Ethical issues in ’observational research’

Does ‘observational research’ need the approval of a research ethics committee? When is patient or client consent needed? These questions are raised in the correspondence (page 87) arising from the study of feeding problems in neonates with meconium-stained amniotic fluid reported in Paediatrics & Child Health(1). The goal of the study was to determine whether feeding problems are more frequent in neonates with meconium-stained amniotic fluid. To ensure unbiased reporting of problems, the nurses who supervised infant feeding were masked to the maternal and delivery details of the infants, and were not informed of the purpose of the study, and attempts were made to wash off the meconium from the babies with stained skin. Babies recognized by physicians at birth to have contraindications to early feeding were excluded from the study.

First, the terms ‘observational study’, ‘research’ and ‘routine care’ should be defined. Observation is the basis for all clinical research, but randomized, controlled, therapeutic trials are usually perceived to be in a unique category, namely, ‘true’ experiments. Observational studies may be based on documentation in archived health records or patient databases maintained by states, insurers, departments or researchers, or may be created prospectively. Nonroutine interventions may have been unplanned or designed prospectively. The observations may be reported individually, or in aggregated and analyzed forms. An observational paper may take the form of a case series, case-control study or cohort study. In the research by Narchi and Kulaylat (1), the authors’ description of their work as a prospective observational study is accurate. Masking of the nursing staff was a planned intervention, not routine practice (see next paragraph).

“Research refers to a class of activities designed to develop or contribute to generalizable knowledge” (2). Markers of research, as opposed to routine care, include the gathering of data beyond those required solely for clinical purposes, the alteration of clinical practices in a way that is instrumental for the research, and the intent to publish the results. The present study had all three ‘prospective’ markers. On the other hand, ’routine care’ or ‘practice’ “refer [sic] to a class of activities designed solely to enhance the well-being of an individual patient” (2). The boundary between practice and research may be fuzzy, as suggested by the response of the authors to Dr Springate’s letter (page 87).

Space does not permit consideration of all ethical aspects of prospective observational research. Below, the author discusses how, as a member of a research ethics board (REB), he would deal with the questions raised by this study. The ‘policy statement’ on Ethical Conduct for Research Involving Humans (3) forms the basis for the policies and practices of Canadian researchers.

Firstly, is REB approval needed for this research? In Canada, “all research that involves living subjects requires review and approval by an REB ... before the research is started” (Article 1.1 [a]) (3). This even includes research involving review of patient records (Article 1.6) (3); in Minnesota, informed consent is also required to review records (4). Research proposals undergo independent scientific and ethical review, owing to the recognition that researchers have an inherent conflict of interest. Scientific review is performed by scientific peers. The determination of compliance with the ethical principles of research in humans must be independent, and the REB membership should include experts in research ethics and the law. Readers who find the notion of independent review superfluous will find an explanation for these demands in the signal paper of Beecher (5) about research completed by some of our older contemporaries and teachers.

Would an REB require parental consent for this research? The principle of “respect for free and informed consent” can be waived by the REB in Canada under specific conditions. Among other criteria, the research should involve no more than minimal risk (roughly, the risk associated with everyday life) and not involve a therapeutic intervention (3). Does masking of the nurses represent a therapeutic intervention? In the author’s opinion, yes. Would it have been practical for the researcher to request free and informed consent from nearly 3000 subjects in one year? Probably not.

In defining and implementing their responsibilities, nurses increasingly see themselves, and are seen by governments and the law, to be independent of physicians. For example, according to the “Medication Administration Standards” of the College of Nurses of Ontario, the nurse “will assess the appropriateness of the medication as prescribed for the client in the particular situation given” and will “follow up with the physician if the order is believed to be inappropriate” (6). The same would apply to a feeding regimen. Clearly in Ontario, it would not be possible to withhold the clinical information that is needed to evaluate patients or clients from nursing staff.

Research ethics questions are difficult to answer, especially when policies and practices are in evolution. Two recent articles about proposed changes to the Helsinki code illustrate the differences of opinion that can exist (7,8). The perceived need to change the code is based to some extent on international variation in approaches to research ethics (7). Moreover, according to one of the commentators: “The right to informed consent does not resonate with all subjects in all cultures” (7). Do standards for research cross national borders? Ethically, probably yes, or at least the World Medical Association thinks so (9). This does not apply to most legal standards, which are, by definition, national.

Could an alternative research design, such as a retrospective case-control study, have answered the authors’ question? Given their level of ‘routine’ nursing surveillance of feeding and documentation, probably yes. If the ‘actions of meconium inside the stomach should be studied further’, would a randomized control trial of gastric lavage for infants born with meconium-stained amniotic fluid be feasible? The current state of knowledge as reflected in the paper of Narchi and Kulaylat (1) provides little or no support for such a trial.

In summary, as a REB member relying on the Canadian Tri-Council Policy Statement, my answers to the two questions posed at the beginning of this commentary would be as follows. First, consent by the patient, client, parent or guardian would be required in Canada for the conduct of this research, primarily owing to the change made in clinical practice for the purpose of the study. Blinding of the nursing staff “to remove any potential bias in reporting observation of feeding patterns” is undoubtedly an intervention in the Canadian context in which nurses accept and are legislated to have responsibility for their actions. Second, the conduct of ‘observational’ research in which consent is not required, retrospective as well as prospective, has required the approval of a REB since October 1999, but not before that date. These answers may not apply to research conducted in other jurisdictions.