Subject Screening
Among other things, the criteria for Institutional Review Board (IRB) approval of research (45 CFR 46.111, 21 CFR 56.111) require that the research:
- minimize risks to subjects, and
- select subjects equitably.
A common mechanism for meeting these requirements, in part, is to clearly define your study population in the study protocol via eligibility requirements (i.e., inclusion and exclusion criteria). Doing so protects subjects by ensuring that the study population is representative of those most likely to benefit from the research and excluding potential subjects who may be at higher risk of harm.
How can subjects be screened and enrolled?
Once eligibility requirements have been defined, a critical protocol development component is planning for how subject eligibility will be confirmed and documented (i.e., subject screening).
The manner in which subjects are screened and enrolled into research will ultimately depend on the nature of the research, though the process will generally fall into one of the following scenarios:
- Scenario A: A potential subject is identified and eligibility is confirmed (e.g., via record review and/or oral history/interview with the subject) prior to obtaining informed consent.
- Scenario B: A potential subject is identified, informed consent is obtained for study participation and the subject undergoes screening following consent. Subjects found to be ineligible during screening are then withdrawn from the research.
- Scenario C: A potential subject is identified and informed consent for screening procedures only is obtained. Enrolled subjects then undergo screening procedures and subjects found to be eligible for participation go on to provide informed consent for study participation. Subjects found to be ineligible are withdrawn.
Consent for screening
A key, yet often overlooked, factor in planning for screening provisions is considering whether informed consent must be obtained from potential subjects prior to the conduct of screening procedures. Similar to the age-old chicken and egg dilemma, screening often becomes a question of which comes first, screening or consent?
Recall the regulations for the protection of human subjects require study teams to obtain informed consent before involving a potential subject in research. Also recall a ‘human subject’ is defined by the regulations as a ‘living individual about whom an investigator…(i) obtains information or biospecimens through intervention or interaction…or (ii) obtains, uses, studies, analyzes or generates identifiable private information or biospecimens.’ As such, provisions for consent must be addressed for screening procedures when screening involves:
- Obtaining (i.e., recording, logging, tracking, or otherwise documenting) identifiable information (e.g., recording a name, date of service, or other identifier in a screening log); or
- Conducting study-specific screening procedures (e.g., collecting a blood sample, conducting a physical or neurological exam that is not part of routine care).
If screening does not require the acquisition of identifiable information (e.g., the study team verbally queries the subject or the medical/academic record is reviewed for eligibility without recording any identifiable information, at any point) or the conduct of study-specific procedures, consent for study participation can be obtained following confirmation of eligibility (Scenario A described above).
When consent for screening is required, study teams have traditionally mimicked Scenarios B or C described above whereby screening procedures are either incorporated into the overall study consent (Scenario B) or a separate screening consent, in some cases a verbal consent script, is created to obtain consent for screening procedures only (Scenario C). In other rare instances, a waiver of consent may be justified.
Consent exceptions under the revised Common Rule
Under the revised Common Rule (effective January 21, 2019), study teams have the additional option of requesting a consent exception for certain screening procedures. The revised Common Rule states:
“An IRB may approve a research proposal in which an investigator will obtain information or biospecimens for the purpose of screening, recruiting, or determining eligibility of prospective subjects without the informed consent of the prospective subject or of the subject’s legally authorized representative, if either of the following conditions are met:
1) The investigator will obtain information through oral or written communication with the prospective subject or legally authorized representative, or
2) The investigator will obtain identifiable private information or identifiable biospecimens by accessing records or stored identifiable biospecimens.”
This means that study teams can request an informed consent exception via their study protocol for the IRB to approve, in lieu of obtaining consent for screening purposes provided the screening procedures meet the conditions identified within the regulations (i.e., screening only involves accessing records/stored biospecimens or obtaining information through oral/written communication). Note, however, not all screening procedures will align with these conditions (e.g., collecting blood samples, conducting physical exams). If the study protocol requires screening procedures that do not meet the requirement for a consent exception, informed consent (either written or verbal, as appropriate) must be obtained prior to conducting the screening procedures.
HIPAA requirements
In addition to consent, study teams conducting research under the University of Rochester Medical Center’s covered entity must further consider how they will comply with the Health Insurance Portability and Accountability Act (HIPAA) when screening procedures require the collection of identifiable health information (reference OHSP Policy 702: HIPAA Privacy Rule for additional information):
- When consent for screening is obtained in writing (either in the overall study consent or a separate screening consent form), HIPAA authorization is routinely included within the consent document.
- When consent for screening is obtained verbally, an altered HIPAA authorization must be requested via the study protocol (an ‘altered’ authorization is required when authorization is obtained verbally because, per HIPAA requirements, authorization requires written agreement or a signature).
- When a consent exception or waiver are requested, either a waiver of HIPAA authorization must be requested via the study protocol or the information collected during the screening process must be limited to a limited data set with a data use agreement in place, if the information will be disclosed outside the covered entity.
Conducting screening procedures
Ensuring consent is appropriately obtained for subject screening, when necessary, is only one piece of the subject screening puzzle. Quality improvement, monitoring and inspection reports often site study teams for findings related to enrolling ineligible subjects into the research and/or inadequately documenting subject eligibility. Additional best practices related to subject screening include:
- When identifying inclusion and exclusion criteria in the study protocol, be specific and objective. Consider all possibilities including but not limited to: age, sex, race, diagnosis requirements, method of diagnosis, treatment requirements, existing or previous conditions and therapies, concomitant and disallowed medications, disease severity, pregnancy and fertility, cognitive function, language fluency, ability to perform specific study-related functions/procedures, and ability to provide informed consent.
- To simplify the screening process, state inclusion and exclusion criteria only once within the protocol; do not include inverse criteria in each respective criteria list. Similarly, the process for screening subjects should only be described once in the study protocol. Repeating descriptions of study procedures across multiple sections of the study protocol (e.g., repeating screening procedures in the recruitment methods, consent process and study procedures section) can set study teams up for error when/if the repeated descriptions are not consistent.
- To aid in the screening process, as appropriate, create reference cards, ‘cheat sheets’ or flowcharts for study team members to quickly reference eligibility criterion and scripts for study teams to follow when verbally screening potential subjects.
- Ensure your study documentation demonstrates your compliance with the screening process described in the study protocol, confirms subject eligibility, and accurately identifies screening outcomes (e.g., withdrawal in the event a subject is found to be ineligible).