The use of heuristics in genetic testing decision-making: A qualitative interview study.

BACKGROUND: Decision-making concerning predictive genetic testing for hereditary cancer syndromes is inherently complex. This study aims to investigate what kind of complexities adults undergoing genetic counseling in Switzerland experience, how they deal with them, and what heuristics they use during the decision-making process.
METHODS: Semi-structured qualitative interviews with eighteen Swiss adults seeking genetic counseling for hereditary cancer syndrome genetic testing and two counseling physicians were conducted and analyzed using a grounded theory approach.
RESULTS: Counselees stated that once they were aware of their eligibility for genetic testing they perceived an inevitable necessity to make a decision in a context of uncertainties. Some counselees perceived this decision as simple, others as very complex. High emotional involvement increased perceived complexity. We observed six heuristics that counselees used to facilitate their decision: Anticipating the test result; Focusing on consequences; Dealing with information; Interpreting disease risk; Using external guidance; and (Re-)Considering the general uncertainty of life. LIMITATIONS: Our findings are limited to the context of predictive genetic testing for hereditary cancer syndromes. This qualitative study does not allow extrapolation of the relative frequency of which heuristics occur.
CONCLUSIONS: The use of heuristics is an inherent part of decision-making, particularly in the complex context of genetic testing for inherited cancer predisposition. However, some heuristics increase the risk of misinterpretation or exaggerated external influences. This may negatively impact informed decision-making. Thus, this study illustrates the importance of genetic counselors and medical professionals being aware of these heuristics and the individual manner in which they might be applied in the context of genetic testing decision-making. Findings may offer practical support to achieve this, as they inductively focus on the counselees' perspective.

Introduction

Individuals suspected to carry genetic variants that lead to hereditary forms of cancer face the decision of whether to take a genetic test [1]. Performed in unaffected individuals, such tests provide a predictive assessment of the risk of developing cancer in the future and can guide preventive measures, such as regular screening, preventive medication, or surgeries. However, such predictive genetic tests also hold important psychosocial implications, can lead to anxiety, and might also indirectly provide risk information for relatives [2]. Moreover, the interpretation of predictive genetic test results is challenging, as cancer risk assessments depend on numerous factors such as the exact genetic variant, family history of cancer, and clinical evidence available for the particular variant [3]. Even a genetic test that does not detect any particular pathogenic genetic variant does not imply that the tested individual is free of genetic risk factors for developing cancer [4, 5]. Finally, the nature of the test’s consequences also depends on many individual factors and involve more medical decisions for the affected individual after the genetic test. For example, women carrying pathogenic variants in the BRCA1 or BRCA2 genes can opt for regular breast cancer screenings or preventive mastectomies to lower cancer risk [6, 7]. The decision-making process in genetic testing for cancer predisposition and other forms of predictive genetic testing is, therefore, considerably complex.

In anticipation of this complex decision-making process, genetic counseling usually accompanies predictive genetic testing in the clinical context. In many countries (including Switzerland) genetic counseling is mandatory before and after predictive genetic testing [8]. Genetic counseling is expected to be performed in a non-directive manner, which in Switzerland is legally determined in the Human Genetic Testing Act (art 14/1). Thus, the counseled individual has a free choice in deciding whether to accept or decline predictive genetic testing.

From an ethical perspective, such a decision should be made intentionally, with an understanding of all relevant available information and in absence of significant external controlling influences [9]. The concept of nondirectiveness in genetic counseling attempts to avoid the imposition of external controlling influences via the healthcare professional, but this principle has been debated since the counseling process as social interaction is inherently influential [10-12]. Still, genetic counselors have an ethical duty to be aware of their potential influence and avoid coercive or manipulative situations. To meet the requirements of intentionality and understanding, the cognitive process of processing factual information is an inherent part of informed decision-making. However, too much information in complex decision-making processes might lead to confusion and information overload [13, 14]. Heuristics, defined as "mental shortcuts or ’rules of thumb’ that decision-makers consciously or unconsciously employ to make judgments of uncertainty" [15], are commonly applied in such complex decision-making processes to avoid overload and facilitate decision-making [16-18]. Theoretical heuristics models distinguish between affect heuristic (the emotional distinction between "good" and "bad"), the representative heuristic (comparison with stereotypes and other schemata), the availability heuristic (reliance on existing knowledge and experience), and anchoring heuristic (the orientation on existing numbers of comparison) [15].

Predictive genetic testing for hereditary breast or ovarian cancer syndromes and hereditary colorectal cancer syndromes (such as Lynch syndrome or hereditary polyposis syndromes) is widely established in the clinical setting. A variety of risk-increasing genetic variants have been identified in this context [19, 20]. They are all not fully penetrant, meaning that a predictive diagnosis of these variants does not necessarily lead to disease outbreaks. In breast cancer, high penetrance genetic variants mean that more than 50% of carriers develop the disease; below 20%, they are considered low penetrance genes; and between 20–50% moderately penetrant [21]. Preventive surgeries or treatments are usually not recommended for carriers of low or moderately penetrant genes [22]. In Switzerland, genetic testing related to hereditary cancer syndromes currently involves targeted or panel testing [23], or, more rarely, exome-wide analyses [24].

In this paper, we aim to analyze how people undergoing genetic counseling in Switzerland deal with the complexity involved in deciding for or against genetic testing for cancer predisposition. We interviewed at-risk adults who attended genetic counseling and decided upon genetic testing for heritable cancer syndromes (hereafter: counselees). We asked them how they experienced the decision-making process and found that their decision was heavily influenced by their life philosophy: while some like to leave life to fate, others prefer control, and genetic testing is perceived as taking control [25]. We also found many instances where counselees talked about how they dealt with the complexities inherent in such a decision-making process. Therefore, we here aim to present a more in-depth analysis of this aspect and investigate the following research questions: What complexities do counselees experience during the predictive genetic testing decision-making process? How do they deal with those and what is the impact of heuristics on the decision-making process? We then seek to extrapolate implications for informed decision-making and how the use of heuristics could be fruitfully addressed in the counseling process.

Most studies investigating heuristics in medical decision-making use hypothetical scenarios and a quantitative approach [26]. Qualitative inquiries that implicitly or explicitly cover the use of heuristics in the genetic testing decision-making progress focus on the UK [27], Canada [28, 29], or the United States [30]. Most qualitative studies distinctively focused on risk perception [31, 32] or psychosocial implications [33, 34]. In contrast to previous inquiries on the role of heuristics in the genetic testing decision-making process, our study takes an inductive approach to investigate the influence of heuristics and focuses on the implications for informed decision-making in the context of genetic testing for inherited cancer risk.

Methods

This work is a secondary analysis from a grounded theory study about the genetic testing decision-making process in the Swiss context, where we found that reducing complexity was an integral part of this process [25]. We applied the COREQ guidelines for reporting qualitative studies [35] (S1 File). We performed semi-structured interviews with at-risk adults who went to genetic counseling regarding genetic testing for hereditary cancer predisposition (thereafter: counselees). To verify early findings and for data triangulation purposes, we additionally interviewed two medical doctors who provided genetic counseling to some of the counselees (thereafter: experts). All participants gave consent before the interview: counselees signed an informed consent form, and experts gave their informed consent verbally, in line with research ethics committee recommendations and the Swiss Human Research Act. The study was approved by the ethics committees of Northwest and Central Switzerland and Bern (No 2017–00316).

Recruitment and data collection

Healthcare professionals providing genetic counseling at the University Hospitals Basel and Bern recruited eligible counselees by handing over the study information leaflet. The exact recruitment procedure varied according to the healthcare professional’s preference: for four individuals, the healthcare professional provided the interviewer with the counselees’ email addresses or phone numbers to contact them directly. In all other cases, individuals interested in participation contacted the interviewer proactively. One potential participant dropped out after initial contact for family reasons. Counselees between the age of 18–70 that were not considered vulnerable due to mental state or pregnancy by the ethics committees that approved the study were eligible. We included both cancer patients and individuals at risk of a hereditary cancer predisposition who attended genetic counseling and had a medical indication for genetic testing according to medical guidelines, such as cancer diagnosis at an early age or significant family history [36, 37]. During the recruitment process, we found that the views of males, healthy individuals, and those deciding against genetic testing were underrepresented yet potentially important for theoretical saturation. We therefore purposefully recruited these participants in a second part of the study. We applied a pragmatic approach to data saturation and critically examined the saturation of themes during the data analysis process [38].

The lead author conducted all interviews between August 2017 and February 2019. Depending on counselee preference, they took place at the University of Basel, Bern University Hospital, or at counselees’ homes. Counselees and the interviewer did not have an established relationship before this study but talked over the phone to discuss the study, its implications, and any remaining questions from participants. They were alone when conducting the interview.

