A general introduction to Biomedical Research Ethics

This article is part of the network’s archive of useful research information. This article is closed to new comments due to inactivity. We welcome new content which can be done by submitting an article for review or take part in discussions in an open topic or submit a blog post to take your discussions online.

Ethical Theory

There are four main ethical theories that form the basis of research ethics:

1. Utilitarianism: The Greatest Good

o Argues that the consequences of an action make that action either moral or immoral.
o An action that leads to beneficial consequences is right or moral; one that leads to harmful consequences is wrong or immoral.
o Known as a consequentialist theory.

2. Kantian Ethics: Duties and Rights

o Argues that the consequences of an action are irrelevant to a moral evaluation of that action.
o It is the motivation behind an action that matters. Actions that are moral are those that are undertaken out of a sense of duty.
o One does it because it is the “right thing to do.”

3. Rawlsian Ethics: Justice or Fairness

o Justice is another important ethical standard.
o Justice involves protecting individual rights, or preventing an injustice to an individual.
o Requires us to compare cases to avoid discriminating or treating people differently that are alike in relevant respects.
o Means treating people fairly.

4. Aristotelian Ethics: The Virtuous Life

o Virtues enable human beings to act in accordance with our “essence” or human nature. The thing that distinguishes humans from all other creatures is our ability to reason.
o Asks what kind of character a person must have to be a moral human being.
o A lifetime of virtuous living and avoidance of vice forms a morally virtuous character.
o A good character is an achievement, not a natural endowment.

What is the role of ethics in research with human participants?

The objective of research is to develop generalizable knowledge to improve mankind. The aims of research are recognized as being good, but research has the potential to inflict harm and to treat participants as just a “means to an end”. Therefore, the role of ethics is to ensure that participants are treated with dignity and respect while they contribute to the social good. Ethics may help us find the ‘least harmful’ route. By protecting participants from harm and promoting their welfare, ethics acts to restrain science from a too utilitarian approach. However, ethics also promotes good science as participants who feel respected may: Actively engage with research requests, answer truthfully, provide critical & honest feedback and return for follow up – therefore increasing the quality of the data.

What are the key principles in research ethics?

NON-MALEFICENCE: “Do no harm”

There should be no intentional injury or harm to participants as a result of participation; researchers are obligated not to deliberately harm participants.

BENEFICENCE:

Minimize potential harms & maximize expected benefits of the research.
Researchers should take active and positive steps to reduce possible harms to a minimum and to maximize anticipated benefits of the research. In some research there may be no direct benefit for the participant, but benefits to society in terms of important knowledge.

RESPECT FOR AUTONOMY: “self-rule”

A person’s freedom of thought and action should be respected and researchers must respect the rights of participants who can make decisions to do so. Researchers must take special measures to protect vulnerable participants whose freedom to make choices is limited, or those with no capacity to choose.

JUSTICE: Fair balance of risks and benefits

Those who stand to benefit from research must contribute to its risks and discomforts. No group of persons should be asked to bear more than their fair share of the burdens of research; no group (e.g. impoverished) should be asked to bear research risks in order that others (e.g. the wealthy) enjoy benefits (new knowledge or products); no group should be deprived of fair access to the benefits of research and no class of person should be unfairly excluded from research (e.g. women) as this denies them relevant knowledge or health interventions.

What makes research ethical?

Community participation

Community participation is based on the right and responsibility to participate in research development activities and it can also offset potential vulnerabilities. It may often include the formation of a Community Advisory Board (CAB) that gives inputs to design (e.g. IC), advises on cultural conventions and expectations and evaluates the impact of the research. Community participation should be based on a genuine partnership geared towards mutual respect, education and consensus building.

Benefits of community participation include: Enhanced cultural appropriateness, increased acceptability of the research to the participating community, fairness and equity regarding important decisions (e.g., adequate incentives) and sound bi-directional information exchange. A good example is HIV vaccine trials in South Africa where community structures are being formed at trial sites (e.g. Gauteng CAB and interim DBN CAB).

However, community participation is not without its complexities: How do you define community - which stakeholders and interest groups must be represented? There may be difficulties in ensuring mandated representation. How do you define participation and at what level and depth should the community participate – at a level of receiving education and information or becoming full and equal partners involved from protocol development to dissemination of results?

Social or scientific value

To be ethical, research must be valuable and society should gain important generalizable knowledge. Researchers cannot expose human beings to inconvenience or risk of harm without possible benefit to society.

