Madison Area Lyme Support Group

The U.S. Food and Drug Administration (FDA) has approved hundreds of drugs over the last several decades with little to no evidence that they work, according to a new investigation by The Lever.

Many of the drugs are permitted to stay on the market, despite ample evidence that they don’t work and that they cause serious and irreparable harm.

The Lever’s two-year investigation into the FDA-approved drugs analyzed government reports, internal FDA documents, investigators’ notes, congressional testimony, court records and more than 100 interviews with researchers, federal officials and patients.

The investigation found that from 2013 through 2022, 73% of drugs approved by the FDA didn’t meet the agency’s four foundational standards required to show the drugs work as expected. Fifty-five of the approved drugs met only one of those four standards, and 39 met none of them.

More than half of drug approvals were based on preliminary data, which meant the pharmaceutical companies didn’t submit evidence that patients had fewer symptoms, showed improvement or had their lives extended.

The approval rate of such drugs has accelerated over the last decade, according to the U.S. Department of Health and Human Services Office of Inspector General.

Cancer treatments, in particular, raised serious red flags. Only 2.4% of the 123 cancer drugs met all of the criteria, and 29 met none. The FDA approved 81% of cancer drugs based on preliminary data.

The report did not evaluate any vaccines.

The Lever wrote:

“These statistics come after billions of dollars and years of lobbying by the pharmaceutical industry and patient advocacy groups pressuring Congress to loosen the FDA’s scientific standards.

“The resulting seismic shift from proving drugs work before they are approved to showing they work only after approval — if ever — has been quietly accomplished with virtually no awareness by doctors or the public.

“Insurers and taxpayers effectively pay for research after drugs hit the market as pharmaceutical companies reap the profits. Patients serve as the unwitting guinea pigs — with very real consequences.”

The outlet also reported that an estimated 128,000 people are killed each year by side effects from prescription drugs prescribed as indicated.

Demand for drugs during the AIDS epidemic led to lowered standards

The FDA regulates $3.9 trillion worth of products each year, including drugs, food, supplements, tobacco and medical devices, according to The Lever.

Until the AIDS epidemic in the 1980s, the agency had stricter regulatory procedures. However, demands by activists seeking faster access to new drugs in the context of the AIDS crisis, with the support of the pharmaceutical industry, resulted in the loosening of requirements for some drugs.

For example, requirements that pharmaceutical companies submit more than one randomized controlled clinical trial showing that a drug is effective meant that researching drugs took time — the entire approval process could take up to 12 years.

In 1992, the FDA created the “accelerated pathway,” allowing companies to submit only preliminary data showing AIDS drug effectiveness. Companies were expected to submit further evidence of effectiveness after the drugs were on the market.

The new rules also allowed companies to win approval without showing clinical outcomes — evidence that a drug positively affected a patient’s life. Instead, they could test for “surrogate outcomes,” considered “reasonably likely to predict” a clinical benefit.

For example, instead of a medication for strokes showing that it stops strokes, it can show a surrogate endpoint, such as controlling blood pressure. The AIDS drug AZT won approval on that basis — it increased the number of T-cells needed to fight viruses, but had no effect on AIDS and instead proved extremely toxic to those who took it.

GSK, the original manufacturer of AZT, reaped $2 billion in profits.

In 1992, Congress formalized the reduced standards in the Prescription Drug User Fee Act, which explicitly directed the FDA to allow approvals based on lower standards.

Pharmaceutical contributions to political campaigns shot up before the bill passed, from $1.9 million in 1990 to $3.6 million in 1992.

FDA approves drugs based on ‘flimsy, contradictory, and inadequate’ evidence

The Lever identified four key criteria drugmakers should meet, according to FDA standards, to assess whether drugs are safe and effective. They are:

• Control group: Patients taking the drug were compared to a control group that was given a placebo or a comparator drug.
• Replication: At least two “well-controlled” trials showed the drug was effective.
• Blinding: Subjects in the studies and the doctors who cared for them don’t know which patients are on the drug and which are in the control group.
• Clinical endpoint: The studies measured the drug’s effect on patients’ survival or function rather than a surrogate measure.

