Inclusion and exclusion criteria
In a clinical trial, the investigators must specify inclusion and exclusion criteria for participation in the study.
Inclusion and exclusion criteria define the characteristics that prospective subjects must have if they are to be included in a study. Although there is some unclarity concerning the distinction between the two, the ICH E3 guideline on reporting clinical studies suggests that
- Inclusion criteria concern properties of the target population, defining the population to which the study's results should be generalizable. Inclusion criteria may include factors such as type and stage of disease, the subject’s previous treatment history, age, sex, race, ethnicity.
- Exclusion criteria concern properties of the study sample, defining reasons for which patients from the target population are to be excluded from the current study sample. Typical exclusion criteria are defined for either ethical reasons (e.g., children, pregnant women, patients with psychological illnesses, patients who are not able or willing to sign informed consent), to overcome practical issues related to the study itself (e.g., not being able to read, when questionnaires are used for assessment of outcomes), or to eliminate factors that may limit the interpretability of study results (e.g., comorbidities). Exclusion criteria may lead to biases in the study's results.
Exclusion criteria
Poorly Justified Reasons for Exclusion:[1]
- Any criteria unless the condition or intervention is specific to the criterion, or the criterion has a direct bearing on condition/intervention/results.
Strongly Justified Reasons for Exclusion:[1]
- Unable to provide informed consent
- Placebo or intervention would be harmful
- Lack of equipoise (intervention harmful)
- Effect of intervention difficult to interpret
Potentially Justified Reasons for Exclusion[1]
- Individual may not adhere
- Individual may not complete follow up
- Individuals do not have reliable information
Example of inclusion and exclusion criteria
Coronary Heart Disease[2]
Include criteria:
- Minimum outcomes: coronary deaths & non-fatal myocardial infarction
- Appropriate measures of Framingham variables (Age, sex, LDL, HDL, total cholesterol, diabetes, smoking status, hypertension)
- Cohort, nested case-control, cardiovascular trial follow-up study (or systematic review or meta-analysis of these study types) that measures a novel risk factor and estimates its predictive value after adjusting for Framingham variables
Exclude criteria:
- No data
- Population or sub-population with known coronary disease or coronary disease equivalent (e.g., diabetes)
- Does not include minimum outcomes
- Does not measure Framingham variables appropriately
- Wrong study design/article format
A lesser studied form of exclusion criteria involves an absence of racial, ethnic, or sexual diversity that results in clinical trials that do not reflect the US population. A recent systematic review of the literature of hearing loss in adults, while representative of the US population in terms of sex, does not adequately represent racial or ethnic diversity.[3]
References
- Van Spall, Harriette (21 March 2007). "Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review". The Journal of the American Medical Association. 297 (11): 1233–40. doi:10.1001/jama.297.11.1233. PMID 17374817.
- Helfand M, Buckley D, Fleming C, et al. (2009). Screening for Intermediate Risk Factors for Coronary Heart Disease. Rockville (MD): Agency for Healthcare Research and Quality (US).
- Pittman, Corinne A.; Roura, Raúl; Price, Carrie; Lin, Frank R.; Marrone, Nicole; Nieman, Carrie L. (2021-07-01). "Racial/Ethnic and Sex Representation in US-Based Clinical Trials of Hearing Loss Management in Adults: A Systematic Review". JAMA Otolaryngology–Head & Neck Surgery. 147 (7): 656. doi:10.1001/jamaoto.2021.0550. ISSN 2168-6181.