The explanation for this lower than expected mortality reduction, predicted by MISCAN, is as follows.
They argued that the estimated mortality reduction from screening may be lower than the mortality reduction predicted by MISCAN (van den Akker-van Marle et al, 1999) because of the lower sensitivity of the UK screening programme in the early years of screening.
The study was powered to detect a mortality reduction in predicted nonsurvivors from 90%% to 45 % with esmolol, with a power of 0.80 and type-1 error of 0.05.
Therefore, our predicted mortality reductions could be an underestimation of the actual effect of adjuvant therapy in the future.
Comparison of observed and predicted mortality reductions in this trial (and in the frequency trial (The Breast Screening Frequency Trial Group, 2002)) may provide further insight into the application of surrogate outcome measures.
The analysis demonstrates that the results are highly sensitive to these two parameters with predicted mortality reductions ranging from 66 (1 month increase in 10%%) to over 800 (6 month increase in 20 %).
Although there is no evidence to indicate that cholinesterase inhibitors improve survival, if the cognitive benefits are allowed to translate to mortality reductions, all treatments are predicted to increase costs relative to no treatment because the additional survival incurs further costs.
While the predicted mortality reduction and life years gained attributed to screening did not vary much across risk factor assumptions, there were small differences in the predicted increase in life years gained resulting from a shift to screening initiation at age 45 rather than a later initiation at age 50 years.
The greatest reduction in observed mortality versus the mortality predicted by TRISS (22% vs 29%) was reported by Hirschmann and colleagues in a Swiss study of 172 university hospital patients with ISS of more than 15 [ 66].
With the 36% improvement in surfactant use seen, to reliably detect the predicted mortality reduction, we would require a trial of collaboratives about nine times larger (9×1500), that is at least 13 500 infants individually randomised.
