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Number needed to treat

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The number needed to treat (NNT) is an epidemiological measure used in communicating the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome (e.g. the number of patients that need to be treated for one of them to benefit compared with a control in a clinical trial). It is defined as the inverse of the absolute risk reduction. It was described in 1988 by McMaster University's Laupacis, Sackett and Roberts. The ideal NNT is 1, where everyone improves with treatment and no one improves with control. The higher the NNT, the less effective is the treatment.

Contents

NNT is similar to number needed to harm (NNH), where NNT usually refers to a therapeutic intervention and NNH to a detrimental effect or risk factor.

Relevance

The NNT is an important measure in pharmacoeconomics. If a clinical endpoint is devastating enough (e.g. death, heart attack), drugs with a high NNT may still be indicated in particular situations. If the endpoint is minor, health insurers may decline to reimburse drugs with a high NNT. NNT is significant to consider when comparing possible side effects of a medication against its benefits. For medications with a high NNT, even a small incidence of adverse effects may outweigh the benefits. Even though NNT is an important measure in a clinical trial, it is infrequently included in medical journal articles reporting the results of clinical trials. There are several important problems with the NNT, involving bias and lack of reliable confidence intervals, as well as difficulties in excluding the possibility of no difference between two treatments or groups.

Variants of NNT are sometimes used for more specialized purposes. One example is number needed to vaccinate.

NNT values are time-specific. For example, if a study ran for 5 years and another ran for 1 year, the NNT values would not be directly comparable.

Statistics

NNT is the reciprocal of the absolute risk reduction i.e. 1/absolute risk reduction. In general, NNT is computed with respect to two treatments A and B, with A typically the intervention and B the control (e.g., A might be a 5-year treatment with a drug, while B is no treatment). A defined endpoint has to be specified (e.g., the appearance of colon cancer in a five-year period). If the probabilities pA and pB of this endpoint under treatments A and B, respectively, are known, then the NNT is computed as 1/(pBpA). NNT is a number between 1 and ∞; effective interventions have a low NNT. A negative number would not be presented as a NNT, rather, as the intervention is harmful, it is expressed as a number needed to harm (NNH). The units of the aforementioned probabilities are expressed as number of events per subject (see worked out example below); therefore, the inverse NNH will be number of subjects per event.

Simple examples

There are a number of factors that can affect the NNT. Let's say we have a disease, and a pill to treat the disease, that should work over the course of a week.

  • PA is the probability of still having the disease after taking the pill (i.e. complement of the probability of being cured after taking the pill). This is the experimental group.
  • PB is the probability of still having the disease after not taking the pill (i.e. complement of the probability of the disease going away by itself). This is the control group, who probably got a placebo pill instead of the real pill.
  • For example, the ASCOT-LLA manufacturer-sponsored study addressed the benefit of atorvastatin 10 mg (a cholesterol-lowering drug) in patients with hypertension (high blood pressure) but no previous cardiovascular disease (primary prevention). The trial ran for 3.3 years, and during this period the relative risk of a "primary event" (heart attack) was reduced by 36% (relative risk reduction, RRR). The absolute risk reduction (ARR), however, was much smaller, because the study group did not have a very high rate of cardiovascular events over the study period: 2.67% in the control group, compared to 1.65% in the treatment group. Taking atorvastatin for 3.3 years, therefore, would lead to an ARR of only 1.02% (2.67% minus 1.65%). The number needed to treat to prevent one cardiovascular event would then be 98.04 for 3.3 years.

    Worked example

    The relative risk is 0.25 in the example above. It is always 1-relative risk reduction, or vice versa. (The signs of the numbers needed to treat and the numbers needed to hurt are reversed: NNT is 3.33 and NNH is −10.)

    References

    Number needed to treat Wikipedia


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