Nurses increasingly participate in clinical trials (Parabor 1997). The nurse may run his/her own trial or may undertake research as part of a diploma qualification or for a higher degree. The nurse may be involved in a trial being run by a medical practitioner or by another nurse. A nurse may be a member of a research ethics committee, which has the task of scrutinising proposals for clinical research in a particular area. Research is integral to good clinical practice. As the Nursing and Midwifery Council (NMC) Code of Professional Conduct provides: ‘6.5 You have a responsibility to deliver care based on current evidence, best practice and, where applicable, validated research when it is available’ (Nursing and Midwifery Council 2002).
Awareness of legal and ethical issues in research is therefore important for reflective practice (Royal College of Nursing 2004). While research is necessary for scientific development and clinical practice it can also prove controversial, as illustrated by the recent press reports concerning six volunteers involved in an anti-inflammatory drugs trial at Northwick Park Hospital in London, who suffered a severe reaction and multiple organ failure within hours of taking the drug (BBC Newsonline 2006). This chapter provides an account of the legal regulation of research and the obligation of the researcher to the research subject.
The first section of this chapter considers the manner in which clinical research is regulated. In the second section, the role of research ethics committees in scrutinising clinical trials and legal principles regulating clinical trials are discussed. In the final section the question of negligence actions brought against nurses and others where research subjects are injured in a clinical trial are considered, along with the role of the nurse in policing unethical researchers.
FRAMEWORK OF REGULATION
The human rights abuses of clinical research in Nazi Germany and in Japan during the middle years of the 20th century resulted in pressure for the regulation of clinical research. Concern to safeguard the human rights of the individual has played an important part in structuring responses to research regulation (McHale & Gallagher 2004). International guidelines were developed, most notably the Nuremberg Code in 1949 and the Declaration of Helsinki, originally produced in 1964 (Plomer 2004). In this country there is no one piece of legislation governing the conduct of all research activity, although certain legislation does govern specific areas such as animal research (Animals (Scientific Procedure) Act 1986) and research undertaken on embryos (Human Fertilisation and Embryology Act 1990). Most recently the European Union Clinical Trials Directive has led to major changes in the legal regulation of drug trials in this country through the Medicines for Human Use (Clinical Trials) Regulations 2004.
A number of guidelines have been published, for example by the Department of Health in the form of the Research Governance Framework (Department of Health 2005a) and the Guidelines for NHS Research Ethics Committees (GAfREC, Department of Health 2001), the Royal College of Physicians (1996) and the Royal College of Nursing (1993). While these guidelines are not legally binding, they suggest conduct that amounts to good research practice and may be referred to in subsequent legal proceedings. The law governing research derives from general principles of civil law and criminal law, along with certain specific statutory provisions such as the Medicines Act 1968 and the Medicine for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031). Clinical research is undertaken across a vast area of scientific activity.
Below is a brief overview of some of the areas of current regulatory activity. Certain research gives rise to particularly difficult ethical issues, requiring careful consideration, for example embryo research, the use of fetal tissue and the research into gene therapy. Embryo research was considered by the Warnock Committee Embryo research is regulated by the Human Fertilisation and Embryology Authority under the Human Fertilisation and Embryology Act 1990. Embryo research was eventually sanctioned after a heated ethical debate regarding the status of the embryo. As with abortion, ethical objections were raised to the use and consequent destruction of embryos for research purposes. The Act represents in many respects a compromise of views allowing controlled research for a limited period of time in the early stages of development of the embryo. The Authority issues licences to researchers to undertake such research as falls within the criteria set out in the legislation. Researchers may undertake embryo experimentation if this comes within the criteria set out in the Human Fertilisation and Embryology Act 1990, which includes promoting advances in the treatment of infertility, increasing the knowledge of congenital disease, increasing knowledge about the cause of miscarriages, developing more effective means of contraception or developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation. The Act bans certain forms of experimentation such as keeping or using an embryo after the appearance of the primitive streak (after 14 days of development), placing an embryo in an animal or replacing the nucleus of a cell of an embryo with a nucleus taken from a cell of any person, embryo or subsequent development of an embryo (cloning through nuclei substitution) (s3(3) Human Fertilisation and Embryology Act 1990). As we shall see in Chapter 9, this area is currently under review by the government (Department of Health 2005b). (For general discussion on one particular issue consequent upon such research – cloning, see Chapter 9.)
