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Information Mastery Skills. Calculating RR, RRR, ARR and NNTs. Consider a clinical trial…. 200 subjects aged 59 years or older, with previous heart disease and type 2 diabetes randomised to two groups: 100 receive the experimental treatment 100 receive the control treatment
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Information Mastery Skills Calculating RR, RRR, ARR and NNTs
Consider a clinical trial… • 200 subjects aged 59 years or older, with previous heart disease and type 2 diabetes randomised to two groups: • 100 receive the experimental treatment • 100 receive the control treatment • Follow-up is a mean of 5 years • Endpoint is a composite of all of the CHD deaths and non-fatal MIs
Results • The treatment is clearly more effective than the control: fewer people suffered CHD-death or non-fatal MI • How can we express how much more effective it is?
Relative risk (RR) or risk ratio • What is the ratio of the rates of CHD-death or non-fatal MI in the two study groups? • RR = 20%/30% = 0.67 (or 0.2/0.3 =0.67) • Subjects who took the experimental treatment for a mean of 5 years were 0.67 times as likely to die from CHD-related causes or suffer a non-fatal MI as those who took the control.
Relative risk reduction (RRR) • By how much has the experimental treatment reduced the risk of CHD-death or non-fatal MI? • RRR = 1-RR = 1-0.66 = 0.33 (or 33%) or • RRR= (difference in event rates)/control event rate • = (0.3-0.2)/ 0.3 = 0.1/0.3 = 0.33 (or 33%) • Subjects who took the experimental treatment for a mean of 5 years were 33% less likely to die from CHD-related causes or suffer a non-fatal MI than those who took the control: the treatment has reduced the risk by one third.
Absolute risk reduction (ARR) or risk difference • How many fewer subjects in the experimental treatment group suffered CHD-death or non-fatal MI? • ARR = 30% - 20% = 10% (or 0.3 - 0.2 = 0.1) • 10% fewer subjects (10 in every 100) who took the experimental treatment for a mean of 5 years did not die from CHD-related causes or suffer a non-fatal MI than those who took the control.
Number needed to treat for benefit (NNT) • On average, how many people needed to take the experimental treatment for one to benefit? • ARR = 10% = 10 in every 100 • NNT = 1 in every 100/10 = 10 • On average, 1 in every 10 subjects who took the experimental treatment for a mean of 5 years did not die from CHD-related causes or suffer a non-fatal MI, who would have done had they all taken the control.
What if the baseline risk is lower? • RR = 2%/3% = 0.67 • RRR = 1-0.67 = 0.33 or 33% • ARR = 3%-2% = 1% • NNT = 100/1% = 100 • On average, 1 in every 100 subjects who took the experimental treatment for a mean of 5 years did not die from CHD-related causes or suffer a non-fatal MI, who would have done had they all taken the control.
Let’s try to show this with a shopping analogy • Apples – were £3 a bag, now only £2 a bag • Amount saved is £1 per bag (Original rate – new rate). • Saving is one third or 33%. (original rate – new rate / original rate; i.e. 3-2 = 1, 1/3 = one third, 1/3 x 100 = 33%
Lets try to show this with a shopping analogy • Apples – were £3 a bag, now only £2 a bag • Amount saved is £1 per bag (Original rate – new rate). • Saving is one third or 33%. (original rate – new rate / original rate; i.e. 3-2 = 1, 1/3 = one third, 1/3 x 100 = 33% • Apples – 30p a bag, now 20p a bag • Saving is 10p a bag • Saving is STILL one third Would you go out and buy apples if the saving was ONLY described as “ONE THIRD OFF”?
We can express harms in the same ways • Relative risk RR = 3%/2% = 1.5 • Relative risk increase (RRI) = 1.5-1 = 0.5 or 50% or • RRI = (difference in event rates)/control event rate • = (0.03-0.02)/0.02 = 0.01/0.02 = 0.5 (or 50%) • Absolute risk increase or risk difference (RD) = 3%-2% = 1% • Number needed to harm (NNH) = 100/1% = 100 • The experimental treatment increased the risk of major bleeds by 50%. On average, 1 in every 100 subjects who took it for a mean of 5 years suffered a major bleed which they would not have done had they all taken the control.
Weighing risks and benefits • In both groups, the experimental treatment reduced the risk of CHD death or non-fatal MI by 33% but increased the risk of major bleeds by 50% • On average, 1 in 10 of the higher-risk subjects benefited but 1 in 100 were harmed • For every 100 treated, 10 benefited and 1 was harmed • On average, 1 in 100 of the lower-risk subjects benefited but 1 in 100 were harmed • For every 100 treated, 1 benefited and 1 was harmed
In pictures www.nntonline.net
In pictures www.nntonline.net
In pictures www.nntonline.net
In pictures www.nntonline.net
In pictures www.nntonline.net
In pictures www.nntonline.net
Now try these! • COPD exacerbation rates: 5% (treatment) vs. 6% (control) • Rate of upper GI perforations, obstructions or bleeds: 3% (treatment) vs. 5% (control) • Stroke or TIA: 21% (treatment) vs. 35% (control) • Proportion of patients reporting “good” or “excellent” improvement in osteoarthritis symptoms: 40% (treatment) vs. 30% (control)
Summary • RR, RRR, ARR and NNT are easy to calculate • Relative risk and relative risk reduction are constant • They tend to look impressive, but on their own they can be misleading • Absolute risk reduction and NNTs give the benefit in the population • The lower the baseline risk, the lower the absolute benefits (and the greater the NNT) for any given relative risk reduction • All the above applies to harms as well as benefits • We need to use absolute and relative terms consistently