http://informahealthcare.

com/pgm
ISSN: 0032-5481 (print), 1941-9260 (electronic)

Postgrad Med, 2015; 127(4): 359–367

DOI: 10.1080/00325481.2015.1022494

CLINICAL FEATURE
ORIGINAL RESEARCH

Odds ratio vs risk ratio in randomized controlled trials

Haribalakrishna Balasubramanian1,2, Anitha Ananthan1,2, Shripada Rao1,2,3 and Sanjay Patole1,3
1
Department of Neonatology, King Edward Memorial Hospital for women and newborns, Perth, Western Australia, Australia, 2Department of Neonatology,
Princess Margaret Hospital for Children, Perth, Western Australia, Australia, and 3Centre for Neonatal Research and Education, University of Western
Australia, Perth, Western Australia, Australia
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15

Abstract Keywords
Objective. Use of odds ratio (OR) in randomized controlled trials (RCTs) has been criticized Odds ratio, risk ratio, randomized controlled
because it overestimates the effect size, if incorrectly interpreted as risk ratio (RR). To what extent trials, effect size
does this make a difference in the context of clinical research is unclear. We, therefore, aimed to
address this issue considering its importance in evidence-based practice of medicine. Methods. History
We reviewed 580 RCTs published in the New England Journal of Medicine between January
Received 26 November 2014
2004 and June 2014 and identified 107 RCTs that reported unadjusted RR (n = 76) or OR (n = 31)
Accepted 20 February 2015
for the primary outcome. For studies reporting ORs, we calculated RRs, and vice versa, using Stata
Published online 7 March 2015
software. The percentage of divergence between the reported and calculated effect size esti-
mates was analyzed. Results. None of the RCTs showed a statistically significant result becoming
insignificant or vice versa depending on the effect size estimate. OR exaggerated the RR in 62%
of the RCTs. The percentage of overestimation was > 50% in 28 RCTs and > 100% in 13 RCTs. The
For personal use only.

degree of overestimation was positively correlated with the prevalence of outcomes (spearman’s
rho = 0.84 and 0.66, p < 0.001). Conclusion. Use of OR instead of RR in RCTs does not change the
qualitative inference of results. However, the use of OR can markedly exaggerate the effect size
in RCTs if misinterpreted as RR and, hence, has the potential to mislead clinicians.

Introduction
Odds ratio (OR) and risk ratio (RR) are the most common
measures of effect size used in randomized controlled trials
(RCTs) to compare the frequency of binary outcomes in the
intervention and control groups [1]. Risk is the “probability
of occurrence of an event,” whereas odds are the “probability
of the event occurring divided by the probability of the event
not occurring” [2,3]. RR is the “ratio of risk of the outcome
in the two groups.” OR is the “ratio of the odds of the
outcome in the two groups” [2,3].
OR and RR are mathematically not equivalent from the
point of statistical interpretation [4]. Textbooks on statistics and
epidemiology state that the OR exaggerates the RR, especially
if the outcome of interest is frequent (> 10%), but this does not
affect the qualitative inference of the results [5,6].
Use of OR in RCTs has been criticized because it overesti-
mates the effect size if the OR is incorrectly interpreted as
the RR [7-12]. The mathematical truism involving RR and
OR clearly explains the potential for overestimation. To what
extent does this make a difference in real life in the context
of clinical research is unclear. We, therefore, aimed to address
this issue considering its importance in evidence-based
practice of medicine.
Methods
We searched PubMed in June 2014 using the following
terminologies: “The New England Journal of Medicine” and
“Randomized controlled trial” and keywords Relative Risk
or Risk Ratio or Odds Ratio. We restricted the search period
to 10 years (2004 – 2014).
To be eligible for inclusion, the RCTs should have reported
the number of participants and events in each group, and the
unadjusted RR or OR. RCTs, where the primary outcome was
continuous or those that reported hazard ratio, relative risk
reduction, efficacy rates, absolute risk difference and incidence
rate ratio, were excluded. RCTs where only adjusted OR or
RR were given were also excluded. We also excluded nonin-
feriority trials with one-sided confidence limits. Trials report-
ing RR and those reporting ORs were grouped separately.
Statistical analysis
Statistical analysis was conducted using the Stata 13.1 soft-
ware (Statacorp LP, 4905, Lakeway Drive, College Station,
Texas, USA). ORs and RRs were calculated for studies in
group 1 and group 2, respectively, using the raw data. Exact
confidence intervals (CIs) were obtained for the calculated

