As we wrote last week, many fewer people benefit from medical therapies than we tend to think. This fact is quantified in a therapy’s Number Needed to Treat,
or N.N.T., which tells you the number of people who would need to
receive a medical therapy in order for one person to benefit. N.N.T.s
well above 10 or even 100 are common. But knowing the potential for benefit is not enough. We must also consider potential harms.
Not
every person who takes a medication will suffer a side effect, just as
not every person will see a benefit. This fact can be expressed by
Number Needed to Harm (N.N.H.), which is the flip side of N.N.T.
For instance, the N.N.T. for aspirin to prevent one additional heart attack over two years is 2,000.
Even though this means that you have less than a 0.1 percent chance of
seeing a benefit, you might think it’s worth it. After all, it’s just an
aspirin. What harm could it do?
But
aspirin can cause a number of problems, including increasing the chance
of bleeding in the head or gastrointestinal tract. Not everyone who
takes aspirin will bleed. Moreover, some people will bleed whether or
not they take aspirin.
Aspirin’s
N.N.H. for such major bleeding events is 3,333. For every 3,333 people,
just over two on average will have a major bleeding event, whether they
take aspirin or not. About 3,330 will have no bleed regardless of what
they do. But for every 3,333 people who take aspirin for two years, one
additional person will have a major bleeding event. That’s an expression
of the risk of aspirin, complementing the fact that one out of 2,000
will avoid a heart attack.
Granted, one out of 3,333 is a pretty tiny risk. But remember that the chance of benefit is pretty small, too.
Sometimes,
though, the N.N.H. can be much lower, even lower than that of N.N.T.,
which suggests the chance of harm is greater than the potential benefit.
Consider screening mammograms, which are considered so essential that they are the only screening tests specifically mentioned in the Affordable Care Act, and coverage for them with no cost sharing is required by the law.
If you look at the data for all randomized controlled trials of breast cancer screening, the N.N.T. for recommending screening to prevent one death from breast cancer
after 13 years of follow-up is 1,477. But further analyses show that
the one woman would have probably died of other causes anyway. There may
be no benefit at all with respect to preventing death from all causes.
Screening with mammograms can cause harm, though. They lead to overdiagnosis, encouraging the provision of therapies that provide no benefits — but do carry risks, and therefore are considered harms.
If we look at those same studies, for every 333 women who are assigned to have a screening mammogram, one extra will undergo a lumpectomy or mastectomy
as a result. One in every 390 women assigned to have a screening
mammogram will undergo an extra course of radiation therapy as a result.
(In these randomized controlled trials, patients are either assigned to
get screening mammograms or they are not. The study then usually looks
at the outcome for all who were assigned to get the mammogram, whether
they actually did or not.)
In
other words, for about every 1,500 women assigned to get screening for
10 years, one might be spared a death from breast cancer (though she’d
most likely die of some other cause). But about five more women would
undergo surgery and about four more would undergo radiation, both of
which can have dangerous, even life-threatening, side effects.
Thus,
N.N.H., paired with N.N.T., can be very useful in discussing the
relative potential benefits and harms of treatments. As another example,
let’s consider antibiotics for ear infections
in children. There are many reasons that parents and pediatricians
might consider treatment. One commonly cited reason is that we want to
prevent serious complication from untreated infections.
Unfortunately, antibiotics
don’t do that, and the N.N.T. is effectively infinite. Antibiotics also
won’t reduce pain within 24 hours. Antibiotics have, however, been
shown to reduce pain within two to seven days. Not all children will see
that benefit, though. The N.N.T. is about 20 for that outcome.
Antibiotics can cause side effects, however, including vomiting, diarrhea or a bad rash. The N.N.H. for side effects in this population is 14.
This means that when a child is prescribed antibiotics for an ear infection,
it’s more likely that he will develop vomiting, diarrhea or a rash than
get a benefit. When patients are presented with treatment options in
this manner, they are sometimes more likely to agree to watchful waiting
to see if the ear infection resolves on its own. For most children with
ear infections, observation with close follow-up is recommended by the American Academy of Pediatrics.
A wealth of N.N.T. and N.N.H. data based on clinical trials is available on a website developed by David Newman,
a director of clinical research at Icahn School of Medicine at Mount
Sinai hospital, and Graham Walker, an assistant clinical professor at
the University of California, San Francisco. But it’s important to
understand that results from clinical trials do not always reflect what
happens in the real world. As criteria for treatment become more
permissive beyond those applied in trials, the N.N.T.s can go up.
But importantly, N.N.H.s often do not. Healthier people are less likely
to see a benefit from antibiotics or an aspirin. But they are not less
likely to have a side effect or complication.
This
is because the harms associated with treatment usually have nothing to
do with the underlying illness. They are caused by the therapy,
regardless of the reason for use. Children will develop diarrhea,
vomiting or rashes
from antibiotics in the same relative amounts no matter why we are
using them. Put another way, clinical trials are designed to target the
class of patients that most likely benefits from treatment, but they are
not targeted to those more or less likely to experience harm. When
treatments are applied in real-world clinical settings, we generally
don’t see changes in the proportion of patients harmed by them relative
to trials.
When
we stray from recommendations for therapies, and broaden the population
given studied treatments, the N.N.T.s often go up, but the N.N.H.s stay
the same. Things are often even worse than the data in studies make
them look. Fewer people benefit, but just as many are harmed.
We
hope that every therapy has a benefit. The N.N.T. shows us that
benefits are often much less likely than many might think. The N.N.H.
can show us how likely we are to have a harm compared with a benefit.
Considering both, especially in light of how practice often differs from
studies, can help us make better decisions about how to care for
ourselves and those we love.
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