1 INTRODUCTION

Incidental findings have received considerable attention since the introduction and application of genome and exome sequencing. These findings are typically defined as the identification of gene variants that have health importance for an individual, discovered in the conduct of clinical sequencing but not related to the disease under investigation (Boardman & Hale, 2018). In 2013, the American College of Medical Genetics and Genomics (ACMG) released recommendations to return incidental findings for 56 selected genes associated with 24 conditions (Green et al., 2013). A revised statement was published by ACMG in 2017 that changed the terminology of ‘incidental findings’ to ‘secondary findings’ because the list of genes were intentionally analyzed as opposed to found incidentally (Kalia et al., 2017). Other significant revisions to the ACMG recommendations included the option for patients to opt out for the return of secondary findings (SFs) and to have a process for curating and updating a list of genes from clinical genomic sequencing over time.

Return of SFs is routinely conducted in the clinical setting and is expected to continue to increase with the rapid growth of next-generation sequencing technology (Shahmirzadi et al., 2014). A survey of genetic counselors reported that many genetic professionals are returning SFs, and this added responsibility has increased challenges to already complex and time-consuming counseling sessions (Smith, Douglas, Braxton, & Kramer, 2015). Another study interviewed genetics specialists' perspectives about disclosure of SFs and found that 62% of participants stated they had personally disclosed and/or discussed SFs to patients (Downing, Williams, Daack-Hirsch, Driessnack, & Simon, 2013). Some of the concerns identified during the return of SFs included inconsistent definitions of SFs, when to inform patients, how to minimize psychological harm, and the need for flexible disclosure guidelines.

As the volume of data that are generated from sequencing increases, the numbers of SFs will likely correspond (Roche & Berg, 2015). Pretest counseling is critical to prepare patients to understand the implications and limitations of testing for the return of SFs (Bernhardt et al., 2015). Further, several publications examined the importance of including patients in the decision of what SFs to receive (Christenhusz, Devriendt, Peeters, Van Esch, & Dierickx, 2014; Smith et al., 2015; Yu, Harrell, Jamal, Tabor, & Bamshad, 2014). While the literature provides support from both healthcare providers and patients for return of SFs, other research has identified potential problems with relying on pretest counseling or informed consent as a stand-alone indication for the return of SFs. Roche and Berg (2015) suggest that ‘even when participants express an intention to learn secondary findings, these initial predictions may not reflect an unequivocal desire for them’. This notion is supported by results from Christenhusz et al. (2014), which state, ‘patients and their families admitted they could not anticipate their own preferences about whether or not to receive results until they were returned’.

Some have argued that there are ethical considerations for both returning and not returning results (Christenhusz, Devriendt, Van Esch, & Dierickx, 2015). Risks of psychological harm to patients may come from overemphasizing the possibility of SF discovery or by disclosing SFs in an insensitive or inappropriate way (Kohane, Masys, & Altman, 2006; Veenstra, Roth, Garrison, Ramsey, & Burke, 2010). This concern of causing psychological harm and duty to protect their patients from the return of SFs was also further supported in interviews with genetic professionals (Downing et al., 2013; Townsend et al., 2012). Common practices and lessons learned from experiences in returning SF results could guide best practices as clinical sequencing continues to gain widespread use (Bernhardt, Kellom, Barbarese, Faucett, & Wapner, 2014).

Identifying how best to practically return SFs to patients within a session is not well documented. Few studies have sought to explore the experiences and strategies of individuals involved in the return of SFs from clinical sequencing. Of those, these studies were either prospective or hypothetical and focused more on attitudes of researchers, healthcare providers, and patients toward the disclosure of SFs (Appelbaum et al., 2014; Ayuso, Millan, Mancheno, & Dal-Re, 2013; Bernhardt et al., 2014; Tabor et al., 2012). As advancements in technology increase the frequency of genome and exome sequencing, studies that describe the actual experiences and content of the discussion of the return of SFs are needed. This study described and categorized the experiences of genetic counselors in the return of SFs from clinical sequencing.

2 MATERIALS AND METHODS

3 RESULTS

For the purpose of this paper, we chose to use the general term ‘secondary findings’ for terms related to any unanticipated, incidental, or discovery findings from the results of genetic testing for diagnostic or management purposes. A total of 21 genetic counselors who represented 56 different return of secondary findings were interviewed. Demographic data on participants are summarized in Table 2. Characteristics of SFs and return practices are outlined in Table 3. The results are organized into four major categories, which include (a) reliance on pretest counseling when returning SFs, (b) how primary test results influenced the level of importance placed on the SFs, (c) patients' two-stage emotional reactions to receiving SFs, and (d) how the return of SFs changed the way genetic counselors offered pretest counseling.

4 DISCUSSION

This study identified lessons learned by genetic counselors who returned secondary findings (SFs) in the clinical setting. Though there was diversity in regards to the types of SFs, medical specialty, other provider involvement, and whether the result return was in person or over the telephone, there were similarities across experiences of the interviewees. For example, the importance of pretest counseling and the severity of the primary test result influenced how the session was managed by the genetic counselor. Strategies were also discussed for managing reactions and questions from patients after receiving SF results. These data can help pinpoint essential pieces of the process for any professional who not only returns SFs to patients, but also those involved with ordering genetic sequencing. As such, a strength of this study is that it conceptualizes common categories despite the different experiences of the interviewees and gives an in-depth understanding of these situations from the provider's perspective.

