Quality prescribing for chronic pain 2026-2029: consultation

22. Appendix I: Numbers Needed to Treat (NNT)

22.1 What is an NNT?

The Scottish Government Polypharmacy Guidance intends to be a practical tool to help prescribers decide when it is appropriate to initiate and continue long-term medicines. In some circumstances it may be appropriate to discontinue treatments. Presentation of the number needed to treat (NNT) for a range of medicines is a tool that prescribers may use to aid discussions with individuals.

Originally described by Laupacis et al.^[189] and cited in Cook and Sackett,^[190] the NNT was introduced as an approach to summarise the effect of treatment in terms of the number of people that need to be treated with a particular therapy to expect to prevent one adverse event over a specified time period.

The NNT is defined as the expected number of people who need to receive the experimental rather than the comparator intervention for one additional person to either incur or avoid an event in each time frame. An NNT of 10 can be interpreted

that one additional (or less) person will incur an event for every 10 participants receiving

the experimental intervention rather than control over a given time frame. This is referred to as the NNT to benefit.

To estimate the probable clinical efficacy of a medicine for an individual, previous versions of this guidance calculated the NNT to capture the likely impact over a 12-month period.

NNT can be used as one factor in assessing the effectiveness of a particular intervention. The NNT is the average number of people who require to be treated for one to benefit compared with a control in a clinical trial. It is expressed as the reciprocal of the absolute risk reduction. For example, if the NNT to prevent one death in five years is 25 people, then the annualised NNT will be 125 (25 x 5).

Concern has been raised regarding the validity of the annualised NNT. McAlister^[191] noted that because the NNT is time-dependent, and not a linear measure over time, an extrapolation cannot be made from the NNT of a five-year trial to the lives of patients over one year in healthcare. This methodology has been used in the Scottish Government Polypharmacy Quality Prescribing Guide (open for consultation from 30 June 2025 to 22 September 2025) since 2012. This is supported by Guthrie et al.^[192] who have proposed that the annualised NNT has value. They argue that if it is assumed that the benefits of a treatment are accrued evenly over time, and continue to accrue after the trial is finished, then the annualised NNT has validity. From a practical standpoint they argue that it offers a more simplistic measure because the prescriber is dealing with one number, rather than the NNT and duration of treatment.

Although the annualised NNT provides a numerical comparison between therapeutic interventions, this information should not be viewed in isolation as there is always a need to consider:

• What is the outcome being avoided? Death is more significant than a vertebral fracture, but different outcomes will be more or less significant to the individual.
• Over what period does the benefit accrue? Two drugs may have the same NNT to avoid one death, but the drug that achieves that over six months is more effective than that which takes 10 years.
• NNTs can be put on the same timescale by multiplying or dividing the NNT appropriately, however, this makes the untested assumption that benefit accrues consistently over time.
• The benefits of a medication should be weighed against medication related harm.
• The number needed to harm (NNH) is the average number of people taking a medication for one to suffer an adverse event. Note that risk of adverse drug reaction (ADR) is higher in older adults.

22.2 How to interpret the NNT and NNH

NNTs are only estimates of average benefit, and it is rarely possible to know precisely what the likely benefit will be in a particular patient. Prescribers and individuals should be aware of a degree of uncertainty since it is usually not possible to calculate valid confidence intervals around NNTs.

The ideal NNT is one, where everyone improves with treatment: the higher the NNT, the less effective is the treatment (in terms of the trial outcome and timescale). So if treatment with a medicine reduces the death rate over five years from 5% to 1% (very effective), the absolute risk reduction is 4% (5 minus 1), and the NNT is 100/4 = 25.

An NNT of 10 can be interpreted that one additional (or less) person will incur an event for every 10 participants receiving the experimental intervention rather than control over a given time frame.

An NNH should ideally be a high value, so large numbers of people are treated before a harm occurs.

The risk to benefit to treatment should be weighed up in each individual and may vary considerably in people with polypharmacy.

22.3 Applicability of trial data to individual adults

The drug efficacy (NNT) table provides trial population and duration information. The closer individuals are in terms of characteristics of trial participants, and duration of treatment to the trial; the more likely they will achieve the expected benefits.

Adults approaching end-of-life have an increased risk of many events, so each individual event has a higher absolute risk. This means that interventions may have a much lower NNT for that adult. This should be balanced against the shorter time they have in life to obtain a benefit, and the increased impact that any harm may have.