Correspondence: Haribalakrishna Balasubramanian, Department of Neonatology, King Edward Memorial Hospital for women and newborns, Bagot
Road, Subiaco, Perth, Western Australia 6008, Australia. E-mail: doctorhbk@gmail.com
 2015 Informa UK Ltd.
 360 H. Balasubramanian et al.
estimates. Logarithmic transformations of the reported and
calculated effect size estimates were performed to assess the
divergence between the two relative measures of association.
The following formula was used to calculate the percentage
of overestimation: [(ln OR – ln RR)/ln RR]  100. The per-
centage of overestimation > 10% was considered relevant.
The correlation between the extent of overestimation and the
prevalence of outcome, and sample size in the included
RCTs was assessed using Spearman’s rank correlation
coefficients. p Values < 0.05 were considered statistically
significant. Scatter graphs were created to provide visual
impression of the correlation between prevalence of outcome
and sample size with the percentage of overestimation.
Wherever logarithmic scales were used, the minimum
percentage of overestimation was considered as 0.1% to
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15
avoid plotting errors.
Results
Initial broad search yielded a total of 580 citations. We
excluded trials where primary outcome was a measured
outcome such as mean/median (n = 68). Trials that reported
hazard ratio (n = 203), absolute risk difference (n = 66), rate
ratio (n = 36), relative risk reduction (n = 26), trials reporting
no outcomes (n = 3), noninferiority trials with one-sided
CIs (n = 6), and meta-analyses reporting pooled effect size
estimates (n = 5) were also excluded. This narrowed the
For personal use only.
study number to 167, which had reported OR or RR. A total
of 46/167 excluded trials reported only adjusted RR (n = 27),
or only adjusted OR (n = 19). A total of 121 RCTs were
eligible for inclusion. Of these, 14 studies were excluded for
discrepancies between the reported and calculated estimates.
Hence, 107 RCTs (76 reporting unadjusted RR and 31
reporting unadjusted OR) were included in our study (Tables 1
and 2).
Majority of the included trials (n = 109, 90%) were multi-
center ones. The sample size in the included trials ranged
from 175 to 62366. The effect size ranged from 0.15 to
6.1 in those reporting RR and 0.08 – 8.6 in those reporting
OR.
The phenomenon of a statistically significant result
becoming insignificant or vice versa depending on the effect
size estimate was not noted in any of the trials (Tables 1
and 2). OR overestimated the effect size in 62% trials
(n = 68). The overestimation was greater than 10% in 68
trials, greater than 50% in 28 and greater than 100% in 13
trials (Tables 1 and 2).
The percentage of overestimation was positively correlated
with the prevalence of the outcome (Spearman
rho = 0.84 and 0.66, p < 0.001, n = 107, Figures 1 and 2)
and negatively correlated with sample size (Spearman’s
rho = 0.62, p < 0.001, n = 107, Figure3). Prevalence of
outcome and sample size had a monotonic relationship with
percentage of overestimation (Figures 1,2 and 3).
The median percentage of overestimation in trials with
statistically significant difference in the primary outcome
(n = 57) was 22.7 (range 0 – 986). In trials where these
results were statistically insignificant (n = 50), the median
percentage of overestimation was 15.8 (range 0 – 296).
Postgrad Med, 2015; 127(4):359–367
Discussion
Our results indicate that qualitative interpretation is not
altered by the type of effect size estimate in RCTs, i.e., a sta-
tistically significant result did not become insignificant and
vice versa. Compared to RR, OR overestimated the effect
size in 44% of the included RCTs. Larger the treatment effect
and higher the prevalence of outcome in either groups,
greater was the percentage of overestimation.
To our knowledge, this is the first study assessing the
influence of OR vs RR on the qualitative inference of results.
We restricted our analyses to clinical trials and chose to study
only primary outcomes since the impact of a trial intervention
mainly applies for the primary outcome for which the trial is
powered.
Conversion of adjusted OR to RR may result in a biased
estimate unless the raw data are made available [13-15].
Hence, we used only unadjusted values to conduct head-to-
head comparison of OR and RR to detect their true influence
on effect size.
CIs and p values are the two parameters used to assess sta-
tistical significance of an association. p Value for the effect
size estimate was not reported in 15 trials. We calculated the
p value in those cases from the provided CIs using formulae
by Altman and Bland [16]. As the divergence between the
RR and OR increased, the variability in the width of their
95% CI also increased. This resulted in a difference in the
observed p value for the effect size estimates. Despite the
difference, there were no conflicts in terms of statistical
significance. Statistical softwares calculate CIs and p value
for OR on the natural log scale, which normalizes the posi-
tively skewed distribution of the OR [17]. This could explain
the minor differences in the p value despite large differences
in the value of RR and OR for a particular outcome. Though
our results did not have any conflict when it comes to statisti-
cal significance, there is a rare chance that a conflict may
occur.
Percentage of overestimation by OR has been considered
to be a function of prevalence of outcome and the clinically
important treatment effect [18,19]. The OR is the RR multi-
plied by (1-p2)/(1-p1), where the RR = p1/p2. If p1 > p2,
then RR > 1 and (1-p2)/(1-p1) > 1, and so OR > RR > 1.
Thus, the larger p1 is relative to p2, the greater OR is relative
to RR. This could mathematically explain the positive corre-
lation between the degree of overestimation and the preva-
lence of outcomes. Clinical trials involving relatively rare
outcomes and small treatment effects are designed to have
large sample sizes. This could have resulted in a negative cor-
relation between sample size and the extent of overestimation
(Figure 3). For a fixed prevalence and treatment effect, the
sample size would not influence the extent of overestimation.
Researchers prefer reporting OR for various reasons. OR
is symmetrical with respect to an outcome. For example, the
OR of outcome “X” is exactly the inverse of the OR of the
outcome “not X” [20]. If the baseline risk of the outcome is
very common (approximately > 80%) in both the treatment
and control groups, OR may be a better estimate than RR in
detecting small differences between groups [3]. However, the
most important reason for using OR is that it is easy to adjust
 DOI: 10.1080/00325481.2015.1022494 Odds ratio vs risk ratio in RCTs 361

Table 1. Calculated odds ratios vs reported risk ratios.

Treatment
group Control group Reported RR Calculated Odds ratio
% of
No Study ID Events Total Events Total RR (confidence interval) p value OR (confidence interval) p value overestimation Ref
1a Allen 2014 14 152 31 148 0.44 (0.24–0.78) 0.006 0.38 (0.2–0.75) 0.005 17.9 [25]
2a Cohen 2013 131 2967 175 3057 0.77 (0.62–0.96) 0.02 0.76 (0.60–0.96) 0.02 5.0 [26]
3a Ferguson 2013 129 275 96 273 1.33 (1.09–1.64) 0.005 1.63 (1.15–2.29) 0.005 71.3 [27]
4a Futier 2013 21 200 55 200 0.38 (0.24–0.61) 0.001 0.31 (0.18–0.53) < 0.001 21.0 [28]
5a Imazio 2013 20 120 45 120 0.44 (0.30–0.72) < 0.001 0.33 (0.18–0.61) < 0.001 35 [29]
6a Shaukat 2013 200 11072 295 10944 0.68 (0.56–0.82) 0.00007c 0.66 (0.55–0.80) < 0.001 7.2 [30]
7a Steg 2013 55 1089 94 1109 0.60 (0.43–0.82) 0.001 0.57 (0.41–0.81) 0.001 10.2 [31]
8a Trehan 2013 137 920 84 923 1.64 (1.27–2.11) < 0.001 1.75 (1.31–2.33) 0.001 13.1 [32]
9a Boonen 2012 9 553 28 574 0.33 (0.16–0.70) 0.002 0.32 (0.15–0.68) 0.002 2.8 [33]
10a Perner 2012 201 398 172 400 1.17 (1.01–1.36) 0.03 1.35 (1.02–1.79) 0.04 91.1 [34]
11a Wei 2012 39 165 85 172 0.48 (0.35–0.65) < 0.001 0.32 (0.20–0.54) < 0.001 55.2 [35]
12a Adzick 2011 53 78 78 80 0.70 (0.58–0.84) < 0.001 0.054 (0–0.21) < 0.001 717.3 [36]
13a Maitland 2011 221 2097 76 1044 1.45 (1.13–1.86) 0.003 1.50 (1.14–1.97) 0.003 9 [37]
14a Decousus 2010 13 1502 88 1500 0.15 (0.08–0.26) < 0.001 0.14 (0.0–0.25) < 0.001 3.6 [38]
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15

15a Lassen 2010 27 1949 74 1917 0.36 (0.22–0.54) < 0.001 0.35 (0.22–0.54) < 0.001 2.8 [39]
16a Stone 2010 101 2416 81 1195 0.62 (0.46–0.82) 0.001 0.60 (0.44–0.81) 0.001 6.9 [40]
17a Van der Gaag 2010 37 94 75 102 0.54 (0.41–0.71) < 0.001 0.23 (0.13–0.43) < 0.001 137.1 [41]
18a Van Santvoort 2010 17 43 31 45 0.57 (0.38–0.87) 0.006 0.30 (0.12–0.71) 0.009 113.5 [42]
19a Cantor 2009 59 537 90 522 0.64 (0.47–0.87) 0.004 0.59 (0.42–0.84) 0.004 18.2 [43]
20a Connolly SJ 2009 134 6076 199 6022 0.66 (0.53–0.82) < 0.001 0.66 (0.53–0.82) < 0.001 0 [44]
21a Connolly 2 2009 832 3772 924 3782 0.89 (0.81–0.98) 0.01 0.87 (0.79–0.97) 0.01 19.8 [45]
22a Plint 2009 34 200 53 201 0.65 (0.45–0.95) 0.02 0.57 (0.35–0.93) 0.03 30.7 [46]
23a Stone 2008 166 1800 218 1802 0.76 (0.63–0.92) 0.005 0.74 (0.6–0.91) 0.006 9.5 [47]
24a Svilaas 2008 84 490 129 490 0.65 (0.51–0.83) 0.001 0.58 (0.43–0.79) < 0.001 26.4 [48]
25a Black 2007 92 2822 310 2853 0.30 (0.24–0.38) < 0.001 0.28 (0.22–0.35) < 0.001 5.8 [49]
26a Fonseca 2007 24 125 43 125 0.56 (0.36–0.86) 0.007 0.45 (0.25–0.80) 0.01 37.8 [50]
27a MancoJohnson 2007 13 29 2 27 6.1 (1.5–24.4) 0.002 10.2 (2.21–) 0.002 28.4 [51]
For personal use only.

