Definition of inclusion and exclusion criteria

Inclusion criteria are used to select participants for a study, determining which subjects can and cannot be included in the research. Inclusion criteria are designed to ensure that the study is set up to produce meaningful results. On the other hand, exclusion criteria prevent certain individuals from participating in the trial, as failing these requirements may compromise the safety of or lead to biased results.

Establishing inclusion/exclusion criteria - together known as eligibility criteria - is an important part of protocol design, and always takes place well before the subjects are recruited.

This brief article begins with inclusion and exclusion criteria examples and definitions in order to highlight the differences and explain the need for well-defined eligibility criteria in order to optimize the scientific merit of clinical trial results.

Importance of inclusion and exclusion criteria in research

Without well-defined inclusion and exclusion criteria, it is difficult for researchers to control bias within a clinical study. Selection bias can occur when subjects are defined too narrowly or restrictively in terms of characteristics such as age, gender or health status, which can lead to biased results due to exaggerated homogeneity in the study population. On the other hand, with too much variability amongst the study population, it might be impossible to establish causative effects of the study drug/treatment due to extreme variations in prognostic factors.

Inclusion and exclusion criteria are also very important for ensuring the safety and well-being of the subjects, by making sure that individuals at higher risk of complications are not given the study drug.

Inclusion criteria examples

Inclusion criteria are the specific characteristics that potential research subjects must possess to qualify for study participation. Examples include specific age ranges, sex, medical diagnoses, or behaviors.

Types of inclusion criteria

Demographic criteria: Include age range requirements (ranging from broad, i.e., “under 65,” to more specific, i.e., “aged 18 to 23”), sex (biological male/female), or ethnicity.

Clinical criteria: Can require meeting certain comorbidities or conditions such as diabetes or depression, or having certain scores on diagnostic tests or symptom severity tests for the condition. Can also specify certain ranges of physiological measures, such as blood pressure or cholesterol levels.

Geographical criteria: May require participants from specific countries, states or regions, or in a more general sense “ability to travel to the study site every 2 weeks for the duration of the study.”

Study-specific criteria: Can include a wide range of unique characteristics required by the specific study, such as education level, history of drug use, etc.

Exclusion criteria examples

Exclusion criteria determine which subjects cannot be part of a research study, typically for safety, ethical, or practical concerns. A general guideline to follow is that exclusion criteria should not be redundant with the inclusion criteria. For example, if the inclusion criteria include an age range of 18-35, then “being over 35 years old” is redundant - and unnecessary - as an exclusion criterion.

Types of exclusion criteria

Demographic: Similar to demographic features as inclusion criteria, demographic exclusion criteria can be related to age, sex, ethnicity/race, etc. Demographic features are particularly prone to redundancy in inclusion/exclusion criteria, so they should only be used to define additional exclusion criteria when the characteristic cannot be defined/captured in the inclusion criteria.

Clinical criteria: Can exclude those with a diagnosis or medical condition that would make them ineligible for participation, typically due to safety concerns. Use of a specific medication or habits/behaviors that may interact with the study drug or result in increased risk (i.e., taking blood thinners or smoking cigarettes) may also exclude certain individuals from participation.

Geographical criteria: Specific location or situation that excludes the participant from being eligible, for example “not being able to travel to a study site for weekly visits” or “living further than 200 km away from the nearest study site.”

Study-specific criteria: Other practical or ethical considerations that relate directly to the specific research questions/study protocol which exclude someone from participating in a clinical trial. Could include things such as “not being able to read,” “inability to personally provide informed consent,” or “not being able to access the internet to complete weekly questionnaires.” Note that efforts should be made to accommodate diverse populations and improve accessibility; in the examples provided, researchers could provide participants with a device equipped with mobile internet access that offers text-to-speech functions to allow illiterate subjects to listen to study surveys rather than having to read them.

Considerations for establishing inclusion criteria and exclusion criteria

1. Relevance

The criteria should directly relate to the research question; i.e., it should be important for the ability to answer the research question. For example, a specific shoe size is likely not a relevant inclusion criteria for a study on a new medication for COPD. Exclusion criteria should be specific enough such that only participants who are at a particularly elevated risk are excluded, without indiscriminately/inadvertently excluding potential eligible participants.

2. Precision

Clear definitions must be established to ensure criteria can be applied consistently. Inclusion and exclusion criteria should not leave room for different interpretations; they should clearly define who is and who isn’t eligible for participation in a study. An inclusion criteria example that does not fulfill this requirement is “being depressed” - a more precise definition is needed in order for the criteria to be applied consistently between participants. A better way to define this criterion would be “a diagnosis of a major depressive episode, lasting for at least 6 weeks.” While being too general could allow ineligible or high-risk individuals into a study, being overly specific can unintentionally exclude potentially eligible candidates and limit the generalizability of the results - finding the balance here is part of the art of protocol design.

3. Feasibility

Criteria must be realistic and practical to check when recruiting study subjects. At first contact (i.e., pre-screening), the eligibility criteria should be clear enough that participants caan make a judgment themselves about whether or not they are eligible. For the later screening stage, researchers should consider the practical implications of the eligibility criteria, including only those that are necessary for ensuring safety and optimizing the scientific merit of the study. If sites are required to perform 15 separate diagnostic tests on each prospect, screening costs will skyrocket, as will the costs (and frequency) of screen failures.

Exclusion vs inclusion criteria

Inclusion criteria are specific characteristics required of potential subjects, while exclusion criteria are characteristics that disqualify potential subjects. Exclusion criteria are essentially the opposite of inclusion criteria - while participants must meet the inclusion criteria to be eligible for a study, they must not meet the exclusion criteria. Defining inclusion and exclusion criteria is an essential part of protocol design, and each criterion should be scrutinized for its relevance, preciseness, and feasibility - in order to ensure participant safety and scientific validity while simultaneously keeping screening costs low and promoting diversity in the study population.

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