Thursday, September 06, 2012

Definition of Screening Failures in Clinical Trials

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  • Consent Withdrawn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
  • Death
  • Other

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”


A D said...

I'm sorry Dr Deng, you have no idea what you're talking about. As someone who has worked in clinical trials for years, I can tell you screening occurs well before any consent is signed. A quick check of GCP will tell you a crucial component is a screening log, which records not only consenting but also non-consenting participants....without which you would have no idea if the population of the study is biased towards one group over another.
Your statistical knowledge is unchallenged, but please leave commenting on the logistics of trials in the hands of those who do it day in and day out.

Web blog from Dr. Deng said...

It is true that there may be screening occurs weel before any consent is signed. However, these activities are considered as 'pre-screening'. During the pre-screening, the patient medical charts can be reviewed for potential candidates for a clinical trial. The official screening for patient particiaption in a clinical trial only starts after the subject/patient signs informed consent.

Jan Hartstra said...

As far as I know, no assessments should be performed prior to signing informed consent. Hence, I do not understand how screening can be performed before the subject signed the ICF.

Anonymous said...

@AD - Any type of assessment or screening prior to an ICF is unethical. Do you work for an IRB reviewed facility? It sounds like possibly this is your process but not compliant with the ethical standards of research.

Anonymous said...

I believe "AD" is referring to pre-screening activities which ARE NOT the same as screening activities.

You may pre-screen potential subjects DETAILS before obtaining informed consent.
You may not screen subjects before obtaining informed consent.

Perhaps as someone who works day-in and day-out on clinical trials, you should brush up on your knowledge before calling someone else out in such a derogatory manner.

Anonymous said...

my 2 cents:
Screening, or parts of it, may be designed to meet the requirements for a minimal risk procedure under 21 CFR 56.102(i).
For example, the risk of drawing a small amount of blood from a healthy individual for research purposes is no greater than the risk of doing so as part of routine physical examination and does not require written consent outside of the research context. The prospective study subjects may then not sign a consent document for the screening activities as outlined under 21 CFR 56.109(c)(1). An information sheet may then be used in order to conduct the screening activities for such study. This will include a description of the screening activities and the reasons for performing such, including a brief summary description of the study. The information sheet will be reviewed and approved by the IRB and will be considered as a tool to be used for the oral informed consent process for screening activities. Non-identifying information about individuals who are screened for a study, but do not actually pursue the study or enroll will be retained in a screening log, to obtain information about the entire pool of individuals interested or potentially eligible for the study.
If the screening indicates that the prospective subject is eligible, the informed consent procedures for the study, as approved by the IRB, will be followed.
This may be suitable in cases where signing the IC is defined as point of enrollment in a study.

Anonymous said...

AD, while all trials may evaluate patients before signing of ICF, none of this data is admissible for screening data. As explained above, you may be working in an unregulated facility.