What Are the Benefits and Harms of Risk Stratified Screening in the NHS Breast Screening Programme: Study Protocol

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: BC-Predict; Other: NHS Breast Screening Programme

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.

• Study Type: Interventional
• Enrollment (Actual): 32298
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M23 9LT
      • Manchester University NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BC-Predict; Women will be sent an invitation letter one to two days after their breast screening invitation letter, directing prospective participants to the online risk assessment platform. Once participants have consented to the study online, they will be directed to the BC-Predict risk assessment questionnaire. Assessment of the online questionnaire during the pilot phase estimated that most women would be able to complete this within 30 minutes. Women who complete the questionnaire will receive 10-year breast cancer risk estimates once they have screened negative for breast cancer, based on the Tyrer-Cuzick model, incorporating mammographic density, and for some women, SNPs (single nucleotide polymorphisms). Women who are identified as being at "high" (>8%) or "moderate" (5% and <8%) 10-year risk will be offered a consultation to discuss prevention options including prescription of chemoprevention drugs and/ or more frequent mammography as part of the NHS Breast Screening Programme.	Other: BC-Predict; BC-Predict is an automated system for offering an assessment of breast cancer risk to women when they receive their NHS Breast Screening Programme invitation, and generating letters to feedback this risk to women and relevant healthcare professionals. Women at higher risk are offered chemoprevention drugs and additional mammography; Other Names: risk stratified screening
Active Comparator: NHS-Breast Screening Programme; Usual care in the NHS Breast Screening Programme, which involves mammography every 3 years for the majority of women	Other: NHS Breast Screening Programme; usual care from NHS Breast Screening Programme, consisting of mammography every three years for most women.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prescription of chemoprevention.	Frequency of women taking up initial prescription of chemoprevention drugs (anastrozole/tamoxifen/raloxifene) from Family History, Risk and Prevention Clinic Data will be collected on each of the following aspects of this: (a) participant agrees/disagrees in clinic to take chemoprevention, (b) chemoprevention not appropriate, (c) chemoprevention appropriate but prescription not filled, (d) chemoprevention appropriate and prescription filled.	6 months after screening appointment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Screening attendance at first offered screening episode	Attendance at NHS Breast Screening Programme appointment	attendance within 6 weeks of first specific appointment offered
Screening attendance within 180 days	Attendance at NHS Breast Screening Programme appointment	within 180 days first appointment offered
number of recalls	number of recalls from NHS Breast Screening programme: (a) technical recalls, (b) for assessment, (c) routine recalls	within 6 months of first appointment offered
Number of breast cancer diagnoses	Number of breast cancers diagnosed	within 6 months of first appointment offered
Uptake of consultation at Family History, Risk and Prevention clinics	Family History, Risk and Prevention clinic attendance, to discuss possibly measures to reduce breast cancer risk	within 6 months of first appointment offered
Enrolment for more frequent screening	Uptake of more frequent screening (e.g. yearly) from NHS Breast Screening programme	within 6 months of first appointment offered
State anxiety	Measured using STAI (Spielberger State Anxiety Inventory) short form. Range 6 to 24. Higher scores indicate higher anxiety.	at 6 months of first appointment offered, controlling for baseline values
Cancer worry	Measured using Lerman Cancer Worry Scale. Range 6 to 24. Higher scores indicate higher cancer worry.	at 6 months of first appointment offered, controlling for baseline values
Informed choices to attend screening or not	Informed choices regarding screening will be estimated from attitudes to screening at baseline, knowledge and screening attendance, using a standard approach reported by Marteau, Dormandy & Michie	at 6 months of first appointment offered, controlling for baseline values

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost consequences	cost consequences analysis to understand the short-term relative impact of the risk feedback intervention (BC-Predict) based on health status (EQ-5D5L), capability (ICECAP-A); and proportion of women starting chemoprevention.	at 6 months of first appointment offered
Variation in uptake of services offered examined by deciles of index of multiple deprivation (as assessed using residential postcode)	The investigators will examine variations in proportion of people offered services (i.e. uptake of NHS Breast Screening programme and BC-Predict), between groups defined by deciles of Indices of Multiple Deprivation (derived from residential postcode). This will assess any potential exacerbation of health inequalities brought about by BC-Predict.	at 6 months of first appointment

Collaborators and Investigators

• Sponsor: University of Manchester
• Collaborators: University of Nottingham; Queen Mary University of London; Manchester University NHS Foundation Trust; National Institute for Health Research, United Kingdom; The Christie NHS Foundation Trust; East Lancashire Hospitals NHS Trust; Breast Cancer Now; Prevent Breast Cancer; East Cheshire NHS Trust; NHS Breast Screening Programme
• Investigators: Principal Investigator: Gareth Evans, MD, Manchester University NHS Foundation Trust

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): December 28, 2021
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; early detection; anxiety; Screening; high risk; chemoprevention; risk stratification; psychological impact; Tyrer-Cuzick; mammographic density
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: RP-PG-1214-20016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data will be shared in anonymised format with bone fide researchers, once main outcomes from the study have been published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No