5 Outcomes

The Diagnostics Advisory Committee (section 11) considered evidence from a number of sources (section 12).

How outcomes were assessed

5.1 The External Assessment Group conducted a systematic review of the evidence on the clinical effectiveness of using the VivaScope 1500 and 3000 imaging systems with dermoscopy and clinical judgement to:

  • help decide whether to biopsy and excise skin lesions in people with suspected skin cancer

  • define the margins of skin lesions for excision in people with skin cancer.

5.2 Evidence on earlier versions of the VivaScope 1500 and 3000 imaging systems, the 1000 and 2500 systems, was also considered because it may provide additional information on the current versions.

Clinical effectiveness

5.3 The External Assessment Group identified 16 studies that met the inclusion criteria for the review. Of the 16 included studies, 13 reported the use of VivaScope or reflectance confocal microscopy (RCM) in diagnosing suspected or equivocal lesions, and 3 reported its use in lesion margin delineation.

5.4 Of the 13 studies reporting lesion diagnosis, 7 used VivaScope 1500 or 3000 imaging systems. Of these 7 studies, 6 used VivaScope 1500 and 1 used VivaScope 1500 and 3000. Four of the studies that used VivaScope 1500 did not include dermoscopy as a comparator. The remaining 6 of the 13 studies used earlier versions of the VivaScope imaging system. Of these, 3 used VivaScope 1000 (2 of which did not include dermoscopy as a comparator), 2 used VivaScope 1000 and 1500 (1 did not include dermoscopy as a comparator), and 1 used VivaScope 2500.

5.5 In 10 of the 13 studies reporting lesion diagnosis, consecutive patients were prospectively enrolled from settings including melanoma or dermatology clinics in tertiary or university hospitals, and 1 study retrospectively selected previously imaged lesions or excised lesions.

5.6 Two of the 3 studies reporting lesion margin delineation used VivaScope 1500 with or without dermoscopy as a comparator and the remaining study used VivaScope 2500.

5.7 Of the 3 studies on lesion margin delineation, 1 retrospectively assessed and interpreted lesion images in patients previously enrolled in 2 university‑based clinics or hospitals and 2 prospectively and randomly recruited patients with lesions from a dermatology department or Mohs surgery unit.

5.8 None of the included studies was conducted in the UK. Most of the 16 included studies were from countries whose skin cancer rates and treatment pathways may be different from the UK settings (8 studies from Australia and Italy, 2 from Brazil and the USA, 2 each from Spain and Australia, and 1 each from China and Canada). Two studies, Alarcon et al. (2014) and Pellacani et al. (2014), which used VivaScope in diagnosis, were conducted in Spain and Italy respectively. Guitera et al. (2013), which used VivaScope in margin delineation, was conducted in Australia and Italy. Expert opinion considered these 3 studies to be the most representative of clinical practice in the UK.

5.9 Most of the included studies had low risk of bias and low applicability concerns regarding patient selection (11 studies), conduct of the index test (13 studies) and reference standard (13 studies). However, the risk of bias for flow and timing was unclear in most of the studies (13 studies) because of poor reporting and insufficient data. Included studies were considered too heterogeneous to have their results combined by meta‑analysis. This was because of study design, patient population, or insufficient reporting of results. Of the outcomes defined in the scope, only diagnostic accuracy and lesion recurrence rate were reported in the included studies.

Diagnostic accuracy in lesion diagnosis

5.10 Diagnostic accuracy was the most commonly reported outcome in studies, reported as sensitivity, specificity, positive predictive value and negative predictive value. Other diagnostic accuracy data such as false positive, false negative and true negative were rarely reported so had to be estimated and calculated using other reported diagnostic data when possible.

