I cannot answer that question. It mystifies me why the Food and Drug Administration allows so many worthless medications on the market. Since I cannot understand the FDA’s motivations, perhaps a more important question is: shouldn’t the FDA remove ineffective drugs quickly? The answer, of course, is yes! But the agency seems more willing to approve drugs that don’t work than to get rid of them once they are found to be disappointing.
The FDA’s Rules for Drug Approvals:
I have been studying the FDA’s rules and regulations for about 50 years. The one abiding principle for drug approvals has always been that the agency only approves medications that are “safe and effective.” That mantra has been repeated for decades.
Drug Safety?
In my humble opinion, the mantra is meaningless. Anyone who watches TV these days routinely sees drug commercials that include a long list of potential complications such as heart attacks, strokes, kidney failure, liver damage, cancer and death.
How does the FDA justify its theoretical requirement that a drug must demonstrate that it is “safe” before getting the FDA’s blessing? That’s a question I wish more prescribers would ask. Perhaps the FDA’s definition of safe is very different from the way most people define safe.
Ineffective Drugs?
What about the effectiveness requirement? When people go to casinos to play blackjack, poker or try their luck at the roulette wheel, they do not use money. Instead, they have to purchase chips. If they win, they can exchange their chips for real money before leaving.
In this example, chips are surrogates for cash. As long as the casino honors its agreement to pay out, everything works just fine.
Imagine what would happen if the casino refused to honor its financial obligations on a Saturday night. I’m pretty sure it would be shut down on Sunday.
Perhaps you can’t relate to casino chips. How about coupons? A lot of people would be mad as all-get-out if the coupons they clipped could not be redeemed at their supermarket.
How Good Are Surrogate Endpoints?
For many years the Food and Drug Administration has been approving medications based on surrogate endpoints. In essence, it’s been accepting chips or coupons from pharmaceutical manufacturers. Have these “bets” paid off?
Far too frequently they have not, and yet the FDA is often slow to act to remove ineffective drugs from the market. Who gets cheated? Not the doctors who prescribe ineffective drugs. Not the pharmacists who dispense ineffective drugs. And not the staffers at the FDA who approve ineffective drugs.
It’s the patients of course! And often they don’t even know that they are taking medications that don’t work to accomplish the goals they may have anticipated.
By the way, an awful lot of physicians do not understand the FDA’s drug approval process. That’s not my opinion. It is the conclusion of a survey published in the journal Health Affairs (Jan. 2024). You can read the shocking results at this link.
Why Do Patients Take Ineffective Drugs?
Most people take a medication in the belief that it will help them live better or longer. The goal is to improve quality of life.
Drug companies and the FDA, on the other hand, have a hard time measuring what doctors call “clinical outcomes” or quality of life. Instead, they often rely on surrogate markers such as cholesterol, blood pressure, blood glucose or amyloid plaque in the brain. But these markers don’t always correlate with outcomes that patients and their families care about.
For example, there have been medications that lowered blood glucose but did not prevent the complications of diabetes. A drug that was extremely effective at lowering bad LDL cholesterol and raising good HDL cholesterol did not prevent strokes or heart attacks. As a result, Eli Lilly abandoned evacetrapib because of “futility.” That’s another way of saying the medication did not work. You can read the details of this oops at this link.
Are Anti-Amyloid Compounds Ineffective Drugs?
Many drug companies have developed compounds that lowered amyloid plaque in the brains of patients with Alzheimer’s disease. Unfortunately, most were dumped because they did not make any difference in patients’ cognitive function.
You can read about anti-amyloid drug failures at this link. Someday neuroscientists will look back on the FDA’s drug approvals for Alzheimer’s disease. My prediction is that in 10 or 20 years the report card for these medications will be quite disappointing.
What About Ineffective Drugs for Cancer?
Cancer patients are the most vulnerable of all. Many are willing to try a new therapy if their oncologist recommends it. Many doctors are impressed by the latest and “greatest” new treatments.
If cancer patients become desperate because a current therapy is not working, they are primed to accept a new treatment. If an oncologist is optimistic, the new medicine may seem like a lifeline.
