We can plot separate graphs for each combination of values of the covariates comprising the interactions. Additionally, none of the supremum tests are significant, suggesting that our residuals are not larger than expected. As an example, imagine subject 1 in the table above, who died at 2,178 days, was in a treatment group of interest for the first 100 days after hospital admission. 147-60. This can be done by multiplying the vector of parameter estimates (the solution vector) by a vector of coefficients such that their product is this sum. ALPHA= p specifies the level of significance pfor the % confidence interval for each contrast when the ESTIMATE option is specified. Subjects that are censored after a given time point contribute to the survival function until they drop out of the study, but are not counted as a failure. The significance level of the confidence interval is controlled by the ALPHA= option. Below we plot survivor curves across several ages for each gender through the follwing steps: As we surmised earlier, the effect of age appears to be more severe in males than in females, reflected by the greater separation between curves in the top graaph. The outcome in this study. A More Complex Contrast In the medical example, you can use nested-by-value effects to decompose treatment*diagnosis interaction as follows: The model effects, treatment(diagnosis='complicated') and treatment(diagnosis='uncomplicated'), are nested-by-value effects that test the effects of treatments within each of the diagnoses. Now lets look at the model with just both linear and quadratic effects for bmi. histogram lenfol / kernel;
To estimate, test, or compare nonlinear combinations of parameters, see the NLEst and NLMeans macros. proc univariate data = whas500(where=(fstat=1));
The null distribution of the cumulative martingale residuals can be simulated through zero-mean Gaussian processes. This option is not applicable to a Bayesian analysis. The test of the difference is more easily obtained using the LSMESTIMATE statement. Notice that id, the individual subject identifier, has been added to the class statement and is also on the repeated statement (with an unstructured correlation matrix), telling proc genmod to calculate the robust errors. If variable exposure is not formatted: If variable exposure is formatted and the formatted value of exposure=0 is 'no': Or, to avoid hardcoding of formatted values: (Among the internal values of exposure, 0 and 1, 0 is the first, regardless of formats. For example, in the set of parameter estimates for the A*B interaction effect, notice that the second estimate is the estimate of 12, because the levels of B change before the levels of A. Institute for Digital Research and Education. In this case, the 12 estimate is the sixth estimate in the A*B effect requiring a change in the coefficient vector that you specify in the ESTIMATE statement. For example, suppose that the model contains effects A and B and their interaction A*B. Finally, the CONTRAST and ESTIMATE statements use the contrast determined above to compute the AB11 - AB12 difference. Models with smaller values of these criteria are considered better models. EXAMPLE 2: A Three-Factor Model with Interactions model lenfol*fstat(0) = gender|age bmi|bmi hr;
model lenfol*fstat(0) = gender|age bmi|bmi hr ;
Note: The terms event and failure are used interchangeably in this seminar, as are time to event and failure time. The LSMESTIMATE statement can also be used. The red curve representing the lowest BMI category is truncated on the right because the last person in that group died long before the end of followup time. However, coefficients for the B effect remain in addition to coefficients for the A*B interaction effect. proc sgplot data = dfbeta;
I would use the CLASS statement (because exposure is a classification variable) and explicitly specify the reference level so that the intended results are clear. of the mean for cell ses =1 and the cell ses =3. Here we demonstrate how to assess the proportional hazards assumption for all of our covariates (graph for gender not shown): As we did with functional form checking, we inspect each graph for observed score processes, the solid blue lines, that appear quite different from the 20 simulated score processes, the dotted lines. Words in italic are new statements added to SAS version 9.22. Looking at the table of Product-Limit Survival Estimates below, for the first interval, from 1 day to just before 2 days, \(n_i\) = 500, \(d_i\) = 8, so \(\hat S(1) = \frac{500 8}{500} = 0.984\). In the code below, we show how to obtain a table and graph of the Kaplan-Meier estimator of the survival function from proc lifetest: Above we see the table of Kaplan-Meier estimates of the survival function produced by proc lifetest. By default, PROC GENMOD computes a likelihood ratio test for the specified contrast. At first glance, we see the PROC PHREG has . An ESTIMATE statement for the AB11 cell mean can be written as above by rewriting the cell mean in terms of the model yielding the appropriate linear combination of parameter estimates. SAS Code from All of These Examples. In very large samples the Kaplan-Meier estimator and the transformed Nelson-Aalen (Breslow) estimator will converge. This indicates that omitting bmi from the model causes those with low bmi values to modeled with too low a hazard rate (as the number of observed events is in excess of the expected number of events). If convergence is not attained in n iterations, the corresponding profile-likelihood confidence limit for the hazard ratio is set to missing. Integrating the pdf over a range of survival times gives the probability of observing a survival time within that interval. As shown in Example 1, tests of simple effects within an interaction can be done using any of several statements other than the CONTRAST and ESTIMATE statements. All In large datasets, very small departures from proportional hazards can be detected. This matches closely with the Kaplan Meier product-limit estimate of survival beyond 3 days of 0.9620. While examples in this class provide good examples of the above process for determining coefficients for CONTRAST and ESTIMATE statements, there