Marks Daily Apple
Serving up health and fitness insights (daily, of course) with a side of irreverence.
2 Oct

NNT (Number Needed to Treat)

467349916 468cb2a946 2As you’ve likely noticed, we’re getting back in touch with our more surly, snarky side this week. It can be fun now and then to channel one’s inner Fuji…. (Frankly, we can’t imagine MDA without it, and we hope you agree.) From energy drinks, we turn to one of our more popular objects of exasperated investigation and sarcastic commentary. What would we do without you, Big Pharma? Suffice it to say, there’s never a dearth of material with you around. And we thank you for that.

Today’s tirade covers how a drug’s effectiveness is reported to the public and to physicians. We’ve all seen the commercials that beam promises like “reduces risk of heart attack by 40%.” Sure, the numbers can sound impressive, but is there more to the story than we’re hearing in those ads? (I’m sure you can’t imagine the answer here.) Should we chalk up our lingering skepticism to smart consumer attitudes or gratuitous cynicism? (Another leading, rhetorical question for good measure.)

Let’s examine. Everyone got their pencils, coffee, popcorn (just kidding), and stress balls ready? Let’s take this thing apart! First off, a bit of review. Some weeks ago we brought you perspective on the “harm-benefit” ratio in pharmaceutical testing. With the myriad of, say, cholesterol targeting drugs out there, you’d think that all that testing to get a new pill on the market would have to prove it’s better than the older, usually cheaper varieties already on the market. We said that would be a big, fat no. As long as they show some degree of effectiveness above that of a sugar pill, that’s all they need to prove. (O.K. – get marketing on it asap! Tell the people what they need!) Allowing companies to measure the efficacy of new pharmaceuticals against placebos instead of “current approved drugs,” we reported, has resulted in a barrage of new drugs no more effective than those already on the market and (this is the truly important part) a dangerous number of new formulations that are more risky than beneficial! “Holy buckets” is right.

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Hmmm, so how can we really judge the effectiveness and safety of these pharmaceutical treatments? If we can’t take the ads – and their claims – purely at face value, what are we supposed to look at? We think that’s an excellent question.

First off, the ads aren’t lying per se. They’re simply reporting on their drug’s effectiveness in a certain way, a way that (by chance) sounds the most advantageous. In drug trials you have what’s called relative risk, and this is often the number we hear on the ads. In a research group of a 1000 people, if 20 people are expected to suffer a heart attack in a given study period and only 10 actually do, whatever pharmaceutical drug being tested on these folks can be credited with halving the risk of heart attack. This “50% reduction” refers to the relative risk. But when you put it in the larger context of the entire group (10 in 1000 – or 1 in 100), suddenly the results don’t seem as dramatic. This means that 100 people needed to be treated with the pharmaceutical drug to stave off heart attack in one lone person. This is the NNT, the number needed to treat, to prevent heart attack. NNT is expressed as a number needed to treat to prevent a single medical event (e.g. heart attack, death, etc.). With adequate research analysis, an NNT can be offered for a given group of people with common risk factors (e.g. NNT among those with high blood pressure to prevent non-fatal stroke, NNT among those who have had a heart attack to prevent a fatal heart attack). An NNT, particularly when it is offered in both a general clinical and risk sub-group format, can provide a more realistic view of a drug’s effectiveness. It can give you and your doctor a clearer picture of what a drug is likely or unlikely to do for you.

Unfortunately, NNT isn’t reported as often as it should be. Despite encouragement for better reporting in randomized controlled trials, NNT is often not included in published studies. We raise this point because we think NNT offers a crucial part of the picture in determining and accepting a given treatment. Relative risk likely can’t tell you much. The full picture depends more on NNT analysis. We suggest doing some serious digging and questioning when considering a nonessential drug treatment.

Now, we’re always taught to consider both sides of an argument. What are the objections to the NNT as a significant and telling measure of a drug’s effectiveness? As mentioned, NNT looks at the power of a treatment to delay a particular negative medical event (e.g. heart attack, need for blood transfusion, death). But the NNT is measured within a set time frame and likely doesn’t/can’t follow the pattern of delay over a prolonged course of treatment/impact (perhaps many years or even decades) in the entire research group. Critics of NNT’s use also say that reporting a drug’s effectiveness in term of NNT will dissuade people who may benefit from the drug. (But perhaps it should in certain cases….)

