Search

We very much appreciate the interest Reifsnider et al. [1] have taken in our perspective on the single technology appraisal (STA) of abiraterone acetate (tradename Zytiga) plus prednisolone (AAP) acetate for the treatment of chemotherapynaı ¨ve metastatic castration-resistant prostate cancer (mCRPC) prepared for the UK National Institute for Health and Care Excellence (NICE) [2, 3]. Here, we respond to the aspects highlighted by Reifsnider et al. [1] and correct factual inaccuracies in their reasoning. The main issues are printed in italics [1]. These points relate to (1) the statistical significance of the COU-AA-302 survival results and (2) the justification of the discrete-event simulation (DES) approach utilised by the company. Reifsnider et al. also highlight aspects that are unrelated to these main points, and we discuss these separately.

Background: Determination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection. Objectives: To assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection. Methods: Twelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using the I2 and Q statistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months’ time horizon. Results: Eighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD -3.19 days, 95% confidence interval (CI) -5.44 to -0.95 days, I2 = 95.2%; four studies], hospital stay (WMD -3.85 days, 95% CI -6.78 to -0.92 days, I2 = 75.2%; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD -2.03 days, 95% CI -4.19 to 0.13 days, I2 = 81.0%; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95% CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95% CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were co