Patient perspectives on the use of categories of conditions for decision making about genomic carrier screening results

Abstract

As expanded genome-scale carrier screening becomes increasingly prevalent, patients will face decisions about whether to receive results about a vast number of genetic conditions. Understanding patient preferences is important to meaningfully demonstrate the ethical goal of respect and support patient autonomy. We explore one possible way to elicit preferences by sorting conditions into categories, which may support patient decision making, but the extent to which categories are helpful is unknown. In the context of a randomized trial of genome sequencing for preconception carrier screening compared to usual care (single disease carrier testing), we interviewed 41 participants who had genome sequencing about their experience using a taxonomy of conditions to select categories of results to receive. We then conducted interviews with an additional 10 participants who were not randomized to genome sequencing, asking them about the taxonomy, their reasons for selecting categories, and alternative ways of presenting information about potential results to receive. Participants in both groups found the categories helpful and valued having a meaningful opportunity to choose which results to receive, regardless of whether they opted to receive all or only certain categories of results. Additionally, participants who received usual care highlighted preparedness as a primary motivation for receiving results, and they indicated that being presented with possible reasons for receiving or declining results for each category could be helpful. Our findings can be used to develop approaches, including the use of categories, to support patient choices in expanded carrier screening. Further research should evaluate and optimize these approaches.

INTRODUCTION

As rapid and low-cost genome sequencing becomes increasingly prevalent in reproductive medicine, clinicians will face new challenges in how to offer expanded carrier screening to patients (Wienke et al., 2014; Benn et al., 2013; Lazarin et al., 2013). Historically, carrier screening in patients with no family history of genetic disease has been primarily population based, with panels developed based on specific populations’ genetic predispositions (ACOG Committee on Genetics, 2009; ACOG Committee on Obstetrics, 2007). However, some commercial laboratories are now offering expanded carrier panels for all patients (Lazarin et al., 2013). This trend toward expanded, genome-scale carrier screening will require new approaches to supporting patients as they decide whether to receive results about a vast number of genetic conditions.

The prospect of expanded carrier screening has long raised questions about what conditions should be offered to patients as screening options and how they should be presented. Some have proposed delineating which genetic conditions should be offered based on their severity, probability, age of onset, treatability, or other characteristics (Lazarin et al., 2014; Rolland & Williams, 2005; Burke et al., 2001; Botkin, 1995). Sorting conditions based on categories that are meaningful to patients may help reduce patients’ decision-making burden (Korngiebel et al., 2016). However, it can be difficult to objectively define the boundaries of these categories (Himes et al., 2017; Wertz & Knoppers, 2002), and critics have argued that categorizing conditions to determine what is offered to patients may have harmful implications for reproductive autonomy and disability rights (Chen & Wasserman, 2017; Parens & Asch, 1999).

Despite this ongoing debate, there is little known about how the use of categories to sort genetic conditions contributes to patients’ decision-making processes or how these categories should be presented. Recognizing the value-based nature of carrier screening decisions (Wilfond & Goddard, 2015), the American College of Medical Genetics and Genomics has noted the importance of providing patients with tailored and transparent information about their screening options (Grody et al., 2013). Recent empirical studies have found that patients prefer to make choices about genome sequencing (Marshall et al., 2016) and expanded carrier screening in particular (Schneider et al., 2016). However, additional evidence is needed to more fully understand how patients prefer to make decisions about expanded carrier screening, including the value of having category options and the extent to which categories are helpful in allowing patients to make meaningful choices.

Here, we present evidence about patients’ decision-making processes in selecting which categories of genome sequencing results to receive. We interviewed two groups of participants after they used a previously developed taxonomy of conditions (Korngiebel et al., 2016; Leo et al., 2016) to select which categories of results they wanted to receive. We asked the first group about their category selections and perspectives on the importance of choice, and we conducted focused follow-up interviews with a second group to confirm and elaborate upon the findings of the initial interviews, probing about their decision-making process, reasons for their selections, and assessments of the initial taxonomy as well as alternative options for presenting information about the results they could choose to receive. Our findings provide needed empirical evidence about how patients make decisions about genomic carrier screening and how different ways of presenting information can support those choices, including the extent to which offering such choices is ethically important as a means of demonstrating respect for patients. As the clinical translation of expanded carrier screening moves forward, these findings can inform research efforts to develop clinical guidelines and standard approaches to providing information, including comparing the trade-offs between patient preferences and clinical costs, measuring patient outcomes such as decisional satisfaction and psychosocial impact, and developing and testing different approaches to presenting information. Moreover, future research findings notwithstanding, it is important to understand patient perspectives on decision making to learn what types of interactions may achieve the ethical goal of demonstrating respect in a way that is meaningful to patients.

METHODS

Overview: NextGen study

Both interview samples consisted of participants who had previously enrolled in the NextGen study at Kaiser Permanente Northwest (KPNW). KPNW is an integrated health care delivery system in the Portland, Oregon metropolitan area. The NextGen study was a randomized trial of preconception carrier screening in which participants either received usual clinical care (single disease carrier testing) or genome sequencing (Kauffman et al., 2017). Prior to randomization and in the presence of a genetic counselor, NextGen participants reviewed a taxonomy of genetic conditions consisting of a checklist of six categories, including five related to carrier status—conditions with significantly shortened lifespan, serious conditions, mild conditions, conditions with unpredictable outcomes, and conditions that begin as adults—and one related to medically actionable conditions in the participant (incidental findings) (Korngiebel et al., 2016; Leo et al., 2016). A study advisory committee comprised of national experts in genetics and genomics sorted gene-condition pairs into these six categories (728 pairs related to carrier status and 114 pairs related to secondary findings) (Himes et al., 2017). Each category included a brief description and one or more examples of the types of conditions included therein. See Table 1. NextGen participants were asked to select which of these categories of results they wanted to receive if they were randomized to genome sequencing, with the exception of conditions with significantly shortened lifespan, which all genome sequencing participants received.

Table 1:

Initial category checklist (Option 1)

Categories of Genetic Conditions	Do you wish to receive these results?
Conditions with significantly shortened lifespan
Most children do not live past early childhood, even with medical interventions Tay-Sachs results in the gradual loss of movement and mental function. Infants develop increasing seizures, vision and hearing loss, and severe mental disability. Death usually occurs by age 4.	Everyone will receive
Serious conditions
Most children will have medical problems that require regular medical visits, daily medications, carefully monitored diets, or surgeries; or will have serious problems with learning, vision, hearing or mobility. Children may have shortened life spans into early adulthood. Duchenne Muscular Dystrophy causes gradual loss of muscle function, beginning at five years of age. Children benefit from wheel chairs, and medications can support breathing and cardiac function, but most people do not live past their 20’s. People with Phenylketonuria (PKU) follow a very restrictive low protein diet for life to avoid problems with learning and behavior. Usher Syndrome causes severe hearing loss from birth and vision loss later in childhood. In adolescence, people develop night blindness and a gradual loss of peripheral (side) vision. Batten Disease causes gradual loss of brain functions, beginning between 5-10 years of age. With gradually worsening seizures, visual problems, and learning. Most children do not live past their teens or twenties. Cystic Fibrosis affects the lungs and digestive system. People with CF require frequent doctor visits and typically take many medications. The average life expectancy is 35 years, but this continues to improve with new treatments.	□ Yes □ No
Mild conditions
Most children will have medical problems that require occasional extra medical visits, occasional medications, a slightly modified diet, or surgery; or will have mild problems with learning, vision, hearing, or mobility. People with Ataxia with Vitamin E Deficiency develop clumsy hand movement, and reduced awareness of body positioning as older children. Later symptoms may include difficulty speaking and loss of some vision. These problems can be reduced with taking Vitamin E daily. Ichthyosis is characterized by scaling of the skin, particularly on the neck, trunk and lower extremities. Typically this scaling improves with age and during the summer months. This condition typically does not affect intelligence or behavior.	□ Yes □ No
Conditions with unpredictable outcomes
It is difficult to predict the outcome for many children. Some children will have more serious versions but others will have more mild versions or no problems at all. Gaucher Disease Type 1 causes degenerative bone disease and low blood counts. While some people develop symptoms in childhood others have few symptoms even as adults. For those who do have these symptoms, treatments can reduce symptoms. Limb Girdle Muscular Dystrophy cause muscle weakness that affects the ability to walk and run. Some people are affected as children but others are not affected until adulthood. Some people lose the ability to walk within 10 years, but other people have less serious problems.	□ Yes □ No
Conditions that begin as adults
Few have any symptoms as children, but medical, behavioral, vision, or hearing problems may begin as adults. Hemochromatosis causes liver, heart, and pancreas problems. The first symptoms typically begin between the ages of 30 and 50, and can be treated relatively effectively, if they even develop at all. Alpha-1 Antitrypsin Deficiency causes emphysema (progressive breathing difficulty and a frequent cough) with symptoms typically developing after age 60 in non-smokers, and after age 40 in smokers.	□ Yes □ No
Conditions in you that are medically actionable (Incidental Findings)
Conditions that are related to your personal health that can be treated, prevented, or detected early, or there is a high risk for a medical problem that can likely be treated, prevented, or detected early. Adults with mutations in a gene that can cause breast cancer and other cancers and can benefit from screening or risk-reducing surgery. Adults with mutations in a gene that can cause life threatening reactions to anesthesia.	□ Yes □ No