Dermoscopy plus VivaScope 1500 compared with dermoscopy

5.11 Three studies compared dermoscopy plus VivaScope 1500 with dermoscopy.

5.12 Alarcon et al. (2014) assessed the impact of RCM analysis on dermoscopically equivocal pigmented lesions. Of the 343 lesions examined using RCM, only 264 were excised and analysed using histopathology (79 lesions were followed up for 1 year without any melanoma diagnosed). The 92 melanomas diagnosed using dermoscopy also had independent VivaScope 1500 examination. Histopathology showed that there were 6 false negatives using dermoscopy alone, and 2 false negatives with dermoscopy plus VivaScope 1500. When dermoscopy plus VivaScope 1500 and dermoscopy alone were compared using the histopathology findings for the 264 excised lesions, there were statistically significant differences in sensitivity in the diagnosis of melanoma (97.8% versus 94.6%; p=0.043 respectively) and specificity in non‑melanoma (92.4% versus 26.7%; p<0.000001 respectively). Using a 2×2 contingency table to compare RCM with dermoscopy and assuming the 79 lesions followed up were true negatives, the sensitivity was 97.8% and 93.5% respectively and the specificity was 94.8% and 49.0% respectively. Therefore, although the sensitivities of RCM and dermoscopy were similar when the 79 lesions were included in the analysis, the specificity for dermoscopy was higher (26.7% versus 49.0%) compared with analysis based on 264 excised lesions.

5.13 Pellacani et al. (2014) prospectively assessed the potential impact of RCM when implemented in a routine melanoma workflow. At dermoscopy, patients were referred to 1 of the following pathways:

  • no further examination

  • referral to RCM:

    • RCM documentation (lesions with consistent suspicious clinical or dermoscopic criteria, already qualified and scheduled for surgical excision)

    • RCM consultation for equivocal lesions, followed by either excision or digital follow‑up.

5.14 In the Pellacani et al. (2014) study, 493 lesions were referred for RCM examination, but 2 patients refused RCM imaging so lesions were excised, and histopathology reported 1 basal cell carcinoma (BCC) and 1 benign lesion. Of the remaining 491 lesions, 183 had RCM documentation and 308 RCM consultations. In the RCM documentation group, histopathology confirmed 110 positives using RCM (23 melanomas, 19 BCCs and 68 benign lesions) and 73 negatives using RCM (73 benign lesions). In all melanomas and BCCs identified at histology, RCM had recommended excision. In the RCM consultation group, RCM identified 81 positives and 227 negatives. Of the 81 RCM positives, excision confirmed 6 melanomas, 19 BCCs and 56 benign lesions. Of the 227 RCM negatives followed up for 3–12 months, 28 showed significant changes but excision confirmed no malignancy, 178 showed no changes and 21 were lost to follow‑up but checks at the local tumour registry identified no excision. Assuming that all of the 21 RCM negatives lost to follow‑up in the RCM consultation group were true negatives, for RCM documentation and RCM consultation the sensitivity was 100% and 100% respectively; the specificity was 51.77% and 78.6% respectively. However, when the 21 RCM negatives lost to follow‑up were excluded, the sensitivity was 100% and specificity was 80.2% for RCM consultation.

5.15 Ferrari et al. (2014) evaluated the most relevant RCM features for melanomas that were difficult to detect by dermoscopy: score 0–2 (featureless lesions), score 3–4 (positive borderline lesions), and score 5–10 (positive 'clear cut' lesions). In the population with a score of 0–2, the presence of at least 1 of the 2 independent parameters accounted for the detection of all 6 melanomas (100% sensitivity; 82.3% specificity). Similarly, in the population with a dermoscopic score of 3–4, the presence of at least 1 of the 2 independent parameters accounted for the detection of 16 of 17 melanomas (94.1% sensitivity; 62.4% specificity).

Dermoscopy plus VivaScope 1500

5.16 There were 4 studies that reported the diagnostic accuracy of VivaScope 1500 after dermoscopy without a comparator.

5.17 Curchin et al. (2011) reported sensitivity and specificity data on 50 equivocal lesions in 42 patients. With VivaScope 1500 after dermoscopy, 12 of 13 melanomas (92.3% sensitivity; 75% specificity), 19 of 22 benign naevi (86% sensitivity; 95% specificity), 6 of 9 BCCs (66.7% sensitivity; 100% specificity) and all 6 squamous cell carcinomas (SCCs) and its precursors (100% sensitivity; 75% specificity) were correctly diagnosed.

5.18 Guitera et al. (2010) assessed which RCM features could distinguish lentigo maligna (LM) from benign macules of the face such as solar lentigo, actinic keratosis and seborrheic keratosis, and tested different algorithms for diagnosing LM. A LM score of 2 or more resulted in a sensitivity of 85% and specificity of 76% for the diagnosis of LM (odds ratio [OR] for LM 18.6; 95% confidence interval [CI] 9.3 to 37.1).

