The US prides itself on the fact that the FDA is arguably the best drug regulatory organization in the world. Yet in less than 5 years of being on the market, 32% of new drugs have bad enough side effects and adverse events that the FDA has had to send doctors warnings about safety and/or put “black box” labels on the drugs. And this was after drugs were on the market a median of 4.2 years.
A new study from the Yale University School of Medicine published in JAMA looked at the 222 new medicines that the FDA approved from 2001-2010. Of those drugs, 3 had to be withdrawn from the market because of safety concerns, about 20% received safety communications from the FDA, and 20% had “black box” warnings slapped on their label, the FDA’s most serious warning. Some drugs received both black box and safety communications, most often for different safety issues.
Are we safe taking new drugs? Pretty much. The good news is that few drugs get pulled from the market because they aren’t effective. The bad news is that we don’t know what the actual health risks are from new drugs. We don’t know what new side effects are or even if adverse events can be caused because the length of clinical trials is short and the number of people the drug is tested on is usually small.
Short Trials With Relatively Few Patients
Most new drugs are tested for only 6 months and on fewer than 1,000 people. Consider that a side effect considered “common” would happen in 1 in 100 people. If there were 700 people in a trial, 7 would have to complain of the same side effect. If it was an “uncommon” — but not “rare” — side effect, then 1 person in 1,000 might report it, and there aren’t even 1,000 people in many trials. That’s why so many side effects are found after the medicine is approved.
There might be a way to predict which new drugs are most likely to have safety problems — which was the goal of the study. If we could predict problem drugs, than patients could be warned of the likely possibility of unknown safety issues and follow-up studies could be more rigorous.
The researchers were able to classify most of the drugs that had postmarket safety events into 4 categories. They are drugs that received:
- “Priority Review” status: Drugs with that designation have to be reviewed within a 6-month window rather than the standard 10-month time frame.
- “Accelerated Approval” status: Drugs being developed for a serious unmet medical need can get this designation and use surrogate markers of disease in their clinical trials instead of actual outcomes (true endpoints). Surrogate markers have been helpful, but can be misleading. For example, Vytorin, a combination of Zocor and Zetia used to lower cholesterol, was shown to decrease LDL (bad) cholesterol and C-reactive protein, both considered “markers” of heart disease. Vytorin was approved based on this surrogate marker. The true endpoint is survival, and out in the real world it was found that patients using Vytorin did not live longer, even though their LDL was lower.
- “Orphan Drug” status: Drugs that treat a rare disease gain a longer period of exclusivity in the marketplace, which prolongs a generic competition. For this study, researchers examined if a drug received an orphan designation for the indication for which it was initially approved.
- Near-Regulatory Deadline Approvals: The FDA has strict deadlines for approving drugs. Those drugs that were approved within 60 days of the deadline were more likely to end up with postmarketing safety problems.
Drugs used to treat psychiatric illnesses or ones known as biologics (genetically-engineered proteins derived from human genes instead of chemical components) had more frequent safety events than others.
Increasing Drug Review Time
We need to consider taking more time to review drugs. Notice that 2 of the red flags have to do with rushing the drug through the review process: Priority Review and Near-Regulatory Deadline Approvals. The difference between a thorough, considered review and one that leads to expensive and time-consuming drug fact label changes and warnings is only days.
A third (Accelerated Approval) allows for shorter study times because of the use of surrogate markers in place of true endpoints.
We need to have rigorous and ongoing postmarket studies of drugs. It’s the only way to keep people safe and to give doctors the information they need to prescribe appropriately.
As for your own health, ask your doctor how long a drug has been on the market. When you consider taking a medicine to improve your health, don’t ask for the newest drug on the block. Unless there is a compelling reason to use a new drug, you may well be better off with older medicines that have proven themselves safe over time.