# What is an NNT? What is...? series Second edition Statistics. Supported by sanofi-aventis

Save this PDF as:

Size: px
Start display at page:

Download "What is an NNT? What is...? series Second edition Statistics. Supported by sanofi-aventis"

## Transcription

1 ...? series Second edition Statistics Supported by sanofi-aventis What is an NNT? Andrew Moore MA DPhil DSc CChem FRSC Senior Research Fellow, Pain Research and Nuffield Department of Anaesthetics, University of Oxford; Editor, Bandolier The number needed to treat (NNT) has become a popular measure of effectiveness of interventions. NNTs are much easier to comprehend than any statistical description, and NNTs for different agents can be easily compared. An NNT is treatment-specific and describes the difference between a treatment and a control in achieving a particular clinical outcome. It can be used to describe any outcome where event rates are available for both a treatment and a control. Clearly defining a useful clinical outcome is the best way of calculating and using NNTs. NNTs calculated from systematic reviews of randomised controlled trials provide the highest level of evidence because systematic reviews contain all the relevant information and the largest numbers of patients available for analysis. NNTs only have utility when the evidence on which they are based fulfils criteria of quality, validity and size. Even data from a systematic review can be compromised. For further titles in the series, visit: An NNT is just one part of the information required in making a purchasing decision. There are many other factors, including adverse effects, costs, and individual, social and medical priorities. 1

2 Relative risk or benefit What is What is Figure 1. Variation of relative risk with control event rate Rationale for using NNTs Why would you want to use something like a number needed to treat (NNT) and complicate the nice statistics such as relative risks (RRs) and odds ratios (ORs) we usually get from clinical trials and meta-analyses? The trouble is that RRs, for instance, depend much more on what happens with a control than with a treatment. Look at Figure 1. In this hypothetical example of a series of trials, we use the same absolute effect a 30% benefit with treatment but vary the event rate for the control group from 1% to 61%; and, yes, control event rates this high do occur in some circumstances, and occur frequently in small trials, because of the random play of chance. You can see that the RR varies massively, from over 30 to just over 1.5; however, the same absolute benefit is given, with an extra 30% of patients benefiting in each case, and in each case the NNT is 3.3. Now look at Table 1, which shows how the NNT varies with the absolute risk increase (the percentage of patients benefiting because of the treatment). In each of these trials, the RR is the same, yet the proportion of patients benefiting from treatment varies from 1% to 44% Control event rate (%) Of course we need statistical outcomes to tell us whether a result is statistically significant, using well-tried, formal tests of significance; however, we need to go further than this because the statistical result is not helpful in making clinical practice decisions. Here the NNT (or NNT to prevent [NNTp], or number needed to harm [NNH] see below) can help to identify the proportion of patients likely to have treatment-specific effects. The best NNT is 1, when everyone experiences benefit with the treatment and no one with the control. The worst NNT is 1, when everyone experiences benefit with the control and no one with the treatment. Between these two extremes, NNT values increase to infinity, when there is no difference between treatment and control. NNTs as a measure of effectiveness Treatment specificity An NNT is treatment-specific. It describes the difference between active treatment and control in achieving a particular clinical outcome. An NNT of 1 means that a favourable outcome occurs in every patient given the treatment and in no patient in a comparison group the perfect result in, say, a therapeutic trial comparing an antibiotic with a placebo, such as in the eradication of Helicobacter pylori infection (Table 2). 1,2 Studies of treatments usually involve big effects in (relatively) small numbers of patients and, therefore, may have better NNTs than those of prophylactic interventions. There are no set limits for NNTs to be considered clinically effective, but it is generally considered that the lower the NNT (the closer to 1), the better. A correctly defined NNT must always specify the comparator, the therapeutic outcome, the duration of treatment necessary to achieve that outcome and the 95% confidence interval (CI). 2

