A Third Of New Drugs Hit The US Market With Side Effects No One Knew About

Let's say you've got some pretty severe arthritis pain. Your doctor prescribes you the same anti-inflammatory they have prescribed everyone else, and it works! This new drug has given you new life! But then, you start hearing disturbing news reports -- the same drug seems to be causing an increase in the rates of heart attacks and strokes. What do you do? How do you weigh the risks and the benefits?

Image: Derek Gavey/Flickr

This happened (albeit with more foul play) with the popular, since-withdrawn anti-inflammatory drug Vioxx. And Vioxx might not be alone. According to a new study, roughly a third of drugs approved by the United States Food and Drug Administration (FDA) seem to have some sort of negative side effect that didn't reveal itself during smaller, pre-market studies. But the study's authors didn't seem surprised, or even upset about the number. After all, a drug coming to market is the biggest clinical trial of all.

"New drugs are called new drugs for a reason: Because they're new," Dr Nicholas Downing, the study's first author from Boston's Brigham and Women's Hospital, told Gizmodo. "Unless you want to test drugs in huge populations, there's going to be uncertainty at the time when the regulator says they're going to approve a drug."

The researchers looked at the public information on all 222 new FDA drug approvals from 2001 to 2010. They found that 71 of them, or 32 per cent, had some adverse effect not caught during the clinical trials. That stuff is supposed to gets caught when drugs go through three phases of testing, which let researchers identify the side effects and ensure the drug actually cures some ill. The new analysis, published in the Journal of the American Medical Association today, found that the rates of undiscovered adverse effects were higher in drugs taken from biological sources, psychiatric drugs and those that received an accelerated and near-deadline approval.

These numbers didn't surprise anyone I spoke to -- prior studies of drugs approved by the Europeans Medicine Agencies (EMA) found similar safety event rates. "The fact that they could identify types of drugs more likely than others, like biologics or psychiatric drugs" was important, and should possibly lead to increased scrutiny once these drugs hit the market, Dr Jean-David Zeitoun, first author of the EMA study, told Gizmodo. And "the fact that they found some kind of link between the deadline and the [safety] events is important".

That last discovery perked the metaphorical ears of one FDA watchdog and a former professor of mine, journalist Charles Seife (who was not involved with the study but is working with its principle investigator on another project). "The researchers are careful to craft their findings in neutral language: These are the characteristics that appear to be associated with safety issues after the drugs and biologics get to market," he told me in an email. "But to me, the implication is that when the FDA is under pressure to move faster, safety seems to suffer." Of course, there could be other interpretations -- he thought the study's sample size was limited, for one.

Seife also thought that anyone hoping the FDA would approve drugs faster (such as US President Donald Trump, for example) should take caution, as did Harvard Medical School Professor Jerry Avorn, who told Gizmodo in an email: "It's another vital piece of data making it clear that FDA should not be in a hurry to approve drugs more quickly, or with less data, as the administration and congress seem to be advocating."

Neither Zeitoun nor Downing thought there was evidence of foul play. Instead, they pointed to a balance of getting drugs approved in time to help people versus studying them long enough to determine all the side effects.

None of the drug companies I reached out to for comment responded. The only thing that Downing (and others) requested was more data on safety and more surveillance of drugs after they're on the market. They really just wanted this data out there so consumers can understand that drug approval is far from a perfect science.

"The learning process doesn't stop at approval, and we need to use high quality clinical and claims data to learn about drugs in the years after," said Downing. "Sometimes we may learn that [drugs] are more or less effective or more or less safe."

The FDA would not comment on this specific study, but did tell Gizmodo that they do post-market monitoring, and are reviewing the paper's findings. Additionally, the agency pointed out that some adverse drug events may occur that people don't report. Americans can get adverse event information from this link by filing a Freedom of Information Act request.

But most importantly, just realise that taking medication is always a balance between risks and benefits.

"Every individual taking prescription medicines has to understand that no medication, even those over the counter or those sold as food supplements, is without risk and no drugs are assessed for long term use," director of research at the UCLA Center for Health Policy Research Nadereh Pourat told Gizmodo in an email.

She continued: "When a doctor tells you that there are no risks associated with long term use of drugs as simple as ibuprofen, this simply means there are no studies that can tell you the risks or that the benefits may outweigh the risks."

[JAMA]

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Comments

    Every drug has a side effect. The only question is how much you have to take and for how long before they become apparent.

    What a can of worms you're opening! Reminds me of the time I was prescribed a painkiller for tendon pain that.. causes spontaneous tendon rupturing - for years after you cease taking it. awesome.

    I'm also glad you said "When a doctor tells you that there are no risks associated with long term use of drugs as simple as ibuprofen, this simply means there are no studies that can tell you the risks or that the benefits may outweigh the risks." given the 10 year study in Denmark of over 10,000 patients found substantial risks associated with it's use. I've better refs than this one but the medical journal it was drawn from is quite well summed up in that article.

    While some of this stems from researchers hiding data such as with the cholesterol studies which found the more cholesterol was lowered, the greater the risk of death, another problem is the egos and $ involved such as described by this science journalist

    but more could be done if people looked up the 'number needed to treat' or NNTT and the 'number needed to harm' or NNTH for drugs they're prescribed. These numbers are widely hidden by medicine because they often can't sell their treatments when people realize the drugs or treatments on offer could in some cases have a greater chance of harming than helping a patient. Prostate screening is a good example, where screening leading to false positives fcks up lives, and false negatives which may allow genuine patients who may have actual symptoms to ignore the signs, thinking they're safe. The end result of screening was found to be a greater number of deaths !

    Or try this horror story.. would you get chemo is you knew the 5 year survival rate was a miserable 2% ? All that pain, cost, misery to have odds of survival that are lower than if you'd done nothing? Sadly of course you would - you'd cling to any lifeline you were thrown.. But how suck is it that chemo is so widely touted as a 'treatment' with 'survival rates' cited by doctors quoted as being much higher.. because they fib and think of 1 year survival rates.

    There's also the cases where doctors never warn of drug interactions with seemingly harmless things like grapefruit which can cause metabolism of many drugs to halt leading to overdoses.. or licorice which can send blood pressure sky high and seriously foul with some meds
    .
    It's a crying shame more doctors don't take their jobs more seriously and look more to the health and well being of their patients, some do but they seem hard to find.

    It's a tricky balancing act. There is obviously a need to be cautious and minimize risk to people who will take the drug but at the same time there is often a pressing need to get them to market so people can actually start taking them. And yes that need is often financial (the drug companies making R&D money back) but there is also the need for sick people to get effective treatments.

    If you look at reports of people with major problems waiting on new drugs you'll see a lot of them are more than willing to take the risk. Which of course raises a question about preying on desperate people with false hope.

    All I can say is I'd hate to be in the FDAs (or Aussie equivalent) shoes because it's a no win situation.

    I don't recall Licorice having to go through a drug trial, or peanuts or seafood or any of the natural agents that can kill. There are so many different combinations of foods, drugs and genes that it is not possible to say anything is totally safe. Who would think water could kill you?
    Drugs should only ever be rushed through approvals if there is no other treatment available and the consequences of no treatment are unacceptable.

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