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Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial.

ABSTRACT: INTRODUCTION:Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating health outcomes and costs of receiving incidental results is critical for the adoption of genomic sequencing into clinical care and to understand the unintended consequences of adoption of genomic sequencing. We aim to evaluate the health outcomes and costs of receiving incidental results for patients undergoing genomic sequencing. METHODS AND ANALYSIS:We will compare health outcomes and costs of receiving, versus not receiving, incidental results for adult patients with cancer undergoing genomic sequencing in a mixed-methods randomised controlled trial. Two hundred and sixty patients who have previously undergone first or second-tier genetic testing for cancer and received uninformative results will be recruited from familial cancer clinics in Toronto, Ontario. Participants in both arms will receive cancer-related results. Participants in the intervention arm have the option to receive incidental results. Our primary outcome is psychological distress at 2 weeks following return of results. Secondary outcomes include behavioural consequences, clinical and personal utility assessed over the 12 months after results are returned and health service use and costs at 12 months and 5 years. A subset of participants and providers will complete qualitative interviews about utility of incidental results. ETHICS AND DISSEMINATION:This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System that provides ethical review and oversight for multiple sites participating in the same clinical trial in Ontario.Results from the trial will be shared through stakeholder workshops, national and international conferences, and peer-reviewed journals. TRIAL REGISTRATION NUMBER:NCT03597165.

SUBMITTER: Shickh S

PROVIDER: S-EPMC6797333 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial.

Shickh Salma S Clausen Marc M Mighton Chloe C Gutierrez Salazar Mariana M Zakoor Kathleen-Rose KR Kodida Rita R Reble Emma E Elser Christine C Eisen Andrea A Panchal Seema S Aronson Melyssa M Graham Tracy T Armel Susan Randall SR Morel Chantal F CF Fattouh Ramzi R Glogowski Emily E Schrader Kasmintan A KA Hamilton Jada G JG Offit Kenneth K Robson Mark M Carroll June C JC Isaranuwatchai Wanrudee W Kim Raymond H RH Lerner-Ellis Jordan J Thorpe Kevin E KE Laupacis Andreas A Bombard Yvonne Y

BMJ open 20191007 10

<h4>Introduction</h4>Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating ...[more]

PMID: 31594892

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Project description:INTRODUCTION:Genome sequencing, a novel genetic diagnostic technology that analyses the billions of base pairs of DNA, promises to optimise healthcare through personalised diagnosis and treatment. However, implementation of genome sequencing faces challenges including the lack of consensus on disclosure of incidental results, gene changes unrelated to the disease under investigation, but of potential clinical significance to the patient and their provider. Current recommendations encourage clinicians to return medically actionable incidental results and stress the importance of education and informed consent. Given the shortage of genetics professionals and genomics expertise among healthcare providers, decision aids (DAs) can help fill a critical gap in the clinical delivery of genome sequencing. We aim to assess the effectiveness of an interactive DA developed for selection of incidental results. METHODS AND ANALYSIS:We will compare the DA in combination with a brief Q&A session with a genetic counsellor to genetic counselling alone in a mixed-methods randomised controlled trial. Patients who received negative standard cancer genetic results for their personal and family history of cancer and are thus eligible for sequencing will be recruited from cancer genetics clinics in Toronto. Our primary outcome is decisional conflict. Secondary outcomes are knowledge, satisfaction, preparation for decision-making, anxiety and length of session with the genetic counsellor. A subset of participants will complete a qualitative interview about preferences for incidental results. ETHICS AND DISSEMINATION:This study has been approved by research ethics boards of St. Michael's Hospital, Mount Sinai Hospital and Sunnybrook Health Sciences Centre. This research poses no significant risk to participants. This study evaluates the effectiveness of a novel patient-centred tool to support clinical delivery of incidental results. Results will be shared through national and international conferences, and at a stakeholder workshop to develop a consensus statement to optimise implementation of the DA in practice. TRIAL REGISTRATION NUMBER:NCT03244202; Pre-results.

Project description:Mixed methods are commonly used in health services research; however, data are not often integrated to explore complementarity of findings. A triangulation protocol is one approach to integrating such data. A retrospective triangulation protocol was carried out on mixed methods data collected as part of a process evaluation of a trial. The multi-country randomised controlled trial found that a web-based training in communication skills (including use of a patient booklet) and the use of a C-reactive protein (CRP) point-of-care test decreased antibiotic prescribing by general practitioners (GPs) for acute cough. The process evaluation investigated GPs' and patients' experiences of taking part in the trial.Three analysts independently compared findings across four data sets: qualitative data collected view semi-structured interviews with (1) 62 patients and (2) 66 GPs and quantitative data collected via questionnaires with (3) 2886 patients and (4) 346 GPs. Pairwise comparisons were made between data sets and were categorised as agreement, partial agreement, dissonance or silence.Three instances of dissonance occurred in 39 independent findings. GPs and patients reported different views on the use of a CRP test. GPs felt that the test was useful in convincing patients to accept a no-antibiotic decision, but patient data suggested that this was unnecessary if a full explanation was given. Whilst qualitative data indicated all patients were generally satisfied with their consultation, quantitative data indicated highest levels of satisfaction for those receiving a detailed explanation from their GP with a booklet giving advice on self-care. Both qualitative and quantitative data sets indicated higher patient enablement for those in the communication groups who had received a booklet.Use of CRP tests does not appear to engage patients or influence illness perceptions and its effect is more centred on changing clinician behaviour. Communication skills and the patient booklet were relevant and useful for all patients and associated with increased patient satisfaction. A triangulation protocol to integrate qualitative and quantitative data can reveal findings that need further interpretation and also highlight areas of dissonance that lead to a deeper insight than separate analyses.

