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Continuing Review & Changes of Protocol
IRB Member Fact Sheet--Version Date: 6-25-2007
Federal regulations require that IRBs review approved studies on at least an annual basis. Federal regulations also require that IRBs review changes of protocol before they are implemented, unless necessary to eliminate an apparent immediate hazard to subjects. The Common Rule, FDA, and VA regulations governing continuing review of protocols and changes of protocol are generally parallel.
IRB Member’s Role: Continuing Review
Continuing review of research, as required by federal regulations, refers to regularly scheduled complete reappraisals of an on-going research project to assure that: (i) the risk/benefit ratio is still acceptable, (ii) the measures taken to safeguard subjects are adequate, (iii) the approved protocol is followed, and (iv) the project reflects any changes that have been made in the regulations and institutional policies and procedures for human subjects research since the last approval. The HS and MR IRBs conduct continuing review of human subjects research at intervals appropriate to the degree of risk, but not less than once per year. The IRB determines on a protocol-specific basis whether protocols require more frequent than annual review.
The HS IRB and MR IRB use a preliminary review system to evaluate applications for continuing review that will be considered by the full IRB. The IRB administrator, or designee, assigns each application for change of protocol to primary reviewers, who are IRB members and who review the application in a preliminary review session (PRS) held prior to a scheduled meeting of the full HS or MR IRB. PRS reviewers must review the continuing review application to determine whether the research continues to fulfill the criteria for approval of human subjects research. The criteria for approval of an application for continuing review are the same as for initial review:
- Risks to subjects are minimized.
- Risks to participants are minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk, and
- Whenever appropriate, risks to participants are minimized by using procedures already being performed on the participants for diagnostic or treatment purposes.
- Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result from the research.
- Selection of subjects is equitable.
- Informed consent will be sought from each prospective subject or the subject's legally authorized representative and appropriately documented.
- When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
- When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
- When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.
Following PRS review, the continuing review application, current informed consent document and any new proposed consent documents along with a staff reviewer report and the written assessments and recommendations from the PRS for each continuing review application scheduled for review at a particular meeting are sent to the full HS or MR IRB. Copies of protocol files for those continuing reviews scheduled for review are available to all IRB members, including any alternate substituting for an IRB member, from the IRB Office before or during the convened meeting. The full HS or MR IRB then makes the determination whether to approve the application, require modifications in the application, defer the application until additional information is obtained, or disapprove the application.
In some cases, continuing review also may be conducted on an expedited basis. Expedited continuing reviews are conducted by HS and MR IRB staff who are IRB members for studies that fall into one of the expedited review categories specified in the regulations. Studies eligible for expedited continuing include the following types of projects:
- where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects, or
- where no subjects have been enrolled and no additional risks have been identified, or
- where the remaining research activities are limited to data analysis; and
- where research is not conducted under an investigational new drug application or investigational device exemption, but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.
IRB Member’s Role: Changes of Protocol
Any change in an approved human subjects research protocol must be reviewed and approved by the IRB before the change can be implemented by the investigator, except when a change is necessary to eliminate apparent immediate hazards to a participant. The investigator is responsible for ensuring that any changes to the protocol are submitted to the IRB for review before the changes are incorporated into the research.
“Full” changes of protocol are reviewed through the full committee review process. Examples of full changes requiring full committee review include, but are not limited to, escalation in the drug(s) dosage(s); introduction of an additional drug(s); addition of a new subject population; and addition of a new invasive procedure. The HS IRB and MR IRB use a preliminary review system to evaluate applications for full changes of protocol. The IRB administrator, or designee, assigns each application for change of protocol to primary reviewers, who are IRB members and who review the application in a preliminary review session (PRS) held prior to a scheduled meeting of the full IRB. PRS reviewers must review proposed full changes to previously approved research to determine whether the modified research continues to fulfill the criteria for approval of human subjects research. The criteria for approval of a change of protocol are the same as for initial review as detailed above.
Following PRS, materials regarding the change of protocol are forwarded to the HS or MR IRB with the staff reviewer’s assessment and that of the primary reviewers. The full HS or MR IRB makes the determination whether to approve the application, require modifications in the application, defer the application until additional information is obtained, or disapprove the application.
In addition, minor changes of protocol also must be reviewed and approved by the IRB. Federal regulations do not define “minor changes”. UW-Madison defines “minor change” as a change that does not adversely affect the risk/benefit ratio of the study or make it less favorable for research subjects. Examples of minor changes include administrative (non-medical) changes; minor changes to consent or HIPAA form; and addition of study personnel or study sites. HS and MR IRB staff who are members of the IRB conduct reviews of “minor” changes on an expedited basis. If it is determined, through the administrative process, that a modification is not “minor” and must be reviewed by full committee, it will be forwarded to the full committee or returned to the investigator with instructions on how to proceed. Any changes approved on an expedited basis are reported to the full IRB.
For further information about continuing review and review of changes of protocol, please contact the Health Sciences IRBs Office at (608) 263-2362 or consult our website at http://www.medicine.wisc.edu/irb.