28a Myburgh 2007 71 214 42 206 1.63 (1.17–2.26) 0.003 1.94 (1.25–3.01) 0.004 35.6 [52]
29a Antman 2006 1017 10256 1223 10223 0.83 (0.77–0.90) < 0.001 0.81 (0.74–0.88) < 0.001 13 [53]
30a Freedman 2006 15 107 37 107 0.40 (0.26–0.61) < 0.001 0.31 (0.16–0.60) < 0.001 27.8 [54]
31a Julius 2006 53 391 154 381 0.34 (0.25–0.44) < 0.001 0.23 (0.16–0.33) < 0.001 36.2 [55]
32a Papanikolaou 2006 58 175 41 176 1.42 (1.01–2.00) 0.04 1.63 (1.02–2.61) 0.04 39.4 [56]
33a Stone 2006 466 4612 538 4603 0.86 (0.77–0.97) 0.015 0.85 (0.74–0.97) 0.016 7.7 [57]
34a Bucaneve 2005 243 375 308 363 0.76 0.001 0.33 (0.23–0.47) < 0.001 304.3 [58]
35a Crowther 2005 7 506 23 524 0.32 (0.14–0.73) 0.004 0.30 (0.13–0.70) 0.005 5.6 [59]
36a Cullen 2005 84 781 119 784 0.71 (0.55–0.92) 0.01 0.67 (0.50–0.91) 0.01 16.9 [60]
37a Golden 2005 92 929 121 931 0.76 (0.59–0.98) 0.0338c 0.73 (0.55–0.98) 0.04 14.6 [61]
38a Mestan 2005 17 70 31 68 0.53 (0.33–0.87) 0.01 0.38 (0.19–0.79) 0.01 52.4 [62]
39a Ridker 2005 221 19934 266 19942 0.83 (0.69–0.99) 0.04 0.83 (0.69–0.99) 0.04 0 [63]
40a Landolfi 2004 8 253 21 265 0.40 (0.18–0.91) 0.03 0.38 (0.17–0.86) 0.02 5.6 [64]
41a Senat 2004 17 72 34 70 0.51 (0.07–0.86) 0.002 0.33 (0.16–0.67) 0.003 64.6 [65]
42b Wald 2014 154 846 138 833 1.11 (0.65–1.87) 0.70 1.12 (0.87–1.44) 0.40 8.6 [66]
43b Yealy 2014 173 885 86 456 1.04 (0.82–1.31) 0.83 1.04 (0.8–1.39) 0.83 0.1 [67]
44b Armstrong 2013 116 939 135 943 0.86 (0.68–1.09) 0.21 0.84 (0.65–1.1) 0.22 15.6 [68]
45b Myburgh 2012 597 3315 566 3336 1.06 (0.96–1.18) 0.26 1.07 (0.95–1.22) 0.27 16.1 [69]
46b Ranieri 2012 223 846 202 834 1.09 (0.92–1.28) 0.31 1.12 (0.9–1.4) 0.34 31.5 [70]
47b Thiele 2012 119 300 123 298 0.96 (0.79–1.17) 0.69 0.93 (0.67–1.3) 0.74 77.7 [71]
48b Brocklehurst 2011 686 1759 677 1734 1.00 (0.92–1.08) 1.00c 1.00 (0.87–1.14) 1.00 0.1 [72]
49b Goldhaber 2011 60 2211 70 2284 0.87 (0.62–1.23) 0.44 0.87 (0.62–1.250 0.53 0 [73]
50b Kastrati 2011 94 861 95 860 0.99 (0.74–1.32) 0.94 0.99 (0.73–1.33) 0.94 0 [74]
51b Carlo 2010 513 21992 793 34160 0.99 (0.81–1.22) 0.6 1.00 (0.9–1.12) 0.93 1 [75]
52b Roberts 2010 305 4993 285 4976 1.07 (0.91–1.25) 0.42 1.07 (0.91–1.26) 0.44 0 [76]
53b Azzopardi 2009 74 163 86 162 0.86 (0.68–1.07) 0.17 0.73 (0.47–1.13) 0.18 108.6 [77]
54b Bottiger 2008 77 525 89 525 0.87 (0.65–1.15) 0.36 0.84 (0.60–1.17) 0.35 25.2 [78]
55b Burn 2008 66 350 65 343 1.00 (0.7–1.4) 1.00c 1.00 (0.68–1.45) 1 0 [79]
56b Fergusson 2008 74 780 93 770 0.79 (0.59–1.05) 0.109c 0.76 (0.55–1.05) 0.10 16.4 [80]
57b Gueugniaud 2008 1143 1442 1142 1452 1.01 (0.97–1.05) 0.611c 1.04 (0.87–1.24) 0.71 295.9 [81]
58b Hutchison 2008 32 102 23 103 1.41 (0.89–2.22) 0.142c 1.59 (0.85–2.95) 0.16 34.9 [82]
59b Kastrati 2008 190 2289 199 2281 0.94 (0.77–1.15) 0.57 0.94 (0.77–1.16) 0.63 0.1 [83]
60b Morris 2008 465 902 493 902 0.94 (0.87–1.02) 0.15 0.88 (0.73–1.06) 0.20 106.7 [84]
61b Rouse 2008 118 1041 128 1095 0.97 (0.77–1.23) 0.80 0.96 (0.74–1.26) 0.84 34.0 [85]
62b Rowan 2008 116 363 119 370 0.99 (0.80–1.23) 0.95 0.99 (0.73–1.35) 1 0 [86]
63b Yusuf 2008 1423 8542 1412 8576 1.01 (0.94–1.09) 0.806c 1.01 (0.94–1.1) 0.74 0 [87]
64b Anand 2007 132 1080 144 1081 0.92 (0.73–1.16) 0.48 0.91 (0.70–1.16) 0.48 13.2 [88]
65b Corwin 2007 337 733 351 727 0.95 (0.85–1.06) 0.34 0.91 (0.74–1.12) 0.40 83.8 [89]
66b Rouse 2007 135 325 123 330 1.1 (0.9–1.3) 0.317c 1.2 (0.87–1.63) 0.3 91.3 [90]
67b Bhatt 2006 534 7802 573 7801 0.93 (0.83–1.05) 0.22 0.93 (0.82–1.05) 0.22 0 [91]
68b Kinsella 2006 282 394 295 392 0.95 (0.87–1.03) 0.24 0.83 (0.60–1.13) 0.26 263.2 [92]
 362 H. Balasubramanian et al. Postgrad Med, 2015; 127(4):359–367