5.19 Rao et al. (2013) assessed the accuracy of VivaScope 1500 compared with histopathology in the diagnosis of 284 cutaneous lesions by 2 readers with different degrees of experience. Malignant lesions diagnosed with VivaScope 1500 by reader 1 represented 66.7%, 74.1% and 37.2% of histologically diagnosed melanoma, BCC and SCC respectively. For reader 2, lesions diagnosed as malignant represented 88.9%, 51.9% and 72.1% of histologically diagnosed melanoma, BCC and SCC respectively. Of the 284 lesions evaluated by both readers, 212 were benign and 72 were malignant based on histopathology.

5.20 Stanganelli et al. (2014) assessed whether combining sequential dermoscopy imaging with VivaScope 1500 could improve melanoma detection and reduce unnecessary excisions. Of 70 lesions, 30 (43%) were classified as melanoma by dermoscopy plus VivaScope 1500. Of these, 11 of 12 were histologically confirmed (11 true positives and 1 false negative), and 19 were false positives.

Dermoscopy plus VivaScope 1000 compared with dermoscopy

5.21 Langley et al. (2007) evaluated the diagnostic accuracy of VivaScope 1000 compared with dermoscopy in patients with benign and malignant melanocytic lesions. The sensitivity of VivaScope 1000 after dermoscopy compared with dermoscopy alone was 97.3% and 89.2% respectively, and the specificity was 83.0% and 84.1% respectively. Using a 2×2 contingency table to estimate histologically proven positive and negative diagnostic tests, the numbers of patients or lesions correctly and incorrectly diagnosed were similar using VivaScope 1000 after dermoscopy compared with dermoscopy alone.

VivaScope 1000

5.22 Two publications from the same trial reported the diagnostic accuracy of VivaScope 1000 without a comparator.

5.23 In the trial by Gerger et al. (2006), 117 melanocytic skin lesions and 45 non‑melanocytic skin lesions were consecutively sampled and examined by 4 independent observers using VivaScope 1000. The overall (total of the 4 observers) diagnostic differentiation of benign from malignant lesions (melanoma and BCC) reached a sensitivity of 94.65%, specificity of 96.67%, positive predictive value of 97.50%, and negative predictive value of 92.99% based on histopathology. In a supplementary publication to Gerger et al. (2006), Gerger et al. (2008) retrospectively evaluated 3709 selected images of 70 lesions (20 malignant melanomas and 50 benign naevi) using VivaScope 1000. The overall performance of the 4 observers who reviewed the images showed a sensitivity of 97.5%, specificity of 99.0%, positive predictive value of 97.5%, and a negative predictive value of 99.0%.

VivaScope 1000 or 1500 compared with dermoscopy

5.24 In a trial by Guitera et al. (2009), the possible additive value of VivaScope 1000 and 1500 in managing melanocytic lesions was evaluated at 2 centres. For the diagnosis of melanoma, there was no significant difference in sensitivities between VivaScope 1000 or 1500 (91%; 95% CI 84.6 to 95.5) and dermoscopy (88%; 95% CI 80.7 to 92.6) but specificities differed significantly: VivaScope 1000 or 1500 had a specificity of 68% (95% CI 61.1 to 74.3) and dermoscopy 32% (95% CI 25.9 to 38.7).

VivaScope 1000 or 1500

5.25 Pellacani et al. (2007) evaluated the sensitivity and specificity of confocal features for the diagnosis of melanoma and benign naevi using RCM score thresholds compared with models obtained from statistical analysis. The VivaScope 1000 or 1500 demonstrated optimal sensitivity for a score of 2 or more (96.3%), with 52.1% specificity.

Dermoscopy plus VivaScope 1500 compared with dermoscopy plus VivaScope 3000

5.26 Castro et al. (2014) compared the accuracy of VivaScope 3000 with VivaScope 1500 in the identification of BCC. Among 54 lesions imaged with both RCM devices, 45 were biopsy‑proven BCCs. Comparison between VivaScope 1500 after dermoscopy and VivaScope 3000 after dermoscopy showed: sensitivity (100% versus 93%), specificity (78% for both RCMs), positive predictive value (96% versus 95%), and negative predictive value (100% versus 70%) respectively.

