masize: Sample size calculation for mediation analysis

In gap: Genetic Analysis Package

Sample size calculation for mediation analysis

Description

The function computes sample size for regression problems where the goal is to assess mediation of the effects of a primary predictor by an intermediate variable or mediator.

Usage

masize(model, opts, alpha = 0.025, gamma = 0.2)

Arguments

model	"lineari", "logisticj", "poissonk", "coxl", where i,j,k,l range from 1 to 4,5,9,9, respectively.
opts	A list specific to the model b1 regression coefficient for the primary predictor X1 b2 regression coefficient for the mediator X2 rho correlation between X1 and X2 sdx1, sdx2 standard deviations (SDs) of X1 and X2 f1, f2 prevalence of binary X1 and X2 sdy residual SD of the outcome for the linear model p marginal prevalence of the binary outcome in the logistic model m marginal mean of the count outcome in a Poisson model f proportion of uncensored observations for the Cox model fc proportion of observations censored early alpha one-sided type-I error rate gamma type-II error rate ns number of observations to be simulated seed random number seed For linear model, the arguments are b2, rho, sdx2, sdy, alpha, and gamma. For cases CpBm and BpBm, set sdx2 = \sqrt{f2(1-f2)}. Three alternative functions are included for the linear model. These functions make it possible to supply other combinations of input parameters affecting mediation: b1* coefficient for the primary predictor in the reduced model excluding the mediator (b1star) b1 coefficient for the primary predictor in the full model including the mediator PTE proportion of the effect of the primary predictor explained by the mediator, defined as (b1*-b1)/b1* These alternative functions for the linear model require specification of an extra parameter, but are provided for convenience, along with two utility files for computing PTE and b1* from the other parameters. The required arguments are explained in comments within the R code.
alpha	Type-I error rate, one-sided.
gamma	Type-II error rate.

Details

Mediation has been thought of in terms of the proportion of effect explained, or the relative attenuation of b1, the coefficient for the primary predictor X1, when the mediator, X2, is added to the model. The goal is to show that b1*, the coefficient for X1 in the reduced model (i.e., the model with only X1, differs from b1, its coefficient in the full model (i.e., the model with both X1 and the mediator X2. If X1 and X2 are correlated, then showing that b2, the coefficient for X2, differs from zero is equivalent to showing b1* differs from b1. Thus the problem reduces to detecting an effect of X2, controlling for X1. In short, it amounts to the more familiar problem of inflating sample size to account for loss of precision due to adjustment for X1.

The approach here is to approximate the expected information matrix from the regression model including both X1 and X2, to obtain the expected standard error of the estimate of b2, evaluated at the MLE. The sample size follows from comparing the Wald test statistic (i.e., the ratio of the estimate of b2 to its SE) to the standard normal distribution, with the expected value of the numerator and denominator of the statistic computed under the alternative hypothesis. This reflects the Wald test for the statistical significance of a coefficient implemented in most regression packages.

The function provides methods to calculate sample sizes for the mediation problem for linear, logistic, Poisson, and Cox regression models in four cases for each model:

CpCm	continuous primary predictor, continuous mediator
BpCm	binary primary predictor, continuous mediator
CpBm	continuous primary predictor, binary mediator
BpBm	binary primary predictor, binary mediator

The function is also generally applicable to the analogous problem of calculating sample size adequate to detect the effect of a primary predictor in the presence of confounding. Simply treat X2 as the primary predictor and consider X1 the confounder.

For linear model, a single function, linear, implements the analytic solution for all four cases, based on Hsieh et al., is to inflate sample size by a variance inflation factor, 1/(1-rho^2), where rho is the correlation of X1 and X2. This also turns out to be the analytic solution in cases CpCm and BpCm for the Poisson model, and underlies approximate solutions for the logistic and Cox models. An analytic solution is also given for cases CpBm and BpBm for the Poisson model. Since analytic solutions are not available for the logistic and Cox models, a simulation approach is used to obtain the expected information matrix instead.

For logistic model, the approximate solution due to Hsieh is implemented in the function logistic.approx, and can be used for all four cases. Arguments are p, b2, rho, sdx2, alpha, and gamma. For a binary mediator with prevalence f2, sdx2 should be reset to \sqrt{f2(1-f2)}. Simulating the information matrix of the logistic model provides somewhat more accurate sample size estimates than the Hsieh approximation. The functions for cases CpCm, BpCm, CpBm, and BpBm are respectively logistic.ccs, logistic.bcs, logistic.cbs, and logistic.bbs, as for the Poisson and Cox models. Arguments for these functions include p, b1, sdx1 or f1, b2, sdx2 or f2, rho, alpha, gamma, and ns. As in other functions, sdx1, sdx2, alpha, and gamma are set to the defaults listed above. These four functions call two utility functions, getb0 (to calculate the intercept parameter from the others) and antilogit, which are supplied.

