Participants filled in EuroQol-5 Dimensions, three-level version (EQ-5D-3L) questionnaires at enrolment, after undergoing mpMRI, after undergoing the CBP and at the end of the study, which was, on average, 42 days after the CBP. As part of the economic evaluation, the EQ-5D-3L profiles were converted into preference-based index scores using the UK tariff.96The index scores after each test were compared with

the values at enrolment. There was no evidence of a change in index score between post mpMRI and

TABLE 16 Assessment of interobserver variability for mpMRI in 132 random cases that were double reported by a second expert urological radiologist, for definition 2 of CS cancer

Radiologist 1

Number of cases by mpMRI score Radiologist 2 1 2 3 4 5 Total 1 0 4 1 0 0 5 2 0 19 15 0 0 34 3 0 9 33 5 0 47 4 0 1 10 7 5 23 5 0 0 0 1 22 23 Total 0 33 59 13 27 132 Notes

Bold indicates perfect agreement between radiologists; green indicates agreement in terms of our primary outcome cut-off point; blue indicates disagreement in terms of our primary outcome cut-off point. Reproduced from Ahmedet al.92 © 2015 The Authors. Published by Elsevier Inc. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

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baseline (change=0.008, 95% CI–0.002 to 0.018). However, there was a large and statistically significant

negative impact after the CBP, with a change of–0.176 (95% CI–0.203 to–0.149). The health-related quality of life (HRQoL) implications of the various diagnostic strategies are explored further in the economic evaluation (seeChapters 48).

Safety

This section summarises the safety information for the CBP, which involved TPM-biopsy followed by TRUS-guided biopsy under the same anaesthesia. The CBP was carried out for the purposes of the study only; it is important to note that the CBP would not be required in routine clinical practice under any protocols developed as a result of PROMIS.

Risk of sepsis

There were nine cases of sepsis after the CBP during the study. There was one case of sepsis prior to the CBP. This equates to a post-CBP risk of sepsis of 9 out of 601 (1.5%, 95% CI 0.7% to 2.8%).

Risk of serious adverse events and side effects

A SAE is defined as any event that leads to death, a life-threatening situation, inpatient hospitalisation, persistent or significant disability, a congenital anomaly/birth defect or another important medical condition.97There were 44 reports of SAEs during the study. This equates to a risk of 44 out of 740

(5.9%, 95% CI 4.4% to 7.9%). Twenty-eight of the events (64%) involved the urogenital system, with the most common events being urinary retention and urinary tract infections or urosepsis. As reported in Risk of sepsis, there were 10 cases of sepsis. There were no deaths up to the time limit for reporting SAEs (30 days after the last study visit). All SAEs, including sepsis cases, were independently reviewed by the independent Data Monitoring Committee to ensure that the rate of sepsis was no higher than that reported for TRUS-guided biopsy on its own. No safety concerns were raised during these reviews. Most men (88%) experienced at least one side effect.Table 17summarises the numbers of any side effects documented at the patients’last study visit.

Difference between two prostate volume

measurements

Average of two prostate volume measurements (ml)

0 10 20 30 40 50 60 70 80 90 100 110 120 130 – 50 – 40 – 30 – 20 – 10 0 10 20 30 40 50

TABLE 17 Numbers of side effects after each test for the 576 patients who underwent all tests

Side effect (nwith missing data) n(%)

mpMRI

Pain/discomfort (15) 11 (2)

Allergic reaction to contrast medium (16) 1 (<1)

Other 3 (<1) CBP Pain/discomfort (13) 362 (64) Dysuria (17) 256 (46) Haematuria (11) 380 (67) Haematospermia (51) 291 (55)

Erectile dysfunction (requiring medication, injection therapy or devices) (48) 76 (14) Urinary tract infection (only if confirmed by a laboratory test) (11) 32 (6)

Systemic urosepsis (9) 8 (1)

Acute urinary retention (12) 58 (10)

Symptoms associated with general/spinal anaesthesia (43) 19 (4)

Other 65 (11)

Total patients with any side effect (8) 501 (88)

Note

Reproduced from Ahmedet al.92© 2015 The Authors. Published by Elsevier Inc. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

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Chapter 4

Economic evaluation approach

Overview

The economic evaluation conducted for PROMIS is presented in four chapters.Chapter 4states the aims and objectives of the economic evaluation and describes the approach used.Chapter 5describes the evaluation of the short-term outcomes associated with using the different diagnostic tests to detect CS cancer.Chapter 6describes the evaluation of the long-term outcomes associated with treatment compared with monitoring of men with prostate cancer.Chapter 7combines the results ofChapters 5and6and presents conclusions on the cost-effectiveness of the diagnostic strategies.

