-------------------------------------------------------------------------------help metapowplotalso see:metasim,metapow-------------------------------------------------------------------------------

Title

metapowplot-- Produces power plots based on meta-analysis

Syntax

metapowplotvarlist,start(#)stop(#)step(#)nit(#)type(string)pow(numlist)[options]

optionsDescription ------------------------------------------------------------------------- Mainstart(#)minimum number of subjects in group 1 (see below)stop(#)maximum number of subjects in group 1 (see below)step(#)step size between start and stop sample sizestype(string)type of study being simulatednit(#)number of simulations the power calculation is based onpow(numlist)cut-off value for determining powerOptional

measure(string)outcome measure used in meta-analysisinference(string)inference statistic on which power is basedp(#)event rate or probability of being diseased dependent on (type)r(#)ratio of patients in two groups; treatment and control or diseased and healthystudies(#)number of new studies to be simulatedmodel(string)meta-analysis model used on pre-existing datanpow(numlist)additional inference statistic on which power is basedci(#)width of confidence interval for power estimate (default=95%)dist(string)distribution of effect sizes used to simulate the new study fromindcalculates power for new study on its ownnip(#)number of integration points used for quadrature in bivariate modelsos(string)inference option for sensitivity and specificity to be used withciwidthorlcigraph(string)type of graph to be plottednociprevents confidence intervals from being displayed on the graphregraphallows the user to re-graph the power curve using alternative graph optionslevel(cilevel)specifies the confidence level for the study confidence intervals -------------------------------------------------------------------------

Description

metapowplotestimates the power of an updated meta-analysis including a new study and plots each value against a range of sample sizes. The program calls on the programmetapowto generate the power estimates. The user needs to input a minimum and a maximum sample size for which they want to calculate a power estimate. The power estimates are stored with their confidence intervals in a file called temppow3 within the working directory.

Options+------+ ----+ Main +-------------------------------------------------------------

start(integer)is the smallest total sample size for a new study that the user wishes to calculate a power value for.

stop(integer)is the largest total sample size for a new study that the user wishes to calculate the power value for.

step(integer)is the step size to be used within the range of total sample sizes specified bystartandstop. A step size of 10 between the range of 10 to 30 would mean that the power would be estimated for sample sizes of 10, 20 and 30.

type(clinical/diagnostic)specifies the type of new study that the user would like to simulate; either a 2-arm clinical trial or a diagnostic test accuracy study.

nit(integer)is the number of simulations that are run on which the estimated poweris based. The larger the number specified the more accurate the estimate will be, but the longer the analysis will take.

pow(numlist)specifies the value used as a cut-off in determining the power. One or two values can be inputted. The value/s represents different things depending on the option chosen forinference.+----------+ ----+ Optional +---------------------------------------------------------

measure(or/rr/rd/nostandard/dor/ss)specifies the outcome measure used in the meta-analysis to pool the results. The odds ratio (or), relative risk (rr), risk difference (rd) and unstandardised mean difference (nostandard) can only be used when simulating a new clinical study. The diagnostic odds ratio (dor) and sensitivity and specificity (ss) can only be used when simulating a new diagnostic accuracy study. The default for a clinicaltypestudy with 4 variables entered into thevarlistis relative risk (rr, the default for a clinicaltypestudy with 6 variables entered into thevarlistis unstandardised mean difference (nostandardand the default for a diagnostictypestudy is sensitivity and specificity (ss).

inference(ciwidth/pvalue/lci/uci)defines the approach to inference used to calculate power. The default is the confidence interval width (ciwidth). This counts the number of times that the confidence interval width of the estimate/s from the updated meta-analysis (i.e. with the simulated study(ies) included) is less than the specified value/s. This option can be used regardless of the measure of accuracy. Two other approaches to inference available arelcianduci. These will count the number of times that the lower or upper confidence interval is higher or lower than a given value respectively. Thelcioption can be used regardless of the measure of accuracy. However, theucioption is currently only available when working with clinical trial data and not diagnostic data. A final option only available when using clinical trial data is thepvalue. This counts the number of times that a p-value is significant to a specified level. When using sensitivity and specificity two values may be inputted intopowforciwidthandlci. This will instruct the program to count the number of times that the confidence interval widths for both sensitivity and specificity are less than their respective specified values. These must be given in the order sensitivity and specificity to be calculated correctly. In order to use theciwidthorlcioptions for just sensitivity or just specificity thesosoption should be used in addition to this option.

p(real)if simulating a new clinical study then this is the estimated event rate in the control group in the new study. When simulating a new diagnostic study this is the estimated probability of being diseased given a positive result in the new study. When this option is not specified by the user, the program will calculate this value by averaging the probabilities across the studies included in the dataset memory. Note thatpis only relevant in the diagnostic framework when using the diagnostic odds ratio (dor) as the option inmeasure.

r(real)is the ratio of patients in the control group to the treatment group when simulating a new clinical study. When simulating a new diagnostic accuracy study this is the ratio of diseased to healthy people if using sensitivity and specificity and the ratio of positive to negative results if using the DOR (default 1).

studies(integer)specifies the number of new studies to be simulated (default 1). When more than one are specified they are all assumed to have the same sample size.

model(fixed/fixedi/random/randomi/bivariate)defines the type of model used to meta-analyse the pre-existing data. The default is the fixed effect Mantel-Haenszel method (fixed) unless the outcome measure is the nonstandardised mean difference in which case the default is the inverse variance method (fixedi). The (fixedi) option specifies a fixed effect model using the inverse variance method. The (random) option uses the random effect DerSimonian & Laird method, taking the estimate for heterogeneity from the Mantel-Haenszel method. The (randomi) option specifies a random effects model using the method of DerSimonian and Laird, with the estimate of heterogeneity being taken from the inverse-variance fixed-effect model. All of the above options call on themetancommand within the program. The final option is the bivariate random effects model (bivariate). This method calls on a combination of themetandiandmidascommands. It may only be specified when simulating a new diagnostic accuracy study.