Table 1. (Continued)
Treatment
group Control group Reported RR Calculated Odds ratio
% of
No Study ID Events Total Events Total RR (confidence interval) p value OR (confidence interval) p value overestimation Ref

69b Lonn 2006 519 2758 547 2764 0.95 (0.84–1.07) 0.41 0.94 (0.82–1.07) 0.37 18.4 [93]
70b Rumbold 2006 56 935 47 942 1.20 (0.82–1.75) 0.57 1.21 (0.82–1.80) 0.36 4.5 [94]
71b De Winter 2005 137 604 126 596 1.07 (0.87–1.33) 0.33 1.09 (0.83–1.44) 0.53 28.3 [95]
72b Fraser 2005 44 986 35 989 1.26 (0.82–1.95) 0.3003c 1.27 (0.81–1.99) 0.30 3.4 [96]
73b Maskell 2005 64 206 60 221 1.14 (0.85–1.54) 0.43 1.21 (0.8–1.83) 0.39 45.5 [97]
74b Finfer 2004 726 3473 729 3460 0.99 (0.91–1.09) 0.87 0.99 (0.88–1.11) 0.88 0 [98]
75b Kastrati 2004 45 1079 43 1080 1.05 (0.69–1.59) 0.829c 1.05 (0.68–1.60) 0.83 0 [99]
76b Prinssen 2004 41 174 31 171 1.3 (0.9–2.0) 0.23 1.4 (0.83–2.34) 0.23 28.2 [100]
a
RCTs with statistically significant results.
b
RCTs with statistically insignificant results.
c
p values not reported in the original study. They were calculated using Altman and Bland formulae.
Abbreviations: OR = Odds ratio; RCT = Randomized controlled trial; RR = Risk ratio.
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15

the estimate for confounding variables [21]. Logistic regres-
sion (which produces adjusted OR) is more popular than the
various models described to adjust the RR (Mantel-Haenszel
RR method, log binomial regression, Poisson regression)
[14,22]. Ideally, randomization should balance the groups
with respect to covariates and obviate the need for adjusted
effect size estimates in RCTs involving large sample sizes.
For personal use only.
Thus, there is no valid reason for not reporting effect size
using RR in RCTs. Development of user-friendly models for
adjustment of RR could minimize the use of ORs in clinical
trials.
Conclusions in RCTs are driven by significance tests, yet,
magnitude of effect is equally important in the assessment of
an intervention. In majority of RCTs, in order to achieve a

Table 2. Calculated risk ratios vs reported odds ratios.

Treatment Control
group group
No Study ID Events Total Events Total Reported OR p value Calculated RR p value % of Over estimation Ref.
a
1 Meyer 2014 13 506 28 499 0.44 (0.23–0.87) 0.02 0.46 (0.24–0.87) 0.02 5.4 [101]
2a Bhatt 2013 257 5472 322 5470 0.79 (0.67–0.93) 0.006 0.79 (0.68–0.93) 0.005 0 [102]
3a Weinstein 2013 38 51 27 65 4.11 (1.85–9.16) 0.00057c 1.79 (1.29–2.5) < 0.001 142.7 [103]
4a Wenzel 2013 3 52 23 52 0.08 (0.02–0.28) < 0.001 0.13 (0.04–0.41) < 0.001 23.8 [104]
5a Von Minckwitz 2012 176 956 144 969 1.29 (1.02–1.65) 0.04 1.23 (1.01–1.51) 0.04 22.7 [105]
6a Cooper 2011 51 73 42 82 2.21 (1.14–4.26) 0.02 1.36 (1.05–1.77) 0.02 158.3 [106]
7a Glauser 2010 81 154 43 146 2.66 (1.65–4.28) < 0.001 1.78 (1.33–2.39) < 0.001 69.8 [107]
8a Kuter 2010 18 157 23 77 0.31 (0.15–0.61) < 0.001 0.38 (0.22–0.67) < 0.001 21.1 [108]
9a Ducharme 2009 43 521 93 526 0.42 (0.29–0.61) 0.00006c 0.47 (0.33–0.65) < 0.001 14.8 [109]
10a Finfer 2009 829 3010 751 3012 1.14 (1.02–1.28) 0.02 1.10 (1.01–1.20) 0.02 37.9 [110]
11a Hacke 2008 219 418 182 403 1.34 (1.02–1.76) 0.04 1.16 (1.01–1.33) 0.04 97.2 [111]
12a Manson 2007 189 537 225 527 0.73 (0.57–0.93) 0.04 0.82 (0.71–0.96) 0.014 58.5 [112]
13a Schmidt 2007 377 937 431 932 0.78 (0.64–0.93) 0.008 0.87 (0.78–0.96) 0.009 78.4 [113]
14a Ullmann 2007 7 291 22 288 0.3 (0.12–0.71) 0.004 0.31 (0.13–0.72) 0.004 2.6 [114]
15a Schmidt 2006 350 963 447 954 0.65 (0.52–0.76) < 0.001 0.77 (0.7–0.86) < 0.001 65.3 [115]
16a Perondi 2004 33 34 27 34 8.6 (1–397) 0.05 1.22 (1.02–1.46) 0.05 985.8 [116]
17b Anderson 2013 719 1382 785 1412 0.87 (0.75–1.01) 0.06 0.94 (0.87–1.01) 0.07 127.8 [117]
18b Barrett 2013 60 2783 52 2782 1.16 (0.77–1.74) 0.49 1.15 (0.8–1.66) 0.5 6.4 [118]
19 b Ciccone 2013 55 181 63 181 0.82 (0.53–1.27) 0.37 0.87 (0.65–1.17) 0.43 42.4 [119]
20b Diegeler 2013 93 1187 99 1207 0.95 (0.71–1.28) 0.74 0.95 (0.73–1.25) 0.76 0 [120]
21b Kirpalani 2013 191 497 180 490 1.07 0.56 1.05 (0.89–1.23) 0.6 39.5 [121]
22b Coleman 2012 49 521 40 529 1.26 (0.82–1.96) 0.303c 1.24 (0.83–1.85) 0.32 7.4 [122]
23 b Carson 2011 351 998 347 1001 1.01 (0.84–1.22) 0.923c 1.01 (0.90–1.14) 0.81 0 [123]
24b Jones 2010 27 58 41 73 0.7 (0.2–1.8) 0.26 0.83 (0.59–1.17) 0.29 91.4 [124]
25b Bellomo 2009 322 721 332 743 1.00 (0.81–1.23) 0.99 1.00 (0.89–1.12) 1.00 0 [125]
26b Bhatt 2009 185 2654 210 2641 0.87 (0.71–1.07) 0.17 0.88 (0.72–1.06) 0.19 8.9 [126]
27b Giugliano 2009 439 4722 469 4684 0.92 (0.80–1.06) 0.23 0.93 (0.82–1.05) 0.25 14.9 [127]
28b Harrington 2009 290 3889 276 3865 1.05 (0.88–1.24) 0.59 1.04 (0.89–1.22) 0.6 24.2 [128]
29b Nguyen 2007 44 217 55 218 0.75 (0.48–1.18) 0.212c 0.80 (0.57–1.14) 0.25 28.9 [129]
30b Scarborough 2007 129 231 120 228 1.14 (0.79–1.64) 0.49 1.06 (0.9–1.25) 0.51 125 [130]
31b Thwaites 2004 121 274 134 271 0.81 (0.58–1.13) 0.22 0.89 (0.75–1.07) 0.23 80.8 [131]
a
RCTs with statistically significant results.
b
RCTs with statistically insignificant results.
c
p values not reported in the original study. They were calculated using Altman and Bland formulae.
Abbreviations: RCT = Randomized controlled trial; RR = Risk ratio.
 DOI: 10.1080/00325481.2015.1022494 Odds ratio vs risk ratio in RCTs 363
800
Spearman rho = 0.843
p < 0.001

