Search and Selection
During the search in PubMed 1264 documents were retrieved. Screening of titles resulted in a sample of 44 documents that concern ethical issues in epidemiology and public health. This set of documents informed us about 6 different guidelines. One document was excluded because the guidelines did not contain a paragraph defining a scope and matter of an ethics review (see Fig. 1). Therefore 5 guidelines were included for further analysis. In Google Scholar, we got an abundance of hits (around 207,000). Therefore, we limited our screening to the first 300 hits sorted by relevance. After this step, we got a list of 22 documents that allowed us to identify 4 guidelines: none of the 4 were new. Therefore, we did not retrieve additional guidelines. In the third search through Google Search (screening limited to first 300 hits), authors (JP and MW) independently retrieved 69 web-documents that were fully screened. Eighteen guidelines were obtained, but only three were incorporated to the sample, others either did not meet inclusion criteria (11 documents, see Fig. 1) or had been previously identified (4 documents, see Fig. 1). Excluded guidelines did not meet one or two of the inclusion criteria: six of them did not define the scope and matter of an ethics review. Three were considered to be too narrow. And three were considered too broad, one of them also did not define the scope and matter of an ethics review. Summing up, we retrieved and finally analyzed 8 documents. Figure 1 presents the consecutive steps of our search and Table 1 contains included and analyzed documents.
Table 1 The list of guidelines included to qualitative analysis
Qualitative Analysis
We identified five main categories in the guidelines that define the IRBs/RECs’ role in epidemiological research. These categories are information policy, protection of subjects, guards for research integrity, formal and operational requirements, type of studies (that are either reviewed or exempt from review). In each category, we distinguished a set of subcategories that describe the specificity of IRBs/RECs’ responsibilities. There are fifty-nine subcategories that are relevant to an ethics review of epidemiological studies. The full list of categories and subcategories is presented in Table 2.
Table 2 The scope and matter of an ethics review in epidemiological studies
Information Policy
IRBs/RECs have authority to review all kinds of information concerning research project, and they assess, how researchers fulfill their obligation to “disclose information”. In epidemiological studies, the duty to inform is not limited to obtaining informed consent. It is not always feasible to inform all subjects, but nevertheless, researchers may have a duty to inform general public and give a participant an opportunity to withdraw from the study. Moreover, epidemiologists, as well as public health workers, have a duty to communities to disclose information about public health threats and major determinants of health and causes of disease. The duty to disclose information covers also communication of study results to the scientific community. Some of the analyzed guidelines require an ethics review of all these aspects of communication with the public and subjects, other limit the scope of an ethics review to some of these issues or even only to the requirement of informed consent.
Protection of Subjects
The second category is “Protection of subjects” and it encompasses all provisions that are envisaged for the protection of study participants. One of the key roles of IRBs/RECs is to ensure that the well-being of participants is not subject to unjustified risk. Some guidelines give IRBs/RECs an important role in protecting privacy and confidentiality, stating that an IRB/REC has to approve all exceptional breaches of confidentiality. Also, most guidelines bestow upon IRBs/RECs a power to decide when and if the requirement to obtain informed consent from the study participants might be waived. There are two different subcategories that refer to informed consent. The first subcategory, “Scope/Content/Procedures of Obtaining informed consent,” is under the broader category “Information policy”; the second, “Waiver of informed consent,” falls under “Protection of subjects”. These two categories are thought to reflect two different aspects of the informed consent requirement. On the one hand, the requirement of informed consent refers to the duty to disclose information. On the other hand, obtaining informed consent is thought to be an instrument protecting the subject’s best interests.
Guards for Research Integrity
The third category, “Guards for research integrity,” refers to powers of IRBs/RECs to guard a study from scientific misconduct. An IRB/REC issues its opinion on scientific and ethical merit of a study and monitors the possible or actual conflict of interests. Also, some guidelines give IRBs/RECs responsibility to report to the authorities the unethical and unlawful behavior of scientists.
Formal and Operational Requirements
The fourth category, “Formal and operational requirements,” contains all important aspects of the institutional functioning of IRBs/RECs. The efficient and ethical work of an IRB/REC requires it to be equipped not only with authority or powers, but also to have adequate administrative procedures in place. IRBs/RECs have to set and announce their rules of proceeding. Members of an IRB/REC are required to have proper competences, which may differ between different members. IRB/REC members also should disclose and avoid conflict of interests.
Type of Studies
According to the guidelines not all epidemiological or public health studies require an ethics review. For instance, according to most guidelines public health surveillance conducted by a governmental institution is not required to be reviewed by an IRB/REC, even if such monitoring uses identifiable data. Many guidelines, however, require an ethics review when identifiable data is being used. The category “Types of studies” summarizes criteria for either necessity of an ethics review or for exemption from the review process.
Similarities/Differences
An important feature of the set of documents is it’s heterogeneity. The guidelines differ with regards to length, scope, form and purpose. The guidelines are issued by different organizations and are intended to serve different goals. None of the subcategories that we distinguished appear in all guidelines. Only one subcategory (B7—waiver of informed consent) appears in seven guidelines. The next most frequent categories that appear in six different guidelines are A1 (scope/content/procedures of informed consent), B1 (subjects’ rights and well-being), B8 (procedures protecting subjects’ privacy and confidentiality), B9 (collecting, use, reuse, sharing, exchanging and final destination of data), and E3 (use of human specimen without informed consent). Subcategories A4 (deviation from the standard written informed consent form), B2 (proper balance between risk and benefits for subjects and public), B12 (safeguards protecting vulnerable subjects), C1 (all ethical aspects of the study), C3 (oversight of the study conduct), C6 (conflict of interests), C7 (ethical approval), D2 (rules of proceeding), E1 (studies involving human beings) and E2 (use of identifiable data without informed consent) appears in five documents.