The semi-structured interview guide included questions about the counselees’ experiences during the genetic testing decision-making process. The interview guide was pilot tested with two healthy volunteers (not included in the study) and adjusted after six and again after eleven counselee interviews based on preliminary findings (see S2 File for the counselee interview guide). We also presented three hypothetical scenarios of genetic testing decision-making and asked them how they would decide in these scenarios, and why. Scenarios were developed to address and enrich counselees’ reflections on risk perception and medical actionability (scenario 1), the relative importance of genetic testing in counselees’ lives (scenario 2), and environmental influence on disease outbreak (scenario 3). Field notes were taken before and after each interview.

Expert interviews were conducted after an initial analysis of all counselee interviews and included questions about issues that emerged during analysis, including questions on uncertainty and risk perception (see S3 File). The purpose of expert interviews was to add the experts’ perspective to the analysis and to compare preliminary findings with expert knowledge. Because no new aspects came up, data collection of expert interviews was completed after two interviews.

All interviews were recorded and transcribed ad verbatim. Interviews in Swiss German dialect were translated into standard German upon transcription and all transcripts were pseudonymized. Transcripts were not returned to participants. For publication purposes, illustrative quotes were translated into English by a native German speaker (IK) and double-checked for accuracy by two co-authors (BMZ, DMS).

Data analysis

We followed a grounded theory approach for data analysis [39, 40] and started the inductive analysis during data collection. MaxQDA 2018 (VERBI GmbH) was used for analysis. Interviews were analyzed by open coding and discussed and reflected on alternative interpretations in memos and group discussions throughout the analysis. By connecting codes and emerging themes with each other, BMZ and IK collaboratively started building concepts and categories. At a later stage, we abductively built hypotheses and tested them on interview data, using the grounded theory coding paradigm [39]. For the here-presented secondary analysis, we took a thematic approach to develop a more in-depth analysis on one of the aspects identified in that interpretive process, aiming to identify patterns and issues related to the use of heuristics. We then critically reexamined the interviews for alternative explanations and additional aspects of the phenomenon. With the expert interviews, we also sought to identify potential additional aspects and alternative explanations. We conducted these interviews after an initial analysis of all counselee interviews and included them in the analysis to examine whether experts supported or contradicted our general understanding of interview data. While all participants commented on the original grounded theory study [25], no additional feedback was sought for this secondary analysis.

Findings

A total of 18 counselees and two experts were interviewed for this study. Their demographic characteristics are presented in Table 1. Interview duration ranged from 27 to 101 minutes (mean duration 59 minutes). The findings first develop how counselees experienced the complexity of genetic testing decision-making and then present six heuristics that counselees commonly described when reflecting on their genetic testing decision-making process. Expert interviews were used to confirm and contrast counselees’ views. Heuristics were perceived in various ways; we report these variations in the subsections of each heuristic. A detailed coding framework is available in S4 File.

Table 1

Demographics of counselees (n = 18).

Gender
Female	14 (78%)
Male	4 (22%)
Age
20–29	1 (6%)
30–39	5 (28%)
40–49	3 (17%)
50–59	5 (28%)
60+	4 (22%)
Test result
Variant-positive	7 (39%)
Variant-negative	8 (44%)
Decided against genetic testing	3 (17%)
Cancer syndrome that was tested for
Lynch syndrome	2 (11%)
Hereditary breast/ovarian cancer	16 (89%)
Other characteristics
At least one blood-related child	12 (67%)
Cancer diagnosis at point of counseling	6 (33%)
Previously detected pathogenic variant in the family	5 (28%)

Experiencing complexity

The counselees’ narratives illustrated their experience of complexity and the degree to which they perceived genetic testing decision-making as complex. Counselees stated that once they were aware of their eligibility for genetic testing they had to make a decision either for or against the test. They perceived an inevitable necessity to make a decision in a context of uncertainty. Some questioned whether and when genetic testing was a perceived (medical, psychological, or life-planning related) benefit compared to leaving one’s destiny to fate.

The question for me is, from an ethical perspective, how much do we need to know about ourselves? Why not leave this to fate? There are two sides to this. (counselee 13)

Perceptions of complexity varied between counselees. While some counselees underlined the difficulty in interpreting a positive or negative test result and in understanding what impact it would have on their lives, others described their decision to be tested as a logical consequence based on the availability and their eligibility of being tested.

We’ve had family reunions from time to time with my cousins and for some, it’s still an issue, even though we’ve known for a couple of years [that a pathogenic genetic variant runs in the family]: ’Maybe we will get tested anyway’. Others say strictly: ‘No, I don’t want to know’. How do you judge that when you have a clear stance and the person in front of you has a different one? It’s just been difficult. For me, it was clear [that I wanted to do the test], and for others, it might be just as clear that they do not want to know. (counselee 14)

So, for them [the counselee’s daughters] it was clear that if I had it [the pathogenic genetic variant], they would take the test right away. […] With us it’s just like that: If something is up, we will do whatever we can to make up for it. (counselee 17)

Emotional involvement seemed to affect the perception of complexity. For example, one counselee explained how the term "mutation" in one of the BRCA genes triggered for her the need for breast removal, which raised negative emotions. By contrast, the term "variant" (used to describe low prevalence genes in genetic counseling, according to this counselee) did not incur such strong emotions, and the decision to analyze such low prevalence genes was perceived as much simpler by this counselee. Conversely, one expert reflected on the difficulty of explaining these variants to counselees in the context of panel testing, stating that those lower risks or variants of unknown significance added complexity that was difficult to communicate. This expert feared that counselees would instead overestimate the risks of these variants.

Another emotionally challenging aspect for some counselees, confirmed by experts, was their family history of cancer. While some reported that they were talking openly about both cancer and its hereditary component, other counselees were reluctant to ask questions regarding family members who died from cancer, because they were afraid of the negative emotions this would generate or because they found it strange to contact distant family members for rather personal questions. For some counselees, this was an important barrier to informed decision-making.

Yes, I had a hard time [asking my family for information]. I didn’t know how to ask my aunt, whether to call or go by or write an SMS, whether I should say why I was asking or just say that I was [generally] interested. […] You don’t know exactly what you might trigger in that person when coming up with these questions […]. (counselee 11)

Observed heuristics and their implications on the decision-making process

We observed six heuristics counselees adopted to deal with the aforementioned complexities: (1) Anticipating the test result, (2) Focusing on consequences, (3) Dealing with information, (4) Interpreting disease risk, (5) Using external guidance, and (6) (Re-)Considering the general uncertainty of life. These heuristics have different implications on the decision-making process (see Table 2 for an overview of the observed heuristics and their impact on counselees’ decisions).

Table 2

Overview of the observed heuristics and their impact on the decision-making process.

Observed heuristics	Influence on the decision
Anticipating the test result	Perceived low risk for positive test -> test no
	Perceived high risk for a positive test -> test yes
Focusing on consequences	Positive test -> preventive action is taken (e.g. mastectomy, regular preventive examinations)
	Negative test -> health care can go back to “normal”
Dealing with information	Postponing the decision
Interpreting disease risk	Polarized ‘all-or-nothing’ risk perception might lead to anxiety or carelessness
Using external guidance	Using the example of others when deciding for or against genetic testing
(Re-)Considering the general uncertainty of life	Having the impression that own choices have only a limited impact on health status/life span

Anticipating the test result

Counselees built expectations concerning the outcome of their genetic test. Those who already knew that a close family member was a carrier of a pathogenic genetic variant referred to their 50:50 chance of having inherited the pathogenic variant. One counselee stated that knowing his mother was a carrier made him cope better with the test result (which turned out to be variant-positive) and also made him more rational during the decision-making process.

For those who were the first in their family to get a test this heuristic was particularly important as they expressed certain expectations:

Somehow, I almost expected that I could carry it [the pathogenic genetic variant], too. I didn’t think, I’m going to do this test and I’ll be negative anyway, but rather thought: well, maybe I’m positive. (counselee 02).

And when I look at my pedigree I know that the risk [of cancer] is certainly increased. (counselee 11).

This preconception influenced and guided the genetic testing decision-making process. Perceiving the risk of carrying a pathogenic genetic variant as low made it easier to decide against genetic testing. Some counselees based this expectation on the pedigree analysis which is part of genetic counseling, while others had a rather intuitive feeling about it.

Focusing on consequences

As confirmed by both experts, genetic counselors are supposed to inform counselees very cautiously about the consequences of genetic testing. Accordingly, many counselees had a clear idea about the next steps to take if the genetic test was positive, e.g. preventive surgery or regular preventive check-ups. It was important to them to think through these consequences before taking the test. To be aware of a positive test result and not take the suggested action seemed a higher psychological burden in terms of fear and uncertainty to some counselees than not taking a genetic test at all.

