Clearly, the ethical treatment of animals and humans taking part in experimental research is a moral obligation of every researcher. But scientists are typically not formally trained to fully appreciate some of the finer points that must be handled in order to avoid unintended physical or (for humans) psychological harm. As a result, guidelines for the treatment of human and animal participants in research studies have been developed at the national level and implemented with great care at the local level throughout the country.
For animal experiments, the guidelines focus on maintaining clean caging and appropriate feeding and most importantly on avoiding unnecessary pain and suffering. For example, in studies using mice to study treatments for cancer, tumors are not allowed to grow beyond the point that causes the animal to suffer. Such guidelines become much stricter than this bare-bones standard when larger mammals are used. Animal research remains a controversial practice with some believing such research should be banned entirely and others arguing that the benefits to humans provides the ethical underpinning for this type of research.
With human subjects, the guidelines are precise and strict and based on an ethical consensus developed over many decades - partly in reaction to questionable experimentation done in the past.
Institutional Review Boards
Each institution receiving federal money to conduct research must establish an Institutional Review Board (IRB) made up of a diverse group of scientists and community members to evaluate the ethical conduct of research conducted there (Institutions not receiving federal dollars must still follow the basic guidelines and make alternate arrangements for an independent evaluation of their research practices). The IRB is charged with ensuring that every research study must be planned:
- To avoid physical or psychological risks to subjects and to be sure those risks are reasonable given the potential benefits to the subject and to the importance of the knowledge gained by the experiment.
- To ensure the voluntary nature of participation.
- To ensure that the risks and benefits of research are shared equitably by different groups in society.
- To protect vulnerable populations who may not have the full capacity to balance the risks and benefits to themselves such as children and the mentally disabled.
- To be sure that Informed Consent is given by every subject that describes in plain English
- the research and what is requested of the subjects,
- anticipated risks and potential benefits,
- alternatives to participation,
- provisions maintaining the subject’s privacy and confidentiality of records, and
- the right to leave the study at any time without any detriment to the subject.
The Informed Consent must be documented.
From time-to-time there might be a conflict between maintaining these ethical standards and what might constitute the best way to gain scientific knowledge. In such cases the ethical considerations must always take precedence.
Example 11.4: Ibuprofen Cream Study Section
Ibuprofen is a leading analgesic and is sold over the counter in a variety of forms to take orally (e.g., in capsules, tablets, and as a liquid). In Europe, Ibuprofen is also available as a gel or cream to apply topically to a sore area, but this form has not yet been approved by the Food and Drug Administration (FDA) in the United States. How should a research study be designed to demonstrate the effectiveness of ibuprofen cream in reducing muscle soreness?
The Statistical Design
The study involved a resistance exercise of the type commonly done in a gym or health club. Previous work by researchers at the University of Massachusetts provided a detailed model for the time course of muscle function and other physiologic reactions to temporary muscle damage due to strenuous exercise. The soreness will reach its peak between 36 hours and 72 hours post-exercise and will subside within a couple of days. Since "soreness" is a difficult concept to quantify, several response variables were used (e.g. a Visual Analog Scale where subjects are asked to point to a spot along a line labeled 0 at one end and 100 at the other corresponding to their level of pain/soreness and told 0 = no pain and 100 = excruciating pain). The study used a matched pairs randomized controlled double-blind strategy. An arm was randomly selected and used in the exercise regime. 48 hours later either the ibuprofen cream or a placebo cream was randomly selected to be applied to the sore muscle in the arm. Soreness levels were measured pre-treatment and every hour for several hours and then each day for several days after treatment. Several weeks later, the opposite arm was exercised and the opposite treatment was used. The analysis could then compare the time course of soreness relief within the same subject. Altogether, full data were obtained on 106 subjects.
Adding Ethical Considerations
The IRB at the University of Massachusetts Amherst approved the written informed consent document used in the ibuprofen cream study. Note the importance for the IRB to have general community representatives on the board to be sure that the instructions and explanations given in the informed consent document were written in plain English and free of scientific jargon. The IRB needed to be sure that the subjects knew what they were volunteering to do: complete an exercise program that would leave them sore - perhaps even very sore - for a few days with little benefit to themselves but of possible benefit to society.
To increase recruitment, many researchers would like to provide a monetary incentive for participation. But this can create a coercive effect, especially on poorer subjects who may wish to end their participation in a research project but can not because of worries about losing the financial incentive. Large incentives violate the ethical principle of participation being completely voluntary. In the ibuprofen trial, subjects were reimbursed for all expenses and provided with meals during their time being measured. As part of being recruited, they also received a free exercise program at a gym (but signing up for the experiment was not a requirement of receiving that benefit) and they received a small amount of money for participating (but could keep that money regardless of whether they decided to leave the experiment early or not).
Avoiding Harm to Subjects
In the ibuprofen study subjects, over 45 years old were given a physical examination by a doctor to be sure they were inadequate health to participate in an exercise regime. All subjects were evaluated for conditions that might make the experiment a danger to them. For example, people with skin conditions or allergies that might be affected by the cream were not asked to participate and women would not be allowed to participate if they were pregnant. A follow-up visit ten days after the exercise regime was provided to be sure that all subjects were completely pain-free at that time and without any adverse residual effects of having participated. Finally, the exercise regime itself was designed to produce only moderate soreness. If the regime created severe pain then the subject would be treated by a doctor immediately and would not be randomized into one of the experimental conditions (this did not happen to any of the subjects taking part - but such backup plans are important to experimental planning).
Ensuring Voluntarism of Participation
As noted above, all researchers must let the subjects know that they can withdraw from participation at any time and for any reason without prejudice. The researchers in the ibuprofen trial added that if a subject decided not to continue their participation for any reason, they would still be provided with free medical care (if they desired) to help them alleviate any residual discomfort that might have been caused by their initial participation.