Condition category
Not Applicable
Date applied
30/10/2018
Date assigned
05/12/2018
Last edited
05/12/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Pathologists (doctors who diagnose disease by studying tissue samples) use a microscope to examine tissue samples collected from patients. This is called light microscopy. It enables them to make a diagnosis and to give information on treatment and prognosis to clinicians (doctors). Digital pathology is a process to scan microscope slides into computer image files (digitised slides) which the pathologist can then examine on a computer screen. Digitised slides can be transferred electronically to allow pathologists to view cases at any location. This makes cases easy to share with colleagues, confirm diagnoses for patients, reduce errors and create better practices for sharing workload between departments. This will save time and resources for the NHS. Computer assisted tools can also be used to help make the diagnosis. None of these benefits can be realised until it is known how pathologists can use digital pathology safely and accurately for routine reporting.

Who can participate?
This study will not directly involve patients; instead, it will use samples from the breast, gastrointestinal tract, skin and kidney that have already been used in diagnosis

What does the study involve?
The present study attempts to explore if the use of whole slide imaging (Digital Pathology) is a safe, reliable and cost effective health technology for diagnosis, in routine clinical practice in comparison to standard microscopy.

What are the possible benefits and risks of participating?
There are no known benefits or risks.

Where is the study run from?
University Hospital Coventry and Warwickshire NHS Trust and 4 other hospitals in the UK

When is the study starting and how long is it expected to run for?
November 2018 to October 2021

Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment programme (HTA) (UK)

Who is the main contact?
Prof. D Snead
Consultant Pathologist
UHCW NHS Trust
Coventry CV2 2DX
02476965429

Trial website

Contact information

Type

Scientific

Primary contact

Prof David Snead

ORCID ID

http://orcid.org/0000-0002-0766-9650

Contact details

Cellular Pathology Department
4th Floor
West Wing
Clifford Bridge Road
Walsgrave
Coventry
CV22DX
United Kingdom
024 76 968320
david.snead@uhcw.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

DS411118

Study information

Scientific title

Multi-centred validation of digital whole slide imaging for routine diagnosis

Acronym

Study hypothesis

Light microscopy diagnosis is safe and reliable in comparison to the use of whole slide imaging (Digital Pathology) in routine practice

Ethics approval

We are at present confirming the requirement for an ethical review.

Study design

Multi-centre randomised comparison study

Primary study design

Other

Secondary study design

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

No participant information sheet available

Condition

Histopathological diagnosis

Intervention

The study involves exploring concordance between the results of histopathological sample analysis performed by pathologists examining the same series of samples using both light microscopy (LM) and digital microscopy (DP). The tissue samples selected for the study will have completed their appropriate clinical assessment at the respective site thus we do not plan any follow up or observation.

Each site will select appropriate samples and these link anonymised samples (glass slides) will be forwarded to University Hospital Coventry and Warwickshire (UHCW). Once received, the samples will be scanned at UHCW and digital slides of the samples will be created additionally, these slides, both glass and digital, will be given study numbers for anonymisation. These samples will then be randomised in batches, for viewing either LM first or DP. On completion of analysis of a particular sample, by all four pathologists, the samples will be returned to their original site.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Intra-pathologist agreement between digital pathology and light microscopy diagnoses, measured by comparing the concordance between the results of pathologists’ diagnoses made by assessment of LM of breast, GI, skin and renal samples, with the same pathologists’ diagnoses of the same samples (intra-rater (pathologists) reliability) using DP.
There will be three categories for the level of agreement; complete agreement, clinically unimportant difference and clinically important difference. For each sample, three sets of agreements will be reported:
1. Whether for each pathologist’s DP and LM diagnoses agree
2. Whether each of the four DP diagnoses agree with the ground truth (GT)
3. Whether each of the four LM diagnoses agree with the GT.
This will be completed after all results have been completed and analysed (20-30 months)

Secondary outcome measures

1. Pathologist agreement to GT and LM vs GT and DP will be measured using using text reports.
1.1. For each pathologist it will be recorded if DP and LM have complete agreement, have clinically unimportant differences or clinically important differences.
1.2. Discordant samples will be circulated to each of the subspecialty pathologists, along with the reference diagnosis. Each subspecialty group will then meet and agree a consensus GT for each discrepant sample using multi-headed microscope discussion and majority view where necessary. The agreement between GT and LM vs GT and DP will then be determined.
2. Inter-pathologist agreement for LM and DP separately will be measured using text reports. Reports without any differences will be deemed concordant, with the concordant diagnosis being accepted as the GT.
3. Individual pathologist non-concordance rates will be measured throughout the study.
4. Costs and benefits associated with DP when compared with LM will be measured for all samples, if feasible, once all samples have been analysed. If not, analysis will be carried out for a purposive sample selected on the basis of clinical materiality and the availability of decision-analytic models in the literature to support cost-benefit calculations.
4.1. The throughput efficiencies of DP vs LM will be measured using simulation models of the pathway to diagnosis and establishment of a fully specified treatment plan.
4.1.1. Pathologists will be asked to provide time and motion data and anonymised summary data from the pathology service will be collected.
4.2. The effect of increased accuracy on choice of treatment will be made using estimates of the cost and health impact of the treatment strategies suggested as a result of DM or LM use.
5. Experiences of pathologists and laboratory staff
5.1. A web-based survey will be conducted along with the pilot study.
5.2. Semi-structured interviews at baseline will explore staff experiences and perspectives on DP.
5.3. Semi-structured interviews 18 months into the implementation of DP will explore staff experiences over time, training needs and the perceived impact on day-to-day working in multidisciplinary teams.