Validity

Even a valuable question can be poorly researched, resulting in unreliable data. Research must also be well designed and conducted (e.g. clear aims, rigorous design, adequate sample, adherence to GCP, sound data analysis). Poorly designed and conducted research is unethical as it exposes subjects to risks and inconvenience for no purpose.

Fair choice of participants

Selection of participants should be fair and just. Participants should be chosen according to the scientific goals of the study and not for non-scientific reasons e.g. it is not acceptable to select participants because they are convenient, or vulnerable, or less able to protect their rights.

Additionally, participants should not be excluded from research without sound justification e.g. children from remote schools should not be excluded due to remoteness. A challenge for researchers is to address potential misperceptions that vulnerable individuals and communities will be unjustly targeted and to demonstrate safeguards that will be taken to offset specified vulnerabilities. This is important in international collaborative research between developed and developing countries.

Volunteers should be chosen to minimize risks. It is possible that potential participants will be eligible for scientific reasons but they may be at substantially higher risk of harm e.g. impoverished and vulnerable to undue inducements. The“Rule of thumb” is that researchers should avoid involving the vulnerable when less vulnerable persons could be involved, that they must justify why vulnerable persons are included and articulate safeguards to minimize risks for vulnerable persons and communities (SA-MRC, 2002).

Individuals and communities should be selected so that the benefits and burdens are fairly distributed. Individuals and groups who bear the burdens of the research should share its benefits (new knowledge or products). Therefore, all effort must be made to convert research findings (if they are sound) into practice - it is not only the policy planners’ prerogative.

Favorable risk- benefit ratio

The potential risks to individual participants must be identified and minimized and the potential benefits of the research must be identified and maximized. After weighing up the risks and benefits, the potential risks to individual participants should be outweighed by the benefits to the individual - or society i.e. a favorable risk-benefit ratio.

Measures must be taken to minimize risk. For example, in a trial to find out the best method to teach English among schools: Both urban and rural schools must be in the sample, if one method is superior but cannot be implemented due to lack of resources and political will that method should not be blindly recommended, if the good method does not take adequate consideration of the economically disadvantaged children it should be stated and not recommended and if the trial shows one method is seriously flawed remedial action should be taken without compromising the research.

Who decides if the potential risks to individual subjects are outweighed by the benefits to the individual or society? It is the responsibility of Research ethics committees at every participating institution, participating communities via establishment of representative participatory structures and each and every individual via informed consent.

Securing access to successful trial products is a way of maximizing the benefits to the individual or society. A good example is the South African AIDS Vaccine Initiative who are making plans to ensure that once a successful vaccine is developed that it will be accessible and affordable to South Africans. Other examples include the AlphaVax – IAVI agreement that spells out commitment to pricing close to cost if licensed.

One potentially difficult area when considering the benefits to risk ratio is the use of placebo controls. This stems from the feelings that a placebo can be deceptive and may appear to consign the placebo group to an “unfair disadvantage”. However, placebo controls may be regarded as acceptable if “clinical equipoise” exists (i.e. there is uncertainty over whether a treatment will be effective), if there is no comparator or if current assays do not permit a useful comparison.

Independent review

Researchers operate at the interface of multiple obligations and interests including undertaking research, publishing findings, acquiring funding, furthering their careers and protecting human subjects. These conflicting interests can potentially bias how researchers perceive their research designs and conduct research. For this reason research should be reviewed by persons independent of the research (“at arm’s length”).This is the responsibility of Research Ethics Committees who must be sufficiently competent and confident to review complex designs.

The review process examines the scientific and ethical quality of the research, minimizes conflicts of interest, and aims to ensure that participants are protected and treated with dignity. In upcoming phase I HIV vaccine trials, the protocols must be reviewed and approved by the FDA in the USA, the MCC in South Africa and ethics committees at every participating institution (E.g. Nelson Mandela REC, Wits REC, MRC REC and Institutional Review Boards in the USA).

Informed consent

Research participants have a right to freely choose whether or not to participate based on an understanding of all relevant information. This ensures that participants will only take part if the research is consistent with their interests, values and preferences (autonomy). However, it can often be easier to assert than to assure in developing country contexts (Emanuel, E., Wendler, D. & Grady, C., 2000).

Generally, informed consent has four key components: Disclosure of information, comprehension or understanding, voluntariness or freedom and explicit formal consent.