So that’s why I am saying, with this test, you have to know very clearly beforehand […] would you agree to have both breasts amputated, and would you have your ovaries removed at the age of 40? (counselee 09)

Thinking through eventual results and consequences, counselees seemed to develop a personal decision tree, which guided them along the testing process. For example, one counselee stated:

I really expected to have it [the pathogenic genetic variant]. Because of the whole family history […]. And I had already planned step by step how to continue […]. I would have done the surgery to remove my breasts, just for prevention, that would have been my next step. (counselee 03)

Consequently, counselees focusing on consequences were reluctant to take a genetic test in the absence of medically actionable consequences in case of a variant-positive test result.

Dealing with information

Those counselees who felt overwhelmed by the complexity of the decision tended to escape the situation by avoiding information on the subject. Young individuals, for example, postponed their decision regarding whether to take a test until consequences such as screening programs or preventive surgeries were recommended due to age.

And I was much younger back then and inexperienced, and I found it difficult. And then with my grandparents, it was even more difficult, I didn’t dare to ask them [about family disease history]. […] That’s why I thought I’d gather my courage for a few more years. (counselee 15)

Some counselees also expressed reluctance to find out the details of their test result. One counselee expressed feelings of doubt and admitted that he agreed to the test before considering the consequences, but still felt obliged to continue so his daughter would know whether she was at risk. Another counselee said her result was inconclusive, which for her implied that the result was not positive, so it was negative, and that was all she wanted to know about it because she did not want to live her life worrying about genetic risks. One expert confirmed that this occurred regularly.

On the other hand, several counselees gathered a lot of information, stating that this was a helpful strategy for them:

I had read a lot about BRCA1 all by myself [before genetic counseling] and I actually know quite a lot about it. And I found it [genetic counseling] very exciting, it was more like an educational event, or like a mutual exchange. (counselee 04)

Proactively gathering information gave those counselees the feeling that they could overcome the inherent complexity. They were eager to learn about their test result and its implications, and it was evident for those counselees that they would take a genetic test.

Interpreting disease risk

Counselees interpreted the potential risk of getting cancer in different ways and rated their risk in case of a pathogenic test result. As one expert stated, informing counselees about disease risk was one of the most difficult tasks in genetic counseling. Some counselees and also experts confirmed that risk numbers were interpreted very individually and that for some, quantifying disease risk made a real difference in terms of coping after a variant-positive test result. These counselees reflected on disease probability by making judgments about relative risk numbers that they perceived as "high" or "low" risks to develop a disease.

One counselee, who was skeptical towards genetic testing, reflected that certainty was never absolute and that even a test result that confirmed the presence or absence of a genetic variant could only give "false certainty" (counselee 09). Another counselee stated that even a low cancer risk was rendered useless the moment one actually gets cancer, which for this counselee was the main reason to reject genetic testing.

Some counselees and one expert stressed the difference between carrying a pathogenic genetic variant and actually getting cancer and distinctively considered themselves healthy. This would only change if cancer was actually diagnosed. One counselee stressed that this aspect mainly made him take the genetic test because knowing the risk would allow for preventive measures to stay healthy. For others, in contrast, carrying a pathogenic genetic variant implied disease. One counselee decided against genetic testing because of that perception. Relatedly, another counselee reflected on the anxious feelings he had while waiting for the test result.

In contrast with these considerations, which reflect a certain understanding of disease risk, some counselees restructured risk information to a binary all-or-nothing matter. This was helpful to them to inform their decision-making process:

I think if I knew I had this mutation, even if the probability is only 40% that I got sick, I would still assume that it happens. (counselee 16).

Relatedly, some counselees reflected on their wish for certainty but understood and acknowledged that this was not realistic in that context:

So, the question is whether I really want to know that [a genetic disease risk]. Actually, I only want to know that I have zero percent [risk] (laughing). (counselee 13)

Consequently, counselees interpreted their disease risks very individually and these interpretations shaped and informed their decision-making process.

Using external guidance

Counselees gave numerous examples of external guidance from family members, health professionals, or health insurance. For some counselees, a major factor was what they thought was best for their children. Experts also confirmed this aspect. Particularly for elderly counselees, this made their decision less complex in the sense that they felt less personally affected:

I have done this consultation not primarily for me but at my daughter’s request, so maybe she was more burdened than I was, I don’t know. (counselee 09).

Some counselees heavily relied on their healthcare professionals’ recommendations concerning genetic testing. Some of those already affected by cancer considered this recommendation as the main factor affecting their decision, and in some cases, the doctor’s recommendation even trumped their own attitude:

To what extent should you contradict your doctor by saying ‘that doesn’t make sense’? I’m not enough of a specialist […] to say ‘this is a foolish idea’. (counselee 12)

Moreover, two female counselees who were rather skeptical towards genetic testing explained that they followed their trusted gynecologists’ advice to go to genetic counseling. It thus depended on the position of the healthcare professional and the attitude of the counselee towards healthcare professionals whether their opinion was used as a heuristic or not.

Some counselees argued that the cost approval by the health insurance facilitated their decision as the medical indication was rechecked and approved. (In Switzerland, health insurance only covers the costs of a genetic test for cancer predisposition if there is a medical indication [41].) So some counselees used the heuristic and gained utility from the fact that their health insurance paid for genetic testing.

Those counselees who decided against genetic testing despite a medical indication did not use such external guidance. Rather, they expressed reluctance to discuss their decision with others who were not part of their closest circle. To them, the decision seemed more complicated because they could not rely on any external guidance. For example, one counselee feared that she would need to justify her decision:

It’s my personal decision and my closest friend knows about it but no one else, that’s really my personal thing, yes. […] Possibly because I don’t know if I had to justify myself why I didn’t do it. (counselee 11)

Popular individuals such as Angelina Jolie were not perceived as a source of external guidance. Most counselees were aware of Angelina Jolie’s public decision to opt for a double mastectomy and a hysterectomy due to a pathogenic BRCA2 variant [42, 43]. Some said it became easier for them to explain their diagnosis to others because the story had raised awareness among the general population, but none of the counselees reported that Angelina Jolie’s example had helped them with their own decision.

(Re-)Considering the general uncertainty of life

Some counselees expressed high awareness of the general uncertainty of life, which made them relativize the importance or impact of the genetic test. Some argued that, even if the test was negative, life was still full of (health) risks. They put risk into perspective by illustrating other everyday risks taken despite knowing better, e.g. cycling without a helmet.

The older I become, the higher the risk that I might have a malfunction in my body, and the health-related risk increases anyway. And it’s not necessarily the same disease I already had. It could be something else, just by chance, it could be a lightning strike. And I still feel like having an accident is more likely than having a disease. And that’s why I am not scared I could die [from cancer] because there is nothing I can do about it anyway. (counselee 10)

While those individuals gained little certainty from a genetic test, others felt empowered by knowing and quantitatively assessing their hereditary cancer risk through a genetic test [25].

Discussion

This study used an inductive approach to identify heuristics used in the genetic testing decision-making process based on qualitative interviews. We found that counselees were very much aware of the complexity inherent to predictive genetic testing decision-making on both a cognitive and an emotional level. We identified six heuristics that counselees used to deal with this complexity. Findings can be aligned with theoretical models of heuristics, including affective, representative, availability, and anchoring heuristics [15]. However, our inductively derived findings indicate that those making the decision intertwine these heuristic types in their individual decision-making process and assign differing practical meaning to them. Our findings provide a deeper understanding of the lived experiences of those going through the genetic testing decision-making process, which can be helpful for healthcare workers providing genetic counseling. Thus, from a practical perspective it is helpful to assess heuristics inductively in a particular context.

Our findings support previous work suggesting that disease risk interpretation has a cognitive as well as an emotional component [44]. Risk interpretation is connected to important uncertainty concerning the probability that a pathogenic genetic test result will actually occur; the ambiguity of whether the pathogenic genetic variant will actually cause disease and whether this could be prevented; and the psychosocial and emotional complexities associated with that assessment [45, 46]. Previous studies have also suggested that decision-makers may use a binary conception of genetic risk as a heuristic for decision-making [32, 47]. Moreover, our finding that social relations (such as respect for (medical) experts or a sense of belonging with family or friends) may be used as external guidance illustrate the wish of some counselees to outsource the decision of whether to take the genetic test to someone else. Other qualitative inquiries about genetic testing decision-making made the same observation [28, 48, 49]. Although it is not per se problematic that people base their medical decisions on relational and social aspects [50], it is important that such external influences are made explicit in genetic counseling.

