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Pink Sheet – NYT v. FDA's Gottlieb On Drug Approval Standards

Pink Sheet – NYT v. FDA's Gottlieb On Drug Approval Standards

Executive Summary

New York Times editorial is critical of approving drugs based on one clinical trial, recommends independent cost benefit analysis.


A New York Times editorial recommending that the US FDA go back to requiring two clinical trials for approval of any drug elicited a series of tweets from Commissioner Scott Gottlieb, who explained the circumstances and rationale for basing approval on one trial.


The editorial, headlined “Easier Drug Approval, at What Price?,” was published in the June 9 issue of the NYT. It asserted that smaller trials make it more difficult to determine a drug’s actual medical value and that lower standards might inhibit innovation by giving companies less incentive to make substantial improvements in their offerings. In addition, it said requiring at least two studies would sharply reduce the odds of false positives and “help to set minimum benefit standards, requiring that a drug improve patients’ lives and health by a certain, measurable amount.”


Gottlieb responded in a same-day tweet that “for serious conditions with small patient populations (rare diseases) a single trial may be accepted to show safety and efficacy, demonstrating clinical benefit. This has helped result in approvals where there were previously no satisfactory approved drugs.”


He included a link to an article on the evaluation of endpoints and evidence in the era of breakthrough therapies, published in The Oncologist last year by FDA staff led by Gideon Blumenthal, acting deputy director of the Office of Hematology and Oncology Products. He also posted a chart from the article that lists 10 recent drug approvals for disease areas that previously did not have any approved therapies available.


The editorial appears to have been prompted by Gottlieb’s address to the American Cancer Society of Clinical Oncology’s annual meeting.

“Decisions to approve new drugs is complex. It balances medical need with available info on safety and efficacy. For disease with large patient populations or not considered serious or life-threatening, FDA generally requires at least 2 well-controlled trials for approval,” Gottlieb said. He also pointed out that for life-threatening disease where there is often no effective therapy, the agency may use surrogate endpoints, such as tumor shrinkage in a cancer trial, and require confirmation of long term benefit in post market studies.


The editorial also suggested that federal officials use independent cost-benefit analysis to set a drug’s list price, stating that the US is the only developed country in the world that doesn’t do this.


Former FDA Commissioner Robert Califf also tweeted a response to the editorial, expressing support for small trials and for assessing a drug’s value.


“We can do both. When unmet need is great or tx effect overwhelming, small trials/studies good. But we must also measure value. Will take larger, longer trials to measure clinical outcomes & costs,” Califf said.

Benefit Standards Vary By Disease

The Friends of Cancer Research felt the editorial was misinformed regarding people’s expectations as to how cancer drugs are developed.


Friends’ CEO Jeff Allen said in an interview that the approval paradigm is different for drugs to treat life-threatening illness and that requiring two clinical trials would grind the system to a halt in oncology. “Front-loading information would add years to the process,” he said.


As for the Times’ suggestion that there be minimum benefit standards, Allen said this is difficult because benefit standards can change over time as new therapies become available and they vary based on the diseases being treated. For example, thyroid cancer has a longer time for disease progression and has several available treatments while pancreatic cancer progresses more rapidly and has few viable treatment options.


“To arbitrarily say you need to increase progression free survival by six months” would be hard to do, Allen said.


Gottlieb also addressed the difficulty of assessing the magnitude of survival. “Owing to the effectiveness of new drugs, the desire of patients to cross over to promising therapies; leaving dying patients on comparator arms for long periods – to measure survival stats – can be hard. So we’re trying to modernize clinical trial design,” he tweeted.


He included a link to his June 2 address to the American Society of Clinical Oncology’s annual meeting, in which he said that by making the development process less costly, less risky, and less time consuming “we can lower the barriers to bringing new science forward with the ultimate goal of making sure more patients can benefit sooner from new advances.”


The speech apparently prompted the editorial, which began by citing Gottlieb’s recent vow “to bring ‘new science’ to market faster, in hopes that patients benefit from treatment advances sooner.”


Gottlieb said the regulatory system needs to address the needs of patients who do not have viable treatment options.


“There are critics who say we should hold drugs back from the market, and demand more pre-market studies proving overall survival endpoints, before we consider approving a new drug,” he said. “I disagree. And I suspect some of the patients who face long odds, for whom available therapy gives them just a slim chance of long-term survival, might also disagree.” (Also see “Gottlieb Uses ASCO Platform To Unveil Two Pilot Programs To Speed Drug Review” – Pink Sheet, 3 Jun, 2018.)…