PROGRAMA GUÍA DE TRABAJO Objetivos
3. DESARROLLO EXPERIMENTAL DE FUERZA ELECTRICA
According to the Common Rule, one way an investigator may intervene on research subjects is by manipulating their environment. With respect to healthcare CRTs, Mann and Reyes5 have interpreted this to mean that an intervention designed to alter a healthcare professional’s practice pattern represents a manipulation of the environment of all patients whose care may be influenced by a professional’s participation in a CRT. Thus, according to Mann and Reyes, every patient of a professional whose care may be influenced by a CRT intervention meets the regulatory definition of a research subject. This claim is
understandable, given that much of the literature on the ethics of CRTs assumes that cluster members (in this case, patients) will necessarily be subjects16,22-25. If correct, their view has considerable implications for the conduct of CRTs. If, in CRTs targeted at health
professionals or health systems, all patients are considered research subjects, the administrative burdens associated with protecting patients as research subjects would threaten the feasibility of many trials. We explore below whether the indirect effects of a research intervention at the group level (such as an educational intervention administered to
health professionals) implies that all individuals within the group (such as the patients of professionals participating in a CRT) must be considered research subjects.
1. Can environmental manipulation make an individual a research subject?
The CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects14 includes in its definition of research any study that manipulates an individual’s social or physical environment, including field studies of pathogenic organisms or toxic chemicals. These guidelines, along with the CIOMS International Ethical Guidelines for Epidemiological Studies17, address issues of informed consent in epidemiologic research and the analysis of harms and benefits for such research. Therefore, without actually defining “research subject” the CIOMS guidelines appear to acknowledge that individuals who may be affected by public health interventions that manipulate the environment such as water fluoridation or pesticide use are, in fact, research subjects14,17.
A broad interpretation of “environmental manipulation” is untenable, however, because it leads to absurd conclusions. It seems impossible that everyone whose environment is manipulated in the context of a research project must be considered a research subject. The term “environment” refers to “the surroundings or conditions in which a person, animal, or plant lives or operates”26. Using this definition, “manipulations of the…subject’s environment” would imply that every person on Earth is a research subject in every research study. For example, studies in particle physics at the Large Hadron Collider (LHC) meet the Common Rule definition of research, in that they are systematic investigations designed to develop generalizable knowledge8. One concern
regarding the LHC project was that some experiments could create microscopic black holes that might be hazardous to the planet and all of its inhabitants27. If we were to employ a broad interpretation of “manipulations of the…subject's environment”, the Common Rule would require that particle acceleration experiments at the LHC be considered a
manipulation of the environment for all human beings, meaning that everyone on Earth must be considered research subjects. This notion seems patently absurd. We therefore require a better understanding of what environmental manipulations are sufficient to make an individual a research subject.
It is helpful to consider what the US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research may have meant when they included “environmental manipulation” in their definition of a research subject. In a paper prepared for the National Commission in 1975 (included in the 1979 Appendix to the Belmont Report), Robert Levine defined research as “…manipulation, observation, or other study of a human being--or of anything related to that human being that might subsequently result in manipulation of that human being--done with the intent of developing new
knowledge and which differs in any way from customary medical (or other professional) practice.”18 Specific reference to manipulation of an individual’s environment did not appear until the National Commission defined a research subject in their 1978 Report and Recommendations on Institutional Review Boards, and this language was incorporated into the Common Rule28. The Common Rule’s reference to manipulation of an individual’s environment took the place of Levine’s “anything related to that human being that might subsequently result in manipulation of that human being.” Exploring the reasons for this
change in regulatory language helps to clarify what kinds of environmental manipulation are sufficiently meaningful to consider an individual a research subject.
Given the sorts of issues being discussed in the research ethics literature at the time, it seems likely that the National Commission was seeking to protect individuals who
participated in studies evaluating the psychological effects of various environmental
stimuli. Inclusion of environmental manipulation in the definition of research subject seems intended to capture research that deliberately manipulated subjects and placed their welfare at risk without direct intervention or physical contact from investigators.
Examples of this type of research include studies examining the psychological and behavioural effects of habitation in simulated fallout shelters sponsored by the US Office of Civil and Defense Mobilization29, and studies evaluating the psychological effects of other environmental manipulations such as sensory deprivation30,31. Environmental manipulations in the Civil Defense studies includes such things as living in a confined space for prolonged periods, crowding, variable air quality, variable availability of potable water and exposure to variations in temperature. The individuals participating in these studies were subjected to physical or psychological discomfort resulting from the manipulation of their environment in the context of a research study. What these studies have in common, then, is that the study interventions placed the welfare of the subjects in jeopardy by manipulation of their environment rather than via direct intervention or physical touching by the investigators.
These practices support a narrower reading of the environmental manipulation clause. We suggest that environmental manipulation must have a direct impact on an individual in order to make him or her a research subject. In other words, the environmental
manipulation must be designed to produce a direct effect on the individuals whose
environment is being manipulated. We believe that this interpretation is consistent with the intent of the National Commission. We will therefore expand our definition of “research subject” to include any individual who is deliberately affected via manipulation of his/her environment by an investigator (Box 1).
