Value in Health - 2002 - Schechtman - Odds Ratio Relative Risk Absolute Risk Reduction and The Number Needed To Treat
Value in Health - 2002 - Schechtman - Odds Ratio Relative Risk Absolute Risk Reduction and The Number Needed To Treat
Value in Health - 2002 - Schechtman - Odds Ratio Relative Risk Absolute Risk Reduction and The Number Needed To Treat
V A L U E I N H E A LT H
ABSTRACT
Introduction: Statistical analyses of data and making Methods: The purpose of this paper is to illustrate, using
sense of medical data have received much attention in the examples, how each measure is used, what it means, and
medical literature, but nevertheless have caused confusion what are its advantages and disadvantages.
among practitioners. Each researcher provides a different Results: Some pairs of measures present equivalent infor-
method for comparing treatments. For example, when the mation. Furthermore, it is shown that different measures
end point is binary, such as disease versus no disease, the result in different impressions.
common measures are odds ratios, relative risk, relative Conclusion: It is recommended that researchers report
risk reduction, absolute risk reduction, and the number both a relative and an absolute measure and present these
needed to treat. The question faced by the practitioner is with appropriate confidence intervals.
then: Which one will help me in choosing the best treat- Keywords: odds ratio, risk reduction, number needed to
ment for my patient? treat, medical decision making.
Newcombe [4] suggests that absolute risk reduction ratio is the ratio between the odds of the treated
is a more basic quantity, with much less potential group and the odds of the control group. It can be
to be misunderstood and is preferable to the NNT, obtained, along with its confidence interval, using
because of the NNT’s singularity problem. He sug- standard statistical software. Both odds and odds
gests that NNT and its CI will be used in an alter- ratios are dimensionless. An odds ratio less than 1
native way, when the absolute risk reduction is well means that the odds have decreased, and similarly,
away from zero. an OR greater than 1 means that the odds have
increased. It should be noted that ORs are hard to
Relative risk and relative risk reduction. The next comprehend [13] and are frequently interpreted as
two popular measures are relative risk (RR) and rel- a relative risk. Although the odds ratio is close to
ative risk reduction (RRR). The relative risk of a the relative risk when the outcome is relatively
treatment is the ratio of risks of the treated group uncommon [12], there is a recognized problem that
and the control group, also called the risk ratio. The odds ratios do not give a good approximation of the
relative risk reduction is derived from the relative relative risk when the initial risk is high [13,14]. Fur-
risk by subtracting it from one, which is the same thermore, an odds ratio will always exaggerate the
as the ratio between the ARR and the risk in the size of the effect compared to a relative risk [15,16].
control group. When the OR is less than 1, it is smaller than the
RR is easy to compute and interpret and is RR, and when it is greater than 1, the OR exceeds
included in standard statistical software. The CI is the RR. However, the interpretation will not,
calculated by exponentiating the lower and upper generally, be influenced by this discrepancy, because
limits of the CI for log(RR), which has the general the discrepancy is large only for large positive or
form negative effect size, in which case the qualitative
conclusion will remain unchanged.
CI = log(RR) ± 1.96 ¥ SE (log(RR) ). (1)
It is worthwhile to note that RR and OR are
However, the simple method for calculating the related as follows:
CI does not perform well [9], and better methods
such as EquivTest [10] and CIA [11] can be used, RR = OR* (1 + (n21 n22) ) (1 + (n11 n12) ) , (2)
although they are not yet widely available. where n11 is the frequency of (yes, group 1); n21 is
One disadvantage of RR is that its value can be the frequency of (yes, group 2); n22 is the frequency
the same for very different clinical situations. For of (no, group 2); and n12 is the frequency of (no,
example, a RR of 0.167 would be the outcome for group 1).
both of the following clinical situations: 1) when the This formula explains why OR approximates
risks for the treated and control groups are 0.3 and RR well when n11 and n21, the frequencies of the
0.05, respectively; and for 2) a risk of 0.84 for the “yes” outcome, are small relative to n12 and n22,
treated group and of 0.14 for the control group. RR respectively. This is known as the “rare outcome
is clear on a proportional scale, but has no real assumption.”
meaning on an absolute scale. Therefore, it is gen- The odds ratio is the only measure of association
erally more meaningful to use relative effect mea- directly estimated from a logistic model, without
sures for summarizing the evidence and absolute requiring special assumptions and regardless of
measures for application to a concrete clinical or whether the study design is follow-up, case-control,
public health situation [12]. or cross sectional [17]. Risks can be estimated only
in follow-up designs. In case-control and cross-
Odds ratio. Odds ratio (OR) is a common measure sectional designs, the OR is a ratio, which depends
of the size of an effect and may be reported in case- on four probabilities as follows:
control studies, cohort studies, or clinical trials. It
can also be used in retrospective studies and cross- Pˆ (E = 1 D = 1) Pˆ (E = 0 D = 1)
sectional studies, where the goal is to look at asso- OR = , (3)
Pˆ (E = 1 D = 0) Pˆ (E = 0 D = 0)
ciations rather than differences. The odds is the
natural measure of effect size in logistic regression where E = 1 if the patient was exposed, E = 0
modeling and can be interpreted as the ratio otherwise, D = 1 if the patient has the disease, and
between the number of patients who fulfill the cri- D = 0 otherwise. It is worthwhile to note that risk
teria and the number who do not or the number of cannot be estimated from a case-control and cross-
events relative to the number of nonevents. The odds sectional studies because they require conditional
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434 Schechtman
probabilities of the type P̂(D|E), which are not 2. Cases 1 and 4 have the same absolute risk reduc-
available. tion, NNT, and odds ratios, but very different
relative risk, relative risk reduction, and risk at
baseline.
