Estimating the Hawthorne Effect in Real-World Blood Pressure Control Trials: An Analysis of the BP Home Trial

BACKGROUND: Results from blood pressure (BP) control interventional trials can inform clinicians and health systems pursuing better BP control, but they must be interpreted cautiously. OBJECTIVE: Deconstruct the observed drop in systolic BP (SBP) into components attributable to increased adherence to previously prescribed medications, regression to the mean, and initiation of new medications. DESIGN: Secondary analysis of BP Home, a pragmatic randomized controlled trial. PARTICIPANTS: Patients owning a smartphone who reported uncontrolled BP at their last clinic visit (> 145 mmHg) and a desire to lower their BP by > 10 mmHg. INTERVENTIONS: In BP Home, participants were randomly assigned to receive one of two devices for self-measurement of BP and followed for up to 24 months via electronic health records (EHR). APPROACH: The primary outcome was EHR-recorded office SBP. We fit SBP trajectories for each participant using linear mixed models, and estimated the contributions of medication adjustments, and increased adherence to pre-existing BP medications due to their enrollment in a research study (i.e., a Hawthorne effect). Regression to the mean was calculated for each participant as the difference between their last measured pre-enrollment SBP and their modeled SBP trajectory at enrollment. KEY RESULTS: Among participants taking BP medications at enrollment, we estimated an average immediate drop in SBP of -4.2 mmHg (95% CI, -5.1 to -3.3; p < 0.001) at enrollment, explainable by increased medication adherence following study enrollment. Starting a new medication class post-enrollment resulted in an SBP drop of -4.1 mmHg (95% CI, -5.3 to -2.8; p < 0.001). The average expected regression to the mean was -3.9 (95% CI, -4.4 to -3.3; p < 0.001). CONCLUSIONS: A significant portion of BP reductions in trials may stem from increased adherence to pre-existing medications arising from enrollment in a research study and enhanced awareness of their elevated BP. NIH TRIAL REGISTRY NUMBER: NCT03796689 (registered on 2019-01-04).