Introduction

Prostate cancer is the most common cancer in men, with approximately 47,000 new cases diagnosed in the UK in 2013. It is the second most common cause of death for men in the UK, with approximately 11,000 deaths per year.1As discussed inChapter 1, prostate cancer is divided into risk groups based on a

combination of PSA level, Gleason score (i.e. cancer grade) and stage (seeTable 1). Low-risk cancer is considered to be CNS because it is unlikely to have a clinical impact during the man’s remaining lifetime. The term‘clinically insignificant’is also commonly used. Intermediate-risk cancer and high-risk cancer have a greater risk of progression and are considered to be CS.

Currently in the UK, all men considered to be at risk of having prostate cancer are invited to undergo a biopsy, usually of the TRUS-guided type, to identify and classify the cancer. The biopsy procedure has adverse health consequences, albeit mostly temporary, and misses a considerable proportion of CS cancers. There are two possible ways of improving the current practice of TRUS-guided biopsy for all men

considered to be at risk: (1) choose another test that is better at detecting CS cancer (better sensitivity) or (2) incorporate additional tests prior to biopsy that might inform the decision to proceed to biopsy (triage test) and/or might improve the sensitivity of biopsy. The mpMRI is in the latter category, because it may enable the selection of patients who should have a biopsy and also provide information to enable targeted biopsies of suspicious areas within the prostate. The mpMRI can be used in combination with TRUS-guided biopsy or other biopsy types to better detect CS cancer and avoid unnecessary biopsies.

The different ways of combining mpMRI and biopsy form a range of diagnostic strategies for prostate cancer. These diagnostic strategies have different costs and health outcomes, in both the short term and the long term. The short-term costs and health outcomes depend on the prices of the tests and their direct health effects and detection rates in men with and without CS cancer. The long-term costs and health outcomes relate to the downstream consequences of treatment decisions, which in turn depend on the detection rates of each test. The short- and long-term costs and health outcomes together determine the most cost-effective way in which to use mpMRI and biopsy (i.e. the cost-effective diagnostic strategy). To inform decisions on how best to use the tests in combination, decision modelling is required to combine the data generated in PROMIS with external information. The clinical data generated in PROMIS provide information on how accurate mpMRI and biopsy are at detecting CS and CNS prostate cancer. However, the data do not provide information on the effect of using mpMRI and biopsy in combination (e.g. the proportion of CS cancers detected when using mpMRI to direct the TRUS-guided biopsy to suspicious lesions). External information is also required to predict the long-term costs and health outcomes of the alternative strategies, based on the proportions who are correctly diagnosed with CS prostate cancer, that is, the quality-adjusted survival and lifetime costs of men according to their cancer

status and diagnostic classification. Decision modelling structures the available evidence using a

mathematical model, combining the different pieces of information to produce an estimate of the costs and health outcomes of the different diagnostic strategies. Health outcomes are typically expressed as quality-adjusted life-years (QALYs), a measure that weights life expectancy with its HRQoL.

An evaluation of the effectiveness of the alternative strategies can rely on the health outcomes associated with each, the most effective strategy being the one conferring the most health to the potential population of users. To ascertain cost-effectiveness, however, the consequences of the additional costs that some of the strategies impose on the NHS also need to be considered. This requires information on the health opportunity cost of diverting resources to more costly interventions. The health opportunity cost is the health benefit forgone by other patients if their interventions are no longer funded in order to release resources for other more costly diagnostic strategies. The cost-effective diagnostic strategy is the strategy that achieves the greatest health gain net of the health opportunity cost.

Previous research98has estimated that £13,000 in additional costs displaces 1 QALY. This is the health

opportunity cost for the NHS of offering a more costly intervention and is often referred to as the

cost-effectiveness threshold. Therefore, the most cost-effective diagnostic strategy is the one that achieves the most QALYs net of its costs, converted into QALYs forgone using the health opportunity cost of £13,000. NICE uses a higher value, of between £20,000 and £30,000 per QALY, to make recommendations to the NHS on the cost-effectiveness of new interventions.99This means that an additional £20,000

–30,000 is assumed to impose on the NHS a loss of 1 QALY.

In document Multiparametric MRI to improve detection of prostate cancer compared with transrectal ultrasound-guided prostate biopsy alone : the PROMIS study (Page 65-69)