3 Table 1. Six hypothetical trials showing variation of NNT with absolute event rates * Trial Number of patients EER CER RR AR increase NNT with outcome (%) (%) (%) Active Placebo * Trials with 1,000 patients each given active treatment or placebo AR: absolute risk; CER: control event rate; EER: experimental event rate; NNT: number needed to treat; RR: relative risk NNT = Calculating an NNT The NNT can be calculated from the simple formula: 1 (proportion benefiting from experimental intervention) (proportion benefiting from a control intervention) A fuller mathematical description is given in Box 1. For prophylaxis, where fewer events occur in the treated group, the calculation shown will produce negative NNTs. You can use those numbers by simply ignoring the sign (the numbers will still be correct), or you can switch the active and control groups around to provide NNTs with a positive sign. NNTs can also be calculated from statistical outputs of clinical trials or systematic reviews, from ORs and from the relative risk reduction (RRR) see the Further reading section below for more information on these statistical measures. There is no absolute value for an NNT that defines whether something is effective or not. NNTs for treatments are usually low because we expect large effects in small numbers of people. Since few treatments are 100% effective and few controls even placebo or no treatment are without some effect, NNTs for very effective treatments are usually in the range of 2 to 4. An exception to this might be the use of antibiotics. The NNT for H pylori eradication with triple or dual therapy, for instance, is 1.1. NNTs may also be calculated for different outcomes; so, to use the same example, the NNT for preventing one ulcer recurrence at one year is 1.8 (Table 2). 1,2 Larger NNTs can be found with useful interventions for instance prophylactic measures where few patients are affected in large populations. Aspirin, which prevents one death at five weeks after a myocardial infarction, has an NNT of 40 but is regarded as beneficial. The same is true for instituting thrombolytic therapy as early as possible Box 1. The key formula Calculating a number needed to treat (NNT) NNT = 1 where: (IMPact/TOTact) (IMPcon/TOTcon) IMPact = number of patients given active treatment achieving the target TOTact = total number of patients given the active treatment IMPcon = number of patients given a control treatment achieving the target TOTcon = total number of patients given the control treatment 3

4 Table 2. Examples of NNTs calculated from systematic reviews 1,2 Treatment Comparator Duration of Outcome NNT (CI) intervention Peptic ulcer Triple therapy Histamine 6 10 weeks Helicobacter pylori 1.1 ( ) antagonist eradication Peptic ulcer Triple therapy Histamine 6 10 weeks Ulcers remaining 1.8 ( ) antagonist cured at 1 year Migraine Oral Placebo Single dose Headache relieved 2.6 ( ) sumatriptan at 2 hours Postoperative Paracetamol Placebo 1,000 mg At least 50% pain 3.6 (3.0 to 4.4) pain single dose relief Fungal nail Terbinafine Griseofulvin 12 or 24 weeks Cured at 2.7 ( ) infection 48 weeks Painful diabetic Antidepressant Placebo At least 50% 2.9 ( ) neuropathy pain relief Postoperative Droperidol Placebo Single dose Prevention for 4.4 ( ) vomiting 48 hours in children undergoing squint correction Peptic ulcer Triple therapy Histamine 6 10 weeks Ulcers healed at 4.9 ( ) antagonist 6 10 weeks Venous Graduated No stockings Episodes of venous 9 (7 13) thromboembolism compression thromboembolism stockings Anticipated Corticosteroids No treatment Before delivery Risk of foetal RDS 11 (8 16) preterm delivery Dog bites Antibiotics Placebo Single course Infection 16 (9 92) Hypertension in Drug No treatment At least 1 year Overall prevention 18 (14 25) the elderly treatments of cardiovascular event over 5 years Myocardial Aspirin alone No treatment Prevention of one 40 infarction 5-week vascular death Myocardial Thrombolytic Later treatment Prevention of one 100 infarction therapy 5 hours 5-week vascular death earlier CI: confidence interval; NNT: number needed to treat; RDS: respiratory distress syndrome (beginning thrombolytic therapy five hours earlier has an NNT of 100). 2 The NNT method is now also being used in other ways. For example, it can be used to examine adverse effects of treatments or interventions, when it becomes the NNH. There are few examples, but, for instance, the use of epidural analgesia during childbirth is reported to produce higher rates of caesarean section. If that were regarded as harm, then the NNH would be Examples of NNT calculations The NNT is the reciprocal of the change in absolute risk brought about by an intervention. What does this mean? A few examples will serve to show how it works. As always, it is 4

