At times, a Sponsor may provide a site with a memo allowing the site to enroll a patient who does not meet all inclusion or exclusion criteria. Or a Sponsor may give the site pre-approval to deviate from the protocol-defined visit windows. Is this waiver enough? Would the investigative site be covered in the event of a federal audit?
What is in the Regulations?
- 812.150 (a) (4): Deviations from the investigational plan
- Prior approval by the sponsor is required for changes in or deviations from a plan, and if these changes or deviations may affect the scientific soundness of the plan or the rights of the subjects, IRB approval is also required
- 812.35 (a) (1): changes in the investigational plan requiring prior approval
- A sponsor must obtain IRB approval prior to implementing a change to the investigational plan
- 312.66: Assurance of IRB review
- The investigator shall assure that he or she will promptly report to the IRB all changes in the research activity and that he or she will not make any changes in the research without IRB approval, except where necessary to eliminate apparent immediate hazards to human subjects.
In addition to the regulations, the Biomedical Monitoring (BIMO) checklist states the following:
- Verify the Investigator followed the study protocol approved by the IRB
- Limited prospective exceptions to the protocol (e.g. agreement between the Sponsor and Investigator to enroll a single subject who does not meet all inclusion/exclusion criteria), like protocol amendments must be reviewed and approved by the IRB prior to implementation.
A review of FDA warning letters indicated investigative sites and Sponsors are being cited by the FDA for failure to obtain IRB approval prior to implementing approved protocol waivers. Various citations are listed below:
- Although you received a letter from the Sponsor’s representative that permitted you to conduct testing outside of the protocol, you never sought or received IRB approval to deviate from the protocol.
- The protocol included a provision that selection criteria maybe waived by the Sponsor-Investigator if approved by the IRB on a case-by-case basis. You failed to obtain advanced IRB approval.
- You received an email from the Sponsor stating it is “ok to ship samples on the next day following collection.” You did not, however, seek or obtain approval from the IRB for that protocol deviation.
It is easy to think that if the Sponsor allowed a waiver or deviation, then that’s enough. Studies move quickly and enrollment is so important – no one wants to miss out on enrolling a potential subject. However, it’s important to ensure all regulations are followed when conducting clinical research – whether you’re the sponsor or the site.
We know this is a hot topic in clinical research. Please share your experiences with us.
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