Institutional Review Board for Health Sciences Research (IRB-HSR)

Managing Protocol After Initial Approval

Continuing Review Process

Background Information:  Continuing Review

Projects requiring review more frequently than annually may include:

In such cases, approvals may be granted for time periods less than one year or, as may be more appropriate, for a limited number of subjects over a period not to exceed one year.

Submission for Continuation Review (Protocol Status Reports)

Reopening an Expired Protocol

Aggregate Review of Research Data

The Data and Safety Monitoring Plan (DSMP) template produced using Protocol Builder when a study presents greater than minimal risk to subjects, asks the Principal Investigator (PI) to determine the appropriate frequency and appropriate content for aggregate reviews.

Responses to these template questions can differ widely depending on the type of risks, and the vulnerability of the study population.  It can be frustrating for the study team to determine what answers best suit the type of risk the study presents to their subjects.  In addition, it is important to note that the responses to these questions must be as accurate as possible since Post Approval Monitors (PAM) will be looking for documentation that aggregate reviews are performed exactly as described in the DSMP.  Therefore the PI will want to be sure to select the appropriate frequency and content in the DSMP.

What is an aggregate review?
Aggregate Review is the cumulative review of specific data that might impact the safety and risk/benefit analysis for a study.

Who is responsible for the aggregate reviews?
If there is not another person or body assessing safety of a study on an ongoing basis (medical monitor, DSMB, etc.) then the responsibility for completing these reviews falls to the PI.  If the study has a Data and Safety Monitoring Board the UVa PI will likely NOT be responsible for aggregate reviews.  In this case it is likely that the DSMP should not have the PI checked as the only person overseeing aggregate safety for the study- because the DSMB is responsible for that function.

Determining the frequency of aggregate review?
For studies that are deemed greater than minimal risk (require full board review), there is a question in the Data and Safety Monitoring Plan template about the aggregate review.  The question reads as follows:

Answer this question ONLY if the PI is the ONLY person responsible for overseeing the safety if the study.

How often will aggregate review occur?

The decision regarding the frequency of PI aggregate review must be based on the amount of risk to which subjects are exposed, the likelihood that previously unknown adverse effects might be discovered, and the vulnerability of the population under study.  Again, if the study  has a Data and Safety Monitoring Board the UVa PI will likely NOT be responsible for aggregate reviews.  In this case it is likely that the DSMP should not have the PI checked as the only person overseeing aggregate safety for the study- because the DSMB is responsible for that function.

Recommendations for Annual Aggregate Review:

For studies that are deemed just slightly greater than minimal risk, an annual review is fine.  These studies require full board, but present only slightly greater than minimal risk to the subjects.  Examples of these kinds of studies include:

Recommendations for Monthly Aggregate Review:
For studies that pose significant risk to the subject, a monthly aggregate review would be appropriate.

Some examples of these kinds of studies include:

Recommendations for Aggregate Review performed at Frequencies other than Annual or Monthly:
For studies that do not fall neatly into “slightly greater than minimal risk” or “significant risk”, an alternate timing for aggregate review (every other month, quarterly, every 6 months, etc) may be appropriate.  These kinds of studies may present moderate risk to subjects and include the following:

Determining the appropriate content for aggregate review:

The DSMP template asks the PI to check what items will be reviewed at the time of aggregate review

How do you do an aggregate review?

  1. At the frequency noted in the DSMP for the protocol, the PI will pull the cumulative information collected thus far for the data points indicated per the DSMP (e.g. AEs, Unanticipated problems etc.). The data may be found in individual case files, in a spreadsheet or in a database from which reports can be generated.   How this data is stored and pulled together or generated for aggregate review must be determined by the study team early in the study.
  2. The PI will review all of the data asking the following questions:
    1. Are there any trends noted? (safety, enrollment, early withdrawal, etc)?
    2. Does the risk/benefit profile remain as previously described in the protocol?
    3. Are there any modifications to the protocol and consent that would diminish additional risks, promote enrollment, encourage subjects to complete the study etc. 
  3. The PI needs to make the following decisions based on the aggregate review:
    1. Is it safe for this study to continue as is; or is a modification required OR must the study be closed?

How do you document the aggregate review?

If only annual aggregate reviews are required, a provision is made to document annual aggregate reviews in the Protocol Status Form which is e-mailed out to study teams prior to Continuation review. If this section of the Protocol Status Form is completed, then no further documentation of an annual review is required.

If the aggregate review must take place at a frequency other than annually, then documentation for the aggregate review should include the following:

The Aggregate Review Form is available to assist in documenting the aggregate review. This form or something similar to this form may be used for documentation purposes.

What documentation must be sent to the IRB-HSR?
There is a question in the DSMP that asks how often documentation of aggregate review will be submitted to the IRB.  If you have determined that an annual submission is sufficient, then you need only complete the Protocol Status Form that is sent to you for the continuation review.  No additional documentation needs to be submitted.

If some other frequency has been checked, submit documentation of aggregate reviews to the IRB at the frequency indicated in the DSMP.  The Aggregate Review Form may be used for this purpose.

What must be maintained in the Study Records/Regulatory Files?
Make sure the documentation of your aggregate reviews is safety stored. This documentation will be reviewed during Post-Approval Monitoring.

Last Modified: Monday, 19-Jun-2017 09:00:24 EDT