A comprehensive two-year investigation has revealed that the Food and Drug Administration approved hundreds of prescription drugs without adequate evidence that they work, raising serious questions about patient safety and the integrity of the nation's drug approval process.
The investigation, conducted by The Lever and the McGraw Center for Business Journalism, analyzed all 429 new drugs approved by the FDA from January 2013 through December 2022. The findings show that 73% of these drugs—311 in total—were approved despite failing to meet the agency's own foundational standards for demonstrating effectiveness.
Systematic Breakdown of Scientific Standards
The analysis evaluated drugs against four essential criteria established by the FDA's own standards and case law:
- Control group: Patients taking the drug were compared to a control group receiving placebo or comparator drug
- Replication: At least two well-controlled trials demonstrated effectiveness
- Blinding: Neither subjects nor doctors knew which patients received the drug versus control
- Clinical endpoint: Studies measured effects on patient survival or function rather than surrogate measures
Only 118 drugs (28%) met all four criteria. Most alarmingly, 39 drugs—more than 9% of the total—failed to meet even a single criterion, meaning they were approved with no comparison group, no blinding, no replication, and no clinical outcomes data.
Cancer Drug Approvals Show Particularly Troubling Patterns
Cancer treatments represented the most concerning category of approvals. Of 123 cancer drugs approved during the study period, only three (2.4%) met all four minimum criteria. Twenty-nine cancer drugs—nearly one in four—met none of the standards.
The investigation found that 81% of cancer drugs were approved based on surrogate outcomes like tumor shrinkage rather than whether patients actually lived longer or felt better. This approach has proven problematic, as subsequent studies show that only 14% of cancer drugs approved on surrogate outcomes between 2008-2012 were later demonstrated to improve real-world survival.
Dr. Reshma Ramachandran, codirector of the Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, emphasized the stakes: "We need an agency that's independent from the industry it regulates and that uses high-quality science to assess the safety and efficacy of new drugs. Without that, we might as well go back to the days of snake oil and patent medicines."
Case Study: Elmiron's Three-Decade Market Presence Without Proof
The drug Elmiron exemplifies the investigation's findings. Approved in 1996 for interstitial cystitis, the bladder medication was authorized with virtually no efficacy data, contingent on the manufacturer conducting a confirmatory study. That study took 18 years to complete and showed patients on Elmiron performed no better than those receiving placebo.
Despite this failure, Elmiron remained on the market. By 2024, hundreds of patients had suffered vision loss or blindness from the drug, with dozens of deaths and 45 hospitalizations from severe colitis reported to the FDA. Dr. Nieraj Jain at Emory University first identified the vision problems in 2018, coining the term "pigmentary maculopathy" for this new cause of blindness.
Patient Laura MacMillan, who took Elmiron for 20 years, experienced both colitis and progressive blindness. "I can't drive anymore," she said. "I had to stop working thirteen years ago. When I get up in the morning, it can take about two hours for the blurriness to subside enough for me to see words on my tablet."
Post-Market Studies Frequently Fail or Never Materialize
The investigation revealed systematic problems with confirmatory studies required after expedited approvals. According to a 2022 analysis by the Department of Health and Human Services Office of Inspector General, more than one-third of drugs approved on accelerated pathways never completed confirmatory trials. When studies were conducted, they took anywhere from months to 12 years—or in some cases, up to 30 years.
Even when post-market studies are submitted, they often provide no meaningful new information. In cancer drugs, 20% of follow-up studies examined the same surrogate outcome used for initial approval, while another 21% used different surrogate endpoints rather than clinical outcomes.
The FDA has created a term—"dangling approvals"—for drugs whose post-market trials failed or weren't conducted by their deadlines. As of 2021, the agency allowed ten of thirty-five cancer treatments to remain on market even after follow-up studies failed.
Financial Impact and Patient Consequences
The financial implications are substantial. From 2018-2021, Medicare and Medicaid spent $18 billion on drugs approved conditionally pending confirmatory trials that had yet to be delivered. Meanwhile, an estimated 128,000 Americans die annually from side effects of properly prescribed medications—more than deaths from all illegal drugs combined.
Dr. Jerome Hoffman, professor emeritus at UCLA and lead analyst for the investigation's database, summarized the core issue: "Most of us imagine that the primary goal of the FDA is to make sure that the drugs it approves are more likely to help people than to harm them. If so, the FDA would require drugmakers to submit rigorous studies. Instead, the agency seems to have forgotten about that goal and is more interested in promoting the interests of industry than protecting the public health."
Historical Context and Industry Influence
The investigation traces current problems to policy changes that began during the AIDS crisis in the 1980s. Under pressure from patient advocates and pharmaceutical companies, the FDA created "accelerated pathways" in 1992, allowing approvals based on preliminary evidence with the expectation that more substantive proof would follow.
Pharmaceutical industry campaign contributions jumped from $1.9 million in 1990 to $3.6 million in 1992, coinciding with passage of the Prescription Drug User Fee Act. This legislation required drug companies to pay fees that funded FDA operations, leading critics to argue that senior agency officials began viewing the industry as "partners" rather than entities to regulate.
Dr. Gregg Gonsalves, an AIDS activist and Yale epidemiologist who participated in the original advocacy efforts, now acknowledges the unintended consequences: "We opened Pandora's Box, and pharma exploited it. We've arrived in hell."
Expert Concerns About Current Direction
The investigation's findings have shocked even seasoned FDA observers. Diana Zuckerman, founder of the National Center for Health Research and a member of the investigation's advisory committee, said: "I've been discouraged about the FDA before, but the last few years have been the worst. The scientific bar is often so low it would be impossible to lower it much further."
The analysis comes as the Trump administration has issued executive orders demanding federal agencies deregulate numerous industries, raising additional concerns about the future of drug oversight. With Martin Makary nominated as FDA commissioner and Robert F. Kennedy Jr. as Health and Human Services secretary, experts worry about further erosion of scientific standards.
The investigation involved a team of four experts, including three physicians, who evaluated scientific studies cited in FDA approval decisions. A fourteen-member advisory committee of physicians, epidemiologists, biostatisticians, and other experts provided guidance and vetted findings for accuracy.
