We used to have tremendous confidence in the FDA. We weren’t the only ones. For decades, the U.S. Food and Drug Administration was respected around the world. That’s because it protected the American public from disastrous drug side effects. In addition, it set a high bar for drug approvals. Pharmaceutical manufacturers had to prove that their drugs actually helped patients more than they harmed them.
Drug Approval Has Changed!
A drug company that wanted the agency to approve its medicine needed to present significant data from two convincing clinical trials. These needed to show that the product was reliably better than an inert but indistinguishable placebo product.
A recent decision by the FDA has undermined its credibility. The agency approved aducanumab (Aduhelm) to treat Alzheimer disease not because it addresses the symptoms or slows a victim’s slide into stupor but because it reduces a marker in the brain. In fact, as the FDA itself explained, it used the accelerated approval pathway because that permits approval based on biochemical measurements instead of clinical improvement. They call this a “surrogate endpoint.”
Is Beta-Amyloid A Boondoggle?
In this case, the marker is beta-amyloid, a tiny piece of a protein found in the brain. No one doubts that the brains of people with Alzheimer disease are full of plaques with bits of beta-amyloid stuck together. The hypothesis is that these plaques cause the disease. But this idea remains unproven and controversial.
Aduhelm does reduce beta-amyloid plaques in the brain. No one disputes that. The question is whether this will make an important difference for patients and their families.
Surrogate Endpoints and Confidence in the FDA?
Changing a surrogate endpoint is not the same as offering clinical improvement. Dr. Matthew Schrag is a neurologist who does research at Vanderbilt University Medical Center. He offered this analogy in the Washington Post (July 16, 2021):
“Even if amyloid does cause Alzheimer’s disease, it does not necessarily mean you can cure the disease by removing it. If someone came to the emergency room with a stab wound, just removing the knife wouldn’t cure them either.”
Surrogate Endpoints and the Heart:
This is not the first time the FDA has approved a drug based on a surrogate endpoint. Alirocumab (Praluent) and evolocumab (Repatha) are recent cholesterol-lowering medications. When added to statins, they dramatically reduce “bad” LDL cholesterol. FDA approved these medications based on cholesterol measurements.
The understanding was that the companies would conduct clinical trials to see if they also prevent heart attacks and death. In a recent review, these drugs lowered LDL cholesterol successfully, but the reduction in death from coronary heart disease was not statistically significant (Journal of Clinical Medicine, Apr. 5, 2021).
Do Cancer Drug Approvals Create Confidence in the FDA?
FDA has also used accelerated approval for cancer drugs. A number of drugs have been approved based on their ability to shrink tumors. That seems like a good thing, but it doesn’t ensure a longer, healthier life.
A commentary in JAMA Internal Medicine (May 28, 2019) noted:
“Response rate is not itself a meaningful clinical outcome; the size of a tumor does not matter if patients’ lives are not extended or if their quality of life is not improved.”
You can read more about why we have lost confidence in the FDA when it comes to new cancer drugs at this link:
FDA’s Accelerated Approval of Cancer Drugs A Big Bust
Patients with hard-to-treat cancers are desperate for new and better cancer drugs. The FDA’s accelerated approval process is supposed to do that. Does it?
Is the FDA Gambling With Your Life?
I wrote an article last year in which I compared the surrogate end points the FDA loves so much with casino chips. How long would a casino stay in business if it didn’t give you money when you “cashed” in your chips? You know the answer to that question! About a nanosecond.
And yet drug companies can take your money for lowering cholesterol, reducing blood sugar or removing beta-amyloid from your brain without demonstrating any clinical benefit. In other words, the outcomes you actually care about (a healthier, longer life) do not have to be established to achieve FDA approval.
Here is a link to that article:
Do Faster FDA Drug Approvals Mean Greater Danger?
Do you trust the FDA to make wise decisions about drug safety and effectiveness? A new study in JAMA says that faster FDA drug approvals may not be better.
Everyone wants the latest, greatest treatment for Alzheimer disease, diabetes, cancer or heart disease. However, we need to be cautious about embracing drugs approved on the basis of surrogate endpoints. These medications, which are frequently extremely expensive, don’t necessarily improve patients’ lives.
What Readers Have to Say About Confidence in the FDA:
Rachel offers her perspective on Tylenol and the FDA:
“Medication, whether over the counter or prescription, has side effects. “Trust Tylenol” is a marketing slogan–nothing more. Sadly, people believe this advertising. My mother always said that each person should be his, or her, own watchdog. My father agreed with her.
“The People’s Pharmacy recently featured an article about whether or not we should trust the FDA. The FDA, the manufacturers of Tylenol and generic acetaminophen products have not done an adequate job of warning the public.”
Linda has also lost confidence in the FDA:
“As a retired Health and Welfare Manager for a national company with 40,000 medically insured employees, and over 36 years experience, I have said that the relationship between the FDA and pharmaceutical manufactures is a case of the fox guarding the henhouse.
“I’m one of those people who read about every side effect any drug is known to have, no matter how benign. I also listen to the TV ads. I lay the blame on the government’s approval to allow the drug companies to advertise their products. Advertising costs money, huge money. Follow the money.”
Marilyn thinks the FDA has lost credibility:
“I think it is terribly sad that the FDA would approve a drug that does not actually work and could bankrupt Medicare. They should be ashamed and obviously need new people with integrity to work for the FDA. Changes definitely need to be made.”
Theresa is a nurse who has lost confidence in the FDA:
“As a retired RN nursing supervisor, I would often reassure patients not to be concerned about their medication because it was FDA approved. Today, even before the current conflict re: Aduhelm, sadly, I would not be able to give the patients any reassurance at all.”
What do you think? Have you lost confidence in the FDA or do you think the agency is doing a great job? Please share your thoughts below in the comment section.
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