Xenotransplantation is regulated by the Xenotransplantation Interim Regulatory Advisory Authority (see Ch. 10). Gene therapy is overseen by a specially created government body, the Gene Therapy Advisory Committee, which imposes stringent requirements on researchers. This chapter focuses upon those clinical trials in which nurses are at present most likely to be directly involved, and discusses general principles of research activity on human subjects. As we shall see below, the conduct of most clinical trials is subject to the consideration of non-statutory bodies – local research ethics committees.
Drug trials and innovative therapies
Before medicines are made used in a clinical trial the use must be ‘authorised’ by the Medical and Healthcare Products Regulatory Agency (Medicines for Human Use (Clinical Trials) Regulations 2004, regs 17–21). Although safeguards in the form of licensing exist in relation to experimental drug therapy, there are at present no equivalent safeguards as regards innovative therapy, such as keyhole surgery. It has been suggested that, in view of the fine line between innovative therapy and research, innovative therapy should be classed as medical research in situations in which the main purpose of therapy is to acquire knowledge, as opposed to care for the patient. In the light of much public concern regarding the use of certain new therapeutic techniques, notably keyhole surgery, the government indicated that it was considering the introduction of legislation in this area (The Times, 21 February 1995). The safety of medical interventions is now the subject of consideration by the National Institute for Health and Clinical Excellence (http://www.nice.org.uk/page.aspx?o=whatwedo). NICE undertakes technology appraisals which include the assessment of new surgical procedures. This includes taking into account clinical evidence as to how well the new procedure will work in addition to looking at economic evidence as to the extent to which this can be seen as constituting value for money.
Animal research
The Animals Scientific Procedures Act 1986 states that, before research can be undertaken on animals, researchers must obtain a licence from the Home Secretary. A Home Office committee examines whether the benefits to be gained from research being undertaken upon these animals justify the suffering that may be occasioned. The practice and ethics of these procedures go beyond the scope of the book and the reader is referred to further sources (see, for example, Fox 1995).
REGULATION OF RESEARCH: GENERAL PRINCIPLES
This section considers the basis of regulation of clinical research involving human subjects and legal principles governing the operation of clinical trials, as well as the criteria that the nurse should satisfy before embarking on a clinical trial. The principles of consent to treatment applicable in the context of research are considered, and the particular issues that arise in the context of certain groups of research subjects such as children and adults lacking mental capacity. This section concludes by examining the role and obligations of the nurse researcher on the wards. Issues of confidentiality and research are considered in Chapter 7.
Before a trial is undertaken, the researcher should obtain approval for the conduct of the trial from a research ethics committee. Where the trial concerns medicinal products the Medicines for Human Use (Clinical Trials) Regulations provide that it is an offence to begin such a trial without ethics committee approval (reg 49). The main guidelines governing the operation of such committees are GAfREC (Department of Health 2001). These recommend that there should be a maximum of 18 members (para 6.1). The Committee should have a mixture of ‘expert’ and ‘lay’ members (para 6.3). The expert members should be drawn from persons with:
At least one-third should be ‘lay members’ (Department of Health 2001, para 6.5). Of these GAfREC provides that at least half must be ‘persons who are not, and never have been, either health or social care professionals, and who have never been involved in carrying out research involving human participants, their tissue or data’ (Department of Health 2001, para 6.7). The members of a research ethics committee must act as individuals and not as a representative of the group from which they have been drawn (Department of Health 2001, para 6.8).
• relevant methodological and ethical expertise in:
• clinical research
• non-clinical research
• qualitative or other research methods applicable to health services, social science and social care research
• clinical practice including:
• hospital and community staff (medical, nursing and other) general practice
• statistics relevant to research
• pharmacy (Department of Health 2001, para 6.4).
Multicentred research ethics committees
Although such committees operate predominantly on a ‘local’ basis, in recent years there have been increasing attempts to facilitate consistency in approach. Where it is proposed to undertake a trial over a number of research centres in different parts of the country the proposal should be referred to one of a number of multicentred research ethics committees governing the approval of multicentred trials (Department of Health 2001, part 8.)
Regulation of research ethics committees
Until recently, research ethics committees were not subject to central coordination save through the production of guidelines by the Department of Health. This has, however, changed somewhat. The operation of research ethics committees in England is today governed by the Central Office for Research Ethics Committees (COREC) (http:www.corec.org.uk). From 1 April 2005 the operation of COREC became part of the National Patient Safety Agency (http://www.npsa.nhs.uk).
