Is the use of digital pathology in routine diagnosis reliable and safe in comparison to standard microscopy?

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)

Current secondary outcome measures as of 17/03/2022:
1. Inter-pathologist level of agreement across the four DP diagnoses and the ground truth (GT).
2. Inter-pathologist level of agreement across the four LM diagnoses and 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. Focus groups / key informant interviews will be undertaken during the pilot study.
5.2. Semi-structured interviews at baseline will explore staff experiences and perspectives on DP.
5.3. Semi-structured interviews at mid-point of study will explore staff experiences over time, training needs and the perceived impact on day-to-day working in multidisciplinary teams.


Previous 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.