Intervention trials pose numerous practical challenges. Procedures must be developed to identify and recruit patients, obtain informed consent, organize the study treatments, and collect and manage data. These procedures determine the feasibility of the study, the likelihood that missing data will not compromise the results, and the possibility that information ancillary to the primary aim, but very important nonetheless, will be obtained along the way. Most decisions about methodology require an assessment of trade-offs. Simplicity, ease of administration, and limited respondent burden must be balanced against the need for careful controls to maintain quality, allow interpretability, and enhance the scope of the information ultimately available from the trial. Each decision also has economic ramifications, and the availability of funds may strongly influence sample size (the number of treatment arms possible) and the specific procedures used to implement the study methods, and collect and manage the data.

Thoughtful compromises are often needed as methodological restrictions, which might enhance scientific rigor on the one hand but impede patient recruitment on the other, are applied. For example, the decision to have an entry criterion of moderate to severe fatigue may enhance the study's ability to identify the effect of a treatment, but also increase the difficulty in identifying appropriate patients for study. A useful compromise may be stratification by the intensity variable, such that an equal number of highly fatigued patients (e.g. fatigue numeric score >4 on an 11-point scale) and less fatigued patients (fatigue score <4) are randomly assigned to each study group. Although stratification can slow recruitment because the study must remain open until all the cells (including those with the more difficult-to-recruit highly fatigued patients) are filled, the approach is more likely to be accomplished than setting a more restrictive entry criterion.