Genetic Predisposition
Conditions
Keywords
Primary Care, Genetic Testing, Risk Assessment, Hereditary Cancer, Implementation
Brief summary
The study intervention involves having patients complete a familial cancer risk assessment survey. Those who are found to be at high risk will be offered genetic testing for a panel of hereditary cancers. A previvor plan will be created to assist patients and their providers in completing the appropriate follow-up for those with a mutation identified.
Detailed description
Current practice guidelines from ACMG (American College of Medical Genetics and Genomics) provide referral indications for cancer predisposition assessment. Identifying patients with high genetic risk for breast, ovary, colon, or other cancers has important clinical ramifications for an individual's healthcare, but genetic risk if often not identified because of testing barriers at several levels. Barriers at the provider level include inadequacies in risk recognition, patient referrals and availability of genetic professionals to provide counseling in a traditional testing paradigm. Barriers at the level of the patient include poor understanding of the availability and benefits of testing and inadequate access to testing services. How to best implement appropriate genomic testing and follow-up care into an operating healthcare system is not known. Issues of communication, clinical flow, reportable actions, and transmission of information and support are of critical importance, and must change and grow to accommodate the new information contained within genomic testing. Studies to date of the implementation process have been conducted in high resourced facilities, under optimal conditions, often not at the system level. Aims include: 1. Compare the efficacy and implementation of two strategies for identifying members of a primary care clinic's population who have a family or personal history of cancer and offering high-risk individuals to obtain genetic testing for cancer susceptibility mutations in a randomized trial. The two methods are: 1) Point of Care (POC) approach: A tablet-based screening for family/personal history of cancer will be offered to all patients aged 25 and up coming in for a routine appointment at the clinic. 2) Direct Patient Engagement (DPE): Emails and letters will be sent to all individuals aged 25 and older in a clinic's population, inviting them to visit a web site for screening for family /personal history of cancer. In both strategies, those determined to be high-risk will receive online education about genetic testing and an invitation to obtain such testing through a web-based platform. Randomization will occur at the clinic level, with half of the clinics using the POC approach and the other half using DPE. Outcomes will be the fraction of the active clinic patient population that completes screening and the fraction of the active clinic patient population that undergoes testing. Hypothesis 1: DPE screening will result in a higher proportion of active patients who screen for familial cancer risk compared with POC screening. Hypothesis 2: Of screened patients, POC patients will produce a higher proportion of tested patients compared with DPE. 2. Identify changes, problems, and inefficiencies in clinical flow and interactions during and after the implementation of genomic testing for cancer risk across primary care clinics. 3. Evaluate the effects of two methods of implementation of genomic screening for cancer risk on patient, provider, and health system leader reports of benefits and harms, satisfaction, perceived quality of care, including across gender, racial/ethnic, socioeconomic, and genetic literacy divides. 4. Evaluate the value (cost-effectiveness) and affordability (budget impact) of each screening strategy.
Interventions
BEHAVIORALPopulation-level screening
The study intervention involves having patients complete a familial cancer risk assessment survey. Those who are found to be at high risk will be offered genetic testing for a panel of hereditary cancers. A previvor plan will be created to assist patients and their providers in completing the appropriate follow-up for those with a mutation identified.
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for Patients: * Age 25 or older * An active patient at a participating clinic (had at least one visit in the past 12 months) * Comfortable reading and writing in English
Exclusion criteria
* Those who do not meet inclusion criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Screening | 1 year | Fraction of the active clinic patient population that completed screening |
| Rates of Testing | 1 year | Fraction of the active clinic patient population that completed genetic testing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Screening and Testing at Healthcare System A | 2 years | The table displays the percentages (i.e., proportions) of screening and testing that occurred in the study. The number of patients screened and the number tested are listed as well, but as the denominators differ, the results for Outcome 6 will be based on scaling the proportions to a theoretical healthcare system with 100,000 patients. This information will then be used along with the incremental costs for a healthcare system with 100,000 patients (Outcome 4) to determine the incremental cost-effectiveness ratios (ICERs) presented in Outcome 7. |
| Total Cost of Each Engagement Strategy | 2 years | This outcome is the total costs for each engagement strategy, scaled to a healthcare system of 100,000 patients. The total costs from the health-system perspective is the sum of program costs and staff costs over 2 years, in U.S. dollars. The cost from the limited societal perspective includes patient costs in addition to health-system costs. The total costs will be used in the incremental cost calculation below. |
