Studies Question FDA’s Drug Approval Process

Two papers published on February 13 in the journal JAMA Internal Medicine bring into question the FDA’s drug approval process, calling for more transparency from the federal agency.

The first paper — a cross-sectional study from researchers at Kaiser Permanente in California — reviewed drug recommendations issued by agencies in Australia, Canada, and the United Kingdom from 2017 through 2020. The team matched all FDA-approved drugs by active ingredient to decision summary reports published by drug regulators and health technology assessment (HTA) agencies in the three countries.

In addition, the researchers assessed regulatory approval concurrence and reasons for negative recommendations. The team then estimated the annual drug cost per patient in the U.S. for drugs not recommended by international agencies.

After analyzing the data, the team found that more than one-fifth of the new drugs approved by the FDA from 2017 through 2020 were either refused marketing authorization or not recommended for reimbursement in the three countries due to unsuitable benefit-to-risk profiles, uncertain clinical benefit, or unacceptably high price.

For example, the European Medicines Agency (EMA) concluded that abaloparatide (Tymlos), betrixaban (an oral anticoagulant drug), and pexidartinib (Turalio) had serious safety issues that outweighed potential clinical benefits. What’s more, istradefylline (Nourianz) and emapalumab (Gamifant) had inconsistent or insufficient evidence supporting their effectiveness.

Additionally, the average cost of the drugs not recommended for approval or reimbursement in the three countries was more than $100,000 per patient per year in the U.S..

The scientists note that as the FDA approves more drugs through accelerated approval pathways, more medications enter the market based on fewer, shorter, or less robust clinical trials.

They also say that at the same time, "launch prices for newly marketed prescription drugs have increased by 20% each year over the past decade, with the median price reaching $180,007 in 2021."

More questions surface

The second study by Harvard and Yale researchers found that from 2018 through 2021, 21 out of 210 drugs approved by the FDA received approval based on studies that did not meet one or more end points or goals.

According to a USA Today report, some drugs approved included treatments for cancer, Alzheimer’s disease, influenza, schizophrenia, ADHD, and other conditions. Moreover, 13 of the 21 drugs were approved through expedited approval pathways.

The scientists suggest these findings question whether the FDA is transparent about some approved drugs’ safety and effectiveness.

In the USA Today report, co-author Reshma Ramachandran, M.D., an assistant professor at Yale School of Medicine, said doctors, patients, and health insurers depend on the FDA to rigorously test new drugs.

She also said the FDA needs to reassure the public "the rubber stamp that they gave — considered the gold standard around the world — really means the drug has been proven to have safety and efficacy that outweighs any risks."