The deal is this. When you begin to look at the NNTs of popular pharmaceuticals, you begin to see huge differences. An NNT chart (click image below for close up) from a pharmaceutical industry piece in Business Week offers a nice (and telling) picture of this range.

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The NNT for antibiotic prescriptions used to treat h. pylori, bacteria strain that can cause ulcers, is 1.1. For every 11 people taking the prescriptions, 10 will be successfully treated. Those are good odds. As you move into the lifestyle “blockbuster” drugs such as Lipitor, you discover that dozens if not hundreds or even a thousand people need to be treated for 1 person to avoid a particular medical event (e.g. heart attack). The number of people who benefit (relative to those treated) is so small for many of these drugs that you have to ask (and can safely assume) that many if not most of these lucky few (and very probably more in the research group) may have benefited the same or more from key lifestyle alterations!

In the background of this picture is the crass, but nonetheless practical consideration of money. How much are you paying for the chance to be one person in a hundred? How much is the government or insurance company paying for you to be part of this lottery? How much are you paying for someone else to be? (We warned you about the crass part. Call us insensitive, but there it is.) We’re happy to pay, mind you, for truly necessary treatments that work for us and for other people, but when it comes to drugs with NNT of 200+? Something about that sticks in our craw. Cads we are, all of us here, for suggesting such a vile sentiment. Can’t we find a better way to spend our health dollars for the good of ourselves and others?

But consider for a second the following. Since we’re on the subject of cholesterol targeting medications, let’s look at the fact that they are the top selling therapeutic class of drugs (by sales $) in the U.S. In 2007, they accounted for $18.4 billion dollars in pharmaceutical sales. (Proton pump inhibitors were next and antipsychotics a close third with each clocking in over $13 billion, by the way.) Let’s look at some hard examples. As the Business Week piece shows, you have to prescribe cholesterol targeting medication to 16-23 people who have heart disease or a history of heart attack in order to prevent a single heart attack in one person. To save one of those people’s lives, the number jumps to 48. When you look at patients without heart disease but risk factors like high blood pressure, you need to “treat” up to 250 people to prevent a heart attack or stroke in one person. To prevent a death in this group, 500 people have to take this medication for 5 years straight.

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Again, $18.4 billion dollars for one class of blockbuster medication in one year alone. Is it unseemly to wonder how many of these people were given these prescriptions after only presenting a single risk factor – a scenario that would be put then squarely in that 250-500+ NNT realm? What about Avandia (blood sugar reducer) prescription, which has an NNT of 1000+ to prevent a single heart attack and other serious medical events related to diabetes? Is it fair to wonder how many have tried adopting (and been consistently and strongly advised by doctors to adopt) effective lifestyle changes (e.g. diet, exercise, stress reduction)?

But there’s more. What about the risk of side effects? What risks are you taking on for the slim chance of being perhaps that 1 in 250 people? How many of those 250 people being treated with a cholesterol targeting drug will suffer muscle pain, mild dementia, gastrointestinal problems, etc. in order for one person to significantly benefit from the drug? Are you comfortable with that gamble as an individual in that group? Are we comfortable as a society saying that these odds are acceptable risks for the millions of people, including children now, who are prescribed these medications each year? Speaking of dramatic acronyms, there’s another that (not surprisingly) gets even less press. It’s a disconcerting little nugget called NNH: number needed to harm. (Now’s a good time to sip your drink and use that stress ball.) NNH in this context represents the number of people who need to take a certain medication for one person to experience a negative outcome. The “harm” here can vary, encompassing everything from experiencing a moderate to serious side effect, the development of a related condition, or death.

The number of people who experience side effects (some worse than the condition being “treated”) is substantial, and the number is growing. Remember the harm-benefit ratio post we reviewed earlier? Donald Light, Professor of Comparative Health Policy at the University of Medicine and Dentistry of New Jersey, explains “[O]ne in seven new drugs is superior to existing drugs, but two in every seven new drugs result in side effects serious enough for action by the [FDA].” These actions Light is referring to come after a drug’s release. And many physicians dismiss patient complaints of side effects (“nearly a third of the time”!) because too many aren’t fully aware of the side effects of these drugs. Researchers found that 60% of patients “said they felt their doctors did not appreciate the impact the symptoms had on their quality of life” when they reported side effects common enough to be listed in the medication’s information materials.