I am all for new immunotherapies for hard-to-treat cancers. But there has to be some meaningful data that they actually deliver what they promise. A study in JAMA (April 7, 2024) reveals that a surprisingly high proportion of cancer drugs that get accelerated approval from the FDA do not live up to expectations.
The FDA uses accelerated approval to allow “promising” drugs on the market based on surrogate markers. The manufacturers promise to conduct clinical trials to see whether the medicines actually provide important clinical benefit. In other words, do they deliver on the promise? If so, they can get regular approval later.
The study examined cancer drugs that got accelerated approval between 2013 and 2023. There were 46 that had at least five years of follow-up data to allow the investigators to evaluate their impact on length of survival or quality of life.
Shockingly, only 43% of them demonstrated clinical benefit during follow-up trials. Twenty-two percent were taken off the market during that time. That means 57% of the approvals did not demonstrate improved progression-free survival or better quality of life over five years. The investigators were concerned about this high failure rate.
Here are the authors’ conclusions:
“Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.”
Let’s Not Forget Phenylephrine When Discussing Ineffective Drugs:
Compared to ineffective cancer drugs, phenylephrine (PE) seems incredibly trivial. And yet Americans have been wasting money on this oral decongestant for decades.
According to a study published in JAMA (Feb. 8, 2024), Americans purchased 20 billion doses of this drug over the last decade. The authors suggest that the bill for phenylephrine-containing products was over $3.4 billion. You can read more about this travesty at this link.
The FDA should have known about concerns with PE effectiveness a long time ago. I wrote about the problems with this oral decongestant in my first book, The People’s Pharmacy (St. Martin’s Press, 1976). That was almost 50 years ago!
I recently found an article on the FDA’s website titled:
“The Current Status of Oral Phenylephrine as a Nasal Decongestant with Dr. Theresa Michele and Dr. Ilisa Bernstein”
The date of this FDA podcast was March 19, 2024.
The Quick Summary:
- The FDA was aware that there were important questions about phenylephrine effectiveness at least as early as 2007.
- An FDA Advisory Committee meeting held on September 11 and 12, 2023, concluded that PE does not work in oral formulations. Here is the FDA’s convoluted description:
“The committee discussed new data on the effectiveness of oral phenylephrine and concluded that the current scientific data do not support that the recommended dosage of orally administered phenylephrine is effective as a nasal decongestant.”
You might think that the Food and Drug Administration might take prompt action now that its own advisory committee suggested this common drug is ineffective. Au contraire. We are talking about a very slow-moving bureaucracy.
Here Is How the FDA Describes Its Timeline:
“If FDA determines that oral phenylephrine is not GRASE [generally recognized as safe and effective] as an OTC nasal decongestant, we intend to initiate a multistep process that will require a proposed order, a 180-day comment period, and then issuance of a final order. The public would have the opportunity to comment on the proposed order.”
But wait…that’s not the end. There could be:
“…the opportunity to provide additional data. During this time, the marketing status of oral phenylephrine would not change.”
If, after all this time:
“…FDA concludes that phenylephrine is not generally recognized as safe and effective as an OTC oral nasal decongestant under the conditions of the relevant OTC monograph, the agency would then issue a final order removing this ingredient from the monograph. Only after FDA issues a final order would manufacturers be required to reformulate or remove OTC monograph products containing oral phenylephrine.”
Trust me when I tell you that this process could take a very long time. I am not holding my breath.
Final Words:
How To Get Ineffective Drugs Off the Market Faster!
I believe that all drugs should have to adhere to the FDA’s mantra that they must be both “safe and effective” before marketing! And we would like the agency to define what it means by “safe and effective.”
Here’s the kicker! I would require pharmaceutical manufacturers to pay back any money they might have made on drugs that turn out not to work. And I am not talking about surrogate endpoints. I am talking about quality-of-life metrics or improved longevity. Those are the outcomes that people actually care about.
In the case of Alzheimer’s disease, it would mean that people actually get their memories back! It would mean that they could recognize friends and family members again. They would be capable of balancing their checkbooks, driving and enjoying activities of daily living. Most important, an effective drug for Alzheimer’s disease would keep patients out of nursing homes!
What Do You Think?
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