Evaluation of a Decision Aid for Incidental Genomic Findings

NCT ID: NCT03244202

Last Updated: 2018-04-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

133 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-12

Study Completion Date

2018-04-02

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Health care providers (HCP) are increasingly using genomic sequencing (GS) to target treatment for patients. However, GS may incidentally reveal inherited risks for thousands of current and future diseases. Guidelines recommend HCP inform patients of incidental GS results. No decision aid (DA) exists to guide patients' decisions about which incidental GS results they wish to learn. This study will evaluate whether the DA followed by genetic counselling (GC) reduces decisional conflict compared to GC alone in a randomized controlled trial (RCT) with 128 patients with a family history of cancer, who have had a negative genetic test and may eligible for GS. A qualitative component with a subset of participants (n=40) will explore patients' preferences for the types of incidental results they wish to receive and their decision making process.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

BACKGROUND: Health care providers are increasingly using GS to diagnose, prognose and treat diseases. GS offers increased sensitivity over classic genetic tests, decreasing time-consuming and costly diagnostic cascades. However, GS may also incidentally reveal inherited risks for many other cancers and diseases. Guidelines recommend doctors inform patients of their incidental GS results. Yet there are limited tools to communicate the scope and implications of the thousands incidental results available to help guide patients' decisions about which results they wish to learn.

Gaps: Decision aids (DAs) are best suited to meet this challenge, but no DA exists to guide patients' decisions about incidental GS results.

Rationale: It is not feasible to counsel patients on the thousands of incidental findings available to make informed choices about which incidental results they wish to receive because of the limited genomics expertise and capacity among oncologists, and the long wait times for genetic counseling. Our DA fills this critical care and translational gap by improving the quality of patients' decisions and saving oncologists time counseling patients on incidental findings.

Preliminary data: 1) DA development: We created an interactive online DA. It begins with a professional whiteboard video (by Dr. Mike Evans) that conveys the key concepts, risks and benefits of learning about incidental GS results to educate patients. It then prepares patients for decision-making using a values clarification exercise (with feedback of their preferences) and a knowledge questionnaire (with correct answers provided after). It ends by asking participants to select result categories they want to learn using a menu tool. 2) Usability testing: We also evaluated the DA's usability with 15 patients in 2 rounds. Interviews demonstrated strong face validity and content comprehension. Most patients found the amount of information 'just right' (11/15), clear (12/15) and balanced (14/15). All patients felt that the information was sufficient to reach a decision, that the DA was easy to use and would recommend it.

OBJECTIVES

1. Evaluate the efficacy of the DA compared to standard genetic counseling (GC)
2. Understand the decision-making patients' use regarding GS and selecting incidental findings.

METHODS

Phase 1 - RCT to evaluate the DA:

Methods: We will evaluate the efficacy of the DA in reducing decisional conflict compared to standard genetic counseling (GC) using a superiority trial.

Population: We will recruit adult cancer patients who are eligible to have GS (i.e., tested negative for the classic gene mutation associated with their cancer - e.g., BRCA1/2, MLH, MSH, PMS, APC, MUTYH) from genetics clinics at Mount Sinai Hospital, Princess Margaret Hospital and Sunnybrook Hospital in Toronto, ON Canada. We will include adults who speak and read English and exclude patients with metastatic/recurrent disease as incidental results are less consequential to this population.

Sample size: TThe primary outcome is decisional conflict; the study requires 64 patients/arm to detect the minimal clinically important difference (MCID) of 0.3 using the Decisional Conflict Scale (DCS) (Appendix 3), assuming a standard deviation of 0.6, an alpha of 0.05 (two-sided) and power of 0.815,16. In the last 3 months, 244 patients with a family history of breast and colon cancer tested negative for their associated classic mutations (BRCA1/2, MLH, MSH, PMS, APC, MUTYH) most of who would be eligible for GS. Extrapolating this over the next 9 months we estimate that there would be 732 eligible patients. It is highly feasible to reach our target of 128 patients.

Participants will be consecutively randomized and allocated from an existing list of eligible subjects using a computer-generated randomization in a 1:1 ratio with random permuted blocks of varying sizes. Patients from each clinic will be randomized separately to ensure we have an even distribution of this population in both arms of the study.

Intervention arm: Participants will view the online DA and then complete the online self-administered measures (below) in one sitting within 14 days of recruitment. Next, they will speak with a GC over the telephone after the DA, using a standardized script. They will then complete the same online measures again after speaking to the GC.

Control arm: The GC will conduct the GC session over the telephone within 14 days of recruitment. A topics script will be used to standardize GC discussions covering standard educational content to enable patients to select incidental GS results (participants will not view the DA nor the video). Participants will complete the online self-administered measures after speaking with the GC.

Outcome: Consistent with the Ottawa Decisional Support Framework, our primary outcome is decisional conflict. Secondary outcomes are: knowledge of GS, satisfaction with decision, preparation for decision-making and anxiety.

Measures: We will use validated scales to assess decisional conflict, knowledge, anxiety, satisfaction with the decision and preparation for decision-making. We will develop a standardized topic script for the GC in each arm, as well as a questionnaire to collect intervention fidelity (e.g., usage statistics, duration of counseling sessions), demographic and clinical characteristics (e.g., cancer status and genetic testing).