Percentage of overestimation
600

400

200

0
0 20 40 60 80
Outcome prevalence in intervention group (when RR < 1)
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15

Figure 1. Correlation between prevalence of outcome and percentage of overestimation (when RR < 1).
Abbreviation: RR = Risk ratio.

1000
Spearman rho = 0.664
p < 0.001
Percentage of overestimation

800
For personal use only.

600

400

200

0
0 20 40 60 80
Outcome prevalence in control group (when RR > 1)

Figure 2. Correlation between prevalence of outcome and percentage of overestimation (when RR > 1).
Abbreviation: RR = Risk ratio.

1000
Spearman rho = -0.621
p < 0.001
Percentage of overestimation

800

600

400

200

0
0 20,000 40,000 60,000
Sample size

Figure 3. Correlation between sample size and percentage of overestimation.

 364 H. Balasubramanian et al.
feasible sample size without sacrificing the power, researchers
tend to use composite outcomes. This increases the frequency
of the outcome; hence, OR can significantly overestimate the
effect size if interpreted as RR.
The Cochrane handbook discusses the issue of OR vs RR
as follows – “The nonequivalence of the RR and OR does
not indicate that either is wrong: both are entirely valid ways
of describing an intervention effect. Problems may arise,
however, if the OR is misinterpreted as an RR. This error in
interpretation is unfortunately quite common in published
reports of individual studies and systematic reviews [23].”
Hence, we agree with the experts, who have pleaded for the
use of RR as a standard for reporting outcomes in clinical tri-
als [3,10,22,24]. If reporting of OR is imperative, RR should
also be presented. However, a survey of 147 studies reporting
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15
OR found that only 3% reported RR in addition [9].
In summary, our results indicate that the qualitative infer-
ence of results based on RR in RCTs does not change when
OR is used. However, OR in RCTs, if interpreted incorrectly as
RR, has the potential to mislead readers with minimal under-
standing of statistics. Standardizing the reporting of binary out-
comes in RCTs by using RR instead of OR is preferable.
Acknowledgments
S. Rao and S. Patole were responsible for the concept and
For personal use only.
design of the study. H. Balasubramanian and A. Ananthan
conducted literature search and analyzed the data. The final
version of the manuscript was written by H. Balasubramanian
and was approved by all the co-authors.
Declaration of interest
The authors have no relevant affiliations or financial involve-
ment with any organization or entity with a financial interest
in or financial conflict with the subject matter or materials
discussed in the manuscript. This includes employment,
consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
References
[1] Magder LS. Simple approaches to assess the possible impact of
missing outcome information on estimates of risk ratios, odds
ratios, and risk differences. Control Clin Trials 2003;24:411–21.
[2] A’Court C, Stevens R, Heneghan C. Against all odds? Improv-
ing the understanding of risk reporting. Br J Gen Pract 2012;62:
e220–3.
[3] Grimes DA, Schulz KF. Making sense of odds and odds ratios.
Obstet Gynecol 2008;111:423–6.
[4] Sistrom CL, Garvan CW. Proportions, odds, and risk. Radiology
2004;230:12–19.
[5] Rothman KJ. Modern Epidemiology. Second ed. Lippincott
Williams & Wilkins, Baltimore; 1998.
[6] Altman DG. Practical statistics for medical research. London:
Chapman and Hall; 1991.
[7] Viera AJ. Odds ratios and risk ratios: what’s the difference and
why does it matter? South Med J 2008;101:730–4.
[8] Holcomb WL Jr, Chaiworapongsa T, Luke DA, Burgdorf KD.
An odd measure of risk: use and misuse of the odds ratio.
Obstet Gynecol 2001;98:685–8.
[9] Ho KM, Marshall RJ, Walters S. Use of odds ratios on anaesthe-
sia related studies. Anaesth Intensive Care 2003;31:392–5.
Postgrad Med, 2015; 127(4):359–367
[10] Katz KA. The (relative) risks of using odds ratios. Arch Derma-
tol 2006;142:761–4.
[11] Tajeu GS, Sen B, Allison DB, Menachemi N. Misuse of odds
ratios in obesity literature: an empirical analysis of published
studies. Obesity (Silver Spring) 2012;20:1726–31.
[12] Knol MJ, Duijnhoven RG, Grobbee DE, Moons KG,
Groenwold RH. Potential misinterpretation of treatment effects
due to use of odds ratios and logistic regression in randomized
controlled trials. PLoS One 2011;6:e21248.
[13] Shrier I, Steele R. Understanding the relationship between risks
and odds ratios. Clin J Sport Med 2006;16:107–10.
[14] McNutt LA, Wu C, Xue X, Hafner JP. Estimating the relative
risk in cohort studies and clinical trials of common outcomes.
Am J Epidemiol 2003;157:940–3.
[15] Grant RL. Converting an odds ratio to a range of plausible
relative risks for better communication of research findings.
BMJ 2014;348:f7450.
[16] Altman DG, Bland JM. How to obtain the P value from a confi-
dence interval. BMJ 2011;343:d2304.
[17] Morris JA, Gardner MJ. Calculating confidence intervals for
relative risks (odds ratios) and standardised ratios and rates.
BMJ 1988;296:1313–16.
[18] Davies HT, Crombie IK, Tavakoli M. When can odds ratios mis-
lead? BMJ 1998;316:989–91.
[19] Sackett DL, Deeks JJ, Altman DG. Down with odds ratios!.
Evidence Based Med 1996;1:164–6.
[20] Cummings P. The relative merits of risk ratios and odds ratios.
Arch Pediatr Adolesc Med 2009;163:438–45.
[21] Simon SD. Understanding the odds ratio and the relative risk.
J Androl 2001;22:533–6.
[22] Knol MJ, Le Cessie S, Algra A, Vandenbroucke JP,
Groenwold RH. Overestimation of risk ratios by odds ratios in
trials and cohort studies: alternatives to logistic regression.
CMAJ 2012;184:895–9.
[23] Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analy-
sing data and undertaking meta-analyses. In Deeks JJ,
Altman DG, eds. Cochrane handbook for systematic reviews of
interventions. The Cochrane Collaboration; 2011. Available
from www.cochrane-handbook.org.
[24] Groenwold RH, Moons KG, Peelen LM, Knol MJ, Hoes AW.
Reporting of treatment effects from randomized trials: a plea for
multivariable risk ratios. Contemp Clin Trials 2011;32:399–402.
[25] Allen PJ, Gonen M, Brennan MF, Bucknor AA, Robinson LM,
Pappas MM, et al. Pasireotide for postoperative pancreatic fis-
tula. N Engl J Med 2014;370:2014–22.
[26] Cohen AT, Spiro TE, Buller HR, Haskell L, Hu D, Hull R, et al.
Rivaroxaban for thromboprophylaxis in acutely ill medical
patients. N Engl J Med 2013;368:513–23.
[27] Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L,
