Scraping the SCOPE barrel
Between 2004 and 2008, the Screening for Pregnancy Endpoints (SCOPE) Consortium collected blood samples from 3529 nulliparous pregnant women at 14-16, and at 19-21 weeks gestation. The idea was to see if they could predict the development of various nasty pregnancy outcomes. In September’s BJOG the consortium report on three biomarkers – PlGF, sFLT-1 and endoglin (click here or here angioPET_BJOG_2013), as predictors of pre-eclampsia. According to the paper only PlGF has any predictive power, and that was modest.
SCOPE was a lovely study. It involved obstetricians from New Zealand, Australia, UK and Ireland, and unlike many previous observational studies in the field the design was registered here before any analyses began. In theory this should have prevented the researchers picking and choosing among biomarkers, or subtly altering the definition of pre-eclampsia to make their favoured biomarker look good.
Unfortunately – I grumbled about it at the time – no biomarkers were prespecified at study registration, so readers have to take on trust that all those tested were reported. The SCOPE website (click here) reveals other reports of lipids, clusterin, vitronectin and high-molecular-weight kininogen, as well as various “proteomic” and “metabolomic” analyses in subsets of the data, so there may have been a bit of cherry picking.
More worryingly, according to the study registration, the consortium planned to test prediction of pre-eclampsia occurring “at any stage during pregnancy after recruitment until delivery or in the first 2 weeks after delivery”. They also pre-specified a secondary analysis for predicting “early onset pre-eclampsia” defined as “pre-eclampsia resulting in delivery at <34 weeks”. However, neither of these outcomes are reported in the paper. Instead they report “pre-term pre-eclampsia” defined as “pre-eclampsia before 37 weeks”. Search as I might I cannot find this endpoint in the registry.
Choosing a new endpoint would be fine if the primary analyses had been reported elsewhere. Two years ago a clinical prediction paper in the BMJ (click here) used the pre-specified definition of pre-eclampsia, but reported no biomarker results. Nor is there any mention of an earlier biomarker report in the present paper, and the SCOPE website doesn’t reveal one either. This looks like data dredging.
Alere, the manufacturer of the PlGF test, “funded the retrieval and shipping of specimens and measured the angiogenic biomarkers”. Did they influence the choice of endpoint?