Figure 1 outlines participant flow. The first interview round involved 34 participants (10 MoST participants, 5 RCA members, 5 carers/family members, and 14 HCPs). In the second round, 4 new participants joined (3 from RCA, 1 carer), while 5 participants were not re-invited based on Omico/RCA advice (3 patients due to death or severe illness, and 2 of their carers). MoST participants had been enrolled in the program up to 3 years ago, most (60%) within the past year. Among carers, 4 were spouses, 1 was the daughter and 1 a sibling of patients from MoST (n = 4) and RCA (n = 2) cohorts. Table 2 shows other characteristics.

Round 1 interviews generated four categories of questions. Illustrative quotations are included below and in Table 3.

1. Questions about the Genomic Testing Process.

Participants suggested the QPL should clarify the purpose of CGP, potential benefits of testing, and whom to contact with questions arising before/after enrolment. They emphasised the importance of clear expectations about what testing involved, including what patients needed to do, realistic timeframes for receiving results, and potential costs.

“How do the results help me? What are they going to be useful for?” (P17_MoST).

2. Questions about Receiving Results.

Common questions related to the types of results patients could receive, who would deliver them, whether there would be enough time to discuss results, and whether plain language would be used. Participants wanted to know who could support them if they were distressed or confused by results; some wanted to know whether follow-up testing of their samples, or re-analysis of their data, may be done in the future as new treatments emerged.

“[I’d like] some reassurance that… we’ll continue to look for more biomarkers as more research becomes available.” (P35_MoST).

3. Questions about Potential Outcomes of Testing.

Participants asked about treatments that may be offered after testing, and the likelihood of actionable results. All participant groups stressed the need to temper expectations through transparent discussions about the modest chance of individual clinical benefit. Many noted that while CGP inevitably raises hopes for effective personalised therapies, multiple barriers to treatment may persist even when an actionable target is identified. The QPL was therefore viewed as an opportunity to promote understanding and support patients and families in coping with uncertainty and possible disappointment.

“Initially you’re excited to get an invitation to participate [in CGP] because there’s an opportunity there for some hope for a customised treatment. So, your thinking is maybe coloured a bit by that, and [my] family too…were excited initially. There’s that emotional layer that’s in there, and you’ve got to be realistic.” (P17_MoST).

“I think most [patients] go in with absolutely no idea… it’s just this wonderful appeal that they’re going to have this personalised medicine approach. So, I think you really have to tell them and educate them about the likely outcome.” (P29_Oncologist).

Many participants wanted to understand whether results may have implications for family or insurance. As the purpose of the MoST program was tumour-focused CGP, a germline result (i.e., indicating a possible heritable variant) would be incidental and require confirmatory testing outside the program. HCPs emphasised the importance of clarifying this distinction. Nonetheless, participants felt that outlining potential positive or negative consequences for relatives was relevant to informed consent for CGP. Some suggested that patients may benefit from guidance around discussing relevant CGP results with relatives.

“It would be really important to make sure that [patients] understand the difference in tumour testing versus germline testing so they don’t get those two confused. [CGP] is specifically for the management of their cancer.” (P21_Geneticist).

“What if [CGP results indicated] something negative? What are those negatives likely to be for my family? Because that could actually influence my consent… I won’t bother because that’s got too many consequences for my kids and grandkids.” (P17_MoST).

4. Questions about the Genomic Study/Research Team

Few participants spontaneously raised questions about the genomic research program or team, but when prompted they felt that knowing the institution/s involved was useful, as it helped patients judge the organisation’s credibility and the staff’s expertise. Some wanted to know about the program’s funding. Altruistic motives were commonly raised; patients wanted to know the purpose, scale and timeframe of the research, and how their participation could help others. Queries around privacy, security, storage and sharing of data were also raised, with some participants emphasising the importance of transparency.

“[I’d want to know] what the overall [research] aim was – that if it doesn’t find anything for me, it’ll still contribute towards a general knowledge base – and whether it was just Australian based or an international project.” (P25_RCA).

As well as discussing specific questions that patients/families may wish to ask about genomic tests and research, participants (hypothetically) reflected on the value of a QPL in this context. Participants liked the idea of a prepared set of questions to consider, because this could help address gaps in understanding that patients might be unaware of, but they also acknowledged that some patient questions may be idiosyncratic. They felt a QPL could be empowering in an emotionally vulnerable situation and prompt clinicians to make space for patients’ and carers’ concerns and queries, thereby supporting them to become more fully informed without necessarily altering their testing decisions. One patient asserted that asking questions of clinicians could improve the care patients receive, and another mentioned searching the internet for suggested questions in anticipation of their diagnosis.