npow(numlist)recalculates the power using a newly specified value for the sameinferencewithout having to re-run the whole program. Instead, it uses the data that is stored in temppow2 and allows alternative approaches to inference to be explored. This is particularly valuable when the required simulation time is lengthy.

ci(real)specifies the width of the confidence interval for the corresponding power estimate (default 95%).

dist(normal/t)specifies the distribution of effect sizes used to sample a value from in order to simulate a new study(ies). The default for the (random) and (randomi) is a predictive distribution based on the t-distribution (t) allowing for heterogeneity between studies (and the uncertainty in the heterogeneity). The default for all other models is the (normal) distribution based on the mean and variance entered inesandvar.

indinstructs the program to calculate the power for the newly simulated study on its own in addition to the newly updated meta-analysis.

nip(integer)specifies the number of integration points used for quadrature when the bivariate model is selected. Higher values should result in greater accuracy but typically at the expense of longer execution times (see Rabe-Hesketh, Skrondal, and Pickles 2005, app. B).

sos(sens/spec)used in addition to theinferenceoption this specifies whether inferences are focused on sensitivity or specificity when usingciwidthorlcias inference options. The default option is to use sensitivity. Ifsosis not specified then the inferences are based on both the sensitivity and specificity and two values should be entered forpow.

graph(lowess/connected/overlay)allows the user to choose the type of line used to connect the specific estimates of power at the specified sample sizes. The default option is aconnectedgraph which plots each point and connects them with a line. The other options are alowessplot, which plots a smoothed line to the specific points, and anoverlayplot, which plots both the points and the lowess curve. Since power is estimated through simulation, there is sampling error in each estimate which will decrease with the number of simulations specified (but also increase evaluation time). Thus smoothing may be desirable if several different but inaccurate estimates are considered. The lowess line should be similar to the connected option for larger simulations.

nociprevents the program from plotting confidence intervals (indicating the sampling error in the estimation of power at specified sample sizes) on the graph.

regraphallows the user to re-graph the power curves with alternative graph options without having to run the simulations for the specified range of sample sizes again.

levelspecifies the confidence level, as a percentage, for the individual study and pooled confidence intervals. This is the level that is given in themetan,metandiandmidascommands when called on to meta-analyses the current data set. The default is level(95).

ExamplesFixed effect Mantel-Haenszel method meta-analysis of clinical trial data using the odds ratio outcome for sample sizes ranging from 10 to 1010 in both the control group and the treatment group of the new study (in increments of 100) and using a p-value of 0.05 for the hypothesis test that the pooled treatment effect is different from 0 to calculate power through 100 iterations for each sample size (i.e. power is based on the proportion os the simulations in which the p-value for the treatment effect being different from 0 is less than 0.05). Note that the program will plot the power curve against the total sample size for the treatment and control groups combined.

. metapowplot e_trt ne_trt e_ctrl ne_ctrl, nit(100) start(10) step(100)stop(1010) measure(or) model(fixed) type(clinical) pow(0.05)inference(pvalue)

Bivariate random effects model for combining diagnostic test accuracy data is used. Both sensitivity and specificity are considered for inferences purposes for sample sizes ranging from 100 to 5000 (in steps of 100) in both the diseased group and the healthy group of the new study and using confidence interval widths of 0.2 and 0.1 for sensitivity and specificity respectively to calculate power through 1000 iterations (i.e. the width of each confidence interval has to be less than these values for the meta-analysis to be considered "significant").

. metapowplot TP FP FN TN, nit(1000) start(100) step(100) stop(5000)measure(ss) model(bivariate) type(diagnostic) pow(0.2 0.1)inference(ciwidth)

Unstandardised mean difference comparing exercise to no treatment in patients with chronic back pain (Ferreira et al. 2012). We investigate the power of the updated meta-analysis when comparing the lower confidence interval to a reduction in pain of 20 points. We vary the sample size of each arm of the new study from 50 to 550 patients in steps of 100.

. use http://fmwww.bc.edu/repec/bocode/m/metapow_eg1. metapowplot nrxpain rxmeanpain rxsdpain ncomppain compmeanpaincompsdpain, nit(100) type(clinical) measure(nostandard) model(random)pow(-20) inference(lci) start(50) stop(550) step(100) graph(lowess)(click to run)

AuthorsMichael J. Crowther, University of Leicester, United Kingdom. Email: michael.crowther@le.ac.uk.

Sally R. Hinchliffe, University of Leicester, United Kingdom. Email: srh20@le.ac.uk.

Alison Donald, University of Leicester, United Kingdom.

Alex J. Sutton, University of Leicester, United Kingdom. Email: ajs22@le.ac.uk.

ReferencesHinchliffe S, Crowther MJ, Phillips RS, Sutton AJ. Using meta-analysis to inform the design of subsequent studies of diagnostic test accuracy (Submitted)

Ferreira ML, Herbert RD, Crowther MJ, Verhagen A, Sutton AJ. When is another clinical trial justified? (Submitted)

Sutton AJ, Cooper NJ, Jones DR, Lambert PC, Thompson JR, Abrams KR. Evidence-based sample size calculations based upon meta-analysis.

Statistics in Medicine2007; 26:2479-2500.

Also seeOnline:

metasim,metapow