Avoiding & Responding to the Most Common IRB Application Stipulations

January/February 2023 Issue

(Note: this article is an update of an article with the same name published in May 2019)

Author(s):

• Lin Themelis, MA, CIP
  IRB Administrator
• Jamie Merrill, MPH, CIP
  IRB Director
• Emily Crowley, MPH, CIP
  Human Research Quality Manager
• Matthew Ogrodnik, MS, CIP
  OHRA Director

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• Introduction
• Primary Sources of Stipulations
• Training & Adding Key Personnel
• Funding Source(s)
• Navigation Menu
• Special Populations
• Design/Procedure
• Risks, Benefits & Justifications for Approval
• Recruitment
• Screening
• Confidentiality
• HIPAA Compliance
• Consent Form
• Data and Safety Monitoring
• Payment and Costs
• Attaching Documents
• Conclusion

Introduction

Submitting to the IRB can be a daunting prospect for both novice and experienced researchers. While each study is different, study teams often encounter similar issues with their submissions.  This article provides tips and tricks on how to avoid the most common pitfalls with your next IRB application. This article is based on a “typical” study and may not apply to studies that you’re currently working on. To dig deeper into these issues, you can also watch a previous CRRO Seminar presentation on this topic, or view the corresponding presentation slides.

Primary Sources of Stipulations

Two common sources of stipulations are inconsistencies and missing information.

Study procedures are often not consistently described across the application, attached protocol, consent forms, and other study materials. When you are completing your IRB application and writing your protocol, please ensure that you cross-check the information in each to ensure that the procedures are described accurately. If you have a separate detailed protocol for an initial expedited or full board study (5th option in Section 4.1 Review Path), then please ensure that you indicate this by checking “Yes” to the Separate Protocol question in Section 8.1 Navigation Menu. If you check “Yes”, the electronic IRB application in the INSPIR system will hide most sections in the IRB application that are redundant with our protocol template. This will help limit inconsistencies between the two. However, you should still be careful to check that there is no conflicting information. Similarly, the study procedures described in the consent form need to match the procedures described in the IRB application and (when applicable) the protocol. Inconsistencies in these materials will result in your study being returned to you for clarifications and corrections, which will delay the final approval.

Missing information is also a common finding. Key information that the IRB needs to make study determinations is often not provided in full; for example:  textboxes in the application are incomplete, or referenced documents are not attached to the submission. Always be sure to read through your application, protocol, and list of documents to double-check that all questions have been answered in full, and that you have not left placeholder language in sections that need to be completed.

Training & Adding Key Personnel

During initial submission reviews, analysts frequently encounter errors related to the Department Chair/Section Chief role. The person to whom the Principal Investigator ultimately reports to is the most appropriate person to fill this role. When the PI is a Department Chair/Section Chief, then this role would still need to be filled by the PI’s superior.  If the PI is a Section Chief, this is most often their Department Chair. Or, if the PI is a Department Chair, the appropriate sign-off is the Chair of the Department of Medicine or Surgery, or, the Dean or Provost.

BMC and BU Medical Campus require that all researchers engaged in human research (i.e., having contact with subjects or their identifiable data) complete formal training prior to starting any research activities. Depending on the type of research, there are several levels of required training. Please see our website for more information on training requirements. Applications will not be approved until all required training has been completed.

Funding Source(s)

If your study does not have external funding, then please either select “Department/Internally Funded” (if the PI is a faculty or staff member) or “Student/Resident/Fellow Research with no External Funding” (if the PI is a student/resident/Fellow and the study is student/resident/Fellow research).

If your study *does* have external funding, then please select one of the other options to accurately reflect the funding source (for example, “Government” for HHS-funded research); and importantly, please add a fully completed entry for each external funder in the Funding Details section. If you do not add a funding details entry for each external funding source, then the application will need to be returned to you so that this can be corrected.

Navigation Menu

The Navigation Menu contains branching logic that generates certain sections based on responses to specific questions. For instance, selecting a separate protocol, or an investigational drug or device, will populate some sections while hiding others.