Misdiagnosis of lesions

VivaScope 1000 or 1500 compared with dermoscopy

5.27 In the trial by Guitera et al. (2009), 15 melanomas (12%) were misclassified by dermoscopy, 11 melanomas (9%) were misclassified by the VivaScope 1000 or 1500, and only 3 (2.4%) by both techniques.

Dermoscopy plus VivaScope 1000 compared with dermoscopy

5.28 In the trial by Langley et al. (2007), there were 5 out of 37 melanomas for which VivaScope 1000 after dermoscopy and dermoscopy alone produced different diagnoses. VivaScope 1000 after dermoscopy correctly classified 4 out of 5 melanomas, whereas dermoscopy alone correctly classified 1 out of 5 melanomas. Additionally, there were 7 benign naevi for which both diagnoses were incorrect. Of the melanomas, 2 were misdiagnosed by the investigator using dermoscopy alone, but correctly diagnosed by dermoscopy plus VivaScope 1000 as amelanotic or hypomelanotic melanomas.

Dermoscopy plus VivaScope 1500

5.29 In the trial conducted by Pellacani et al. (2014), overall the VivaScope 1500 proposed diagnosis was concordant with histopathological diagnosis in 216 of 283 (76.3%) evaluated cases. BCC was the most accurate diagnosis (37 of 38; 97.4%), then melanoma (24 of 28; 85.7%). Spitz nevus was the most frequently misclassified diagnosis (accurate diagnosis: 4 of 13; 30.8%); 6 were misclassified as Clark's naevi and 3 as melanoma.

Diagnostic accuracy in margin delineation

Dermoscopy plus VivaScope 1500 compared with dermoscopy

5.30 Guitera et al. (2013) analysed patients with LM and lentigo maligna melanoma to determine whether VivaScope 1500 mapping might alter patient care and lesion management. Out of 60 positive sites for LM confirmed by histopathology, 55 (5 false negatives) had been confirmed by VivaScope 1500 and 21 (39 false negatives) by dermoscopy. Of 125 LM sites confirmed as negative by histopathology, 121 (4 false positives) had been confirmed by VivaScope 1500 and 122 (3 false positives) by dermoscopy. Histopathology also showed 17 of 29 patients with visible lesions had evidence of subclinical disease more than 5 mm beyond the edge of the dermoscopically identified margin. In addition, both the length and width of the dermoscopically visible area of the lesion were on average 60% smaller than the final corresponding dimensions determined by VivaScope 1500. Therefore, the visible area was on average less than 40% of the area that was treated based on VivaScope 1500 mapping findings.

VivaScope 1500

5.31 Pan et al. (2012) investigated the feasibility of VivaScope 1500 in defining the margins of lesions clinically suggestive of BCC before surgery. The margins of 10 lesions were evaluated using VivaScope 1500, and biopsies of the margins were used to confirm the results. In 7 of 10 (70%) cases, the margins of the cancer were identified using VivaScope 1500 and confirmed by histopathological analysis. In 3 of 10 (30%) cases, the margins of the lesions could not be detected because of the unevenness of the surface.

VivaScope 2500

5.32 Bennassar et al. (2014) evaluated the sensitivity and specificity of ex vivo imaging with fluorescence confocal microscopy for detecting residual BCC in Mohs tissue excisions, and calculated the time invested up to the diagnosis for both fluorescence confocal microscopy and frozen sections. The overall sensitivity and specificity of detecting residual BCC in surgical margins was 88% and 99% respectively. The number of images or mosaic correctly diagnosed as true positive was 79 (89%) and true negative was 390 (99.7%). There was only 1 (0.3%) false positive. In addition, on average VivaScope 2500 reduced the evaluation time by 18 minutes (p<0.001) when compared with the processing of a frozen section.

Lesion recurrence in margin delineation

5.33 The trial conducted by Guitera et al. (2013) reported that of 17 patients with LM that was surgically excised, 2 (12%) had re‑excisions (margins were confirmed by histopathology). Regarding future recurrence, the study reported that no recurrence of LMs treated surgically was observed in any patient by last follow‑up (median follow‑up 37 months; range 7–66 months). However, this observation was based on a small number of LMs excised.

Change in management in margin delineation

5.34 In the trial conducted by Guitera et al. (2013), VivaScope 1500 mapping changed the management of lesions in 27 patients (73%): 11 patients had a major change in their surgical procedure, and 16 were offered radiotherapy or imiquimod treatment. Treatment was surgical in 17 of 37 patients.

