed unethical research practices employed in 22 trials published in United States medical journals since World War II.6 One such trial allowed the transplantation of malignant melanoma from a patient into her healthy mother in an attempt to produce anti-melanoma serum; both patient and mother died of metastatic malignant melanoma. Another involved the injection of malignant cells from cancer patients into elderly and debilitated inmates of the Jewish Chronic Disease Hospital. In another, the Tuskagee Syphilis Study, patients known to be infected with Treponema pallidum, were followed up for long-term sequelae without intervention. By the 1980’s it became apparent that ethically dubious experiments were not confined to the United States.7
Such revelations resulted in a public outcry both within and outwith the medical profession. Institutional Review Boards/Ethics Committees were set up to formally examine all research protocols before they could accrue patients. The requirement for ‘informed consent’is now enshrined in the World Health Organisation (WHO) International Ethical Guidelines for Biomedical Research Involving Human Subjects (1993). The WHO is now considering a revision of the Declaration of Helsinki, particularly regarding the use of placebos in RCTs with interesting differences of opinion being expressed on the issue.8
In the everyday medical treatment of patients, consent is often implicit, e.g. by extending one’s arm to have a cannula sited, the patient tacitly consents to that procedure. Prior to potentially more hazardous treatments, such as surgery or chemotherapy, written informed consent is routinely sought. That this consent is not always formal, is an indication of the trust patients have in their doctors. In this setting, patients rightly assume that the doctor’s motives are well-intentioned and that he is unlikely to recommend any treatment that would do more harm than good, i.e. the doctor is motivated by beneficence. This assumption is tested, however, when the doctor moves from his role as physician to that of clinical researcher. The primary goal of the physician/surgeon is to treat, while that of the researcher is to test a scientific hypothesis. Doctors who are researchers, therefore, face a potential conflict of interest between what is good for the current patient, future patients (good of society), the research centre (prestige, remuneration), or himself (career advancement, prestige or remuneration). Because of this, fully informed consent prior to entry into clinical trials is mandatory. Through the process of full disclosure, patients who volunteer for clinical trials must adequately understand:
Truog et al (1999) and others have argued that the requirements for consent in clinical trials are too rigorous, and that the same level of disclosure is not required in routine practice.9 It is argued that a relaxation of informed consent requirements to those of everyday practice would allow more unimpeded research. Some of the commonly cited reasons to relax the informed consent requirements include the following:
patients may be distressed by detailed information regarding aims, methods, randomisation and risks10
it is not required if invasiveness and risk is minimal, especially when obtaining informed consent might compromise the study’s results11
that the good for society is more important than individual rights and patients are less likely to join randomised trials when fully informed (utilitarian argument)12
Each of these arguments has been roundly dismissed by Len Doyal, Professor of Medical Ethics at the University of London, as (respectively) (i) "tired and discredited paternalism", (ii) "impossible to predict as well as unethical" and (iii) "an attack on human dignity...[and] moral integrity of the uninformed volunteer".13 The latter utilitarian argument is further refuted by evidence indicating that improving informed consent can actually boost accrual rates by up to 50%.14
HOW INFORMED CONSENT MAY BE IMPROVED
In order to facilitate the disclosure process we commonly employ information sheets. However, as a result of increasing complexity of some clinical studies and possibly medico-legal reasons, there is a tendency for these information sheets to evolve into lengthy, turgid documents which paradoxically may detract from patient understanding. Over 20 years ago Gray et al (1978) showed that, as assessed by standard accepted criteria, only 7% of consent forms could be deemed ‘readable’. Ten years later,15 LoVerde et al (1989) showed that consent forms were becoming increasingly unreadable and lengthy, with probably no improvement in patient understanding.16 In 1994, Grossman et al (1994) found that only 1-6% of any consent form could be read by 12-year olds, while accurate reading of an average consent form required a minimum 2 years college education.17 Readability and comprehension, however, may be substantially improved by having the information sheets checked, or written, by a professional linguist.18
A study by Simes et al (1986) compared total disclosure by written consent form with interactive verbal disclosure at the discretion of the investigator.19 While the former was associated with better patient understanding, full written disclosure also resulted in an initial increase in trial-related anxiety and less willingness to participate in the study. However, 3 or 4 weeks after the full written disclosure process, there was no significant detrimental impact on physician-patient relationship. It is important to point out that patients in this study received information either by full written disclosure or verbal discretionary disclosure, not both, while in most situations a combination of the two is employed. In fact, a third method, namely that of information in electronic form, is now becoming commonplace.
More and more patients and their relatives are accessing the Internet in order to obtain information regarding their diagnosis, prognosis and treatment options. While initially some doctors may have felt threatened by patients bearing reams of down-loaded information from the Internet, we now realise that the Internet could provide another, more popular, means of communicating with patients. The Internet is a maze with many monsters, however, since there is no control over content, many of the claims by individuals, companies, and institutions are either unsubstantiated or wholly misleading. Looking for information regarding "cancer", a search of the Internet using the popular search engine ‘Alta Vista’ yielded 3,058,730 web sites. Using the same search engine to look-up "breast cancer" identified 362,001 pages. Patients, therefore, should be directed to good quality web sites, which provide accurate, up-to-date and relevant information. Such sites include, in the US:
The use of taped interviews with the patient or even pre-prepared videos for the patient to review in their own time, may become more widespread in future.20
We suggest the following 3-stage disclosure process:
The Science and Technology Committee of the House of Commons have very recently reported on "Cancer Research - A Fresh Look", and identified as a high priority the need to increase the number of adult cancer patients entering clinical trials.21 The incentive to conduct clinical research becomes ever harder, but we must overcome the bureaucratic hurdles if progress is to be made. Where there are options in management, truly well informed consent to a procedure, therapy or trial, is a vital part of establishing the doctor/patient relationship, which if successful will benefit accrual to clinical trials and, of equal importance, give immediate benefit to the individual patient.
Copyright date: 5th February 2001
Correspondence: Professor J. F. Smyth, Professor of Medical Oncology, ICRF Medical Oncology Unit, MRC Building, Western General Hospital, Crewe Road, Edinburgh EH4 2X,U.K.
Email: j.smyth@icrf.icnet.uk
©2001 The Royal College of Surgeons of Edinburgh, J.R.Coll.Surg.Edinb.