Initiation of aspirin in early gestation for the prevention of pre-eclampsia


Author's Reply


The valiant defence by Roberge et al.[1] of the PREDO triallists[2] is admirable, but I respectfully disagree with all three of their points.

First, the trial registration makes no mention of this being a pilot study, and it states that the target number of participants is 1000. Readers are surely entitled to read that as the number of participants intended to be randomised, not the number screened.

Second, first-trimester testing requires proper test accuracy studies, not another randomised trial. We already have evidence that aspirin prevents pre-eclampsia. Once we know how accurate the test is we can calculate the number needed to treat, and parents and obstetricians can decide for themselves whether this justifies taking aspirin. Obstetric research has long been bedevilled by trials of test and treatment combinations that are often almost impossible to interpret, instead of proper test accuracy studies followed by randomised trials of treatments.[3]

Finally, small trials are a bad way to design definitive trials. Trials should be powered on the basis of the minimum effect size (delta) which experts and patients judge would justify the inconvenience of taking the treatment. Aspirin trials need to be large, because the inconvenience of taking a tablet a day is small, so even a small benefit is worth having. According to my computer program a trial to detect a reduction in pre-eclampsia from 13% to 5% would require only 224 participants per group (type 1 error 0.05, type 2 error 0.2). But there would be a 90% chance of such a trial being negative if the true effect of aspirin (delta) was a reduction from 13% to 11%. Parents would surely wish to take aspirin for a 2% reduction in severe pre-eclampsia, so this is too high a chance of ending up with a dangerously misleading type 2 error.

There are plenty of treatments in pregnancy that require evaluation by randomised controlled trials, but aspirin is no longer one of them.