This conclusion is consistent with the language enshrined in the Final Report of the National Bioethics Advisory Commission. In their 2001 Report and Recommendations: Ethical and Policy Issues in Research Involving Human Participants, the Commission agrees that the term “subject” “…connotes the fact that the individual is ‘subjected’ to an action by the investigator.”32 The Commission specifically recommends that “…Research be considered to involve human participants when individuals 1) are exposed to
manipulations, interventions, observations or other interactions with investigators or 2) are identifiable through research using biological materials, medical and or other records, or databases.”32
2. Do indirect effects of CRT interventions on health professionals or health systems make patients research subjects?
Mann and Reyes have construed a change in physicians’ practice patterns that result from educational or quality improvement interventions in a CRT to be a manipulation of
their patients’ environment, therefore requiring those patients to be considered research subjects5. We respectfully disagree.
First, in order to turn an individual into a research subject, the environmental
manipulation must be designed to produce a direct effect on that individual. This is not the case in CRTs that intervene on health professionals. The CRT design is chosen because the interventions under study are cluster-level interventions. The interventions being evaluated in these studies are intended to change health professionals’ behaviour by increasing professionals’ use of evidence-based strategies to improve care. Patients are not being directly manipulated by interventions administered to their health professionals.
Second, even if a change in a professional’s practice pattern did constitute a deliberate manipulation of patients via a manipulation of their environment (a claim that we do not grant), that manipulation does not jeopardize patients’ interests and is therefore not sufficient to warrant considering patients as research subjects. Examining the
distinction between clinical research and clinical practice is again helpful with respect to this issue. Levine writes,
“If a physician proceeds in his interaction with a patient to bring what he considers to be the best available technique and technology to bear on the problems of that patient with the intent of doing the most possible good for that patient, this may be considered the pure practice of medicine. By contrast, if a physician interacts with an individual with the intent of developing new
knowledge (not primarily for the benefit of that individual), this activity may be classified as research.”18
When a health professional participates in a CRT, her patients may still fully entrust their welfare to her because she has no conflicting obligations to the trial itself. Physicians in this situation are subjects themselves, not investigators. Although the professional may have received an intervention aimed at improving practice, the professional is still expected to act in the best interests of her patients and in accordance with professional practice standards. As Henderson puts it, “In the studies in which an administrative intervention does not directly interpose between the physician and the patient, the patient’s treatment remains under the direction of the physician and is not removed by the process of randomization33.” Therefore, effects on practice patterns do not jeopardize the welfare interests of the patients of a health care provider participating in a CRT. Simply being a patient of a professional participating in a CRT of an educational, knowledge translation, or quality improvement intervention does not make one a research subject.
Some studies evaluate patient-level effects as an outcome measure. The fact that a patient-level effect may be measurable is relevant to patients only insofar as their private health information may be used, or they may be asked to submit to surveys or additional examinations to evaluate the outcome of the CRT. Patients of professionals participating in a CRT of an educational or quality improvement intervention need be considered subjects only if they are directly intervened upon by or interact with investigators, or if their identifiable private information is used.
This conclusion does not necessarily hold for patients in CRTs evaluating alternative modes of health service delivery. These CRTs aim to evaluate the effect of different methods of providing care. This is different from CRTs of interventions directed at providers that aim to increase the use of evidence-based care while maintaining the fiduciary relationships that providers have to patients. Examples include CRTs evaluating the effect of employing specialist nurses in asthma management34 or the use of case managers for the reduction of inpatient length of stay on medical wards35. These CRTs are being conducted because the efficacy of the mode of delivery is uncertain. Randomization in clusters is undertaken for logistical reasons and to avoid experimental contamination. A trial evaluating the effect of an experimental mode of delivery is thus akin to a trial that evaluates an experimental treatment. Novel modes of healthcare delivery are therefore best thought of as direct patient-level interventions rather than environmental manipulations. In such studies, the patients would be research subjects because they are directly intervened upon.
3. Implications for CRTs in fields other than healthcare
In some CRTs, particularly in public health, the purpose of the experimental
interventions is to deliberately manipulate individuals via their environment. For example, in the COMMIT study, billboards, and mass media ads (environmental manipulations) were intended to produce behavioural change in smokers living in intervention
communities36. Another CRT evaluating interventions aimed at individuals via
environmental manipulation is a CRT comparing rates of diarrheal illness in communities randomly assigned to water treatment with flocculant disinfectant or a control37. In these
studies, the purpose of the environmental manipulation is to intervene on individual residents. The residents of communities in such studies are therefore research subjects and entitled to regulatory protections. This does not necessarily mean that informed consent is required from all residents. Rather, many of these studies of environmental manipulations would meet regulatory criteria for a waiver of informed consent8,15,17.
CRTs in education are roughly analogous to CRTs in healthcare: the teacher-student relationship has many of the characteristics of a fiduciary relationship19. If a CRT is used to evaluate the effect of a continuing education intervention for teachers, the indirect effect of the change in teachers’ performance on students will not require that students be
considered research subjects. However, CRTs of experimental curricular programs may be more similar to CRTs evaluating novel methods of health service delivery, and may require treating students as research subjects.