For Poisson model, The function implementing the approximate solution based on the variance inflation factor is poisson.approx, and can be used for all four cases. Arguments are EY (the marginal mean of the Poisson outcome), b2, sdx2, rho, alpha and gamma, with sdx2, alpha and gamma set to the usual defaults; use sdx2=\sqrt{f2(1-f2)} for a binary mediator with prevalence f2 (cases CpBm and BpBm). For cases CpCm and BpCm (continuous mediators), the approximate formula is also the analytic solution. For these cases, we supply redundant functions poisson.cc and poisson.bc, with the same arguments and defaults as for poisson.approx (it's the same function). For the two cases with binary mediators, the functions are poisson.cb and poisson.bb. In addition to m, b2, f2, rho, alpha, and gamma, b1 and sdx1 or f1 must be specified. Defaults are as usual. Functions using simulation for the Poisson model are available: poisson.ccs, poisson.bcs, poisson.cbs, and poisson.bbs. As in the logistic case, these require arguments b1 and sdx1 or f1. For this case, however, the analytic functions are faster, avoid simulation error, and should be used. We include these functions as templates that could be adapted to other joint predictor distributions. For Cox model, the function implementing the approximate solution, using the variance inflation factor and derived by Schmoor et al., is cox.approx, and can be used for all four cases. Arguments are b2, sdx2, rho, alpha, gamma, and f. For binary X2 set sdx2 = \sqrt{f2(1-f2)}. The approximation works very well for cases CpCm and BpCm (continuous mediators), but is a bit less accurate for cases CpBm and BpBm (binary mediators). We get some improvement for those cases using the simulation approach. This approach is implemented for all four, as functions cox.ccs, cox.bcs, cox.cbs, and cox.bbs. Arguments are b1, sdx1 or f1, b2, sdx2 or f2, rho, alpha, gamma, f, and ns, with defaults as described above. Slight variants of these functions, cox.ccs2, cox.bcs2, cox.cbs2, and cox.bbs2, make it possible to allow for early censoring of a fraction fc of observations; but in our experience this has virtually no effect, even with values of fc of 0.5. The default for fc is 0.

A summary of the argumentss is as follows, noting that additional parameter seed can be supplied for simulation-based method.

model	arguments	description
linear1	b2, rho, sdx2, sdy	linear
linear2	b1star, PTE, rho, sdx1, sdy	lineara
linear3	b1star, b2, PTE, sdx1, sdx2, sdy	linearb
linear4	b1star, b1, b2, sdx1, sdx2, sdy	linearc
logistic1	p, b2, rho, sdx2	logistic.approx
logistic2	p, b1, b2, rho, sdx1, sdx2, ns	logistic.ccs
logistic3	p, b1, f1, b2, rho, sdx2, ns	logistic.bcs
logistic4	p, b1, b2, f2, rho, sdx1, ns	logistic.cbs
logistic5	p, b1, f1, b2, f2, rho, ns	logistic.bbs
poisson1	m, b2, rho, sdx2	poisson.approx
poisson2	m, b2, rho, sdx2	poisson.cc
poisson3	m, b2, rho, sdx2	poisson.bc
poisson4	m, b1, b2, f2, rho, sdx1	poisson.cb
poisson5	m, b1, f1, b2, f2, rho	poisson.bb
poisson6	m, b1, b2, rho, sdx1, sdx2, ns	poisson.ccs
poisson7	m, b1, f1, b2, rho, sdx2, ns	poisson.bcs
poisson8	m, b1, b2, f2, rho, sdx1, ns	poisson.cbs
poisson9	m, b1, f1, b2, f2, rho, ns	poisson.bbs
cox1	b2, rho, f, sdx2	cox.approx
cox2	b1, b2, rho, f, sdx1, sdx2, ns	cox.ccs
cox3	b1, f1, b2, rho, f, sdx2, ns	cox.bcs
cox4	b1, b2, f2, rho, f, sdx1, ns	cox.cbs
cox5	b1, f1, b2, f2, rho, f, ns	cox.bbs
cox6	b1, b2, rho, f, fc, sdx1, sdx2, ns	cox.ccs2
cox7	b1, f1, b2, rho, f, fc, sdx2, ns	cox.bcs2
cox8	b1, b2, f2, rho, f, fc, sdx1, ns	cox.cbs2
cox9	b1, f1, b2, f2, rho, f, fc, ns	cox.bbs2

Value

A short description of model (desc, b=binary, c=continuous, s=simulation) and sample size (n). In the case of Cox model, number of events (d) is also indicated.

References

\insertRef

hsieh98gap

\insertRef

schmoor00gap

\insertRef

vittinghoff09gap

See Also

ab

Examples

## Not run: 
## linear model
# CpCm
opts <- list(b2=0.5, rho=0.3, sdx2=1, sdy=1)
masize("linear1",opts)
# BpBm
opts <- list(b2=0.75, rho=0.3, f2=0.25, sdx2=sqrt(0.25*0.75), sdy=3)
masize("linear1",opts,gamma=0.1)

## logistic model
# CpBm
opts <- list(p=0.25, b2=log(0.5), rho=0.5, sdx2=0.5)
masize("logistic1",opts)
opts <- list(p=0.25, b1=log(1.5), sdx1=1, b2=log(0.5), f2=0.5, rho=0.5, ns=10000,
             seed=1234)
masize("logistic4",opts)
opts <- list(p=0.25, b1=log(1.5), sdx1=1, b2=log(0.5), f2=0.5, rho=0.5, ns=10000,
             seed=1234)
masize("logistic4",opts)
opts <- list(p=0.25, b1=log(1.5), sdx1=4.5, b2=log(0.5), f2=0.5, rho=0.5, ns=50000,
             seed=1234)
masize("logistic4",opts)

## Poisson model
# BpBm
opts <- list(m=0.5, b2=log(1.25), rho=0.3, sdx2=sqrt(0.25*0.75))
masize("poisson1",opts)
opts <- list(m=0.5, b1=log(1.4), f1=0.25, b2=log(1.25), f2=0.25, rho=0.3)
masize("poisson5",opts)
opts <- c(opts,ns=10000, seed=1234)
masize("poisson9",opts)

## Cox model
# BpBm
opts <- list(b2=log(1.5), rho=0.45, f=0.2, sdx2=sqrt(0.25*0.75))
masize("cox1",opts)
opts <- list(b1=log(2), f1=0.5, b2=log(1.5), f2=0.25, rho=0.45, f=0.2, seed=1234)
masize("cox5",c(opts, ns=10000))
masize("cox5",c(opts, ns=50000))

## End(Not run)

gap documentation built on Aug. 26, 2023, 5:07 p.m.