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The Drugging of America: NNT and You

Never heard of it?NNT” stands for “Number Needed to Treat.” It’s a metric that assesses the effectiveness and the risks of a given treatment. NNT means the number of people who need to be treated to have a beneficial effect on one person.

In fact, it’s not that simple, but the overall result tells you that if, say, you give aspirin to 100 headache sufferers, 85 of them will be helped, 10 of them will not be helped, and 5 will be harmed. (No, those are not real figures! 🙄 ) You get the idea: it allows you to estimate the likelihood that a given treatment will help you (or anyone) and the chances that it could do harm.

In an age of overprescription, this is something you need to know.

There’s an extremely interesting site that explains the concept in detail and applies it to quite a few widely prescribed drugs, tests, ailments, and treatments. It’s called The NNT. When you first arrive at their landing page, the site is a little difficult to learn to navigate. But persist: it’s worth the effort. The statistical theory behind the concept is sophisticated and requires some effort to grasp. However, the results are pretty straightforward.

Here’s a video that describes the idea:

Once you see what they’re talking about, you can start to explore the site. And lemme tellya: it’s an eye-opener.

A real-world implication

Our discussion of the Drugging of America was kicked off by my own experiences with doctors trying to get me on blood pressure meds — even though I do not have high blood pressure. If I would just start swallowing pills right away, I was told, I could avoid  having a heart attack or stroke. If I declined to do so, surely I would soon drop dead of one or the other, and very likely fall to the kitchen floor, there to die alone of thirst or shock after many helpless hours of suffering.

I began to look into this and discovered that in fact the drugs do little or nothing to prevent such catastrophic events. This is confirmed by a little exploration at The NNT. In one five-year study, no patients were helped by the use of anti-hypertension drugs, but one in 12 were harmed. In another five-year study, lives were saved for 1 in 125 patients who had verifiably high blood pressure (mine is far below the numbers cited in either of these studies), 1 in 67 were helped in that they did not experience a stroke, and 1 in 100 did not have a heart attack. Meanwhile, 1 in 10 were harmed by the medication’s side effects.

Neither of these studies presents implications that are simple. It’s important to read the discussion that comes with the report. In the second study, for example, the researchers point out that “antihypertensive medicines are effective for reducing the risk of cardiovascular problems, but possibly to varying degrees. Their impact is therefore complex and multifaceted, and distilling this into a single number is not as valuable as individualizing.” Further calculation shows that among 50-year-old men, you would have to treat 238 people to prevent one heart attack and 227 to prevent one heart attack. For 50 year-old women: treat 568 to prevent a heart attack and 310 to prevent a stroke. These numbers drop as age increases: at age 65, treating just (!) 101 men will prevent one heart attack, and treating 88 men will prevent one stroke; for 65+ women, treat 294 to prevent one heart attack and 120 to prevent one stroke.

What that means is this:

Sure. If you take these drugs, you may protect yourself from a cardiovascular event some time in the next five years. But it’s far more likely that you will not have any such event, one way or the other.

Meanwhile, the drugs do have side effects. They are not entirely benign:

Harms of BP medications are very real, but not as well documented in trials as benefits. Roughly 10% stop a drug due to intolerability (NNH* 10) and types of side effects vary between antihypertensive classes, including some that can be severe (angioedema, syncope, arrhythmias, electrolyte disturbances, etc.). Many of these side effects are dose related. Moreover, there is increasing documentation of a long held suspicion, namely that antihypertensives may increase fall risk and therefore risk of major injury, particularly for elderly patients.7 As always, in addition to side effects there is the inconvenience of, among many other issues, blood pressure measurement, dose and drug alterations, cost, and pill burden. These concerns are not addressed in trials but may impact quality of life in various ways and degrees.

Entertaining, isn’t it?

Far more entertaining is a trip around the site to explore some of the other ailments for which Big Pharma and its sister medical industries would like to treat us. Take a look, for example, at the NNT for routinized mammography. Over ten years of routine testing, no women’s lives were saved if they had no palpable signs of breast cancer, but 1 in 2 were harmed by a false positive result (folks: that’s HALF of the women subjected to routine mammography!) and 1 in 5 (twenty percent!) were harmed by unnecessary surgical procedures.

Indeed, widespread mammography may cost more lives than it saves.

You know, as we were working our way up to the point of lobbing off my boobs, one of the doctors at the Mayo — an oncologist — told me quite frankly that further surgery was “probably overtreatment” (her exact words). The prominent surgeon who treated me told me, also in these words: “You do not have cancer.” The reason they wanted to proceed was the uncertainty associated with DCIS: nobody knows whether this commonplace phenomenon proceeds to cancer, and if it does, how it does and under what circumstances. So, if a possibly benign condition is discovered in the course of routine mammography, you are sucked into a treatment vortex that is very difficult to escape. Few women in their right mind, if told that they “may” or “probably will” develop a malignancy are going to decline surgery. The resulting harms are very drastic, indeed. The report notes:

Importantly, overall mortality may not be affected by mammography because breast cancer deaths are only a small fraction of overall deaths. This would make it very difficult to affect overall mortality by targeting an uncommon cause of death like breast cancer. If this is the reason for trial data demonstrating no overall mortality benefit then it means that it would take millions of women in trials before an overall mortality difference was apparent, a number far higher than the current number of women enrolled in such trials. If this is the proper explanation then any important impact on mortality exists, it is small enough that it would take millions of women in trials to identify it. This belies the public perception of mammography.

