Number needed to treat and Number needed to harm
The Number Needed to Treat (NNT) and Number Needed to Harm (NNH) values for each outcome was also calculated for each drug using their risk differences, and are shown in Table 13 - Table 15.
Table 13 Natalizumab versus placebo (Comparator) at time of approval
Submission | After Registration | |
Natalizumab vs. interferon beta-1a | 1.041 | 1.013 |
Natalizumab vs. glatiramer acetate | 1.036 | 1.008 |
Natalizumab vs. placebo | 1.239 | 1.211 |
Outcome | Natalizumab Risk / 1000 pts | Comparator Risk / 1000 pts | Risk Difference (95% CI) / 1000 pts | NNT | NNH | 95% CI | |||||
Benefits | Convenience Benefits | Convenience (weight 0.6%) | - | - | - | (-, | -) | - | - | (-, | -) |
Medical Benefits | Relapse (weight 3.9%) | 280 | 540 | -260 | (-326, | -195) | 4 | - | (-5, | -3) | |
Disability Progression (weight 5.6%) | 110 | 230 | -120 | (-, | -) | 9 | - | (-, | -) | ||
| | | | | | | | | | | |
Risks | Infection | Reactivation of serious herpes viral infections (weight 6.7%) | 80 | 70 | 10 | (-26, | 45) | - | 100 | (-38, | 23) |
PML (weight 55.9%) | 1 | 0 | 1 | (-, | -) | - | 1000 | (-, | -) | ||
Liver Toxicity | Transaminases elevation (weight 11.2%) | 50 | 40 | 10 | (-16, | 38) | - | 100 | (-62, | 27) | |
Reproductive Toxicity | Congenital abnormalities (weight 5.6%) | - | - | - | (-, | -) | - | - | (-, | -) | |
Neurological Disorders | Seizures (weight 5.6%) | 0 | 0 | 0 | (-, | -) | - | - | (-, | -) | |
Other | Infusion/Injection reactions (weight 2.8%) | 236 | 180 | 56 | (6, | 114) | - | 18 | (167, | 9) | |
Hypersensitivity reactions (weight 1.1%) | 90 | 40 | 50 | (20, | 82) | - | 20 | (50, | 13) | ||
Flu-like reactions (weight 1.1%) | 399 | 400 | -1 | (-114, | 114) | 1000 | - | (-8, | 9) | ||
| | | | | | | | ||||
Higher for Natalizumab | | ||||||||||
Higher for Comparator | | ||||||||||
Table 14 Natalizumab versus glatiramer acetate (Comparator) at time of approval
Outcome | Natalizumab Risk / 1000 pts | Comparator Risk / 1000 pts | Risk Difference (95% CI) / 1000 pts | NNT | NNH | 95% CI | |||||
Benefits | Convenience Benefits | Convenience (weight 0.6%) | - | - | - | (-, | -) | - | - | (-, | -) |
Medical Benefits | Relapse (weight 3.9%) | 280 | 490 | -210 | (-, | -) | 5 | - | (-, | -) | |
Disability Progression (weight 5.6%) | 110 | 180 | -70 | (-, | -) | 14 | - | (-, | -) | ||
| | | | | | | | | | | |
Risks | Infection | Reactivation of serious herpes viral infections (weight 6.7%) | 80 | 70 | 10 | (-26, | 45) | - | 100 | (-38, | 23) |
PML (weight 55.9%) | 1 | 0 | 1 | (-, | -) | - | 1000 | (-, | -) | ||
Liver Toxicity | Transaminases elevation (weight 11.2%) | 50 | 40 | 10 | (-16, | 38) | - | 100 | (-62, | 27) | |
Reproductive Toxicity | Congenital abnormalities (weight 5.6%) | - | - | - | (-, | -) | - | - | (-, | -) | |
Neurological Disorders | Seizures (weight 5.6%) | 0 | 0 | 0 | (-, | -) | - | - | (-, | -) | |
Other | Infusion/Injection reactions (weight 2.8%) | 236 | 269 | -33 | (-, | -) | 31 | - | (-, | -) | |
Hypersensitivity reactions (weight 1.1%) | 90 | 60 | 30 | (-, | -) | - | 34 | (-, | -) | ||
Flu-like reactions (weight 1.1%) | 399 | 399 | 0 | (-114, | 114) | - | ∞ | (-8, | 9) | ||
Higher for Natalizumab | | ||||||||||
Higher for Comparator | | ||||||||||
Table 15 Natalizumab versus interferon beta-1a (Comparator) at time of approval
Outcome | Natalizumab Risk / 1000 pts | Comparator Risk / 1000 pts | Risk Difference (95% CI) / 1000 pts | NNT | NNH | 95% CI | |||||
Benefits | Convenience Benefits | Convenience (weight 0.6%) | - | - | - | (-, | -) | - | - | (-, | -) |
Medical Benefits | Relapse (weight 3.9%) | 280 | 450 | -170 | (-, | -) | 6 | - | (-, | -) | |
Disability Progression (weight 5.6%) | 110 | 140 | -30 | (-, | -) | 34 | - | (-, | -) | ||
| | | | | | | | | | | |
Risks | Infection | Reactivation of serious herpes viral infections (weight 6.7%) | 80 | 70 | 10 | (-26, | 45) | - | 100 | (-38, | 23) |
PML (weight 55.9%) | 1 | 0 | 1 | (-, | -) | - | 1000 | (-, | -) | ||
Liver Toxicity | Transaminases elevation (weight 11.2%) | 50 | 40 | 10 | (-16, | 38) | - | 100 | (-62, | 27) | |
Reproductive Toxicity | Congenital abnormalities (weight 5.6%) | - | - | - | (-, | -) | - | - | (-, | -) | |
Neurological Disorders | Seizures (weight 5.6%) | 0 | 11 | -11 | (-23, | 0) | 91 | - | (43, | ) | |
Other | Infusion/Injection reactions (weight 2.8%) | 236 | 312 | -76 | (-, | -) | 14 | - | (-, | -) | |
Hypersensitivity reactions (weight 1.1%) | 90 | 40 | 50 | (20, | 82) | - | 20 | (13, | 50) | ||
Flu-like reactions (weight 1.1%) | 399 | 608 | -209 | (-320, | -98) | 5 | - | (3, | 10) | ||
Higher for Natalizumab | | ||||||||||
Higher for Comparator | | ||||||||||
Note: The use of NNT/NNH has been criticised as it does not allow different outcomes to have different amounts of importance. The development of this to the weighted Net Clinical Benefit overcomes this concern of the NNT method.