How Should IRBs/RECs Protect Participants?
The main task of IRBs/RECs is usually defined as protection of participants’ rights and interests (B1) and the fair distribution of risk and benefits (B2). In most of the guidelines, one can find provisions that an IRB/REC has a responsibility to oversee procedures and means of protecting confidentiality and privacy of research participants (B8). Guidelines usually stipulate that personal data should be physically and electronically protected properly. Some, for instance JAPAN-EGES, give a very detailed description of protection measures: systematic, human, physical, and technological. This also implies that IRBs/RECs should have expertise in reviewing such procedures and technologies (D6).
What Information has to be Given to Subjects?
Participants have a right to be properly informed about research. One of the basic responsibilities of an IRB/REC is to monitor informed consent procedures (A1). But this obligation is differently described in the guidelines. In most guidelines, one can find only general provisions that an IRB/REC should review or/and monitor informed consent forms and procedures. But, for instance, CIOMS-IEGES and JAPAN-EGES explicitly list the information that must be provided to research participants. The CIOMS-IEGES list is intended to exhaust probably all possible variants and leave to the IRB/REC’s discretion which elements from the list should be included in a particular informed consent form. Moreover in some circumstances subjects cannot be fully informed about the very nature of the study; in other cases, the IRB/REC might even allow for the deception of subjects (A5). Only two guidelines consider this possibility and give the IRB/REC authority to judge whether such an instrument is ethically and scientifically justified (CIOMS-IEGES, IEF-EGE).
Almost all guidelines refer to the process of communication with the public; nevertheless, not all give an IRB/REC an authority to assess the plan of communication (A8). An IRB/REC might approve the method and timing of communication of results (A9). For instance, according to EGEE “Studies in progress should not report results to the media without prior authorization by a properly constituted IRB/REB (International Society for Environmental Epidemiology 2012).” IEA-GEP contain a whole paragraph devoted to media communication of results, but do not mention the necessity for IRB/REC review (International Epidemiological Association 2007). Authority of IRBs/RECs may embrace as well a plan of publication of multicenter research. According to CIOMS-IEGES, individual researchers should not independently publish the results and the data should be analyzed by the research steering committee (Council for International Organizations of Medical Sciences 2008).
How Should IRBs/RECs Operate?
Streamlining of the review procedure is essential for the speed and efficacy of research. Cooperation between IRBs/RECs is allowed by different guidelines. Nevertheless local IRBs/RECs might have the authority to “prevent a study that they believe to be unethical” (Council for International Organizations of Medical Sciences 2008). In addition, local IRBs/RECs are given the same task to “protect the research subjects” (Council for International Organizations of Medical Sciences 2008).
The issue of unnecessary delay to the instigation of the research due to inflexible an ethics review is directly addressed both in IEA-GEP and in CIOMS-IEGES (C3, D4, D11). Also EGEE guidelines point out that the process of review might unduly slow down the study (International Society for Environmental Epidemiology 2012). There is a common opinion that IRBs/RECs should not apply the same standards to more risky interventional research and relatively safe observational studies. The system of IRB/REC review was originally designed for regional and local studies. Therefore, it poses a challenge for epidemiological studies, which cover large populations in many sites.
What Kinds of Studies Should Lie Within the Scope of the Irbs/Recs Review?
Most guidelines require ethical approval of all research involving humans (C7), although the same guidelines in certain cases allow exemption from review. Usually studies that do not require an ethics review are those based on simple aggregation of already existing records (E13) or use of administrative databases and records without personal identifiers (E9). Also routine public health surveillance or research in states of emergency on a societal scale (e.g. an epidemic) are exempted from an ethics review (E11). In other types of studies, especially in cases when researchers use biospecimens and identifiable records without informed consent, an ethics review is explicitly required. Our analysis therefore shows that in most guidelines there are two independent conditions for an ethics review in epidemiological studies. The first is involvement of human beings. If a study involves human beings, it should be approved by an IRB/REC. CIOMS-IEGES determine that research involves human beings when either the investigator directly obtains information from individuals and groups, or otherwise acquires identifiable private information. Other guidelines either do not contain more precise definition of studies involving humans or do not give such a definition at all (e.g. IEA-GEP). The second condition is the classification of a researchers’ activity. A researcher might either conduct biomedical research or practice public health. Public health practice does not require an ethics review, in contrast to epidemiological research (E11). Nevertheless, the borderline between research and practice in epidemiology and public health is blurred. Public health practice is associated with gathering information and production of generalizable knowledge and in many cases it poses the same risks as research (Willison et al. 2014). The guidelines do not provide a conceptual distinction between research and practice. The difference between research and public health practice has rather a legal and institutional than essential character (E10). Some suggest that in case of doubt, whether a certain activity constitutes research or practice the question should be answered by an IRB/REC (McKeown and Leaner 2009).