Medical Imaging Emerges in Clinical Trials: A 2007 Assessment
CenterWatch 2007
The FDA, in an effort to increase new drug approvals, has identified imaging as an important technology for assessing new therapeutics and accelerating drug development in the future.
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By Ken Faulkner, PhD, Vice President of Medical Imaging
PAREXEL International
Scientific and technological advances across a broad range of therapeutic areas are fueling a rapid increase in the utilization of medical imaging throughout the clinical trial process. Many study sponsors now rely on advanced imaging modalities such as computed tomography (CT), ultrasound, magnetic resonance imaging (MRI), and positron emission tomography (PET) for primary and surrogate endpoints to assess novel therapies at every stage of development: validating early-stage drug candidates; establishing safety and efficacy during pivotal trials; and supporting regulatory submissions.
While these technologies provide substantial benefits that can accelerate the development of innovative drugs and biologics, they also present trial sponsors with an array of new challenges, such as:
- Selecting the right imaging endpoints for a particular indication that will be predictive of the targeted clinical outcome
- Developing suitable imaging protocols and disease-assessment criteria
- Collecting the appropriate data to achieve market approval, at a time when regulatory guidance on medical imaging submissions is still evolving
- Maintaining imaging quality across multiple trial sites – a growing issue with the increasingly global nature of clinical trials
A sponsor’s decisions about these medical imaging issues can spell the difference between a successful product development program and one that ends in failure or delay – an outcome that no bio/pharmaceutical company can afford in this era of rapidly escalating development costs and intense global competition. These decisions are further complicated by the continuous scientific and technological advances in the use of medical imaging, as well as by the evolving regulatory environment. With so much at risk for every clinical trial, many bio/pharmaceutical companies are turning to external partners with specific imaging, therapeutic, and regulatory expertise to help them make better-informed medical imaging decisions for their drug development programs.
Selecting the appropriate endpoints
One of the most valuable areas where sponsors can effectively utilize medical imaging is during early-phase drug development. At this stage, sponsors are trying to determine which investigational products they should move forward into larger clinical trials. Imaging technologies can be effective tools to speed up the comparative analysis of potential therapies in a product portfolio by quickly demonstrating which drug candidates have the fastest or longest-lasting impact on the targeted disease site, or which ones have the least negative impacts on other parts of the body. With the right imaging data, sponsors can make earlier and better-informed “go/no-go” decisions about their products, which should accelerate development times and reduce the risk of costly late-stage failures.
However, sponsors face a major challenge in utilizing medical imaging during early product development – selecting appropriate endpoints that have the greatest chance of predicting a therapy’s actual impact on clinical endpoints. The key question that must be addressed is: Will the endpoint being measured by the imaging technology be an accurate predictor of the drug’s effect on the targeted clinical endpoint?
For some indications, the endpoints are well validated. In many types of cancer, for example, tumor growth or shrinkage as a surrogate endpoint is directly related to the clinical endpoints of remission or longer-term survival. MRI, CT, and other imaging modalities can provide fast and non-invasive evidence of the potential efficacy of novel cancer treatments. Diseases affecting bones and joints – such as osteoporosis or rheumatoid arthritis – also have relatively clear-cut imaging measurements that are closely related to the desired clinical outcome, such as increased bone density, development and progression of skeletal erosions, or greater range of joint motion.
For many other conditions, however, the correlation between surrogate endpoints and clinical endpoints is much less clear. In cardiovascular disease, for example, there are many measurements that have been linked with possible cardiac problems – such as high cholesterol, high blood pressure, and obesity – but even the most accurate measurements of a drug’s affect on these surrogate endpoints have not been fully validated to accurately predict whether a therapy will help a patient avoid cardiac problems in the future. Neurological disorders such as Alzheimer’s disease also lack validated surrogate endpoints. Although advanced imaging technologies can accurately measure changes in brain volume and function, those changes have not been causally linked to specific diseases. Choosing a surrogate imaging endpoint that proves to be an ineffective indicator of the clinical endpoint would be a costly, time-consuming error for any development program.
Choosing the technology
Another medical imaging challenge facing sponsors is choosing which imaging modality to use for the clinical measurements. This is not just a technological decision. There are many other important criteria that must be considered as part of the decision-making process for incorporating medical imaging into a clinical trial:
Cost: Many advanced imaging systems are very expensive and time-consuming to operate. The cost of using a particular imaging technology can have a significant impact on the overall cost and length of a trial, both critical factors in a time of tight budget projects, short timelines, and intense competition.
Availability: The availability of a specific imaging technology – and the expertise to operate it – may limit the areas where a trial can be conducted. Although clinical trials are becoming more global, some advanced imaging systems are not commonly in use outside North America and Western Europe, which can greatly complicate the process of selecting potential trial sites and recruiting patients.
Validation: The existence of validated imaging protocols and disease-assessment criteria for the targeted indication are vital to the imaging technology decision. In many cases, the rapid advancements in imaging technology have outpaced the establishment of a medical consensus about the validity of the technology for evaluating a disease – creating uncertainty about the acceptability of imaging data for some modalities and diseases. A sponsor must be able to demonstrate that the selected technology and imaging protocols are appropriate for the disease being targeted by the potential therapy.
Regulatory Guidelines: Current regulatory guidelines lag behind the development of advanced imaging technologies in many cases. Without clear regulatory guidance, a sponsor faces the difficulty of deciding what types of imaging data to collect to support market approval in different regions of the world. Collecting insufficient images, or the wrong images, can cause regulatory questions and delays. Collecting too much imaging data – given the cost of operating these complex systems – will unnecessarily increase trial times and costs.
Quality Control: Maintaining data quality and consistency are key considerations for clinical trials using medical imaging technology – especially where the image acquisition will take place at multiple sites with differing equipment, technical capabilities, and medical practices. Strong quality controls, standard operating procedures, and image-acquisition protocols are essential to maintain consistency and avoid regulatory issues that could delay market approvals.
Given the many issues surrounding the use of medical imaging in clinical trials – plus the rapid rate of scientific and technological change for both the diseases and the imaging technologies – using a strategic partners with specific expertise in imaging technology, protocols, and regulations often represents the best approach to avoid pitfalls and take advantage of the many benefits that advanced imaging technology can provide. With the right imaging partner, sponsors can overcome the challenges and take advantage of the power of medical imaging to accelerate product development and bring their important therapies to patients who need them around the world.
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