(HealthDay News) — Conventional clinical trials are unable to detect clinically important heterogeneity in intensive blood pressure (BP) treatment effects, according to a modeling study published online in the Annals of Internal Medicine.

Sanjay Basu, MD, PhD, from Stanford University in Palo Alto, Calif., and colleagues performed a theoretical modeling study in a population of US adults to identify whether large, clinically important differences in benefit and harm can be hidden among patients (heterogeneous treatment effects [HTEs]) in BP trials. The authors used data from 2 trials comparing standard with intensive BP treatment and from the National Health and Nutrition Examination Survey 2013 to 2014.

The researchers found that in base-case analysis, clinically important HTEs could explain the differences in outcomes between 2 trials of intensive BP treatment, with decreasing benefit with each additional agent (adding a second agent reduces cardiovascular disease risk, but adding a fourth agent had no benefit) and increasing harm at low BP. In sensitivity analyses, despite large samples, conventional treat-to-target trial designs had poor power to detect HTEs (<5%), and produced biased estimates. Despite small samples, a trial with sequential randomization to more intensive therapy achieved greater than 80% power and unbiased HTE estimates.

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“Clinically important heterogeneity in intensive BP treatment effects remains undetectable in conventional trial designs but can be detected in sequential randomization trial designs,” the authors write.

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  1. Basu S, Sussman JB, Hayward RA. Detecting Heterogeneous Treatment Effects to Guide Personalized Blood Pressure Treatment: A Modeling Study of Randomized Clinical Trials. Ann Intern Med. 3 January 2017. doi: 10.7326/M16-1756.