Austin P, et al. High-frequency oscillation in early acute respira-
tory distress syndrome. N Engl J Med 2013;368:795–805.
[28] Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M,
Neuschwander A, et al. A trial of intraoperative low-tidal-
volume ventilation in abdominal surgery. N Engl J Med
2013;369:428–37.
[29] Imazio M, Brucato A, Cemin R, Ferrua S, Maggiolini S,
Beqaraj F, et al. A randomized trial of colchicine for acute
pericarditis. N Engl J Med 2013;369:1522–8.
[30] Shaukat A, Mongin SJ, Geisser MS, Lederle FA, Bond JH,
Mandel JS, Church TR. Long-term mortality after screening for
colorectal cancer. N Engl J Med 2013;369:1106–14.
[31] Steg PG, van ’t Hof A, Hamm CW, Clemmensen P,
Lapostolle F, Coste P, et al. Bivalirudin started during
emergency transport for primary PCI. N Engl J Med
2013;369:2207–17.
[32] Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ,
Maleta KM, Manary MJ. Antibiotics as part of the management
of severe acute malnutrition. N Engl J Med 2013;368:425–35.
[33] Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J,
Langdahl B, et al. Fracture risk and zoledronic acid therapy in
men with osteoporosis. N Engl J Med 2012;367:1714–23.
[34] Perner A, Haase N, Guttormsen AB, Tenhunen J,
Klemenzson G, Åneman A, et al. Hydroxyethyl starch
 DOI: 10.1080/00325481.2015.1022494
130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med
2012;367:124–34.
[35] Wei JT, Nygaard I, Richter HE, Nager CW, Barber MD,
Kenton K, et al. A midurethral sling to reduce incontinence after
vaginal prolapse repair. N Engl J Med 2012;366:2358–67.
[36] Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK,
Johnson MP, et al. A randomized trial of prenatal versus
postnatal repair of myelomeningocele. N Engl J Med
2011;364:993–1004.
[37] Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P,
Akech SO, et al. Mortality after fluid bolus in African children
with severe infection. N Engl J Med 2011;364:2483–95.
[38] Decousus H, Prandoni P, Mismetti P, Bauersachs RM, Boda Z,
Brenner B, et al. Fondaparinux for the treatment of superficial-
vein thrombosis in the legs. N Engl J Med 2010;363:1222–32.
[39] Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D,
Ramirez LM. Apixaban versus enoxaparin for thromboprophy-
laxis after hip replacement. N Engl J Med 2010;363:2487–98.
[40] Stone GW, Rizvi A, Newman W, Mastali K, Wang JC, Caputo R,
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15
et al. Everolimus-eluting versus paclitaxel-eluting stents in
coronary artery disease. N Engl J Med 2010;362:1663–74.
[41] van der Gaag NA, Rauws EA, van Eijck CH, Bruno MJ,
van der Harst E, Kubben FJ, et al. Preoperative biliary drainage
for cancer of the head of the pancreas. N Engl J Med
2010;362:129–37.
[42] van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS,
Boermeester MA, Dejong CH, et al. A step-up approach or
open necrosectomy for necrotizing pancreatitis. N Engl J Med
2010;362:1491–502.
[43] Cantor WJ, Fitchett D, Borgundvaag B, Ducas J,
Heffernan M, Cohen EA, et al. Routine early angioplasty after
fibrinolysis for acute myocardial infarction. N Engl J Med
2009;360:2705–18.
For personal use only.
[44] Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J,
Parekh A, et al. Dabigatran versus warfarin in patients with
atrial fibrillation. N Engl J Med 2009;361:1139–51.
[45] Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M,
Chrolavicius S, Yusuf S. Effect of clopidogrel added to aspirin
in patients with atrial fibrillation. N Engl J Med
2009;360:2066–78.
[46] Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R,
et al. Epinephrine and dexamethasone in children with bronchi-
olitis. N Engl J Med 2009;360:2079–89.
[47] Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ,
Brodie BR, Dudek D, et al. Bivalirudin during primary
PCI in acute myocardial infarction. N Engl J Med
2008;358:2218–30.
[48] Svilaas T, Vlaar PJ, van der Horst IC, Diercks GF, de Smet BJ,
van den Heuvel AF, et al. Thrombus aspiration during primary
percutaneous coronary intervention. N Engl J Med
2008;358:557–67.
[49] Black DM, Delmas PD, Eastell R, Reid IR, Boonen S,
Cauley JA, et al. Once-yearly zoledronic acid for treatment
of postmenopausal osteoporosis. N Engl J Med 2007;356:
1809–22.
[50] Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Pro-
gesterone and the risk of preterm birth among women with a
short cervix. N Engl J Med 2007;357:462–9.
[51] Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B,
Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic
treatment to prevent joint disease in boys with severe hemo-
philia. N Engl J Med 2007;357:535–44.
[52] Myburgh J, Cooper DJ, Finfer S, Bellomo R, Norton R, Bishop N,
et al. Saline or albumin for fluid resuscitation in patients with trau-
matic brain injury. N Engl J Med 2007;357:874–84.
[53] Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M,
Sadowski Z, et al. Enoxaparin versus unfractionated heparin
with fibrinolysis for ST-elevation myocardial infarction. N Engl
J Med 2006;354:1477–88.
[54] Freedman SB, Adler M, Seshadri R and Powell EC. Oral ondan-
setron for gastroenteritis in a pediatric emergency department. N
Engl J Med 2006;354:1698–705.
[55] Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL,
Kaciroti N, et al. Feasibility of treating prehypertension with
Odds ratio vs risk ratio in RCTs 365
an angiotensin-receptor blocker. N Engl J Med 2006;354:
1685–97.
[56] Papanikolaou EG, Camus M, Kolibianakis EM, Van Landuyt L,
Van Steirteghem A, Devroey P. In vitro fertilization with single
blastocyst-stage versus single cleavage-stage embryos. N Engl J
Med 2006;354:1139–46.
[57] Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM,
Moses JW, et al. Bivalirudin for patients with acute coronary
syndromes. N Engl J Med 2006;355:2203–16.
[58] Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS,
Martinelli G, et al. Levofloxacin to prevent bacterial infection in
patients with cancer and neutropenia. N Engl J Med
2005;353:977–87.
[59] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS,
Robinson JS. Effect of treatment of gestational diabetes mellitus
on pregnancy outcomes. N Engl J Med 2005;352:2477–86.
[60] Cullen M, Steven N, Billingham L, Gaunt C, Hastings M,
Simmonds P, et al. Antibacterial prophylaxis after chemotherapy
for solid tumors and lymphomas. N Engl J Med 2005;353:988–98.
[61] Golden MR, Whittington WL, Handsfield HH, Hughes JP,
Stamm WE, Hogben M, et al. Effect of expedited treatment of
sex partners on recurrent or persistent gonorrhea or chlamydial
