Number needed to treat
Encyclopedia
The number needed to treat (NNT) is an epidemiological
measure used in assessing 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 (i.e. the number of patients that need to be treated for one 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. 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.
Variants 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 it was found that the NNT was 100 during this 5 year period, in one year the NNT would have to be multiplied by 5 to correctly assume the right NNT for only the one year period (in the example the one year NNT would be 500).
pA and pB of this endpoint under treatments A and B, respectively, are known, then the NNT is computed as 1/(pB – pA). 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 (required) per event.
. 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. 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.
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 99.7 for 3.3 years.
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome (i.e. the number of patients that need to be treated for one to benefit compared with a control in a clinical trial). It is defined as the inverse of the absolute risk reduction
Absolute risk reduction
In epidemiology, the absolute risk reduction or risk difference is the decrease in risk of a given activity or treatment in relation to a control activity or treatment. It is the inverse of the number needed to treat....
. It was described in 1988. 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.
Variants are sometimes used for more specialized purposes. One example is number needed to vaccinate
Number needed to vaccinate
Number needed to vaccinate is a metric used in the evaluation of vaccines, and in the determination of vaccination policy. It is a specific application of the number needed to treat metric that incorporates the implications of herd immunity....
.
NNT values are time-specific. For example, if a study ran for 5 years and it was found that the NNT was 100 during this 5 year period, in one year the NNT would have to be multiplied by 5 to correctly assume the right NNT for only the one year period (in the example the one year NNT would be 500).
Derivation
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 probabilitiesProbability
Probability is ordinarily used to describe an attitude of mind towards some proposition of whose truth we arenot certain. The proposition of interest is usually of the form "Will a specific event occur?" The attitude of mind is of the form "How certain are we that the event will occur?" The...
pA and pB of this endpoint under treatments A and B, respectively, are known, then the NNT is computed as 1/(pB – pA). 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
Number needed to harm
The number needed to harm is an epidemiological measure that indicates how many patients need to be exposed to a risk-factor over a specific period to cause harm in one patient that would not otherwise have been harmed. It is defined as the inverse of the attributable risk...
(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 (required) per event.
Relevance
The NNT is an important measure in pharmacoeconomicsPharmacoeconomics
Pharmacoeconomics refers to the scientific discipline that compares the value of one pharmaceutical drug or drug therapy to another. It is a sub-discipline of health economics. A pharmacoeconomic study evaluates the cost and effects of a pharmaceutical product...
. If a clinical endpoint is devastating enough (e.g. death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
, heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
), drugs with a high NNT may still be indicated in particular situations. If the endpoint is minor, health insurers
Health insurance
Health insurance is insurance against the risk of incurring medical expenses among individuals. By estimating the overall risk of health care expenses among a targeted group, an insurer can develop a routine finance structure, such as a monthly premium or payroll tax, to ensure that money is...
may decline to reimburse drugs with a high NNT. 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.
Example: statins for primary prevention
For example, the ASCOT-LLA manufacturer-sponsored study addressed the benefit of atorvastatinAtorvastatin
Atorvastatin , sold by Pfizer under the trade name Lipitor, is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms...
10 mg (a cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
-lowering drug) in patients with hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
(high blood pressure) but no previous cardiovascular disease (primary prevention). The trial ran for 3.3 years, and during this period the relative risk
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
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 99.7 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.)See also
- Number needed to harmNumber needed to harmThe number needed to harm is an epidemiological measure that indicates how many patients need to be exposed to a risk-factor over a specific period to cause harm in one patient that would not otherwise have been harmed. It is defined as the inverse of the attributable risk...
— the converse for side-effectAdverse effect (medicine)In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
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