Is U.S. Food and Drug Administration (FDA) approval the gold standard for whether a drug truly does what it’s supposed to? Not according to a recent analysis. A review by Harvard and Yale researchers found that one-in-ten drugs approved by the FDA between 2018-2021 failed one or more of the stated endpoints.
Dr. Reshma Ramachandran, an assistant professor at Yale School of Medicine who co-authored the study, said doctors, patients and health insurers depend on the FDA to rigorously vet new drugs.
The federal agency 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,” she said.
The researchers reviewed FDA documents to compare clinical trial results with the stated endpoints of the trials. Of the 21 drugs that fell short:
- Four targeted different types of cancer
- Three targeted influenza and other infectious diseases
- Three were psychiatric drugs, including for schizophrenia and ADHD
- Others targeted blood cancers and Alzheimer’s, and lung, digestive and genetic diseases
Researchers undertook this study due to FDA’s controversial approval of the Alzheimer’s drug aducanumab (Adulhelm). A subsequent Congressional investigation found Adulhelm’s approval rife with irregularities. Moreover, an approved drug with uncertain benefits doesn’t sell at a huge discount like a failed product on Groupon. When Adulhelm was approved the company announced a price tag of $57,000 a year, although it has since been reduced largely due to the controversy. All 6.5 million Alzheimer’s patients are potential customers with Medicare paying nearly all of their bills.
Why would the FDA approve drugs with ambiguous trial results? In the late 1980s there was outright corruption and bribery at the FDA but nobody has suggested that is the case now. FDA staffers have a shared goal of getting drugs through the pipeline. Drug approvals are a measurable output at the FDA, especially drugs for dreaded diseases like cancer and Alzheimer’s.
Another possible reason for approving marginal drugs is what public choice economics refers to as regulatory capture. Regulatory capture occurs when regulators begin to see their goals as aligned with the industry they regulate, even if approval criteria hasn’t been met. Then there is the uncomfortable fact that FDA salaries are probably one-third to one-half of what similar skills within the drug industry pays. Knowledge of the internal procedures as well as the FDA’s regulatory framework makes former FDA staffers’ skills in high demand once they leave the federal agency. There may be the perception that staffers who are obstructionist during their time at the FDA fare worse when it comes to landing industry jobs once they leave the FDA. If this sounds farfetched, I’m not the only one who thinks this way. A few years ago I was listening to an interview on National Public Radio about the opioid crisis. Purdue Pharma stood accused to marketing addictive painkillers far beyond what should have been considered appropriate. The interviewer asked the guest, a regulatory expert, why the FDA didn’t intervene. After discussing the literature about untreated pain and so on, the guest finally said something like, “you have to realize, the regulators are hoping for lucrative jobs in the industry as some point.”
The FDA could certainly cut through its bureaucracy and move drugs through the approval process faster. However, that doesn’t mean accepting ambiguous results for drugs with unproven efficacy.