The other scenario analyses (Zaphiriou) found 280pg/ml to be the most cost effective NT-proBNP threshold. The committee considered that the change in result from the Zaphiriou study was due to the high proportion of HF-REF patients in the population, supporting their previous hypothesis that the greater the proportion of heart failure likely to see benefits from treatment the more likely a lower threshold will be more cost effective. Further limitations of the analysis are described in the full model write up in Appendix O. Overall, this original analysis was considered to be directly applicable with potentially serious limitations. 5.1.6 Evidence statements Clinical Plasma BNP Five studies explored the diagnostic test accuracy of plasma BNP for diagnosing chronic heart failure. The quality of the included evidence ranged from high to very low. Evidence was downgraded due to risk of bias and imprecision due to the range of the confidence interval around the point estimate. A number of studies were also downgraded due to indirectness as a result of the study population having a prevalence of CHF much higher than that of a representative sample or due to a lack of information regarding the reference standard used in the study. Two high quality studies (n=206 and n=122) reported a high sensitivity of plasma BNP at the thresholds 30pg/ml and 77pg/ml (95 (89-98) and 97 (83-100) respectively) which met the pre specified threshold of 95% set by the committee for possible recommendation. A further single study (n=200) reported a high specificity of 100 (97-100) at the threshold 400pg/ml. The committee placed an emphasis on specificity for the very high rule in threshold of 400pg/ml of which this study met the specificity threshold. 