Background: Translation of findings from randomised controlled trials (RCT), the foundation of evidence-based medicine, into clinical practice requires an understanding of relationships between patient characteristics, treatment practices and outcomes. We propose a novel technique, External Validity Analysis (EVA), to evaluate applicability of findings from a large RCT, comparing baseline characteristics, interventions and outcomes between the RCT and a large clinical database.
Aim: To perform EVA of the findings of a randomised controlled trial (ESTHER-1) to a population in an Australian clinic setting. To demonstrate this method, we evaluated the discordance in first cycle follicle-stimulating hormone (FSH) exposure and outcomes between the two populations, to inform clinical practice.
Materials and methods: In this retrospective, descriptive analysis, we compared practices and outcomes between the follitropin alfa 'conventional' dosing arm of the ESTHER-1 trial and a selected comparable clinic subpopulation of patients who underwent controlled ovarian stimulation using FSH.
Results: Mean FSH exposure was 34% higher in the clinic subpopulation than in the trial subpopulation, resulting in higher average ovarian response without improving the likelihood of clinical pregnancy or live birth.
Conclusions: EVA allowed for the comparison of a trial population with a selected clinic population with similar characteristics. With respect to FSH consumption, this analysis revealed higher exposure to FSH in the clinic setting without a corresponding benefit. The comparison reveals population differences as well as the potential to improve clinical outcomes through a reappraisal of current practices and objectives in gonadotropin dose selection.
Keywords: clinical trial; follicle-stimulating hormone; in vitro fertilisation; ovarian stimulation; real-world clinical trial.
© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.