If we aim for counselees to make an informed decision, meaning that they make their decision incorporating relevant information, these heuristics have differing implications. Table 3 gives a structural overview of our discussion on how these heuristics may influence informed decision-making. We generally grouped them into group A heuristics (helpful to informed decision-making) and group B heuristics (potentially impairing informed decision-making).

Table 3

Potential influence of observed heuristics on informed decision-making.

Group	Observed heuristics	Assessment regarding informed decision-making
A	Anticipating the test result	Usually assisted by a pedigree analysis which serves as an external mapping of intuitive feelings–> no harm
A	Focusing on consequences	Experience of self-efficiency
A	Dealing with information	In our sample, not harmful; counselees returned to the topic if they wanted to. Important to have information available that people can rely on when they are ready
B	Interpreting disease risk	In general a common and useful heuristic, but in combination with strong emotions it could be potentially harmful to informed decision-making
B	Using external guidance	Can assist the coping mechanism, not harmful as long as family members and healthcare professionals are aware of their role and do not try to manipulate the decision
B	(Re-)Considering the general uncertainty of life	Might be helpful to avoid being stuck in long recurrent reflections, on the other hand, health care and prevention do have a positive impact on health status/life span, and therefore leaving everything to chance might cause serious harm

On the one hand, the use of heuristics has been widely accepted as a human coping mechanism and are seen as an integral part of decision-making, particularly in complex and uncertain situations [51-53]. Indeed, health psychology research has successfully demonstrated that affective and heuristic components often strongly influence medical decision-making [26, 54]. They can help guide the genetic testing decision-making process [55]. Indeed, group A heuristics (Table 3) were perceived as beneficial by the counselees in our study as they helped them to operationalize information to make their decision, which is useful to be encouraged in genetic counseling [56]. They all are based on simple decision trees with yes/no-options: "If XY happens, I will do Z", which is based on the heuristics of factual knowledge [16]. Consequently, complex information became manageable on a cognitive level and perceived uncertainty decreased on an emotional level, resulting in a logical sequence of actions. Experts also confirmed that they supported this heuristic by proactively discussing potential implications and consequences with counselees in genetic counseling sessions. Counselees who avoided information about genetic testing at some point also tended to apply this kind of if-then logic: For example, the rationale to seek more information and do the genetic test once it is more easily accessible. Genetic counseling encourages this kind of reasoning by illustrating the consequences of a negative or positive result of the genetic testing and the respective preventive options [57].

On the other hand, while group B heuristics (Table 3) also seem to facilitate decision making but also have potentially harmful aspects in the sense that they might hinder informed decision-making or foster anxiety and other psychosocial problems. Therefore, these heuristics should receive special attention in genetic counseling. Group B heuristics tend to trigger strong emotions, such as absolute euphoria or profound unhappiness in case of a negative or positive result in genetic testing. These strong emotions might complicate the decision-making process and cause psychosocial harm. They might hinder individuals to make an informed decision because, in the presence of strong emotions, it is also more complicated to process information, particularly in uncertain situations [58]. For instance, the (re-)consideration of the uncertainty of human life is the counterexample to the above-mentioned decision tree heuristic. Instead of logical decision sequences, such reasoning might become circular, with no escape. This might produce stress, a feeling of losing control, and desperation. On the other hand, such considerations of inherent life uncertainty reflect counselees’ general life philosophy, as our group found in a different analysis based on the same data [25]. Consequently, our findings underline how vital it is for informed decision making that genetic counselors attempt to understand the values and life philosophy of their individual counselees and address them, as those preferring to leave life to fate might be more prone to enter harmful cycles of brooding. Nonetheless, when trying to resolve misunderstandings of facts, genetic counselors still generally have the ethical and legal duty to respect their counselees’ decisions even if they appear irrational, but they may point out hasty or irrational decision making. They may even legitimately refuse to prescribe genetic testing if providing it would be unethical, and there is also an absolute negative right of the counselee to refuse testing even if the geneticist finds that it is indicated [59].

In our sample, the heuristic of avoiding information was not perceived or interpreted as impairing informed decision-making, as it mainly concerned young individuals who opted for genetic testing later in life. Others deliberately chose not to learn more about certain particular implications of their genetic test, which to them was more important than knowing the details. Yet, information avoidance has been reported as problematic to informed decision-making in the genetic counseling literature [60]. Because visiting at least one genetic counseling session was an inclusion criterion to participate in this study, none of the counselees avoided the topic completely, which might be the reason why it was not considered problematic in our study.

Our findings are limited to the decision-making context of predictive genetic testing for hereditary cancer syndromes. Our counselees’ situations were characterized by incomplete disease penetrance (meaning that carrying a pathogenic genetic variant does not necessarily lead to disease) and conducted genetic tests were generally limited to target-specific or panel analyses [23]. However, other circumstances of genetic testing might lead to different complexities and, therefore, to differing use of heuristics.

This was a qualitative study involving 18 counselees and two experts. We experienced difficulty in recruiting enough patients and had to stop recruitment after two and a half years for reasons of time constraints. (This did not apply to experts where we decided to stop recruitment based on theoretical saturation.) When assessing data saturation for themes during the data analysis process, we found the themes identified well saturated and confirmed by expert interviews. Still, the demographic distribution of the sample might point to potential shortcomings in terms of theoretical saturation. First, we had interviewed 14 women and only four men. Second, most participants considered testing for hereditary breast/ovarian cancer syndrome, which is comparatively well-known among the general public [61, 62] and well established in the clinical setting [63]. These factors might influence decision-making as compared to less established hereditary cancer syndromes. Third, because counselees were recruited through counseling physicians, those deciding against genetic testing were difficult to recruit and are underrepresented (only three of the interviewed counselees decided against testing). Those counselees who completely refuse genetic testing might not even bother seeing a genetic counselor and are thus not included in this study, even though from a conceptual perspective these views might have been an interesting addition to our findings. However, this does not affect the practical relevance of this study, as findings include views of those seeing a genetic counselor.

Conclusion

This study confirms that heuristics are a natural part of human decisions and are not opposed to informed decision making by those going through the decision making process of genetic testing for inherited cancer risks. On the contrary, heuristics are crucial in guiding counselees through the complexities of genetic testing decision-making. However, some heuristics can increase the risk of misinterpretation or exaggerated external influences. As this may impair informed decision making, it is important to adequately address heuristics in genetic counseling. Our findings further imply that strong emotions (both positive and negative) require special attention as they might lead to hasty decisions as a result of plain patterns. They might also hinder successful information transfer. To address these emotions along genetic counseling is important. It will be helpful for informed decision-making if the identified heuristics are addressed in genetic counseling to maximize their benefits and minimize the potential impairment some of them might cause. As such, the study underlines the importance of patient-centered, personalized genetic counseling that has the resources to address patient-specific heuristics and interpretations.

Author details and COREQ checklist.

(DOCX)

Click here for additional data file.

Interview guide patient interviews.

(DOCX)

Click here for additional data file.

Interview guide expert interviews.

(DOCX)

Click here for additional data file.

Coding framework.

(DOCX)

Click here for additional data file.

19 May 2021

PONE-D-21-09002

Decision making in genetic testing for hereditary cancer: Patients’ approaches to complexity

PLOS ONE

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Reviewer #1: While this research contributes to a more comprehensive understanding of decision-making about genetic testing in the context of hereditary cancer, the manuscript would benefit from the following:

1. A description of the study sample, including the variability that is represented in the participants. The rational for recruiting 2 physicians was missing and would perhaps be important as much of the introduction and discussion focusses on the role of genetic counsellors.

2. Further development of the findings. While the authors present a theoretical structure based on identified heuristics, it was not necessarily clear the ways in which the identified heuristics influenced decision making in an in-depth manner. Additional detail would strengthen the findings.

3. Categorization of heuristics as unproblematic vs problematic. The description of the heuristics as unproblematic vs problematic in the discussion appears to be the authors interpretations and more fitting in the findings section. However, it was not clear what the authors meant by unproblematic vs problematic - for whom? problematic in what way? for what end goal - patient coping and adjustment, making of an informed decision, making a decision that aligns with values and beliefs, making a decision that mitigates family conflict?? There seems to be inherent assumptions about what is a "good" versus a "bad" decision making process that if made explicit would provide greater clarity of the authors arguments. I also found that determination of the heuristics as either unproblematic or problematic was not sufficiently supported by the presented data or findings and that the binary was not necessarily support by the description in the 3rd column of Tables 1 & 2.

4. The authors state (page 19, line 393) that"the results are still valid," This language about validity in the context of grounded theory/qualitative research requires clarification and perhaps revision depending on the authors conceptualization and use of the term valid here.

