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| ID | Type | Description | Link |
|---|---|---|---|
| REC Reference 24/NW/0294 | Other Identifier | North West Preston Research Ethics Committee |
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| Name | Class |
|---|---|
| University of Cambridge | OTHER |
| University of Manchester | OTHER |
| London School of Hygiene and Tropical Medicine | OTHER |
| Institute of Cancer Research, United Kingdom |
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PROTECT-C is a research study offering genetic testing to people to see whether they have a genetic change that increases their risk of breast, ovary, bowel, and/or womb cancer. This is regardless of whether they or their families have had cancer.
Breast, ovary, bowel, and womb cancers make up half of all cancers in women. Around 15-20% (15 to 20 in 100 cases) of ovary and 3-4% (3 to 4 in 100 cases) of breast, womb, and bowel cancers are linked to cancer genes and may be prevented. People with a genetic change that puts them at increased risk of any of these cancers have ways to help them manage their risk through the NHS. This may include screening to find cancers earlier when they are easier to treat, and surgery or medication to prevent cancers from developing. This can save lives.
Currently, genetic testing is only available on the NHS to people who meet certain criteria. For example, those who have had certain cancers, have a strong family history of cancer, or those with Jewish ancestry. But many people may not have a strong family history or meet NHS testing criteria. This means that this system of testing misses 50% to 80% of people (50 to 80 in 100 people) who have a genetic change. It is thought that only around 3 in 100 people overall who have a genetic change that increases their risk of cancer know about it. Given the effective screening and preventive options that are available, this represents a huge, missed opportunity to prevent cancers or find them earlier.
The PROTECT-C study aims to evaluate the option of offering genetic testing to everyone who may want it. This is regardless of whether they or their families have had cancer. We will offer genetic testing to 5000 people. People may take part if they:
PROTECT-C is a completely digital study. The study team will give participants access to an app developed specifically for this study. They can download this app using a smartphone or tablet or access it on any internet browser using a computer or laptop. Before they can access the app, participants will need to complete a consent form. They will also be asked to fill in a short questionnaire about themselves and their health. The PROTECT-C app contains information to help participants decide if they would like to have genetic testing. If they decide to have genetic testing, they will complete a consent form for genetic testing on the app. The study team will send them a saliva based test kit in the post.
The study will look at how many people decide to have genetic testing and how many of them are found to have a genetic change. It will evaluate their experience with using the app and how this approach to genetic testing affects their quality-of-life, satisfaction, and mental well-being. This will give us a better understanding of how well the app works as a way of offering genetic testing to people. The study is interested to see how people found to be at increased risk decide to manage their risk. We will assess the uptake of screening and prevention options. Few participants will be invited to have 1:1 interviews by the study team. This will evaluate their experience of making a decision about genetic testing and taking part in the study. Taking part in these interviews is optional. The study will also assess if this way of offering genetic testing to people is affordable for the NHS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Genetic testing | Experimental | Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk prediction |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk | Genetic | Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk for all women (including trans-men, and non-binary individuals with female reproductive organs) over the age of 18 years independent of any family or personal history of cancer. |
| Measure | Description | Time Frame |
|---|---|---|
| Pathogenic variant (PV) prevalence for multiple moderate to high penetrance CSGs (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) in women from unselected population-based genetic testing compared with FH-based genetic testing | The primary outcome measure is the proportion of women with one or more CSGs who have undergone genetic testing and received a valid result. PV prevalence will be estimated by the number of observed PVs divided by the total number of individuals tested. An overall rate and CSG specific rates will be calculated. Standard NHS criteria at time of the study (i.e. Amsterdam-2 Criteria for Lynch Syndrome and 10% BRCA probability threshold for HBOC) will be used to evaluate family history criteria for genetic testing. The proportion of PVs fulfilling NHS testing criteria (FH positive) will be estimated. 95% Confidence Intervals for these outcomes will be calculated as per methods specified in the SAP (statistical analysis plan). | 1 year after completing recruitment |
| Measure | Description | Time Frame |
|---|---|---|
| Satisfaction and regret (Satisfaction) | Satisfaction is measured as the proportion of positive responses to the statement "I am satisfied with the decision I have made" | measured at acceptance, 21 days, 6 months and 12 months |
| Satisfaction and regret (Regret) |
| Measure | Description | Time Frame |
|---|---|---|
| To determine the uptake of population-based genetic testing | Proportion of women with who consent to undergo genetic testing (amongst those consenting to the study) 6 months after return of the last test result. | 6 months after return of the last test result |
| Proportion of women categorised as moderate and high risk of breast cancer (BC) and moderate and moderate and high risk of ovarian cancer (OC) |
Inclusion Criteria:
Exclusion Criteria:
Women, trans men, and non-binary people with female reproductive organs who are ≥18 years at consent
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ranjit Manchanda, PhD | Contact | +44 8008620236 | r.manchanda@qmul.ac.uk | |
| Caitlin Fierheller, PhD | Contact | +44 8008620236 | protectc.study@qmul.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Ranjit Manchanda, PhD | Wolfson Institute of Population Health, Queen Mary University of London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wolfson Institute of Population Health, Queen Mary University of London | Recruiting | London | EC1M 6BQ | United Kingdom |
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| Label | URL |
|---|---|
| PROTECT-C Web site | View source |
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Patient data may be shared after completion of study and publication of all results, on reasonable request and communication from the Chief Investigator - via email - r.manchanda@qmul.ac.uk
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| OTHER |
| University of Leeds | OTHER |
| Imperial College London | OTHER |
| University College, London | OTHER |
| VU University Medical Center (VUmc) | UNKNOWN |
| St George's, University of London | OTHER |
Interventional cohort study offering genetic testing for moderate to high penetrance Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and a personalised breast and ovarian cancer risk prediction using a digital app and saliva based DNA testing.
