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FDA-Regulated Clinical Trial Starts for Oncology Continue to Climb
• As measured by new commercial IND submissions to the FDA's Center for Drug Evaluation and Research (CDER), clinical trial starts for new oncology drugs grew by 13% in 2007.
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By George Mills, M.D., Vice President, Medical Imaging Consulting, Perceptive Informatics
Advanced imaging technologies such as positron emission tomography (PET) have revolutionized the practice of medicine, allowing physicians to view biologic activity at the molecular level in the human body through the use of radiopharmaceuticals, bioluminescence agents, and other imaging biomarkers. The combination of powerful imaging technology and biomarkers also holds tremendous promise as a tool to speed up the development of new drugs by facilitating the early evaluation of potential therapies to more quickly identify promising candidates.
Although molecular imaging offers substantial potential benefits for drug developers, the practical application of this technology in clinical trials has been significantly hampered by a lack of standardization. While individual medical centers have been using molecular imaging in their research, there were no industry-wide, FDA-approved CMC standards for the production of specific biomarkers; no general protocols covering the qualifications of imaging centers or the calibration of their equipment; and no protocols for how the images should be captured and interpreted. This lack of broad-based industry and regulatory standards has made the use of molecular imaging technology in large-scale, multi-center trials virtually impossible.
However, the integration of molecular imaging into the clinical trial process took a major step forward in October 2008 with the announcement by the Society for Nuclear Medicine (SNM) that it had created a Molecular Imaging Clinical Trials Network to speed up the process of establishing molecular imaging standards. SNM is an international scientific and medical organization with more than 17,000 members that specialize in molecular imaging. The SNM initiative brings together the US Food and Drug Administration (FDA), pharmaceutical product developers, imaging sites, and biomarker manufacturers to facilitate the use of molecular imaging in multi-center clinical trials. This centralized effort will provide drug developers with key elements that are essential for employing molecular imaging in large-scale trials, including:
- FDA-approved, centralized INDs for the use of approved biomarkers, which can be incorporated by reference into drug developers’ specific INDs
- Standards for imaging centers, and a registry of certified centers with the capabilities and willingness to participate in multi-center trials
- Protocols for the production of molecular biomarkers, and a registry of approved manufacturers
- Protocols for image capture and assessment
The importance of molecular imaging
Why is the advancement of molecular imaging so important for drug developers? From a scientific point of view, molecular imaging technologies give researchers the ability to detect the biological activity of a potential therapy at its earliest stages. In oncology research, for example, molecular imaging can be used to view the effect of a cancer treatment on individual cancer cells within a tumor. Traditional imaging technologies like magnetic resonance imaging (MRI) can only detect anatomical changes, such as whether a tumor is shrinking or not over a period of time. The ability to screen a therapy for efficacy at the cellular level with surrogate endpoints should allow researchers to more quickly identify the potential of new treatment approaches – helping the most promising ones move forward faster, and reducing the time and expense of testing those with the least potential.
The study of Alzheimer’s disease is another major area of research focus that could greatly benefit from more widespread use of molecular imaging. A technology such as PET could be used to rapidly assess the impact of a new therapy on the production of beta amyloid proteins, for example, and guide researchers toward treatments that have a greater chance for success against this devastating disease – without having to wait for longer-term comparisons of cognitive loss or other indicators.
Because molecular imaging can quickly pinpoint the activity of a therapy in groups of patients, this technology may have even greater potential for drug researchers by aiding their ability to identify the patients who are most likely to benefit from particular treatment approaches. If scientists can more easily correlate certain types of positive therapeutic responses with specific ethnic, gender, age, or genetic groups, then targeted therapies could be developed based on those correlations that have a greater potential of efficacy in those groups. While the era of “individualized medicine” is still many years away, molecular imaging could play a crucial role in turning that promise into reality.
All of these possibilities are dependent on the ability of drug developers to apply the power of molecular imaging in clinical trial settings, which typically involve hundreds or thousands of patients and dozens of investigator sites. Without approved, industry-wide protocols and standards for the use of biomarkers and molecular imaging in clinical studies, the use of these technologies is impractical for large-scale trials. That is why the recent announcement by SNM and the establishment of the Molecular Imaging Clinical Trials Network is a major step toward moving these powerful tools into the mainstream of pharmaceutical research and development.
Moving forward
The key goal for the Network is the creation of a centralized IND Imaging Biomarker Use Pathway for the application of imaging biomarkers in clinical trials. Components of the pathway will include:
- Creation and approval of centralized INDs for biomarkers of interest, which will be available to all drug developers who support the project
- Identification and qualification of imaging centers that want to participate in clinical trials
- Identification and qualification of biomarker manufacturers
- Creation of standardized imaging protocols
The Network will work closely with the FDA to assure proper definition of imaging and manufacturing protocols for the INDs of selected biomarkers – helping to ensure that biomarker data from these studies will be acceptable for inclusion in a New Drug/New Biologic applications. SNM has already received FDA approval for one biomarker: F‑18 fluorothymidine (FLT), an investigational PET imaging biomarker that has shown promise for demonstrating tumor proliferation. A multi-center (4 site) demonstration trial for F‑18 FLT is expected to begin in early 2009.
Other major projects that are currently underway include the Imaging Site Registry, beginning with PET imaging centers and manufacturers; an Imaging Qualification Program to certify imaging sites; and a Manufacturing Site Registry to identify and qualify biomarker manufacturers that can meet the CMC protocols defined in the INDs.
These developments will play a vital role in moving molecular imaging forward. As the standards and protocols for the use of molecular imaging and biomarkers become more established over the next few years, this technology should help researchers more quickly identify the most promising approaches for a variety of devastating diseases, such as cancer and Alzheimer’s disease.
PAREXEL offers a broad array of knowledge and experience in the application of molecular imaging for clinical research. Experts in the company’s Clinical Research Services group and the Medical Imaging Division of Perceptive Informatics – PAREXEL’s technology subsidiary – can help sponsors leverage the capabilities of the latest imaging modalities and the use of biomarkers as surrogate endpoints in multiple therapeutic areas.