A side note about the side effect numbers and NNH… Before any study is completed, a number of people routinely drop out and aren’t counted in the final tabulations. This is typical and entirely expected with any human research group. And it’s inevitable that some of these people drop out due to their experience (understood at the time or not understood) of related side effects. Because they didn’t complete the study, they can’t be counted in the official study numbers, and it’s unlikely we ever hear or read anything about them.

We spend a lot of time complaining about Big Pharma (no, seriously?). But our problem isn’t (entirely) with the development, distribution and sales of truly essential medications. It’s with the culture of pill popping suggested by marketing ploys (and fueled by many influences in our society), a culture that diminishes the importance of basic health knowledge and the power of individual lifestyle choices. Manipulation for profit. We think people deserve better – more (and more accurate and relevant) information, higher standard testing and disclosure, and better opportunities to discuss medical concerns and diverse treatment options with their care providers. Exploring the NNTs of suggested prescriptions is part of this picture – for the patient and the care provider. Perhaps it’s a sad state of affairs when we have to bring suspicion, a certain dose of cynicism, and a magnifying glass to our consideration of medical treatment. We’d argue, however, that it’s the smart thing to do.

Now it’s your turn to weigh in with your insights and responses. Tell us what you think.

incurable_hippie, Ruud Rook, tomsaint11 Flickr Photos (CC)

Further Reading:

Deconstructing Healthcare in America – A Modest Proposal

The Beginning of the End: Statins for Children

Control Your Lifestyle, Control Your Genes

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You want comments? We got comments:

Imagine you’re George Clooney. Take a moment to admire your grooming and wit. Okay, now imagine someone walks up to you and asks, “What’s your name?” You say, “I’m George Clooney.” Or maybe you say, “I’m the Clooninator!” You don’t say “I’m George of George Clooney Sells Movies Blog” and you certainly don’t say, “I’m Clooney Weight Loss Plan”. So while spam is technically meat, it ain’t anywhere near Primal. Please nickname yourself something your friends would call you.

  1. Wow, I was unfamiliar with NNT. I dont take any perscription medication so i have never really spent too much time looking into it. Those numbers are pretty scary though!

    Son of Grok wrote on October 2nd, 2008
  2. Prescription drugs kills people every year. Side effects can be worse than what you take the drug for. Taking a pill for one problem but ending up with more problems from “many” side effects. For many people, taking prescription drugs does more harm than good,it kills some, and others suffer those side effects, that’s Sad!

    Donna wrote on October 2nd, 2008
  3. Also, what about the danger of becoming “addicted” to these prescription drugs. That’s another problem that happens to some people.

    Donna wrote on October 2nd, 2008
  4. Great reading! Gives me a lot to think about. If nothing else, I will look-up a given prescription’s side effects BEFORE purchasing the item. The side effects most often sound worse than the condition intended to be treated. I think that people are so overexposed to the pharmaceutical ads (in all media) that they don’t even bother to listen anymore, like a bad radio commercial spot.

    Conny wrote on October 2nd, 2008
  5. I had a discussion with my mother (RN, Professor of Nursing) last night about the relative safety of drugs in the US vs. Canada (or Mexico). She disagreed with my assertion that the FDA isn’t terribly interested in making sure my prescriptions are really designed to help, but rather that they are slightly less likely to harm than help. I was unfamiliar with NNT, but will definitely look more into that so as to be better armed for my next argument.

    Thanks for informative post (as usual)!

    Amy wrote on October 2nd, 2008
  6. Very useful information. Though, I’d be careful to use the ineffectiveness of Lipitor as a poster boy for all pharmaceuticals. I wonder what the NNT of Viagra is?