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Regret is measured as the proportion who score 10 or less using the Decision Regret Scale questionnaire (scale 5-25 where 5 indicates completely dissatisfied and 25 indicates completely satisfied). |
| measured at acceptance, 21 days, 6 months and 12 months |
| Quality of life using EQ5D- 5L | Quality of Life is measured using the EORTC Questionnaire EQ5D- 5L. Mean score (range 0-1) with higher scores indicating higher quality of life. | Pre-genetic testing and at 21 days, 6 months and 12 months |
| Psychosocial wellbeing - Cancer worry | a. Cancer worry score is measured using the Cancer Worry Scale questionnaire (4-item Cancer Worry Scale questionnaire on a 4-point Likert scale). Mean Cancer Worry Scale score (range 4-16) and self-reported VAS score (range 0-100); with higher score indicates greater concern | Pre-genetic testing and at 21 days, 6 months and 12 months |
| Psychosocial wellbeing - Risk perception | Risk perception is measured as the proportion responding as at "high or much higher" chance of cancer to the statement "compared with other people of your age, do you think your chances of getting cancer at some point in your life are…" | Pre-genetic testing and at 21 days, 6 months and 12 months |
| Psychosocial wellbeing - Anxiety and depression | Anxiety is measured using the Hospital Anxiety and Depression Scale (HADS) anxiety questionnaire- Anxiety score (7-item questionnaire on a 4-point Likert scale). Depression is measured using the HADS depression questionnaire -(7-item questionnaire on a 4-point Likert scale). Scores range from 0-21 with higher scores indicating higher levels of anxiety/depression. | Pre-genetic testing and at 21 days, 6 months and 12 months |
| Psychosocial wellbeing - Distress | Distress is measured using the Impact of Events (IES) questionnaire (22-item IES questionnaire on a 5-point Likert scale). Mean score IES Intrusive scale (range 0-35) and IES Avoidance scale (range 0-38); where higher scores indicate greater distress. | Pre-genetic testing and at 21 days, 6 months and 12 months |
| Psychosocial wellbeing - Impact | Impact is measured using the Multidimensional Impact of Cancer (MICRA) questionnaire. Mean score overall (range 0 -105) with separate scores for distress, positive experiences and uncertainty. MICRA distress scale (range 0-30), MICRA positive experiences scale (range 0-20) and MICRA uncertainty scale (range 0-45); where higher scores indicates higher impact. | Pre-genetic testing and at 21 days, 6 months and 12 months |
| Uptake of risk management options | Uptake of risk management options (for breast, ovarian, endometrial and bowel cancers) are measured using self-reported, clinical and/or registry data
| collected annually over 8 years |
| Uptake of cascade testing | Uptake of cascade testing is measured as the total number of people who undergo cascade testing per family in an individual with a PV in a CSG at 2 years after the return of the last test result | 2 years post return of last result in those recruited |
| VUS carrier frequency | measured as the proportion of VUS carriers in women who have undergone testing at 6 months after return of the last test result | 6 months after return of the last test result |
| Cost-effectiveness of genetic testing | Is measured by incremental cost-effectiveness ratio (ICER) comparing population testing strategy with a family history based testing strategy. ICER per QALY is compared to the NICE willingness to pay threshold in the UK (£30,000/QALY). Incremental costs, incremental QALYs and number of cancers/deaths prevented will be calculated and one-way and probabilistic sensitivity analysis undertaken. | 12 months after return of last test result - initial analysis |
Number of women categorised as moderate or high risk for BC or moderate or high risk for OC using the CAN-RISK model Number of women categorised as moderate or high risk for BC using the Tyrer-Cuzick model Number of women categorised as moderate or high risk of BC using the Tyrer-Cuzick model, and difference compared with use of the CAN-RISK model |
| 6 months after return of the last test resut. |