Assessing the risk
A researcher must satisfy the committee that the project is ethical and that any risk posed to research subjects is of an acceptable level. Factors that the committee must consider include any discomfort or distress the project may cause the research subject, any hazards that may arise during the project and precautions that should be introduced to deal with them, and the extent to which the research subject’s health will be affected by involvement in a trial. The Royal College of Physicians 1996 guidelines state helpfully the following:
What if a volunteer is prepared to accept a risk that is more than minimal of participation in a clinical trial? Some people will take risks of a very high order for altruistic reasons. A person may volunteer to be involved in a trial to help researchers develop a cure for a condition suffered by a close relative. It is unclear whether it is lawful for a research subject to consent to involvement in a very high risk trial. As was noted earlier in relation to consent to treatment, English law does not allow a person to consent to any harm. If a research subject included in a high-risk trial dies, then there is the possibility that a researcher would be prosecuted for manslaughter.
“Benefit may be weighed against risk in two different ways. First and most obviously the patient may benefit. This is typified in a therapeutic trial where at least one of the treatments offered may be beneficial to the patient. Benefits may be considerable, for example, in cancer treatment and may counter balance even high risk to the individual. Second, society rather than the individual may benefit. In such situations however large the benefit to expose a participant to anything more than a minimal risk needs very careful consideration and would rarely be ethical.
Inducements to participate
Many trials are undertaken using volunteers. While some may be willing to give up their time out of altruism, many trials would simply not go ahead unless some inducements were given. A small financial inducement may be given to compensate for time spent and potential inconvenience caused. But while payment of small sums may be acceptable, there is a danger that an unethical researcher may offer large sums to encourage participation in a trial imposing an undue risk. Similarly, some payments to researchers may be unethical.
If the researcher receives payment on the basis that the more patients are recruited the larger the fee, there is a danger that researchers may place undue pressures on patients and others to be included in the research. Nonetheless, the level of any inducement given to the NHS body, health professionals, researchers or subjects to participate in clinical research is a factor that will be considered by a local research ethics committee when considering whether to approve a clinical trial (Department of Health 2001, para 9.15, k). Inducements to research subjects may of course be other than financial. For example, pressure may be put on nurses by nurse researchers to participate in clinical trials because it is something that is expected of them. Such pressure is unjustifiable. It is important to ensure that subjects give full and free consent to entry into any trial.
Consent
As with any clinical procedure, it is vital to obtain consent from a research subject before a trial commences. The nurse may have the task of obtaining a patient’s consent to participation in a trial or, even if not involved in initially obtaining consent, the nurse may be drawn into the process if a patient later approaches her/him and asks questions about the trial. Ensuring that research subjects are given adequate information is an important part of the role of a research ethics committee. What information must be given to the research subject in a clinical trial? A distinction should be drawn between therapeutic and non-therapeutic trials. Therapeutic research is research intended to benefit an individual patient. Non-therapeutic research is research that is unlikely to or will not benefit the research subject (whether a patient or healthy volunteer) personally. The consent guidelines were revised following controversy concerning one particular clinical trial.
In May 2000 the UK government announced that they would be con-ducting a review into the consent process for clinical research in the NHS. This was in response to the study that was undertaken at the North Staffordshire hospital NHS Trust by Professor David Southall. A trial was conducted upon neonates who suffered respiratory failure, considering the effect of treatment using continuous negative extrathoracic pressure rather than standard ventilation. Parents whose two children received the procedure complained. The first died while on a ventilator and 10 months later a second child was discovered to have brain damage. In neither case, it was claimed, had it been explained to the patients that this was an experimental procedure. The review of the trial conducted by Professor Rod Griffiths, a director of public health in the West Midlands regional office of the National Health Service Executive, was highly critical (Griffiths 2000). It stated that ‘the apparent lack of adequate explanation, of choice and consequent properly elicited and recorded consent and involvement in later decision making’ was unacceptable. The professor heading the trial had not ‘ensured that each member of staff who might be involved in the project was trained or supervised to ensure that they were doing what the research project said they should’. The ethics committee that approved the trial was also the subject of criticism. It was claimed that the committee had not examined the proposal sufficiently. In fact, it was the case that failures of management and supervision were, in the view of the report ‘virtually built into the design’. The report commented that: ‘In effect the combination of a slightly complacent local research ethics committee, an enthusiastic and assertive researcher, and a vacuum in research governance in the trust led this trial to run in a less than adequate way’. Both consultants were subject to disciplinary action, and it appears that nurses who were involved in the trial were also subject to investigation by the UKCC. The report has recommended that formal guidance on research governance within the NHS should be developed. Until this is developed at NHS level the report recommended that the Trust should develop its own guidance. They also recommended that there should be cooperation between the Department of Health and professional and regulatory bodies to consult and produce agreed guidelines that clarify issues of consent for participation in clinical trials.