Project description:BACKGROUND:Current medical practice includes the application of genomic sequencing (GS) in clinical and research settings. Despite expanded use of this technology, the process of disclosure of genomic results to patients and research participants has not been thoroughly examined and there are no established best practices. METHODS:We conducted semi-structured interviews with 21 genetic and non-genetic clinicians returning results of GS as part of the NIH funded Clinical Sequencing Exploratory Research (CSER) Consortium projects. Interviews focused on the logistics of sessions, participant/patient reactions and factors influencing them, how the sessions changed with experience, and resources and training recommended to return genomic results. RESULTS:The length of preparation and disclosure sessions varied depending on the type and number of results and their implications. Internal and external databases, online resources and result review meetings were used to prepare. Respondents reported that participants' reactions were variable and ranged from enthusiasm and relief to confusion and disappointment. Factors influencing reactions were types of results, expectations and health status. A recurrent challenge was managing inflated expectations about GS. Other challenges included returning multiple, unanticipated and/or uncertain results and navigating a rare diagnosis. Methods to address these challenges included traditional genetic counseling techniques and modifying practice over time in order to provide anticipatory guidance and modulate expectations. Respondents made recommendations to improve access to genomic resources and genetic referrals to prepare future providers as the uptake of GS increases in both genetic and non-genetic settings. CONCLUSIONS:These findings indicate that returning genomic results is similar to return of results in traditional genetic testing but is magnified by the additional complexity and potential uncertainty of the results. Managing patient expectations, initially identified in studies of informed consent, remains an ongoing challenge and highlights the need to address this issue throughout the testing process. The results of this study will help to guide future providers in the disclosure of genomic results and highlight educational needs and resources necessary to prepare providers. Future research on the patient experience, understanding and follow-up of recommendations is needed to more fully understand the disclosure process.

Project description:BackgroundSharing trial results with participants is an ethical imperative but often does not happen. We tested an Enhanced Webpage versus a Basic Webpage, Mailed Printed Summary versus no Mailed Printed Summary, and Email List Invitation versus no Email List Invitation to see which approach resulted in the highest patient satisfaction with how the results were communicated.Methods and findingsWe carried out a cluster randomised, 2 by 2 by 2 factorial, nonblinded study within a trial, with semistructured qualitative interviews with some patients (ISRCTN96189403). Each cluster was a UK hospital participating in the ICON8 ovarian cancer trial. Interventions were shared with 384 ICON8 participants who were alive and considered well enough to be contacted, at 43 hospitals. Hospitals were allocated to share results with participants through one of the 8 intervention combinations based on random permutation within blocks of 8, stratified by number of participants. All interventions contained a written plain English summary of the results. The Enhanced Webpage also contained a short video. Both the Enhanced Webpage and Email contained links to further information and support. The Mailed Printed Summary was opt-out. Follow-up questionnaires were sent 1 month after patients had been offered the interventions. Patients' reported satisfaction was measured using a 5-point scale, analysed by ordinal logistic regression estimating main effects for all 3 interventions, with random effects for site, restricted to those who reported receiving the results and assuming no interaction. Data collection took place in 2018 to 2019. Questionnaires were sent to 275/384 randomly selected participants and returned by 180: 90/142 allocated Basic Webpage, 90/133 Enhanced Webpage; 91/141 no Mailed Printed Summary, 89/134 Mailed Printed Summary; 82/129 no Email List Invitation, 98/146 Email List Invitation. Only 3 patients opted out of receiving the Mailed Printed Summary; no patients signed up to the email list. Patients' satisfaction was greater at sites allocated the Mailed Printed Summary, where 65/81 (80%) were quite or very satisfied compared to sites with no Mailed Printed Summary 39/64 (61%), ordinal odds ratio (OR) = 3.15 (1.66 to 5.98, p < 0.001). We found no effect on patient satisfaction from the Enhanced Webpage, OR = 1.47 (0.78 to 2.76, p = 0.235) or Email List Invitation, OR = 1.38 (0.72 to 2.63, p = 0.327). Interviewees described the results as interesting, important, and disappointing (the ICON8 trial found no benefit). Finding out the results made some feel their trial participation had been more worthwhile. Regardless of allocated group, patients who received results generally reported that the information was easy to understand and find, were glad and did not regret finding out the results. The main limitation of our study is the 65% response rate.ConclusionsNearly all respondents wanted to know the results and were glad to receive them. Adding an opt-out Mailed Printed Summary alongside a webpage yielded the highest reported satisfaction. This study provides evidence on how to share results with other similar trial populations. Further research is needed to look at different results scenarios and patient populations.Trial registrationISRCTN: ISRCTN96189403.

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Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial.

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Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial.

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