In all clinical trials, the typical process starts with a screening period. The screening period starts with the signing of the informed consent. During the screening period, inclusion/exclusion criteria for the study participation will be checked / tested. Subjects who meet all inclusion criteria and do not meet any exclusion criterion will be eligible to be randomized (in randomized trial) or to be dosed (in non-randomized trial). Those who are not eligible for randomization or dosing will be considered as ‘screening failures”.
It seems to be a straightforward concept. However, there could be confusions if there are subjects who are not randomized or dosed due to other reasons (for example consent withdrawal, family relocation, death during the screening period,…). These situations may not be part of the inclusion/exclusion criteria, but still cause the subjects not to be randomized or dosed.
What is the definition of “screening failures”? Will screening failures only refer to subjects who do not meet the inclusion/exclusion criteria?
In the most recent version of CDISC Clinical Research Glossary, the term Screening (of Subjects) is defined as “A process of active consideration of potential subjects for enrollment in a trial’ and the term Screen Failure is defined as “Potential subject who did not meet one or more criteria required for participation in a trial.” This definition of Screening Failure is accurate only if all other situations (such as consent withdrawal, lost to follow up,…) are part of the inclusion/exclusion criteria.
In ICH E3 (STRUCTURE AND CONTENT OF CLINICAL STUDY REPORTS), while no definition of Screening Failures are provided, it has the following statement and the example flow chart.
“…It may also be relevant to provide the number of patients screened for inclusion and a breakdown of the reasons for excluding patients during screening, if this could help clarify the appropriate patient population for eventual drug use.”
The annex IV b above implied that there could be multiple reasons for screening failures and inclusion/exclusion criteria would just be one of these reasons.
For example, in a clinical trial, we could have a case report form to ask the reasons for screening failures and we could have the following list of reasons:
Primary reason for screening failure:
- Adverse Event
- Patient Non-compliance
- Consent Withdrawn
- Inclusion/exclusion criteria not met
- Lost to follow-up
Therefore, a more accurate definition of Screening Failures may be as following “Potential subjects who were screened for the study participation, but were not enrolled (randomized or dosed) for the study”