Past exam of the mathematics course of the University of Cambridge 2013 iii Paper 32 1 a Solution Created 2026-10-03 Updated 2026-10-07
For independent binomial distributions in the two trial arms, the estimate of the log risk ratio isThe delta method gives ; replacing by the sample proportion gives , where is the event count. Adding the independent arm contributions therefore givesThe standard error is . Using the stipulated normal quantile two, the approximate confidence interval isThe point estimate of the risk ratio is , corresponding to approximately 79% lower mortality risk in the transfusion arm. Exponentiating the endpoints gives an approximate 95% confidence interval for the risk ratio of . It includes one, so the trial is compatible with no difference as well as substantial benefit or some harm. The point estimate favours transfusion, but the data are too imprecise to establish a difference at the 5% level. These are large-sample approximations, especially rough with only one event in an arm. A frequentist confidence interval describes repeated-sampling coverage, not a 95% posterior probability for this fixed parameter.
Past exam of the mathematics course of the University of Cambridge 2013 iii Paper 32 1 b Solution Created 2026-10-03 Updated 2026-10-07
Let be each trial's estimated log risk ratio, with estimated sampling variance . A fixed-effect meta-analysis models the independent estimates as , with one common true log risk ratio . Differentiating the Gaussian log-likelihood, or minimizing , gives inverse-variance weights andThe variance follows directly by adding independent variances of the weighted estimates: .
Using the printed rounded estimates and standard errors, , soThe pooled risk ratio is about . An interval using the same quantile two is on the log scale, so it includes no effect. Recomputing all trial estimates from the event counts would change the last digits because the printed log estimates and errors are rounded.
The key assumptions are independent trials, a common true treatment effect on this chosen log scale, approximately unbiased and approximately normal trial estimates, and suitable sampling-variance estimates. The common-effect assumption is stronger than merely studying the same named treatment: systematic population, treatment or design differences may produce genuine heterogeneity. For an unbiased interpretation of the pooled evidence, inclusion of studies must also not depend selectively on their results. Treating the plug-in variances as fixed is the usual approximation in the displayed variance formula.
Past exam of the mathematics course of the University of Cambridge 2013 iii Paper 32 1 c Solution Created 2026-10-03 Updated 2026-10-07
Publication bias occurs when the availability or publication of a study depends on its results, for example their direction or statistical significance. The published studies then need not represent all studies meeting the review's eligibility criteria. This is different from unbiased studies simply having large sampling errors.
If mortality reductions favouring transfusion are more likely to be published than null or unfavourable findings, the observed log risk ratios will tend to be too negative and the pooled risk ratio too small. The apparent benefit will then be exaggerated. An ordinary meta-analysis interval ignores uncertainty about the missing evidence and may have poor coverage even if its sampling-variance calculation is correct for the studies included. The direction of bias depends on which results are preferentially made available; publication bias does not invariably favour a particular treatment.
Past exam of the mathematics course of the University of Cambridge 2013 iii Paper 32 1 d Solution Created 2026-10-03 Updated 2026-10-07
A funnel plot places each estimated log risk ratio horizontally and its standard error vertically, with the most precise studies at the top. Under a common-effect model without selective availability, less precise estimates should spread approximately symmetrically around the underlying effect. The plotted dashed limits are the pooled estimate plus or minus twice the standard error; they illustrate the expected sampling spread, not a test of publication bias by themselves.
Funnel plot of the ten transfusion trial estimates, with inverse-variance pooled effect and approximate sampling limits
. The least precise estimates are mostly far to the left, whereas the most precise estimates are close to zero. The reported regression slope means that increasing the standard error by one unit is associated with a decrease of about in the estimated log risk ratio. Its 95% confidence interval excludes zero, and gives evidence against a zero slope under that regression model. This is evidence of a small-study effect: less precise trials report stronger apparent benefit.
There is evidence consistent with publication bias, but asymmetry does not identify its cause. Selective availability of favourable small studies is a plausible explanation. Genuine differences in patient populations, trial quality, interventions or effect modification could also generate the pattern, and there are only ten trials. The given outcome-on-error regression should be interpreted as specified; it is not automatically the original standardized-effect-on-precision form of an Egger test. The plot and slope justify investigating missing studies and sensitivity to selection, rather than concluding that publication bias has been proved.
