Avoiding & Responding to the Most Common IRB Application Stipulations

May 2019 Issue

Author(s):

  • Lin Themelis, MA, CIP
    IRB Administrator
  • Jamie Merrill, MPH, CIP
    IRB Administrator
  • Emily Crowley, MPH, CIP
    Senior IRB Analyst
  • Kathryn Jones, MPH, CIP
    Senior IRB Analyst II

PRINT

 

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 highlights key takeaways from the recent monthly CRRO seminar given by the BMC/BU Medical Campus IRB Analysts on May 8, 2019 on some 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 watch our presentation or view our presentation slides.

As always, if you have questions about a specific study, please email us at medirb@bu.edu or drop by to see us during our weekly drop-in hours.

 

Primary Sources of Stipulations

Two common sources of stipulations are inconsistency and missing information.

Study procedures are often not consistently described across the application, attached protocol, consents and other study materials.

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.

Proofreading the submission for consistency and completeness before submitting can help to avoid a significant number of stipulations.

 

Training & Adding Key Personnel

During initial submission reviews, analysts frequently encounter errors related to the Department Chair/Section Chief role. The Principal Investigator’s superior 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.  Often, this person is 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.

Internal Study Personnel are personnel who are primarily affiliated with BMC or BU Medical Campus and should be added using the Internal Personnel Change Request Form through INSPIR. External Study Personnel are defined as personnel from institutions other than BMC or BU Medical Campus. If external personnel are engaged in human subjects research, then they must be added through an authorization agreement.  Please contact IRB Coordinator, Roz Schomer at roz@bu.edu for study-specific questions about authorization or reliance agreements.

 

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, populate some sections while hiding others.
Of note, the Navigation Menu contains a question about attaching a separate protocol. A separate protocol is required only 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.

An affirmative answer to the separate protocol question collapses the application to avoid duplication of information. The sections of the application that follow must be completed in full--it is not acceptable to refer to the attached protocol in these instances. If you choose to attach a separate protocol when it is not needed, then the IRB may still request that the entire application be completed if the protocol is incomplete.

 

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.

 

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.

 

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.

 

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).

Recruitment materials need to be submitted as final versions and comply with all requirements, such as making it clear that your study involves research and not treatment and not overemphasizing study payment by using big and bolded text.

 

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, 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 mastercode is kept separate 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’s institutional requirements for this kind of data.
  3. Use the right words: Coded means data labeled with a code for which a mastercode exists; De-identified means that you had identifiers but they are entirely and utterly destroyed now (all 18, 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. Generally speaking, BMC and BU both require that you store all research data for at least seven years after closure of your study.

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

 

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 may 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 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.

 

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 if you do not have a Word version available (i.e., sponsor-created protocol).

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.

 

Conclusion

This article conveys 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! Feel free to reach out to us via phone at 617-358-5372, via email (medirb@bu.edu) or in-person at IRB drop-in hours.