Role of the RN/APRN in Policy Evaluation

Omics research ethics considerations Janet K. Williams, PhD, RN, FAANa,*, Cindy M. Anderson, PhD, CRNP, ANEF, FAHA,

FNAP, FAANb a College of Nursing, The University of Iowa, Iowa City, IA

b College of Nursing, The Ohio State University, Columbus, OH

A R T I C L E I N F O

Article history: Received 29 January 2018 Accepted 29 May 2018 Available online 6 June 2018.

Keywords: Omics Research Ethics Nursing

A B S T R A C T

Background: Pending revisions to the Common Rule include topics consistent with respect for persons, justice, and beneficence for research subjects in studies using omics technologies and are relevant to omics research. Purpose: Synthesize trends in bioethics, precision health, and omics nursing science for novice and experienced nursing scholars from which to consider bioethics questions. Methods: Review topics addressed in the National Institute of Nursing Research (NINR) strategic plan, Common Rule pending revisions, and publications regard- ing human subjects protection policies. Discussion: Omics research involves decisions regarding understandable in- formed consent, broad consent, data sharing, trust, equal benefit, equal access, societal variables, privacy, data security, and return of findings to participants. Conclusion: Principles of respect for persons, justice, and beneficence as articu- lated in the Belmont report and reflected in the American Nurses Association (ANA) Code of Ethics provide guidance for human subjects protection procedures to advance omics and nursing science. Cite this article: Williams, J. K., & Anderson, C. M. (2018, JULY/AUGUST). Omics research ethics considerations. Nursing Outlook, 66(4), 386–393. https://doi.org/10.1016/j.outlook.2018.05.003.

Although recognition of the importance of bioeth- ics in human subjects research is not new, laboratory techniques involving omics technologies, the poten- tial for use of personal information or biospecimens beyond currently envisioned studies, and a vision of precision or personalized health strategies all create a climate within which implementation of research bioethics introduces new examination of bioethics issues. The term omics refers to technologies and methods used for identification of actions and roles of molecules that constitute cells (Ferranti, Grossmann, Starkweather, & Heitkemper, 2017) and may include, Role of the RN/APRN in Policy Evaluation

“identifiable biospecimens and biospecimens that are newly obtained through direct interaction with a person” (Bierer, Barnes, & Lynch, 2017, p. 787). Scientific inquiry into the associations of omics with human health and disease may involve collection of multiple sources of data including information or biospecimens from or about living individuals. For example, biospecimens with the addition of phenotypic or other personal data relevant to the research question to be answered are necessary for precision health analytics. Findings from omics research may be used to monitor individual risk, to develop new knowledge, to contribute to personalized

Components of this paper were presented by Dr. Williams at the 2017 American Academy of Nursing Panel discussion on Policy on Pre- cision Health: Addressing the Intersections Between Omics, Informatics and Bioethics. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

* Corresponding author: Janet K. Williams, College of Nursing, The University of Iowa, 50 Newton Road, Iowa City, A 52242. E-mail address: janet-williams@uiowa.edu (J.K. Williams).

0029-6554/$ — see front matter © 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.outlook.2018.05.003

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interventions, or to contribute to understanding of how environment interacts with an individual’s phys- iology (Ferranti et al., 2017). Thus, the conduct of human subjects research involving omics methods requires adherence to bioethical principles underlying the federal and institutional policies.

Considerations of bioethics questions are informed by major policies that provide the context within which omics nurse scientists conduct their studies. Proposed changes to the Common Rule (Federal Policy for the Protection of Human Subjects: Six Month Delay of the General Compliance Date of Revisions While Allowing the Use of Three Burden-Reducing Provisions During the Delay Period, 2018) reflect advances in research designs and procedures that affect protection of human sub- jects. Important issues addressed in the pending revised Common Rule are components to be considered in studies involving humans using omics research. The purpose of this article is to synthesize trends in bio- ethics, precision health, and omics nursing science for novice and experienced omics nursing scholars from which to consider bioethics questions that are rele- vant to their programs of omics research.