infection. N Engl J Med 2005;352:676–85.
[62] Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neuro-
developmental outcomes of premature infants treated with
inhaled nitric oxide. N Engl J Med 2005;353:23–32.
[63] Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM,
Manson JE, et al. A randomized trial of low-dose aspirin in the
primary prevention of cardiovascular disease in women. N Engl
J Med 2005;352:1293–304.
[64] Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G,
Patrono C, et al. Efficacy and safety of low-dose aspirin in
polycythemia vera. N Engl J Med 2004;350:114–24.
[65] Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y.
Endoscopic laser surgery versus serial amnioreduction for severe
twin-to-twin transfusion syndrome. N Engl J Med
2004;351:136–44.
[66] Wald A, Corey L, Timmler B, Magaret A, Warren T, Tyring S,
et al. Helicase-primase inhibitor pritelivir for HSV-2 infection.
N Engl J Med 2014;370:201–10.
[67] Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA,
Pike F, et al. A randomized trial of protocol-based care for early
septic shock. N Engl J Med 2014;370:1683–93.
[68] Armstrong PW, Gershlick AH, Goldstein P, Wilcox R,
Danays T, Lambert Y, et al. Fibrinolysis or primary PCI in ST-
segment elevation myocardial infarction. N Engl J Med
2013;368:1379–87.
[69] Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D,
et al. Hydroxyethyl starch or saline for fluid resuscitation in
intensive care. N Engl J Med 2012;367:1901–11.
[70] Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS,
Finfer S, et al. Drotrecogin alfa (activated) in adults with septic
shock. N Engl J Med 2012;366:2055–64.
[71] Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG,
Hausleiter J, et al. Intraaortic balloon support for myocardial
infarction with cardiogenic shock. N Engl J Med 2012;367:
1287–96.
[72] Brocklehurst P, Farrell B, King A, Juszczak E, Darlow B,
Haque K, et al. Treatment of neonatal sepsis with intravenous
immune globulin. N Engl J Med 2011;365:1201–11.
[73] Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G,
Knabb RM, Weitz JI. Apixaban versus enoxaparin for thrombopro-
phylaxis in medically ill patients. N Engl J Med 2011;365:2167–77.
[74] Kastrati A, Neumann FJ, Schulz S, Massberg S, Byrne RA,
Ferenc M, et al. Abciximab and heparin versus bivalirudin for
non-ST-elevation myocardial infarction. N Engl J Med 2011;
365:1980–9.
[75] Carlo WA, Goudar SS, Jehan I, Chomba E, Tshefu A, Garces A,
et al. Newborn-care training and perinatal mortality in develop-
ing countries. N Engl J Med 2010;362:614–23.
[76] Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC,
Leveno KJ, et al. Vitamins C and E to prevent complications of
pregnancy-associated hypertension. N Engl J Med 2010;362:
1282–91.
 366 H. Balasubramanian et al.
[77] Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL,
Juszczak E, et al. Moderate hypothermia to treat perinatal
asphyxial encephalopathy. N Engl J Med 2009;361:1349–58.
[78] Bottiger BW, Arntz HR, Chamberlain DA, Bluhmki E,
Belmans A, Danays T, et al. Thrombolysis during
resuscitation for out-of-hospital cardiac arrest. N Engl J Med
2008;359:2651–62.
[79] Burn J, Bishop DT, Mecklin JP, Macrae F, Mo €slein G,
Olschwang S, et al. Effect of aspirin or resistant starch on colo-
rectal neoplasia in the Lynch syndrome. N Engl J Med 2008;
359:2567–78.
[80] Fergusson DA, Hebert PC, Mazer CD, Fremes S, MacAdams C,
Murkin JM, et al. A comparison of aprotinin and lysine ana-
logues in high-risk cardiac surgery. N Engl J Med
2008;358:2319–31.
[81] Gueugniaud PY, David JS, Chanzy E, Hubert H, Dubien PY,
Mauriaucourt P, et al. Vasopressin and epinephrine vs. epineph-
rine alone in cardiopulmonary resuscitation. N Engl J Med
2008;359:21–30.
[82] Hutchison JS, Ward RE, Lacroix J, Hebert PC, Barnes MA,
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15
Bohn DJ, et al. Hypothermia therapy after traumatic brain injury
in children. N Engl J Med 2008;358:2447–56.
[83] Kastrati A, Neumann FJ, Mehilli J, Byrne RA, Iijima R,
Bu€ttner HJ, et al. Bivalirudin versus unfractionated heparin
during percutaneous coronary intervention. N Engl J Med
2008;359:688–96.
[84] Morris BH, Oh W, Tyson JE, Stevenson DK, Phelps DL,
O’Shea TM, et al. Aggressive vs. conservative phototherapy for
infants with extremely low birth weight. N Engl J Med
2008;359:1885–96.
[85] Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY,
Mercer BM, et al. A randomized, controlled trial of magnesium
sulfate for the prevention of cerebral palsy. N Engl J Med
For personal use only.
2008;359:895–905.
[86] Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metfor-
min versus insulin for the treatment of gestational diabetes. N
Engl J Med 2008;358:2003–15.
[87] Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H,
et al. Telmisartan, ramipril, or both in patients at high risk for
vascular events. N Engl J Med 2008;358:1547–59.
[88] Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, Budaj A, et al.
Oral anticoagulant and antiplatelet therapy and peripheral arterial
disease. N Engl J Med 2007;357:217–27.
[89] Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG,
Heard S, et al. Efficacy and safety of epoetin alfa in critically ill
patients. N Engl J Med 2007;357:965–76.
[90] Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom EA,
Spong CY, et al. A trial of 17 alpha-hydroxyprogesterone
caproate to prevent prematurity in twins. N Engl J Med
2007;357:454–61.
[91] Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR,
Boden WE, et al. Clopidogrel and aspirin versus aspirin alone
for the prevention of atherothrombotic events. N Engl J Med
2006;354:1706–17.
[92] Kinsella JP, Cutter GR, Walsh WF, Gerstmann DR, Bose CL,
Hart C, et al. Early inhaled nitric oxide therapy in premature new-
borns with respiratory failure. N Engl J Med 2006;355:354–64.
[93] Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M,
et al. Homocysteine lowering with folic acid and B vitamins in
vascular disease. N Engl J Med 2006;354:1567–77.
[94] Rumbold AR, Crowther CA, Haslam RR, Dekker GA,
Robinson JS. Vitamins C and E and the risks of preeclampsia
and perinatal complications. N Engl J Med 2006;354:1796–806.
[95] de Winter RJ, Windhausen F, Cornel JH, Dunselman PH,
Janus CL, Bendermacher PE, et al. Early invasive versus selec-
tively invasive management for acute coronary syndromes. N
Engl J Med 2005;353:1095–104.
[96] Fraser WD, Hofmeyr J, Lede R, Faron G, Alexander S,
Goffinet F, et al. Amnioinfusion for the prevention of the
meconium aspiration syndrome. N Engl J Med 2005;353:909–17.
