The Importance of Protocol Compliance in Imaging Studies

Joseph Pierro MD and David Raunig PhD | |

Good Clinical Practices (GCP) as well as U.S. Code of Federal Regulations and other international regulations covering clinical research mandate all people involved in a clinical trial understand and follow the principles which are summarized in FDA Form 1572 (Statement of Investigator)1. Specifically this document provides details on the site investigator’s team qualifications to perform the research study and informs the investigators of their obligations to comply with FDA regulations.

Given that imaging is often a “supporting” endpoint, we often see that imaging personnel, i.e. imaging technicians, radiologists etc., are not listed on Form 1572. With that in mind, the purpose of this blog is to outline the expectations and practices imaging providers should follow to be compliant with relevant regulations.

Ideally, the imaging team should be listed on Form 1572 for all trials. Our experience has shown that listing imaging members as sub investigators results in higher protocol compliance and data quality. This is especially relevant in studies where imaging has primary importance – studies of biomarkers and the development of novel imaging methods.

Over the last few decades, imaging data has become more important in regulatory approvals especially in the area of oncology and using the structure of Form 1572 reinforces the imaging team’s commitment to:

  • Perform the imaging exams defined in the study protocol
  • Provide image interpretations and:
  • Store the data in a standard format for data submission.

The imaging team should be made aware of any protocol updates released after study start up as their performance and compliance is expected; noncompliance may result in an audit finding(s). This latter point is something we often find that imaging teams do not understand especially when they haven’t been included in Form 1572.

Imaging protocol compliance is important for imaging standardization in multi-center trials to permit data pooling and analysis of results across clinical sites. To avoid protocol deviations, all imaging personnel involved in supporting the trial should be trained on the protocol requirements, even when the protocol calls for standard of care or routine imaging as performed during daily routines. This training record should be documented and archived within the radiology departments together with other study documents (e.g. study protocol, investigators brochure, imaging manuals/protocols and calibration records, etc.).

To ensure imaging teams understand the protocol requirements, our experience has shown that higher data quality may be obtained when the imaging team includes the smallest number of technologists and radiologists as reasonably practical to perform and meet study objectives.

Using the “whoever-is-on-staff-for-the-day” approach often leads to higher levels of imaging protocol noncompliance as these individuals are often not aware of the study needs or requirements and are almost certainly unaware of their regulatory GCP and FDA Form 1572 responsibilities. At worst, this can and does lead to missing or non-evaluable data and all of the problems that causes.

The study project coordinators also need to ensure the imaging department is aware that a research study subject has been scheduled and that department staff clearly communicate this to the imaging technician to ensure adherence to the study protocol requirements.

Check back soon for our next blog, where we’ll discuss the value of standardized imaging protocols in clinical trials as a means to achieve higher levels of image consistency and better data quality.

 Joseph Pierro, MD is the Medical Director of Imaging at ERT and David Raunig, PhD is the Senior Principal Imaging Statistician at ERT.

References

https://www.fda.gov/media/78830/download

 

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