Washout Period or Withholding/Postponing Standard Treatment Guidance
Version Date: June 16, 2016
The purpose of this document is to provide guidance to research teams regarding requirements for informing the IRB of washout periods or withholding/postponing standard treatment.
Displaying the washout/withholding section
This section will only display when a study team selects the box for “Washout period or withholding/postponing standard treatment” in the “Special Procedures” section of the ARROW application.
The washout/withholding/postponing box should be selected when a study requires washout of medications taken by any or all subjects or the withholding or postponement of standard treatments or medications. The box should be selected for studies in which the withholding or postponement of standard treatment occurs prior to enrollment in the study or after enrollment in the study.
Examples of washout periods that would require inclusion and justification in the application are the washout of psychiatric medications or the washout of medications prior to protocol specific interventions (e.g., lumbar puncture).
Examples of withholding/postponing standard treatments that would require inclusion and justification in the application are withholding of a standard treatment that could otherwise be taken while on study for scientific purposes or the postponing of a standard treatment for a period longer than might occur as part of clinical care.
The “Washout period or withholding/postponing standard treatment” box generally does not apply to treatment studies when the washout or withholding/postponement of treatments are considered to be eligibility criteria and are assumed to be clinical decisions made outside of the study. An example of this would be a clinical trial that excludes individuals currently taking anticoagulants. In this example, the IRB would consider the washout or withholding/postponement of anticoagulants to be a clinical determination made between the subject and their clinician in order to take part in the clinical trial.
Completing the washout/withholding section questions
Question 1.2: Will this study involve washing out, withholding, or postponing standard treatment?This response should be answered “Yes” if washout/withholding/postponement will be performed as part of the research. This includes situations in with the washout/withholding/postponement occurs before screening and is not a clinical decision.
Question 1.2.1: If yes, describe what standard treatment will be washed out, withheld or postponed.This response should include a detailed description of the treatment or medications that will be washed out, withheld, or postponed and whether this will apply to all or some subjects. A detailed description of how long the washout/withholding/postponement is and if it is in consultation with a primary care physician should also be included. In addition, a description should be included as to whether any over-the-counter drugs, such as aspirin, are included in the washout/withholding/postponement period or can still be taken by subjects.
Question 1.2.2: If yes, provide justification for the washout, withholding, or postponing of standard treatment.This response should describe the justification for the washout, withholding, or postponement that is required. A detailed justification is required so the IRB can adequately assess the risks and benefits of the washout/withholding. Justification may be for scientific or subject safety reasons.
Question 1.2.3: If yes, explain how subjects will be monitored for safety during this period.This response should explain the procedures in place to monitor subject safety during the washout/withholding period. The monitoring procedures will vary based upon the risk level of the washout/withholding and the amount of time that the washout/withholding period will occur. For withholding/postponement, the monitoring plan should include information on complications, such as disease progression, will be monitored. A description of stopping rules may be required for situations where subjects will be withdrawn from the study so that standard treatment can be resumed or started. In addition, the IRB may expect consultation and sign-off with the subject’s primary care provider in certain situations.
Other sections of the application to address washout/withholding
The following sections of the application will also need to address washout, withholding, or postponing:
Section 5 Research Design and Procedures: Continued
If the washout/withholding involves a standard treatment that would be considered an alternative to participation or represents how the patient population is treated clinically, the standard treatment should be described in this section.
Section 6 Risks and Benefits
If the washout/withholding presents any potential physical risks to subjects, then these risks need to be described in the “Risks: Physical Interventions” section of the application. Potential physical risks include withdrawal symptoms, increased risks of adverse events related to washout/withholding, and/or potential for disease progression.
Section 10 Informed Consent
Subjects should be informed about the washout/withholding requirements in the consent form, including any requirements during screening. This would include addressing the procedures for washout/withholding and the risks associated with stopping or postponing standard treatment. If subject monitoring will occur, then the monitoring plan should also be detailed.
Elements of a Protocol Guidance
Review of FDA-Regulated Research Policy
Completing the Special Considerations and Procedures Page in ARROW