| Incremental Cost-effectiveness Ratio (ICER) Per Patient Screened; Incremental Cost-effectiveness Ratio Per Patient Tested | 2 years | This outcome is the Incremental Cost-effectiveness Ratio (ICER). The ICER estimates how much the DPE strategy costs, relative to the POC strategy (DPE minus POC), to improve the outcome measure by 1 unit (in this case one additional patient screened or one additional patient tested). The ICER is calculated by using the difference in costs (outcome 4) divided by the difference in outcome (outcome 6). When the numerator is positive and the denominator is negative (as it is for screening), general practice is to state the second strategy (DPE in this case) was dominated by the first strategy (the standard, which is POC in this case). A negative ICER can be misinterpreted, making this clarification necessary. |
| Incremental Patients Screened; Incremental Patients Tested | 2 years | This outcome is the comparative (incremental) difference between the two different engagement strategies in screening and testing outcomes. The total patients screened and tested for each arm are presented in outcome 5 above. The proportions for these outcomes were then scaled to a healthcare system of 100,000 patients and the incremental difference was calculated by comparing the DPE arm to the POC arm (DPE minus POC). Scaling the numbers to a healthcare system of 100,000 patients is necessary for this component to be compatible with the costs for a healthcare system of 100,000 patients given in Outcome 4, in order to calculate the ICERs (Outcome 7). |
| Incremental Cost When Comparing Two Engagement Strategies | 2 years | This outcome is the comparative (incremental) cost of two different engagement strategies for population-based risk assessment for hereditary cancer genetic screening and testing in primary care. The total costs for each arm are presented in outcome 3 above. The incremental cost is the difference in total costs when comparing the DPE arm to the POC arm (DPE minus POC). |
Countries
United States
Participant flow
Recruitment details
12 primary care clinics (units) were randomized to use one of two engagement strategies. Patients who had an appointment at a clinic randomized to the POC arm were approached using the POC strategy (described below). Patients seen at a DPE clinic were approached using the DPE strategy. Recruitment began in September of 2020 and ended in February of 2023.
Pre-assignment details
As randomization was done by clinic, 115,484 individuals started the study (115,319 patients; 165 primary care providers). The 95,623 patients seen during the 12 month window set by the study protocol serve as the denominator for the main outcomes (proportion of patients who completed the cancer risk assessment screening; proportion of patients who completed genetic testing). 20,184 individuals were officially enrolled through completing surveys or the cancer risk assessment screening.
Participants by arm
| Arm | Count |
|---|---|
| Point of Care Clinics in the point of care (POC) arm approached patients at the time they came in to the clinic for a routine visit with their primary care provider. The familial cancer risk screening was completed using electronic tablets in the waiting room or, in the case of a telehealth visit, through telephone contact before the visit. Patients identified as likely to benefit based on their risk profile, were offered genetic testing for a panel of hereditary cancers. | 12,316 |
| Point of Care Clinics in the point of care (POC) arm approached patients at the time they came in to the clinic for a routine visit with their primary care provider. The familial cancer risk screening was completed using electronic tablets in the waiting room or, in the case of a telehealth visit, through telephone contact before the visit. Patients identified as likely to benefit based on their risk profile, were offered genetic testing for a panel of hereditary cancers. | 6 |
| Direct Patient Engagement Clinics in the direct patient engagement (DPE) arm contacted patients by postal mail and email to provide a link to the online familial cancer risk screening tool. This occurred one to three months after the patient had a routine visit with their primary care provider. Patients identified as likely to benefit based on their risk profile, were offered genetic testing for a panel of hereditary cancers. | 5,582 |
| Direct Patient Engagement Clinics in the direct patient engagement (DPE) arm contacted patients by postal mail and email to provide a link to the online familial cancer risk screening tool. This occurred one to three months after the patient had a routine visit with their primary care provider. Patients identified as likely to benefit based on their risk profile, were offered genetic testing for a panel of hereditary cancers. | 6 |
| Total | 17,910 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not complete any study assessment | 50,303 | 44,997 |
Baseline characteristics
| Characteristic | Point of Care | Direct Patient Engagement | Total |
|---|---|---|---|
| Age, Continuous Patients who completed a baseline survey | 61.7 years STANDARD_DEVIATION 15.2 | 61.0 years STANDARD_DEVIATION 15.3 | 61.3 years STANDARD_DEVIATION 15.3 |
| Age, Continuous Patients who completed cancer risk assessment screening | 59.0 years STANDARD_DEVIATION 16.2 | 58.0 years STANDARD_DEVIATION 14.9 | 58.9 years STANDARD_DEVIATION 15.1 |
| Ethnicity (NIH/OMB) Patients Hispanic or Latino | 21 Participants | 37 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Patients Not Hispanic or Latino | 997 Participants | 1046 Participants | 2043 Participants |
| Ethnicity (NIH/OMB) Patients Unknown or Not Reported | 110 Participants | 108 Participants | 218 Participants |
| Ethnicity (NIH/OMB) Providers and Clinic Leaders Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Providers and Clinic Leaders Not Hispanic or Latino | 30 Participants | 23 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Providers and Clinic Leaders Unknown or Not Reported | 9 Participants | 8 Participants | 17 Participants |
