Protocol Design - Inclusion and Exclusion Criteria

Investigators must include in their protocols a thorough description of the study population. The first priority is that the subject population have the attributes that will make it possible to accomplish the purpose of the research. The investigator must specify inclusion and exclusion criteria for participation in a study. Inclusion criteria are characteristics that the prospective subjects must have if they are to be included in the study. Exclusion criteria are those characteristics that disqualify prospective subjects from inclusion in the study. Inclusion and exclusion criteria may include factors such as age, gender, race, ethnicity, type and stage of disease, the subject’s previous treatment history, and the presence or absence (as in the case of the “healthy” or “control” subject) of other medical, psychosocial, or emotional conditions. Healthy, or control, subjects may be defined as those individuals who are free of certain specified attributes of non-health. Additional information on screening potential subjects for attributes of non-health is available in the Specific Guidance on Special Issues section of this module. Defining inclusion and exclusion criteria increases the likelihood of producing reliable and reproducible results, minimizes the likelihood of harm to the subjects, and guards against exploitation of vulnerable persons.

An example of inclusion criteria for a study of chemotherapy of breast cancer subjects might be postmenopausal women between the ages of 45 and 75 who have been diagnosed with Stage II breast cancer. An exclusion criterion for this study might be abnormal renal function tests, if the combination of study drugs includes one or more that is nephrotoxic. In this case it would be required to specify which tests of renal function are to be performed to evaluate renal function and the threshold values that would disqualify the prospective subject (e.g., serum creatinine above 1.9 mg/dl). Social science research generally does not have defined exclusion criteria. Rather, ethnographic research usually defines the community of interest and seeks to include the broadest sampling of individuals who meet the inclusion criteria. For example, in an ethnographic study of Amazonian communities and their use of forest products, individuals living near the Amazonian forest would be included. Within these communities everyone would be eligible to participate.

Furthermore, the investigator must be prepared to provide a rationale in case one or more of the inclusion or exclusion criteria is questioned. The investigator should review the inclusion and exclusion criteria and decide if any group(s) is inappropriately excluded. If the justification for the exclusion of this group is not reasonable with regard to the risks, benefits, and purpose of the research, then this group should be included. In the breast cancer study example discussed above, there would be no justification for the exclusion of minority women, but there is justification for the exclusion of men (based upon the target population of the research.) As noted in this example, the requirement that groups not be excluded without adequate justification does not mean that it is never appropriate for exclusion criteria to be based on race, gender, or age. For example, some ethnographic research, by definition, may be limited to a certain ethnic group. To assess the rationale for selecting certain subject groups, the investigator needs to review information on the distribution of the health condition in the general population. Research that has the potential to benefit men, women, and children or different races should target a population of subjects that is diverse enough to distinguish differing effects, risks, and benefits. No group or individual subject should be excluded without a scientifically sound reason or a requirement of the regulations to do so.