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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Per Med. Author manuscript; available in PMC 2017 September 27.
Published in final edited form as:
PMCID: PMC5616214
NIHMSID: NIHMS904500

How do providers discuss the results of pediatric exome sequencing with families?

Abstract

Aim

This study provides preliminary data on the process and content of returning results from exome sequencing offered to children through one of the Clinical Sequencing Exploratory Research (CSER) projects.

Materials & methods

We recorded 25 sessions where providers returned diagnostic and secondary sequencing results to families. Data interpretation utilized inductive thematic analysis.

Results

Typically, providers followed a results report and discussed diagnostic findings using technical genomic and sequencing concepts. We identified four provider processes for returning results: teaching genetic concepts; assessing family response; personalizing findings; and strengthening patient–provider relationships.

Conclusion

Sessions should reflect family interest in medical management and next steps, and minimize detailed genomic concepts. As the scope and complexity of sequencing increase, the traditional information-laden counseling model requires revision.

Keywords: genetic counseling, genetic sequencing, genetic testing, pediatric, provider communication

Background

Clinical genome and exome sequencing (CGES) are used to diagnose conditions with a suspected genetic cause [1]. The overall detection rate of disease causing variants ranges from 6 to 57%, depending on the indication for testing and methods for variant identification and classification [24]. CGES may become a first tier test for evaluating children with a suspected monogenic disorder, thereby dramatically reducing the length and emotional burden of the diagnostic odyssey experienced by many families of children with rare disorders [5,6]. Increasingly, CGES for prognostic and treatment-related purposes will diffuse beyond specialized research and into standard care [7].

Research across the ethical, legal and social spectrum reports best practices for engaging families in CGES, including providing pretest education, obtaining informed consent to prepare families for results and helping families make decisions about learning secondary findings [810]. Such secondary findings may include variants in genes for medically actionable Mendelian conditions, as well as other categories of findings including those related to nonmedically actionable genetic conditions, carrier status and pharmacogenetics results. Importantly, since public expectations of gaining useful information from CGES are high [9,11], preparing families to maintain realistic expectations about the spectrum and utility of possible results, including the uncertainty associated with some results, is critical [9,12,13].

Despite the attention to informed consent, few empirical efforts address the ways providers deliver CGES findings and discuss their implications or utility with families. Providers may face challenges discussing CGES results with patients due to the potentially large numbers of results, the uncertainty of some findings and the lack of familiarity of patients and many clinicians with genomic processes and sequencing results [14]. Clinicians may experience distress when returning genetic testing results if they anticipate families will respond with emotional intensity or if they are concerned about their skill in explaining complex genomic concepts [15,16]. Genetics professionals often focus on communicating genome-based scientific information with less attention to nuanced and variable psychosocial issues [14,17,18]. Such communication involves heavy use of technical jargon that may overwhelm, confuse and frustrate families [19] whose primary concerns center on medical management, daily care and quality of life [20,21].

Despite increasing clinical enthusiasm for CGES, little is known about how providers approach the return of sequencing results to families. This study seeks to fill this gap as a critical first step in the development of best practice recommendations that can be tailored to the needs of providers across specialties and to support robust dialogue with families about CGES.

Materials & methods

The Pediatric Sequencing (PediSeq) Project at The Children’s Hospital of Philadelphia, as part of the National Human Genome Research Institute’s Clinical Sequencing Exploratory Research (CSER) Consortium, offered exome sequencing to children from five disease cohorts, including unexplained hearing loss, cardiac arrhythmias, mitochondrial disease, intellectual disability and platelet disorders. Institutional review boards at The Children’s Hospital of Philadelphia and the University of Pennsylvania approved this study protocol.

Protocol

A detailed description of subject recruitment and informed consent process is published elsewhere [22,23]. Briefly, clinicians from five disease-specific clinics providing care to children from the study cohorts recruited participants during an initial or follow-up clinic visit. Many had previous genetic testing. At the time of consent, families were told they would automatically receive diagnostic and immediately medically actionable secondary findings. In addition, families could opt to receive secondary findings, including results for nonimmediately actionable childhood and adult-onset conditions and carrier status. Families could not receive results for adult-onset conditions without treatment, such as neurodegenerative diseases. Parents indicated preferences for receiving secondary findings during or shortly after the informed consent session, and providers confirmed these selections at the time results were returned.

