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how to read forest plot

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how to read forest plot

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Endgames

ENDGAMES

STATISTICAL QUESTION

Philip Sedgwick reader in medical statistics and medical education

Centre for Medical and Healthcare Education, St Georges, University of London, Tooting, London, UK

of antibiotic treatment compared with appendicectomy for the

primary treatment of uncomplicated acute appendicitis.

Randomised controlled trials were included if they investigated

adult patients presenting with uncomplicated acute appendicitis,

diagnosed by haematological and radiological investigations.

The primary outcome measure was the presence of

complications, including wound infection, perforated

appendicitis, or peritonitis. Four randomised controlled trials

were identified.1 The results of the meta-analysis for

complications were presented in a forest plot.

uncomplicated acute appendicitis: forest plot for

complications

a) Not one of the four trials showed a significant difference

between antibiotic treatment and appendicectomy in the risk

of complications.

b) The forest plot is drawn on a linear scale.

c) A relative risk less than 1.0 represents a reduced risk of

complications for antibiotic treatment compared with

appendicectomy.

d) The meta-analysis of complications showed a relative risk

reduction of 31% for antibiotic treatment compared with

appendicectomy.

e) No significant heterogeneity existed between the sample

estimates of the population relative risk.

Answers

Statements a, c, d, and e are all true, whereas b is false.

antibiotic treatment with appendicectomy for the treatment of

uncomplicated acute appendicitis. The primary outcome in each

trial was complications. For each trial a relative risk was derived

that compared the risk of complications for antibiotic treatment

relative to appendicectomy. Relative risk has been described in

previous questions.2 3 Each sample relative risk was an estimate

of the population parameterthat is, the relative risk that would

be observed if antibiotic treatment was compared with

appendicectomy for the entire population of all adults with

uncomplicated acute appendicitis. The purpose of the

meta-analysis was to combine the results of the four trials and

achieve a single estimate of the population relative risk of

complications for antibiotic treatment compared with

appendicectomy.

The forest plot presents the results of the meta-analysis

graphically. The trials are identified by their principal author

on the left side. For each treatment group in the four trials, the

number of participants who experienced a complication and the

total number in each group are shown in the column headed

Events/total. These data were used to calculate the estimated

relative risk and 95% confidence interval, shown on the right

for each trial and represented graphically in the centre. Because

the data for Events/total for antibiotic treatment are presented

first, followed by those for appendicectomy, the presented

relative risks therefore represent the risk of complications for

antibiotic treatment relative to appendicectomy. The sample

relative risk is represented by a square and its associated 95%

confidence interval by the horizontal line. The size of each

square is proportional to the sample size of the trial.

For all four trials the 95% confidence interval for the population

relative risk included 1.0, and therefore not one of them

demonstrated a significant difference between treatment groups

in the risk of complications (a is true). The relation between the

95% confidence interval for a relative risk and 5% level of

significance when hypothesis testing has been described in a

previous question.4

p.sedgwick@sgul.ac.uk

For personal use only: See rights and reprints http://www.bmj.com/permissions

Subscribe: http://www.bmj.com/subscribe

Page 2 of 2

ENDGAMES

associated 95% confidence intervals are plotted on a logarithmic

scale (b is false). As the 95% confidence intervals were

originally calculated on a logarithmic scale, they therefore

appear symmetrical about the sample relative risk in the forest

plot. The solid vertical line in the centre of the graph is the line

of no effectthat is, a relative risk of 1.0, which represents

no difference in risk between antibiotic treatment and

appendicectomy. A relative risk smaller than 1.0 would imply

that the risk of complications was reduced for antibiotic

treatment, relative to appendicectomy (c is true), whereas the

risk would be increased if the relative risk was larger than 1.0.

Therefore, as indicated on the forest plot, a relative risk less

than unity favours antibiotic treatment, whereas one greater

than unity favours appendicectomy.

A total overall estimate of the population relative risk was

obtained by pooling the relative risks from the four trials.

However, the trials did not contribute equally to the pooled

result, as the total estimate was not an average of the individual

estimates. The contribution of each trial is indicated under the

heading Weight (%). The percentage weight contributed by

a trial is determined by the precision of its sample estimate of

the population parameter, and trials with more precise

estimatesthose with narrower confidence

intervalscontributed more.

presented in the row labelled Total and is given as 0.69 (95%

confidence interval 0.54 to 0.89). It is graphically represented

by a diamond; the centre of the diamond equals the total overall

relative risk, whereas the extreme points indicate the limits of

the 95% confidence interval. The vertical dotted line through

the centre of the diamond and graph represents the overall

estimated relative risk. Therefore, the meta-analysis of

complications showed a relative risk reduction of 31% for

antibiotic treatment compared with appendicectomy (d is true).