Background

The Federal Policy for the Protection of Human Sub- jects, also known as the Common Rule, was first developed in 1981 in response to consequences of failed oversight of human research participants (Hodge & Gostin, 2017). Findings from a 1979 conference, titled the Belmont report, defined the basic ethical prin- ciples of the United States Health and Human Services (Federal Policy for the Protection of Human Subjects: Six Month Delay of the General Compliance Date of Revisions While Allowing the Use of Three Burden-Reducing Provisions During the Delay Period, 2018) human subjects research protection regulations (The Belmont Report, 1979). In 2015, a systematic plan to revise the Common Rule was published by the Office for Human Research Protections (Federal Policy for the Protection of Human Subjects, 2017), which is cur- rently pending implementation (Federal Policy for the Protection of Human Subjects: Six Month Delay of the General Compliance Date of Revisions While Allowing the Use of Three Burden-Reducing Provisions During the Delay Period, 2018). The Common Rule guides the in- stitutional review board (IRB) oversight of individual research protocols, with IRBs charged with assuring the protection of human subjects in individual research studies, including those employing omics approaches and methods. The ANA Code of Ethics represents pro- fessional expectations and provisions that are applicable and relevant to human subject research (American Nurses Association, 2015). Specifically, respect for human dignity, primacy of the patient’s interests, protection of rights to privacy and confidentiality, obligation to advance health and human rights and reduce disparities,

and integrating social justice are relevant consider- ations in omics research. These elements share values with the principles of respect for persons, justice, and beneficence, which are reflected in the Common Rule. The unique considerations for omics investiga- tion require additional assurance that basic ethical principles are integrated in the study design and im- plementation to assure protection of human subjects.

Bioethical Considerations for Precision Health

Attention to bioethics and omics in nursing science re- search is timely as there is an increasing focus on the concept of precision or personalized health. Precision medicine has been defined as consisting of disease treat- ment and prevention approaches that take into account individual variability in molecular, genomic, cellular, clin- ical, behavioral, environmental, and/or physiological dimensions (Collins & Varmus, 2015). Another defini- tion describes the goal as identifying an individual’s predisposition to a disease and ways an individual re- sponds to treatment through integration of personal and investigational data at the individual level (Dzau & Ginsburg, 2016). Labeled by various terms, for example, targeted, personalized, and precision; and referring to medicine and/or health, this concept will be referred to in this synthesis as precision health. This is generally described, as it pertains to the health of each individ- ual. However, these concepts have yet to be fully articulated as being relevant to populations for whom societal as well as genetic factors and clinical care in- fluence and public health (Bayer & Galea, 2015), as the concept of precision health may eventually be applied to both individuals and populations. Role of the RN/APRN in Policy Evaluation

The focus on precision health is reflected in lan- guage and major components of the 2016 National Institute of Nursing Research (National Institute of Nursing Research, 2016) strategic plan. In particular, each of the first three components, symptom science, well- ness, and self-management, relies on discovery and/ or application of information about individual factors necessary to understand risk of, occurrence of, or man- agement of symptoms (Grady, 2017a, 2017b). The cross- cutting areas of technology and development of nurse scientists also are closely linked with knowledge nec- essary to move the precision health components of nursing science forward. Nurse scientists are uniquely poised to advance discovery in precision health at both the individual and population levels. This underscores the need to clarify considerations of bioethical prin- ciples in omics research, integral to protecting research participants in the generation and implementation of knowledge regarding the priorities of precision science, big data, health determinants, and global health (Eckardt et al., 2017). This forward movement of science using new methods and technologies such as omics rests on conduct of research that does not violate principles of bioethics. The three principles of the Belmont report that undergird the Common Rule provide a framework for

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considering new challenges for protection of human sub- jects (Table 1).