Sample and data collection: Genome sequencing group

At the time of initial study enrollment, NextGen participants who were randomized to genome sequencing consented to potentially being contacted for a follow-up interview approximately one year following receipt of their results. Our goal was to engage approximately 40 participants in an in-depth reflection about their genome sequencing result experience. We invited couples as well as women with non-participating partners. Interviews were conducted in person or by phone, and couples were typically interviewed separately but sometimes together, according to the participants’ preferences. The interview guide explored a range of topics pertaining to the study and genome sequencing result experience, including: recollection and reaction; actions taken or not; value/utility to self and reproductive decisions; and overall reflections of their experience. The interview guide specifically explored two questions about category selection at the time of consent (“How did you feel about choosing the category of results and how/why did you make this decision?”), and the value of having choice in the selection of results (“How important was it for you to have choice in those categories?”). Interviews took place between May 2016 and February 2017 and lasted approximately one hour each. Participants provided informed consent at the start of the interview and were not compensated separately from their compensation for the NextGen study.

Sample and data collection: Usual care group

To gain more detailed insight into NextGen participants’ thought processes and confirm our initial interview findings with participants whose responses would not be shaped by their genome sequencing results, we also conducted focused interviews with participants who received usual care. In these interviews, we asked participants to walk through the category selection process, using cognitive interviewing methods including think-aloud and probing techniques (Collins, 2003; Jobe & Mingay, 1989). Interviews were conducted by phone using a semi-structured interview guide, which asked participants to reflect on their initial process of deciding which results they wanted to receive, then to revisit the initial checklist and discuss why they or somebody else might or might not want to receive results in each category. The interview guide concluded with several questions about carrier screening in general and the participant’s reactions to three alternative checklist options. Before each interview, we emailed each participant a file including the initial category checklist (Option 1), as well as three alternative options to consider. Option 2 asked participants to make a global yes/no decision for all categories. Option 3 asked participants to decide separately for each individual genetic condition. Option 4 modified the initial checklist by: (a) combining serious and mild conditions into a “significant conditions” category, (b) removing the example conditions but keeping the brief descriptions, and (c) adding common reasons why someone might want or not want to receive each category of results. See Table 2. Interviews took place between June and September 2016 and lasted approximately one hour each. Participants provided informed consent at the start of the interview and received a gift card as compensation.