When sequencing analysis was completed, a team of laboratory directors, genetic counselors, clinical geneticists and specialty physicians reviewed sequence variants and the clinical and family history to classify variants definitively or possibly explaining the child’s presenting condition as pathogenic, likely pathogenic, variants of uncertain significance (VUS) or likely benign. A laboratory director generated a 14-page report that included these categories of diagnostic variants in addition to pathogenic or likely pathogenic secondary findings, if the family opted to have them returned. The first page of the report summarized all the findings (the first page of a prototypic report is included in Figure 1). Beginning on the second page, the report included tables listing each finding with its associated inheritance pattern, mutation type and other characteristics of each reported variant (Figure 2). The report also contained a summary of the clinical implications and recommendations for each finding.

Figure 1
Page 1 of sample PediSeq exome sequencing report summarizing all findings.
Figure 2
Table from page 2 of sample PediSeq exome sequencing report detailing results related to the primary clinical indication.

Data collection

The results reports were completed between 8 and 27.5 (mean: 20; SD: 4.7) months after enrollment, at which point the study coordinator contacted parents and asked to schedule a meeting for results disclosure. The clinicians returning results were not provided with any guidance as a part of the study as to how or which results should be discussed with participants. Immediately before results were discussed, the clinician asked for consent from parents and assent from children 7 years and older, to digitally record the results disclosure sessions. We selected the first 25 return of results sessions involving participants under 20 years of age and transcribed these audio recordings (no participants declined to have their session audiotaped).

We also obtained the exome sequencing laboratory report, and made note of all findings for these 25 participants. Twenty opted to receive all secondary findings; two declined to learn adult-onset, medically actionable findings; and three declined learning carrier status findings.

Transcript analysis

We used Braun and Clarke’s [24] process for inductive thematic analysis for data coding and analysis with a primary focus on semantic (spoken or explicit) themes and a secondary focus on latent (process) themes. Thematic analysis involves multiple, systematic and explicit readings of transcripts toward the development and refinement of themes describing a given phenomenon. Themes are patterns in the data with often nuanced prevalence within and between points of data with relevance to the research questions.

The research team included a senior genetic counselor with over 40 years of practice experience and a PhD prepared licensed clinical social worker, both of whom had faculty positions at the University of Pennsylvania and extensive experience conducting qualitative grounded theory, narrative and case study research in translational genomics. The study coordinator, a graduate student and an undergraduate student completed the qualitative analysis team; none of these individuals were involved in returning sequencing results to study participants.

To initiate analysis, the research coordinator checked all transcripts against audio recordings for accuracy and selected five using the principles of maximum variation [25]. All five members of the research team developed deep familiarity with the data by independently conducting open coding on this set of five transcripts. Each investigator kept a detailed audit trail listing emergent, or in vivo codes and a priori codes which were anticipated based on findings from previous stages of the research program [22]. The full team then came together to collapse and define the parameters of similar codes, and to discuss discrepancies toward consensus [26]. The list of codes generated during this meeting became our initial working codebook.

To check the dependability and credibility of the codebook [27], the research coordinator randomly selected three additional transcripts to test the scope and specificity of codes. Five members of the research team independently analyzed these three transcripts using the codebook and noted gaps and redundancies. Upon meeting, the team discussed and resolved via consensus any remaining discrepancies to yield a final codebook. After coding of eight full transcripts no new codes had emerged, signaling preliminary saturation [28].

The final codebook was parsed into categories of codes to distinguish behaviors initiated by providers, such as attributing meaning to findings, mechanisms to covey complex concepts, checks for understanding and attempts to engage participants. We distinguished these codes from those related to proband and family behaviors, including discussion of expectations, expressing emotional reactions, seeking comfort and clarity and inquiring about implications for other family members. A third category captured interactions between providers and families, including codes such as building the patient-provider relationship, supporting family communication and determining next steps. In this paper, we focus primarily on our analysis of codes relating to provider behaviors (an excerpt from our codebook can be found in Table 1).

Table 1
Codebook excerpt of codes relating to the theme ‘Teaching basic and complex concepts’.

