Condition category
Cancer
Date applied
13/05/2019
Date assigned
07/11/2019
Last edited
07/11/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
3D mammography improves the detection of small breast cancers and may decrease the number of women without cancer who are recalled for further tests.
The study compares both the cost and effectiveness of 3D mammography with standard mammography in breast cancer screening. The results of the study will be used to decide whether to use 3D mammography routinely in the National Screening Programme.

The accuracy of two view digital x-ray mammography (2DDM) in breast cancer screening is limited because of superimposition of normal breast structures onto a two dimensional image. Mammography signs of breast cancer may be obscured, particularly in women with dense glandular breast tissue, resulting in delay in diagnosis of cancer. Interval cancer data shows that up to 4000 women per annum (2.88 per 1000 screened) are diagnosed with breast cancer in the interval between screens. Conversely, superimposition of normal tissues may produce features on mammography which are suspicious for cancer and lead to unnecessary recall for further diagnostic tests.

Digital Breast Tomosynthesis (DBT) is an x-ray mammography technique which involves acquiring multiple low dose projection images over a limited angular range (less than 50 degrees). These projection images are reconstructed into a set of images consisting of parallel planes, typically 1mm apart throughout the breast, and provide three dimensional information to the film reader. A synthetic 2D mammogram (S 2D) has been developed using the data from the reconstructed DBT images.

Studies of DBT + 2DDM in screening have shown increased invasive cancer detection rates and lower false positive recall rates. There may be increased costs related to the technology and reading times.

The aim of this trial is to measure the impact and cost-effectiveness of DBT + 2DDM or S 2D in routine screening compared to standard 2DDM.

Who can participate?
Women aged 50-70 years attending for routine breast cancer screening

What does the study involve?
Trial participants who have provided informed consent will be offered either their standard mammography (2D mammography) or their standard mammography and 3D mammography when they come for their routine breast screening appointment

What are the possible benefits and risks of participating?
Having mammograms every 3 years for 20 years very slightly increases the risk of getting cancer over a woman’s lifetime, but the benefits of screening and early detection are considered to far outweigh the risks of having the x-ray. If you take part in the trial and have 3D mammography you will receive an additional dose of radiation roughly equivalent to having an extra mammogram. The radiation dose from a mammogram is approximately the same as three months of natural background radiation that we are all exposed to in everyday life

Where is the study run from?
King's College Hospital NHS Foundation Trust, UK

When is the study starting and how long is it expected to run for?
From May 2019 for seven years

Who is funding the study?
Hologic Inc., USA

Who is the main contact?
1. Dr Mike Michell
Michael.michell@nhs.net
2. Ms Mahrufa Choudhury
mahrufa.choudhury@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Dr Michael J Michell

ORCID ID

Contact details

King's College Hospital NHS Foundation Trust
Breast Radiology
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
+44 (0)2032993875
Michael.michell@nhs.net

Type

Scientific

Additional contact

Mr Mahrufa Choudhury

ORCID ID

Contact details

King's College Hospital NHS Foundation Trust
Breast Radiology
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
+44 (0)20 3299 6413 Ext 36413
mahrufa.choudhury@nhs.net

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

NCT03733106

Protocol/serial number

33373

Study information

Scientific title

Prospective randomised trial of digital breast tomosynthesis (DBT) plus standard 2D digital mammography (2DDM) or synthetic 2D mammography (S 2D) compared to standard 2D digital mammography in breast cancer screening

Acronym

PROSPECTS

Study hypothesis

The aim of this trial is to measure the impact and cost-effectiveness of Digital Breast Tomosynthesis (DBT) + two view digital x-ray mammography (2DDM) or synthetic 2D mammogram (S 2D) in routine screening compared to standard 2DDM.

Ethics approval

Approved 09/02/2017, London - Dulwich Research Ethics Committee (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH; +44(0) 20 7972 2561; NRESCommittee.London-Dulwich@nhs.net), ref: 17/LO/0054

Study design

Randomized; Interventional; Design type: Screening, Diagnosis, Imaging

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Breast cancer

Intervention

DBT is a new X-ray mammography technology which overcomes some of the principle disadvantages of 2DDM which are due to tissue superimposition. Studies of screening using DBT in addition to 2DDM in Europe and North America have shown an increase in invasive cancer detection and a decrease in false positive recall rate. This study is designed to measure the impact of DBT on the effectiveness of mammography screening and the cost to the NHS. The proposed trial design is prospective RCT. Potential participants are women aged 50-70 years who are invited for routine screening mammography. The control group will undergo standard 2DDM; the intervention group will undergo DBT + 2DDM. For the intervention group, S 2D images will be generated from the DBT reconstructed images. A total of
100,000 participants are required (50,000 in the control group, 50,000 in the intervention group) in order to demonstrate a significant effect of DBT on interval cancer rates between the two study groups. All cases will be double read. In the intervention group, one read will be DBT+2DDM, one read will be DBT+S 2D.

Recruitment and consent
Clinics available for trial recruitment will be identified by the local screening service and will be randomised to control or intervention by a central online randomisation process. Women invited to the trial clinics will be sent the Participant Information Sheet with the invitation for screening. On arrival for screening, potential trial participants will be asked if they have received the Participant Information Sheet, if they have any questions about the trial, and whether they wish to participate. If the woman wishes to participate, she will be asked to sign a trial consent form.
Women who consent to participate will undergo 2DDM (control group) or 2DDM+DBT (intervention group)according to the clinic randomisation process.
Women who decline to participate will be offered standard 2DDM screening.