Table 2:

Revised category checklist (Option 4)

Categories of Genetic Conditions	Reasons you may want this category	Reasons you may not want this category	Do you wish to receive these results?
Conditions with significantly shortened lifespan	To end the search for a diagnosis when the child is born.	It is important to you to experience pregnancy and having a child, regardless of the outcome.	Everyone will receive
Most children do not live past early childhood, even with medical interventions.
Significant conditions	To avoid a pregnancy that could lead to a child with a very serious disease.	Knowing about conditions with no cure could be stressful and create worry during a pregnancy.	□ Yes □ No
Most children will have medical problems that require regular medical visits, daily medications, carefully monitored diets, or surgeries; or will have problems with learning, vision, hearing or mobility. Children may have shortened life spans into early adulthood.
Conditions with unpredictable outcomes	Ability to avoid a having child that may have a disease.	Knowing is worse when the range of possible disease ranges from no disease to very sick.	□ Yes □ No
It is difficult to predict the outcome for many children. Some children will have more serious versions but others will have more mild versions or no problems at all.
Conditions that begin as adults	Ability to better predict and plan for the future, including watching for new treatment options.	Worry about stigma or your child being labeled based on a condition that won’t happen for several decades.	□ Yes □ No
Few have any symptoms as children, but medical, behavioral, vision, or hearing problems may begin as adults.
Conditions in you that are medically actionable (Incidental Findings)	Ability to take medical action to prevent or treat disease.	Wouldn’t want the results to be something that you think about all the time, causing stress and anxiety.	□ Yes □ No
Conditions that are related to your personal health that can be treated, prevented, or detected early, or there is a high risk for a medical problem that can likely be treated, prevented, or detected early.

Data analysis

All interviews were recorded, transcribed verbatim, de-identified, and uploaded to online qualitative analysis software for data management. For the genome sequencing group, we generated code reports of participant responses to the two relevant questions. We then conducted content analyses of data from both groups, using a combination of a priori codes derived from interview questions and inductively derived codes identified using open-coding techniques (Bernard & Ryan, 2010; Strauss & Corbin, 2008; Patton, 2002). For the genome sequencing group, an experienced qualitative researcher (JLS) reviewed the reports multiple times to categorize responses to each question and summarize the common reasons given for endorsement of a theme. For the usual care group, two experienced qualitative researchers (SAK, KMP) iteratively developed, tested, and applied a coding scheme then summarized the content of each code to develop themes. Analysis summaries for both groups were shared and discussed with the research team to aid in consensus of interpretation (Denzin & Lincoln, 2011).

Institutional Review Board approval

This study was approved by the KPNW Institutional Review Board.

RESULTS

Participant characteristics

We invited 93 genome sequencing participants approximately 12-18 months following receipt of genome sequencing results, of whom 37 declined and 54 (59%) agreed to be interviewed. Of those, 41 participants (27 women and 14 male partners) were asked the two questions about category selection and choice and are included in this analysis.

We also contacted 31 usual care participants approximately six months after they enrolled in the NextGen study, to reach a target of 10 interviews. Of those approached, 14 were unable to be reached, 7 declined or were unavailable, and 10 (32%) completed the interview. Participant characteristics for both groups are shown in Table 3.

Table 3:

Participant characteristics at study enrollment

	Genome sequencing participants (n=41)	Usual care participants (n=10)
Age (years)
Range	25-42	24-38
Mean (standard deviation)	32.8 (4.2)	31.5 (4.4)
Sex (female)	28 (68%)	10 (100%)
Race*
White	39 (95%)	10 (100%)
Black	0 (0%)	1 (10%)
Asian	4 (10%)	0 (0%)
Native Hawaiian or other Pacific Islander	1 (2%)	1 (10%)
Hispanic ethnicity	0 (0%)	2 (20%)
Education
Some college/Associate’s degree	8 (20%)	0 (0%)
Bachelor’s degree	19 (46%)	3 (30%)
Graduate degree	14 (34%)	7 (70%)
Employment status
Employed or self-employed	37 (90%)	9 (90%)
Unemployed (looking)	0 (0%)	1 (2%)
Unemployed (not looking) or homemaker	2 (5%)	0 (0%)
Student	2 (5%)	0 (0%)
Gross annual income (US$)
20,000-29,999	1 (2%)	0 (0%)
30,000-39,999	2 (5%)	2 (20%)
40,000-59,999	3 (7%)	2 (20%)
60,000-79,999	5 (12%)	0 (0%)
80,000-99,999	9 (22%)	2 (20%)
100,000-149,999	16 (39%)	3 (30%)
150,000+	5 (12%)	1 (10%)
Marital status
Married	29 (71%)	6 (60%)
Divorced or separated	2 (5%)	1 (10%)
Never married	9 (23%)	2 (20%)
No response	1 (2%)	1 (10%)
Has children	12 (29%)	5 (50%)

