1. Number Needed To Treat (NNT)
How many patients would you need to treat with Intervention A instead of Intervention B before you would expect to encounter one additional positive outcome of interest?
Number Needed To Harm (NNH)
How many patients would you need to treat with Intervention A instead of Intervention B before you would expect to encounter one additional outcome of interest that you would like to AVOID?

2. Calculating NNT (or NNH) is Easy
What is the NNT for an outcome for Drug A versus Drug B?
fA = frequency of outcome for Drug A
fB = frequency of outcome for Drug B
Attributable Risk (AR) = fA – fB
NNT= 1/AR
By convention, when not presenting fractions, we round up the NNT to the next higher whole number
For example, Drug A results in remission 50% of the time, but Drug B results in remission 20% of the time.
NNT = 1/[ ] = 1/0.30 = Round up to 4

3. ∞ NUMBER NEEDED TO TREAT 1000 100 10 1
An NNT of ∞ occurs when both interventions have the same rate for the outcome measured
NNT values of this magnitude are irrelevant when comparing interventions except when evaluating the utility of immunizations or when examining lethal outcomes
1000
Double and triple digit NNT values are usually not important when comparing routine efficacy measures, but may become important regarding adverse outcomes that have long-term consequences
100
NUMBER NEEDED TO TREAT
Single digit NNT values are usually important enough to see differences in routine clinical practice 10 9
A NNT of 9 is a small effect size; NNT of 8.96 equals Cohen’s d of 0.2 4
A NNT of 4 is a medium effect size; NNT of 3.6 equals Cohen’s d of 0.5 3
A NNT of 3 is a large effect size; NNT of 2.3 equals Cohen’s d of 0.8 1
A NNT of 1 can only occur if one intervention has a rate of 100% for the outcome measured and the other intervention has a rate of 0%
Citrome L. Compelling or irrelevant? Using number needed to treat can help decide. Acta Psychiatr Scand Jun;117(6):412-9.

4. What is an Acceptable NNT for Drug vs. Placebo
What is an Acceptable NNT for Drug vs. Placebo? A “good” NNT is usually a single digit and the lower the number the better, but how high an NNT is still acceptable?  
NNT:
2-3
4-6
7-9+
Treatment-Resistant
Acute/Chronic Conditions
e.g. SSRI-resistant MDD
Very Treatable
Acute Conditions
e.g. Acute Agitation
Somewhat Treatable
Acute/Chronic Conditions
e.g. Osteoarthritic Pain
Want NNT < NNH
NNH advantages may make some higher NNTs acceptable
NNH disadvantages may make some lower NNTs unacceptable 4

5. What is an Acceptable NNH for Drug vs. Placebo
What is an Acceptable NNH for Drug vs. Placebo? We usually want a NNH that are double digits or greater, but how low a NNH is still acceptable? 
NNH:
<10
10-100
>100
Adverse events that are mild or moderate,
usually do not lead to discontinuation, and are usually temporary or cause no distress
and do not pose a serious health risk
e.g. Mild nausea, or sedation during mania
Adverse events that may lead to discontinuation but not associated with serious immediate health risks; alternatives do not have a better profile
e.g. Moderate weight gain
Adverse events that pose a significant health risk; for very severe adverse outcomes NNH values greater than 1000 may be more acceptable
e.g. Acute hemorrhage, serious rash 5

6. What is an Acceptable NNH vs. NNT
What is an Acceptable NNH vs. NNT? NNH usually > NNT, but how low an NNH vs. NNT is acceptable?  
NNH >> NNT
NNH > NNT
NNH ≤ NNT
When comparing a desired beneficial outcome with a very severe adverse event
e.g. agranulocytosis vs. stabilizing treatment-resistant schizophrenia
When comparing a desired beneficial outcome with an adverse event that is usually mild or moderate but that may still lead to discontinuation
e.g. sedation vs. depression response
When comparing a desired beneficial outcome with an adverse event that is usually mild or moderate but that is usually temporary and does not lead to discontinuation
e.g. dry mouth vs. depression response
NNT advantages may make some lower NNHs acceptable
NNT disadvantages may make some higher NNHs unacceptable 6

7. The Ratio of NNH to NNT is Called Likelihood to be Helped or Harmed (LHH) What is an acceptable LHH? 
NNH >> NNT
NNH > NNT
NNH ≤ NNT
When comparing a desired outcome, e.g. remission, with a very severe adverse event
When comparing a desired outcome, e.g. remission, with an adverse event that is usually mild or moderate but that may still lead to discontinuation
When comparing a desired outcome, e.g. remission, with an adverse event that is usually mild or moderate but that is usually temporary and does not lead to discontinuation 7

8. Example #1: Lurasidone
Citrome L. Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Clin Schizophr Relat Psychoses Jul;6(2):76-85.