Mammography reading
The mammograms will be double read. For women in the intervention group, one read will be DBT+2DDM, one read will be DBT+S 2D

Data recording
The results of film reading will be recorded for each film reader on the National Breast Screening Computer System(NBSS) in the normal way. For women who undergo treatment, details of pathology and treatment will be recorded on NBSS. A trial database will be kept and managed with all image data, reader data and outcome data for all participants.

Results and reporting
Cancer detection rates, the pathological characteristics of screen-detected and interval cancers, interval cancer rates, false-positive rates will be collected.
After 18 months, preliminary results of cancer detection and false-positive recall rates will be available. The size and lymph node status of the Grade 2 and Grade 3 invasive cancers in the control and intervention groups will be used to estimate the effect of DBT on breast cancer mortality compared to standard 2D screening. Later, when interval cancer data becomes available, a more robust estimate of the effect of DBT will be made

Economic evaluation of DBT
We will undertake a detailed study of the cost of screening with 2DDM and with DBT and either S2D or 2DDM. Capital and maintenance costs related to screening technologies will be obtained from the manufacturers or finance departments at the screening centres and amortized appropriately according to predicted lifetime. Staff costs and overheads for screening centres and image reading centres will be derived from centre finance departments. The time taken to record images with each screening modality, and the time to read images will be determined and combined with centre costs to estimate a total cost per mammographic screen for each of the screening centres in the trial.
Costs associated with the follow-up of a positive screen will be determined in consultation with screening centres. Patient costs will be estimated on the basis of typical attendance times valued at average gross wage rate along with estimates of average travel costs. We will undertake a cost-utility analysis of DBT + S2D (or 2DDM) compared to current practice (2DDM). The primary analysis will consider an NHS perspective and include future related costs of screening (diagnosis and treatment of Breast cancer). A societal perspective which includes patient costs of attending screening and follow-up will be examined in a sensitivity analysis. The primary analysis will consider the costs and consequences of Breast screening with either modality over the trial follow-up period. We will estimate the impact on health and treatment costs of cancers detected by predicting treatment costs and mortality according to age and prognostic factors at diagnosis. Mortality will be weighted for quality of life to estimate the Quality Adjusted Life-Years (QALYs) lost to Breast cancer in each arm. A QALY is a measure of health outcomes which combines longevity and quality of life. If overall costs er in the DBT arm the data will be combined to estimate an Incremental Cost-Effectiveness Ratio (ICER) for DBT and allow comparison against accepted thresholds of £20,000 to £30,000 per QALY. The trial data will be
bootstrapped (a resampling technique to quantify the impact of uncertainty in the data) and the results presented as a Cost-Effectiveness Acceptability Curve (CEAC). The CEAC plots the probability an intervention is cost-effective according to the value placed on the health outcome and after allowing for sampling uncertainty.
In addition to this analysis, we will build a simulation model of Breast cancer. The model will utilize data on costs, sensitivity and specificity of each screening modality taken from the trial data along with data from the literature on the natural progression of Breast cancer to estimates costs associated with screening and treatment of Breast cancer and quality-adjusted life-expectancy over women's lifetimes. The model will fully incorporate uncertainty around parameter estimates and the main outputs will be the mean ICER across simulations and the CEAC

Intervention type

Other

Phase

Drug names

Primary outcome measure

Cost-effectiveness of breast cancer screening with each method by measuring cancer detection rates, interval cancer rates, size and lymph node status of Grade 2 and 3 invasive cancers at ...

Secondary outcome measures

Measured from two to seven years following recruitment start:
1. Impact of screening on screening recall rates, benign biopsy rates at diagnostic assessment and at surgery measured using patient records
2. Effect of screening on patient groups according to breast density, type of screen, age, measured using patient records
3. Develop methods for measuring reader performance with DBT + 2DDM or S2D screening
4. Retrospective reader studies to measure the effect of other screening strategies
5. Patient preferences for breast cancer screening with the two methods measured using a questionnaire at recruitment

Overall trial start date

13/02/2017

Overall trial end date

01/04/2025

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Women aged 50-70 years attending for routine breast screening using x-ray mammography
2. Able to provide informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 100000; UK Sample Size: 100000

Participant exclusion criteria

Does not meet inclusion criteria

Recruitment start date

28/05/2019

Recruitment end date

28/05/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

King's College Hospital NHS Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Surrey And Sussex Healthcare NHS Trust
East Surrey Hospital Canada Avenue
Redhill
RH1 5RH
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
St. James's University Hospital Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

North Bristol NHS Trust
Frenchay Hospital
Bristol
BS16 1JE
United Kingdom

Trial participating centre

Barts and the London NHS Trust
The Royal London Hospital Whitechapel Rd Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Royal Free London NHS FoundationTrust
Royal Free Hospital Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

Breast Test Wales
South East Wales Breast screening Centre 18 Cathedral Road
Cardiff
CF11 9LJ
United Kingdom

Trial participating centre

Sandwell and West Birmingham Hospitals NHS Trust
City Hospital Dudley Road
Birmingham
B18 7QH
United Kingdom

Sponsor information

Organisation

King's College London

Sponsor details

161 Denmark Hill
London
SE5 8EF
United Kingdom
+44 (0)2032993841
kch-tr.research@nhs.net

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Hologic, Inc.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository. Trial participant data will be stored on the national screening computer system (NBSS). Access to data on NBSS is password protected and is in accordance with the regulations and operating procedures within each of the trial sites. Access to trial participant data at the trial sites is limited to those involved in the direct clinical care of trial participants and the local trial data manager. The managers of the Central Trial Database at RSCH will need limited access in order to set up the anonymization process

Intention to publish date

31/12/2027

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

13/05/2019: Trial's existence confirmed by the NIHR.