Genome sequencing participant interviews (n=41)

Category selections and reasons

All but two genome sequencing interviewees chose to receive all categories of results. The most common reason given was the perception that it is better to have more information than not; for example, one participant described that she is “the type of person who likes information—having more information is not bad.” About a third of participants also noted that they did not want to be left wondering about what they could have found if they had chosen less than everything:

“Once I made the decision to do it, then I wanted to know all of it. It’s one thing if there are unknown unknowns. And it’s a different thing if there are known unknowns. If I hadn’t gotten tested and there were results I did not know about them [because of limited categories], then I don’t think I could do that.”

Additionally, some participants said the information would help them plan for their and their child’s future, and two said they might as well take full advantage of the chance to get genome sequencing at no cost to them. The two participants who did not choose all categories said that knowing unpredictable and adult onset outcomes was not worth the worry, and one felt it was the child’s decision whether to learn their genome sequencing results.

Value of having choice

Despite the fact that the vast majority of genome sequencing interviewees wanted to receive all results, they also overwhelmingly supported the importance of having a choice of which results to receive, with most participants stressing the importance of choice and the remainder saying it was potentially important to others but not critical for them. All of the participants who felt having choice was personally important said it was an expected step in showing respect for patients. One participant elaborated:

“Choice is very important. I think I initially went in thinking there would be things that I would have to know even if I didn’t want to&. Then after meeting with the genetic counselor I was like, ‘Okay, I do want to know everything.’ So having that choice was important and not having it may have been a deal breaker.”

Many said having the choice gave them a sense of control and was an important part of making personal decisions about health and reproductive planning. A few also said it could help relieve anxiety about uncertainty. Those who felt less sure about the need for choice questioned why some people would not want to know all the information possible in this context but understood choice might be important for others who might have fears or anxieties regarding this information. Only one participant expressed a preference for fewer options when making this decision, saying the current category selection process felt overwhelming and complex, but still wanted to have some ability to make choices.

Usual care participant interviews (n=10)

Category selections

In the usual care interviews, six participants said they wanted to receive all categories of results. Of the remaining four, none wanted adult onset results. Additionally, one did not want mild, one did not want unpredictable, and one wanted neither mild nor unpredictable results.

Primary reason to receive results: Preparedness

Across all categories, preparedness was the most common reason that usual care interviewees cited for wanting to receive results. This often centered on a general sense that more information is better. For example, one participant described the importance of preparation and information as a reason for choosing to receive unpredictable results:

“I don't anticipate this being as much [about] not continuing the pregnancy, but more of wanting to do some research, and talk to some people, and think about what this means, and how we need to set up our life, and what kinds of things we need to prepare for.”

Another commented that some people could be driven simply by a desire to know as much information as possible:

“Some people calm themselves with information. So even if the thing that they're researching doesn't end up coming to fruition for their family you could feel that you've kind of armored yourself with information.”

Participants also cited several specific aspects of preparation, including: making discrete decisions about conception or prenatal care; accommodating a child after birth; seeking out medical, financial, and/or social supports; making necessary lifestyle changes; starting the emotional acceptance process; avoiding surprises; researching and starting treatments; and preparing the child for what is to come. See Table 4.

