The generalizability of trial data; A comparison of β-blocker trial participants with a prospective cohort of women taking β-blockers in pregnancy

Objective: To evaluate the generalizability of randomized controlled trial (RCT) data to obstetric practice, using the example of β-blocker therapy. Study design: Descriptive comparison of characteristics of participants, interventions, and outcomes assessed between a meta-analysis of trials of β-blocker therapy in pregnancy, and a prospective cohort of β-blocker exposed callers to Motherisk, a Teratology Information Service. Results: 72 women (cohort) and 34 trials with 2474 participants (meta-analysis) were compared. The generalizability of trials was limited by an inadequate description of maternal demographics and indications for β-blockers, and a focus on the effectiveness of β-blockers as antihypertensives rather than on reproductive risks. Conclusions: Some of these limitations could be rectified. Others cannot, such as evaluation of teratogenicity (for ethical reasons) or all indications for a drug (for practical reasons). Reference to observational literature is, and will likely remain, necessary to address the 'harm' side of the therapeutic equation in pregnancy.