Cancer Health Assessments Reaching Many

Number of people found to have a pathogenic (P) or likely pathogenic (LP) variant in one of the cancer genes associated with Lynch syndrome or hereditary breast and ovarian cancer

Time frame: For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory.

Population: CHARM participants who were sent a saliva collection kit, returned their sample to the laboratory, had successful DNA extraction, and sequencing was completed. There was no randomization, and therefore no separate arms for this analysis.

Measurement of the degree to which participants shared their genetic test results with various family members will be assessed using a validated survey tool

Time frame: Assessed 6 months post result disclosure

Population: For this analysis, participants were not pre-specified to be separated by type of genetic counseling administered. Survey data from 562 CHARM participants who received genetic test results and completed survey questions on family communication were available for analysis.

Downstream healthcare utilization of specific recommended procedures (e.g., colonoscopy, mammography, surgery) will be compared between CHARM participants who received at least one actionable risk management recommendation from study genetic counselors and those who did not receive an actionable risk management recommendation.

Time frame: Within 12 months of participant receiving information about their hereditary cancer syndrome risk

Population: For this analysis participants were not pre-specified to be separated by type of genetic counseling administered. The analysis sample excluded participants: 1) inadequate exome sequencing sample; 2) died or disenrolled before result disclosure; 3) for each procedure (e.g. mammography, colonoscopy, risk-reducing mastectomy ) individuals without relevant organ(s) at study entry. 4) Except for colonoscopy, those who did not reported their sex at birth as female.

This novel measure consisted of 4 items adapted from the Patient Assessment of Communication Effectiveness scale, 8 items developed by the consortium related to participants' overall satisfaction with the results and experience of results disclosures, and 6 items that focused on key elements of modified genetic counseling. Items were measured on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Using principal-axis factor analyses using oblique rotation, we found the 3-factor solution (accounting for 62.5% of the variance in the items) to provide adequate simple structure with conceptually meaningful factors and thus, created subscale scores for each set of items (6 loaded on each factor): genetic counseling relationship score, communication difficulty score, and communication ease score. The possible mean scores can range from 1 to 5, with higher scores indicating a better outcome.

Time frame: 2 weeks post genetic results disclosure

Population: The number analyzed in each row differs from overall number analyzed because some participants did not respond to all questions in the survey resulting in missing data. For each analysis we used all available data.

Perceived understanding of results This novel 5-item measure asked, Thinking about only your cancer genetic test result, please rate how strongly you agree or disagree with each of the following statements. The 5 items were assessed on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). A principal-axis factor analysis strongly supported a 1 factor solution (accounting for 65.4% of the variance in these items), providing evidence for structural validity, and a Cronbach's α of 0.90, providing strong evidence for internal consistency. The scale was scored using the mean; thus, the possible scores can range from 1 to 5, with higher scores indicating greater understanding.

Time frame: 2 weeks post genetic result disclosure

Population: Of the 827 patients with samples sequenced, 352 received results using modified genetic counseling and 344 received results using traditional genetic counseling. A total of 65 patients received their negative results by mailed letter, 3 declined to receive results, and 63 were lost to follow up. Of the 696 patients randomized, 582 completed the post-results survey. Of these 582, 571 provided the responses required for inclusion in this analysis.

Measurement of participant's understanding of the recommended care based on their genetic test result will be assessed using a validated survey tool

Time frame: 2 weeks post result disclosure, 6 months post result disclosure

Population: The study determined that collecting the data on this secondary outcome was not feasible and did not include these questions on surveys or interviews. We did not analyze this outcome.

Participant's perceived utility of obtaining genetic testing and genetic counseling were assessed. Data collection used semi-structured qualitative interviews. Analyses were conducted using a modified grounded theory approach and explored the five utility domains of the model: clinical, emotional, behavioral, cognitive, and social. The analysis examined how well this multifaceted perceived utility model applied to the responses provided during the interviews. The qualitative data was not quantified in any way and can not be represented in a tabular format.

Time frame: Qualitative interviews were conducted within 1 month of results disclosure; a subset of these participants were interviewed again at 6 months post-results disclosure.

Number of people with pathogenic variants found in genes related to common carrier conditions

Time frame: For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory.

Population: 810 is the number of CHARM participants who were sent a saliva collection kit, returned their sample to the laboratory, had successful DNA extraction, affirmatively chose to receive additional findings, and sequencing was completed. Samples from participants who did not choose additional findings were not tested for carrier conditions. There was no randomization, and therefore no separate arms for this analysis.~.

Number of people with pathogenic variants found in genes related to medically actionable hereditary conditions (other than cancer)

Time frame: For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory.

Population: 827 is the number of CHARM participants who were sent a saliva collection kit, returned their sample to the laboratory, had successful DNA extraction, and sequencing was completed. There was no randomization, and therefore no separate arms for this analysis.