Cost effectiveness

Systematic review of cost‑effectiveness evidence

5.35 The External Assessment Group conducted a search to identify economic studies investigating the cost effectiveness of VivaScope 1500 and 3000 in the diagnosis of skin lesions suspected as skin cancer and in the margin delineation of malignant skin lesions, including LM, before surgical treatment. No studies were considered eligible for inclusion in the systematic review.

5.36 During the development of this report, the company made available to the External Assessment Group an unpublished study of the cost effectiveness of RCM in the diagnosis of skin lesions suspected as skin cancer. The study had a retrospective design, and therefore did not meet the inclusion criteria for economic evaluations. However, because there was a lack of relevant economic evidence on the cost effectiveness of VivaScope, this study was accepted in the systematic literature review. This study is academic in confidence at the time of writing this draft guidance.

Economic analysis

5.37 The External Assessment Group developed a de novo economic model designed to assess the cost effectiveness of VivaScope 1500 and 3000 in the diagnosis of skin lesions suspected as skin cancer and in the margin delineation of malignant skin lesions, including LM, before surgical treatment.

5.38 According to the study populations that were identified as relevant for the economic evaluation of VivaScope, 3 separate 'part' economic models were developed:

  • Use of VivaScope in the diagnosis of equivocal lesions suspected as melanoma. This model assessed the cost effectiveness of VivaScope 1500 and 3000 as 1 integrated system, assuming that both devices would be available for the diagnosis of equivocal lesions but that each would be used as appropriate according to the location of the equivocal lesion to be examined.

  • Use of VivaScope in the diagnosis of suspected BCC lesions after a positive or equivocal finding in dermoscopy. As with the previous model, this model assessed the cost effectiveness of VivaScope 1500 and 3000 as 1 integrated system, assuming that both devices would be available for the diagnosis of suspected BCC lesions but that each would be used as appropriate according to the location of the skin lesion to be examined.

  • Use of VivaScope for the margin delineation of LM before surgery. This model assessed the cost effectiveness of VivaScope 3000 as a stand‑alone device, because only this device is appropriate for margin delineation.

5.39 Five economic analyses were carried out, examining the cost effectiveness of VivaScope:

  • Diagnostic assessment of equivocal lesions suspected as melanoma (integrated use of VivaScope 1500 and 3000).

  • Diagnostic assessment of lesions suspected as BCC after a positive or equivocal result in dermoscopy (integrated use of VivaScope 1500 and 3000).

  • Diagnostic assessment of skin lesions suspected as skin cancer, either melanoma (after an equivocal finding in dermoscopy) or BCC (after a positive or equivocal finding in dermoscopy) – this analysis combined the results of the 2 respective 'part' models.

  • Margin delineation of LM before surgical treatment (using VivaScope 3000 as a stand‑alone device).

  • Diagnostic assessment of skin lesions suspected as either melanoma or BCC, and the margin delineation of LMs (integrated use of VivaScope 1500 and 3000) – this analysis combined the results of all 3 'part' models.

5.40 The final economic analysis synthesised all cost and effectiveness data from each of the 'part' economic models to give an estimate of the overall cost effectiveness of the VivaScope imaging system used for all indicated purposes assessed in economic modelling in a skin cancer multidisciplinary team service.

Diagnostic economic model for suspected melanoma lesions after an equivocal finding in dermoscopy

Model structure

5.41 A decision tree followed by a Markov model was constructed to assess the cost effectiveness of VivaScope in the diagnosis of lesions suspected as melanoma after an equivocal finding in dermoscopy. The model structure was determined by clinical expert advice and the availability of relevant data. Dermoscopically equivocal lesions suspected as melanoma in people aged 55 years were either: examined with VivaScope 1500 or 3000 followed by excision and biopsy or discharge; or managed in routine clinical practice, comprising excision and biopsy of the suspicious lesions and monitoring of equivocal lesions.

Model inputs

5.42 The model was populated with data derived from the clinical‑effectiveness review, published literature and routine sources of cost and prevalence data. Where published data were unavailable, the External Assessment Group used expert opinion to derive estimates to populate the model. A discount rate of 3.5% was applied to both costs and effects. Because diagnostic accuracy data were not synthesised, the base‑case economic analysis used data on the diagnostic accuracy of VivaScope 1500 in people with equivocal lesions suspected as melanoma from Alarcon et al. (2014) and Pellacani et al. (2014) in 2 separate analyses, because these 2 studies were considered to be the most representative of the UK setting.