Respect for Persons

The first principle in the Belmont report is respect for persons. “Respect for persons involves the recognition that individuals are afforded dignity and autonomy in making their own choices” (New York State Department of Health, 2014). Respect for persons is implemented when a fully informed consent process is completed, and the participation in research is truly voluntary. A review of the recent literature on ethical, legal, and social implications of personalized genomic medicine re- search identified informed consent as one of the major topics addressed in the majority of the 299 reviewed pub- lications (Callier et al., 2016).

Understandable Consent

Having the capacity to understand what one is being asked to agree to do is integral to consideration of respect for persons. Omics research represents additional com- plexity due to the functional literacy for the wide scope of omics terms and procedures necessary to consent. A common understanding of the language of omics is limited across virtually all stakeholder groups. This means that potential research subjects, the research community, health-care providers, and parties in- volved in health systems and the management of health data may not understand the omics terms and lan- guage. Ample evidence continues to accumulate that health-care providers are not comfortable with their understanding of the meaning or use of genomic in- formation in clinical practice (Williams, Feero, Leonard, & Coleman, 2017). Researchers are likely well informed about the methods they use but may not be conver- sant in methods used in other branches of omics science. It is commonly recognized that the public may not fully

understand the content of an informed consent docu- ment (Menikoff, Kaneshiro, & Pritchard, 2017), and this may be compounded in an omics research environ- ment. In the clinical setting, one group of public hospital patients who were recipients of genomic information regarding genetic testing for hereditary cancer syn- dromes found some of the information about genomics to be unnecessary, difficult to understand, and/or not addressing what they needed to know to maintain their health (Joseph et al., 2017).

The consent process must assure omics literacy and confirm understanding among potential research par- ticipants to achieve human subjects protection. The creation of informed consent documents that are un- derstandable to potential participants is essential. Considerations of health literacy and language are re- quired when preparing the consent document, selecting words that are understandable in the person’s language.

Considerations in omics research extend beyond the understanding of risks and benefits of research participation, incorporating potential implications of findings. The plan for sharing omics data must be clarified. Interpretation of findings may be limited by the current state of the science and the absence of clear implications for individual or population health. As omics discovery is advancing at a rapid pace, consid- erations for sharing findings at a future time when new evidence of health implications emerge should be considered.

Key Points

Researchers may consider how to improve clarity in the informed consent process. If an informed consent doc- ument is lengthy, starting the document with a concise and focused presentation of the summary of key points that are most likely to be useful to a reasonable person has the potential to aid in understanding the reasons why they might or might not want to participate (Sugarman, 2017). The intent of a key points summary is to remedy a perception that, in general, informed consent documents are lengthy and can be difficult to understand (Menikoff et al., 2017). However, the re- searcher will need to be aware of what specific aspects of the research are important or have value to the subject, and to recognize that these may vary across in- dividuals who qualify for the research study (Corsmo & McAllister, 2017). Role of the RN/APRN in Policy Evaluation

Personal Utility

In addition to matching the information with the per- son’s capacity to understand it, the idea of personal utility is important to consider. Personal utility refers to the value that information has for an individual. In omics research, the value of scientific information to the individual must be considered. When one is consider- ing omics information, personal utility or value is likely to vary. This means that explanations of the potential

Table 1 – Selected Elements of Omics Bioethics Research Considerations Respect for persons 1. Understandable informed consent process 2. Key points 3. Personal utility of research participation 4. Broad consent Justice 1. Trust 2. Equal opportunity to benefit from research 3. Equity in access to care 4. Inclusion of societal variables Beneficence 1. Privacy of research subjects 2. Confidential data management 3. Benefits and risks if findings are returned to research

subjects

i J LUUU^S

Why Don’t We See More Translation of Health Promotion Research to Practice? Rethinking the Efficacy-to-Effectiveness Transition I Russell E. Glasgow, PhD, Edward Lichtenstein, PhD, and Alfred C, Marcus, PhD