As the 95% confidence interval did not include 1.0, the total

overall estimate was therefore significant at the 5% level of

significancethat is, there was a significant difference between

treatments in the risk of complications. The P value for the test

of significance of the total overall estimate was 0.004, as shown

in the text Test for overall effect: z=2.91, P=0.004,

corroborating the inference from the 95% confidence interval.

The value for z is the test statistic resulting from the statistical

test used to derive the P value.

A meta-analysis must incorporate a statistical test of

heterogeneity to assess the extent of variation between the

sample estimates. Statistical tests of heterogeneity have been

described in a previous question.5 Statistical homogeneity would

have existed in the above example if the sample relative risks

were similar in magnitude and the variation between them was

no more than expected when taking samples from the same

populationthat is, any variation between them was minimal.

If statistical homogeneity did not exist, then statistical

heterogeneity would be present, and the sample estimates would

differ substantially. The result of the statistical test of

heterogeneity influences how the total overall estimate would

have been obtained. Furthermore, the presence of heterogeneity

might suggest that the relative risk of complications differed

between subgroups in the population.

the text Test for heterogeneity: 2=1.08, df=3, P=0.78, I2=0%.

The test is performed in a similar way to traditional statistical

hypothesis testing, there being a null and alternative hypothesis.

Simply, the null hypothesis indicates that homogeneity exists,

while the alternative hypothesis states that heterogeneity is

present. The P value for the test of heterogeneity was 0.78,

indicating that there was no evidence to reject the null hypothesis

in favour of the alternative. Therefore, the conclusion was that

homogeneity existed between the sample estimates (e is true).

The value for 2 is the test statistic resulting from the statistical

test used to derive the P value. The value for degrees of freedom

(df) equals the number of trials minus one and is used along

with the test statistic to calculate the P value.

Higgins I2 statistic is often also used to test for heterogeneity.

This statistic represents the percentage of variation between the

sample estimates that is due to heterogeneity. It can take values

from 0% to 100%, with 0% indicating that statistical

homogeneity exists between the sample estimates. Significant

statistical heterogeneity is often considered to be present if I2 is

50%. The value of I2 in the above example is 0%, corroborating

the inference of the statistical test that statistical homogeneity

existed (e is true).

sample estimates, a so called fixed effects meta-analysis was

performed; this is indicated in the headings of the forest plot.

If statistical heterogeneity had existed (that is, if statistical

homogeneity had not existed), a random effects meta-analysis

would have been undertaken. The difference between these

approaches is the method used to calculate the total overall

effect. A random effects meta-analysis produces a wider

confidence interval for the total overall effect than a fixed effects

meta-analysis, resulting in a less accurate total overall effect

size.

Not one of the four trials demonstrated a significant difference

between treatments in the risk of complications for patients with

uncomplicated acute appendicitis. However, the total overall

estimate from the meta-analysis confirmed a significantly

reduced risk of complications for antibiotic treatment compared

with appendicectomy. This is one of the advantages of a

meta-analysis. By combining results from across studies, it

aggregates the numbers of study participants, thereby providing

a total overall estimate that has increased power and precision.

This means that a significant effect may be seen overall that

was not seen in any of the individual studies.

The researchers concluded that antibiotics were effective and

safe and merited consideration as primary treatment for patients

with uncomplicated acute appendicitis.

Competing interests: None declared.

1

2

3

4

5

Varadhan KK, Neal KR, Lobo DN. Safety and efficacy of antibiotics compared with

appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of

randomised controlled trials. BMJ 2012;344:e2156.

Sedgwick P, Marston L. Relative risks. BMJ 2010;341:c3983.

Sedgwick P. Absolute and relative risks. BMJ 2012;345:e5613.

Sedgwick P. Confidence intervals and statistical significance: rules of thumb. BMJ

2012;345:e4960.

Sedgwick P. Meta-analyses: tests of heterogeneity. BMJ 2012;344:e3971.

BMJ Publishing Group Ltd 2012

Subscribe: http://www.bmj.com/subscribe

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