9. Citrome L. Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Clin Schizophr Relat Psychoses Jul;6(2):76-85.

10. A LHH of 5. 0 for lurasidone 160 mg/d for response vs
A LHH of 5.0 for lurasidone 160 mg/d for response vs. parkinsonism can be interpreted that “lurasidone treatment at 160 mg/d is 5 times more likely to help the patient (≥30% decrease in PANSS) than harm the patient (parkinsonism).” For olanzapine 15 mg/d, NNT vs. placebo for ≥30% decrease in PANSS from baseline is 4 and NNH for weight increase ≥7% at study endpoint is 4, yielding a LHH of 1.0, which can be interpreted as “olanzapine treatment at 15 mg/d is equally likely to help the patient (≥30% decrease in PANSS) as harm the patient (weight gain ≥7%).”
Citrome L. Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Clin Schizophr Relat Psychoses Jul;6(2):76-85.

11. Number Needed to Treat or Harm vs. Placebo
Example #2: Vilazodone
Number Needed to Treat or Harm vs. Placebo
Efficacy - NNT
Tolerability - NNH
Citrome L. Vilazodone for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract Apr;66(4):

12. The total number of sexual AEs pooled from the two trials is 41 for the 440 subjects randomized to vilazodone 40 mg⁄ d vs. 4 of 437 randomized to placebo (i.e. 9.3% vs. 0.9%); NNH for vilazodone vs. placebo is thus 12 (95% CI 9–18).
US FDA. Vilazodone Drug Approval Package. 1 March
Citrome L. Vilazodone for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract Apr;66(4):

13. NNT vs. placebo for response for vilazodone 40 mg⁄d in the 8-week pivotal trials is 8 and the NNH vs. placebo for discontinuation because of an AE is 27. LHH = NNH⁄NNT = 27 ⁄ 8 = 3.4
Thus, vilazodone 40 mg d is 3.4 times more likely to result in a therapeutic response than a discontinuation because of an AE
If the desired outcome is remission, the applicable NNT is 14. LHH in this case would be 27 ⁄ 14 = 1.9; for remission, vilazodone 40 mg⁄d is 1.9 times more likely to achieve that goal than result in a discontinuation because of an AE
One potentially relevant example of LHH is for the outcome of achieving response vs. encountering nausea, LHH = 6 ⁄ 8 = 0.75
This means that the likelihood of achieving a response is actually less than the likelihood of encountering nausea; in other words, nausea is 1.3 times more likely to be encountered than a therapeutic response
This may not be relevant if the nausea is time-limited and easily managed
Citrome L. Vilazodone for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract Apr;66(4):

14. Example #3: Inhaled Loxapine
Effect sizes are consistent
Citrome L. Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder. Int J Clin Pract Mar;66(3):

15. Inhaled Loxapine 5 mg for Agitation Associated with Schizophrenia: Response on the PANSS-Excited Component
NNT (95% CI)
Effect sizes more robust after 10 minutes.
Time (minutes)
Minutes 10 20 30 45 60 90
120
Loxapine responders (%)
17.2
29.3
46.6
50.0
57.8
61.2
62.9
Placebo responders (%)
6.1
15.7
27.8
32.2
38.3
Citrome L. Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder. Int J Clin Pract Mar;66(3):

16. Inhaled Loxapine 10 mg for Agitation Associated with Schizophrenia: Response on the PANSS-Excited Component
NNT (95% CI)
Effect sizes more robust after 10 minutes.
Time (minutes)
Minutes 10 20 30 45 60 90
120
Loxapine responders (%)
18.8
42.9
57.1
70.5
71.4
74.1
69.6
Placebo responders (%)
6.1
15.7
27.8
32.2
38.3
Citrome L. Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder. Int J Clin Pract Mar;66(3):