“Ultimately, mom has the call”: Viewing clinical trial decision making among patients with ovarian cancer through the lens of relational autonomy

Abstract Objective This study employs the concept of relational autonomy to understand how relational encounters with family members (FMs) and care providers may shape decisions around ovarian cancer patients’ clinical trial (CT) participation. The study also offers unique insights into how FMs view patients’ decision making. Methods In‐depth interviews were conducted with 33 patients with ovarian cancer who had been offered a CT and 39 FMs. Data were inductively analysed using a thematic approach and deductively informed by constructs derived from the theory of relational autonomy (RA). Results Patients’ relationships, experiences and social status were significant resources that shaped their decisions. Patients did not give equal weight to all relationships and created boundaries around whom to include in decision making. Doctors’ recommendations and perceived enthusiasm were described as influential in CT decisions. Both patients with ovarian cancer and their FMs maintained that patients have the “final say,” indicating an individualistic autonomy. However, maintaining the “final say” in the decision‐making process is constitutive of patients’ relationships, emphasizing a relational approach to autonomy. FMs support patients’ autonomy and they do so particularly when they believe the patient is capable of making the right choices. Conclusions Although ethical principles underlying informed consent for CT participation emphasize individual autonomy, greater attention to relational autonomy is warranted for a more comprehensive understanding of CT decision making.


| INTRODUC TI ON
Potential research participants in clinical trials (CTs) must be informed of their right to self-determination and be provided an in-depth description of foreseeable benefits, risks of the trial and alternatives to participation as part of the process of informed consent. 1 Rational decision models and shared decision-making approaches focus on the individual patient's autonomy in CT decision making. [2][3][4][5] However, social circumstances, including experiences, education, relationships and racial and cultural identification, all of which inform one's selfhood and therefore one's decision making, may result in departures from idealized, standardized or anticipated decision processes. 6 Indeed, reports indicate that the process by which patients with cancer make CT participation decisions is diverse and poorly understood. 6,7 The decision-making process itself can be viewed as a "silent factor" in CT decision making, although much of the literature assumes shared decision making among patients, providers and family members (FMs) is preferred. 6 Research on ethical CT presentation highlights the need to enhance patients' autonomy by meeting ethical obligations and reforming informed consent processes so that they are an ongoing interactive process that prioritizes patients' privacy as well as creates opportunities for patients to interact with their social network. 2,4,5,8,9 Understanding how patient's autonomy is enacted is significant to the broader CT participation literature as it can inform efforts that seek to optimize trial enrolment among patients with cancer. However, there has been little focus on how patients' autonomy is embedded within family involvement in treatment decision making. [10][11][12][13] Illness is not an isolated event that occurs at the individual level, but rather it can be a challenging circumstance that evolves from a family's history, and which can impact its future.
The objective of this research was to understand the social and familial contexts that shape cancer patients' and their family members' decision to enrol in a CT focusing on how family and other social engagement promote patients' overall agency. Specifically, we set out to understand patients' perceptions of their experiences around who, when and how others are engaged in CT decision making, and how those interactions shape their decisions, as well as how FMs perceive their own participation. As a guiding concept, we employ the relational autonomy (RA) theory 14 to understand these relational and social engagements. Relational autonomy is an umbrella term for a feminist reconfiguration of traditional notions of autonomy which are based upon a fixed, unchanging, independent and rationalistic conceptualization of an individual selfhood. 14,15 Within traditional notions of autonomy, informed consent and clinical decision making are viewed as an individual and rational exercise free from the influence of others. [2][3][4] Instead, RA casts the individual's selfhood as iteratively shaped by, experienced and produced through interconnected relationships with others, and through the individual's own biography, emotions and social experiences. 14,15 Personal autonomy, therefore, is realized through a dynamic web of social, historical, class, racial, gendered and cultural contexts, [14][15][16][17] with inherent uneven power relations embedded within this complexus. In this article, we conceive RA as an approach that involves examining how one's sense of self, one's autonomy and one's decisions are developed and (re)confirmed in the context of daily interactions and experiences 14,16,18 From the perspective of   RA, clinical decision making and informed consent are considered to   be shaped by, and dependent upon relationships with others 14-17 and deliberately, one's autonomy.
Ovarian cancer provides a highly relevant disease context in which to examine CT decision making. Rates of recurrence after treatment are high, 19 and a majority of patients diagnosed with this cancer eventually face drug-resistant disease and recurrence which limit treatment options to novel agents or regimens that are only available through CTs. [19][20][21][22] Social and disease factors including finances, family obligations and quality of life are important considerations in ovarian cancer treatment decision making. 23 This presents an opportunity to explore the topic of autonomy in decision making-which is portrayed as rational model-in the context of a lethal disease where patients are faced with decisions that impact both their medical and social situation.