Reviewer #2: Overview:

The overall thematic of heuristics to evaluate the decision-making process in genetic-testing for hereditary cancer is respected. The paper shows the perspective of those who have to make the decision to take the genetic-test or not, and to cope with the decision they made and the results. In situations of uncertainty and complexity, the relationship between at-risk persons and health professionals are important. This qualitative research brings to light the perspective of those directly concerned.

However, there are some points to be changed or improved. First two major changes: add the demographic table and complete the section limitations accordingly. Second, don’t use “should”. The other points mentioned in the detailed review are minor.

NB: I did not have access to the 2 supporting information files.

Detailed review:

1. The title speak about patients, but not all participants were patients. In the demographics table disclosed in the initial study (reference 25) there are 6 participants with cancer and 5 with a known mutation in the family. It means that 7 to 12 participants may not be patients per se, but only candidates for genetic-testing.

2. Introduction and methodology

The study is a second analysis of qualitative data, which is possible in qualitative research in order to develop more in-depth analysis. In this secondary analysis, there is an intention to deepen the analysis based on an initial framework of heuristics. It is a thematic approach based on a modified approach to grounded theory and not a typical grounded theory methodology.

The reference 18 (Peters 2006) is cited identifying four heuristics in the introduction. I will recommend to also cite the definition of heuristics from this paper “the mental shortcuts or“rules of thumb” that decision makers consciously or unconsciously employ to make judgments of uncertainty” as heuristics is one of the main research question in the final paragraph of the introduction and it is also the aim of the data analysis in the section methodology.I will also recommend to be more coherent in the declared aim of the research and the aim of data analysis between introduction and methodology.

3. Findings

a. Demographics are missing. You need to cite or reproduce the table from the initial published study (reference 25). It is a very relevant table as we can see important data for the discussion and the limitations of your study.

b. Experiencing complexity. This first result is important as it gives the complexity of the situation: emotion, family context, uncertainty…The issue of language with “mutation” versus “variant” could be more developed (if the data allow it) as it has a direct implication on how medical doctors /genetic counsellor could speak.

c. Six heuristics themes are identified.

This part is the result of interpretation and complex analysis that I cannot assess precisely without doing again the whole analysis, which is not the purpose of this review.

I will recommend adapting the title “avoiding information” as this section speaks also about some participants who gather a lot of information. Moreover, those who postpone the decision may do it, not because they want to avoid information, but because they wait to reach the age when a medical prescription will be made which means in Switzerland the age when the social insurance will cover the cost. Maybe the title could be “dealing with information” or something like that. In the table 1 of the discussion, this could be changed without modifying the sense.

In the section “using external guidance” you mention this need for a medical indication to cover the cost. But in the recruitment part of the methodology, it is written lines 121-122 that : “They all had a medical indication for genetic testing according to Swiss or international medical guidelines, particularly cancer diagnosis at an early age or important family history”. It means that retrospectively some participants who took the test were influenced by the cost, but there are also 3 patients with medical indications who did not take the test in the sample. It seems that the external guidance based on cost might be only relevant to the young ones postponing the test.

The title “(Re-)Considering the general uncertainty of life” is referring to the results of the first paper (ref.25). You could mention it there, even if it is then well described in discussion.

4. Discussion

It is always difficult to draw normative conclusions from empirical data. The presentation in tables has the merit to organize the reflection.

The recommendation to genetic counsellors to take into account the values and emotions of patients, the external influencing factors, seems reasonable. There is nothing new, but the study has the advantage to confirm it from the perspective of those who have to make the decision. It brings sense to what genetic counsellors are doing.

However: Avoid “should” in the abstract line 40, in the discussion lines 371, 373 374, and in the conclusion line 405. This research paper has not the authority to command a “should”. Rather try to formulate this with some sentences showing how important it is for medical doctors prescribing genetic-testing, and for genetic counsellors to …….”. If the genetic counsellor is not prepared to listen to values and context of the at-risk person, the Swiss law will not make compulsory to have a consultation with her/him before deciding on genetic-testing.

5. Limitations:

The gender bias has to be mentioned in the limitations. There are 14 women and only 4 men. Most of the participants (n=16) have an history of breast / ovarian cancer. Without any discriminating approach, it is well known that there is a gender effect in the balance cognitive/emotional reaction. Breast cancer is also the most frequent cancer in women and is intensively publicly mentioned (for instance campaign for mammography). This could also explain that few recruited participants decided not to take the test.

Reviewer #3: In this manuscript, Zimmermann et al. use a grounded theory approach to explore the heuristics used by participants during decision making to undergo predictive genetic testing for hereditary cancer syndromes. They identify 6 heuristics used by participants to help simplify their decisions; and they further divide these 6 heuristics as either problematic or unproblematic, depending on whether they did or did not have aspects that the authors judged to be potentially harmful or create anxiety or psychosocial concerns.

The paper is well written and addresses an important clinical topic, namely participant decision making for predictive testing for cancer risk. By extension, the heuristics identified are useful for those providing counseling about such testing.

It is not clear however, why the authors chose to include 2 counseling physicians in their interviews; and furthermore, having decided to include counseling physicians, why they included only 2 of them, while there are 18 participants who were deciding whether to undergo testing or not. Based on the Methods described, it appears that the physicians were interviewed after the interviews of the patients and the physician interviews asked them about “…issues that emerged during analysis.” It isn't clear to me whether they had already developed their heuristics prior to physician interviews, or whether there was anything of patient responses shared with the physicians. This information would be valuable to include in their Methods.

Subsequent to the Methods section, there is no mention of the physician interviews, and the heuristics and the remainder of the manuscript focuses only on the patient responses.

So, from a methodological standpoint, it would be helpful for the authors to describe the rationale for inclusion of physicians, since it appears that the physician responses were not used to identify the heuristics. If on the other hand, physician responses were in some way helpful for identification of heuristics or for other issues such as validating the complexity of such counseling, then this should be included in both Results and Discussion. And, from a scientific standpoint, it would be helpful for the authors to report on any differences and similarities between findings in the patient and physician groups. On the other hand, if the heuristics identified are all the result of analysis of patients’ interviews, perhaps inclusion of physician interviews is not pertinent to the overall results of the analysis and don’t merit inclusion.

Reviewer #4: The authors have investigated an important and timely research topic with clear practice implications. I have made suggestions to improve the transparency and structure of this manuscript.

General comments

1. I suggest using a qualitative reporting checklist like the COREQ guidelines to enhance the transparency of methods. [Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. International journal for quality in health care. 2007 Dec 1;19(6):349-57.]

Introduction

2. It would be helpful to include a clear discussion of the evidence gap that that authors have intended to address. What has been done on this topic before and what is the novel contribution of this work? Separate paragraphs to address the evidence gap and the specific objectives of this study would improve the introductory section.

Methods

3. Can the authors please explain the context of the “larger grounded theory study” that they refer to in the first sentence?

4. It is unclear why the authors interviewed 18 patient participants and only 2 physicians. How was the decision made to interview only 2 physicians? Similarly, why did recruitment stop at 18 patients? There is no mention of thematic saturation included in the methods description.

5. Why were pregnant people excluded from interviews?

6. Please explain how the interview guide was developed. Was literature review or pilot testing involved? How were the hypothetical vignettes developed? Was the guide revised throughout the interview process?

7. Were the physician interviews analyzed along with the patient (at-risk) participants, or separately?

8. Did the authors collect demographic information from participants? E.g. age/ gender etc? If so, please report.

9. I am curious as to why research participants are referred to as “at risk individuals” throughout the paper. Switching between different terms such as “participants” and “at risk individuals” is unclear.

Results

10. The beginning of the results section would benefit from a high-level summary of the major themes/ sub-themes generated through the analysis, as a preface to the more detailed description.

11. As above, this section would benefit from a description of the characteristics of the participants, if this information was collected.

12. Could the authors please attach the final coding framework as an additional supplemental document? Attaching and linking the results section to the framework may help to provide a clearer structure to this entire section.

13. Within the results section, can the authors speak to any of these themes where participants were generally consistent in their opinions, versus where opinions varied? This would also help to frame the discussion around practice implications.

14. For ease of reading, I suggest pulling all direct quotes out of the paragraphs and including in indented, italicised font.

15. The link between the patient participants and the 2 physician participants remains unclear. The authors may consider reporting their results separately, given that two separate interview guides were used, and only 2 physicians were included.

Discussion

16. I suggest placing tables 1 and 2 and the associated discussion into the results section

17. This section would benefit from a more comprehensive discussion of how findings deviate or align with existing work related to values and preferences related to hereditary cancer genetic testing. Specifically (and as mentioned in introduction comments) what is novel about this contribution to the evidence base and how can findings be used to inform practice/ policy/ future research?