1. Information

Participants must be informed of the aims, purpose and duration of the study, the methods to be used (e.g. randomization, placebo, blinding), practical aspects (VCT, tests, visits, use and storage of tissue samples, etc.), potential risks (e.g. trial related discrimination), expected benefits (e.g. counseling), the right to withdraw, compensation for research related injury, confidentiality (and limits if any) and personal implications.

However, transmission of complex information, compounded by language differences and problems with translation, can make this information sharing difficult. Information transmission is typically viewed as a one way process, whereas it is best conceptualized as bi-directional, in that researchers and counselors should make every effort to hear the expectations and motivations of potential participants. The content of “what” must be transmitted is governed by disclosure requirements, but should also be supplemented by recommendations from community representatives and it should be constantly assessed.

2. Comprehension

Disclosure is not sufficient alone; participants’ comprehension must be ensured and assessed. However, there are many complexities that make understanding hard to assess:

a) Social desirability: The tendency for potential participants to make a decision based on the desire to avoid the disapproval of researchers or peers. This impacts on reported understanding.

b) An overemphasis on understanding of technical aspects (e.g. placebo) and less on understanding of implications for a participant’s personal and social life.

c) “Tests of understanding” may emphasize technical aspects and assess short-term memory but not actual understanding of the personal consequences.

These difficulties can be overcome by researchers and counselors enhancing comprehension through creating an optimal environment for decision making (vs. “consent counselling”), ensuring the use of counselors with a “values match” to potential participants, encouraging dialogue and discussion with family, allowing time to reflect, being sensitive to the process aspects of counseling (e.g. social desirability, non-verbal cues) and using multiple methods of assessing comprehension.

3. Voluntariness

Participants must be free to choose whether or not to participate and be free of coercion (threat of negative sanction) or undue influence to participate such as using excessive incentives that pressure the participant to volunteer against their better judgment. Special care must be taken with participants who are considered vulnerable and therefore constrained in their ability to make free choices. Researchers can promote participants’ freedom by:

a) Adequate assessment of specific vulnerability factors and attempting to offset them. E.g. education to offset lack of familiarity with research; avoiding undue incentives to offset impoverishment.

b) Providing participants with ways to voice concerns and monitor the impact of participation. E.g. CABs; trial site counselors.

c) Reminding participants of the right to withdraw.

Current SA-MRC guidelines (2002) provide strict conditions for the participation of minors. Minors can only participate in non-therapeutic research if:

a) They will be exposed to no or negligible risk of harm (commensurate with daily life in a stable society or routine psych or medical exams).

b) The same research could not be done equally well on adults, and the results will be valuable for minors.

c) Consent of the parent or legal guardian and assent of the minor child is obtained.

d) Assent of the child.

4. Formal explicit consent

Participants must indicate their consent in an explicit manner through signing a written consent form. However, indemnity driven consent forms may be long or unwieldy and written consent forms are sometimes seen as substitute for the bidirectional process. The essential obligation is for researchers to empower participants to make decisions and create the conditions where participants can make decisions in their best interests. (SA-MRC, 2002, Lindegger, G. & Richter, L., 2000).

A further complication around informed consent is the issue of communitarian cultures; some argue that it is inappropriate to secure first person consent (‘imperialism”) and that legitimate parties such as husbands and traditional leaders can give proxy consent for women. However, first person informed consent is the best safeguard against potential exploitation and therefore the substantive principle must apply. A solution can be found by demonstrating respect for multi-person involvement through procedural implementation of consent e.g. endorsement of the community leader to enter the community and respecting participants’ choice to involve significant others.

Respect for dignity

Once enrolled, researchers should respect the dignity of participants in an ongoing manner by respecting their right to withdraw at any time (“revocable”), monitoring their welfare throughout the research (ongoing social harm monitoring or “social impact analysis” and Data Safety and Monitoring Boards), informing volunteers of research results and respecting confidentiality of freely volunteered data. Confidentiality minimizes the risk of harm (e.g., stigma if HIV testing is involved) and respects participants’ rights to choose to whom and what personal information is disclosed. Participants must consent to the ways in which confidentiality will be maintained (e.g., using codes instead of identifiers and restricted access to data), how the results will be published and any limits to confidentiality where these apply.

Authors: Sisira Siribaddana, Doug Wassener.This article was developed by Sisira Siribaddana and draws from a presentation by Doug Wassener.

For a free a Free online course on "Introduction to Research Ethics" visit http://www.ccghe.jhmi.edu/CCG/distance/HIV_Courses/

This article originally appears on the Global Health Trials resources. Please visit us for more resources relating to trials.