PHOTOGRAPHY : MEDICALRF.COM, GETTY IMAGES
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The role of medical imaging shifts dramatically between early and late phases of drug development, from detecting early signals
to being a surrogate endpoint that determines safety and efficacy of a new treatment. Early on, sponsors are searching for
biomarkers that characterize the pharmacokinetic and pharmacodynamic profile of an investigational compound. Later, they are
looking to define surrogate endpoints as substitutes for clinical endpoints that could take years to achieve.
Making the transition from early stage imaging in small studies to late-stage, multicenter trials can be challenging for sponsors
who have not formulated a development plan to incorporate imaging technologies well ahead of their potential use in pivotal
Phase III trials. For these sponsors, bringing imaging into earlier phases helps to establish a continuum in the development
of potential biomarkers into potential surrogates. It also enables sponsors to make faster and better informed go/no-go decisions
about the future of investigational compounds.
This article describes the role of imaging in each phase of clinical trials and how planning and regulatory guidances can
help stakeholders incorporate imaging into the process to improve outcomes. It also focuses on how imaging changes from its
early purpose of identifying biomarkers in small, single site studies to its later function as a tool for surrogate endpoints
in multicenter trials.
Early imagingMuch of the emphasis on imaging has traditionally occurred in later phase studies, using technologies such as magnetic resonance
imaging (MRI) and multislice computerized tomography (CT). But with advances in methodologies such as positron emission tomography
(PET), single-photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI), a gradual increase
in the amount of early phase imaging is taking place.
The intent of imaging differs among Phases I, II, and III (see Table 1), as it moves from serving mostly an exploratory function
in early studies that are not well-controlled to large, multicenter, well-controlled clinical trials (see Figure 1) with defined
endpoints and outcomes.
Imaging in Clinical Trials
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At the beginning, the goal of imaging is to find prebiomarkers, which are signals, and the meaning of the initial results
may not be clear. The work is typically conducted at a single site or at a handful of investigative sites, mostly at academic
institutions. The same investigators who enroll and manage the research patients also perform the imaging and image analysis,
so by their very nature, the studies are biased. As the data generated are not FDA-bound, regulatory rigor is not a prerequisite.
Figure 1. A look at imaging and its purpose throughout the drug lifecycle, from early to late phase studies.
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To start the process of incorporating early imaging into a clinical development plan, stakeholders might focus on maximizing
its value. If an imaging modality or compound seems to hold promise, they might consider using the FDA's exploratory Investigational
New Drug (IND) process, an underutilized tool that offers the chance to competitively analyze multiple imaging compounds or
modalities prior to routine first-in-human studies.
