Completing a first-rate review

Essentials of a Good Reviewer

  • Knowledgeable of the regulations, research, and the IRB process
  • Thorough
  • Thoughtful
  • Collaborative with investigators, the IRB staff, and colleagues on the panel
  • Reasonable

The IRB Mission: To protect the rights and welfare of research participants

The IRB is charged with the responsibility of reviewing and overseeing human subject research. The IRB review process is designed to protect the rights and welfare of human subjects by ensuring equitable selection of participants, assuring adequate informed consent, assessing and minimizing risks and maintaining privacy and confidentiality.

How IRBs Got Started

  • Tuskegee Syphilis Study came to light in the early 1970’s
  • National Commission created by Congress to develop principles and policy for research oversight (the Belmont Report)
  • Peer review (i.e. the IRB) is established as an essential component of research ethics
    • Informed consent
    • Investigator integrity

The Office for Human Research Protections

OHRP is an office within the Dept. of Health & Human Services (DHHS) that deals with the ethical oversight of research.

Tip for interpreting the regs: “Know the lingo”

  • “Must” = Required
  • “Should” = Recommended or Suggested

Title 45 Code of Federal Regulations, Part 46

45 CFR 46 consists of Subparts A-D:

  • Subpart A: “The Common Rule”
  • Subpart B: Additional protections related to research involving fetuses, neonates, and pregnant women
  • Subpart C: Additional protections related to research involving prisoners
  • Subpart D: Additional protections related to research involving children

Key Points to Consider

Risk

Is the risk to the participant minimized? Have the investigators done everything they can to ensure the participants are only exposed to risk absolutely necessary to conduct the research?

Validity

Will the study yield results that matter?

Consent

Is the consent document clear & easy to understand? Is the consent document written appropriately for the population being studied?

Assessing Risk

Minimal Risk

The probability and magnitude of harm and discomfort anticipated in research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological tests

Greater than Minimal Risk

Not minimal, or “less than” minimal risk.

Minimizing Risk (45 CFR 46.111)

How do we ensure the risks to participants are minimized?

  • Use procedures consistent with sound research design and which do not unnecessarily expose subjects to risk
  • Whenever appropriate, use procedures already being performed on the subjects for diagnostic or treatment purposes

The Risk/Benefit Ratio

The risk/benefit ratio is the comparison of the risk of a situation to its related benefits. For research that involves more than minimal risk of harm to the subjects, the investigator must assure that the amount of benefit clearly outweighs the amount of risk.

"The job of the IRB is toevaluate ethics... it has no business commenting on the science of a research study."

Validity

45 CFR 46.111

In order to approve research, risks to subjects are minimized by using procedures which are consistent with sound research design. Ethical science is good science.

It is unethical to pose any risk to subjects if no valid results will be obtained from the project.

Declaration of Helsinki (2000)

Human research must conform to accepted scientific principles and be based on thorough knowledge of the literature. Human research should only be done if the importance of the objective outweighs the risks and burdens to participants.

When Should the IRB Require a Change in the Study Design?

If a change in the study design will meaningfully reduce the risk to participants without compromising the study results, the Board should not approve the study until the change is made.

Note: If the study is less than minimal risk and the design is flawed (but not fatally), there is no real ethical justification for the IRB to require mandatory revisions to the study design (For example, undergraduate student research projects).

Consent

  • Is there a thoughtful and thorough plan in place to document informed consent?
  • Is the process of obtaining consent adequately described?
  • Have any waivers been requested? Are they approvable/appropriate?
  • Are all of the required elements of informed consent present?
    • Your Reviewer Checklist, the IRB consent template, and the IRB staff will help you with this.

