How do doctors know if a new drug is really better than the ones already available?
This is an important question because new drugs come out every year and if one works better at, say, reducing the chance of a heart attack, then it's probably worth prescribing.
On the other hand a new drug will have no established track record, so there will often be a lot we don't know about it. Also, it will almost certainly be far more expensive than the drugs it's trying to replace. So it might cost our patients thousands of dollars for no added benefit. Worse, we know from studies that patients will often stop an expensive medication mid-course if they can't afford it. Might it be better in those cases to prescribe a generic medication that is almost as good?
This came up when a patient of mine who had just had a heart attack told me his cardiologist had put him on a new drug called Effient. It cost him $100 a month even with insurance. Heart attacks are caused by blocked coronary arteries and a common therapy is to use a tiny metal cage called a "stent" to hold the blocked artery open. The problem is that blood clots can form in these cages, causing new heart attacks. Drugs like Effient are prescribed to prevent this.
Another, more common drug for this is Plavix. Plavix is generic now (clopidrogel), cost as little as $10/month without insurance and has worked well for over a decade. But my patient told me his Cardiologist had run a test on him that showed that Plavix would not be as effective for him as Effient.
So, my patient is spending more than $1,000 a year extra to minimize his chance of having another heart attack, or so he's been told. But is that really what my patient is buying? Let's look at the evidence.
Plavix has been used since 1997 to help prevent blood clots from forming in arteries, and many studies showed that Plavix is especially good at preventing clots from forming in stents. But a few years ago it was discovered that up to one fourth of the people given Plavix didn't metabolize it well, so perhaps Plavix was less effective in these people.
But there's a tricky point here: "less" isn't always the same as "not enough." After all, two aspirin work as well for your headache as five. So studies were done to check if deaths, strokes or heart attacks occurred more often in patients treated with Plavix if they didn't metabolize it properly. Some studies seemed to show a difference, and others didn't. Still, the FDA decided to issue a warning for Plavix in 2010, stating that a drug other than Plavix should be used on the poor metabolizers.
Conveniently, at about this time, Effient was approved by the FDA. Effient is metabolized differently than Plavix so perhaps it was better for the poor metabolizers--no one wants to take a chance with heart attacks. Still, Effient has very little track record and costs more than many people on a fixed income could afford.
So before we get out the checkbook, we should probably make sure that Effient is really better. In fact, do we even know if it's as good as Plavix? No one had done a study to prove that switching people to Effient, even if they metabolized Plavix poorly, really helped. Finally, in November 2012, a study was published in the New England Journal of Medicine to address this.
There were over 2,400 people in the study. All of them had recently received stents for severe heart disease. Half of them were treated the traditional way (no blood tests to warn against Plavix resistance) and the other half were screened for Plavix resistance and treated accordingly. Both groups were followed for a year after receiving their stents.
And it didn't matter. It made no significant difference which treatment these people received. In fact, the group that was screened and had their therapies modified did slightly worse.
Now, the makers of Effient will tell you that this is only one study and we shouldn't jump to conclusions before more studies are done. That's good advice. It might still be that Effient is a little better and the next study will show that. But it might also be that Plavix is a little better and the next study will show that instead. And we've been using Plavix since the '90's, so it's very unlikely we'll get a nasty surprise about it. That isn't always true for the newer drugs.
There are a number of lessons that can be learned from this example and it's important for all doctors to consider the following whenever we write prescriptions:
-- New drugs are sometimes hugely beneficial, but they are always expensive and experimental (by definition). Several medications have been taken off the market after their release because of serious (and previously unknown) side effects. Some of our best drugs are older than my oldest patients. So before you try the expensive "new kid on the block," try to make sure it's fixing something that really needs to be fixed.
-- Almost all initial research on a new medication is done by the pharmaceutical company that makes it. Even with the best intentions, they're more likely to see what they want to see, and there are many examples where their intentions weren't the best. Often, new medications that did better in industry-funded studies don't do so well in follow up studies. Be suspicious of any study that's funded by a pharmaceutical company.
-- Prescribing very expensive medications when inexpensive alternatives are available doesn't just waste people's money. If someone can't afford their medication, they often won't buy it. No medication is effective if it isn't taken.
Remember, new and expensive doesn't always mean better. Sometimes that extra cost is just money for nothing.