There is the potential for high‐dimensional information about patients collected in clinical trials (such as genomic, imaging, and data from wearable technologies) to be informative for the efficacy of a new treatment in situations where only a subset of patients benefits from the treatment. The adaptive signature design (ASD) method has been proposed for developing and testing the efficacy of a treatment in a high‐efficacy patient group (the sensitive group) using genetic data. The method requires selection of three tuning parameters which may be highly computationally expensive. We propose a variation to the ASD method, the cross‐validated risk scores (CVRS) design method, that does not require selection of any tuning parameters. The method is based on computing a risk score for each patient and dividing them into clusters using a nonparametric clustering procedure. We assess the properties of CVRS against the originally proposed cross‐validated ASD using simulation data and a real psychiatry trial. CVRS, as assessed for various sample sizes and response rates, has a substantial reduction in the computational time required. In many simulation scenarios, there is a substantial improvement in the ability to correctly identify the sensitive group and the power of the design to detect a treatment effect in the sensitive group. We illustrate the application of the CVRS method on the psychiatry trial.