Managing Research Study Compliance Flashcards
What is source documentation?
The source documentation is the complete medical record of the subject before, during, and after the trial.
What are examples of case histories?
case report forms and supporting data including, for example, signed and dated consent forms, medical records including, progress notes of the physician, the individual’s hospital chart, and the nurses’ notes.
The case history for each individual shall document that informed consent was obtained prior to participation in the study.
What is Investigational Product Accountability (IP)?
To be accountable for the IP includes, but is not limited to, documenting the conditions under which the test article was shipped, stored, administered, returned, and/or destroyed along with any special labeling or quality control measures that may be required
Examples: Investigator Responsibility and maintaining dispensing and accountability log
What is an adverse event AE?
-Any untoward medical occurrence
-Patient or clinical investigation subject
-administered a pharmaceutical product
-does not necessarily have to have a casual relationship with treatment
What are examples of AE?
- Any unfavorable and unintended sign (including abnormal laboratory value
- Any symptom
- Any disease
- Temporarily associated with the use of a medical product
- Whether or not considered related to the medical product
What is a suspected adverse reaction?
An AE for which a casual relationship to the investigational product is at least a reasonable possibility, i.e- a causal relationship can not be ruled out
What is an unexpected adverse event or adverse reaction?
It’s when there is not identified in nature, severity, or frequency in the current Investigator’s brochure.
-Nature: the event has not been reported previously
-Severity: prior reports were of mild intensity, but the current event is of moderate or severe intensity
-Frequency: In the investigator’s Brochure, the frequency was 1% but has increased to 5% in the current study
What is a suspected and unexpected adverse reaction (SUSAR)?
An adverse reaction that is both serious and unexpected.
FDA Form 3500
The sponsor must notify the FDA and all the participating investigators of any adverse events associated with the use of a drug that are both serious and unexpected.
*This should be done as soon as possible but no more than 15 calendar days after the sponsor’s initial receipt of information.
What must be reported to the FDA within 7 calendar days?
An unexpected fatal or life-threatening experience associated with the use of the drug. Followed by a written report no more than 15 calendar days after the initial receipt of the information.
What does the FDA have the authority to inspect?
-clinical investigators
-Institutional Review Boards
-Sponsors/Monitors
-Contract Research Organizations
-Other entities submitting clinical data in an NDA
How will the FDA inspect Sponsors?
-How were data managed, verified, and quality assured?
-Were statisticians qualified by training and experience?
-Was the statistician analysis plan followed?
What are the types of FDA Investigator inspections?
-PDUFA-Related Inspections
*“Routine” Inspections
-Triggered by submission of an NDA (NME, pivotal studies not conducted in the US, only foreign data)
*Direct Inspections
-“For cause”
-Triggered by allegations that raise concerns regarding data integrity or the rights, welfare, and safety of study subjects have been compromised.
What are potential inspection “Triggers”
-Participation in the pivotal study
-High enrollment
-Irregularities in drug management
-A high percentage of subjects excluded from the per-protocol population
FDA Inspection-Investigators
-Investigator (PI) notification
-Typically, a phone call 3-5 days in advance from the inspector
-Scheduling via phone call or email
-Data are determined by the inspector
-FDA investigator arrives and presents picture ID and notice of inspection (Form FDA 482)
-Introductory meeting
What will happen at the FDA inspection?
*Interview of key personnel
-PI
-Coordinator
-Ancillary groups (pharmacy, lab)
*Inspection of records
-Regulatory files
-Case files, including data
-IP documentation
-SOPs
*Facility Tour
*Exit interview, issuance of summary of observations (Form FDA 483)
What is the result of the inspection?
-Investigator written response to 483 within 15 days
-Report written by Inspector
-Report evaluated by the FDA center assigning the inspection; outcome classified
Investigator receives letter with results
-No action indicated (NAI)
-Voluntary action indicated (VAI)
-Official action indicated (OAI)
Does the FDA inspect IRBs?
- Routine inspections every 5 years
- Directed -concern about IRB practices
What documents will the FDA request from the IRB?
-IRB membership
-Procedure and guidelines
-Minutes of meetings
-Materials submitted by the investigator
-Any other material about the study
What will the FDA inspect an IRB?
-Criteria for selecting studies:
-Interview staff
-Obtain information about policies and procedures (compliance with 21 CFR 56)
-May request to observe an IRB meeting
-Track one or more studies through the regulatory process
-Studies reviewed by the IRGB during the 3 years before the inspection
What are the outcomes of the FDA inspections for the IRB?
-Noncompliance with regulations will result in a written or verbal summary of observations to an IRB representative (FDA form 483)
-IRB and/or institution must respond in the designated time
-FDA may re-inspect to confirm the adequacy of corrective actions
IRB receives a letter from the FDA
*IRB will receive a letter with the following results:
-No action indicated (NAI)
-Voluntary action indicated (VAI)
-Official action indicated (OAI)
*A warning letter may be considered when violations can be corrected through specific actions by the IRB.
What are the other actions that can be taken by the FDA?
-Withholding authority to approve new studies
-Directing that no new subjects be enrolled in current studies
-Terminating ongoing studies
-If noncompliance creates a significant risk to the rights and welfare of human subjects the FDA will notify state and federal authorities an other partners with direct interest
-IRB may be disqualified
