FDA, ilaç geliştirilmesi ve klinik araştırma hızını arttırmak için kılavuz hazırladı (İng)

FDA: New Plan to Speed Drug Development

By David Pittman, Washington Correspondent, MedPage Today

Published: December 26, 2012

WASHINGTON — The FDA has issued guidance outlining how drug companies can select patients more likely to show a benefit from a studied drug and how companies can help improve the speed and efficiency of clinical trials.

In draft guidance published last week, the agency outlined specific examples of how drug developers can exclude poor potential candidates and select those more likely to show a clinical benefit.

For instance, if a drug company is studying a lipid-lowering drug meant to reduce heart attack risk, it may choose diabetic patients because they’re more likely to have heart attacks and show an effect from the drug.

The FDA called these types of study designs “enrichment strategies” or “enriched studies.”

“These are potentially powerful strategies for the pharmaceutical industry because appropriate use of enrichment could result in smaller studies, shortened drug development times, and lower development costs,” Bob Temple, MD, deputy director for clinical science in the FDA’s Center for Drug Evaluation and Research, wrote in a blog post on the agency’s website.

The 42-page guidance listed several examples of ways enriched studies have been used to approve drugs already.

In one example, the FDA noted trastuzumab (Herceptin) showed a significant survival of 5 months for metastatic breast cancer in patients with high HER 2/neu expressing tumors — about 25% of all breast cancer patients. However, it showed less than 2 months’ survival improvements in all patients overall.

The strategy of focusing part of the trial on the specific population of patients with high HER 2/neu-expressing tumors “ultimately supported use of the drug in the marker-selected population despite the significant cardiotoxicity that emerged,” the guidance noted. “The much smaller mean effect … that would have been observed in an unselected population and the fact that only about one-fourth of patients would have benefited might have made approval difficult to support in the face of the observed cardiotoxicity of the drug.”

The FDA approved the cystic fibrosis drug ivacaftor (Kalydeco) which works in just 4% of CF patients with a specific genetic abnormality. If all CF patients were included in a trial, a effect would have been impossible to detect, Temple said.

A similar strategy was used in the lung cancer treatment crizotinib (Xalkori).

“Conducting a clinical study in a patient population that has a larger than average response to treatment can greatly reduce the number of patients needed in the study and can direct the treatment to the patients in whom the drug actually works,” Temple said.

The agency notes that trials must still be well controlled and doesn’t lower the risk-benefit threshold new drugs must meet to gain approval. There also must be a strong rationale for researching the enriched population, and studies of a more general population need also be conducted.

The FDA focused on three sets of enrichment strategies:

• Strategies to decrease heterogeneity: Excluding patients whose disease or symptoms improve spontaneously or whose measurements are highly variable
• Prognostic enrichment strategies: Choosing patients with a greater likelihood of having a disease-related endpoint event or a substantial worsening in condition
• Predictive enrichment strategies: Choosing patients more likely to respond to the drug due to their physiology or disease characteristic

Alexander Varond, attorney with Hyman, Phelps, and McNamara in Washington, D.C., wrote on his firm’s blog that the guidance is “a welcome step towards providing sponsors with insight into FDA’s thinking” and “will serve as an important guide for future clinical design.”

He noted that this study method should be approached with caution if trying to generalize results. The FDA will likely note the enrichment strategies and the specific patients studied in a drug’s labeling.

The FDA noted these concerns in the guidance.

“When considering use of an enrichment design, it is important to consider whether the enrichment strategy can be used in practice to identify the patients to whom the drug should be given and whether the drug might be useful in a broader population than will be studied,” the guidance stated.

The FDA is accepting comments on the draft guidance until Feb. 15.