February 2013, Vol 2, No 1

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The Supportive Face of the FDA in the Advancement of Personalized Medicine

Robert E. Henry

The Last Word

In a presentation at the 2011 World Health Care Congress, Vicki Seyfert-Margolis, PhD, the FDA’s Senior Advisor for Science Innovation and Policy, delivered information that demonstrated how the medical sector of healthcare has no exclusive claim to creativity in methods for facilitating the success of personalized medicine. Her findings underscore the fundamental makeup of healthcare as a fusion of 3 sectors: clinical, business, and government. Therefore, the move to enriched, personalized medicine in cancer is the child of 3 proud parents: medical, business, and government.

She discussed the deep commitment by the FDA to helping pharma improve its research and development process by reducing the cost of new drug approvals, which had increased by 60% from 2000 to 2005 – when the cost of failures is included. Failure, then, is a major culprit obstructing personalized medicine advances. The question becomes how to accelerate fast-fail research? She brought evidence of something private researchers could not know: that because outcomes are not shared among competing companies, “…each failure is repeated many times.” Now, when Einstein was glibly making his point about insanity being that matter of doing the same thing over and over again while expecting a different result, he may not have been thinking of including in this syndrome the current reward system and its unintended consequence of confidential research causing this peculiar form of insanity to be practiced by quite sane scientists. She then explained how the FDA is working to diminish this cycle of repeat failure that threatens the economic viability of research into the biologicals so important to personalized medicine in oncology.
Tactical options for avoiding this “research insanity” are extensive and under way. A central theme is a science enclave and data repository “…to improve FDA’s management of scientific data about regulated products and improve regulatory decision-making [to] facilitate integration of scientific data – across studies, within studies, combine with outside data, [and] enable collaborations.” It would “create structured scientific data repositories that support the acquisition, validation, integration, and extraction of data from the increasingly large and complex data sets received by the Agency [and] make use of enhanced analytical tools and techniques that enable scientists, and ultimately reviewers, to search, model, and analyze data to enable personalized medicine and to conduct better safety and efficacy analyses.”

Seyfert-Margolis’ presentation in itself can go far to erase the stigma of the FDA as a force for impeding progress. Government is keenly aware that personalized medicine in cancer care is not a passing fad, and it has no intention of watching passively while private research spends itself into insolvency and brings down the roof upon the heads of cancer treatment innovation. Witness another signal event – this one recent and impressive.

In December 2012 the FDA issued a document that can help drug companies by accelerating approvals and reducing failures. Titled Guidance for Industry: Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products, this 42-page document draft advises pharma to select those patients most likely to show a benefit from a studied drug, enriching the patient study pool and so increasing the speed and accuracy of ascertaining the drug’s or biological’s potential to stop the cancer’s spread. It is axiomatic that personalized medicine is based on treating patients who are enriched through biomarker and other predictive methods, and the guidance document draft explores the clinical implications of this premise.

The results demonstrate a desirable risk/benefit ratio. The guidance described several examples of the process of securing approval. One was trastuzumab, with a significant survival of 5 months for metastatic breast cancer in patients with high HER2/neu-expressing tumors (a quarter of breast cancer patients) but less than 2 months’ survival improvements in the overall patient population. The report states that focusing part of the trial on the enriched patients with high HER2/neu-expressing tumors “…ultimately supported use of the drug in the marker-selected population despite the significant cardiotoxicity that emerged. 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.”

We find 2 lessons for personalized medicine from these examples. The first centers on the cause-and-effect application of these initiatives spawned by the FDA. The second is more diffuse, but no less valuable: the dispelling of stereotypes and consequent broadening of appreciation of the way in which healthcare works. Empirically, the guidance document draft underscores the time-honored premise of personalized medicine as an exercise in an enriched patient pool. The other lesson underscores the integrated, multistakeholder, trisector nature of the process of care: medicine, business, and government. The implication is to regard fellow stakeholders from different sectors as colleagues, not adversaries, with systems changes worthy of integrating into those from other sectors and groups. The core beneficiary, of course, will be the patient, who has appeared with life-and-death questions that are best served by a multilateral process of care. Listening to one another increases the chances of patient survival exponentially. Collegiality, support, and respect are in order for those from other fields, who regard themselves as just what they are: fellow healers in the mysterious initiative that is personalized medicine in cancer care.

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