Table 4:

Aspects of preparation

Aspect of preparation	Exemplar quote
Making discrete decisions about conception or prenatal care	“It's helping us make a decision on what we would do with a pregnancy. It's helping us be prepared if we decide to keep it.”
Accommodating a child after birth	“My child would still be my child. And so I'd just get ready to start thinking about, I don't know, how to best accommodate them. Clumsy hand movement and reduced body awareness seems like manageable things that we could tackle together.”
Seeking out medical, financial, and/or social supports	“There are still certain aspects that you have to know. Like, what are you supposed to do for treatment. … What kind of insurance do you need, or what are you going to…You know, they're going to be paying for their providers. What kind of treatment options are there and things like that.”
Making necessary lifestyle changes	“My life would be significantly impacted, and my child's life would be significantly impacted. So as I think about somebody who works full time and this means a lot of things about my life that might not be possible.”
Starting the emotional acceptance process	“I think that you can eventually get used to anything and have that become normal or accept it. And so I guess I would want to start that process as early as possible. And if some of these things do … continue to get gradually worse, I think I'd rather have the time for me and my husband to accept it together.”
Avoiding surprises	“It's a little scary to think about having a child that has one of these diseases. But I think that, again, that it would be much scarier if it was a complete surprise.”
Researching and starting treatments	“These diseases it seems could benefit from treatment and early detection; I imagine physical therapy. And, just the very unpredictable nature of it would make me want to do more research on my own, like if I knew that there was a high risk for that. Yeah, I would want to do more research.”
Preparing the child for what is to come	“I do think that these are things that I would want to know about and help prepare my future child for. But I also feel like these are things that they would deal with when they're adults, and not necessarily something that I would be dealing with. So I don't know, I think it would be helpful if I could tell my future child, you're more likely to get this disease here. And they could be prepared for it as adults.”

Reasons not to receive results

Regardless of whether they chose to receive results or not, usual care interviewees identified several similar concerns or potential concerns for receiving results across all categories. Many noted that people might decline results out of a desire to avoid the stress of learning something that cannot be changed, particularly if termination is not an option. For example, one participant described the potential emotional impact of finding out genetic information:

“Sometimes ignorance is bliss. I think if you know your child inside you is going to have severe defects or problems, it's kind of a depressive…maybe more of a depressing pregnancy versus kind of a happy one. So I think a lot of people maybe don't want to know. And especially if there's not a whole lot you can do about it, what's the point other than more worries.”

Another participant, describing the feeling of guilt that could come with a genetic diagnosis, explained that “it's like now that you sought the answers out you're effectively the one that caused that to become your child's reality.” In addition, a few participants raised concerns about the possibility of false positives or questions about access to health care or insurance in the future. Others suggested people might want to avoid having to do extra research, attend additional medical visits, or take the preventative steps necessary to change outcomes related to an identified genetic condition.

In considering the value of receiving results relative to these concerns, there was variation between categories, with some participants suggesting mild conditions might be too insignificant, unpredictable conditions too variable, adult onset conditions too far-off and indefinite, and medically actionable incidental findings too unchangeable, to justify the anxiety and worry involved in receiving those results. See Table 5.

Table 5:

Reasons for not choosing categories

Category	Exemplar quote
Serious	“If there is like nothing to do about it and it's—at the end it's going to be the death sentence kind of disease, then I don't know. … I kind of think that the less you know, the less you're going to think about it. And you're not going to stress over something you don't know or you don't have yet.”
Mild	“These seem like conditions that one could—[my child] and I could learn how to manage, and navigate and figure out. … It seems like a condition that people—that causes discomfort, and people have feelings about. But that it seems like they're things that are pretty manageable. And they're not—they're not going to cause early death.”
Unpredictable	“If the information doesn't tell you anything conclusive, then there's not a whole lot of point to having it.”
Adult onset	“I feel like anything that's going to happen as an adult, nobody even is guaranteed to live to be an adult. You could have an accident, you could—you never really know. … So to me something that's going to start in mid to late adulthood is not really something to worry about in terms of not having a pregnancy or needing to know before the child's born.”
Medically actionable (incidental findings)	“A lot of people feel like, oh well, I don't want to know. If it happens, it happens. If it doesn’t, it doesn’t. … [For example,] my uncle never went [to get tested]. And then when they asked him about it he said, well, … if I'm not having any kids I'm not going to pass it along to them. So I don't really feel like I need to be tested.”