Of note, the Navigation Menu contains a question about attaching a separate protocol. A separate protocol is required for studies that meet the definition of a clinical trial, and that involve a medical intervention (drug, biological agent or device) or a surgical intervention/procedure intended to modify a health outcome, or, for any clinical trial that is multi-site or receives NIH funding.

Special Populations

In the Subjects section, you need to make a distinction between the “will be recruited” and the “will be targeted” groupings. “Will be recruited” applies if even one member of that group (e.g., minors, pregnant women, prisoners) is anticipated to be a subject. “Will be targeted” is for populations that are the principal focus of your research (e.g., students, homeless, individuals with psychiatric disorders, terminally ill patients). You can incidentally enroll an individual in one of these “will be targeted” groups without prior approval. However, if you know that you will be targeting these individuals, you must indicate so in your application. For both types of groups, you must describe how you will comply with the requirements for additional protections.

This section also contains a question about whether you need to access HIV testing status (both that the test has occurred and the results of the test) prior to obtaining written informed consent from the patient. When answering this question, please carefully consider whether your study involves medical record pre-screening for eligibility; and if it does, whether this inclusion/exclusion criteria pre-screening will involve evaluating HIV testing status. If it will, then you need to check “Yes” and add explicit confirmation that HIV testing status will not be disclosed to any non-BMC research staff member prior to written consent being obtained, in order to demonstrate compliance with Massachusetts state law.

Design/Procedure

The two most common issues the IRB encounters in this section are (1) insufficient detail and (2) copying-and-pasting from a grant submission. This section should be plainly written and provide the IRB with enough detail to understand exactly what will happen during your study.  You need to focus on providing sufficient information to answer the questions in the application, but also avoid confusing and unnecessary detail. Do not copy and paste from the grant application; otherwise, the submission will be returned to you for revision.

This section also requests information about how you will have access to a population that will allow you to fulfill recruitment of your proposed sample size. For an explanation of why this information is important, please review the CR TIMES Feature Article entitled: Fulfilling Your Sample Size: What is Required and Why - May 2021. You need to provide quantitative data to answer this question; for example, the approximate number of patients seen at BMC each year that fit these criteria. If you need assistance with obtaining this type of information, please contact the Clinical Data Warehouse (CDW) for Research.

Risks, Benefits & Justifications for Approval

In this section, list the risks, how they will be mitigated, what the benefits of the study are, and how risks to subjects are reasonable in relation to anticipated benefits. All studies have risks, even chart reviews where there is a risk of loss of confidentiality. It is important to distinguish between direct and indirect benefits. Direct benefits are those experienced by the individual subjects, while indirect benefits are those to science or society at large. Compensation is not considered a study benefit, and, thus, cannot be included in this section.

Recruitment

Explaining how you will recruit subjects is one of the more detailed sections of the application. By far, the most common issue here is that recruitment strategy lacks sufficient information. For instance, “We’re going to recruit from our own patients in the XXX clinic” is not acceptable. An excellent mantra for both the recruitment and consent sections is: “who, where, when and how”. If you need to access medical records or the daily schedule to identify potentially eligible subjects, then make sure the HIPAA section is completed (see the presentation slides for detailed guidance).

Screening

If your study team is interacting with potential subjects before consent in order to confirm eligibility, then you need to describe your screening process. If you are interacting with potential subjects in person or by phone, then you must use a screening agreement (oral or written brief consent script). Here, one of the most common stipulations involves an incomplete screening section; so, take care to read and respond to all the questions and prompts in the sub-sections.

Confidentiality

Arguably one of the most important mechanisms to minimize research-related risk, this section regularly contains four easy-to-rectify mistakes:

1. If the data are coded, then you need to explicitly state that the master-code is stored and secured separately from the coded data.
2. If you’re using identifiable PHI, then you need to note that you will store and transmit this data only on machines that fulfill BMC or BUMC  institutional requirements (depending on the home institution of the PI) for this kind of data.
3. Use the right words: Coded means data labeled with a code for which a master-code exists; De-identified means that you had identifiers but they are entirely removed from the dataset (all 18 identifiers, if HIPAA applies); Anonymous means that you never collected or stored identifiers with your data. Most often, people say “de-identified’ when they mean “coded”.
4. BMC and BU both require that you store all research data for at least seven years after closure of your study. Therefore, please do not state that data will be destroyed in a shorter timeframe..

