Baseline data is collected after consent is obtained. In some studies, the population from which the study sample is recruited has a high prevalence of fatigue and patients can be screened with a brief verbal item about fatigue to determine eligibility. Eligible patients can then be recruited directly, sign consent, and be given the baseline assessment questionnaire packet. In other studies, particularly those involving treatment-related fatigue, the protocol may need to stipulate repeated verbal screening of cases to identify those who become eligible as fatigue develops. Patients who develop fatigue are asked to provide consent and then complete baseline data.

In studies that randomly assign treatments, randomization typically occurs prior to baseline data collection. Following data collection, the appropriate study interventions are implemented. The protocol must be very specific in defining this process. The intervention may require weeks and involve titration (gradual dose adjustment, increasing exercise, or other). Repeated data collection should again be timed to provide relevant information about time course or accruing effects, as well as information about maximum effect.

There has been very little experience in the practical administration of controlled drug trials for fatigue. In the absence of this experience, it is prudent to adopt lessons gained during many decades of controlled trials of analgesic drugs. These lessons involve design considerations (parallel group vs. crossover); use of placebo, active placebo, and active controls; and other approaches to ensure study sensitivity.