Inclusion and exclusion criteria are characteristics defined in the protocol that are used to determine which persons are suitable for participation in a clinical trial. Inclusion criteria describe required characteristics, while exclusion criteria exclude persons from participation if risks, confounding factors or a lack of scientific suitability are present. Together, they define the study population without replacing an individual medical eligibility decision.
Function in the protocol and study design
The protocol must clearly describe the population and the criteria for its selection. Criteria may relate, for example, to diagnosis, disease stage, age, prior treatment, laboratory values, comorbidities or reproductive requirements. They should be derived directly from the research question, benefit-risk assessment and endpoints of the trial. Imprecise, contradictory or non-operational criteria lead to inconsistent decisions between trial sites and thereby jeopardize the comparability of the data.
The criteria also control the transferability of the results. A narrowly defined population may be justified in early development phases or to reduce a specific risk. For later trials, however, the selection should appropriately take into account the groups of persons who are likely to use the medicinal product. ICH E8(R1) therefore requires a definition of the population aligned with the study objectives; ICH E6(R3) emphasizes that populations should not be excluded without scientific justification.
Implementation before enrollment
The criteria are assessed before enrollment on the basis of the information and examinations provided for in the protocol. These may include medical history, findings, laboratory results, prior treatments or pregnancy testing. The assessment is documented in a traceable manner in the source data. A person may only be randomized or assigned to a study intervention once the required inclusion criteria have been confirmed, no exclusion criterion is present and valid informed consent has been obtained. The decision must be based on the verifiable information available at the time of enrollment. For subsequent data reviews, it must be clearly attributable to the respective participant and the applicable protocol version.
The sponsor must formulate criteria in such a way that trial personnel can apply them consistently. Changes must not be resolved through informal individual decisions, but may require an amendment to the protocol. If a person is enrolled contrary to a criterion, this is to be assessed as a protocol deviation, documented and evaluated with regard to participant well-being and data quality. The criteria therefore do not serve to produce desired results, but to ensure a prospectively justified, consistent selection.
Distinction between screening and screening failure
Inclusion and exclusion criteria are the substantive eligibility rules. Screening, by contrast, refers to the process provided for in the protocol in which information is collected and assessed against these rules. This may also include preliminary examinations. Screening may begin before it is conclusively established whether a person meets all the criteria; it is therefore not synonymous with enrollment.
Screening failure generally refers to a screened person who does not meet all the requirements before enrollment or who is not enrolled for another reason documented in compliance with the protocol. The term describes the outcome of this process step, not a separate exclusion criterion and not a failure on the part of the person. It must also be distinguished from study discontinuation: in the case of a screening failure, enrollment in the trial has not yet taken place. Terms such as proceedings, ICMJE authorship criteria and the Committee for Advanced Therapies each refer to other regulatory or technical contexts and not to criteria for selecting study participants.
Relevance for clinical trials
In project practice, the criteria determine recruitment pathways, training of trial personnel, recruitment duration and the evaluability of the population. Criteria that can only be assessed using specific findings or time-dependent prior treatments are particularly critical. Monitoring and quality management therefore assess whether the source documentation supports the decision, whether screening and randomization data are consistent and whether deviations have been appropriately addressed.
Full-service CROs such as Mediconomics support the protocol-compliant formulation and operational assessment of inclusion and exclusion criteria, for example through feasibility, recruitment planning, training of trial sites, monitoring of source documentation and evaluation of deviations. In this process, project management, Clinical Operations, data management and biostatistics coordinate the definitions with the intended analysis population.
Frequently Asked Questions (FAQ)
Are inclusion criteria always medical criteria?
No. In addition to medical requirements, they may concern, for example, the ability to participate in visits, contraceptive requirements or the availability of legally valid informed consent, provided that they are objectively justified and described in the protocol.
Is every person who is not enrolled a screening failure?
The term is used for a person who has undergone the intended screening process and is not enrolled before enrollment. Mere contact or a preliminary assessment without formal screening does not necessarily establish this status.
May criteria be changed during an ongoing study?
Changes may affect the protocol and persons already enrolled. They must therefore be scientifically justified, assessed from a regulatory perspective and implemented as a protocol amendment in accordance with the applicable procedures.
Regulatory references
- ICH E6(R3) Good Clinical Practice, Annex B – requires the protocol to describe the population as well as the inclusion and exclusion criteria and the screening.
- ICH E8(R1) General Considerations for Clinical Studies, Section 5.1 – relates the definition of the study population to the study objectives and generalizability.
- Regulation (EU) No 536/2014 – establishes the EU framework for the authorization and conduct of clinical trials of medicinal products.