18. The following sentence requires clarification/ elaboration, “Because our results should inform genetic counseling practice, our results are still valid, even though from a conceptual perspective the view of those even refusing to go to genetic counseling would have been highly interesting.”

19. Pending elaboration on recruitment methods, the authors may need to include additional limitations related to their sampling and cessation of recruitment (e.g. why were 18 interviews conducted with 18 at risk individuals and only 2 with physicians)

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Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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15 Jun 2021

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

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2. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter.

RESPONSE: Based on the Swiss Human Research Act (HRA) and the ethics approval obtained for this study, we are legally bound to keep the identity of study participants confidential. Due to the highly identifiable topic of this research (personal and family disease history for relatively rare diseases – hereditary cancer syndromes – and the regionally limited recruitment method, interview transcripts cannot be fully anonymous. We do provide anonymized quotes within the manuscript to illustrate our findings (corresponding to transcript excerpts) and thus confirm with the journal's "guidelines for qualitative data".

Reviewer #1

While this research contributes to a more comprehensive understanding of decision-making about genetic testing in the context of hereditary cancer, the manuscript would benefit from the following:

RESPONSE: We are grateful for reviewer 1's feedback on our study and will reply to their comments in detail below.

Methods

1. A description of the study sample, including the variability that is represented in the participants. The rational for recruiting 2 physicians was missing and would perhaps be important as much of the introduction and discussion focusses on the role of genetic counsellors.

RESPONSE: We have included the demographics of counselees as Table 1 (see results section). We also provide now a rationale for recruiting two experts in the methods section. It now reads: "Expert interviews were conducted after initial analysis of all counselee interviews and included questions about issues that emerged during analysis, including questions on uncertainty and risk perception (see Supporting information file S2). The purpose of expert interviews was to add the experts' perspective to the analysis and to compare preliminary findings with expert knowledge. Because no new relevant aspects came up, data collection of expert interviews was completed after two interviews. "

Results

2. Further development of the findings. While the authors present a theoretical structure based on identified heuristics, it was not necessarily clear the ways in which the identified heuristics influenced decision making in an in-depth manner. Additional detail would strengthen the findings.

RESPONSE: We have included more explicit references in the findings on how heuristics influenced decision-making. An additional overview is given in Tables 2 and 3.

Discussion

3. Categorization of heuristics as unproblematic vs problematic. The description of the heuristics as unproblematic vs problematic in the discussion appears to be the authors interpretations and more fitting in the findings section. However, it was not clear what the authors meant by unproblematic vs problematic - for whom? problematic in what way? for what end goal - patient coping and adjustment, making of an informed decision, making a decision that aligns with values and beliefs, making a decision that mitigates family conflict?? There seems to be inherent assumptions about what is a "good" versus a "bad" decision making process that if made explicit would provide greater clarity of the authors arguments. I also found that determination of the heuristics as either unproblematic or problematic was not sufficiently supported by the presented data or findings and that the binary was not necessarily support by the description in the 3rd column of Tables 1 & 2.

RESPONSE: Thank you, we have rephrased this to be more clear on the context of informed decision-making. Indeed, implications on informed decision-making was not based on the data directly but our interpretation of the findings. We therefore find it more suitable to separate those from what was actually grounded in interview data and kept this part in the discussion. We made this more transparent in the paper.

4. The authors state (page 19, line 393) that "the results are still valid," This language about validity in the context of grounded theory/qualitative research requires clarification and perhaps revision depending on the authors conceptualization and use of the term valid here.

RESPONSE: Thank you, we agree with this reviewer that the term "valid" would need further explanation. We decided that it is easier to rephrase the meaning of our argument, avoiding this term. It now reads: "Those counselees who completely refuse genetic testing might not even bother seeing a genetic counselor and are thus not included in this study, even though from a conceptual perspective these views might have been an interesting addition to our findings from a conceptual perspective. Yet, this does not affect the practical relevance of this study."

Reviewer #2

Overview: The overall thematic of heuristics to evaluate the decision-making process in genetic-testing for hereditary cancer is respected. The paper shows the perspective of those who have to make the decision to take the genetic-test or not, and to cope with the decision they made and the results. In situations of uncertainty and complexity, the relationship between at-risk persons and health professionals are important. This qualitative research brings to light the perspective of those directly concerned.

However, there are some points to be changed or improved. First two major changes: add the demographic table and complete the section limitations accordingly. Second, don’t use “should”. The other points mentioned in the detailed review are minor.

NB: I did not have access to the 2 supporting information files.

RESPONSE: We thank reviewer 2 for their helpful comments. We have addressed this reviewer's suggestions and requests and reply to them in detail below.

Detailed review:

1. The title speak about patients, but not all participants were patients. In the demographics table disclosed in the initial study (reference 25) there are 6 participants with cancer and 5 with a known mutation in the family. It means that 7 to 12 participants may not be patients per se, but only candidates for genetic-testing.

RESPONSE: Thank you, we have addressed this issue by revising the title and, in the manuscript, by consistently referring to "counselees" when talking about those making the decision for or against genetic counseling, "experts" for genetic counseling physicians, and "participants" when referring to all of them together (experts + counselees).

2. Introduction and methodology

The study is a second analysis of qualitative data, which is possible in qualitative research in order to develop more in-depth analysis. In this secondary analysis, there is an intention to deepen the analysis based on an initial framework of heuristics. It is a thematic approach based on a modified approach to grounded theory and not a typical grounded theory methodology.

RESPONSE: Thank you, we have acknowledged this comment in the "data analysis" subsection.

The reference 18 (Peters 2006) is cited identifying four heuristics in the introduction. I will recommend to also cite the definition of heuristics from this paper “the mental shortcuts or“rules of thumb” that decision makers consciously or unconsciously employ to make judgments of uncertainty” as heuristics is one of the main research question in the final paragraph of the introduction and it is also the aim of the data analysis in the section methodology.I will also recommend to be more coherent in the declared aim of the research and the aim of data analysis between introduction and methodology.

RESPONSE: Thank you, we followed this suggestion and introduced the definition as used by Peters et al 2006.

3. Findings

a. Demographics are missing. You need to cite or reproduce the table from the initial published study (reference 25). It is a very relevant table as we can see important data for the discussion and the limitations of your study.

RESPONSE: Thank you, we have included the participant demographics as Table 1.

b. Experiencing complexity. This first result is important as it gives the complexity of the situation: emotion, family context, uncertainty…The issue of language with “mutation” versus “variant” could be more developed (if the data allow it) as it has a direct implication on how medical doctors /genetic counsellor could speak.

RESPONSE: Thank you, we added an additional sentence on that topic. It reads: "Conversely, one expert reflected on the difficulty of explaining these variants to counselees in the context of panel testing, stating that those lower risks or variants of unknown significance added an additional layer of complexity that was difficult to communicate. The expert rather feared that counselees would overestimate the risks of these variants."

c. Six heuristics themes are identified.

This part is the result of interpretation and complex analysis that I cannot assess precisely without doing again the whole analysis, which is not the purpose of this review.

I will recommend adapting the title “avoiding information” as this section speaks also about some participants who gather a lot of information. Moreover, those who postpone the decision may do it, not because they want to avoid information, but because they wait to reach the age when a medical prescription will be made which means in Switzerland the age when the social insurance will cover the cost. Maybe the title could be “dealing with information” or something like that. In the table 1 of the discussion, this could be changed without modifying the sense.

RESPONSE: Thank you, we adapted as suggested.

In the section “using external guidance” you mention this need for a medical indication to cover the cost. But in the recruitment part of the methodology, it is written lines 121-122 that : “They all had a medical indication for genetic testing according to Swiss or international medical guidelines, particularly cancer diagnosis at an early age or important family history”. It means that retrospectively some participants who took the test were influenced by the cost, but there are also 3 patients with medical indications who did not take the test in the sample. It seems that the external guidance based on cost might be only relevant to the young ones postponing the test.

RESPONSE: We think that there is a misunderstanding that we attempted to avoid by reformulating the part on health insurance coverage: participants were not influenced by cost but the external reference point of the health insurance's decision to cover their test gave them an additional reason to take the test (health insurance wouldn't cover it if test was useless).

The title “(Re-)Considering the general uncertainty of life” is referring to the results of the first paper (ref.25). You could mention it there, even if it is then well described in discussion.

RESPONSE: Thank you, we have added the reference as suggested.

4. Discussion

It is always difficult to draw normative conclusions from empirical data. The presentation in tables has the merit to organize the reflection.

