Its aim was to see if calcium supplementation starting before conception reduced pre-eclampsia in late pregnancy. So the main analytical issue was that some (as it turned out, many) women would not get pregnant, so would not be at risk of pre-eclampsia.
In the paper they restricted the analyses to those women who were randomised, became pregnant, and reached 20 weeks gestation, which resulted in a lot of women not being in the final analysis; 1355 were randomised but only 579 were included in the analysis. Main problem is that with so many exclusions we don’t have any guarantee that the randomised groups are stil comparable; conception and early pregnancy loss could be related to the intervention.
The most obvious alternative, analysing the groups as randomised, doesn’t seem ideal either - so what would be the best way to proceed with the analysis of this and similar trials? [I have my own ideas but very interested to see what others would recommend as I’ve never seen this issue really nailed down]
Essentially the same problem crops up in other contexts e.g. neonatal outcomes after interventions in pregnancy, but it seems particularly severe in this trial because of the large numbers excluded.