| Research approach
This study used an applied qualitative health research approach 24 focusing on patients' and FMs' perspectives on their experiences around decision making in CT participation and how findings could be applicable in CT enrolment decisions. We used an integrated approach of applied thematic analysis 25,26 which involves a combination of inductive (themes emerging from participant's responses) and deductive (constructs from RA) coding. All participants provided informed consent and were assured of anonymity and confidentiality.
Ethics approval was obtained prior to initiating the study.

| Recruitment and data collection
The data for this study were collected from January 2012 through December 2014. Specific procedures surrounding methods and recruitment have been previously reported. 27,28 We used a purposeful sampling approach. 29 Eligible patients had a diagnosis of ovarian cancer (epithelial ovarian carcinoma, primary peritoneal carcinoma or fallopian tube cancer), had been offered a CT (at one of two comprehensive cancer centres in the Midwest of the USA) and were willing to nominate at least one FM to participate in a separate interview. Nominated FMs were contacted to participate in an interview subsequent to enrolling the patient. Family members included biological and social relatives.
Data were gathered using a semi-structured interview guide.

| Analysis
In an integrated approach, we began with an inductive analysis 25,26,30 to identify major themes. Inductive data analysis was conducted by a team of five qualitative researchers in the areas of family studies, health services research, behavioural science, and medical sociology. Researchers met regularly to discuss and compare emerging themes, and categories. Subsequently, constructs from RA were applied as a sensitizing concept to the emergent themes, thereby allowing the analysis to be a process in which RA could explain the contexts within which patients with ovarian cancer make CT decisions, including their social context. Data management and analysis were aided by qualitative analysis software (NVIVO 11.1; QSR International PTY ltd.). Illustrative quotes are denoted by participant number; for patients, age (in years) follows, while for FMs, their gender and relationship to the patient follows their participant number.

| RE SULTS
Participant characteristics have been reported earlier. 27,28 Briefly, a total of 72 participants (33 patients with ovarian cancer and 39 FMs) were interviewed across both study sites. Patients' mean age was 59 ± 9.9 (range 36-76). Seventy percent (n = 23) of patients were married or in a relationship, and 30% were never married, widowed, separated or divorced (n = 10). More than half (58%) were not working for pay (n = 19), and 55% had a bachelor's degree or higher (n = 18). The vast majority of the patient sample (94%, n = 31) selfidentified their race/ethnicity as White, non-Hispanic.
Findings for this study are categorized into three main themes that portray the relational aspects influential in patients' decisions around CT participation. The first theme, "relational engagement in CT decisions among patients with ovarian cancer," emphasizes the multiple relationships that influence patient's experience of selfhood and their decisions regarding CT participation. The second theme, "familial roles and perceptions of the patient's decisions," is an account of how FMs perceive their role in the decision-making process.
Ultimately, patients make decisions regarding whether or not to participate in a CT that are informed by multiple relationships, which is discussed in the third theme "maintaining the final say."

