346. Consent and Early Withdrawal or Cessation of Participation

Updated July 1, 2021

Federal Regulations for Consent Related to Cessation of Participation

The voluntary nature of participation in research requires the investigators to inform each participant she/he/they may discontinue participation in an ongoing research study, without penalty or loss of benefits to which she/he/they may be otherwise entitled (per general requirements for informed consent at 45CFR46.116 item (b)(8)). A participant can leave a research study at any time. When withdrawing from the study, the participant should let the research team know that he/she/they wishes to withdraw. A participant may provide the research team with the reason(s) for leaving the study, but is not required to provide their reason.

Per 45CFR46.116 items (c) (2) and (4), when applicable researchers must inform each participant of:

• the anticipated circumstances under which the Principal Investigator (PI) may terminate a participant’s participation in the study, regardless of the participant's consent; and
• the consequences of a participant's decision to withdraw from non-exempt research and the procedures for orderly and safe termination of her/his/their participation.

Other information and nonbinding recommendations may be found in the OHRP guidance for withdrawal of participants.

The IRB application requires University and affiliate researchers to describe plans both for investigator and participant-initiated withdrawal. The consent form templates and instructions address the requirements for informed consent and discontinuation of participation, including requirements to inform participants of anticipated conditions under which termination of participation may occur.

Reasons for Discontinuation of Participation

Depending on the type of study, the participant may be given a variety of instructions for ending his/her/their participation in the study. For instance, a participant may be given instructions on how to safely stop using study medications. Instructions may also be given on who to contact if there are any questions or concerns that arise after completing the study. The research team may need to have the participant return so that he/she/they can be monitored for any future adverse effects from the study treatments, procedures, or interventions. For evaluation and reporting purposes, researchers may ask participants for their reasons for early withdrawal.

Information about the reasons a participant chooses to end her/his/their participation in the study allows the PI and the IRB to identify potential problems related to the conduct of the research. For example, high withdrawal rates secondary to serious adverse events require:

• re-consideration of both the magnitude and probability of research risks may be greater than originally anticipated and
• re-evaluation of the reasonableness of risks in relationship to expected benefits.

An investigator may terminate an individual’s participation in a research study to:

• protect a participant from excessive risk or risk with a demonstrated lack of benefits (e.g., a participant experiences serious side-effect without the anticipated therapeutic effects), or
• maintain the integrity of the data (e.g., a participant is not following study procedures or may be deliberately providing false information).

Whenever an investigator terminates an individual’s participation in research, the investigator must explain to the participant the reasons for the termination and, as appropriate, other treatment options available to the participant.

The continuing review/progress report form requires PIs to note the number of and summarize the reasons for early withdrawals.

Depending on the screening and enrollment processes, screen failures may or may not comprise a reason for participant withdrawal. For example, screen failures may NOT be noted as withdrawals when informed consent for the primary study is obtained after the eligibility screening and only from individuals determined to be eligible for the study.

Regardless of the reasons for the withdrawal, the PI and the IRB must consider the following:

• procedures for safe discontinuation of participation;
• retention and use of the data already collected about a discontinued participant; and
• the conditions under which the researchers may collect data about the participant following her/his withdrawal from the study.

Safe Discontinuation of Participation

When investigators anticipate unfavorable consequences for participants who withdraw from a research study, both anticipated consequences of and planned safeguards for early withdrawal must be disclosed in the IRB application and consent documents.

Retention and Use of Data Collected Prior to Participant Withdrawal

University and affiliate investigators may retain and use data collected prior to participant withdrawal, including Protected Personally Identifiable Information (PPII) (see IRB Policy Manual Definitions), as long as the uses are consistent with the study purpose and procedures as described in the IRB application and consent documents. If the study involves collection of health information, at the time of withdrawal, the research participant should let the research team know if he/she/they will allow the continued collection and use of his/her/their health;information by the researchers. At its discretion, the IRB may require the PI to include processes for participants to ask that their PPII be removed from the data-set if retention of personal identifiers may pose risks to participants after their withdrawal from the study (e.g., research data involves illegal or stigmatizing behaviors).

This policy does not preclude PIs from voluntarily including procedures for participants to ask that their data be destroyed or excluded from analysis, as long as these processes are described in the IRB application and the research is not regulated by FDA.

NOTE: Participant data cannot be removed from an FDA-regulated study. The data collected about the participant up to the point of withdrawal must remain in the study database.

Discontinuation of Research Activities Following Participant Withdrawal

The investigator must discontinue the following research activities for any participant who withdraws from an ongoing study:

• interacting or intervening with the participant to obtain data about him or her for the research study;
• collecting or receiving (from any source), additional identifiable private information about the participant to be used for the research study; and
• observing or recording (without interaction or intervention with the participant) additional identifiable private information about the participant or her/his behavior to be used for the research study.

Continuation of Research Activities Following Participant Withdrawal

A participant may withdraw from:

• all components of a research study; or
• the primary interventional component of a study while agreeing to the continuation of other research activities to which she/he/they previously consented.

University and affiliate investigators may ask a participant who is withdrawing whether she/he/they wishes to allow follow-up and further data collection subsequent to their withdrawal from the interventional portion of the study.

Follow-up activities may be implemented post-withdrawal under the following two conditions:

1. The participant is informed of and agrees to the follow-up procedures.
2. The follow-up activities are described in the IRB application, and the consent form the participant signed or when applicable, the information sheet provided to the participant.

A participant's agreement to continue with non-interventional components after withdrawal from the primary intervention allows the investigator to complete follow-up activities involving the collection of private information:

• through interaction (e.g., follow-up scans, biometric or physical examinations, interviews, or questionnaires);
• from the participant's medical, educational, or other private records; or from healthcare providers, teachers, or other sources as specified in the application and consent documents.

The PI is responsible for explaining to the participant which non-interventional components will continue.

Participant Withdrawal from Clinical Trials

Clinical trials are designed to evaluate the safety and effectiveness of specific interventions in the management of diseases or disorders. Continued participation in the secondary components of a research study may be particularly important in such trials.

If a participant wants to withdraw from a clinical trial, the PI may clarify if the participant wishes to withdraw from the study entirely, or only from the interventional components. During this clarification, the PI may let the participant know the importance of collecting follow-up safety data about the participant.

Collection of Clinical Outcome or Public Information Post-Withdrawal

When a researcher is also a participant's physician or treating clinician, early withdrawal may trigger the need for follow-up for clinical purposes (i.e., post-withdrawal assessments and documentation of the course of the illness/condition). In such situations, there must be a separation of:

• roles for the researcher serving as clinician; and
• study-related interventions and clinical procedures.

Following a participant's withdrawal from a research study, the researcher-clinician may wish to use information from the clinical follow-up procedures to be used for research. Assuming such a situation was not described in the original application and consent document, the PI must obtain the participant-patients consent for the use of clinical information for the research. The PI must obtain IRB approval for an amendment to the protocol and an addendum to the consent document. The consent addendum would specify the information the researcher-clinical would obtain from the participant's clinical records to use for the research.

If a participant withdraws from the research intervention for a study and does not consent to continued follow-up of associated clinical outcome information, the investigator cannot access the participant's medical or other confidential records requiring the participant's consent, for purposes related to the study.

Under these conditions, the clinician/researcher may:

• review and use information about the participant that was collected before the participant's withdrawal from the study, and
• consult public records (i.e., those establishing survival status) for information about a participant who withdrew.