Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis.

OBJECTIVE: To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive. DESIGN: Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making. POPULATION: A hypothetical cohort of 1000 men with suspected prostate cancer. INTERVENTIONS: mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men. OUTCOME MEASURES: We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters. RESULTS: In 1000 men, mpMRI followed by MRI-targeted biopsy 'clinically dominates' TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis. CONCLUSIONS: Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters.

Testing for sexually transmitted infections among students: a discrete choice experiment of service preferences.

OBJECTIVES: To assess preferences among students for sexually transmitted infection (STI) testing services, with a view to establishing strength of preference for different service attributes. DESIGN: Online discrete choice experiment (DCE) questionnaire. SETTING: South East of England. PARTICIPANTS: A convenience sample of 233 students from two universities. OUTCOMES: Adjusted ORs in relation to service characteristics. RESULTS: The study yielded 233 responses. Respondents' ages ranged from 16 to 34 years with a mean age of 22 years. Among this sample, the respondents demonstrated strong preferences for a testing service which provided tests for all STIs including syphilis, herpes and HIV (OR 4.1; 95% CI 3.36 to 4.90) and centres staffed by a doctor or nurse with specialist knowledge of STIs (OR 2.1; 95% CI 1.78 to 2.37). Receiving all test results, whether positive or negative, was also significantly preferable to not being notified when tests were all negative ('no news is good news'; OR 1.3; 95% CI 1.16 to 1.5). The length of time waiting for an appointment and the method by which results are received were not significant service characteristics in terms of preferences. Patient level characteristics such as age, sex and previous testing experience did not predict the likelihood of testing. CONCLUSIONS: This study demonstrates that of the examined attributes, university students expressed the strongest preference for a comprehensive testing service. The next strongest preferences were for being tested by specialist STI staff and receiving negative as well as positive test results. However, it remains unclear how strong these preferences are in relation to characteristics which were not part of the study design and whether or not they are cost-effective.

Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model.

BACKGROUND: In lower-income countries, WHO recommends a population-based approach to antiretroviral treatment with standardised regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Our aim was to study the potential consequences of such monitoring strategies, especially in terms of survival and resistance development. METHODS: A validated computer simulation model of HIV infection and the effect of antiretroviral therapy was used to compare survival, use of second-line regimens, and development of resistance that result from different strategies-based on viral load, CD4 cell count, or clinical observation alone-for determining when to switch people starting antiretroviral treatment with the WHO-recommended first-line regimen of stavudine, lamivudine, and nevirapine to second-line antiretroviral treatment. FINDINGS: Over 5 years, the predicted proportion of potential life-years survived was 83% with viral load monitoring (switch when viral load >500 copies per mL), 82% with CD4 cell count monitoring (switch at 50% drop from peak), and 82% with clinical monitoring (switch when two new WHO stage 3 events or a WHO stage 4 event occur). Corresponding values over 20 years were 67%, 64%, and 64%. Findings were robust to variations in model specification in extensive univariable and multivariable sensitivity analyses. Although survival was slightly longer with viral load monitoring, this strategy was not the most cost effective. INTERPRETATION: For patients on the first-line regimen of stavudine, lamivudine, and nevirapine the benefits of viral load or CD4 cell count monitoring over clinical monitoring alone are modest. Development of cheap and robust versions of these assays is important, but widening access to antiretrovirals-with or without laboratory monitoring-is currently the highest priority.

Economic evaluations of calcineurin inhibitors in renal transplantation: a literature review.

People receiving a renal transplant require long-term treatment with immunosuppressant drugs. Contemporary regimens usually include a calcineurin inhibitor (CI), either ciclosporin or tacrolimus, in conjunction with at least one other drug. The aim of this study was to review the economic literature relating to the choice of CIs in patients following renal transplantation, with the specific intention of highlighting the challenges in estimating their cost effectiveness.A systematic literature search and narrative analysis was carried out, and 12 studies of varying quality and complexity were reviewed. All of the studies compared ciclosporin, azathioprine and a corticosteroid (CAS) with tacrolimus, azathioprine and a corticosteroid (TAS) but only three also evaluated the costs and effects of other possible treatment regimens. A variety of different evaluative frameworks were employed, from single randomised controlled trial-based studies over relatively short-time periods (6 months) to more complex Bayesian modelling techniques.The studies were broadly consistent in concluding that TAS was more effective than CAS in terms of reducing the rate of acute rejection episodes. Of the studies that undertook decision modelling, all but one estimated that TAS was associated with better graft-related outcomes such as rejection-free life-years, patient-survival and QALYs. Six of the studies concluded that the healthcare costs associated with TAS were lower than those for CAS. A seventh study suggested that TAS was the least costly option if costs were considered over a relatively long time period (14 years). Only one study clearly concluded that CAS was more cost effective than TAS.Clinical evidence clearly shows that TAS is more effective than CAS in terms of reducing the incidence of acute rejection following renal transplantation. The majority of published economic evaluations suggest that TAS is also the more cost-effective option. However, the economic evaluations contained a number of methodological limitations, undermining the confidence that can be attached to their results. Future economic evaluations of the CIs, and immunosuppressants in general, should address these issues in order to produce more robust cost-effectiveness estimates. Most importantly, they should evaluate a wider range of potential treatment options.

Exploration of the difference in results of economic submissions to the National Institute of Clinical Excellence by manufacturers and assessment groups.

OBJECTIVES: A recent study showed that estimates of cost-effectiveness submitted to National Institute for Health and Clinical Excellence (NICE) by manufacturers had significantly lower incremental cost-effectiveness ratios (ICERs) than those submitted by university-based Assessment Groups. This study extends that analysis. METHODS: Data were abstracted from relevant NICE documentation for thirty-two of eighty-two possible appraisals. RESULTS: The results from the analysis showed that sources of the difference in ICERs appear to be the effectiveness estimates relating to the comparator technology and the cost estimates relating to the technology under evaluation. That is, manufacturers estimated lower average benefits for the comparator technology and lower costs relating to the technology under evaluation compared with estimates submitted by the Assessment Groups. CONCLUSIONS: These findings may be particularly important, given the introduction of the "Single Technology Appraisal." Considerable difficulties were encountered when undertaking this study, highlighting, above all else, the complexity of explaining why results from economic evaluations purporting to answer the same question diverge.