| Race (NIH/OMB) Patients American Indian or Alaska Native | 7 Participants | 11 Participants | 18 Participants |
| Race (NIH/OMB) Patients Asian | 21 Participants | 31 Participants | 52 Participants |
| Race (NIH/OMB) Patients Black or African American | 14 Participants | 17 Participants | 31 Participants |
| Race (NIH/OMB) Patients More than one race | 33 Participants | 38 Participants | 71 Participants |
| Race (NIH/OMB) Patients Native Hawaiian or Other Pacific Islander | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Patients Unknown or Not Reported | 49 Participants | 55 Participants | 104 Participants |
| Race (NIH/OMB) Patients White | 1000 Participants | 1037 Participants | 2037 Participants |
| Race (NIH/OMB) Providers and Clinic Leaders American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Providers and Clinic Leaders Asian | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Providers and Clinic Leaders Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Providers and Clinic Leaders More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Providers and Clinic Leaders Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Providers and Clinic Leaders Unknown or Not Reported | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Providers and Clinic Leaders White | 31 Participants | 20 Participants | 51 Participants |
| Region of Enrollment United States | 12316 Participants | 5582 Participants | 17898 Participants |
| Sex/Gender, Customized Female (Patients) | 7359 Participants | 3834 Participants | 11193 Participants |
| Sex/Gender, Customized Female (Providers and Clinic Leaders) | 21 Participants | 16 Participants | 37 Participants |
| Sex/Gender, Customized Male (Patients) | 4481 Participants | 1693 Participants | 6174 Participants |
| Sex/Gender, Customized Male (Providers and Clinic Leaders) | 12 Participants | 10 Participants | 22 Participants |
| Sex/Gender, Customized Unknown (Patients) | 436 Participants | 22 Participants | 458 Participants |
| Sex/Gender, Customized Unknown (Providers and Clinic Leaders) | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Rates of Screening
Fraction of the active clinic patient population that completed screening
Time frame: 1 year
Population: Patients 25 years of age or older, comfortable speaking English, who had an appointment at one of the participating clinics during the 12 month recruitment window.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Point of Care | Rates of Screening | 9892 Participants |
| Direct Patient Engagement | Rates of Screening | 3813 Participants |
p-value: 0.0074Chi-squared
Primary
Rates of Testing
Fraction of the active clinic patient population that completed genetic testing.
Time frame: 1 year
Population: Patients 25 years of age or older, comfortable speaking English, who had an appointment at one of the participating clinics during the 12 month recruitment window.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Point of Care | Rates of Testing | 757 Participants |
| Direct Patient Engagement | Rates of Testing | 717 Participants |
p-value: <0.0001Chi-squared
Secondary
Incremental Cost-effectiveness Ratio (ICER) Per Patient Screened; Incremental Cost-effectiveness Ratio Per Patient Tested
This outcome is the Incremental Cost-effectiveness Ratio (ICER). The ICER estimates how much the DPE strategy costs, relative to the POC strategy (DPE minus POC), to improve the outcome measure by 1 unit (in this case one additional patient screened or one additional patient tested). The ICER is calculated by using the difference in costs (outcome 4) divided by the difference in outcome (outcome 6). When the numerator is positive and the denominator is negative (as it is for screening), general practice is to state the second strategy (DPE in this case) was dominated by the first strategy (the standard, which is POC in this case). A negative ICER can be misinterpreted, making this clarification necessary.
Time frame: 2 years
Population: Costs and outcomes were compared between the two arms, with POC as the comparator (standard); in other words DPE minus POC. This combination of the two arms was the prespecified analysis. Cost effectiveness was calculated at the per-patient level, then scaled to apply to a theoretical healthcare system with 100,000 patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Point of Care | Incremental Cost-effectiveness Ratio (ICER) Per Patient Screened; Incremental Cost-effectiveness Ratio Per Patient Tested | ICER per additional patient screened from health-system perspective | -7 $ per additional patient |
| Point of Care | Incremental Cost-effectiveness Ratio (ICER) Per Patient Screened; Incremental Cost-effectiveness Ratio Per Patient Tested | ICER per additional patient screened from limited societal perspective | -6 $ per additional patient |
| Point of Care | Incremental Cost-effectiveness Ratio (ICER) Per Patient Screened; Incremental Cost-effectiveness Ratio Per Patient Tested | ICER per additional patient tested from health-system perspective | 140 $ per additional patient |
| Point of Care | Incremental Cost-effectiveness Ratio (ICER) Per Patient Screened; Incremental Cost-effectiveness Ratio Per Patient Tested | ICER per additional patient tested from limited societal perspective | 124 $ per additional patient |
Secondary
Incremental Cost When Comparing Two Engagement Strategies
This outcome is the comparative (incremental) cost of two different engagement strategies for population-based risk assessment for hereditary cancer genetic screening and testing in primary care. The total costs for each arm are presented in outcome 3 above. The incremental cost is the difference in total costs when comparing the DPE arm to the POC arm (DPE minus POC).