The gap between research and practice is well documented. We address one of the underlying reasons for this gap: the assumption that effectiveness research naturally and logically follows from successful efficacy research. These 2 research traditions have evolved different methods and values; consequently, there are inherent differ- ences between the characteristics of a successful efficacy intervention versus those of an effectiveness one. Moderating factors that limit robustness across settings, popu- lations, and intervention staff need to be addressed in efficacy studies, as well as in effectiveness trials. Greater attention needs to be paid to documenting intervention reach, adoption, implementation, and maintenance. Recommendations are offered to help close the gap between efficacy and effectiveness research and to guide evaluation and possible adoption of new programs. (Am J Public Health. 2003;93:1261-1267). Role of the RN/APRN in Policy Evaluation

Despite a growing literature documenting pre- vention and health promotion interventions that have proven successful in well-controlled research, few of these interventions are consis- tently implemented in applied settings. This is true across preventive counseling services for numerous target behaviors, including tobacco use, dietary change, physical activity, and behavioral heailth issues (e.g., alcohol use, de- pression). Several recent reviews and meta- analyses have documented this gap,”^ and the task forces on both clinical preventive services and community preventive services have noted that in several areas there is insufSdent ap- pUed evidence available to make recommenda- tions at present ̂ “̂ Most of the Healthy People 2000 objectives^ were not met, and the even more ambitious goals in Healthy People 2010 are similarly unlikely to be met without signifi- cant changes in the status quo.̂ ‘* To meet these challenges, we will need to have substantially more demonstrations of how to effectively im- plement recommendations in typical settings and in locations serving minority, low-income, and rural populations facing health disparities. Role of the RN/APRN in Policy Evaluation

This situation is not unique to preventive in- terventions, as strikingly documented in the re- cent Institute of Medicine report Crossing the Chasm^ which summarizes the similar state of affairs regarding many medical and disease management interventions. For example, there

is increasing consensus on evidence-based diabetes management practices to prevent complications and on the importance and cost- effectiveness of these practices.'” However, these recommendations—and especially those related to lifestyle counseling and behavioral issues—are poorly implemented in practice.”^”*

This gap between research and practice is the result of several interacting factors, includ- ing limited time and resources of practition- ers, insufficient training,” lack of feedback and incentives for use of evidence-based practices, and inadequate infrastructure and systems organization to support translation.®’̂ In this article, we focus on another reason for the slow and incomplete translation of re- search findings into practice: the logic and as- sumptions behind the design of efficacy and effectiveness research trials.

EFFICACY AND EFFECTIVENESS TRIALS

Many of the methods used in current pre- vention science are based on 2 influential pa- pers published in the 1980s: Greenwald and Cullen’s’^ description of the phases of cancer control research and Flay’s analysis of efficacy and effectiveness research.’^ Both papers ar- gued for a logical progression of research de- signs through which promising intervention

ideas should proceed. These papers had many positive effects in helping to establish preven- tion research and enhancing acceptability among other disciplines. However, they may also have had an important and inadvertent negative consequence that derives from the assumption that the best candidates for effec- tiveness studies—and later dissemination—are interventions that prove successful in certain types of efficacy research. We argue that this assumption, or at least the way in which it has been operationalized over the past 15 years, has often led to interventions that have low probability of success in real-world settings.

To understand this point, it is necessary first to briefly review the seminal papers by Flay’̂ and Greenwald and Cullen.’̂ Efficacy trials are defined by Flay as a test of whether a “pro- gram does more good than harm when deliv- ered under optimum conditions.”‘*”””” Effi- cacy trials are characterized by strong control in that a standardized program is delivered in a uniform fashion to a specific, often narrowly defined, homogeneous target audience. Owing to the strict standardization of efficacy trials, any positive (or negative) effect can be directly attributed to the intervention being studied.