[97] Maskell NA, Davies CW, Nunn AJ, Hedley EL, Gleeson FV,
Miller R, et al. U.K. Controlled trial of intrapleural streptokinase
for pleural infection. N Engl J Med 2005;352:865–74.
Postgrad Med, 2015; 127(4):359–367
[98] Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R.
A comparison of albumin and saline for fluid resuscitation in
the intensive care unit. N Engl J Med 2004;350:2247–56.
[99] Kastrati A, Mehilli J, Schuhlen H, Dirschinger J, Dotzer F,
ten Berg JM, et al. A clinical trial of abciximab in elective
percutaneous coronary intervention after pretreatment with
clopidogrel. N Engl J Med 2004;350:232–8.
[100] Prinssen M, Verhoeven EL, Buth J, Cuypers PW,
van Sambeek MR, Balm R, et al. A randomized trial comparing
conventional and endovascular repair of abdominal aortic aneur-
ysms. N Engl J Med 2004;351:1607–18.
[101] Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C,
Beyer-Westendorf J, et al. Fibrinolysis for patients with
intermediate-risk pulmonary embolism. N Engl J Med 2014;
370:1402–11.
[102] Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG,
Hamm CW, et al. Effect of platelet inhibition with cangrelor dur-
ing PCI on ischemic events. N Engl J Med 2013;368:1303–13.
[103] Weinstein SL, Dolan LA, Wright JG, Dobbs MB. Effects of
bracing in adolescents with idiopathic scoliosis. N Engl J Med
2013;369:1512–21.
[104] Wenzel S, Ford L, Pearlman D, Spector S, Sher L,
Skobieranda F, et al. Dupilumab in persistent asthma with
elevated eosinophil levels. N Engl J Med 2013;368:2455–66.
[105] von Minckwitz G, Eidtmann H, Rezai M, Fasching PA,
Tesch H, Eggemann H, et al. Neoadjuvant chemotherapy and
bevacizumab for HER2-negative breast cancer. N Engl J Med
2012;366:299–309.
[106] Cooper DJ, Rosenfeld JV, Murray L, Arabi YM, Davies AR,
D’Urso P, et al. Decompressive craniectomy in diffuse traumatic
brain injury. N Engl J Med 2011;364:1493–502.
[107] Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D,
Masur D, et al. Ethosuximide, valproic acid, and lamotrigine in
childhood absence epilepsy. N Engl J Med 2010;362:790–9.
[108] Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I,
Selleslag D, et al. Romiplostim or standard of care in patients with
immune thrombocytopenia. N Engl J Med 2010;363:1889–99.
[109] Ducharme FM, Lemire C, Noya FJ, Davis GM, Alos N,
Leblond H, et al. Preemptive use of high-dose fluticasone for
virus-induced wheezing in young children. N Engl J Med
2009;360:339–53.
[110] Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et
al. Intensive versus conventional glucose control in critically ill
patients. N Engl J Med 2009;360:1283–97.
[111] Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A,
Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours
after acute ischemic stroke. N Engl J Med 2008;359:1317–29.
[112] Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD,
Hsia J, et al. Estrogen therapy and coronary-artery calcification.
N Engl J Med 2007;356:2591–602.
[113] Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ,
Ohlsson A, et al. Long-term effects of caffeine therapy for apnea
of prematurity. N Engl J Med 2007;357:1893–902.
[114] Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P,
Langston A, Tarantolo SR, et al. Posaconazole or fluconazole
for prophylaxis in severe graft-versus-host disease. N Engl J
Med 2007;356:335–47.
[115] Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ,
Ohlsson A, et al. Caffeine therapy for apnea of prematurity. N
Engl J Med 2006;354:2112–21.
[116] Perondi MB, Reis AG, Paiva EF, Nadkarni VM, Berg RA.
A comparison of high-dose and standard-dose epinephrine in
children with cardiac arrest. N Engl J Med 2004;350:1722–30.
[117] Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C,
et al. Rapid blood-pressure lowering in patients with acute intra-
cerebral hemorrhage. N Engl J Med 2013;368:2355–65.
[118] Barrett JF, Hannah ME, Hutton EK, Willan AR, Allen AC,
Armson BA, et al. A randomized trial of planned cesarean or
vaginal delivery for twin pregnancy. N Engl J Med
2013;369:1295–305.
[119] Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M,
Sterzi R, et al. Endovascular treatment for acute ischemic stroke.
N Engl J Med 2013;368:904–13.
 DOI: 10.1080/00325481.2015.1022494
[120] Diegeler A, Borgermann J, Kappert U, Breuer M, Bo€ning A,
Ursulescu A, et al. Off-pump versus on-pump coronary-artery
bypass grafting in elderly patients. N Engl J Med 2013;368:
1189–98.
[121] Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A,
Roberts RS. A trial comparing noninvasive ventilation strategies
in preterm infants. N Engl J Med 2013;369:611–20.
[122] Coleman T, Cooper S, Thornton JG, Grainge MJ, Watts K,
Britton J, et al. A randomized trial of nicotine-replacement
therapy patches in pregnancy. N Engl J Med 2012;366:808–18.
[123] Carson JL, Terrin ML, Noveck H, Sanders DW,
Chaitman BR, Rhoads GG, et al. Liberal or restrictive trans-
fusion in high-risk patients after hip surgery. N Engl J Med
2011;365:2453–62.
[124] Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG,
Arria AM, et al. Neonatal abstinence syndrome after
methadone or buprenorphine exposure. N Engl J Med 2010;363:
2320–31.
[125] Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, et al.
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 06/24/15
Intensity of continuous renal-replacement therapy in critically ill
patients. N Engl J Med 2009;361:1627–38.
For personal use only.
Odds ratio vs risk ratio in RCTs 367
[126] Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S,
Montalescot G, et al. Intravenous platelet blockade with
cangrelor during PCI. N Engl J Med 2009;361:2330–41.
[127] Giugliano RP, White JA, Bode C, Armstrong PW,
Montalescot G, Lewis BS, et al. Early versus delayed, provi-
sional eptifibatide in acute coronary syndromes. N Engl J Med
2009;360:2176–90.
[128] Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM,
Gibson CM, et al. Platelet inhibition with cangrelor in patients
undergoing PCI. N Engl J Med 2009;361:2318–29.
[129] Nguyen TH, Tran TH, Thwaites G, Ly VC, Dinh XS,
Ho Dang TN, et al. Dexamethasone in Vietnamese adolescents
and adults with bacterial meningitis. N Engl J Med 2007;357:
2431–40.
[130] Scarborough M, Gordon SB, Whitty CJ, French N, Njalale Y,
Chitani A, et al. Corticosteroids for bacterial meningitis in adults
in sub-Saharan Africa. N Engl J Med 2007;357:2441–50.
[131] Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT,
Nguyen TC, et al. Dexamethasone for the treatment of tubercu-
lous meningitis in adolescents and adults. N Engl J Med
2004;351:1741–51.