RESPONSE:

The recommendation to genetic counsellors to take into account the values and emotions of patients, the external influencing factors, seems reasonable. There is nothing new, but the study has the advantage to confirm it from the perspective of those who have to make the decision. It brings sense to what genetic counsellors are doing. However: Avoid “should” in the abstract line 40, in the discussion lines 371, 373 374, and in the conclusion line 405. This research paper has not the authority to command a “should”. Rather try to formulate this with some sentences showing how important it is for medical doctors prescribing genetic-testing, and for genetic counsellors to …….”. If the genetic counsellor is not prepared to listen to values and context of the at-risk person, the Swiss law will not make compulsory to have a consultation with her/him before deciding on genetic-testing.

RESPONSE: Thank you, we have reformulated the sections mentioned, avoiding the term "should".

5. Limitations:

The gender bias has to be mentioned in the limitations. There are 14 women and only 4 men. Most of the participants (n=16) have an history of breast / ovarian cancer. Without any discriminating approach, it is well known that there is a gender effect in the balance cognitive/emotional reaction. Breast cancer is also the most frequent cancer in women and is intensively publicly mentioned (for instance campaign for mammography). This could also explain that few recruited participants decided not to take the test.

RESPONSE: Thank you, we have acknowledged this in the limitations section.

Reviewer #3

In this manuscript, Zimmermann et al. use a grounded theory approach to explore the heuristics used by participants during decision making to undergo predictive genetic testing for hereditary cancer syndromes. They identify 6 heuristics used by participants to help simplify their decisions; and they further divide these 6 heuristics as either problematic or unproblematic, depending on whether they did or did not have aspects that the authors judged to be potentially harmful or create anxiety or psychosocial concerns.

The paper is well written and addresses an important clinical topic, namely participant decision making for predictive testing for cancer risk. By extension, the heuristics identified are useful for those providing counseling about such testing.

It is not clear however, why the authors chose to include 2 counseling physicians in their interviews; and furthermore, having decided to include counseling physicians, why they included only 2 of them, while there are 18 participants who were deciding whether to undergo testing or not. Based on the Methods described, it appears that the physicians were interviewed after the interviews of the patients and the physician interviews asked them about “…issues that emerged during analysis.” It isn't clear to me whether they had already developed their heuristics prior to physician interviews, or whether there was anything of patient responses shared with the physicians. This information would be valuable to include in their Methods.

Subsequent to the Methods section, there is no mention of the physician interviews, and the heuristics and the remainder of the manuscript focuses only on the patient responses. So, from a methodological standpoint, it would be helpful for the authors to describe the rationale for inclusion of physicians, since it appears that the physician responses were not used to identify the heuristics. If on the other hand, physician responses were in some way helpful for identification of heuristics or for other issues such as validating the complexity of such counseling, then this should be included in both Results and Discussion. And, from a scientific standpoint, it would be helpful for the authors to report on any differences and similarities between findings in the patient and physician groups. On the other hand, if the heuristics identified are all the result of analysis of patients’ interviews, perhaps inclusion of physician interviews is not pertinent to the overall results of the analysis and don’t merit inclusion.

RESPONSE: We thank reviewer 3 for their insightful comments and their positive assessment of our study. The rationale to include expert interviews was to verify and contrast our findings with the perspective of genetic counseling experts. We conducted them after initial analysis of all patient interviews and included in the interview guide the aspects we deemed most relevant for our findings. Relevant for this paper, we included questions concerning uncertainty and risk perception. We have clarified the role of expert interviews in the methods section, it now reads: "Expert interviews were conducted after initial analysis of all counselee interviews and included questions about issues that emerged during analysis, including questions on uncertainty and risk perception (see Supporting information file S2). The purpose of expert interviews was to add the experts' perspective to the analysis and to compare preliminary findings with expert knowledge. Because no new relevant aspects came up, data collection of expert interviews was completed after two interviews." We also implemented the expert interviews more visibly in the findings, stating in what instances their perspectives were in line or contrasting views of counselees.

Reviewer #4

The authors have investigated an important and timely research topic with clear practice implications. I have made suggestions to improve the transparency and structure of this manuscript.

RESPONSE: We thank reviewer 4 for their extensive and insightful comments that indeed were very supportive to improve the paper from our perspective. We reply to this reviewer's comments in detail below.

General comments

1. I suggest using a qualitative reporting checklist like the COREQ guidelines to enhance the transparency of methods. [Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. International journal for quality in health care. 2007 Dec 1;19(6):349-57.]

RESPONSE: We have consulted and report on the COREQ checklist in Supporting Information File S1.

Introduction

2. It would be helpful to include a clear discussion of the evidence gap that that authors have intended to address. What has been done on this topic before and what is the novel contribution of this work? Separate paragraphs to address the evidence gap and the specific objectives of this study would improve the introductory section.

RESPONSE: Thank you, we have introduced a separate paragraph after presenting the aims of the study that includes a small literature review to illustrate the research gap that we intend to fill, which reads: "By contrast to previous inquiries on the role of heuristics in the genetic testing decision-making process, our study takes an inductive approach to investigate the influence of heuristics and focusses on the implications for informed decision-making in the context of genetic testing for inherited cancer risk."

Methods

3. Can the authors please explain the context of the “larger grounded theory study” that they refer to in the first sentence?

RESPONSE: We have added some more contextual information.

4. It is unclear why the authors interviewed 18 patient participants and only 2 physicians. How was the decision made to interview only 2 physicians? Similarly, why did recruitment stop at 18 patients? There is no mention of thematic saturation included in the methods description.

RESPONSE: We added more information on the rationale for recruitment, why it stopped and our approach to data saturation in the methods section. It now reads: "During the recruitment process, we found that the views of males, healthy individuals, and those deciding against genetic testing were underrepresented yet potentially important for theoretical saturation. We therefore purposefully recruited for these participants in a second part of the study. Yet, we had difficulties recruiting enough patients and had to stop recruitment after twoandahalf years for reasons of time constraints. We applied a pragmatic approach to data saturation and critically examined saturation of themes during the data analysis process [28]."

We also added information on the role and rationale behind the expert interviews: "Expert interviews were conducted after initial analysis of all counselee interviews and included questions about issues that emerged during analysis, including questions on uncertainty and risk perception (see Supporting information file S2). The purpose of expert interviews was to add the experts' perspective to the analysis and to compare preliminary findings with expert knowledge. Because no new relevant aspects came up, data collection of expert interviews was completed after two interviews."

5. Why were pregnant people excluded from interviews?

RESPONSE: This was purely for organizational reasons; including pregnant women would have rendered the study to a higher risk-level in terms of ethics approval. We have rephrased to make this more clear in the methods section, it now reads: "Counsellees between the age of 18-70 that were not considered vulnerable due to mental state or pregnancy were eligible."

6. Please explain how the interview guide was developed. Was literature review or pilot testing involved? How were the hypothetical vignettes developed? Was the guide revised throughout the interview process?

RESPONSE: We have added additional explanations in the methods section. It reads: "The interview guide was pilot tested with two healthy volunteers (not included in this study) and adjusted after the six interviews and again after eleven interviews based on preliminary findings (see Supporting information file S1 for the interview guide). We also presented three hypothetical scenarios of genetic testing decision-making and asked them how they would decide in these scenarios, and why. Scenarios were developed to address and enrich counselees' reflections on risk perception and medical actionability (scenario 1), relative importance of genetic testing in counselees' lives (scenario 2), and environmental influence on disease outbreak (scenario 3)."

7. Were the physician interviews analyzed along with the patient (at-risk) participants, or separately?

RESPONSE: We have specified accordingly, it reads: " With the expert interviews, we also sought to identify potential additional aspects and alternative explanations. They were analysed along with the other interviews."

8. Did the authors collect demographic information from participants? E.g. age/ gender etc? If so, please report.

RESPONSE: Thank you, we have included the participant demographics as Table 1.

9. I am curious as to why research participants are referred to as “at risk individuals” throughout the paper. Switching between different terms such as “participants” and “at risk individuals” is unclear.

RESPONSE: Thank you, we attempted to make this more clear by consistently referring to "counselees" when talking about those making the decision for or against genetic counseling, "experts" for genetic counseling physicians, and "participants" when referring to all of them together (experts + counselees).

Results

10. The beginning of the results section would benefit from a high-level summary of the major themes/ sub-themes generated through the analysis, asc a preface to the more detailed description.

RESPONSE: We have implemented a short introductory paragraph at the beginning of the findings.

11. As above, this section would benefit from a description of the characteristics of the participants, if this information was collected.

RESPONSE: Thank you, we have included the participant demographics as Table 1.

12. Could the authors please attach the final coding framework as an additional supplemental document? Attaching and linking the results section to the framework may help to provide a clearer structure to this entire section.

