Guidance from the UI Health Care Investigational Drug Service
Herky Hint: Vulnerable Subject Populations
Research with Prisoners: Subpart C and Related UI Policies
Guidance From the UI Health Care Investigational Drug Service
The Investigational Drug Service (IDS) is charged by the UI Health Care Pharmacy and Therapeutics (P&T) committee to “review and support investigational medication studies to ensure patient safety and adherence to UI Health Care policies.”
The Investigational Drug Service pharmacists must conduct two reviews:
1) IDS Review to ensure safe handling, preparation, and storage of investigational medications, and
2) P&T Safety Review of trial documents to ensure all medications are used safely in research subjects.
The responses provided in HawkIRB Section V.1. – 8. will trigger P&T and IDS reviews. While new applications may contain some missing information, modifications frequently result in inconsistencies that slow the review process.
A safety review must be done by the IDS if the study involves
the administration of investigational new drugs or drugs that are given "off-label",
FDA approved drugs that are given as a component of a research protocol,
any other substance that is ingested (with the exception of enteral feedings such as baby formulas, unless they contain a non-Generally Regarded as Safe [GRAS] ingredient), or
any other substance that is injected, inhaled, or applied to the body.
To speed the review and approval process, IDS staff provides the following guidance:
Complete the Investigational Drug Study Standard Charge Worksheet (IDS) before attaching it to HawkIRB. Empty or incomplete IDS charge sheets frequently slow the approval process.
Generate the IDS charge sheet in HawkIRB (under “Other Review Attachments” on the Application Index) to use the version for the current fiscal year.
Provide accurate information in Section XIV of HawkIRB modification forms that trigger P&T/IDS reviews:
Section XIV.1 (new drugs added) (Correlates to changes in Section V.8)
Section XIV.4 (change in therapy dose or duration)
Section XIV.7 (new risks) (Correlates to changes in Section VIII.)
Section XIV.10 (changes to Investigator Brochure or package insert)
Recent instances of inaccurate responses to Section XIV.4 are addressed in the following scenarios:
Scenario #1: Protocol change in the order of administration of study medications.
XIV.4 should be answered yes.
Scenario #2: Protocol change in the amount of time allowed before the study drug could start.
XIV.4 should be answered yes. XIV.10 may also need to be yes as it is likely the Investigator’s Brochure will be updated as a result of this.
Attach the Pharmacy Manual if one is available from the sponsor. If this is not provided up front, please request it from the sponsor and attach it in the ‘P&T IDS’ section on the Other Review Attachments page. Note: This is not an IRB requirement. The IRB does not review nor “approve” attachments in the Other Review section(s) as these are specific to the designated committee(s). . The pharmacy manual provides specific information IDS needs for ordering medications, receiving shipments, handling, storage, dispensing and preparation of investigational drugs for the study.
Provide accurate and complete information in the Cost section of the Informed Consent Document. P&T IDS reviews and may provide feedback for the Cost section during their review of a project. There can be delays in approval if the consent form is not clear and consistent with the protocol and the rest of the HawkIRB application. Note: the Cost section is also reviewed by Research Billing Compliance.
Additional information is available on the P&T Committee page of the Human Subjects Office website.
Herky Hint: Vulnerable Subject Populations
By Rachel Kinker, MPA
The Federal regulations (45 CFR 46, Subparts B, C and D) mandate the protections for vulnerable subject populations in research, including; pregnant women and fetuses, children and prisoners. Guidance regarding vulnerable subjects is also provided in Section II, Part 7.C-N of the UI IRB Standard Operating Procedures (SOP) & Researcher Guide. Vulnerable subjects are addressed in the HawkIRB application in Section VI.
Items VI.1 through VI.5.
The first questions in section VI. ask about adult subjects. The consent process for adults is also required in section VII.D.29.
Items VI.6 through VI.12.
The second group of questions in section VI. ask about child/minor subjects.
If children are included in the study population, child assent and parental consent will need to be described in section VII.D.30 and uploaded to the application.
Item VI.13: Subject Population
Describe the subject population(s)
If there is only one subject population, indicate that in the response
If there are multiple subject populations describe each
Indicate how subjects are selected
Include any descriptions of control group(s)
The description in this section should all be in lay person language
Specify the inclusion and exclusion criteria for each group
Specify the inclusion and exclusion criteria if it varies by subject population
Responses should be consistent throughout the application, specifically in section VII.D Project Description, recruitment, enrollment, and consent.
Note: VA Research involving subjects with PTSD will have additional protections and precautions.
Item VI.26: Pregnant Women
Respond ‘yes’ if the project is about pregnant women or if the study is specifically recruiting women based on their pregnancy status.
Indicate ‘yes’ if the study may want to collect data about the pregnancy/outcome of a female partner of a male enrolled subject. The pregnant woman may need to be enrolled in the study depending on the information collected
Select ‘no’ if women who are pregnant may be enrolled but the study is not about pregnant women
Note: Pregnant women cannot be enrolled in studies being conducted at the VAMC
Item VI.27: Fetuses
If obtaining medical record information about the fetus, it is likely medical record information about a pregnant woman, in which case VI.26 would be ‘yes’
Note: fetuses cannot be enrolled in studies conducted at the VA
Item VI.37 Prisoners
If ‘yes’ is selected, the project will require review by a Prisoner Advocate during the IRB review process.