All 25 transcripts were then uploaded into NVivo 10 and recoded, using the interrater reliability function in NVivo to assure consistency. A graduate student and an undergraduate research assistant then coded all 25 transcripts using the finalized codebook. A final check confirmed no new codes or themes emerged during final coding.

Simultaneous to open coding, the research team identified the need to evaluate the structure of these sessions, a feature that was not captured in the early analysis. To capture session structure, the senior genetic counselor worked with the study coordinator and an undergraduate student to re-read transcripts to produce a structured summary of each, focused on: session length; type of providers present in the session; family members present; contribution of each provider to the session; order that topics were presented in the session; relative amount of time spent on discussing each topic; and topics (if any) and provider communication techniques that elicited participant engagement. Together, these two strategies enabled us to analyze both the process of delivering exome sequencing results and the structural content of those sessions.

Rigor

The team met regularly to discuss ongoing analysis and resolve coding discrepancies using the consensual qualitative method [26]. The coding strategy enabled checks for dependability and credibility of the codebook through a stepwise progression from purposive selection of transcripts for analysis to random selection as a check. The team completed two checks of saturation, after independent coding of eight transcripts and then again at completion of coding all 25 transcripts. The research coordinator maintained a detailed audit trail to document the steps toward increased dependability and confirmability throughout analysis. Collaboration across applied disciplines helped the research team to remain reflexive and responsive to participant voices.

Results

Session structure & overview

Participants

One or more of seven genetic counselors, six physicians and one nurse, most of whom had ongoing relationships with families from the clinical settings where participants were recruited, returned results to children and their families (see Table 2). A genetic counselor was present in all but two sessions. All providers had at least some previous experience returning clinical exome sequencing results. One or both parents were present in all sessions. In 52% of sessions, the participating child also attended the session. In eight cases, other family members, including siblings, aunts and a grandmother also attended the session.

Table 2
Characteristics of PediSeq disclosure sessions.

General structure of return of result sessions

Data on session format were derived from review of the session summaries. Sessions lasted between 7 and 100 min (median: 27; mean: 36; SD: 20.7). In all sessions, providers, regardless of type, started by briefly reviewing the purpose of the PediSeq study and reminded the family that sequencing was done to identify an underlying genetic cause of the child’s condition. In nearly all sessions, the provider gave the family the 14-page laboratory report to guide discussion of the findings, usually closely following the information displayed on summary tables for each type of finding (Figure 2). Consistent with the ordering of results in the report, results relating to the reason for sequencing (‘primary findings’) were always disclosed first, followed by secondary medically actionable findings, and then carrier status findings. In several sessions, family comments and questions suggested they scanned ahead of the provider in the report. Providers reoriented family members to return to the result being discussed currently, and indicated that other results would be discussed soon.

Providers devoted the majority of each session to discussing primary results. In the three cases where there was a positive secondary medically actionable finding, providers spent considerable time describing the associated clinical implications of the finding and plans for follow-up. Providers usually spent only a few minutes discussing any carrier status results.

When present in the session, the physician generally took the lead discussing results, focused on pathophysiology and explained how the identified genetic variant could be associated with the child’s condition. Physicians also discussed medical management in light of findings. Genetic counselors focused on technical aspects of sequencing, genetic concepts, inheritance patterns, risks to family members, and carrier status results, if present.

Content & process of result session: thematic analysis

As providers returned exome sequencing results to families, they engaged in behaviors that we grouped thematically to align with four central processes: teaching basic and complex genetic concepts; assessing family response and understanding; personalizing sequencing findings; and strengthening relationships with families. For each of these themes, providers used a range of tools and approaches that emerged from our coding scheme during analysis, to disclose, describe, and discuss concepts and implications they perceived as relevant for the family to understand and act on results. Below we describe the four processes and the associated tools utilized by providers, along with anonymized quotes illustrating each.

Teaching basic & complex genetic concepts

The majority of disclosure sessions were occupied by providers verbally teaching families concepts that providers judged to be important for families’ understanding of sequencing results. This theme captured providers’ discussion of basic genomic concepts as a foundation for understanding the sequencing process and results. Guided by the laboratory report, providers utilized the following tools: a basic tutorial of genetic concepts and explanations of the scientific vernacular used to describe sequencing and genetics.

