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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 Barbara E. Tardiff, M.D., M.B.A.
Corporate Vice President, Data Sciences
PAREXEL International
Nearly 43 percent of Phase III clinical trials fail to meet their primary objectives, according to the 2008 Bio/Pharmaceutical Source Book. Given that each failure costs tens of millions of dollars and years of development time, this is a sobering statistic. No biopharmaceutical or medical device company can afford such a devastating outcome in today’s highly competitive marketplace and challenging economy. Yet the failures continue to occur with disheartening regularity.
How can the industry reduce the risk of pivotal trial failure? One approach that allows a company to learn more about a prospective product before getting into the expensive pivotal clinical trials is a Proof of Concept program, which offers a faster, less-expensive way to test the potential of a new product. A well-designed Proof of Concept study can provide vital clinical evidence about a product’s risk/benefit profile, e.g. intended effects, pharmacodynamics, or early signals of efficacy – data that helps sponsors make more informed “go/no-go” decisions about their products. This early evaluation should provide sufficient fundamental knowledge of the mechanism-of-action and safety profile to facilitate design of a development plan that thoroughly addresses clinical and business risks and provides a path to successful first-cycle approval. While this may appear as a tall order, gathering the data needed to identify and mitigate potential risks and inform decisions is infinitely more cost-effective at the Proof of Concept stage than during a pivotal study.
The adoption of the Discover—Learn—Confirm paradigm has placed renewed emphasis on Proof of Concept strategies and the role they play in the drug development continuum. Also known as exploratory, pilot, or proof of principle studies, Proof of Concept includes studies where a compound is used in patients (with the targeted indication) with the explicit goal of finding signals of a product’s activity early in the development process. For some biologic products, a broader program of exploratory studies may be warranted to help identify and mitigate safety risks that could arise in later development. What is important is that Proof of Concept studies are part of a thoughtful and deliberate development strategy, unique to the product and commercialization goals and not a preset or one-dimensional formula.
What are the characteristics of a typical Proof of Concept program?
- A patient population that has the disease or condition being targeted, with the potential to show change in a meaningful observational measure in the short term
- A relatively small number of patients – usually between 20-150
- A short duration of exposure to the compound – just long enough to observe an effect
- An analysis strategy that demonstrates indication of a compound achieving its intended purpose, although not necessarily designed to provide statistical evidence
- Study designs that generate initial patient safety data relative to the disease state and product exposure
- Study designs that deliver the information needed to make informed decisions in the most cost-effective way
- A sense of urgency and emphasis on rapid completion
Proof of Concept studies may be conducted at dedicated Phase I units or at conventional investigator sites such as hospitals and academic medical centers, depending on patient and scientific needs.
Early assessment should provide the information needed to reach informed “go/no-go” decisions on new products before committing to the cost and risk of later phase trials. A Proof of Concept program is generally considered “successful” if:
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The data suggest that no further research be conducted on the product
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The data suggest that a compelling business case can be made to proceed with a different therapeutic target
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The data suggest development proceed as planned with a clear understanding of clinical and safety risk and potential regulatory hurdles
This is not to say all individual Proof of Concept studies are successful.
For smaller companies without resources to bring a molecule fully through the development process, Proof of Concept studies can increase the potential value of a product by answering some key scientific and efficacy questions – helping increase the NPV (net present value) of the products and increase licensing opportunities.
Proof of Concept studies are also in alignment with the US Food and Drug Administration’s Critical Path Initiative. The Initiative encourages the pharmaceutical industry to take greater advantage of exploratory INDs, biomarkers (such as advanced imaging technologies), and other approaches to more rapidly screen potential drug candidates and identify those with the greatest promise, as a means to help reduce the high cost and risk of drug development.
For companies that want to take advantage of the benefits of Proof of Concept programs, PAREXEL offers specific early drug development research experience in regulatory affairs, medical expertise, clinical pharmacology, and advanced technologies such as medical imaging across a wide range of therapeutic areas. PAREXEL can also provide access to specialized, hospital-based, First-in-Human (Phase I) facilities and other specialized early phase trial sites around the world.