Perspectives on alternative ways of organizing results options

Overall, usual care interviewees liked the use of categories (Options 1 and 4) and said it simplified their decision. One said she preferred the categories “because I feel differently about different types of information.” Even those who wanted to receive all categories of results said they liked having the information and options. Some worried that simply asking for a global yes or no (Option 2) could lead people to say no to everything out of fear, even if they might have wanted to get some of the information:

“That question with one box, no explanations, and nothing to read, kind of makes me want to panic check no.”

On the other hand, participants thought that selecting individual conditions from the full list (Option 3) would be confusing and overwhelming, although some suggested it might be helpful as additional background information or as a double-checking tool for people who were interested in a specific condition.

When presented with an alternative option that combined the serious and mild categories (Option 4), a few participants preferred to keep them separate because they felt they had different implications regarding lifespan and treatment options. However, most were comfortable with combining them, either because they could still get the results they wanted or because they agreed it is hard to draw a line between what counts as serious versus mild. One elaborated on this distinction:

“I do think that the adjective that you use is going to change people's response to it. Because I think especially if you don't have familiarity with the conditions, that if people are told that it's serious they're going to react differently to it than if they're told that it's mild or maybe even significant.”

Most participants also found the descriptions and examples on the checklist helpful, although one commented that the names of the conditions were “Greek to me.” Overall, however, participants thought the details were helpful in picturing how a child would be affected by a particular condition:

“The specifics helped me picture how that would affect my life more. … If I had just had the [description], children may have shortened life spans into early adulthood, that's too general for me to really picture what that means. But then you've got wheelchairs, do not live past their twenties, I can picture that. Low protein diet, I can picture that. Hearing loss from birth, that's easier for me to imagine.”

Finally, most participants thought it would be helpful to see a list of reasons why people might or might not want to receive each category of results, but in general did not think reading those reasons would change their decisions. In the unpredictable and adult onset categories in particular, some thought it would be especially useful to hear different perspectives to understand the extent to which their views aligned with those of others.

DISCUSSION

Our findings suggest that providing patients choices about categories of results to receive for expanded carrier screening can demonstrate respect for patients and support patient autonomy. Although most participants chose to receive all the categories they were offered, both interview groups emphasized the importance of being able to make a choice, even if they were choosing everything. Additionally, several of the usual care interviewees elaborated about certain categories that they perceived as being less valuable relative to their concerns, and most were able to appreciate different reasons that others might have for choosing between categories, which highlights how providing patients a meaningful opportunity to decline certain results can demonstrate respect for patient autonomy. In previous studies, patients have similarly identified individual choice as a critical element of their decision-making process, even if they chose to receive all categories of results they were offered (Wade & Elliott, 2017; Marshall et al., 2016; Schneider et al., 2016; Clift et al., 2015; Facio et al., 2013), particularly among patients of non-European ancestry (Fiallos et al., 2017). However, in the context of our study, which included patients of reproductive age who were actively engaged in family planning, an emphasis on choice may be especially important for preserving patients’ sense of control over their reproductive decisions. Additionally, offering choices may demonstrate respect from and build trust with the providers with whom these patients may have ongoing relationships.

Despite the potential value of offering choices about categories for expanded carrier screening, there are also potential challenges that must be considered. There is a logistical cost to laboratories including the need to track choices, develop different workflows depending on which choices are made, and conduct quality assurance on compliance with the choices that are selected. These costs and barriers to the laboratories must also be considered in designing future programs. For example, a recent study illustrated a similar tradeoff by showing that while some researchers initially preferred a multi-step consent process to offer secondary findings, upon consideration of resource constraints, many switched to prefer a traditional consent process (Appelbaum et al., 2015). Given the small, qualitative nature of our study, quantifying the value of having category choices, by measuring decisional satisfaction, psychosocial outcomes, and outcomes related to perceived respect and trustworthiness, in comparison to the costs and logistical challenges for laboratories will be an important next step for future studies on expanded carrier screening. Even if, ultimately, it is determined that the costs outweigh the benefits of offering choices, continuing this research may nevertheless help shape the content of expanded carrier screening by identifying which results are important to patients. In addition, it may suggest that alternative approaches to address trust, respect, and satisfaction are needed in the process if choices are not offered.

