Biomedical research ethics

Biomedical research is needed for the development of medicine. It provides the scientific evidence to improve health care by providing knowledge and information on the usefulness and effectiveness of diagnostic, therapeutic and preventive procedures. Moreover, biomedical research contributes to increase our understanding of the etiology, pathophysiology and risk factors of diseases.

In other words, biomedical research is the careful, meticulous, systematic, diligent inquiry or examination of current knowledge, undertaken to establish facts or principles. Researchers strive to better understand the causes of disease, expand knowledge to discover better ways to prevent ill health, and to develop beneficial medications, and procedures to treat and cure diseases and conditions that cause illness and death. For all these reasons biomedical research should be considered a moral obligation for all physicians and health professionals (37% of you answered correctly via the clickers).

Ethical biomedical research encompasses not only the attainment of moral aims or purposes but also the application of morally acceptable means to obtain them. Therefore, scientific rigor is a necessary condition but not a sufficient one; not all what is scientifically feasible may be acceptable from an ethical standpoint.

Ethics is a set of moral obligations that define what is right and wrong in our practices and decisions. Scientists have long maintained an informal system of ethics and guidelines for conducting research, but documented ethical guidelines did not develop until the mid-twentieth century, after a series of well-publicized ethical breaches and war crimes.

 

During World War II, Nazi scientists launched, among others, a series of studies designed to test the limits of human exposure to the elements with the final aim of better preparing German soldiers. For instance, some experiments addressed the effects of hypothermia in humans. During these experiments, concentration camp prisoners were forced to sit in ice water or were left naked outdoors in freezing temperatures for hours. Numerous victims were left to freeze to death while others were eventually re-warmed with blankets or warm water, or underwent experimental rewarming attempts that left them with permanent injuries. War crimes during World War II led to the Nüremberg Code (1947).

In 1932 the U.S. Public Health Service started the “Tuskegee Study”, an experiment on black men in the late stages of syphilis. These men, for the most part illiterate sharecroppers from one of the poorest counties in Alabama, were never told what disease they were suffering from or of its seriousness. They were only informed to be treated for “bad blood”, and their doctors had no intention of curing them of syphilis at all. The experiment was aimed to collect data from autopsies of the participating men, and they were thus deliberately left to degenerate under the ravages of tertiary syphilis, which can include tumours, heart disease, paralysis, blindness, insanity, and death.

The following video summarizes the atrocities of the “Tuskegee Syphilis Study” and has served us to reflect on the ethical implications and consequences.

Infamous cases of fraud and misconduct highlight the need for a system of ethics to ensure proper behaviour and reliable research in science. As a result of the Tuskegee Syphilis Study (1932-1972), the U.S. Congress passed the National Research Act in 1974. The Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to oversee and regulate the use of human experimentation and defined the requirements for Institutional Review Boards. To assure that research is conducted in accordance with basic ethical principles, the Commission considered:

1. the boundaries between biomedical and behavioral research and the accepted and routine practice of medicine,
2. the role of assessment of risk-benefit criteria in the determination of the appropriateness of research involving human subjects,
3. the establishment of appropriate guidelines for the selection of human subjects for participation in such research, and
4. the nature and definition of informed consent in various research settings.

The Belmont Report

The work of the National Commission led to The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research which was presented in 1978 and published in 1979 that states that “persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well being”. The Belmont Report summarized and defined the basic ethical principles of respect, justice and beneficence, thereby representing the origins of modern research ethics.

 
Basic Ethical Principles

1. Principle of autonomy: recognizes the rights of individuals to self-determination. The respect for persons incorporates at least 2 ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection.
This principle of respect for persons thus translates into two separate moral requirements:
(i) to acknowledge autonomy and
(ii) to protect those with diminished autonomy.
To respect autonomy is to give weight to the person’s autonomous considered opinions and choices while refraining from obstructing their actions unless they are clearly detrimental to others. Withholding information necessary to make a considered judgment, when there are no compelling reasons to do so represents a lack of respect.

However, it has to be highlighted that not every human being is capable of self-determination. The capacity for self-determination matures during an individual's life, while some individuals lose this capacity wholly or in part as a consequence of illness, mental disability, or circumstances that severely restrict liberty. Respect for the immature and the incapacitated requires protecting them as they mature or while they are incapacitated. Respect for persons demands that subjects enter into the research voluntarily and with an adequate information (informed consent).

2) Principle of justice: refers to the ethical obligation of fairness and equality in health resources and treatment. The conception of justice is especially relevant to protect vulnerable groups. In this regard, the selection of research subjects needs to be scrutinized in order not to be discriminatory. It should be determined whether some classes (e.g., welfare patients, particular racial and ethnic minorities, or persons confined to institutions) are being systematically selected simply because of their easy availability, their compromised position, or their manipulability, rather than for reasons directly related to the research condition being studied. Furthermore, justice demands that when research leads to the development of therapeutic devices and procedures, these not provide advantages only to those who can afford them as well as that such research should not unduly involve persons from groups unlikely to be among the beneficiaries of subsequent applications of the research.

3) Principle of beneficence: means the obligation to act in the best interest of patients maximizing possible benefits and minimizing possible harms. Individuals are treated in an ethical manner not only by respecting their decisions, but also by making efforts to secure their well-being. This principle establishes the need to carefully evaluate the risk-benefit relation; learning what will in fact be beneficial may require exposing persons to risk. The imperative posed by this principle is to decide when it is justifiable to seek certain benefits despite the risks involved, and when the benefits should be foregone because of the risks. Moreover, this principle implies the professional competence of the researchers involved to warrant maximization of benefits and the reduction of risk that might occur from the investigation.

The concept of non-maleficence considers that it is more important not to harm your patient, than to do them good; this is embodied by the Latin expression “primum non nocere”, "first, do no harm".

The Declaration of Helsinki

The Declaration of Helsinki represents one of the most relevant documents in the history of research ethics as the first significant effort of the medical community to regulate research itself. With the primary purpose to set international ethical principles for research involving human participants the World Medical Association (WMA), the Declaration of Helsinki was originally enacted in 1964 and forms the basis of most subsequent documents. It has undergone various revisions (the most recent at the General Assembly in October 2013) since its first promulgation. Given that 2014 marked the 50th anniversary of the Declaration of Helsinki, the WMA developed its eighth version of the Declaration updating and revising the 2008 version with the core aim of the working party to preserve the unique character and status of the document. The first draft was out for public consultation until June 15th, 2013 while the final revised and updated version was published in JAMA in November 2013. Major changes with respect to the 2008 version were carried out regarding both its structure and content. Noteworthy, the duty of physicians expands not only to promote and safeguard health but also well-being. The articles pertaining to vulnerable populations have also been changed to better capture several important ethical principles. Although the WMA has been congratulated for the work performed and the transparency of the process, it was agreed that the declaration has not undergone radical change representing “an evolution rather than a revolution”. Additional distinctive aspects contemplated in the 2013 version include appropriate access of underrepresented groups to participation in medical research, the need for compensation for study participants who are inadvertently harmed, and attempts to further clarify the role of placebos, the need to register every study involving human subjects in a publicly accesible database before recruitment of the first subject, provision for post-trial arrangements in advance of study start, and the ethical obligation to publish and disseminate the study results, even if they are negative or inconclusive.

• Understand and remember the basic ethical principles of respect, justice and beneficence derived from the Belmont Report.
• Study in detail the 2013 revision of the Declaration of Helsinki together with the changes introduced as compared to the 2008  version (pdfs available at ADI).
• Learn the characteristics and content of the written informed consent.