Costs

5.43 Costs considered in this economic model included:

  • Cost of diagnostic assessment of a suspected melanoma with VivaScope after an equivocal finding in dermoscopy.

  • Cost of routine management (cost of excision or monitoring of suspected melanomas).

  • Cost of managing confirmed melanomas (true positives) after diagnostic assessment.

  • Cost of missed melanomas (false negatives) that were identified at a later time.

  • Cost associated with metastatic melanoma and terminal illness.

Health‑related quality of life

5.44 The utility values applied to each health state were derived from the published literature. People in the model experienced utility (or disutility) associated with 1 or more of the following:

  • Disutility due to excision and biopsy of a lesion suspected as melanoma that caused distress as well as anxiety while waiting for the results.

  • Disutility due to permanent scarring after surgical excision of a lesion on head or neck.

  • Health‑state‑related utility, which was associated with the stage of melanoma (in people with melanoma) or with the average utility of the general population (in people without a melanoma).

Base‑case results

5.45 For the purposes of decision‑making, the incremental cost‑effectiveness ratios (ICERs) per quality‑adjusted life year (QALY) gained or lost were considered. The following assumptions were applied in the base‑case analysis:

  • The model assumed that confirmed skin cancer lesions were of the same type of cancer as initially suspected (in the case of this model, melanoma), although occasionally skin cancers identified might be of a different type to that initially identified by the clinician at dermoscopy.

  • People whose lesions were shown not to be a melanoma on biopsy were assumed to have a benign tumour that did not need treatment and were discharged after the (unnecessary) excision and biopsy.

  • The diagnostic accuracy of VivaScope 3000 in equivocal lesions suspected as melanoma was assumed to be equal to that of VivaScope 1500 in the economic model, because of lack of relevant data specific to VivaScope 3000.

  • Excision and biopsy was considered in the economic model to be the 'gold standard' for the diagnosis of melanoma, that is, it was assumed to have 100% sensitivity and specificity.

5.46 The cost‑effectiveness of VivaScope in the diagnostic assessment of suspected melanomas with an equivocal finding in dermoscopy was affected by the diagnostic accuracy data used in the model, when VivaScope was assumed to be exclusively used for this purpose. Using the more 'optimistic' diagnostic data from Alarcon et al. (2014) resulted in a probabilistic ICER of £9362 per QALY gained. The 'less favourable' diagnostic data from Pellacani et al. (2014) resulted in an ICER of £25,453 per QALY gained. When using VivaScope was expanded to include other indications assessed in the economic analysis, VivaScope became the dominant strategy, that is, it was more effective and less costly than routine management of equivocal lesions suspected as melanoma.

Sensitivity analyses

5.47 One‑way sensitivity analyses were performed on all input parameters that were given a probability distribution in the economic model. The results of the one‑way sensitivity analyses were reported as the incremental net monetary benefit associated with the VivaScope imaging systems, assuming a maximum acceptable ICER of £20,000 per QALY gained.

5.48 The following inputs had the greatest impact on the model for the diagnostic assessment of suspected melanomas:

  • percentage of people experiencing permanent disutility due to scarring

  • disutility due to anxiety while waiting for the biopsy results

  • percentage of equivocal lesions excised under routine management

  • permanent disutility due to scarring from first excision

  • annual volume of suspected melanomas eligible for examination for VivaScope (if VivaScope was used exclusively for examination of suspected melanomas)

  • VivaScope sensitivity and specificity

  • prevalence of melanomas in equivocal lesions

  • cost of first excision

  • disutility due to first excision.

5.49 It should be noted that when VivaScope was assumed to be used exclusively for the diagnosis of suspected melanomas and when diagnostic data from Alarcon et al. (2014) were used in the model, the only parameter that potentially resulted in a negative incremental net benefit was the disutility due to anxiety. When VivaScope was assumed to be used exclusively for the diagnosis of suspected melanomas and when diagnostic data from Pellacani et al. (2014) were used in the model, several parameters resulted in negative incremental net benefits. However, when the assumption on the use of VivaScope was changed to include all indications, none of the influential parameters resulted in a negative incremental net benefit.