It is important to note that screening mammography saves some number of individual lives in the sense that there are almost certain to be women whose breast cancer is amenable to curative treatment at the time it is identified by mammography, but not amenable to cure at the time it is identified by physician examination or self-examination. However the number of cancers for which the window of curative potential exists exclusively during this time is likely to be small, and however many lives are saved in this way an equal number appears to be lost due to radiation from mammograms, or overdiagnosis, or false positives, or some combination of the three. The NNT that we calculate here is designed to be a tool for those attempting to make decisions about health care interventions, and in aggregate the best available evidence suggests there is no overall benefit to screening mammography. This should not be taken to mean that some individuals are not saved—it is likely that they are—however an equal number of individuals appear to lose their lives due to mammography, and there is no way to know which group one will eventually fall into….

A circumspect, and patient-centered, response to the UK review provides a brief, smart data analysis suggesting that screening mammography is taking significantly more lives than it is saving.8 This latter review takes into account improvement in cancer treatments and likely overdiagnosis (using the US data, which were published after the UK-commissioned review), and finds that the short and long-term sequelae of radiation therapy in cancer treatment regimens is leading to two to three lives taken by mammography for every one life saved (my emphasis). We have nonetheless chosen to retain the ‘Red’ (data suggest no benefit) rating of screening mammography rather than change to ‘Black’ (data suggest harms>benefits), as this review presents a best-guess projection about modern day impact.

As a final note, it is important to be aware that the primary reason for the failure of screening mammography is the ongoing inability to determine which cancer cells in which humans represent a true threat to the host. If this could be determined successfully then any screening test like mammography would be a success. Should technology and science advance to the point where prognosticating based on clinical material (i.e. biopsy cells or mammogram characteristics or individual’s biologic characteristics) was overwhelmingly accurate and reliable, early detection programs of all sorts would all become far more likely to result in life-saving benefits.

Let’s take a look at some of the other issues addressed by NNT studies.

Hmmmm…. Lookee here: bisphosphonates to fend off bone fractures in post-menopausal women. Bisphosphonate is known humorously among doctors as “Drano in a pill.” It will eat up your gut if you’re not very careful in the way you take it. Friend of mine was put on this stuff, and after three years or so was told, mirabilis! it had cured her osteoporosis. Righto!

But what does a controlled study tell us?

After three years of bisphosphonate treatment, no fractures were prevented among women who had never had a bone fracture. However, a number of the subjects were harmed…and the harms come under the heading of “mighty unpleasant.” One of them is necrosis (dying off) of the bones in  your jaws! Another is increased risk, over five years, of certain kinds of hip fractures.

In the break-a-leg department, gulping vitamin D does nothing to prevent hip fractures, unless you’re frail, elderly, and institutionalized. It can make you good and sick, though. In a study of elders living in the community (as opposed to in nursing homes), none were helped, but 1 in 36 suffered kidney stones or kidney damage.

How about prostate cancer? How are those PSA tests working out for you, guys? In six randomized controlled trials enrolling 387,286 patients, none were helped (“help” being defined as “preventing death from any cause; preventing death from prostate cancer”). But 1 in 5 were harmed, by being made to undergo a biopsy after a false-positive test.

“Why,” the researchers ask, “does detection of prostate cancer not lead to increased survival? This is not clear, but the data from this large review strongly argue against routine PSA screening in the asymptomatic man. The strategy of routinely screening all men with PSA tests leads to interventions that are not saving lives and may be causing harm. The USPSTF recommendation has stirred many partisans on both sides of the issue. PSA supporters have criticized the USPSTF decision (faulting problems with the PLCO and ERSPC trials) and some have suggested complex modeling to better identify candidates for PSA screening. It seems that the position of the American Urological Association (AUA), a long time staunch supporter of routine PSA testing, is evolving in this direction as well.”

Surely something good must come of some treatments???

Yes. Applying mild hypothermia after CPR in the event of a heart attack does have some benefit. One in six were helped (by that they mean the patient survived without brain damage) and none were harmed.

Topical capsaicin (the hot-pepper salve some people use for sore muscles and scar pain) reportedly helped 1 in 10 to 12 people with pain related to herpes, and 1 in 11 experienced relief from neuropathic pain related to HIV; none were significantly harmed.

Steroids can help people suffering from pharyngitis (sore throat): one in three were helped; none were harmed.

And, in healthy people, the Mediterranean diet apparently works better than anti-hypertensives to prevent heart disease.

Inform yourself before proceeding with any treatment, prescription or over-the-counter.

Of course, NNT is only one tool among many to help you assess what doctors are telling you, what your body is telling you, and what we know about various treatments. Remember: I am not a doctor. But even though I am not a doctor and you are not a doctor, it still behooves us to take a firm hand in whatever treatment is proposed for us.

Talk to your doctor about your questions and concerns. If you have any doubt or dissatisfaction with what she or he says, get a second opinion. If you’re still uncertain, get a third opinion. The more you know and the more you understand, the more likely it is that you will get the best treatment possible.

This is the second in a series on excessive medical treatment of Americans