Analysis: Consistent with the Ottawa Decision Support Framework, our primary outcome is decisional conflict, assessed via the validated Decisional Conflict Scale (DCS). Knowledge is the secondary outcome, will be measured by the Cliseq genomic sequencing questionnaire and a set of internal developed knowledge questions. Satisfaction and anxiety with also be assessed. Satisfaction will be measured using the Satisfaction with Decision scale (SWD) and the Preparation for Decision Making scale (PrepDM). Anxiety will be measured using the state subscale of the State-Trait Anxiety Inventory (STAI). We will also include a demographics and cancer history questionnaire.

The analysis of outcomes will follow the intention-to-treat (ITT) approach. Mean DCS, SWD, PrepDM and STAI scores will be compared using a t-test. Knowledge scores will be assessed by summing the number of correct responses to the questions, and compared using t-tests. Linear regression will be used in a secondary analysis to account for known predictors for decisional outcomes such as education. Secondary analyses will compare the mean DCS, knowledge, SWD, PrepDM and STAI scores before and after GC in the intervention arm to explore the additional benefit of GC after the DA. Un/adjusted mean differences and 95% confidence intervals will be reported. We will use descriptive statistics to report participants' characteristics.

Phase 2 - qualitative study of decision making for incidental results:

A subset of study participants will be asked to take part in a qualitative interview about their decision-making regarding selecting incidental findings. These semi-structured interviews will take place over the phone with a total of 40 participants. For the qualitative component a purposeful sample of study participants will be used. We will target a mix of participants across ages, cancer type and stage, gender, and study group to assess the varying approaches to decision-making. At total of 40 participants will take part in the qualitative component.

Analysis: Qualitative data analysis will draw on grounded theory methodology. We will sort the data by searching for themes/patterns and variations within and across interviews using HypeRESEARCH. Coding, which is the first stage in the analysis process, will involve 'labeling' the data with descriptive codes. Two team members will independently code each transcript. Consensus on coding will be reached through comparison and discussion among these members. The second stage will involve constant comparison, where codes and their content will be compared across interviews to discern common and divergent themes and issues across them. The final stage is selective coding, which integrates all the codes under a central phenomenon to build a theory. Validation methods include triangulation and member checking.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Decision Aid Plus Counselling

Participants will use a decision aid to learn about genomic sequencing and select which incidental findings they would like to receive from genomic sequencing. After using the decision aid the participants will speak with a genetic counsellor over the phone about their choice.

Group Type EXPERIMENTAL

Decision Aid Plus Counselling

Intervention Type OTHER

The Genomics ADViSER is an decision aid designed to inform patients about genomic sequencing (GS) and aid them selecting which incidental findings they would like to receive from GS.

Genetic Counselling Only

Participants will a genetic counsellor over the phone to learn about genomic sequencing and select which incidental findings they would like to receive from genomic sequencing.

Group Type ACTIVE_COMPARATOR

Genetic Counselling Only

Intervention Type OTHER

Participants will learn about genomic sequencing and incidental findings by speaking directly with a genetic counsellor and select which incidental findings they would like to receive with a genetic counsellor.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Decision Aid Plus Counselling

The Genomics ADViSER is an decision aid designed to inform patients about genomic sequencing (GS) and aid them selecting which incidental findings they would like to receive from GS.

Intervention Type OTHER

Genetic Counselling Only

Participants will learn about genomic sequencing and incidental findings by speaking directly with a genetic counsellor and select which incidental findings they would like to receive with a genetic counsellor.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients with a family history of cancer
* Received a negative single gene test for a cancer gene mutation (e.g., BRCA1/2, MLH, MSH, PMS, etc.) or received a negative panel test
* Speak and read English

Exclusion Criteria

* Are in advanced stage cancer (stage 5)
* Received positive panel testing or panel sequencing
* Have not had single gene testing related to their primary cancer condition (e.g., BRCA1/2 for breast/ovarian cancer, MLH, MSH, PMS colorectal cancer, etc.)
* Received a positive genetic test for a cancer gene mutation (e.g., BRCA1/2, MLH, MSH, PMS, APC, MUTYH, etc.)
* Do not speak or read English
* Family member participating in the study
* Participant in usability study of the DA
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Unity Health Toronto

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Yvonne Bombard, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Michael's Hospital and University of Toronto

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status

Sunnybrook Hospital

Toronto, Ontario, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Canada

References

Explore related publications, articles, or registry entries linked to this study.

Shickh S, Clausen M, Mighton C, Casalino S, Joshi E, Glogowski E, Schrader KA, Scheer A, Elser C, Panchal S, Eisen A, Graham T, Aronson M, Semotiuk KM, Winter-Paquette L, Evans M, Lerner-Ellis J, Carroll JC, Hamilton JG, Offit K, Robson M, Thorpe KE, Laupacis A, Bombard Y. Evaluation of a decision aid for incidental genomic results, the Genomics ADvISER: protocol for a mixed methods randomised controlled trial. BMJ Open. 2018 Apr 26;8(4):e021876. doi: 10.1136/bmjopen-2018-021876.

Reference Type DERIVED
PMID: 29700101 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

16-052

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Pediatric Reporting of Adult-Onset Genomic Results
NCT03832985 COMPLETED EARLY_PHASE1
Overcoming Barriers to Accessing Genetic Medicine
NCT05064241 ACTIVE_NOT_RECRUITING NA