Genetics 101

All providers discussed both broad and focused genetic concepts underlying sequencing and the family’s particular finding(s). It was apparent that providers believed detailed explanations of genetic concepts, including those not directly related to a particular finding, would help families understand their results, but the scope and amount of relayed information frequently became a source of confusion or diminished family engagement.

Providers usually started by probing the family’s baseline understanding of genetics by asking if they studied genetics in school. After often perfunctory answers from families, providers then launched into a general lesson in genetics. They frequently started by describing chromosomes, genes and variants:

“Chromosomes are structures that hold all of our genes. We have 46 of them total, 23 pairs. With each pair, you get one chromosome from mom and one from dad”.

After presenting the basics of genetics, providers discussed more complicated processes to explain scientific terminology presented in the laboratory report. Providers usually established that the report would guide them through the session, before moving on to the details contained within:

“So the first page is just the summary of the whole report and then the next pages just go through the different sections and then I think every section says ‘not detected’ … and standard language that there are limitations and on one of the pages we list the limitations”.

Genetics as a second language

Language used in the laboratory report contained difficult words specific to the field of genetics. Providers, aware that families were likely unfamiliar with the terminology used, attempted to make families comfortable with the parlance of genetics. However, by teaching ‘genetics as a second language’, providers were calling on families to master a substantial new syntax and vocabulary in the course of the single session.

Providers attempted to define the scientific terms included in the report as they read through it with the participants:

“And you’ll see it says ‘homozygous for a pathogenic variant in the GJB2 gene.’ So homozygous means that she has two changes …. And the way hearing loss is most commonly inherited is in what we call a ‘recessive’ fashion, meaning that you need a change in both of those two copies in order to have hearing loss”.

“…you see the 416 written? So at the four hundred and sixteenth position, the ‘G’ got changed to an ‘A’…”

Providers frequently used analogies in an effort to provide recognizable examples to help families understand how genes work or how mutations in genes affect their function:

“We do kind of a spelling check. Just like if you enter Google.com … if you miss a ‘g’ or if you replace a ‘g’ with a ‘t’, then …”

Yet, they also made heavy use of scientific jargon and gave long explanations to attempt to educate families about specific findings included in the report:

“It is a change that just makes a stop sign. It is reading … the DNA is just a code of letters and that code just tells the protein how it should be made. When it’s reading the code, all of a sudden it comes across a stop sign and so it’s not making the full protein. So as a result of this, you do not have a functional protein and it cannot do its job. And so that’s why you’re having these symptoms. So the gene has a spelling change that just instructs it to stop in the middle. And that … we have functional studies, we have studies to support that yes, that smaller protein does not help and is related to this symptom. So we have enough evidence to tell you that this is the cause”.

In some cases, family members vocalized misunderstanding a provider’s explanation. For example, in response to the provider’s use of the term ‘protein’ associated with gene expression, one father incorrectly understood the use of this term to indicate a nutritional problem and asked:

  • Father: “It’s not like somebody should just take more protein?”
  • Provider: “No, no, no!”

Long explanations of findings, especially for VUSs, appeared to be especially confusing and frustrating to families. For one family, the providers returned four VUSs in genes potentially associated with the proband’s cardiac condition. The proband’s presentation was atypical and the family history included symptomatic individuals on both the maternal and paternal side. As providers discussed the four variants, each family member expressed confusion, and the mother finally asked: “So how is this in any way accurate?”

Provider tools to increase understanding, overall, were inadequate to address the proband’s and/or family’s needs. Families often scanned ahead of providers as they read through the report and, thus, missed discussion of findings as their attention was elsewhere. Parent and proband questions frequently indicated deep confusion about terms and processes.

Assessing family response & understanding

Providers recognized that families’ familiarity and comfort with genomic concepts and the nuances of exome sequencing might be limited. They further recognized the need to evaluate comprehension as they introduced new and complex concepts, described findings via the report, and shared the limitations of testing. Providers utilized three primary tools to engage in families’ experience receiving results: probing for family understanding of genetic concepts, assessing the imagined value of sequencing and eliciting feedback about their results and the disclosure experience.

