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Expedited Drug Development Pathway

Previous Section: Building the Infrastructure to Drive and Support Personalized Medicine

Sometimes during the development of a new drug to treat a serious or life-threatening disease that has few therapeutic options, the new treatment performs much better than standard-of-care in the early trials. While there is general agreement that such a drug should be developed quickly, there is not a common understanding of how to appropriately speed up development while simultaneously gathering adequate evidence about the performance of the product.

During the HIV epidemic in the early 1990s, experts from many fields came together to rapidly work through the science underlying the disease and devise programs for AIDS drug development. The result was a relatively efficient development process and availability of effective anti-HIV drugs.

As we continue to gain an understanding of the mechanisms that underlie diseases at a molecular level, a situation similar to AIDS drug development is emerging in a number of disease areas, including oncology, infections, and genetics. Investigational drugs with the potential to be significant advances over current therapy are being found in early trials.

For example, targeted therapies, such as those used with a diagnostic that classifies patients or predicts responses, are being studied in larger numbers. Trials for targeted therapies frequently use what are known as enrichment strategies to screen and select patients to determine if they are likely to respond to a treatment based on a clinical feature such as the presence of a particular gene mutation or other biomarker. The clinical trials are then performed on this subset of patients, which is often small. Because these patients are selected based on their suspected response to therapy, dramatic responses are in some cases observed in early trials. This effect is similar in tests of anti-infective agents, such as antibiotics that target a particular bacterium, as well as in genetic disorders where treatment is targeted to address a particular genetic defect.

The early discovery of a potential breakthrough therapy raises ethical and trial design issues. It is important to gain confidence that the effects seen in the early trials are real, and to understand the safety risks of the new drug. On the other hand, from an ethical standpoint, it is important to make sure that people with serious diseases are getting the best possible therapy. In these situations, the clinical trials for the drug's development must be compressed and the evidence about its effects gathered in the most efficient manner possible; however, there is not a good understanding in the biomedical community about how to accomplish this.

Additionally, there are questions surrounding the use of an expedited drug pathway, such as:

  • Can FDA, drug developers, and investigators agree on a threshold to determine when a treatment poses “exceptional promise” and should thus be treated in an expedited fashion?
  • Can seamless drug development programs be created to utilize natural history data or adaptive trial design concepts to compress drug development time?
  • What are the ethical issues involved in identifying a promising intervention? How should the needs of all patients with the disease be balanced against the need for better therapy for an individual?
  • Can surrogate outcome measures that could be used for accelerated approval be rapidly identified?
  • Can we arrive at a consensus view of the goal of monitoring commitments companies will make once a product is on the market after such a development program, such as scientific expectations and timelines?

To respond to these challenges, FDA will hold a series of scientific meetings with academic investigators, patient groups, drug developers, statistical and methodological experts, and ethicists to achieve a common understanding of steps that can be taken when an investigational drug being studied for a serious disease with no acceptable treatment option shows exceptional promise. CDER will then publish a draft guidance on an expedited development pathway based on the outcome of these meetings.

FDA is also working on two more immediate and related steps toward expedited drug development. First, the Agency is developing a draft guidance on enrichment strategies in clinical drug development. This is a major step forward for speeding progress for targeted therapies and will lay out many strategies for selecting the patients most likely to benefit from a particular drug. These enrichment strategies are expected to improve the efficiency of clinical trials and serve as a source of expedited drug development.

Second, as a working example of an expedited pathway, CDER will publish a draft guidance on the use of pathologic complete response (pCR)—when no clinical evidence of a disease remains—as a surrogate endpoint for accelerated approval in primary high-risk breast cancer. This guidance will outline a relatively seamless pathway that could be followed from a multi-drug screening trial such as I-SPY 2 to an accelerated approval. This would speed the availability of targeted therapies for breast cancer.


In March 2010, the I-SPY 2 Trial was launched. This is a groundbreaking clinical trial model that will help quickly and efficiently test promising drugs in development for women with high-risk, rapidly growing breast cancers. During the trial, drugs are individually targeted to the biology of each woman's tumor. By applying an innovative trial design, researchers then use data from one set of patients' treatments to decide treatment for future women who join the trial. This will help the researchers learn more quickly which investigational drugs will be most beneficial for women with certain biomarkers.


Table of Contents: Driving Biomedical Innovation

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