FDA and OHRP
Jerry Menikoff of OHRP & Jean Toth-Allen of FDA
both presented at a Regulatory Affairs Public Forum at the ACRP Global Conference on Sunday, May 1st.Speaking for FDA were Leslie Ball, MD, Director of the Division of Scientific Investigations (DSI) which initiates the majority of Bioresearch Monitoring inspections at FDA. Also from FDA was Jean Toth-Allen, PhD, Biophysicist, Office of Special Medical Programs. Jerry Menikoff, MD, JD, spoke on the panel as the Director of the US Office for Human Research Protection. The Association of Clinical Research Professionals hosted the forum in a setting more reminiscent of a TV game show than a professional panel that was complete with theme music and multi-colored columns highlighting the stage. However the questions posed were the ones on everyone’s minds and the speakers gave some good answers.
Please note that the Plenary Session on the Regulatory Affairs Public Forum was recorded and is available on the ACRP website for free.
One question brought up the issue of sponsor oversight of outsourced clinical trial responsibilities. Toth-Allen said that the sponsor is ultimately responsible for all of the clinical trial responsibilities and only CROs are specifically mentioned in the regulations. She emphasized the need to have SOPs in place covering how they are going to oversee contracts of vendors and what the contracts should cover. Leslie Ball said that DSI had an increased focus on sponsor and CRO inspections.
Dr. Ball said that she thinks sponsors should look at three qualities when selecting vendors:
1. The overall capability of the organization and staff.
2. That contracts clearly point out who is responsible for specific responsibilities.
3. That the sponsor oversees the vendor’s activities while the trial is ongoing.
When Does FDA Inspect?
Another area of interest was when and where FDA would inspect. Both Leslie Ball and Jean Toth-Allen said that FDA was focusing more on inspections during the actual conduct of the study and not just when a sponsor makes an application to the agency.
Dr. Ball said that with the shift to more sponsor/CRO inspections that FDA inspections were looking at sponsor oversight of ongoing trials. She also said that DSI was developing a risk-based site selection tool that looked at three different levels. First, at the application level, did the application pose certain risks that FDA needed to consider. Then at the trial level, tending to focus on pivotal trials. Then at the site level, were there complaints or a history of non-compliance. She also said that they were looking at data from the application such as the rate of subjects dropping out or very high or very low rates of adverse events.
Dr. Ball also emphasized
Dr. Leslie Ball, FDA
that FDA looked at what they considered important, specifically data integrity for primary efficacy endpoints or key safety indicators, and oversight by the sponsor. She noted that many things that are routinely listed on a Form FDA 483, Inspectional Observations, such as study drug accountability sometimes didn’t find their way to a Warning Letter that focused on items of significance to the approval of the application.
Another interesting discussion was on the topic of online informed consent forms, which are beginning to appear. Jerry Menikoff said it depended on the nature of the study when an online consent might be appropriate. Jean Toth-Allen spoke of the need for a verification process, that the online consent was given by a real person.
Finally the panel discussed electronic medical records (EMRs).
Discussion on Electronic Medical Records in
All three panelists supported the use of EMRs. Toth-Allen said that if an EMR is used in a clinical trial then the institution needs to provide access to verify the record, that it was not acceptable to for monitors to be told that you can’t see it, which elicited a hearty round of applause from the many monitors in attendance. Dr. Ball noted that there were a lot of advantages to EMRS. “You can actually read them,” she said. She also emphasized that EMRs should have the same criteria for clinical trials, that they should be ALCOA
– Attributable, Legible, Contemporaneous, Original and Accurate. She also said that although they may not need to be Part 11 compliant, they did need to have an audit trail so that all changes to the record could be traced.
To view the Regulatory Forum visit the
ACRP Website on the Plenary Sessions
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