Randomization to randomization probability: Estimating treatment effects under actual conditions of use.

Blinded randomized controlled trials (RCT) require participants to be uncertain if they are receiving a treatment or placebo. Although uncertainty is ideal for isolating the treatment effect from all other potential effects, it is poorly suited for estimating the treatment effect under actual conditions of intended use-when individuals are certain that they are receiving a treatment. We propose an experimental design, randomization to randomization probabilities (R2R), which significantly improves estimates of treatment effects under actual conditions of use by manipulating participant expectations about receiving treatment. In the R2R design, participants are first randomized to a value, π, denoting their probability of receiving treatment (vs. placebo). Subjects are then told their value of π and randomized to either treatment or placebo with probabilities π and 1-π, respectively. Analysis of the treatment effect includes statistical controls for π (necessary for causal inference) and typically a π-by-treatment interaction. Random assignment of subjects to π and disclosure of its value to subjects manipulates subject expectations about receiving the treatment without deception. This method offers a better treatment effect estimate under actual conditions of use than does a conventional RCT. Design properties, guidelines for power analyses, and limitations of the approach are discussed. We illustrate the design by implementing an RCT of caffeine effects on mood and vigilance and show that some of the actual effects of caffeine differ by the expectation that one is receiving the active drug. (PsycINFO Database Record

High Intensity Interval- vs Moderate Intensity- Training for Improving Cardiometabolic Health in Overweight or Obese Males: A Randomized Controlled Trial.

PURPOSE: To compare the effects of six weeks of high intensity interval training (HIIT) vs continuous moderate intensity training (MIT) for improving body composition, insulin sensitivity (SI), blood pressure, blood lipids, and cardiovascular fitness in a cohort of sedentary overweight or obese young men. We hypothesized that HIIT would result in similar improvements in body composition, cardiovascular fitness, blood lipids, and SI as compared to the MIT group, despite requiring only one hour of activity per week compared to five hours per week for the MIT group. METHODS: 28 sedentary overweight or obese men (age, 20 ± 1.5 years, body mass index 29.5 ± 3.3 kg/m2) participated in a six week exercise treatment. Participants were randomly assigned to HIIT or MIT and evaluated at baseline and post-training. DXA was used to assess body composition, graded treadmill exercise test to measure cardiovascular fitness, oral glucose tolerance to measure SI, nuclear magnetic resonance spectroscopy to assess lipoprotein particles, and automatic auscultation to measure blood pressure. RESULTS: A greater improvement in VO2peak was observed in MIT compared to HIIT (11.1% vs 2.83%, P = 0.0185) in the complete-case analysis. No differences were seen in the intention to treat analysis, and no other group differences were observed. Both exercise conditions were associated with temporal improvements in % body fat, total cholesterol, medium VLDL, medium HDL, triglycerides, SI, and VO2peak (P < 0.05). CONCLUSION: Participation in HIIT or MIT exercise training displayed: 1) improved SI, 2) reduced blood lipids, 3) decreased % body fat, and 4) improved cardiovascular fitness. While both exercise groups led to similar improvements for most cardiometabolic risk factors assessed, MIT led to a greater improvement in overall cardiovascular fitness. Overall, these observations suggest that a relatively short duration of either HIIT or MIT training may improve cardiometabolic risk factors in previously sedentary overweight or obese young men, with no clear advantage between these two specific regimes (Clinical Trial Registry number NCT01935323). TRIAL REGISTRATION: ClinicalTrials.gov NCT01935323.