Much of the literature on the return of SFs still focuses on the types of SFs and the choice of the patient to receive the SF as well as debates around what is medically actionable, the professional duty of a provider to do no harm, and whether SFs should be a targeted part of any testing (Saelaert, Mertes, De Baere, & Devisch, 2018). Further, there are no clear guidelines or steps for how this information should be returned within the clinical setting, thus leaving many professionals who do not have counseling expertise to deliver difficult information in the ever-growing application of genomics into clinical care. Numerous publications still state the need for more in-depth description of the actual experience of the clinical encounter to return SFs (Burke et al., 2013; Townsend, Adam, Birch, & Friedman, 2013). Yet, despite the recognition for more data about the lived experience of the clinical encounter during the return of SFs and documentation of how to best deliver this information, research evidence is still limited about the actual experiences of how SFs are returned.

However, the existing evidence does provide some guidance for helping professionals develop communication strategies for returning SFs to patients. This is highlighted by Boardman and Hale (2018), who synthesized evidence from 15 studies to form general categories for whether or not to return SFs. These categories could be used as a way to report the results from this study into suggestions to genetic counselors of what to expect, strategies, and information that may be useful when disclosing SFs to patients. Their recommendations included disclosing (a) the strength of the genotype/phenotype correlation; (b) the impact, severity, and treatability of the associated genetic disease; and (c) the relevance of the SF beyond the index case (Boardman & Hale, 2018). These recommendations generally correlated with strategies used by the counselors in this study.

The first category of whether to return SFs was relevant to our results. Interviewees considered the severity of the index case and the severity of the SF during the session. This guided the content of the information and how much discussion should be placed on the SF. Participants stated that pretest counseling for the possibility of receiving an SF from clinical genetic sequencing was fundamental. It not only guided the return process but it influenced how patients reacted to receiving the information. Consistent with other research literature, adequately counseling patients on what to expect during pre-counseling is as important as whether or not to return SFs and allowing patients to opt out (Kalia et al., 2017). Although this finding offers little guidance for professionals returning SF results when thorough pretest counseling was not conducted, it is consistent with conclusions from other studies that emphasize the need for pretest counseling (Christenhusz et al., 2014; Clayton & McGuire, 2012; Strong, Zusevics, Bick, & Veith, 2014).

Further, when dealing with the emotional responses and problem-based coping of patients discussed in this study, the interviewees used strategies to maximize patient comprehension, encouraged appropriate medical actions by the patient, and helped patients adjust to receiving unexpected health information; all of which can be incorporated when returning SFs in the second category by Boardman and Hale (2018). As described in our study, there were typically two stages of emotional reactions by patients when receiving SF results. The first was surprise, followed by problem-based coping about next steps. Discussing the emotions associated with surprise described by the interviewees that ranged from ‘very emotional to complete stoicism’ may help providers develop strategies to help the patient process emotions. As such, during pretest discussions or during the return of SFs, providers could give examples of how some people reacted to receiving such information and what they might do if an SF were to be discovered. Genetic counseling in this setting could include anticipatory activities, such as using a scenario which can be helpful when patients are unfamiliar with a disorder and/or have no family history of a condition associated on the ACMG list (Green et al., 2013). However, as noted above, providers must negotiate the delicate balance of placing too much emphasis on the SF during pretest counseling and causing unnecessary anxiety (Veenstra et al., 2010).

Problem-based coping after the emotional surprise of the SF was identified as the second stage of reactions by patients by the interviewees. Using the impact, severity, and treatability of the associated genetic disease, then identifying steps for helping patients cope with the SF was suggested. Some of these included future medical management, family communication, and reproductive risk. Preparation and strategies about these concerns and how to best help patients should be considered when delivering SFs.

Finally, the third category of ‘relevance of the SF beyond the index case’ was incorporated into the interviewees' experiences for returning SFs in this study. Participants reported that SF results were typically returned at the same time as the rest of the test results. In cases that involved significant primary results, participants reported that the patient and their family's ability to comprehend or even hear the SF was often lost. This finding could inform a new practice of returning primary results and significant SF results in two separate visits and may need to be contracted in the initial pretest counseling session. Another consideration is if the patient did not remember pretest counseling, it may be necessary to conduct a pre-session again to prepare them for the return of SFs, especially if there is a significant time delay from when the testing was conducted.

While our study offers in-depth, qualitative data describing genetic counselors' practices for returning SF results, and their perceptions of patient reactions to such results, it does have limitations. The data relied on accurate recall of past experiences. There are many variables that could contribute to the interviewees' experiences, and it is possible that self-selection by counselors to participate in this study may not reflect the experiences of other genetic counselors who return SFs. It may be that those counselors for whom the return of SF results was novel were more likely to respond. However, this study provides a good start for understanding the process of returning SFs and identified common categories across different experiences of the interviewees. Identifying how to deliver genetic findings sensitively to patients is critical, and studies have shown that we know much about what patients think they want to learn (Clift et al., 2015). This study fills a gap in the literature by describing the actual experiences of genetic counselors who returned SFs in the clinical setting.

AUTHOR CONTRIBUTIONS

Carly Rost made a substantial contribution to the conception, acquisition, analysis, and interpretation of the research. She also drafted the work, gave final approval of this version for publishing, and agreed to be accountable for all aspects of the work. Karin Dent made a substantial contribution to the conception and interpretation of the research. She also critically revised the work, gave final approval of this version for publishing, and agreed to be accountable for all aspects of the work. Jeffrey Botkin made a substantial contribution to the conception and interpretation of the research. He also critically revised the work, gave final approval of this version for publishing, and agreed to be accountable for all aspects of the work. Erin Rothwell made a substantial contribution to the conception, analysis, and interpretation of the research. She also critically revised the work, gave final approval of this version for publishing, and agreed to be accountable for all aspects of the work.

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