Researchers raise concern in a new study about the speed with which the FDA is approving some drugs because of how much less evidence was required for approval. File Photo by ragonmages/Shutterstock

New drugs are being approved by the U.S. Food and Drug Administration for patients based on less and less solid evidence, thanks to incentive programs that have been created to promote drug development, a new study shows.

Researchers report that more than 8 out of 10 new drugs in 2018 benefited from at least one special program that streamlines the approval process.


The result is that patients are being prescribed pricey new medications that have not been tested as rigorously, said lead researcher Jonathan Darrow, an assistant professor at Harvard Medical School.

"The evidence standards have changed, but it's not clear that physicians, let alone patients, understand either the basic FDA approval standard or that requirements have become increasingly flexible over the past 40 years," Darrow said.

The share of new drugs supported by two strong clinical trials, rather than just one, decreased from 81 percent to 53 percent between the 1990s and the 2010s, researchers found.

The time that the FDA spent reviewing each new drug dropped during the same period, from 2.8 years in the late 1980s to about 7.6 months in 2018, Darrow added.

This might be good news if highly effective new drugs were reaching the market quicker, but other research has found that the large majority of newly approved drugs offer modest benefits over existing therapies, he said.

"In many cases, you can get almost all of the benefit of the new drugs by taking older drugs," such as generics, Darrow said.


The programs also haven't really improved the number of new drugs approved each year, either.

"Even with that flexibility, there has been no strong upward trend in the number of drug approvals, which on average has remained about 30 new drugs approved per year since the 1980s," Darrow said.

The average annual number of new drug approvals was 34 from 1990-1999, decreasing to 25 from 2000-2009 and then increasing to 41 from 2010-2018, researchers found.

In a statement, the FDA said that the new study "covers a very wide range of issues," and "we are concerned that the researchers do not adequately consider the marked changes in the types of drugs and the patient populations targeted by development programs that FDA now reviews, compared to those from just 10 or 20 years ago, nor the type, quality, and extent of data FDA routinely receives now compared to decades ago."

The agency added that it believes that a failure to take those "marked changes" into account "can result in inaccurate conclusions."

HealthDay also reached out to PhRMA, a trade group representing the pharmaceutical industry, but did not receive comment.

Since the 1980s, various programs have been enacted by U.S. Congress or developed by the FDA to promote the creation of drugs for rare diseases or accelerate approval of promising medications that could benefit multitudes, researchers said in background notes.

"In 2018, more than 80 percent of new drugs benefited from at least one special program," Darrow said.

These programs have weakened the review process by requiring the FDA to accept more flexible evidence, he said.


For example, evidence of a drug's effect on cholesterol levels or tumor size can be used to get it approved, rather than evidence that the drug helped people live longer or feel better or avoid emergencies such a heart attacks, Darrow said.

But there's been no benefit from these programs in terms of how long it takes a company to create a new drug, he said.

"We found there was a relatively stable period between when clinical trials began and when drugs were approved. We did not see a steep decline in the clinical development period," Darrow said.

Disturbingly, the FDA has also become more financially reliant on money from pharmaceutical companies, researchers found.

The amount of the FDA budget that comes from the pharmaceutical industry has increased from about $300 million in the 1990s to just over $4 billion in the 2010s, researchers found. These fees are used to accelerate review times, researchers said.

The FDA has tried to offset the accelerated approval process by requiring companies to track drug effectiveness and safety after it's reached the market, Darrow noted.

"But in the meantime, the agency is allowing doctors and patients to use the drug while the additional information is being collected," Darrow said. "Once drugs are available, they are available to all patients due to off-label prescribing, and those patients may not realize those drugs were approved on the basis of limited evidence or that more evidence is still being collected."

The findings were published Jan. 14 in the Journal of the American Medical Association.


These accelerated review programs have driven up health care costs needlessly, said Dr. Joshua Sharfstein, vice dean for public health practice and community engagement at Johns Hopkins Bloomberg School of Public Health in Baltimore.

The new study provides "an opportunity to pause for a minute and say, 'Can we get the benefit that's intended at perhaps a lower cost, and focus the incentive on products that are going to make the most difference?'" said Sharfstein, who wasn't part of the research.

For example, the Orphan Drug Act was intended to promote the development of drugs for very rare diseases, but "a lot of these incentives have benefitted companies that are selling drugs for many, many patients," Sharfstein said.

"I think that it's very important for FDA to study which incentives, under what circumstances, really lead to medications that make a huge difference for patients, and propose more efficient ways to apply those incentives," Sharfstein noted.

More information

The U.S. Food and Drug Administration has more about the drug development and review process.

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