Effectiveness trials are defined as a test of whether a “program does more good than harm when delivered under real-wOrld condi- tions.”‘*”‘””̂ ” They typically standardize avail- ability and access among a defined popula- tion while allowing implementation and levels of participation to vary on the basis of real- world conditions. The primary goal of an ef- fectiveness tried is to detennine whether an intervention works among a broadly defined population. Effectiveness trials that result in no change may be the result of a lack of proper implementation or weak acceptance or adherence by participants.’*’^

Greenwald and Cullen’̂ proposed 5 phases of intervention research presumed to unfold in

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a sequential fashion. This continuum begins with Phase I research to formtiJate and develop intervention Jiypotheses for future study. Phase II studies develop methodologies that can be used in future efBcacy or effectiveness studies. Phase III (efficacy) studies test intervention hy- potheses, using methods that have been tested in Phase Jl. TJius, Phase III studies are de- signed to test interventions for efBcacy, vnth an emphasis on internal validity, tJie purpose of wJiich is to establish a eausal link between the intervention and outcomes. Given this empha- sis on internal control, Greenwald and Cullen note that Phase III studies can be conducted in settings and witb stimples that will “optimize in- terpretation of efBcacy,” including study sam- ples tbat may be more homogeneous tban tbe ultimate target population, and settings tbat will maximize management of and control over tbe researcb process. Role of the RN/APRN in Policy Evaluation

Tbe main objective of Phase fV (effective- ness) studies is to measure tbe impact of an in- tervention when it is tested witbin a population tbat is representative of tbe intended target au- dienee. Given that Pbase JV studies should yield results tbat are generalizable, there is also tbe presumption tbat tbe context and setting for delivering tbe intervention should likewise be generalizable to tbe intended program users. Jn Pbase V studies, effective Pbase JV in- terventions are translated into large-scale dem- onstration projects. Tbe major concern is im- plementation fidelity of an intervention tbat will now be introduced witbin even broader populations, including entire communities. Tbis final pbase (dissemination researeb), wbere col- laboration and coordination witb various com- munity partners is likely to receive even greater attention, is intended to provide tbe necessary data and experience to move inter- ventions into public bealth service programs at tbe national, regional, state, and local levels.

Greenwald and Cullen spedficaUy advocated tbat intervention researcb unfold in a system- atic fasbion, building on and extending tbe body of science acctimulated in previous pbases. By explicitly defining tbe difference be- tween Pbase JJJ and Pbase IV researcb as being an empbasis on internal control versus repre- sentativeness, botb Flay and Greenwald and CuUen assumed tbat successful Pbase III trials would lead naturally to Pbase fV trials. Unfor- tunately, tbis bas not ocaured.””‘^” Instead, we

currently find ourselves in a situation in wbicb we bave many small-scale efBcacy studies of unJoiown generalizability and few suceessiuJ ef- fectiveness trials.̂ ”̂ ^ In particular, we know very little about tbe representativeness of par- ticipants, settings, or intervention agents partici- pating in bealtb promotion research.”^’

Altbougb tbe National Gancer Institute no longer empbasizes tJiis linear “pbases of re- searcb” model,^”’^” tbe model was extremely influential in guiding an entire generation of researeb; many researcbers, reviewers, and editors still use tbis framework wben design- ing, ftmding, and evaluating research—and in deciding wbat types of studies are needed to advance a given area. Similar pbase models are influential in evaluating prevention effec- tiveness^^ and in developing drug therapies. In tbe remainder of tbis article, we discuss bow tbis well-intentioned and logical pbase of researcb paradigm may bave fallen sbort of its intended goal, and propose approacbes to remedy tbe present situation.

Our primary thesis is tbat tbis “triekle- down” model of bow to translate researcb into practice—namely, tbat tbe optimal way to develop disseminable interventions is to progress from efBcacy studies to effectiveness trials to dissemination projects—is inherently flawed, or at least incomplete. We posit that given tbe respective cultures, values, and methodological traditions tbat bave devel- oped witbin efBcacy versus population-based effectiveness researcb, it is bigbly unlikely

tbat interventions tbat are successful in efB- cacy studies will do well in effectiveness stud- ies, or in real-world applications. Role of the RN/APRN in Policy Evaluation