Time frame: 2 years
Population: Costs and outcomes were compared between the two arms, with POC as the comparator (standard); that is DPE minus POC. Costs were calculated at the per-patient level and scaled to apply to a theoretical healthcare system with 100,000 patients. As this outcome is the difference between the two strategies, only one value is calculated using the data from the two arms combined. The total costs per arm used for this calculation are shown in outcome 3 above.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Point of Care | Incremental Cost When Comparing Two Engagement Strategies | Incremental cost from health-system perspective | 56,340 cost in $ |
| Point of Care | Incremental Cost When Comparing Two Engagement Strategies | Incremental cost from limited societal perspective (includes patient costs) | 49,955 cost in $ |
Secondary
Incremental Patients Screened; Incremental Patients Tested
This outcome is the comparative (incremental) difference between the two different engagement strategies in screening and testing outcomes. The total patients screened and tested for each arm are presented in outcome 5 above. The proportions for these outcomes were then scaled to a healthcare system of 100,000 patients and the incremental difference was calculated by comparing the DPE arm to the POC arm (DPE minus POC). Scaling the numbers to a healthcare system of 100,000 patients is necessary for this component to be compatible with the costs for a healthcare system of 100,000 patients given in Outcome 4, in order to calculate the ICERs (Outcome 7).
Time frame: 2 years
Population: NOTE: percentages (i.e., proportions) shown in Outcome 5 were scaled to a healthcare system of 100,000 patients before calculating these incremental differences. Outcomes were then compared between the two arms (DPE minus POC). As this outcome is the difference between the two strategies, only one value is calculated using the data from the two arms combined. Again, differences were calculated after scaling the proportions, rather than simply using the participant counts from Outcome 5.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Point of Care | Incremental Patients Screened; Incremental Patients Tested | Incremental patients screened | -8,105 participants |
| Point of Care | Incremental Patients Screened; Incremental Patients Tested | Incremental patients tested | 404 participants |
Secondary
Rates of Screening and Testing at Healthcare System A
The table displays the percentages (i.e., proportions) of screening and testing that occurred in the study. The number of patients screened and the number tested are listed as well, but as the denominators differ, the results for Outcome 6 will be based on scaling the proportions to a theoretical healthcare system with 100,000 patients. This information will then be used along with the incremental costs for a healthcare system with 100,000 patients (Outcome 4) to determine the incremental cost-effectiveness ratios (ICERs) presented in Outcome 7.
Time frame: 2 years
Population: Data from only one of the participating healthcare systems were used. There were 3 clinics in the POC arm and 3 clinics in the DPE arm. The percentages (i.e. proportions) in the table are based on study participant counts. These proportions will be scaled to a healthcare system of 100,000 patients when calculating the incremental differences for Outcome 6.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Point of Care | Rates of Screening and Testing at Healthcare System A | Patients screened | 4,327 Participants |
| Point of Care | Rates of Screening and Testing at Healthcare System A | Patients tested | 233 Participants |
| Direct Patient Engagement | Rates of Screening and Testing at Healthcare System A | Patients screened | 1,370 Participants |
| Direct Patient Engagement | Rates of Screening and Testing at Healthcare System A | Patients tested | 254 Participants |
Secondary
Total Cost of Each Engagement Strategy
This outcome is the total costs for each engagement strategy, scaled to a healthcare system of 100,000 patients. The total costs from the health-system perspective is the sum of program costs and staff costs over 2 years, in U.S. dollars. The cost from the limited societal perspective includes patient costs in addition to health-system costs. The total costs will be used in the incremental cost calculation below.
Time frame: 2 years
Population: Data from only one of the participating healthcare systems were used. There were 3 clinics in the POC arm and 3 clinics in the DPE arm. Costs were calculated at the per-patient level and scaled to apply to a theoretical healthcare system with 100,000 patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Point of Care | Total Cost of Each Engagement Strategy | Cost from health-system perspective | 640,776 cost in $ |
| Point of Care | Total Cost of Each Engagement Strategy | Cost from limited societal perspective (includes patient costs) | 648,395 cost in $ |
| Direct Patient Engagement | Total Cost of Each Engagement Strategy | Cost from health-system perspective | 697,116 cost in $ |
| Direct Patient Engagement | Total Cost of Each Engagement Strategy | Cost from limited societal perspective (includes patient costs) | 698,350 cost in $ |