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NNT can be TNT for blowing up pharma marketing claims

NNT can be TNT for blowing up pharma marketing claims

Picture of William Heisel

A new drug comes on the market that promises to improve people's eyesight. "Clarivue! Make your cloudy days sunny again!"

Your editor says, "This Clarivue is like Viagra for eyeballs. It's going to be flying off the shelves. Write up something for the Web in the next hour."

Your next move should be to find out the NNT: the number needed to treat. It will help you answer the most important question: How many people would need to take Clarivue in order for one person to actually see better?

This is the number that John Carey used as the springboard for his revelatory look at statins in BusinessWeek. It's the number that two University of Oxford professors have said "is simple to remember and directly supports efforts to work with patients to make the best possible clinical decisions for their care."

Put another way, the NNT is the number of patients that would need to undergo a particular treatment over a specific time period in order to see their health improve beyond what would have happened had they done nothing or had they undergone a different treatment.

A low number means a drug is highly effective with a broad range of people. Four people take it, and one sees better. For a vaccination, for example, the NNT might be one. A high number means the drug may be effective but only with a narrow set of people.

As Carey pointed out, Pfizer has advertised Lipitor as reducing the risk of heart attack by 36%. But the NNT is actually 100. That "crucial point is hiding in plain sight in Pfizer's own Lipitor newspaper ad," Carey wrote:

The dramatic 36% figure has an asterisk. Read the smaller type. It says: "That means in a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor."

Now do some simple math. The numbers in that sentence mean that for every 100 people in the trial, which lasted 3 1/3 years, three people on placebos and two people on Lipitor had heart attacks. The difference credited to the drug? One fewer heart attack per 100 people. So to spare one person a heart attack, 100 people had to take Lipitor for more than three years. The other 99 got no measurable benefit. Or to put it in terms of a little-known but useful statistic, the number needed to treat (or NNT) for one person to benefit is 100.

Compare that with, say, today's standard antibiotic therapy to eradicate ulcer-causing H. pylori stomach bacteria. The NNT is 1.1. Give the drugs to 11 people, and 10 will be cured.

Of course, very few drugs have an NNT near 1. The key – as with writing about absolute risk when writing about relative risk – is to provide readers the full picture of a drug's benefit. Is it worth it for 40 people to spend $100 a month for three years just so one of them can avoid a heart attack? Maybe so, especially if it is your spouse, child, parent or sibling who avoids the heart attack, but what if that number jumps to 400? And what if your employer (General Motors) is going out of business because of skyrocketing medical costs or your government is footing the bill?

Along with Carey's article, BusinessWeek ran a stunning graphic showing the NNTs for several drugs that illustrated how NNTs can be different depending on the type of people taking the drug. Statins work wonderfully in people who have had a heart attack or who have signs of heart disease. In that group, the NNT is between 16 and 23. If you've been to the ER with your life flashing before your eyes, you like those odds. For people without heart disease, the NNT shoots up to higher than 500. That should give pause to people who like to say that statins should be put in drinking water. (Carey's example of Lipitor having an NNT of 100 was based on a specific clinical trial.)

NNTs are not often called out in drug studies, especially the ones sponsored by drug companies, but if a company is pushing a new drug as a breakthrough, you should ask for the NNT. Chances are good that you will have to follow Carey's footsteps and calculate the NNTs for yourself. (You can find more great examples of NNTs here.) But the math is simple. Let's recap using another expert source, Dr. Leslie  Citrome at New York University School of Medicine in her excellent Journal of Family Practice article on NNTs.

First determine the difference between the frequencies of the outcome of interest for two interventions.

Then calculate the reciprocal of this difference.

For example, let's say drugs A and B are used to treat depression, and they result in 6-week response rates of 55% and 75%, respectively. The NNT to see a difference between drug B versus drug A in terms of responders at 6 weeks can be calculated as follows:

Difference in response rates=0.75–0.55=0.20


In this example, you would need to treat 5 patients with drug B instead of drug A to see 1 extra responder. If the NNT had been 5.5, you would round up to the next whole number (6) because you can't treat a fraction of a person.

Interpreting the importance of NNT values is easy, too. The smaller the NNT, the larger the clinical difference between interventions; the larger the NNT, the smaller the difference.

An NNT of 100 or more usually means little difference exists between interventions for the outcome of interest.

An NNT of 2 would be hugely important and is rarely encountered.

So the next time an actual Clarivue pops into view, read the fine print and find your way to the NNT.

Related posts:

Blog » Q&A with John Carey: Peeling back the label on cholesterol drugs

10 Things I Learned at AHCJ 2010

Should Vioxx still be on the market?Danger! Writing about relative risks can lead your readers astray

At the next pharma love fest, spend some time with absolute risk

Talking Risk: Vioxx, statistics and other complexities



Picture of Duncan Echelson

Thank you for the links on NNTs and for highlighting their importance for a quick and clear map of the value of drugs and procedures.  So far, so good. However, to expect most people to be able to generate NNT numbers or to extract them from their physicians or the drug manufacturers is a very optimistic of you.

The problem is simple, the vast majority of those with access to NNT statistics have little interest in generating or sharing them.  in fact, in many instances, it is to their financial and professional interests to keep these figures either unknown or safely tucked away in publications.  

I truly wish this were not the case but even a thorough search for NNT number for a broad range of drugs and treatments comes up with comparatively few results.

However, here is one google result which has a fairly extensive database of NNT figures.  The source is an evidence based medicine site in Canada.  The link puts you on the NNT definition page with links to tables of NNT statistics organized by medical field.

I hope that with the efforts of persons such as yourself that in time more sources for easy access to absolute/relative figures as well as NNT statistics will be created. Thanks.

Picture of

Hello Mr. Heisel,

I'd like to know where to find the article that shows the results "3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor.". I know the reference is to an old ad to sell lipitor using Dr. Robert Jarvik's image and I've been looking for this paper for a while now with no luck. I'd be very happy to read the original.

Thank you.

Picture of

I believe each person should calculate their personal benefit by determining their own risk (which certainly can be tricky and depends on some risk calculator being accurate.) For the trial where 3% had a heart attack vs 2% having a heart attack, a way to look at it is that it didn't benefit 99%: the 97% who weren't going to have a heart attack, plus the 2% who did anyway. So far that's not surprising; it's just another way of wording exactly what is said here. But suppose we accurately (key word "accurately") knew that our risk of having a heart attack over a time span was 80%. Of this group, 20% wouldn't have a heart attack anyway, and 51% will anyway, leaving 29% who will benefit. NNT about 3. That may be enough to say taking it is worth it. Of course, it assumes that 80% figure is accurate; that the 36% relative risk reduction holds across all risk categories, and that the side effects are minimal (they are not in may cases.) Also, that's great; but an NNT of 3 means two out of 3 won't benefit; so everyone should do more to improve their chances since we don't know who the "lucky" one will be.

Also, doctors recommend statins if the risk is greater than 7.5%. In that case, we're back into the more absurd realm: 97.5% of people won't benefit (92.5% who won't have the heart attack, plus 5% who will anyway) so the NNT is 40 (1/0.25). I wouldn't take such a dangerous drug if the NNT was any higher than 2! But that's just my tolerance. Others may have a higher or lower threshold.


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