    McFly wrote on October 2nd, 2008
  7. This country is extremely oversaturated by drug companies that need only report positive ‘surrogate endpoint’ results, without any standards on NNT and, more importantly, NNH. These companies, along with the predatory insurance companies, have driven the state of American health to inhumanity.
    Barack and McCain are about to give us a whole month more of lip service regarding their convoluted plans to provide Americans with some decent level of health care but it seems to me that the solution is simple. Like foods report Nutrition Facts, every drug must come with a label with three numbers on it: NNT, NNH, and NNK (kill). Maybe then, Big Pharma would stop shelling out countless billions on R&D with marginal benefit but marketability. Maybe then, drugs of significant importance won’t be so pricey. Maybe then, insurance would be more inclined to pay out for things like pricey oncology consultations, as they’re not being bled by idiotic crap like Lipitor.
    Sorry of the rant.

    PS- Protect Vermont!!

    VT-XFitter wrote on October 3rd, 2008
  8. Here in Canada there are many good drug plans that enable people to have all kinds of drugs without needing to pay for them. It doesn’t matter if you’re employed, a senior, a child, a student, or on welfare, the gov’t will see to it that you get your drugs. I have often heard people comment on what a good thing it is that they don’t have to pay for all their drugs or else they wouldn’t be able to take them.

    Oh, yes, it is a good thing to be able to take all those drugs for FREE!!

    ….posted with great cynicism!

    new_me wrote on October 3rd, 2008
  9. Interesting article with a lot to think about.

    I’ve been on cholesterol lowering meds for over 20 years now. Began as an apparently healthy 35 y.o. woman with a total cholesterol reading of 260, but with an HDL of 18 that did not improve with exercise. Within 6 weeks of beginning treatment, my cholesterol dropped to “acceptable” levels, and my HDLs rose to 80.

    I know I am an exception to the rule. My heritage (eastern european) means that it’s likely my ancestors were among those people getting that statin (bacteria?) in their milk products for generations. Likely my “genetic liver” came to expect it in the food. At the lowest dosage available, I get incredible results.

    I am not using my experience to argue for a chemical nation. I agree that there are too many people who turn first to drugs instead of diet, exercise, life-style adjustments. Who expect their life to always be perfect. However, it is likely that if I hadn’t have taken a fairly aggressive stand 20 years ago (nobody wanted to treat a healthy pre-menopausal woman for life), I would have had my first heart attack by now.

    Deb wrote on October 3rd, 2008
  10. NNT is an interesting and informative way of looking at the usefulness of drugs.

    I wonder what the NNT would be for non-drug lifestyle changes, such as regular and a non-junk-food diet. I wonder if the NNT for such lifestyle behaviors is smaller (and therefore more effective) for preventing disease and premature death than many of the drugs mentioned.

    –Gary

    Gary wrote on October 3rd, 2008
  11. Looks like I’m a couple of years late. But whate the heck.

    Partial disclosure: I work in the healthcare industry, and I’m very familiar with pharmaceutical claims and the bases for them.

    First, let me say that, yes, pharamceutical companies have way too much power over what we learn about health, especially drugs. The system needs to be revised at the root. Pharmaceutical advertising (as all advertising) is very much weighted in its favor, and is certainly not everything you need to know (or everything your doctor needs to know, which is scarier). As a nation, and probably as a world, we are horrible at risk analysis. We worry about things that don’t happen. We ignore things that are significant threats. And we have no idea how to balance the possible benefits and risks of our medications. We not only don’t know what NNT is, we don’t have the mathematical education to understand it and a hundred others like it.

    That being said, I think your insistence that new medications be required to show significant better NNTs than ones already on the market is (pardon the pun) ill thought out.

    Not everyone reacts to every drug in the same way. Drug A may have an NNT of 80 and a few side effects while drug B has an NNT of 550 and a 30% risk of skin rash, but that doesn’t mean you, personally, will benefit from Drug A and not drug B. Having several different formulations around can, if used properly, can be a great advantage. In addition, drugs, even with similar MOAs, can have different efficacy and safety profiles in different subpopulations.

    Drug safety is not (just) a matter of getting the FDA to tighten up their standards. It mostly means patients and doctors honestly and seriously evaluating risks and benefits in relation to particular drugs in particular patients. (And the start of that would be allowing doctors to have the time to get to know their patients and their drugs.)

    I just surfed in (I was googling NNT for a paper I’m editing), but I’ll be reading more of your blog.

    Professor Longnose wrote on April 2nd, 2011

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