NIH Investigator Manual for Human Subjects Research

Chapter 8 - Subject Withdrawal from Research

Overview

Key points

Participants have the right to withdraw from (i.e., discontinue participation in) research at any time.
It is your responsibility to ensure that timely and accurate documentation relating to withdrawal of a participant is noted in the electronic medical record.

What does it mean when a participant withdraws from all parts of my research study that is not FDA regulated?

When a participant decides to withdraw from all components of a research study, you must discontinue research activities involving the participant's participation such as the following:

Interacting or intervening with the participant in order to obtain data about for the research study (e.g., administering an experimental drug, performing a tissue biopsy, drawing blood, etc.).
Obtaining additional identifiable private information about the participant for the research study by collecting or receiving such information from any source.
Obtaining additional identifiable private information about the participant for the research study by observing or recording private behavior without interacting or intervening with the participant.

What happens when a participant wants to withdraw from the primary intervention of the study but wishes to continue other research activities?

Sometimes, a participant wants to withdraw from the primary interventional component of a study but is willing to continue other research activities described in the IRB-approved protocol and informed consent document that involve participation of the participant, such as the following:
- Obtaining data about the participant through interaction with the participant (e.g., follow-up interviews, physical exams, blood tests, or radiographic imaging); or
- Obtaining identifiable private information from the participant's medical, records or from the participant's healthcare providers.
- When a participant's withdrawal request is limited to discontinuation of the primary interventional component of a research study, research activities involving other types of participation for which the participant previously gave consent may continue.
Continued participation in secondary components of a research study may be particularly important in clinical trials designed to evaluate the safety and effectiveness of specific interventions in the management of diseases or disorders. For this reason, the Office for Human Research Protections (OHRP) guidance on this topic recommends that when a participant decides to withdraw from a clinical trial, the investigator conducting the clinical trial should ask the participant to clarify whether they wish to withdraw from all components of the trial or only from the primary interventional component of the trial. If the latter, research activities involving other components of the clinical trial, such as follow-up data collection activities, for which the participant previously gave consent may continue.
OHRP also recommends that the investigator explain to the participant who wishes to withdraw the importance of obtaining participant follow-up safety data.
For example: Consider an IRB-approved clinical trial testing the safety and effectiveness of an experimental chemotherapy regimen in participants with lung cancer that involves the following sequential procedures for each participant:
- Intervening with the participant by administering up to six monthly cycles of the experimental chemotherapy regimen.
- Intervening with the participant by performing follow-up scans at intervals defined in the protocol.
- Obtaining information about the participant's health status through interviews and physical examinations during the treatment phase and after completion of the investigational interval as defined in the protocol.
- Analyzing data that includes identifiable private information about the participant to determine complete and partial response rates following the experimental chemotherapy.
  THEN
- The participant tells the investigator that they want to withdraw from the study after the second monthly cycle of the experimental chemotherapy regimen because of unacceptable side effects.
- The investigator may then ask the participant if they are willing to undergo the follow-up scans, interviews, and physical examinations that were described in the IRB-approved protocol and in the informed consent document signed by the participant.
- If the participant agrees, these follow-up activities involving the participant may continue.

What happens if, as an investigator, I decide to terminate a participant's participation out of concern that the primary research intervention is exposing the participant to an unacceptable level of risk?

If you decide to terminate a participant's participation because of the concern that the primary research intervention is exposing the participant to an unacceptable level of risk, provide them with reason/s for this action. It is recommended that you also explain to the participant the importance of obtaining follow-up safety data.
Ask the participant whether they are willing to participate in other research activities described in the subject's signed informed consent document, such as:
- obtaining data through interaction with the participant; or
- obtaining identifiable private information from the participant's medical records or healthcare providers.
If the participant agrees, these other research activities for which the participant previously gave consent may continue.

What should be documented when a participant withdraws from a research study?

Document whether the withdrawal of the participant resulted from a decision by the participant or by the investigator, and the reasons for the withdrawal, if known.
Document whether the withdrawal was from all components of the research study or just the primary interventional component.
Document any follow-up that is required in the protocol and ensure that any and all post-withdrawal follow-up is completed as indicated in your research protocol.
Ensure that your documentation in the electronic medical record system is complete, accurate, and contains all pertinent dates relating to events that resulted in the withdrawal of the participant, especially the date of withdrawal from your research study.

May I retain and analyze date already collected about a participant who withdraws from my research study or whose participation is terminated by the investigator?

The OHRP guidance on this topic interprets the HHS regulations as allowing investigators to retain and analyze already collected data relating to any participant who chooses to withdraw from a research study or whose participation is terminated by an investigator without regard to the subject's consent, provided such analysis falls within the scope of the analysis described in the open IRB-approved protocol. This is the case even if that data includes identifiable private information about the subject.

Can investigators honor participants' requests to have their data excluded from any analysis?

For research not subject to regulation and review by FDA, investigators can choose to honor a research participant's request that the investigator exclude the participant's data from any analysis. For example, an investigator studying social networks in a community may agree to omit all of the data they have collected from a subject in the study at the request of that subject.

What are investigator responsibilities when a participant withdraws from a research study that is FDA regulated?

When a participant withdraws from an FDA-regulated clinical trial, the data collected on the participant to the point of withdrawal remains part of the study database and may not be removed. Information on this process is addressed in the FDA's Guidance for Sponsors, Clinical Investigators, and IRBs Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials the details of which are described in the next few bullets.
As an investigator, you may ask a participant who is withdrawing whether they wish to provide continued follow-up and further data collection after withdrawal from the interventional part of the study.
- Under this circumstance, the discussion with the participant would distinguish between research interventions and continued follow-up of relevant clinical outcome information, (e.g., medical course, laboratory results obtained via chart review), and address the maintenance of privacy and confidentiality of the participant's information.
If, in this circumstance, the participant agrees to continued follow-up of associated clinical outcome information as described above, you must obtain the participant's informed consent for this limited participation in the study (assuming such a situation was not described in the original informed consent form). In accordance with FDA regulations, IRB approval of informed consent documents would be required.
If a participant withdraws from the interventional portion of a study and does not consent to continued follow-up of associated clinical outcome information, you must not access the participant's medical or other confidential records for study-related purposes. However, you may review study data related to the participant collected prior to the participant's withdrawal from the study, and may consult public records, such as those establishing survival status.

Chapter 9 - Reporting Research Related Events or New Information to the IRB