Informed Consent In Clinical Trials

By Jan Sleigh, Senior Research Nurse

A BRIEF HISTORY OF INFORMED CONSENT

Informed Consent is:

‘The process of agreeing to take part in a study based of access to all relevant and easily digestible information about what participation means, in particular, in terms of harms and benefits’[1]

‘A fundamental principle underlying ethical practice is Informed consent ’ [2]

The Nuremberg code of 1947 is generally regarded as the first document to set out ethical regulations in human experimentation based on informed consent. New research, however, indicates that ethical issues of informed consent in guidelines for human experimentation were recognised as early as the nineteenth century.

First Prussian directive on informed consent 1891

In 1891 the Prussian minister issued a directive to all prisons that tuberculin for the treatment of tuberculosis “must in no case be used against the patient’s will.” [3]

The Neisser Case 1898

In 1898 Albert Neisser, discoverer of the gonococcus and Professor of dermatology and venereology at the University of Breslau, published clinical trials on serum therapy in patients with syphilis. In order to find a method of syphilis prevention he injected cell free serum from patients with syphilis into patients who were admitted for other medical conditions. Most of these patients were prostitutes, who were neither informed about the experiment nor asked for their consent. When some of them contracted syphilis Neisser concluded that the “vaccination” did not work. However, he argued that the women did not contract syphilis as a result of his serum injections but contracted the disease because they worked as prostitutes.

In 1898 the public prosecutor investigated the case, and Neisser was fined by the Royal Disciplinary Court. The court ruled that, though Neisser as a well known medical authority may have been convinced that the trials were harmless, he should have sought the patients’ consent. Not questionable science, but lack of patients’ consent was the main principle for the legal judgment.

Reich 1931

Because of criticism of unethical human experimentation in the political press and in parliament as well as in the context of a political reform of criminal law in Germany, in 1931 the Reich government issued detailed “guidelines for new therapy and human experimentation”. The guidelines clearly distinguished between therapeutic (“new therapy”) and non-therapeutic research (“human experimentation”) and set out strict precautions. Without exception non-therapeutic research could be performed only with the subject’s informed consent, therapeutic research could be performed without explicit consent but only in a medical emergency and if it was deemed to be in the patient’s best interest.

The Nuremberg Code 1947

A well-known chapter in the history of research with human subjects. An American military tribunal opened criminal proceedings against 23 leading German physicians and administrators for their willing participation in war crimes and crimes against humanity. Among the charges were that German physicians conducted medical experiments on thousands of concentration camp prisoners without their consent. Most of the subjects of these experiments died or were permanently crippled as a result.

As a direct result of the trial, the Nuremberg Code was established in 1948, stating that “The voluntary consent of the human subject is absolutely essential,” making it clear that subjects should give consent and that the benefits of research must outweigh the risks.

Although it did not carry the force of law, the Nuremberg Code was the first international document which advocated voluntary participation and informed consent.

Declaration of Helsinki 1964

In 1964, the World Medical Association established recommendations guiding medical doctors in biomedical research involving human subjects. The Declaration governs international research ethics and defines rules for “research combined with clinical care” and “non-therapeutic research.” The Declaration of Helsinki was revised in 1975, 1983, 1989 and 1996 and is the basis for Good Clinical Practices used today.

The National Research Act 1974

The U.S. Congress signed the National Reseach Act into law, creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission was charged with:

Identifying the basic ethical principles that should govern medical research involving people, and then recommending steps to improve the Regulations for the Protection of Human Subjects.

The Belmont Report 1979

After four years of work, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research issued “The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research.” The report sets forth three principles underlying the ethical conduct of research:

  1. respect for persons: recognizing the
    autonomy and dignity of individuals, and the need to protect those with
    diminished autonomy (i.e., impaired decision-making skills), such as
    children, the aged, and the disabled;
  2. beneficence: an obligation to protect
    persons from harm by maximizing benefits and minimizing risks;
  3. justice: fair distribution of the
    benefits and burdens of research.

The Belmont Report explains how these apply to research practices; for example, it identifies informed consent as a process that is essential to the principle of respect. In response to the report, both the U.S. Department of Health and Human Services and the U.S. Food and Drug Administration revised their regulations on research studies that involve people.

DEFINITION OF INFORMED CONSENT 

Informed Consent for a Clinical Trial involves two essential parts

A  Process  and A Document

Clinical trial participants are asked to agree to the proposed study care plan in writing. This is called informed consent.

The main purpose of the informed consent process is to communicate to the purpose of the study, its risks and benefits, the alternatives, what would be expected of the participant. The participant has the right to make decisions about their own health and medical conditions.

If a physician suggests a clinical trial that a participant is eligible for, meeting the inclusion and exclusion criteria, the participant will need information in order to make a decision about whether to participate in the trial.

The Informed Consent Process involves a discussion between the research team and the participant. It involves a nurse or doctor explaining the details and the facts about the trial, to enable the participant to decide whether or not to take part. It should take place in an unhurried, private atmosphere where the participant has time to review the document and ask questions. The process is based on complete disclosure of the facts. During this process, the study coordinator or principal investigator should endeavour to establish a rapport and trusting relationship with the potential participant and they should be approached in a respectful manner with the person obtaining consent introducing themselves by name. The participant is given the opportunity to ask questions and raise any concerns. It is a continuing process throughout the trial providing updates and any new information that may influence the participant s continuation in the trial.

The Informed Consent Documents include an information sheet and a consent document. The information sheet contains comprehensive details of the trial and the treatment including rationale for the trial, expected duration, possible risks and benefits, proposed procedures, as well as adverse effects, using simple language and a format that is clear and understandable for potential research participants. The consent form provides a space for the subject and the investigator to sign to confirm the informed consent process. The coordinator or investigator should thoroughly review each section of the informed consent and information leaflet with the participant.

The researcher should determine the ability of the potential participant to understand the information and give consent before proceeding further. The idea is not to coerce but to provide the participant with the facts. The informed consent document is a signed, legal document. It should be read carefully and fully understood before signing.

Special attention must be given to meeting the needs of vulnerable populations such as children, the critically ill, or the mentally impaired.

Informed consent is not a contract and a participant may withdraw from a trial at any time, and without any reason, without it compromising the participant’s future treatment.

 

[1] Parahoo K (2006) Nursing research: principles, process and issues (2nd edition), Basingstoke: Palgrave Macmillan.

[2] Dobson C (2008) Conducting research with people not having the capacity to consent to their participation: a practical guide for researchers, Leicester: British Psychological Society.

[3] Official Regulations as to Tuberculin in Germany and Italy.JAMA 1891;16:492.(Original German publication:Ministerial-Blatt fur
die gesamte innere Verwaltung in den Koniglich Preu(beta)ischen Staaten 1891;52:27.)

[4] A Guide to understanding Informed Consent; The National Cancer Institute. www.cancer.gov (accessed Sep 2009)

 

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