Further validation of the Perceptions of Uncertainties in Genome Sequencing scale among patients with cancer undergoing tumor sequencing.

It is important to understand how individuals perceive uncertainties and the consequent impact on their psychological well-being and health behavior. The Perceptions of Uncertainties in Genome Sequencing (PUGS) scale measures clinical, affective, and evaluative uncertainties about information from sequencing. The PUGS scale has been shown to be valid and reliable among individuals receiving results about their genomes. This study assessed whether its validity generalized to patients with cancer undergoing tumor sequencing. Exploratory factor analysis (EFA) was conducted on data from the Molecular Screening and Therapeutics Program (n = 310) to identify a measurement model. Confirmatory factor analysis (CFA) was used to determine the adequacy of the resulting fit. EFA identified the same three-factor structure reported previously. CFA confirmed that the measurement model yielded a good fit (χ2 /df = 3.72, CFI = 0.96, SRMR = 0.05, and RMSEA = 0.09) and satisfied convergent and discriminant validity. These findings provide further evidence of the validity and reliability of the PUGS scale in measuring three types of uncertainty. Continued application will facilitate an evidence-based approach to intervention and enhance understanding of what it is like to receive results. In turn, this will improve clinical outcomes as undergoing sequencing becomes an increasingly common experience.

Patient perspectives on molecular tumor profiling: "Why wouldn't you?"

AIM: This study explored the attitudes of patients with advanced cancer towards MTP and return of results, prior to undergoing genomic testing within a research program. METHODS: Participants were recruited as part of the longitudinal PiGeOn (Psychosocial Issues in Genomics in Oncology) study involving patients with advanced/metastatic solid cancer who had exhausted therapeutic options and who were offered MTP in order to identify cognate therapies. Twenty patients, selected by purposive sampling, were interviewed around the time they gave consent to MTP. Interviews were audio recorded, transcribed and analysed using thematic analysis. Themes identified in the transcripts were cross-validated via qualitative responses to the PiGeOn study survey (n = 569; 63%). RESULTS: All interviewed participants gave consent to MTP without reservation. Three themes were identified and further supported via the survey responses: (1) Obvious agreement to participate, primarily because of desire for new treatments and altruism. (2) The black box - while participant knowledge of genomics was generally poor, faith in their oncologists and the scientific process encouraged them to proceed with testing; and (3) Survival is the priority - receiving treatment to prolong life was the priority for all participants, and other issues such as identification of a germline variant were generally seen as ancillary. CONCLUSION: Having advanced cancer seemed to abrogate any potential concerns about MTP. Participants valued the research for varied reasons, but this was secondary to their priority to survive. While no negative attitudes toward MTP emerged, limitations in understanding of genomics were evident.

Preferences for return of germline genome sequencing results for cancer patients and their genetic relatives in a research setting.

Germline genome sequencing (GS) holds great promise for cancer prevention by identifying cancer risk and guiding prevention strategies, however research evidence is mixed regarding patient preferences for receiving GS results. The aim of this study was to discern preferences for return of results by cancer patients who have actually undergone GS. We conducted a mixed methods study with a cohort of cancer probands (n = 335) and their genetic relatives (n = 199) undergoing GS in a research setting. Both groups completed surveys when giving consent. A subset of participants (n = 40) completed semi-structured interviews. A significantly higher percentage of probands thought people would like to be informed about genetic conditions for which there is prevention or treatment that can change cancer risk compared to conditions for which there is no prevention or treatment (93% [311] versus 65% [216]; p < 0.001). Similar results were obtained for relatives (91% [180] versus 61% [121]; p < 0.001). Themes identified in the analysis of interviews were: (1) Recognised benefits of GS, (2) Balancing benefits with risks, (3) Uncertain results are perceived as unhelpful and (4) Competing obligations. While utility was an important discriminator in what was seen as valuable for this cohort, there was a variety of responses. In view of varied participant preferences regarding return of results, it is important to ensure patient understanding of test validity and identify individual choices at the time of consent to GS. The nature and value of the information, and a contextual understanding of researcher obligations should guide result return.

Assessment of the Value of Tumor Variation Profiling Perceived by Patients With Cancer.

Importance: Use of tumor molecular profiling (MP) is entering routine clinical practice; however, little is known about how much and why patients value MP. Objective: To examine the perceived value of MP to patients with advanced cancer and factors associated with perceived value. Design, Setting, and Participants: A cross-sectional survey that included willingness-to-pay trade-off scenarios was administered to participants after consent and before MP. A total of 777 participants (94% response rate) were recruited from the Molecular Screening and Therapeutics Program. Eligible patients had advanced solid cancers of any histologic type, were receiving or had completed their last line of effective therapy, had an Eastern Cooperative Oncology Group Performance Status 0 to 3, and had sufficient accessible tissue for MP. The participants were recruited between October 24, 2017, and March 12, 2019, and data analysis was conducted from March 13 to April 14, 2019. Main Outcomes and Measures: Willingness to pay for MP was assessed via hypothetical trade-off scenarios varying in the actionable return rate (1%, 20%, or 40%) and cost (A$0, A$300 [US$210], A$1000 [US $700], A$3000 [US $2100], or A$10 000 [US $7000]). Ordinal regressions were used to explore factors associated with willingness to have and pay for MP. Results: Of 777 participants (405 women [52%]; mean [SD] age, 55.47 [14.26] years), 689 patients (89%) would have MP for as little as a 1% actionable return rate. Fifty-six patients (7%) would require at least a 20% return rate and 11 patients (1%) would require at least a 40% return rate. Fifteen patients (2%) consistently chose not to have the test; 6 participants (0.8%) had missing values on this item. Participants were willing to pay a median of A$1000 if the actionable return rate was 1% and A$3000 for an actionable return rate of 20% to 40%. Of 762 individuals who agreed to testing, 482 patients (64%) were consistently unwilling to pay A$10 000, regardless of the actionable return rate. Patients born in Australia or New Zealand were more likely to want MP (eg, participants born in South Asia had an ordered odds for the tipping point of 7.74 [95% CI, 1.67-36.05; P = .009] times higher than Australian- and/or New Zealand-born participants). Patients born in Australia or New Zealand were also more willing to pay A$1000 or A$3000 (eg, participants born in Western Europe had an ordered odds for the tipping point for paying A$1000 of 1.74 [95% CI, 1.01-3.00; P = .048] times higher than Australian- and/or New Zealand-born participants). People with a medical- or science-related occupation and with more negative attitudes toward uncertainty were more likely to pay A$10 000 (eg, A$10 000 tipping point-ordered odds of participants with a medical- or science-related occupation was 0.49 [95% CI, 0.7-0.87; P = .02] times that of participants without a medical- or science-related occupation). Conclusions and Relevance: This study found apparent high interest in but lower willingness to pay for MP among patients with advanced cancer. Ability to pay may limit access to MP. Ongoing societal debate is required to establish the value of MP and whether subsidization is needed to ensure equity of access.