Probing for understanding

All providers, but especially the genetic counselors, paused to ask families whether they were following their explanations. These evaluations were often perfunctory, such as asking, “So did all of that information make sense?” or “Do you have any questions?” Most families responded to these prompts with one-word answers, which providers did not probe. While these periodic pauses allowed families to ask clarification questions, there was no measure or assessment of whether families understood the full significance or take-home message of their results. Families rarely interjected with questions, but when they did, their questions often revealed deeper misunderstandings or confusion. Providers responded to family questions with brief summaries or repeated extensive explanations of genomic processes. In this example, the provider responded to a mother’s question about the risk for having a second affected child:

“There is something called germline mosaicism or gonadal mosaicism, and it’s something that theoretically can happen to any dominant disease that’s not passed from a parent. There’s a subset of egg or sperm cells that just have the mutation. It hasn’t been reported in this condition because it’s so new, but it’s been reported occasionally in pretty much every other dominant condition. Well, probably not every, but every other that’s been studied long enough or it’s been known long enough that why do two healthy parents have two children with the same disease. And it’s just what we call germline mosaicism. They did studies in the 1980s, so…”

Managing expectations

None of the probands in this sample experienced a change in their care as a direct result of the primary findings obtained from sequencing. Most families expressed disappointment in the limitations of CGES and the uncertainty of the implications of some findings. This pressured providers to articulate the value of sequencing to families. Providers discussed the altruistic nature of family participation with no direct benefit to the child or family. More critically, they spoke optimistically about potential future benefit. Providers cited the promise of future utility regardless of the type of finding and spoke about the need to grow a database to interpret VUS findings, and advances in technology that would improve diagnosis and treatment. This provider gave an assessment of why findings were still valuable in an imagined future context:

“…but knowing is a good thing because if some treatment gets developed based on the function of this gene, then we’ll know that’s going to apply to [Proband]”.

Some families expressed relief that no secondary, and on a few occasions that no primary, findings had been identified. In reaction to the potential false reassurance a lack of findings may have represented to families, most providers talked about the technical limitations of testing, such that not all genes are sequenced and all sequence variations are not interpreted, meaning that a negative result does not mean that genetic changes are not present:

“Even if it says it’s an exome sequencing test, it’s not a 100% test. So it’s a possibility that you are a carrier for some unknown variants in certain genes that we are not looking into and we aren’t reporting”.

Eliciting feedback

Some providers paused, usually toward the end of the session, to ask families how they were feeling about results. Families usually responded very briefly and providers did not push the conversations further. A few providers solicited feedback about the session more generally. In this particular case, the provider invited recommendations for improving results disclosure:

“Are there any things that you would suggest that we would do differently about how we return the results or how we manage this in a clinical practice? Or even in a research study, for that matter. And be honest. You’re not going to hurt our feelings”.

Whether or not feedback was elicited by the provider, families spoke little about their reactions to findings and/or the format of the disclosure session.

Personalizing findings

All providers discussed findings in the context of the patient and family history and the families’ disease experience. This allowed them to personalize information in a shared medical language with families. Family involvement in the session increased substantially when providers turned from explaining genetic concepts to discussing medical management and recommendations for next steps.

Medical management

Families asked, and sometimes expressed concern, about immediate and future medical management and health implications, particularly related to possible changes in treatment or prognosis resulting from primary and secondary findings. Since the 25 families in our sample did not have altered care resulting from their primary findings, all providers assured families that they were doing everything they could with their current medical management:

“We know there was something genetically wrong that they inherited. But it’s not going to really change anything”.

In the few cases where there were positive secondary medically actionable findings, providers discussed the prognosis and implications for the proband’s medical care. Here, where a secondary finding indicated malignant hyperthermia, the provider explained the importance of including the results in the proband’s medical record:

“That needs to be put in the clinical chart because it’s really medically important that anybody who gives you anesthesia knows that you have that”.

Steps

Many probands were part of families with multiple affected members, and providers used this information to extrapolate significance and implications of findings for the proband, as well as other family members, and to provide recommendations for follow-up care for the family:

“So the fact that we have kind of seen it in you and in the sister kind of makes us think that this was not a de novo change in the sense this was not new in [Proband]. So what we recommend is probably getting this verified in a clinical lab and then probably having … if you think your extended family members will benefit from this result, then you can share it with them and have them get tested”.