In investigating why so many participants chose to receive all categories of results, our interviews with the usual care group revealed preparedness to be the key motivation for most participants, which previous studies on genome sequencing results disclosure have also identified as an important motivation (Clift et al., 2015; Facio et al., 2013). While the specific preparatory actions—such as emotional acceptance, logistical coordination, or preventative interventions—may vary across individuals and genetic conditions, our findings suggest that for many patients in our population, selecting categories of carrier screening results is viewed as an act of preparing for the responsibilities of parenthood. Some participants noted that carrier results could have implications for reproductive decisions about conception or termination, but the greater value to most participants was the potential relevance of the information to their future child’s life. This tendency to view genetic information as valuable in its own right, rather than as a step toward a specific reproductive decision, conforms to an increasingly common view of reproductive genetic testing in which personal utility is highly influential on patients’ choices (Clift et al., 2015; Facio et al., 2013; Press et al., 2011), and suggests that this view is shared by patients who are of reproductive age and actively engaged in family planning. In light of this perspective, patients who are offered carrier screening may find it beneficial to receive information that acknowledges the potential value of carrier results for preparation and information, in addition to their more immediate implications for reproductive decision making.

Furthermore, this study offers several valuable insights into how certain approaches to presenting information may support patients’ needs. First, participants found the use of categories helpful to support their decision making, noting that the category format allowed them to make a meaningful choice in a simplified manner. Second, they found the presentation of potential reasons why someone might want or not want to receive results informative; even though many said that reading them would not change their decision, reviewing these reasons could empower patients to trust their inclinations in the face of external pressures to receive or decline certain results. Third, participants’ perceptions of the value of the examples was somewhat mixed; some participants found them helpful to provide specifics, while others found them overwhelming. Further work is needed to more thoroughly evaluate how each of these approaches (categories, reasons, and examples) supports patient decision making, including how much each approach contributes to patients’ ability to make a meaningful choice and how it effects patients’ decisional satisfaction and other psychosocial measures. Nonetheless, this study suggests that presenting information in a simple taxonomy of categories like our initial and alternative checklists (Options 1 and 4) has the potential to support patients in making thoughtful choices about genomic carrier screening and feeling confident in those choices (Stacey et al., 2017; Fagerlin et al., 2011). While there may be minimal variation in terms of actual category selections, our results suggest that providing and supporting choice may help give patients a sense of control over the information they choose to receive and to feel they have thoroughly prepared for their roles as parents.

Limitations

This study has some limitations. First, the questions about categories and choice were not a central part of the interview guide for the genome sequencing group, so data from these participants are not as in-depth as for the usual care participants. Second, we purposefully oversampled usual care participants who did not choose to receive all results in their initial decision, so the proportion of participants who chose to receive results in each category does not necessarily represent the larger population. Third, our study population was limited to KPNW patients who were interested in genomic screening, had already had genetic testing from their provider, and had seen a brief background presentation on genetics, so our results may over-represent a positive and relatively well-informed view of genomic screening; however, we hypothesize that choice may be perceived as even more valuable among participants who are less familiar with and/or less predisposed to seek out genetic testing. Fourth, our participants were primarily non-Hispanic White, highly educated, and of relatively high income. Further study on patients’ decision-making processes is needed in more diverse populations. Finally, this small, quantitative analysis only addresses a small number of patients’ perspectives and does not incorporate considerations about costs or other logistical challenges for clinical practice, which are necessary to understand before clinical recommendations can be made on the basis of our findings.

CONCLUSION

In light of the increasingly complicated decisions patients will face due to the clinical translation of expanded carrier screening, our findings offer further evidence in favor of providing patients with choices and presenting categories of conditions to support them in making those choices. While this study offers some additional suggestions for how results information could be presented beyond simply using categories, further research on the ethical implications and logistical tradeoffs of these approaches is needed to develop and optimize clinical guidelines.