An adaptive design for optimizing treatment assignment in randomized clinical trials
Abstract
The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the variances of potential outcomes conditional on baseline covariates. Approximating these optimal designs requires information about the conditional variance functions, which is often unavailable or unreliable at the design stage. As a practical solution to this dilemma, we propose a multi-stage adaptive design that allows the treatment assignment mechanism to be modified at interim analyses based on accruing information about the conditional variance functions. This adaptation has profound implications on the distribution of trial data, which need to be accounted for in treatment effect estimation. We consider a class of treatment effect estimators that are consistent and asymptotically normal, identify the most efficient estimator within this class, and approximate the most efficient estimator by substituting estimates of unknown quantities. Simulation results indicate that, when there is little or no prior information available, the proposed design can bring substantial efficiency gains over conventional one-stage designs based on the same prior information. The methodology is illustrated with real data from a completed trial in stroke.
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis
- Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials
- Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials
- Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta‐analysis, and network meta‐analysis of randomized trials with 94,283 participants
- Screen time increases overweight and obesity risk among adolescents: a systematic review and dose-response meta-analysis
- Exposure to WHO AWaRe antibiotics and isolation of multi-drug resistant bacteria: a systematic review and meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.