8 ...? series What is First edition published Authors: Andrew Moore and Henry J McQuay This publication, along with the others in the series, is available on the internet at The data, opinions and statements appearing in the article(s) herein are those of the contributor(s) concerned. Accordingly, the sponsor and publisher, and their respective employees, officers and agents, accept no liability for the consequences of any such inaccurate or misleading data, opinion or statement. Supported by sanofi-aventis Published by Hayward Medical Communications, a division of Hayward Group Ltd. Copyright 2009 Hayward Group Ltd. All rights reserved. 8

### What is critical appraisal?

...? series Second edition Evidence-based medicine Supported by sanofi-aventis What is critical appraisal? Amanda Burls MBBS BA MSc FFPH Director of the Critical Appraisal Skills Programme, Director of

### Reporting Clinical Trial Results To Inform Providers, Payers, And Consumers

Reporting Clinical Trial Results To Inform Providers, Payers, And Consumers Conventional analyses of clinical trials can underestimate potential risks and benefits to patients. by Rodney A. Hayward, David

### Clinical Trials: What You Need to Know

Clinical Trials: What You Need to Know Clinical trials are studies in which people volunteer to test new drugs or devices. Doctors use clinical trials to learn whether a new treatment works and is safe

### HTA. How to develop cost-conscious guidelines. M Eccles J Mason. Methodology. Health Technology Assessment NHS R&D HTA Programme

Health Technology Assessment 2001; Vol. 5: No. 16 Methodology How to develop cost-conscious guidelines M Eccles J Mason Health Technology Assessment NHS R&D HTA Programme HTA HTA How to obtain copies of

### Indirect comparisons Methods and validity

Indirect comparisons - Methods and validity SUMMARY REPORT Indirect comparisons Methods and validity July 2009 HAS - Department of Medecines Assessment 1/66 Indirect comparisons - Methods and validity

### First question to ask yourself Do you really need to do a randomised controlled trial (RCT)?

So, you think you want to run a Randomised Controlled Trial? Do you know what is meant by: blinding, stratified randomisation, intention-to-treat analysis, surrogate outcomes, generalisability, confounding

### GUEST EDITORIAL. Twenty Statistical Errors Even YOU Can Find in Biomedical Research Articles. Tom Lang. Tom Lang Communications, Murphys, Ca, USA

5():-7, GUEST EDITORIAL Twenty Statistical Errors Even YOU Can Find in Biomedical Research Articles Tom Lang Tom Lang Communications, Murphys, Ca, USA Critical reviewers of the biomedical literature have

### Special review. Supporting life after stroke. A review of services for people who have had a stroke and their carers

Special review Supporting life after stroke A review of services for people who have had a stroke and their carers January 2011 About the Care Quality Commission The Care Quality Commission (CQC) is the

### How to put the evidence into practice: implementation and dissemination strategies

How to put the evidence into practice: implementation and dissemination strategies Handbook series on preparing clinical practice guidelines Endorsed February 2000 NHMRC National Health and Medical Research

### Waste and Inefficiency in the U.S. Health Care System. Clinical Care: A Comprehensive Analysis in Support of System-wide Improvements

Waste and Inefficiency in the U.S. Health Care System Clinical Care: A Comprehensive Analysis in Support of System-wide Improvements ABOUT NEHI The New England Healthcare Institute (NEHI) is an independent,

### How to review the evidence: systematic identification and review of the scientific literature

How to review the evidence: systematic identification and review of the scientific literature Handbook series on preparing clinical practice guidelines Endorsed November 1999 NHMRC National Health and

### What is a systematic review?

What is...? series Supported by sanofi-aventis Second edition Evidence-based medicine What is a systematic review? Pippa Hemingway PhD BSc (Hons) RGN RSCN Research Fellow in Systematic Reviewing, School

### Placebo interventions for all clinical conditions (Review)

Hróbjartsson A, Gøtzsche PC This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2010, Issue 1 http://www.thecochranelibrary.com

### Engaging patients in their healthcare

Engaging patients in their healthcare HOW IS THE UK DOING RELATIVE TO OTHER COUNTRIES? ANGELA COULTER PICKER INSTITUTE EUROPE APRIL 2006 Picker Institute Europe The Picker Institute works with patients,

