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Milwaukee Journal Sentinel Story on Use of Surrogate Measures

October 30, 2014
Earlier this week, John Fauber of the Milwaukee Journal Sentinel wrote an article on measures used to determine whether new medicines for serious and life-threatening diseases should reach patients. Fauber seem(s) to suggest that the use of surrogate measures – such as tumor shrinkage – do not provide evidence of drug efficacy.

The story fails to present a balanced view of the complex benefit-risk assessments that the FDA must carefully consider when reviewing applications for expedited and/or Accelerated Approval, which are designed to enhance the ability of patients to receive life-altering and potentially life-saving drugs in a timely and scientifically rigorous manner.

Sponsors must demonstrate through robust data that a surrogate endpoint has reasonably likely meaningful clinical outcomes for patients. Surrogate and intermediate clinical endpoints may be laboratory or clinical measurements or other biological responses that can be used to measure therapeutic effect earlier than morbidity or mortality, which often takes years to measure, particularly for slowly progressing diseases.

Accelerated Approval on the basis of a surrogate endpoint followed by confirmatory studies can help patients enormously by providing access to important therapeutic options years earlier than under “traditional” approval. For instance, an FDA analysis of a subset of oncology drugs approved under Accelerated Approval and subsequently converted to regular approval (i.e., post-market data demonstrated fully that the drugs were safe and effective) found that patients had access to those Accelerated Approval products on average 4.7 years earlier than had the drug been approved under the traditional approval pathway, according to a study in the Journal of the National Cancer Institute.

Another FDA analysis of all oncology Accelerated Approvals found that the median development time for new drug application new molecular entities (NDA NMEs) approved under Accelerated Approval was 5.5 years versus 7.3 years for those that received traditional approval, according to another study in the Journal of Clinical Oncology. In other words, patients had access to those cancer treatments – in many cases the only therapy available to them – nearly 2 years sooner than had Accelerated Approval not been available. For patients facing a cancer death sentence, two years is equivalent to a lifetime.

All of FDA’s approval programs, including Accelerated Approval, use the same rigorous standards for safety and efficacy. Sponsors must demonstrate substantial evidence of effectiveness consisting of adequate and well-controlled investigations—in many cases two studies. The FDA uses rigorous standards for demonstrating safety and efficacy, while using scientific judgment to apply these standards within the context of a particular disease, its severity, and the availability of alternative treatment options in order to carefully balance the benefits and risks of a therapy. Accelerated Approval and FDA’s other expedited programs do not lower or amend FDA’s approval standards in any way, but allow for more suitable approaches to meet those standards in a timely manner for life-threatening conditions and serious diseases. An analysis of FDA approval data suggests that 95% of the drugs approved on the basis of a surrogate endpoint under FDA’s Accelerated Approval program ultimately confirmed the clinical benefit for patients. In those few cases where benefit has not been confirmed, the system has successfully led to withdrawal of the indication.

The Accelerated Approval program is highly successful in improving patient access to therapies for important unmet medical needs, while maintaining FDA’s high standards for demonstrating safety and efficacy.