Quality Control in Standardized Clinical Trials. “Oh, Say, Can I See Your QC?”. CTN 107. Presentation Objectives. At the conclusion of this discussion, participants will be able to: Describe why accurate documentation of QC procedures is important in clinical trials.
Quality Control in Standardized Clinical Trials
“Oh, Say, Can I See Your QC?”
At the conclusion of this discussion, participants will be able to:
Regulations & Guidelines about Quality Control of Imaging and Radiopharmacy Equipment
Introduction to the Topic
Quality Control of imaging and radiopharmacy equipment is important to sponsors, FDA, IRB, and our patients.
“The Food and Drug Administration also reviews study plans before the trial begins, as well as during the trial.
The FDA and ethics committees have neither fame nor fortune at stake and can shut down clinical trials if the risk for participants becomes greater than expected.”
“Only 50% of submitted imaging data in a large industry trial was able to used because of poor quality and sites making changes to the protocol”
QC of imaging equipment is fundamental to the goal of image standardization in imaging and therapy trials.
QC failure of imaging and radiopharmacy equipment represents:
Potential loss of data
Inability to provide accurate quantification
Wastes our patient’s time
Lack of standardization from site to site
Quality Control: Definition
The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial related activities have been fulfilled.
“ There is NOT a specific regulation that requires sites to perform adequate quality control for research protocols, but the need for excellence is implied in many of the good clinical practice documents. “
Declaration of Helsinki
“Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, as appropriate, animal experimentation.”
Dose Calibrator QC
The Dose Calibrator time clock should ALWAYS match the PET Scanner time clock.
GET ONE !
Glucometer Quality Control (Daily)
PET/CT Daily Quality Control
No Cracks !!
No Dents !!
No Glue !!!
Any & All Phantom integrity issues MUST be reported to the manufacturer and the Vendor during clinical trials!
PET/CT Uniformity Phantom
Required by most manufacturers:
Monthly and Annually
Phantom and Table Must Be Level !!!
Monthly SUV and Uniformity Validation
PET-CT Quality Control Log
Normal operations include the following 3 tasks (in order):
CT Daily Quality Control
CT Daily QC Phantom
Linearity - Linear attenuation coefficients tracked linearly with a specific material density
The mean CT numbers of air (-1000 HU), water (0 HU), and acrylic (120 HU) displayed within an ROI should be consistent with the defined value +/- manufacture specified tolerance
Uniformity – ROIs distributed in homogeneous material should indicate consistent signal (HUs) and noise
Are All CTs Created Equal?
A CT Protocol is comprised of:
–Surview ( scout, pilot, scan-o-gram)
–Helical or Conventional Prescribed Scan
– ROI means
– ROI standard deviation range
- mAs setting accuracy
– Filament adaptation
• MTF & Slice thickness
– Physics layer
• Check error log
LAP Laser Alignment Phantom
Lasers are mounted on the walls and ceiling of the scanner room
Inform your vendor if using special appliances such as flat pallet and wing board for treatment planning
(2.10) All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification.
(2.13) Systems with procedures that assure the quality of every aspect of the trial should be implemented.
The research patient is in your department.
You discover the sponsor specific QC procedure that was supposed to be performed within five days of the participants imaging session was instead performed at ten days. What do you do?
Even if the calibration value was normal, the
sponsor must be notified since it will be
considered a protocol deviation.
– Document the situation for the sponsor, and
initial and date the note.
– Create a plan within the department to make
sure the QC is performed with the study
The investigator is responsible for and agrees to:
(Form FDA 1572): “I agree to conduct the study(ies) in accordance with the relevant, current protocol(s) and will only make changes in a protocol after notifying the sponsor, except when necessary to protect the safety, rights, or welfare of subjects.
3. Following the protocol, including requirements for quality control, is key to image standardization between sites.
Investigator record keeping and record retention
21CFR312 Sec. 312.62
(c)Record retention. An investigator shall retain records required to be maintained under this part for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated;
or, if no application is to be filed or if the application is not approved for such indication, until 2 years after the investigation is discontinued and FDA is notified.
If your departmental QC procedures vary from the manufacturer’s recommendations, provide reference documentation for why your procedures are adequate.
I.The pharmaceutical sponsor may or may not be an expert in imaging technology.
1.If corrective actions are taken (such as motion correction software), document what was done and why.
2.Save all original data
Considerations for Research QC
A. If you are not able to sit in on the PI Training Module then read the protocol thoroughly. Ask the sponsor, if not specified, “Are there additional QC procedures?”
B. Document QC performed for each patient study, and archive the daily and weekly QC with the patient data so it can be retrieved easily if there is a question.
C. Carefully document deviations from the QC required by the protocol, or deviations to your usual departmental QC.
In the radiopharmacy, document routine QC on instrumentation, or document where it can be located for an FDA audit.
E. Use proper record-keeping and documentation processes
1. Record primary data on source document records; sign and date all entries
2. Do not erase, use white-out, or otherwise cause an entry to be illegible.
3. All errors should be indicated with a line-through the entry, the correct entry written to the right or above the original, and the initials and date of the person who made the correction
F. Some research protocols will require more than usual QC (for example, uniformity floods more frequently than required by camera manufacturer, or additional acquisitions to determine detector sensitivity or resolution)
1. If a specific quantification protocol will be used
2. If imaging data is being sent to a central reader
3. If the isotope used in unusual or if standard radiopharmacy QC protocols do not assure quality of the investigational product
SUV PhantomVendor Phantom
Clinical Trial Phantom
Imaging Quality Control is required as part of the clinical protocol, QC data may be submitted to the FDA as part of the New Drug Application Process
Quality Control Data is:
Subject to potential audit by the FDA if it is collected as part of the research protocol.
C.Considered a protocol violation, if not performed properly, which are detailed in the final study report; depending upon the seriousness of the omission, the patient data may not be evaluable.
D.Some research protocols will not require more QC procedures than are routinely performed by the imaging department. In that case, detailed records should be kept of all QC that pertains to the patient being imaged on study.
Virtual Scopics Research Phantom-Counts
Considerations for Research QC
ALWAYS perform QC BEFORE the patient
procedure is started!!!!
Dose Calibrators (daily, weekly, annual)
Gluco- meters (daily)
PET Scanner (daily, monthly, annual)
CT Scanner (daily, monthly, annual)
From: "Mr. Big” <[email protected]>
To: xxxxx@ aol.com
Date: 1/15/2010 3:49 PM
Subject: Novartis ABCD1234 : Site: 0514
Notification of Final Qualification‑ PET
Thank you for submitting the First Subject PET‑CT Images on the XXXXX
Scanner for the Novartis ABCD1234 study. These images have passed
our internal Quality Inspection.
<Your Institution> has now completed the Final Qualification Process
for PET. We sincerely appreciate you and your site's efforts throughout this
qualification process. Virtual-Scopics is very excited to be working with you.
Associate, Site Management