Research conducted with prisoners from the Iowa Department of Corrections (IDOC) has specific requirements. The Principal Investigator (PI) will need to contact the IDOC research director to receive the document outlining the proposal requirements.
Template language regarding prisoners must be included in the Informed Consent Document
If conducting a longitudinal study (that was not previously approved to enroll prisoners) and a subject becomes a prisoner during the study, a modification form must be submitted and the response to VI.37 must be changed to ‘yes.’ The modification must be approved before the subject can continue participation, or they must be withdrawn from the study.
Note: For VA projects, a category will open on the Attachments page of the HawkIRB application requesting a Chief Research and Development Officer (CRADO) waiver. Prior to submission, the application must have a completed and attached waiver from the CRADO.
Items VI.38 to VI.45 require descriptions of the study procedures and additional precautions in place to protect the rights and welfare of prisoners as subjects.
For more information about prisoners as subjects, see this month's IRB Connection article.
Research with Prisoners: Subpart C and Related UI Policies
Under the “Criteria for IRB approval of research” in the federal regulations of the department of Health and Human Services (HHS) (45 CFR 46.111(a)(3), include the requirement to assess the equitable selection of subjects. The IRB is instructed to “be particularly cognizant of the special problems of research that involves a category of subjects who are vulnerable to coercion or undue influence…”
The HHS regulations contain additional subparts that address specific protections required for vulnerable populations including pregnant women and neonates (Subpart B), prisoners (Subpart C), and children (Subpart D).
The focus of this article is Subpart C, the related UI policies, and additional requirements from the Iowa Deportment of Corrections (IDOC).
45 CFR 46 Subpart C
For research involving prisoners, HHS regulations specify that the IRB must be certain that specific conditions are met for biomedical and behavioral research conducted or supported by HHS:
Permissible Research Category: The research must fall within one of the categories allowed under §46.306(a)(2).
No Undue Influence: Any benefits offered to prisoners for participating must not be so significant that they impair the prisoner’s ability to assess the risks and make a voluntary decision.
Comparable Risk: The risks involved must be similar to those that non-prisoner volunteers would accept.
Fair Subject Selection: The process for selecting participants must be fair and free from manipulation by prison staff or inmates. Random selection is required unless justified otherwise.
Clear Communication: Information about the study must be presented in a language that is understandable to the prisoner population.
Parole Neutrality: Participation in the research will not influence parole decisions, and this must be clearly communicated to the prisoners.
Post-Study Care: If follow-up care is needed after the study ends, appropriate arrangements must be made, considering the varying lengths of prisoners’ sentences.
The types of research that may be conducted with prisoners under 45 CFR 46.306(a)(2) are:
Criminal Behavior and Incarceration Studies: Research on the causes, effects, and processes of incarceration or criminal behavior is allowed, as long as it poses no more than minimal risk and inconvenience to the participants.
Institutional and Sociological Studies: Studies focusing on prisons as institutions or prisoners as a population are permitted, again provided they involve no more than minimal risk and inconvenience.
Research on Prisoner-Specific Conditions: Research on issues that particularly affect prisoners (e.g., hepatitis, drug addiction, sexual assault) is allowed, but only after the Secretary of Health and Human Services consults with experts in relevant fields (e.g., penology, medicine, ethics) and publishes a notice of intent to approve the research in the Federal Register.
Health and Well-being Interventions: Research aimed at improving the health or well-being of prisoners is permitted. If the study involves assigning some prisoners to control groups that may not benefit, it must also go through expert consultation and public notice before proceeding.
UI Guide
When conducting research with prisoners, UI policy required that the informed consent document include a section addressing the fact that participation or non-participation in the research will have no effect on the duration of incarceration or terms of parole. (UI Investigator’s Guide/IRB Standard Operating Procedures Section II, Part 7.N.)
Iowa Department of Corrections (IDOC)
For research that will be conducted with prisoners within the Iowa Department of Corrections, approval from the IDOC research director is required. The Principal Investigator (PI) will need to contact the research director to receive the document outlining the proposal requirements.
Sarah Fineran, M.A. Research Director
Central Office
Iowa Department of Corrections
510 E 12th Street, Des Moines, Iowa 50319
Direct Line: 515-725-5718
The IDOC proposal submission must be completed in its entirety and submitted to the IDOC. The submission will require either a copy of a pending or IRB approved application with the completed IDOC proposal. Once IDOC approval has been received, a copy of their approval must be attached to the HawkIRB Application to proceed with the IRB review of adding a prisoner population.
For additional information about research with prisoners and HawkIRB, see this month’s Herky Hint.
Questions about this topic? You can email the HSO Education and Outreach team or come to Office Hours to speak directly to a member of the HSO team.
Have an idea for an IRB Connection newsletter article? Let us know!