The authors note that these criteria don’t guarantee “sound scientific evidence,” but make up the minimum criteria to determine whether the drugmakers have provided “substantial evidence” to support their claims.

Only 28% of drugs approved over the 10 years studied met the four criteria. Twenty-nine percent met three criteria and more than 9% didn’t meet any of them.

“That doesn’t mean these drugs don’t work, but it does mean the FDA approved them without knowing whether they are more likely to help patients than hurt them,” the authors wrote.

More than a quarter of the drugs were for cancer, and one in four of those drugs didn’t meet any of the criteria. That’s because companies commonly get cancer drugs approved based on surrogate outcomes, like tumor shrinkage, rather than on clinical outcomes, such as reduced mortality or decreased symptoms.

“Experts say the FDA should have no illusions regarding the unreliability of such surrogate outcomes, especially since these outcomes fail to take into account the harms a drug may cause, such as liver failure and anemia,” the authors wrote.

A notable example includes the agency’s accelerated approval in 2008 of the drug Avastin to treat metastatic breast cancer.

Made by Genentech and marketed by Roche, Avastin netted $6.8 billion by 2010. Eventually, five clinical trials failed to show any clinical improvements for patients on the drug. Instead, they showed the drug caused blood clots, perforated intestines, stroke, heart problems and kidney malfunction.

The FDA eventually withdrew its approval of the drug in November 2011, but in the process, the agency and patients were attacked and harassed by the drugmakers. The FDA has since been reluctant to withdraw approval for drugs, according to The Lever.

Drugmakers that get drugs approved today on the accelerated pathway are supposed to conduct post-marketing trials to confirm the safety and effectiveness. However, more than one-third of those approved drugs have never had such a trial.

“The FDA continues to approve medicines based on evidence as flimsy, contradictory, and inadequate,” the authors wrote. “Citing the need for ‘flexibility’ and the importance of encouraging drug development when there are few treatment options, the agency has all but abandoned its hard-won standards for sound science, according to numerous experts.”

What about vaccines? 

The Lever created a database that readers can search to determine how many of the four criteria drugs approved between 2013 and the end of 2022 meet.

The list — and the investigation — does not include vaccines.

Children’s Health Defense Senior Research Scientist Karl Jablonowski said vaccine trials have similar variability in meeting the criteria laid out in The Lever investigation.

He added that even clinical trials that might claim to meet the criteria often do so “in name only.”

For example, testing against placebos that are other vaccines or that include the adjuvant contained in the vaccine doesn’t provide true safety data.

He said:

“A placebo specifically does not have a medical effect, except in vaccine research where the ‘placebo’ may constitute all the excipients [components added as preservatives or to increase effectiveness] less the antigen. The excipients contain the chemicals, or adjuvants, that agitate the immune system and get it to pay attention to the antigen.

“The more alarming the adjuvant is to the immune system, the more likely it is to create durable immunity to the co-administered antigen. But adjuvants are really nasty chemicals, and are by no means a healthy baseline.”

Jablonowski also said clinical trials aren’t always blinded, even if they claim to be. For example, the Pfizer-BioNTech study of the COVID-19 vaccine shows that the number of patients who withdrew from the study was 45% greater in the placebo group than in the vaccinated group.

“Statistically, there is a 0.02% chance that the study was actually blinded, or 99.98% chance it was unblinded,” Jablonowski said.

Many vaccines test for antibodies, rather than for protection against disease. “The more uncommon a disease is, the larger a trial must be to capture statistical significance,” according to Jablonowski.

Other vaccines, like Merck’s HPV vaccine Gardasil, which the company touts as protecting women against cervical cancer, were never clinically tested against cancer outcomes, because it takes such cancers a long time to develop.

“There is no such thing as a prospective 30-year clinical trial, so the HPV vaccine was approved without establishing the primary clinical outcome,” he said.

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