5.50 When diagnostic accuracy data from Pellacani et al. (2014) were used and VivaScope was assumed to be exclusively used for the diagnostic assessment of suspected melanomas, the use of VivaScope became less cost effective in the different scenarios. However, when wider use of VivaScope was assumed for all indications, the results were unaffected by the scenarios tested.

5.51 Two‑way sensitivity analyses were performed to test the impact of different combinations of sensitivity and specificity of VivaScope on its cost effectiveness in the diagnostic assessment of equivocal lesions suspected as melanoma. The results indicated that VivaScope needs to have a relatively high diagnostic accuracy in order to be cost effective, particularly when it is used exclusively for the diagnostic assessment of suspected melanomas.

5.52 The effect of a change in the percentage of equivocal lesions suspected as melanoma that are excised under routine management was also analysed. The ICER was less than £20,000 per QALY gained when the percentage of equivocal lesions excised was approximately 10% and below, or 60% and above.

Diagnostic economic model on lesions suspected as basal cell carcinoma after a positive or equivocal dermoscopy finding

Model structure

5.53 A decision tree followed by a Markov model was constructed to assess the cost effectiveness of VivaScope in the diagnosis of lesions suspected as BCC that had a positive or equivocal finding in dermoscopy. The model structure was determined by clinical expert advice and availability of relevant data. People aged 63 years, with lesions suspected for BCC after a positive or equivocal finding in dermoscopy, were either examined with VivaScope 1500 or 3000 followed by treatment or diagnostic biopsy or had a diagnostic biopsy for confirmation of BCC. The model assumed that confirmed cases of skin cancer were of the same type of cancer as initially suspected (in the case of this model, BCC), although occasionally skin cancers identified might be a different type to that initially identified by the clinician at dermoscopy.

Model inputs

5.54 The model was populated with data derived from the clinical‑effectiveness review, published literature and routine sources of cost and prevalence data. Where published data were unavailable, the External Assessment Group used expert opinion to derive estimates to populate the model. A discount rate of 3.5% was applied to both costs and effects. Diagnostic accuracy data for VivaScope were taken from the results of the systematic review of clinical evidence. Castro et al. (2014) reported the sensitivity and specificity of both VivaScope 1500 and VivaScope 3000 in the diagnosis of suspected BCC in patients presenting with at least 1 suspicious lesion for BCC (clinically and dermoscopically) who were recruited from 2 dermatology skin cancer clinics. According to this study, the sensitivity of VivaScope 1500 and VivaScope 3000 was 100% and 93.3% respectively. The specificity of both systems was 77.8%.

Costs

5.55 Costs considered in this economic model included the cost of diagnostic assessment with VivaScope after a positive result in dermoscopy, the cost of diagnostic biopsy, and cost of treatment (including cost of unnecessary treatment for skin lesions with a false positive result in VivaScope examination).

Health‑related quality of life

5.56 The utility values applied to each health state were derived from the published literature.

5.57 Patients in this model experienced a reduction in their health‑related quality of life for one of the following reasons:

  • diagnostic biopsy that caused distress as well as anxiety while waiting for the results

  • surgical treatment (all people having surgical excision or Mohs surgery in the model) and unnecessary non‑surgical treatment (people with false positive lesions)

  • permanent scarring after surgical treatment of a lesion on head or neck.

Base‑case results

5.58 For the purposes of decision‑making, the ICERs per QALY gained or lost were considered. The following assumptions were applied in the base‑case analysis:

  • Confirmed cases of skin cancer were of the same type of cancer as initially suspected (in the case of this model, BCC), although occasionally skin cancers identified might be of a different type to that initially identified by the clinician at dermoscopy.

  • Diagnostic biopsy was considered in the model to be the 'gold standard' for the diagnosis of BCC, that is, it was assumed to have 100% sensitivity and specificity.

5.59 VivaScope was the dominant strategy, that is, it was more effective and less costly, when used for assessing suspected BCCs, regardless of whether it was used exclusively for assessing BCCs or all indications (suspected melanomas and LMs).

Sensitivity analyses

5.60 The following inputs had the most impact in the model for the diagnostic assessment of suspected BCCs:

  • percentage of people experiencing permanent disutility due to scarring from biopsy

  • disutility due to anxiety while waiting for the results

  • diagnostic biopsy cost

  • prevalence of BCC in examined lesions

  • permanent disutility due to scarring from biopsy

  • annual volume of suspected BCCs that would be examined with VivaScope

  • disutility due to biopsy

  • percentage of patients treated with surgery

  • sensitivity of VivaScope 3000

  • number of lesions per person

  • percentage of people experiencing permanent disutility due to scarring from surgery.