Providers frequently reminded families that the expression of pathogenic variants is unpredictable and often associated with uncertainty in medical management. The provider above uses phrases like ‘kind of’ and ‘probably’ to express uncertainties. Despite uncertainty associated with the findings themselves, providers offered what they were certain they could deliver: an ongoing commitment to continued medical management and, in most cases, an ongoing and exhaustive search for a diagnosis. Many providers encouraged families to continue seeking out their care and resources and indicated that they would continue to evaluate their exome for answers, especially when the family history and/or phenotype strongly suggested an underlying genetic cause. This provider was explicit about a desire for an ongoing partnership, as exemplified by usage of the pronoun ‘we’ in describing the future steps that could be taken to find a diagnosis:

“I don’t want you to be too disappointed that we didn’t find anything, because sometimes we have to keep looking and learning and eventually we get there”.

Providers also offered resources and referrals to families in response to findings. This provider referred the family to a retinal eye specialist to follow up on the secondary findings indicating a risk for retinal blindness:

“I think it would be good for her to see retinal eye doctor who is a specialist”.

Another provider offered a family support resources to help cope with the experience of having a condition:

“There’s a good family group for this condition, and I can write that down for you. And they have some of the information about the family meeting”.

Strengthening relationships with families

Providers recognized that families struggled with information overload and intense emotions during disclosure sessions. As a result, providers made attempts to connect emotionally with families. We saw evidence of two primary strategies that providers utilized, whether consciously or unconsciously, to enhance the bond with families. These included: validating the family’s questions and experiences and appreciating the family’s contribution to research.

Validating

Validating is a core feature of active listening in which providers conveyed recognition, acceptance, and understanding of family questions and reactions to results. Most providers validated information concerns and gaps in response to informational checks or questions regarding understanding of test results and/or genetic concepts. This helped balance knowledge discrepancies between providers and families:

“It’s a very good question, and you’re thinking about it correctly”.

In a few instances, providers validated the family’s emotional experience of sequencing. This promoted a partnership with families:

  • Mother: “With these genetic syndromes, now we feel like part of something because we never had a diagnosis. We had no sense of focus. A sense of –”
  • Provider 1: “Belonging”.
  • Mother: “Belonging. Yes, that’s the word. And now, we know that we belong to this group right now”.
  • Provider 2: “Right. And you can connect with other families who’re going through the same”.

Appreciating

At the end of sessions, providers usually expressed their appreciation for the family’s willingness to participate in research:

“It’s studies like this that will help us. So, we really, really appreciate your being involved”.

These statements demonstrated gratitude to families who were already heavily involved in medical systems. Most providers emphasized a collective societal benefit gained from families’ participation, although this was particularly emphasized when the family received uninformative results:

“You’re not only helping yourself, but you’re helping society by helping us as medical community to learn what this means to patients”.

Discussion

We identified four main process themes in providers’ approach to discussing CGES results with families: teaching genetic concepts, assessing family response, personalizing findings and strengthening relationships with families. The majority of time in sessions was devoted to discussing results by teaching genetic concepts. This focus likely occurred because the providers in this study chose to return results by structuring the session around the content of a long and complicated laboratory report. This led to sessions characterized by the use of jargon and genomics education that placed a high literacy burden on families. High oral literacy demands and heavy use of technical language can be a barrier to patient understanding, engagement, and satisfaction with the clinical interaction, and may result in a less interactive encounter [29,30]. Indeed, most families in the present study stayed silent during long provider explanations of genetics and the results report, and many participants read ahead in the report, possibly searching for results that they perceived to be most relevant. Those participants who were vocal generally asked for clarification of terms or expressed confusion around the technical aspects of genomics. For some, this confusion also led to questioning the meaning and accuracy of findings.

Genome-based health literacy demands

There is little consensus about the scope of biomedical information patients need to understand to act appropriately upon genetic test results [31,32]. Our findings indicate that the level of detail providers conveyed to families may be too great. The educational approach taken by genetics providers in the present study is not unusual [14,17], but may warrant significant revision as sequencing technology and findings become increasingly complex and common in clinical care [33]. Indeed, whether genetic counselors deliver information in a teaching model characterized by minimal interactivity, or via a counseling model characterized by significant client engagement, sessions are often information-laden [34]. Since many individuals cannot process more than five pieces of information at one time [35], providers must recognize the limits inherent in educating families about all the nuances of testing processes and results. For example, patients may not need to know or understand the type of mutation detected. Communicating fewer details, rather than more, may improve overall understanding, especially for patients with low literacy skills [33,36]. Pediatric participants, who were present in about half of the sessions analyzed, may be especially confused when results are returned in such a highly technical manner. Tailored strategies will likely be needed to engage them in these discussions and ensure they have a developmentally appropriate understanding of the findings and implications for their health care [22,23].

Providers in this study used conventional laboratory reports as a guide for highly technical disclosures. Patient-friendly genomic test reports, and their supporting literature, emphasize the importance of including an interpretative summary that: uses lay language, addresses the meaning of results for the patient’s future, and recommends next steps pursuant to findings [32,37]. Developing brief and simple patient-friendly reports would aid provider communication and patient understanding within the clinical encounter and beyond [38]. Web-based resources could supplement basic information given by providers and allow patients to choose which information to pursue in depth to meet their information seeking needs. Providers, too, would benefit from educational materials to help them present easily comprehensible information. Although the recently developed ‘Guide to Interpreting Genomic Reports: A Genomics Toolkit’ available through the National Human Genome Research Institute website provides clinician education about potential results available through genomic sequencing, the toolkit does not address how to discuss results with patients.

The tools necessary to build relationships are, perhaps, the ones with which providers are most familiar and comfortable since they apply across settings. Such relationships are critical to the ongoing partnerships providers articulated an interest in maintaining with participants. Yet, providers in the present study often missed opportunities to attend to patient confusion, disappointment, or frustration in order to build toward even stronger relationships. Instead, they frequently relied on explanation of genetics to assuage a family’s concern rather than identifying the concern and validating the emotional content at that point. Disappointment over findings and the potentially overwhelming volume of technically complex information may also prevent families from responding to provider probes for feedback in a thoughtful and thorough manner.

Discussing limitations, medical management & next steps

While providers spent considerable time discussing technical aspects of testing and findings, families were most engaged in the session, and asked more questions, when medical management and next steps in their diagnostic odyssey were being discussed. This observation is consistent with Krabbenborg’s [20] finding that parents are most interested in the impact sequencing results have on the care and health of their child. Families may prefer that providers focus on changes to clinical care pursuant to CGES, rather than on understanding the details of testing. Additionally, CGES may also imply risk for diseases and carrier status in other family members, thus potentially raising a host of other questions about next steps for testing and medical follow-up.

Many patients and study participants undergoing genomic sequencing have unrealistically high expectations that testing will yield results that will be medically useful [9,12]. Indeed, it has been suggested that many hold a ‘therapeutic misconception’ about the likelihood that sequencing will lead to diagnostic or therapeutic benefits [39]. Because the exome sequencing results rarely changed current clinical management for participants in the study, clinicians opted to address questions about treatment by highlighting the current limitations and future promise of sequencing. Provider’s discussion of the limitations of testing emphasized genetics as an evolving science; they spoke with enthusiasm about the potential future benefits to participants regardless of their current results. Potential future reclassification of VUS results and better future tests excite clinicians by representing ‘a promise of knowledge yet to come’ [40]. Indeed for decades, geneticists have longitudinally followed patients with a likely genetic diagnosis with the hope that in the future, with improved genetic testing and identification of more genetic syndromes, the patient’s precise diagnosis would become clear. The provider, rather than the patient and family, takes on the responsibility of figuring out what is wrong [41,42]. However, because of high patient and public expectations of genetic testing and CGES [9,11], such promises may not resonate with families. For many parents, CGES is seen as a last resort for answers [43]. Like many families undergoing CGES in the pediatric setting [6], families in this study were engaged in long diagnostic odysseys and may not have derived solace from the promise of future answers. Our follow-up interviews with families three months after return of results will shed light on this question. Although advances will be made, providers must temper their enthusiasm so as not to set false expectations for rapid breakthroughs.

All providers discussed the benefits of participation in terms of altruism, although this was especially emphasized when a diagnosis had not been found. Previous research suggests that as patient perceived personal benefit of genetic testing decreases, perceptions of altruistic benefits increase [44]. This finding clearly fits for providers, as well, as it aligns with our findings that providers emphasized altruism in the absence of individual benefit to the child or family. Providers likely underscored the benefit to research and others in the future in an attempt to assuage perceived family disappointment due to the lack of diagnostic findings, or perhaps to create ongoing partnerships with families in the research endeavor [41].