### Unrealistic Optimism About Future Life Events

Journal of Personality and Social Psychology 1980, Vol. 39, No. 5, 806-820 Unrealistic Optimism About Future Life Events Neil D. Weinstein Department of Human Ecology and Social Sciences Cook College,

### The use of antipsychotic medication for people with dementia: Time for action

The use of antipsychotic medication for people with dementia: Time for action A report for the Minister of State for Care Services by Professor Sube Banerjee An independent report commissioned and funded

### For which strategies of suicide prevention is there evidence of effectiveness?

HEN synthesis report July 2012 For which strategies of suicide prevention is there evidence of effectiveness? Ann Scott Bing Guo Abstract Suicide is a serious global public health problem; it is associated

### Focus on preventable admissions

Trends in emergency admissions for ambulatory care sensitive conditions, 2001 to 2013 Ian Blunt October 2013 About this work programme This QualityWatch Focus On report examines trends in emergency admissions

### New Deal For Young People: Evaluation Of Unemployment Flows. David Wilkinson

New Deal For Young People: Evaluation Of Unemployment Flows David Wilkinson ii PSI Research Discussion Paper 15 New Deal For Young People: Evaluation Of Unemployment Flows David Wilkinson iii Policy Studies

### What is a QALY? What is...? series. Second edition. Health economics. Supported by sanofi-aventis

...? series Supported by sanofi-aventis Second edition Health economics What is a QALY? Ceri Phillips BSc(Econ) MSc(Econ) PhD Professor of Health Economics, Swansea University A quality-adjusted life-year

### Sawtooth Software. How Many Questions Should You Ask in Choice-Based Conjoint Studies? RESEARCH PAPER SERIES

Sawtooth Software RESEARCH PAPER SERIES How Many Questions Should You Ask in Choice-Based Conjoint Studies? Richard M. Johnson and Bryan K. Orme, Sawtooth Software, Inc. 1996 Copyright 1996-2002, Sawtooth

### Authorizing Dried Cannabis for Chronic Pain or Anxiety

THE COLLEGE OF FAMILY PHYSICIANS OF CANADA LE COLLÈGE DES MÉDECINS DE FAMILLE DU CANADA Authorizing Dried Cannabis for Chronic Pain or Anxiety preliminary guidance September 2014 This guidance document

### READ MORE READ BETTER? A META-ANALYSIS OF THE LITERATURE ON THE RELATIONSHIP BETWEEN EXPOSURE TO READING AND READING ACHIEVEMENT M. Lewis S. J.

READ MORE READ BETTER? A META-ANALYSIS OF THE LITERATURE ON THE RELATIONSHIP BETWEEN EXPOSURE TO READING AND READING ACHIEVEMENT M. Lewis S. J. Samuels University of Minnesota 1 Abstract While most educators

### Testing a Hypothesis about Two Independent Means

1314 Testing a Hypothesis about Two Independent Means How can you test the null hypothesis that two population means are equal, based on the results observed in two independent samples? Why can t you use

### Cycling & Health. What s the evidence? Nick Cavill & Dr Adrian Davis Public health advisors to Cycling England

Cycling & Health What s the evidence? Nick Cavill & Dr Adrian Davis Public health advisors to Cycling England CONTENTS ForEwOrd 5 Executive Summary 7 Introduction 9 1. A Brief History 11-12 2. THE IMPORTANCE

### GAME OF LIFE HOW SPORT AND RECREATION CAN HELP MAKE US HEALTHIER, HAPPIER & RICHER

GAME OF LIFE HOW SPORT AND RECREATION CAN HELP MAKE US HEALTHIER, HAPPIER & RICHER 2 The Sport and Recreation Alliance The Sport and Recreation Alliance is the independent umbrella body for the national

### Access all ages. Assessing the impact of age on access to surgical treatment

Access all ages Assessing the impact of age on access to surgical treatment Contents 1 Forewords 2 2 Executive summary 4 3 Methodology 7 4 Background 9 5 The impact of age on access to surgery, by procedure

### Caring for each other, Caring for ourselves

HEALTH & SOCIAL SERVICES WHITE PAPER Caring for each other, Caring for ourselves Public consultation Welcome to the White Paper from Health and Social Services. We hope you enjoy reading it, and look forward