5.61 However, none of the parameters had an impact great enough to turn the incremental net benefit to negative values, even when VivaScope was used exclusively in the diagnostic assessment of suspected BCCs.

5.62 A two‑way sensitivity analysis for the diagnosis of suspected BCCs showed that any combination of sensitivity and specificity from values as low as 0.40 resulted in VivaScope being a cost‑effective strategy (the maximum ICER, when sensitivity and specificity were 0.40, was £7083 per QALY gained).

Pre‑surgical margin delineation economic model

Model structure

5.63 The study population for this model comprised patients with LM, aged 70 years, having margin delineation before surgery. The aim of examination of LMs with VivaScope before surgical removal was the accurate definition of tumour margins. A decision tree followed by a Markov model was constructed to assess the cost effectiveness of VivaScope in margin delineation of LMs before surgical treatment. The model structure was determined by clinical expert advice and availability of relevant data. Patients aged 70 years with a LM planned for surgical excision either had their tumour examined with VivaScope 3000 for margin delineation before surgery, or had routine lesion management, comprising pre‑surgical assessment of LM margins with dermoscopy or clinical judgement.

Model inputs

5.64 The model was populated with data derived from the clinical‑effectiveness review, published literature and routine sources of cost and prevalence data. Where published data were unavailable, the External Assessment Group used expert opinion to derive estimates to populate the model. A discount rate of 3.5% was applied to both costs and effects.

5.65 The impact of VivaScope on surgical outcomes after pre‑surgical margin delineation of LMs was taken from the results of the systematic review of clinical effectiveness. The values used in the model were taken from Guitera et al. (2013) and are described in section 5.34.

Costs

5.66 Costs included the cost of:

  • pre‑surgical mapping of LMs with either VivaScope 3000 or dermoscopy or clinical judgement

  • treatment with either surgical excision or Mohs surgery

  • potential future treatment due to recurrence.

Health‑related quality of life

5.67 The utility values applied to each health state were derived from the published literature. Patients in this model experienced a reduction in their health‑related quality of life for one of the following reasons:

  • surgical treatment (either surgical excision or Mohs surgery)

  • permanent scarring after surgical treatment of a LM on the head or neck.

Base‑case results

5.68 For the purposes of decision‑making, the ICERs per QALY gained or lost were considered. The following assumptions were applied in the base‑case analysis:

  • LMs did not progress to lentigo maligna melanomas, because the relative risk was low as a result of all LMs in the model being treated.

  • The risk of recurrence of LMs after margin delineation using VivaScope 3000 was equal to the risk of recurrence of LMs after Mohs surgery, regardless of the type of surgical treatment (surgical excision or Mohs surgery) after mapping with VivaScope 3000 (this was considered by clinical experts to be a conservative assumption).

  • After 10 years, the risk of recurrence was zero.

5.69 Regarding margin delineation of LMs, mapping with VivaScope was cost effective, even if it was used exclusively for this purpose, as indicated by an ICER of £11,651 per QALY gained. When use of VivaScope was expanded to other indications covered in this economic analysis, VivaScope became the dominant option, that is, it was more effective and less costly.

Sensitivity analyses

5.70 The following inputs had the most impact on the cost effectiveness of pre‑surgical mapping of LMs using VivaScope:

  • probability of incomplete surgical excision after routine mapping

  • probability of annual recurrence after surgical excision

  • probability of incomplete surgical excision after mapping with VivaScope

  • permanent disutility due to scarring from surgical treatment

  • percentage of people with permanent disutility from scarring

  • probability of annual recurrence after VivaScope mapping and surgical excision

  • VivaScope mapping (staff) time

  • cost of surgical excision

  • number of Mohs stages under routine mapping

  • disutility due to surgery.

5.71 When it was assumed that VivaScope was used only for the mapping of LMs before surgical treatment, negative incremental net benefits were possible for several parameters. However, when a wider use of VivaScope was assumed, the incremental net benefit remained positive under any values of the influential parameters examined.

  • National Institute for Health and Care Excellence (NICE)