| Relational engagement in CT decisions among patients with ovarian cancer
As Sherwin 14  Medical background or scientific expertise was a noted characteristic of FM inclusion in the decision-making process, particularly those who could interpret CT information and discuss treatment options. Yet the same characteristic was also noted as potentially excluding FMs from the decision-making process in some cases.
For example, one patient recounted that she did not involve her daughter in decision making because her daughter's background in pharmacology had previously led her to make comments about CT participants being "guinea pigs." Another patient [17a, age 68] recounted, "…if I talk to somebody, well, they might hedge a little bit and then it makes you start thinking -are you making the right thing [decision]?" Other reasons for excluding FMs from discussions about trial participation included a desire to avoid creating perceived emotional and psychological burdens for FMs, particularly when taking into consideration the age and health condition of FMs.
For many patients, the decision to enrol in a CT was based on knowledge acquired from physicians, and in some cases, information about the trial was presented as a recommendation to participate.
Doctors' comments that were reported by patients in the interviews such as, "you would be a good candidate for it," "there is a silver lining in here" and "it's a great idea" were identified by patients as powerful in shaping their CT participation decisions. Given the complexity of CT information and treatment decisions in general, a doctor's recommendation or information obtained from internet searches had the power to shape how patients understood the relative benefits and risks of participating in a way that FMs did not. As such, a doctor's recommendation was seldom questioned by patients; although decisions were left to patients, patient understanding of the trial-and particularly, the trial's benefits-was shaped by physician language. RA asserts that one's educational, occupational and personal biographical experiences and characteristics inform the decisions one makes. 17 For some patients, these personal characteristics and social positions were considered assets and resources that provided them with the necessary skills for making CT participation decisions. [

| Familial roles and perceptions of the patient's decision
This theme considers how FMs perceive their role in the CT participation decision process and how they view patients' autonomous decision making. Some FMs positioned themselves as passive while others saw themselves as active in the decision-making process.
When asked about how much control they had over the final decision, most of them said they had none, although they noted that they were comfortable with the decision made by the patient.
FMs in our study largely confirmed that the ultimate decision rests with the patient, especially in the light of their realization that the patient is the one who will bear the burden of trial participation, including potential side-effects. Family members reported considering factors such as travel and cost, but they also spoke about a desire to make any concessions that would benefit the patient.
Some FMs talked about their passivity being a precaution against negative outcomes of the CT and the potential for regret. Other FMs reported that they were willing to provide their opinions but that the patient was independent enough to make a decision.  Clinical trials were often presented alongside other treatment options, and the initial presentation for some patients was at the time when their provider was asking them to decide a course of care, for example, at the first appointment following a surgery.

| Maintaining the final say
Furthermore, patients who travelled to the clinic from a greater distance described the need to make a decision while they were at the clinic because that decision would trigger a blood draw, medication order or test that needed to be completed before they left for home. Finally, two participants in this study described negative experiences from taking information home for reflection and discussion with family. By the time those patients made a decision to participate, the trial slots were no longer available. These experiences thus shaped those patients' subsequent views on the trial decision-making process and the factors that influence autonomous decision making.

| D ISCUSS I ON
This study explored how social and familial contexts shape CT participation decisions among patients with ovarian cancer. Using RA as a guiding concept, we identify CT participation decision making as a complex relational process shaped by patients' engagement with health-care providers, FMs and friends, and informed by patients' broader social history and contemporary social context. Our findings are suggestive that, rather than viewing autonomy as having independence from extraneous influences and simply having the capacity to act with intent, 31 autonomy is both mediated and constituted by relational, familial, social, structural and situational dimensions and, thus, should be valued as such. 14,15,32 In participate in a CT, as has been established elsewhere. [33][34][35][36] In a relational approach, autonomy is known to occur within and as a result of relationships and interactions [14][15][16]36 Within this web of interactions, there were varying levels of influence, and patients were selective as to who, how, and when to engage others. study is significant; notably, the inclusion of the FM perspective serves to contextualize our assertion that efforts to understand CT participation decision making must be attentive to the importance of the relational context in which disease is experienced.

| CON CLUS ION
The findings of this study suggest that the concept of autonomy in health care in general, and CT participation decision making in particular, should consider the relational contexts, disease factors, health-care system and CT design factors that shape patient decisions. Central to decision making is that patients reflect on their own and others' views when they consider trial participation. Interactions between patients and their FMs as well as how patients interpret/ understand health-care providers' recommendations for CT are important in patients' decisional autonomy.

ACK N OWLED G EM ENTS
We

CO N FLI C T O F I NTE R E S T S
None.