Results
Hypothetical Example Real Example
A hypothetical example, used in part by McQuay The following example [18] is a prospective study,
and Moore [5], will be used to illustrate the differ- which compares the incidences of dyskinesia after
ent measures accompanied by their CIs. The study ropinirole (ROP) or levodopa (LD) in patients with
aims to compare the recurrence of migraine early Parkinson’s disease. The results show that 17
headaches in a control group receiving placebo and of 179 patients who took ropinirole and 23 of 89
a treated group receiving a new antimigraine prepa- who took levodopa developed dyskinesia. The data
ration. For the sake of illustration, we examine four are summarized in Table 2.
different possible outcomes for the control and The risk of having dyskinesia among patients
treatment groups, denoted by C1 and M1 for study who took LD is 23/89 = 0.258, whereas the risk
1, C2 and M2 for study 2, C3 and M3 for study 3, of developing dyskinesia among patients who took
and C4 and M4 for study 4. It is assumed that all ROP is 17/179 = 0.095
groups were of 1000 individuals. Therefore, the absolute risk reduction is
At the end of the study, migraine recurred in ARR = 0.258 - 0.095 = 0.163.
30% of control group C1 (risk, 0.3), 5% of treat-
The variance of ARR is given by
ment group M1, 84% of control group C2, 14% of
treatment group M2, 10% of control C3, 1.7% of V (ARR) = 0.258(1 - 0.258) 89 +
treatment group M3, and in 95% and 70% for C4 0.095 (1 - 0.095) 179 = 0.00263. (4)
and M4, respectively, as summarized in Table 1.
The measures used are absolute risk reduction with Therefore, a 95% confidence interval for the dif-
95% CI, risk, number needed to treat with 95% CI, ference in proportions is given by
relative risk with 95% CI, risk reduction, odds, and 0.163 ± 1.96 ¥ 0.00263 = (0.0636 - 0.264),
odds ratio with 95% CI.
It can be seen that: where 1.96 is the upper percentile of 2.5, taken
from a standard normal table for 95% CIs.
1. The first three cases have the same relative risk The number needed to treat and its CI are
and relative risk reduction, while case 4 is sig- obtained from ARR and its CI by taking the recip-
nificantly different. However, the absolute risk rocals as NNT = 1/ARR = 1/0.163 = 6.13, and its
reduction, NNT, and odds ratios are significantly CI is given by (1/0.264 - 1/0.063) = (3.79 - 15.87).
different in the three cases studied. (For odds The relative risk is 0.095/0.258 = 0.368
ratios, case 2 is different from cases 1 and 3, The confidence interval is obtained as follows: a
which are similar.) CI for the log of RR is obtained, and the lower and
Table 1 The basic measures and corresponding 95% CIs for four cases*
C1 M1 C2 M2 C3 M3 C4 M4
Event 300 50 840 140 100 17 950 700
No event 700 950 160 860 900 983 50 300
Risk of event 0.3 0.05 0.84 0.14 0.1 0.017 0.95 0.7
ARR 0.25 0.70 0.083 0.25
CI 0.217–0.283 0.656–0.744 0.062–0.104 0.217–0.283
NNT 4 1.43 12.05 4
CI 3.53–4.60 1.34–1.52 9.65–16.02 3.53–4.60
RR 0.167 0.167 0.17 0.74
CI 0.125–0.222 0.143–0.195 0.102–0.282 0.706–0.769
RRR 0.833 0.833 0.83 0.26
Odds 0.429 0.053 5.25 0.163 0.111 0.017 19 2.33
OR 8.14 0.123 32.25 0.031 6.42 0.156 8.15 0.123
CI 0.090–0.168 0.024–0.04 0.092–0.262 0.090–0.168
*Ci and Mi (i = 1, . . . 4) are the hypothetical control and treated groups, respectively.
Abbreviations: ARR, absolute risk reduction; NNT, number needed to treat.
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Reporting Odds, Risk, and Number Needed to Treat 435
Table 2 Frequency of dyskinesia in patients with early is influenced by how the benefit is presented—in rel-
Parkinson’s disease ative or absolute terms. They found that the
Presence of dyskinesia framing of benefit or risk in relative versus absolute
Yes No Total terms may have a major influence on patient
preference. The medication whose benefits were
Levodopa 23 66 89
Ropinirole 17 162 179 expressed in relative terms was chosen by 56.8% of
Totals 40 228 268 patients, whereas 14.7% chose the medication
whose benefit was expressed in absolute terms.
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sures of effect in binary analyses of randomized with early Parkinson’s disease who were treated
trials. J Clin Epidemiol 1994;47:881–9. with ropinirole or levodopa. N Engl J Med
15 Deeks JJ. When can odds ratios mislead? BMJ 2000;342:1484–91.
1998;317:1155–6. 19 Malenka DJ, Baron JA, Johansen S, et al. The
16 Sackett DL, Deeks JJ, Altman DG. Down with framing effect of relative and absolute risk. J Gen
odds ratios! Evidence-Based Med 1996;1:164–6. Intern Med 1993;10:543–8.