GAfREC requires research ethics committees to consider the informed consent process (Department of Health 2001, para 9.17). It requires that there must be:
“
a. full description of the process for obtaining informed consent, including the identification of those responsible for obtaining consent, the time-frame in which it will occur, and the process for ensuring consent has not been withdrawn
b. the adequacy, completeness and understandability of written and oral information to be given to the research participants, and, when appropriate, their legally acceptable representatives
c. clear justification for the intention to include in the research individuals who cannot consent, and a full account of the arrangements for obtaining consent or authorisation for the participation of such individuals
d. assurances that research participants will receive information that becomes available during the course of the research relevant to their participation (including their rights, safety and well-being)
e. the provisions made for receiving and responding to queries and complaints from research participants or their representatives during the course of a research project.
Information provision and the randomised controlled trial
Providing full information recognises the autonomy of the research subject. Without informed consent, research subjects may not realise that they are being subjected to procedures aimed at benefiting future patients rather than themselves. However, there are certain situations in which researchers may wish to withhold information from patients. Take randomised controlled trials: some patients included in a trial recover not because of the effect of new medication but simply because they think that they have been given a new drug. This is known as the ‘placebo effect’. In an attempt to overcome this problem, researchers undertake randomised controlled trials. Research subjects are divided into two groups: one group is given the treatment, the other is given a placebo or dummy treatment. The patient does not know whether s/he is receiving the real or the dummy treatment. A variant on this is the ‘double-blind’ trial: in this type of trial, neither the clinician nor the research subject knows whether the patient has been given the treatment or an inert substance. It is particularly important for patients to appreciate that they are being entered into a randomised clinical trial and that there is a risk of missing out on a standard course of treatment. When providing information about the trial, researchers must ensure that all subjects are told that they are free to withdraw at any stage.
The law and information provision in clinical research
There are no statutes or decided cases in English law stating how much information should be given to subjects in clinical research. A research subject may claim that provision of inadequate information constitutes the tort of battery. As stated earlier in relation to consent to medical treatment, the courts have stated that as long as a patient gives general consent to an operation being undertaken then health-care professionals will not be liable in battery (Chatterson v. Gerson [1981] QB 432 at 443). But would the same test be applied to clinical research? In the Canadian case of Halushka v. University of Saskatchewan it was held that the failure of researchers to provide the subject with full information constituted a battery, Hall J.A. said: ‘The subjects of medical experimentation are entitled to a full and frank disclosure of all the facts, probabilities and opinions which a reasonable man might be expected to consider before giving consent’ ([1965] 53 DLR (2d) 436 at 438).
It is suggested that the adoption of such an approach, requiring a broad duty of disclosure to those entering a non-therapeutic trial, is desirable. What of patients included in therapeutic trials? The difficulty here is that if patients included in trials had to be given a full explanation this would give such patients the right to receive more information than a patient receiving any other therapy. At present it seems likely that the courts would hold that a patient is entitled to the same level of disclosure whether therapy is given as part of treatment or as therapeutic research.
It may be necessary to undertake research using patients brought unconscious into Casualty who are in a critical condition. Research projects involving such patients should be examined with particular care. If it is possible to anticipate that a patient may be subject to an unexpected event, such as complications during childbirth, then the researchers should obtain the patient’s consent before labour begins.
Duty to inform – negligence
While a research subject may have been given some information as to the trial such that an action in battery may be difficult to establish, a research subject may claim that a researcher acted negligently because inadequate information was provided as to the risks posed by involvement in the trial. In the context of medical treatment, we noted that, while for many years the courts were prepared to hold that a health-care professional was not negligent as long as s/he gave the patient such information as would have been provided by a responsible body of professional nursing opinion (Sidaway v. Bethlem Royal Hospital Governors [1985] AC 871), in recent years the courts have indicated that they may be moving towards a ‘prudent patient’ test (Pearce v. United Bristol NHS Trust (1999) PIQR P53). Does the duty differ in relation to clinical research?
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