| PV prevalence for individual CSG : BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6 | PV prevalence for "individual" CSG : BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6 calculated by Proportion of women who have undergone genetic testing and found to have a "specific" CSG Proportion of women identified as FH positive in women who test positive with PVs in "individual" CSGs | 6 months after return of the last test result. |
| Satisfaction and regret with population-based testing Longer term | Satisfaction: 1-item ("I am satisfied with the decision I have made") on a 5-point Likert scale Regret: Score as calculated from the 5-item Decision Regret Scale on a 5-point Likert scale. Measured as the proportion who score 10 or less using the Decision Regret Scale questionnaire (scale 5-25 where 5 indicates completely dissatisfied and 25 indicates completely satisfied). | Years 2, 3 post-test result |
| The experience of using and usability of the PROTECT-C app | 9-questions from App Evaluation Questionnaire. Evaluated separately for women who accept and decline genetic testing using. Accept/decline and 6-month post-test questionnaire.
| 6-month post-test result (or decision not to test in decliners) |
| Use of a helpline in population testing - Proportion | Helpline evaluation questionnaire and telephone or booking system record database. b. Reasons for helpline use- Proportion of consented women who called by reason c. Mode of helpline use - Proportion of calls by mode of use d. Ease of access - Proportion who found the helpline "very easy or easy" to use in those who used the helpline e. Satisfaction- Proportion who were "very satisfied or satisfied" with the helpline in those who used the helpline | Accept/decline, 21-days and 6-month post-test questionnaire |
| Use of a helpline in population testing - Frequency | Helpline evaluation questionnaire and telephone or booking system record database. a. Frequency of use of helpline- Total number of calls and proportion of consented women who contacted the helpline f. Frequency of use of booking system- Total number of people who used the online booking system | Accept/decline, 21-days and 6-month post-test questionnaire |
| Impact of genetic testing on health behaviours - Vitamin, alcohol, physical activity | specific measures on Lifestyle and Behaviours using a customised questionnaire. Measuring average change in proportions between the baseline questionnaire and 6-month post-test questionnaire, as well as 1-3 year questionnaire in women who consent to genetic testing.
| baseline questionnaire and 6-month post-test questionnaire, as well as 1-3 year questionnaire |
| Impact of genetic testing on health behaviours - Diet | specific measures on Lifestyle and Behaviours using a customised questionnaire. Measuring average change in proportions between the baseline questionnaire and 6-month post-test questionnaire, as well as 1-3 year questionnaire in women who consent to genetic testing. - Diet: Meat/Vegetable/Fruit consumption measured on a 7-point Likert scale for each | baseline questionnaire and 6-month post-test questionnaire, as well as 1-3 year questionnaire |
| Impact of genetic testing on health behaviours - Smoking | specific measures on Lifestyle and Behaviours using a customised questionnaire. Measuring average change in proportions between the baseline questionnaire and 6-month post-test questionnaire, as well as 1-3 year questionnaire in women who consent to genetic testing. - Smoking frequency (current/former/never) and quantity | baseline questionnaire and 6-month post-test questionnaire, as well as 1-3 year questionnaire |
| Women's motivations and experiences of panel genetic testing and personalised BC and OC risk estimation for cancer screening and prevention | Qualitative interview transcripts. Nvivo will be used to identify themes, index, chart, map, synthesize and interpret data, including comparison between relevant groups. | For decliners - Baseline (post decision) For those with a PV or moderate or high risk result - Baseline (post decision), 9-12 months post decision For VUS: Baseline (post decision), 12-18 months post decision |
| Impact of return of VUS results - Reclassification | VUS reclassification recorded on the study database (updated every 6-months) and returned to participant.
| End of study (end of year 8) |
| Impact of return of VUS results - Quality of life | VUS reclassification recorded on the study database (updated every 6-months) and returned to participant. - Quality of life and psychosocial outcomes in individuals with VUS, over time (baseline, 6 months, 1-3 years) | End of study (end of year 8) |
| Feasibility of running a study within a trial (SWAT): performance uptake | Performance uptake report. Proportion of individuals who registered on the website and indicated they received a letter, who could be linked to which type (one of two) of letter. To be reported at 6 months. | 6 months post last recruit. |
| Effectiveness of different letters on registration interest in the trial | Self-reported letter type within the registration questionnaire. Difference in proportions of those who received each letter and registered from those invited, by letter type. To be reported at 6 months | Reported at 6 months after recruitment completed. |
| Evaluate association of sociodemographic factors | Measures on the first questionnaire including:
| 6 months post last test result. |
| Quality of life EQ5D-5L longer term - EQ5D score | Quality of life measured using EORTC EQ5D-5L score (5 domains each with 5 levels). Mean EQ5D score (range 0-1) with higher score indicating higher quality of life. Evaluation of change in proportions/average scores between pre-genetic testing questionnaires, 6-months and 1-3 years post-test questionnaires in women who consent to genetic testing | baseline, 6 months, 1 year, 2 year, 3 years |
| Quality of life EQ5D-5L longer term - Visual Analogue Scale | Quality of life measured using self-reported Visual Analogue Scale (VAS) score (range 0-100) with higher score indicating higher quality of life. Evaluation of change in proportions/average scores between pre-genetic testing questionnaires, 6-months and 1-3 years post-test questionnaires in women who consent to genetic testing | baseline, 6 months, 1 year, 2 year, 3 years |
| Psychosocial wellbeing longer term - Cancer worry | Evaluation of change in proportions/average scores between pre-genetic testing questionnaires, 6-months and 1-3 years post-test questionnaires in women who consent to genetic testing. Mean cancer Worry Scale score (4-item Cancer Worry Scale questionnaire on a 4-point Likert scale) (range 4-16) with higher score indicates greater concern. | Pre-genetic testing, 6months, 1 year, 2 years, 3 years |
| Psychosocial wellbeing longer term - Risk pereception | Evaluation of change in proportions/average scores between pre-genetic testing questionnaires, 6-months and 1-3 years post-test questionnaires in women who consent to genetic testing. Risk perception is measured as the proportion responding as at "high or much higher" chance of cancer to the statement "compared with other people of your age, do you think your chances of getting cancer at some point in your life are…" | Pre-genetic testing, 6months, 1 year, 2 years, 3 years |
| Psychosocial wellbeing longer term - Anxiety and Depression | Evaluation of change in proportions/average scores between pre-genetic testing questionnaires, 6-months and 1-3 years post-test questionnaires in women who consent to genetic testing. Anxiety is measured using the Hospital Anxiety and Depression Scale (HADS) anxiety questionnaire- Anxiety score (7-item questionnaire on a 4-point Likert scale). Depression is measured using the HADS depression questionnaire -(7-item questionnaire on a 4-point Likert scale). Scores range from 0-21 with higher scores indicating higher levels of anxiety/depression. | Pre-genetic testing, 6months, 1 year, 2 years, 3 years |
| Psychosocial wellbeing longer term - Distress | Evaluation of change in proportions/average scores between pre-genetic testing questionnaires, 6-months and 1-3 years post-test questionnaires in women who consent to genetic testing. Distress is measured using the Impact of Events (IES) questionnaire (22-item IES questionnaire on a 5-point Likert scale). Mean score IES Intrusive scale (range 0-35) and IES Avoidance scale (range 0-38); where higher scores indicate greater distress. | Pre-genetic testing, 6months, 1 year, 2 years, 3 years |
| Psychosocial wellbeing longer term - Impact | Evaluation of change in proportions/average scores between pre-genetic testing questionnaires, 6-months and 1-3 years post-test questionnaires in women who consent to genetic testing. Impact is measured using the Multidimensional Impact of Cancer (MICRA) questionnaire. Mean score overall (range 0 -105) with separate scores for distress, positive experiences and uncertainty. MICRA distress scale (range 0-30), MICRA positive experiences scale (range 0-20) and MICRA uncertainty scale (range 0-45); where higher scores indicates higher impact. | Pre-genetic testing, 6months, 1 year, 2 years, 3 years |
| ID | Term |
|---|---|
| D003123 | Colorectal Neoplasms, Hereditary Nonpolyposis |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009386 | Neoplastic Syndromes, Hereditary |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| C448305 | RAD51C protein, human |
| C094443 | G-T mismatch-binding protein |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
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