Bivariate sensitivity analysis on the unit cost of tests
A sensitivity analysis varied the unit costs of TRUS-guided biopsy and mpMRI by±50% from their base-case
values (£182 and £403, respectively) and used four unit costs of TPM-biopsy: (1) base case (£1370), (2) base case+25% (£1713), (3) base case–25% (£1028) and (4) microcosting conducted for PROMIS (£1872). The
results are presented in area graphs showing the cost-effective diagnostic strategy for each combination.
Scenario using payment-by-results tariff unit costs
The unit costs of the tests can depend on the source of information. The NHS reference costs110are used
in the base case. These reflect the average cost across all health-care providers. The cost charged to commissioners is, however, indicated in the PbR tariff.112The unit costs of TRUS-guided biopsy and mpMRI
are similar between the NHS reference costs and PbR tariff, at £403 compared with £339, respectively, and £182 compared with £188, respectively. In contrast, the unit cost of TPM-biopsy is different between the two sources; £931 (NHS reference costs)110compared with £1370 (PbR tariff).112Because the unit
costs of the tests is anticipated to have an impact on the cost-effectiveness results, the model was run probabilistically using the PbR tariff for the unit costs.
Threshold sensitivity analysis
Additional threshold sensitivity analysis was carried out, aiming to identify the parameters that can have an impact on the results and indicate the changes in values that change the cost-effective strategy. This analysis is run deterministically; this means that the point estimates are used rather than the full distribution to reduce the running time of the decision model.Table 39summarises the threshold sensitivity analysis and its rationale.
Impact of repeated testing over time
In the base case, men with intermediate-risk cancer who are misclassified as having low-risk cancer are assumed to receive active surveillance. Their long-term outcomes are predicted from the intermediate-risk subgroup of the observation arm of PIVOT. This assumes that men misclassified will not receive radical treatment in the future. In practice, however, there is the possibility that men are correctly classified in one of the monitoring episodes of the active surveillance protocol and receive radical treatment at that point. The evidence on repeated testing and monitoring is, however, sparse. The population of individuals for retesting (i.e. those who initially tested negative) will differ from the overall PROMIS population and is likely to differ by the diagnostic strategy initially implemented. This means that the accuracy of retesting cannot be drawn from the general literature but needs to be drawn from studies that specifically focus on retesting. In addition, between the initial test and retesting, the disease may progress in risk category, the rate of which is unknown. For these reasons, the analysis cannot explicitly consider retesting. However, exploratory analyses were conducted by considering that a proportion of men misclassified in year 0 (i.e. in the first diagnostic episode), and who have not progressed to metastatic disease in subsequent years, can be correctly classified through retesting. These patients are assumed to receive radical treatment at that time point. Given the absence of information, the outcomes after radical treatment are unchanged. A threshold sensitivity analysis finds the smallest change in parameter values that change the cost-effective strategy from the base case. The lifetime discounted QALYs and costs for treatment delays are calculated in the long-term model. In order to do this, the model assumes that treatment is received 1–5 years post referral from primary care. The model calculates the lifetime discounted QALYs and costs as the weighted average of the QALYs and costs for delays each year weighted by the proportion of men detected each year.
COST-EFFECTIVENESS OF DIAGNOSTIC STRATEGIES
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Value of future research
In addition to the uncertainty from the structural assumptions explored above, the cost-effectiveness results are also uncertain because of uncertainty in the parameter inputs, as represented by their CIs (or other measures of uncertainty such as standard errors). The cost-effectiveness results are presented in terms of their expected values, CIs and probability that a strategy is cost-effective. This means that there is a probability that the strategy expected to be cost-effective is actually not cost-effective. This has consequences in terms of the net health achieved from choosing this strategy. The difference between the net health achieved from choosing this strategy and the net health achieved by choosing the strategy that is always cost-effective represents the health losses attributable to uncertainty. These health losses can also be thought of as the health gain from solving this uncertainty through future research (i.e. the value of future research). The value of future research in health terms can be converted into monetary units to indicate the maximum investment to solve this uncertainty.113
TABLE 39 Threshold sensitivity analysis
SA1: relative sensitivity of MRI-targeted TRUS-guided biopsy (‘W’) in detecting CS cancer
The inputs used in the base case are obtained from the systematic review and meta-analysis by Schootset al.105
TRUS-guided and mpMRI definitions and cut-off points used in the studies included in the meta-analysis may not directly map to those used in PROMIS. Increased sensitivity of‘W’biopsy will improve the cost-effectiveness profile of strategies starting with mpMRI. Increased sensitivity of‘Z’biopsy will improve the cost-effectiveness of strategies including a second biopsy post negative biopsy and suspicious mpMRI SA2: relative sensitivity of MRI-targeted
second TRUS-guided biopsy (‘Z’) in detecting CS cancer
SA3: prevalence of intermediate-risk cancer vs. low-risk cancer
Men in PROMIS had a higher than expected prevalence of intermediate-risk (CS) cancer (0.53) and a lower than expected probability of not having cancer (0.28); men referred for diagnosis may have a lower probability of having intermediate-risk cancer and a higher probability of not having cancer. This can affect the cost-effectiveness results because the increased probability of CS cancer favours more sensitive strategies
SA4: probability of NC
SA5: risk of death from TRUS-guided biopsy
There is some evidence that TRUS-guided biopsy may increase the risk of death, mainly because of sepsis, although this is uncertain (seeAppendix 5). The base case assumes that biopsy has no risk of death. Including risk of death from TRUS-guided biopsy will improve the health outcomes of strategies with fewer TRUS-guided biopsies
SA6: reduced quality-adjusted survival from incorrect classification as NC
In the base case, men incorrectly classified as having NC have the same outcomes as men incorrectly classified as having low-risk cancer. However, their quality-adjusted survival may be lower because they may not be tested in the future as frequently as men classified as having low-risk cancer
SA7: reduced clinical effectiveness of radical treatment
The base case assumes that radical treatment in men with intermediate-risk (CS) cancer is cost-effective, as indicated by the results of the prediction of long-term outcomes, which is based on PIVOT. However, radical treatment may be less effective in improving survival. Therefore, the cost-effectiveness of radical treatment may have been overestimated. This scenario tests how reductions in the effect of radical treatment affect the cost-effectiveness of the diagnostic strategies
SA8: HRQoL impact of TRUS-guided biopsy
The base case assumes that TRUS-guided biopsy has no HRQoL consequences. However, this may be incorrect because this is a procedure that requires anaesthesia and may have complications. This sensitivity analysis tests the impact of assuming that TRUS-guided biopsy has a fraction of the impact of TPM-biopsy, from 10% of its impact to its full impact (–0.176), over the same period of 2 weeks
NC, no cancer; SA, sensitivity analysis;‘W’biopsy, TRUS-guided biopsy after a suspicious mpMRI result;‘Z’biopsy, TRUS-guided biopsy after a TRUS-guided biopsy that did not detect cancer and a suspicious mpMRI result.