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Relative risk, Risk difference and Odds ratio

When the data to be analyzed consist of counts in a cross-classification of two groups (or conditions) and two outcomes, the data can be represented in a fourfold table as follows:

 Group 1Group 2Total
Number with positive outcomeaca+c
Number with negative outcomebdb+d
Totala+bc+da+b+c+d

Several statistics can be calculated such as relative risk and risk difference, relevant in prospective studies, and odds ratio, relevant in retrospective case controls studies.

How to calculate Relative Risk

The relative risk (RR), its standard error and 95% confidence interval are calculated as follows (Altman, 1991).

The relative risk or risk ratio is given by

Formula for relative risk$$ RR = \frac {a/(a+b) } { c/(c+d) } $$

with the standard error of the log relative risk being

Formula for standard error of relative risk$$ \operatorname{SE} \left \{ \operatorname{ln}\left(RR\right) \right \} = \sqrt { \frac {1}{a} + \frac {1}{c} - \frac {1}{a+b} - \frac {1}{c+d} } $$

and 95% confidence interval

Formula for confidence interval of relative risk$$ \operatorname{95\%\text{ } CI} = \operatorname{exp} \Big( \text{ } \operatorname{ln}\left(RR\right) - 1.96 \times \operatorname{SE} \left \{ \operatorname{ln}\left(RR\right) \right \} \text{ } \Big) \quad \text{ to }\quad \operatorname{exp} \Big(\text{ } \operatorname{ln}\left(RR\right) + 1.96 \times \operatorname{SE} \left \{ \operatorname{ln}\left(RR\right) \right \} \text{ }\Big)$$

Risk difference

The risk difference (RD) and its 95% confidence interval are calculated according to Newcombe & Altman (2000)

Formula for risk difference$$ RD = \frac {a} {a+b} - \frac {c} {c+d} $$

The recommended method for the calculation of the risk difference, which is a difference between proportions, requires the calculation of the confidence intervals of the two proportions separately. MedCalc calculates exact binomial confidence intervals for proportions (Armitage et al., 2002). With l1 to u1 being the 95% CI of the first proportion p1 and l2 to u2 being the 95% CI of the second proportion p2, the 95% confidence interval for the difference is given by

Formula for confidence interval of risk difference$$ \operatorname{95\%\text{ } CI} = RD - \sqrt { (p_1-l_1)^2 + (u_2-p_2)^2 } \quad \text{ to }\quad RD + \sqrt { (p_2-l_2)^2 + (u_1-p_1)^2} $$

In the context of meta-analysis, the standard error and 95% confidence interval are calculated according to Deeks & Higgins (2010), where the standard error is defined as

Formula for standard error of risk difference (meta-analysis context)$$ \operatorname{SE} \left \{ RD \right \} = \sqrt { \frac {a \times b}{ \left ( a+b \right )^3} + \frac {c\times d}{\left (c+d\right )^3} } $$

and 95% confidence interval

Formula for confidence interval of risk difference (meta-analysis context)$$ \operatorname{95\%\text{ } CI} = RD - 1.96 \times \operatorname{SE} \left \{ RD \right \} \quad \text{ to }\quad RD + 1.96 \times \operatorname{SE} \left \{ RD \right \} $$

How to calculate Odds Ratio

The odds ratio (OR), its standard error and 95% confidence interval are calculated as follows (Altman, 1991).

The formula for odds ratio is:

Odds ratio formula$$ \begin{align} OR & = \frac {a/b} {c/d} \\ & = \frac {a \times d } { b \times c} \end{align}$$

with the standard error of the log odds ratio being

Formula for standard error of odds ratio$$ \operatorname{SE} \left \{ \operatorname{ln}\left(OR\right) \right \} = \sqrt { \frac {1}{a} + \frac {1}{b} + \frac {1}{c} + \frac {1}{d} } $$

and 95% confidence interval

Formula for confidence interval of odds ratio$$ \operatorname{95\%\text{ } CI} = \operatorname{exp} \Big( \text{ } \operatorname{ln}\left(OR\right) - 1.96 \times \operatorname{SE} \left \{ \operatorname{ln}\left(OR\right) \right \} \text{ }\Big) \quad \text{ to }\quad \operatorname{exp} \Big(\text{ } \operatorname{ln}\left(OR\right) + 1.96 \times \operatorname{SE} \left \{ \operatorname{ln}\left(OR\right) \right \} \text{ }\Big)$$

Notes

Where zeros cause problems with computation of effects or standard errors, 0.5 is added to all cells (a, b, c, d) (Pagano & Gauvreau, 2000; Deeks & Higgins, 2010).

In meta-analysis for relative risk and odds ratio, studies where a=c=0 or b=d=0 are excluded from the analysis (Higgins & Thomas, 2021).

Literature

Recommended book

Principles of Biostatistics
M Pagano, K Gauvreau

Buy from Amazon US - CA - UK - DE - FR - ES - IT

Principles of Biostatistics is aimed at students in the biological and health sciences who wish to learn modern research methods.

The book is divided into three parts. The first five chapters deal with collections of numbers and ways in which to summarize, explore, and explain them. The next two chapters focus on probability and introduce the tools needed for the subsequent investigation of uncertainty. It is only in the eighth chapter and thereafter that the authors distinguish between populations and samples and begin to investigate the inherent variability introduced by sampling, thus progressing to inference. Postponing the slightly more difficult concepts until a solid foundation has been established makes it easier for the reader to comprehend them.