Overall trial start date

01/11/2018

Overall trial end date

31/10/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Histopathology samples:
Case identification and selection will take place between January 2019 – January 2022 at five participating NHS histopathology departments. All samples are collected for the purpose of routine histopathology reporting and only entered into the validation study on completion of their clinical review at the respective NHS participating site, with the following specification:
1. Breast (Belfast, Lincoln & Nottingham) – A total of 600 sequential samples including 200 cancer screening biopsies enriched with at least 10% resected tumours (moderately difficult) and 10% difficult cases: low grade ductal carcinoma in situ, atypical hyperplasia, screening category B3 and B4, lesions with calcium oxalate (Weddellite calcification), sclerosing and papillary lesions, and micrometastases.
2. GI (Coventry, Belfast & Nottingham): – A total of 600 sequential samples including 200 cancer screening biopsies enriched with at least 10% resected tumours (moderately difficult) and 10% difficult: oesophageal dysplasia, polyp cancers, inflammatory bowel disease, minimal change colitis, graft versus host disease, giardiasis, cytomegalovirus, H. pylori and herpes virus infection.
3. Skin (Coventry, Belfast & Lincoln) : A total of 600 sequential samples enriched with at least 10% non-basal cell carcinoma cancer resections (moderately difficult) and 10% difficult: sentinel nodes, dysplastic naevi, spitz naevi, lentigo maligna, early and desmoplastic melanoma, herpes virus infection, leischmaniasis, leprosy, amyloid, angioscaroma, and Kaposis sarcoma.
4. Renal (Coventry, Nottingham & Oxford): A total of 200 sequential native biopsies for glomerular, tubulointerstitial and vascular disease and transplant biopsies for graft rejection. No enrichment is planned in the renal biopsy group as all of these biopsies are difficult to report.

Staff (for the qualitative part of the study):
Staff employed at the participating sites, including any of the following:
1. Pathologists
2. Trainee doctors
3. Biomedical scientists
4. Biomedical assistants
5. Advanced practitioners
6. Medical laboratory assistants

Participant type

Other

Age group

Other

Gender

Both

Target number of participants

2000 samples

Participant exclusion criteria

Cases with either broken or missing slides

Recruitment start date

01/02/2019

Recruitment end date

30/06/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospital Coventry and Warwickshire NHS trust
Clifford Bridge Road
Coventry
CV22DX
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Hucknall Road, Nottingham
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

United Lincolnshire Hospitals NHS Trust
Greetwell Rd
Lincoln
LN2 5QY
United Kingdom

Trial participating centre

John Radcliffe Hospital Oxford NHS Trust
Headley Way, Headington,
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Belfast Health and Social Care Trust
Faculty of Medicine, Health & Life Sciences, Elmwood Exchange, 90 Lisburn Road,
Belfast
BT9 6AG
United Kingdom

Sponsor information

Organisation

University Hospital Coventry and Warwickshire (UHCW) NHS Trust

Sponsor details

Clifford Bridge Road
Walsgrave
Coventry
CV22DX
United Kingdom
02476966197
R&DSponsorship@uhcw.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

NIHR-HTA

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We plan the following papers for peer review, open access publication, following presentation at national and international conferences:
1. Multi-centre study measuring the precision and accuracy of digital whole slide imaging in the reporting of histopathology samples
2. Is digital pathology an alternative to conventional light microscopy for reporting of renal biopsies? – Implications for the future of renal pathology in the NHS
3. Experiences of using digital whole slide imaging for routine histopathology reporting in the NHS – a multi-centre study
4. The cost of implementing digital pathology solutions in the NHS and the expected return on investment
5. The cost of diagnostic inaccuracies in histopathology and can these be mitigated by adopting digital pathology?
6. How pathologists examine digital whole slide images – can improved examination technique reduce error?
7. Reporting the findings of the eye tracking data from the DP arm in relation to diagnostic accuracy across the study

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/10/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes