Clinical trial NCT04359420: What Are the Benefits and Harms of Risk Stratified Screening in the NHS Breast Screening Programme: Study Protocol
Official title: What Are the Benefits and Harms of Risk Stratified Screening as Part of the NHS Breast Screening Programme: Study Protocol for a Multi-site Non-randomised Comparison of BC-Predict Versus Usual Screening
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
Screening
risk stratification
high risk
psychological impact
early detection
mammographic density
chemoprevention
Tyrer-Cuzick
anxiety
Lead sponsor: University of Manchester
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: Breast Cancer Now
name: Prevent Breast Cancer
name: Queen Mary University of London
name: University of Nottingham
name: Manchester University NHS Foundation Trust
name: East Lancashire Hospitals NHS Trust
name: East Cheshire NHS Trust
name: NHS Breast Screening Programme
name: The Christie NHS Foundation Trust
First posted: 2020-04-24
Enrollment: 32298
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A non-randomised fully counterbalanced study design will be used, to include equal numbers of participants from all sites who will be offered NHS-BSP and BC-Predict. Specifically, in the initial 8-month time period, women eligible for breast screening in three screening sites will be offered BC-Predict, whilst women in two screening sites are offered usual NHS-BSP. In the following 8-month time period the study sites switch to offer the other intervention (NHS-BSP rather than BC-Predict; and vice versa). This will allow estimates of effect to be obtained from both within-sample and between-sample analyses.
Primary purpose: PREVENTION

Brief summary: This study aims to identify key benefits and harms of integrating risk stratification (the BC-Predict intervention) into the NHS Breast Screening Programme. A non-randomised fully counterbalanced study design will be used, whereby women from screening sites will be offered usual NHS Breast Screening Programme or BC-Predict for an eight month period, followed by a cross-over point where women at each site will be offered the other invention during an eight month period.

Detailed description: In principle, risk-stratification as a routine part of the NHS breast screening programme (NHS-BSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE (National Institute of Health and Care Excellence) approved more frequent screening and/ or chemoprevention to be realised for women who are at increased risk, but are unaware of this. The invesigators have developed BC-Predict, which is offered to women when invited to NHS-BSP and collects information on risk factors (self-reported information on family history and hormone-related factors, mammographic density and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict then produces risk feedback letters, and invites women at moderate or high risk to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Key objectives of the present research are to quantify important potential benefits and harms, and to identify the key drivers of the relative cost-effectiveness of embedding BC-Predict into NHS-BSP.

A non-randomised fully counterbalanced study design will be used, to include equal numbers of participants from five screening sites who will be offered NHS-BSP and BC-Predict. Specifically, in the initial 8-month time period, women eligible for NHS-BSP in three screening sites will be offered BC-Predict, whilst women in two screening sites are offered usual NHS-BSP. In the following 8-month time period the study sites switch their offers. In total 16000 women will be invited to BC-Predict, and compared with 16000 women offered standard NHS-BSP. Key potential benefits including uptake of BC-Predict, risk consultations, chemoprevention and additional screening will be obtained from NHS-BSP and Family History, Risk and Prevention Clinic records for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires. Health economic analyses will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHS-BSP.

Eligibility criteria: Inclusion Criteria:

* born biologically female,
* invited for either (a) first breast screening appointment (any age) or: (b) aged 57-63 years (only at East Cheshire and East Lancashire breast screening programmes),
* able to provide informed consent and complete a risk assessment questionnaire.

Exclusion Criteria:

* previously has had breast cancer,
* has had bilateral mastectomy, or
* has previously participated in the related PROCAS (Predicting Risk Of Cancer At Screening) study

Primary outcomes:
measure: Prescription of chemoprevention.
timeFrame: 6 months after screening appointment
Secondary outcomes:
measure: Screening attendance at first offered screening episode
timeFrame: attendance within 6 weeks of first specific appointment offered
measure: Screening attendance within 180 days
timeFrame: within 180 days first appointment offered
measure: number of recalls
timeFrame: within 6 months of first appointment offered
measure: Number of breast cancer diagnoses
timeFrame: within 6 months of first appointment offered
measure: Uptake of consultation at Family History, Risk and Prevention clinics
timeFrame: within 6 months of first appointment offered
measure: Enrolment for more frequent screening
timeFrame: within 6 months of first appointment offered
measure: State anxiety
timeFrame: at 6 months of first appointment offered, controlling for baseline values
measure: Cancer worry
timeFrame: at 6 months of first appointment offered, controlling for baseline values
measure: Informed choices to attend screening or not
timeFrame: at 6 months of first appointment offered, controlling for baseline values
Other outcomes:
measure: Cost consequences
timeFrame: at 6 months of first appointment offered
measure: Variation in uptake of services offered examined by deciles of index of multiple deprivation (as assessed using residential postcode)
timeFrame: at 6 months of first appointment
Locations:
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: Greater Manchester
Study officials:
affiliation: Manchester University NHS Foundation Trust
name: Gareth Evans, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: French DP, Astley S, Brentnall AR, Cuzick J, Dobrashian R, Duffy SW, Gorman LS, Harkness EF, Harrison F, Harvie M, Howell A, Jerrison A, Machin M, Maxwell AJ, McWilliams L, Payne K, Qureshi N, Ruane H, Sampson S, Stavrinos P, Thorpe E, Ulph F, van Staa T, Woof V, Evans DG. What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420). BMC Cancer. 2020 Jun 18;20(1):570. doi: 10.1186/s12885-020-07054-2.