“As a patient, you feel like you can’t query anything… So, I think something that’s formalised for questions you can ask, emotionally, that’s actually quite a helpful thing. It could also be good for the doctor to have the mindset that patients do have reasonable questions, and they need to allocate time to listen to those questions and explain.” (P02_RCA).

“I’m not saying it would have changed my consent, but it would have probably felt more comprehensive, what I knew about the process I was going into. So that would have been helpful.” (P17_MoST).

Many participants preferred receiving a QPL several days before the consultation in which genomics participation would be discussed and/or finalised: “People can read [the QPL] before their chat with the research coordinator, then in the appointment they can [seek] clarification… and then that will cement it because…you hear about the same thing in two different ways.” (P21_Geneticist).

However, some HCPs involved in the MoST consent process were concerned about giving questions to patients without supplying answers. They therefore suggested including with the questions a prepared general answer to each one: “I guess my worry is that they’d have a list of questions and start to think about the answers, that they could be potentially misinformed answers, as in, they’ll create an answer in their head and then that’s what they’ll believe and understand, versus knowing what the accurate answer is.” (P27_Research staff).

Following iterative research team discussions, participants’ proposed questions were organised into three categories: (i) Comprehensive Genomic Profiling, (ii) Results of CGP, and (iii) About the Genomic Research Study. In line with several participant recommendations and QPL templates, a fourth section titled ‘Add your own questions’ was included to encourage patients to write additional questions, if desired.

Although the original plan was to develop model answers as a separate resource to support consent staff discussions, interview feedback supported integrating answers directly into the QPL, creating a patient-facing question-and-answer (Q&A) tool. Answers were kept general and brief, covering the fundamental information while accurately reflecting CGP processes within the MoST program. Participants emphasised the importance of encouraging patients to seek personalised information from clinical/research professionals. Use of the SHeLL Health Literacy Editor led to extensive textual edits, including shorter sentences, reduced complexity, active-voice phrasing, and simpler vocabulary (where possible). Following revision, the question list was assessed at Grade 7.4 and the full Q&A at Grade 8.4 readability level.

Overall, participants viewed the draft questions and answers positively, perceiving the QPL as valuable for patients considering participation in a CGP study.

Structure, Content and Scope. Participants endorsed the section order and “liked the range of questions” (RCA). The scope was highlighted as a strength, with comments that the tool had “really good coverage” (Carer), included “very important questions to ask” (MoST), and addressed “everything I would have considered” (MoST). Minor structural edits were suggested, such as combining related questions or splitting multi-part items. All participant groups re-emphasised the importance of explaining that a patient may still be unable to take part in a treatment trial even if a biomarker and relevant trial were found. One clinician suggested reassuring patients that their oncologist would continue providing the best available treatments, regardless of CGP outcomes. Additional suggested content included: why CGP testing takes time, and sources for further support (e.g., advocacy groups).

Readability. Participants from all groups found the wording easy to understand overall, valuing clear explanations of technical terms and avoidance of jargon. Patients commented that key concepts were “explained beautifully” (MoST) and that the QPL struck a “good balance between not needing a degree to understand, as well as not dumbing it down” (RCA). The “simple and plain language” (HCP) was perceived as appropriate for a range of audiences, including those with lower literacy or from culturally and linguistically diverse backgrounds; one participant compared it favourably with the MoST Participant Information Statement. Only minor wording changes were suggested.

Utility and Implementation. Patients and HCPs viewed the QPL as a helpful supplement to routine information. Patients felt “empowered by” the tool, with one saying it offered “a bit of autonomy and a sense of control” (RCA). Carers valued the resource giving “permission for patients to ask questions, without premise or judgement” and felt a prepared list “takes stress off patients from having to come up with questions in a stressful setting.” Participants favoured reviewing the QPL in advance so they could “look over [it] with family” (RCA) to prepare for discussion and decision-making. Its perceived value lay in helping “arm patients with all the relevant information and means to receive more” (HCP).

The final question list (Table 4) includes a brief explanatory introduction followed by 29 items in three categories: Comprehensive Genomic Profiling, Results of CGP, and About the Genomic Research Study, followed by an ‘Add Your Own Questions’ section. The complete Q&A is provided in the Supplementary Material. Since the MoST program has completed recruitment, answers were slightly adapted to reflect Omico’s Cancer Screening Program, which now offers CGP in a similar format to MoST.