Limitations

The present study is limited by its racially homogenous sample and would benefit from a more diverse perspective, as well as from a larger sample size and the involvement of providers from multiple institutions and disciplines. Since sessions occurred in person and our analysis was based off of transcripts, we could not analyze the nuances of nonverbal communications between providers and patients. Moreover, we did not perform a formal assessment of patient provider communication through the use of tools to measure clinical dialogue, nor did we formally assess the oral literacy demands of the return of results sessions. Such assessments are planned for the future. As an observational study, we were unable to analyze the thoughts and feelings of families during the session unless explicitly stated. We are currently conducting interviews with families 3–4 months after receipt of results in order to better gauge understanding of and response to results, and to gather recommendations for improving the process for results disclosure. Last, our sample consisted of the first return of results sessions performed as a part of our on-going study, and providers may have altered their disclosure techniques as a result of lessons learned in vivo. Future research might evaluate techniques providers developed as they gained more experience returning CGES findings.

Conclusion

While largely confined to specialty clinics at this time, future integration of genomic testing technologies, such as CGES, in the primary care setting is expected. As these technologies both diffuse into clinical care and yield increasingly complex and uncertain results, traditional information-laden strategies for educating patients must be adapted. However, to develop effective communication materials for the general public, scientific experts first need to understand what information people need and want to know, as well as the efficacy of various information delivery modalities, to facilitate understanding and informed medical decision-making [31]. A patient-centered approach, focusing on the individual’s context and needs, is an increasingly recognized necessity in the genomic era [45]. Physicians, too, would benefit from a simplified report so that they are able to understand and convey appropriate and desired information. This is especially critical as genomic medicine becomes standard in primary care over the coming years, and physicians are tasked with integrating and monitoring findings for medical usefulness. Finally, providers must be conscious of helping patients set reasonable expectations for future diagnostic and therapeutic breakthroughs relating to genomics.

Summary points

  • Clinical genome and exome sequencing is currently utilized for the diagnosis of suspected genetic diseases and is expected diffuse into standard care.
  • There is little research as to how sequencing results are disclosed and discussed with families. The present study seeks to fill this gap so as to facilitate the development of best practice recommendations.
  • As part of a Clinical Sequencing Exploratory Research (CSER) project, we recorded and analyzed, using inductive thematic analysis, 25 sessions where one or more of seven genetic counselors and six physicians returned diagnostic and secondary pediatric sequencing results to families.
  • We found that providers spent the majority of each session discussing diagnostic findings and utilized a results report as a guide. This resulted in the use of highly technical language to describe genomic and sequencing concepts, which often led to confusion in families.
  • As providers returned exome sequencing results to families, they engaged in behaviors that we grouped thematically to align with four central processes: teaching genetic concepts; assessing family response; personalizing sequencing findings; and strengthening relationships with families.
  • Providers utilized the following tools during the process of teaching genetic concepts: a basic tutorial of genetic concepts; and explanations of the language used to describe sequencing and genetic phenomena.
  • Providers utilized three primary tools to engage in families’ experience of receiving results: assessing the imagined value of sequencing; probing for families’ understanding of genetic concepts; and eliciting feedback about the disclosure experience.
  • Providers utilized two methods to personalize sequencing results: discussing medical management; and making recommendations for next steps in light of sequencing results.
  • Providers utilized the following tools to strengthen their relationships with families: validating the families’ questions and experiences; and appreciating the families’ contribution to research.
  • Families were most vocal discussing medical management and next steps, and least vocal discussing technical details of sequencing.
  • Given the complexity of clinical genome and exome sequencing and its growing scope, traditional information-laden models of counseling that place high genomic literacy demands on patients, are no longer tenable. Ideally, sessions should instead be tailored to patient interest in medical management and next steps, with patient-friendly supplementary information available if desired.

Acknowledgments

Financial disclosure

This research was supported by grant #1U01HG006546-01 from the National Human Genome Research Institute (NH-GRI).

No writing assistance was utilized in the production of this manuscript.

Footnotes

Competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Ethical conduct of research

The study was approved by the institutional review boards at The Children’s Hospital of Philadelphia and the University of Pennsylvania. Informed consent was obtained from all participants.

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