Inclusion and exclusion criteria should be selected to yield a study sample that is relevant to the research question, willing to accept participation, likely to complete the study's tasks once consent is signed, and unlikely to present complications that would undermine the validity of the data collected. Eligibility for the study typically begins with appropriate demographics and criteria related to the disease or its therapy. The inclusion criterion for fatigue considers the issues for case definition discussed previously. In most situations, a fatigue duration of one or two weeks is sufficient to consider the symptom significant enough to study.

To systematically implement the intervention under study, the investigator must ensure reliable procedures and exquisite quality control. Studies of non-pharmacological interventions may require a written resource guide and detailed training of researchers, followed by testing to establish uniformity in the intervention across individuals. Controlled drug trials also rely on investigator training and typically require a research pharmacist, who prepares the study and comparator drugs, and dispenses these to a researcher based on a pre-determined randomization protocol.

The protocol stipulates the methods and timing of data collection. As discussed previously, there are numerous options that vary in the timing and breadth of information obtained. The usual desire to collect as much data as possible must be tempered by the pressing concern about respondent burden in a fatigued and medically ill population. Perceived or actual respondent burden can result in poor recruitment and patient drop-out. Given this risk, the investigator should try to base decisions about these procedures on actual experience rather than presumptions about the study population, if possible. In the absence of any meaningful experience from which to judge the capabilities of the population, it is prudent to build a pilot phase into the study.