The independent review of imaging and clinical data in oncology clinical trials is becoming increasingly important in supporting
trial outcomes. The key to designing a successful independent review process centers on prospectively defining the methodology
for the review.
Early in the development of an independent review process, several key documents are generated and signed off as agreements
between a sponsor and imaging core lab. These documents include a project plan, Independent Review Charter, and the Investigator
Site Manual.
Prospective vs. Retrospective
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Through these documents, the sponsor and imaging core lab define a solid review method by describing how the independent review
will be performed, the types of reviewers involved, data to be collected from the investigator site, and the assessments the
independent reviewers will provide.
Often the sponsor is able to manage the process by managing the review process documentation. However, while documents may
represent an ideal methodology, the review process can break down due to unrealistic expectations, lack of experience and
expertise, poor communication, and numerous sustainability issues that can dismantle even the most well-defined independent
review. Three key documents
As a core document, the project plan describes timelines and budgets, but can also be used to prospectively define the communication
and data management plan between the sponsor and imaging core lab. This document also defines how investigator sites will
be qualified by the lab and the methodology by which queries from the core lab to the site will be managed.
Balancing Act: Stringent vs. Adequate
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One of the ultimate goals of the project plan is to identify any risks that may impact data collection for the independent
review and to form a plan for how those risks will be prevented and how any anticipated risks will be mitigated.
The project plan is heavily influenced by the Independent Review Charter, and ideally these two documents are developed in
tandem. The charter defines the overall review process, including the image schedule; types of images and clinical data to
be reviewed; the oncology assessment criteria (i.e., RECIST, WHO, IWC, etc.); the types and number of reviewers; the relationship
between reviewers (i.e., double reviews with adjudication, single reviews, joint reviews); and reviewer qualifications.
Sponsors are often eager to have a charter in place for review and approval by regulatory authorities, but many times the
key thought leaders involved in designing the charter from the sponsor side, such as the medical lead for the study and the
clinical protocol manager, are not aware of the implications of their decisions. One common pitfall in designing an independent
review process is dictating stringent data collection activities and review requirements in the charter.
Early stages of an independent review design are more often focused on medical and regulatory issues rather than operational
logistics. As a result, the need for rapid charter development to meet a regulatory deadline excludes other groups such as
the sponsor's data management from the charter development process until too late in the process. That is to say, stringent
data collection activities and review requirements defined in the charter and project plan are often implemented with little
forethought to the overall logistical and financial burden that these stringent requirements place on the trial. Inevitably,
many trials that initially mandate very rigorous data collection guidelines are relaxed after a period of prodigious effort
to enforce compliance.