RESPONSE: We have included the coding framework as supplementary file 3.

13. Within the results section, can the authors speak to any of these themes where participants were generally consistent in their opinions, versus where opinions varied? This would also help to frame the discussion around practice implications.

RESPONSE: Generally, we found highly individual and variable experiences which we attempted to outline in our findings. We purposefully refrain from making any quantitative claims (in the sense that some experiences were more often mentioned than others) to avoid readers to make relative quantitative conclusions (such as some experiences are more common than others). Due to low sample size, this is not an interpretation we can take from this study.

14. For ease of reading, I suggest pulling all direct quotes out of the paragraphs and including in indented, italicised font.

RESPONSE: We formatted the results section as suggested.

15. The link between the patient participants and the 2 physician participants remains unclear. The authors may consider reporting their results separately, given that two separate interview guides were used, and only 2 physicians were included.

RESPONSE: The purpose for the expert interviews was to add an additional perspective and verify our findings. That is also why only two expert interviews were conducted; they did not reveal any new insights and were seen as an indication of theoretical saturation. We have included a number of direct references where experts confirmed or contrasted the views of counselees in the results section.

Discussion

16. I suggest placing tables 1 and 2 and the associated discussion into the results section

RESPONSE: We have decided to merge these tables and then present the implications on the decision-making process as an overview table in the results section. However, as the implications for informed decision-making is based on our own interpretation of the findings and not grounded in the data itself (the participants did not explictly reflect on how informed their decision was; we rather used references from the bioethics literature to make such interpretations), we found it more suitable to place these in the discussion section for clarity.

17. This section would benefit from a more comprehensive discussion of how findings deviate or align with existing work related to values and preferences related to hereditary cancer genetic testing. Specifically (and as mentioned in introduction comments) what is novel about this contribution to the evidence base and how can findings be used to inform practice/ policy/ future research?

RESPONSE: Thank you, we have restructured the discussion: we first align our findings with existing work and then focus on implications for informed decision-making, stressing more clearly that our inductive, context-specific approach is of practical relevance and the framing of informed decision-making is, to our knowledge, unique.

18. The following sentence requires clarification/ elaboration, “Because our results should inform genetic counseling practice, our results are still valid, even though from a conceptual perspective the view of those even refusing to go to genetic counseling would have been highly interesting.”

RESPONSE: Thank you, we have revised and clarified the meaning of our argument. It now reads: "Those counselees who completely refuse genetic testing might not even bother seeing a genetic counselor and are thus not included in this study, even though from a conceptual perspective these views might have been an interesting addition to our findings from a conceptual perspective. Yet, our findings are still relevant from a practical perspective, as they include views of those seeing a genetic counselor."

19. Pending elaboration on recruitment methods, the authors may need to include additional limitations related to their sampling and cessation of recruitment (e.g. why were 18 interviews conducted with 18 at risk individuals and only 2 with physicians)

RESPONSE: We have extended the limitations section according to potential shortcomings in theoretical saturation based on participant demographics.

Submitted filename: Response to reviewers.docx

Click here for additional data file.

21 Jul 2021

PONE-D-21-09002R1

The use of heuristics in genetic testing decision-making: A qualitative interview study

PLOS ONE

Dear Dr. Zimmermann,

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Prof. Ritesh G. Menezes, M.B.B.S., M.D., Diplomate N.B.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: N/A

Reviewer #3: Yes

Reviewer #4: N/A

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The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: (No Response)

Reviewer #3: Yes

Reviewer #4: No

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Reviewer #3: Yes

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The comments were well answered. The paper is interesting and it is good to be able to publish and reflect on well explained qualitative research. The choice of "minor revisions" concerns a few points of English that are a bit awkward and a few typos. It's not a big thing and an additional proofreading by a native English speaker could improve the flow of lecture.

Reviewer #3: (No Response)

Reviewer #4: 1. The justification for two additional interviewees (experts) remains unclear. Although the authors have included the interview guide, expert quotes are not included in the results or highlighted in the discussion. The analytic approach to the expert interviews is not clearly reported.

2. My previous comment regarding a characterization in variation in preferences was not intended to suggest that the authors apply a quantitative approach to the analysis by reporting proportions. Rather, it would be helpful to provide a descriptive understanding of where opinions varied (or were consistent) across participants.

3. Exclusion of pregnant people remains unclear. If this was an issue for ethical approval, please estate that in the paper.

4. The authors appear to have uploaded multiple versions of the appending documents (interview guides)

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Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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4 Oct 2021

We thank the two reviewers for their additional comments. We react to them in detail below.

Response to reviewers

Reviewer #2: The comments were well answered. The paper is interesting and it is good to be able to publish and reflect on well explained qualitative research. The choice of "minor revisions" concerns a few points of English that are a bit awkward and a few typos. It's not a big thing and an additional proofreading by a native English speaker could improve the flow of lecture.

Author response: We thank reviewer 2 for their positive response. An English native speaker with a degree in English language has revised the language of the paper.

Reviewer #3: (No Response)

Reviewer #4: 1. The justification for two additional interviewees (experts) remains unclear. Although the authors have included the interview guide, expert quotes are not included in the results or highlighted in the discussion. The analytic approach to the expert interviews is not clearly reported.

Author response: We thank reviewer 4 for their comments and clarifications. We highlighted the analytic approach in the methods section (page 10), it reads: “We conducted these interviews after an initial analysis of all counselee interviews and included them in the analysis to examine whether experts supported or contradicted or general understanding of interview data.” It also reads in the first section of findings: “Expert interviews were used to confirm and contrast counselees' views.” Along with this analytic approach, we repeatedly highlighted in the results where experts supported or contrasted our findings. For example, on page 13 it reads: “Conversely, one expert reflected on the difficulty of explaining these variants to counselees in the context of panel testing, stating that those lower risks or variants of unknown significance added complexity that was difficult to communicate. This expert feared that counselees would instead overestimate the risks of these variants.”

While we do indirectly cite experts in the results, we chose not to select direct quotes from experts. When selecting illustrative quotes, we attempted to illustrate our findings while maintaining a readable structure to the readers. We think that the quotes from counselees serve this purpose better.

The reason why expert views are not highlighted in the discussion is because they mainly supported our findings. This was also why we stopped recruiting experts after two interviews. We did consider where we could include expert views in the discussion, but decided that it was beyond the scope to do this more prominently because we did not ask them directly about group A and B heuristics.

2. My previous comment regarding a characterization in variation in preferences was not intended to suggest that the authors apply a quantitative approach to the analysis by reporting proportions. Rather, it would be helpful to provide a descriptive understanding of where opinions varied (or were consistent) across participants.

Author response: We thank reviewer 4 for the clarification. Indeed, our whole analytic approach aimed at examining variations and consistencies among counselees and experts. We report consistencies through the topics (heuristics) that were commonly reported, and then describe in detail the various views reported by participants. We clarified this in the first paragraph of the findings section (page 10).

3. Exclusion of pregnant people remains unclear. If this was an issue for ethical approval, please estate that in the paper.

Author response: It was indeed an issue of the ethics committee to not include vulnerable people, including pregnant women. We rephrased in the methods section, it now reads on page 8: “Counselees between the age of 18-70 that were not considered vulnerable due to mental state or pregnancy by the ethics committees that approved the study were eligible.»

4. The authors appear to have uploaded multiple versions of the appending documents (interview guides)

Author response: This is because we used different interview guides for patient and experts – File S2 is the interview guide used for patients, File S3 is the interview guide used for expert interviews.

Submitted filename: Response to reviewers.docx

Click here for additional data file.

15 Nov 2021

The use of heuristics in genetic testing decision-making: A qualitative interview study

PONE-D-21-09002R2

Dear Dr. Zimmermann,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Prof. Ritesh G. Menezes, M.B.B.S., M.D., Diplomate N.B.

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #4: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #4: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #4: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This was a well written and interesting manuscript reporting the findings of a qualitative analysis of the complexity of genetic testing decision making and the use of heuristics. The articulation of ways in which heuristics were useful and potentially not useful to counselees (Table 3) was appreciated and will likely be of use to clinicians. The authors appear to have addressed previous reviewer concerns and I raise no additional concerns.

Reviewer #4: Thank you for your careful responses to the suggested revisions. The authors have thoughtfully responded to each of my comments.

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Reviewer #1: Yes: Fuchsia Howard

Reviewer #4: No

18 Nov 2021

PONE-D-21-09002R2

The use of heuristics in genetic testing decision-making: A qualitative interview study

Dear Dr. Zimmermann:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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on behalf of

Prof. Dr. Ritesh G. Menezes

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PLOS ONE