If you have questions about appropriate data storage methods, then please refer to this CRRO presentation by the Privacy and Security officers of BMC and BUMC, or contact the presenters directly.

HIPAA Compliance

The first question in this section should be checked “Yes” if you will access any protected health information (PHI) prior to obtaining signed HIPAA authorization from the patients’ whose PHI you will access. So, you will need to check “Yes” if you are conducting a retrospective chart review study without consent, or if you are conducting medical record pre-screening to identify potentially eligible patients to approach about the study. In this latter scenario, it is important that all questions in this section are answered only in relation to the data accessed and collected *before* subjects sign the consent form with HIPAA authorization language. Oftentimes, the IRB will need to return the study to you for correction because the information provided in this section address all data collected in the study. For example, this section asks:

When and how will you destroy any identifiers linked to the data?

If you are completing this section because you are conducting medical record pre-screening prior to obtaining signed informed consent, then you should only describe when and how you will destroy identifiers linked to the data that are collected *prior* to consent; for example, describe what you will do with identifiers for patients who are determined to be ineligible, or who decline to participate after being approached with information about the study. The IRB does not need information about all data collected from consenting subjects during the course of the study.

Consent Form

It is important to always use the latest version of the IRB-approved consent templates unless there is a sponsor-provided consent available.

The IRB may still ask your team to revise some of the sponsor language if it does not align with BMC/BU Medical Campus IRB policy. The following points should be kept in mind:

• For Exempt studies, such as studies involving surveys and interviews with adults, a consent statement (“Exempt Information Sheet”) should be used instead of the full consent template.
• Take care to pay close attention to the instructions in the consent template and not to modify approved template language.
• Consent forms should aim to be understandable at an 8th grade level or below.
• Review the signature lines carefully and select only what applies to your study.
• Certificate of Confidentiality language is required for all NIH-funded studies.
• Include the correct headers/logos and contact information found in the template.

Data and Safety Monitoring

There are specific Data and Safety Monitoring requirements depending on the risk level of the study. For minimal risk studies, simply complete the relevant section in the IRB application, stating that Unanticipated Problems, Adverse Events, and protocol deviations will be reported to the IRB as required by IRB policies.  For greater than minimal risk studies, a Data Safety Monitoring Plan is required, which is usually part of the separate protocol.

Payment and Costs

Any payment for participation or reimbursement of travel costs is not considered a benefit. It is important to carefully consider the payment amount, method and timing in research because the payment scheme (depending on the research) may potentially represent undue influence to participate. Cost refers to costs that the subject may be responsible for covering, such as parking or co-pays for clinical procedures; do not describe costs of the research that are incurred by the study team.

Attaching Documents

All study documents need to be submitted as “clean” versions because the IRB cannot approve documents with tracked changes. If possible, please submit all documents in Word formatting. PDF versions are acceptable for most types of documents if you do not have a Word version available (i.e., sponsor-created protocol). However, you must always attach consent forms as Word documents.

For amendments, updated documents must be attached as a revision to the current approved document. This is especially true for consent forms. Attaching modified documents as revisions helps the IRB to compare documents to see changes more clearly.  Also, revisions help to keep track of study changes over time. If updated documents are attached as new standalone versions, then the IRB will likely return your study so that this can be corrected, thus delaying the review.

Conclusion

This article describes the most common stipulations encountered in typical submissions. You can also consult the IRB website for templates and detailed instructions. While these tips and tricks may not apply to your particular study, we hope that it provides basic information that can be used in most studies. Keep in mind that the IRB applies its interpretation of regulations and institutional policies on a study-by-study basis, which means that our guidance and suggestions may also vary from study to study.

Navigating the submission process can be challenging, but remember that we are here to help! Please always feel free to email us at medirb@bu.edu when you have questions about your specific study.