Criteria for Approval of Research

  • Risks are minimized
  • Risk/Benefit Ratio is reasonable
    • Risk/Benefit Ratio: The comparison of the risk to its related benefits.
    • Benefit: Includes direct benefit to the participant, and anticipated benefit to society.
  • Equitable selection of participants
  • Informed consent is obtained as needed
  • Consent is documented as required
  • Data is monitored to ensure safety of participants
  • Privacy and confidentiality is protected
    • Privacy: People. Are embarrassing or sensitive activities conducted in a private room? Are research staff trained not to use participant names in public hallways? Etc.
    • Confidentiality: Data about people. Are the laptops being used for data entry encrypted? Is the office where the charts are stored locked at all times?
  • Vulnerable populations are protected

Conducting a Review: Design Your Own Systematic Method

Establish a routine for reviewing the application. For example:

  1. Skim the Consent Document(s).
  2. Don’t worry too much about taking notes or making revisions, just get an idea of what’s going on in the study...
  3. Read the Protocol Application
  4. Read the supporting documents thoroughly. Take notes as needed.
  5. Re-read the Consent Document(s) carefully. Make sure the document makes sense now that you are familiar with the rest of the application. Are participants being informed of everything they need to know?
  6. Complete the appropriate checklists.

Requesting Revisions

Will a change in the application be likely to improve the welfare of research subjects to a meaningful degree? If not, approve the study without the change; if so, require the change be made prior to approval.

Are my revisions clear? The IRB staff will be communicating your requests to the study team. Make sure it is clear what you are asking for.

Don’t worry too much about correcting typos, formatting, etc., unless the correction will significantly improve the document or change the meaning of the document. Revisions should be substantive and meaningful.

Enter Your Review

Make sure you submit your checklist. This will be the signal to your coordinator that you are done with your review. The coordinator will use your checklist as a guide to draft the minutes.

Presenting Your Review

New Study Application

Primary Reviewer:

  • Limit the summary of the study to 1-2 minutes
  • Be precise about the changes required to the study
  • End your presentation with a recommendation for the vote (pending the secondary reviewer’s comments)

Secondary Reviewer:

  • Focus on any areas of disagreement with the primary reviewer
  • Discuss the Consent Document and consent process
  • End your presentation with a recommendation for the vote

Continuing Review Application

  • Summarize the study (1-3 sentences)
    • Progress of the study
    • Enrollment status
      • Open/closed, suspended
      • Over/under accrued
    • Number of participants accrued
  • Have there been any adverse events (AE) or unanticipated problems (UP) since the last continuing review? Has any new information emerged that changes the risk to participants?
    • DSMB findings, if applicable
    • Withdrawals, complaints, multi-center reports, etc.
  • Provide a summary of any significant Amendments since last review. Have any of the changes required revisions to the Consent Document?
  • Have there been any significant changes to the Consent Document since the last continuing review?
  • Is the document still accurate and appropriate?

Modification Application

  • Summarize the study (1-3 sentences).
  • Describe the changes that are being requested.
  • State whether or not the changes will affect the risk/benefit ratio of the overall study.
  • State whether or not the changes are acceptable/approvable.

The Board Meeting

A place to make decisions, not gather information

Ask questions before the meeting; contact the study team, IRB staff, and fellow board members. Come with your revisions ready to go.

Keep your meeting coordinator informed. If you contact the study team, make sure your coordinator knows what’s going on. They are the final gate keepers that ensure your revisions have been included in the final version of the application!

Deferring a Study

If I disapprove a study, what happens?

The study is returned to the study team for additional revision. The study comes back to the same panel and reviewer the following month for re-review.

Expedited Review

  1. Coordinator assigns an expedited action to a designated reviewer
  2. Reviewer receives a notice via email that they have been assigned to review the application
  3. Expedited reviewer completes appropriate checklist(s) and sends them to the coordinator
  4. If needed, revisions are requested from the study team by the Coordinator
  5. Expedited reviewer or coordinator reviews revisions, depending on nature of changes
  6. Coordinator completes processing, sends determination letter to PI

You will likely be designated as an Expedited Reviewer in about 2 months.

Hot Discussion Topics

Some topics get more discussion time during the meeting than others... It’s helpful to have members in the room that really know their stuff about these issues. The IRB staff can help.

  • Vulnerable populations
    • Child Categories
    • Participants with diminished cognitive capacity/LARs
  • Waivers
    • Waivers of parental permission
  • Randomization to placebo-only arm
    • Placebo guidelines
  • DSMPs
  • Research-related injury/sponsor liability
  • IND/IDE
  • Tissue/Specimen Banking