are other statements available that perform means comparisons more easily. It appears the probability of surviving beyond 1000 days is a little less than 0.2, which is confirmed by the cdf above, where we see that the probability of surviving 1000 days or fewer is a little more than 0.8. See. We thus calculate the coefficient with the observation, call it \(\beta\), and then the coefficient when observation \(j\) is deleted, call it \(\beta_j\), and take the difference to obtain \(df\beta_j\). Write down the model that you are using the procedure to fit. It is called the proportional hazards model because the ratio of hazard rates between two groups with fixed covariates will stay constant over time in this model. However, it can happen (and it did in your example) that the CLASS statement uses level '1' of that explanatory variable as the reference level so that the sign of the corresponding parameter estimate changes and the inverse hazard ratio and confidence limits are computed,here: the hazard ratio of "no exposure" vs. The last 10 elements are the parameter estimates for the 10 levels of the A*B interaction, 11 through 52. The EXP option provides the odds ratio estimate by exponentiating the difference. For example, we execute the following SAS codes on the dummy ADTTE As the hazard function \(h(t)\) is the derivative of the cumulative hazard function \(H(t)\), we can roughly estimate the rate of change in \(H(t)\) by taking successive differences in \(\hat H(t)\) between adjacent time points, \(\Delta \hat H(t) = \hat H(t_j) \hat H(t_{j-1})\). label row-description <,row-description>. Values of the PLSINGULAR= option must be numeric. Examples: PHREG Procedure References The PLAN Procedure The PLS Procedure The POWER Procedure The Power and Sample Size Application The PRINCOMP Procedure The PRINQUAL Procedure The PROBIT Procedure The QUANTREG Procedure The REG Procedure The ROBUSTREG Procedure The RSREG Procedure The SCORE Procedure The SEQDESIGN Procedure The SEQTEST Procedure For a row vector of the contrast matrix , define to be equal to ABS if ABS is greater than 0; otherwise, equals 1. If PROC PHREG finds a contrast to be nonestimable, it displays missing values in corresponding rows in the results. The cell means can also be obtained by using the ESTIMATE statement to compute the appropriate linear combinations of model parameters. We write the null hypothesis this way: The following table summarizes the data within the complicated diagnosis: The odds ratio can be computed from the data as: This means that, when the diagnosis is complicated, the odds of being cured by treatment A are 1.8845 times the odds of being cured by treatment C. The following statements display the table above and compute the odds ratio: To estimate and test this same contrast of log odds using model 3c, follow the same process as in Example 1 to obtain the contrast coefficients that are needed in the CONTRAST or ESTIMATE statement. The ESTIMATE statement syntax enables you to specify the coefficient vector in sections as just described, with one section for each model effect: Note that this same coefficient vector is given in the table of LS-means coefficients, which was requested by the E option in the LSMEANS statement. For example, if there were three subjects still at risk at time \(t_j\), the probability of observing subject 2 fail at time \(t_j\) would be: \[Pr(subject=2|failure=t_j)=\frac{h(t_j|x_2)}{h(t_j|x_1)+h(t_j|x_2)+h(t_j|x_3)}\]. Shared Concepts and Topics. With mixed models fit in PROC MIXED, if the models are nested in the covariance parameters and have identical fixed effects, then a LR test can be constructed using results from REML estimation (the default) or from ML estimation. DIFF=ALL requests all differences, and DIFF=REF requests comparisons between the reference level and all other levels of the CLASS variable. It is not at all necessary that the hazard function stay constant for the above interpretation of the cumulative hazard function to hold, but for illustrative purposes it is easier to calculate the expected number of failures since integration is not needed. Suppose you want to test whether the effect of treatment A in the complicated diagnosis is different from the average effect of the treatments in the complicated diagnosis. Since treatment A and treatment C are the first and third in the LSMEANS list, the contrast in the LSMESTIMATE statement estimates and tests their difference. INTRODUCTION The PROC LIFEREG and the PROC PHREG procedures both can do survival analysis using time-to-event data, . 1469-82. See the "Parameterization of PROC GLM Models" section in the PROC GLM documentation for some important details on how the design variables are created. Here are the steps we use to assess the influence of each observation on our regression coefficients: The dfbetas for age and hr look small compared to regression coefficients themselves (\(\hat{\beta}_{age}=0.07086\) and \(\hat{\beta}_{hr}=0.01277\)) for the most part, but id=89 has a rather large, negative dfbeta for hr. Expressing the above relationship as \(\frac{d}{dt}H(t) = h(t)\), we see that the hazard function describes the rate at which hazards are accumulated over time. The value for must be between 0 and 1; the default value is 1E4. If the MULTIPASS option is not specified, PROC PHREG . Firths Correction for Monotone Likelihood, Conditional Logistic Regression for m:n Matching, Model Using Time-Dependent Explanatory Variables, Time-Dependent Repeated Measurements of a Covariate, Survivor Function Estimates for Specific Covariate Values, Model Assessment Using Cumulative Sums of Martingale Residuals, Bayesian Analysis of Piecewise Exponential Model. You must be familiar with the details of the model parameterization that PROC PHREG uses (for more information, see the PARAM= option in the section CLASS Statement). The ODDSRATIO statement in PROC LOGISTIC and the similar HAZARDRATIO statement in PROC PHREG are also available. You can use the same method of writing the AB12 cell mean in terms of the model: You can write the average of cell means in terms of the model: So, the coefficient for the A parameters is 1/2; for B it is 1/3; and for AB it is 1/6. Proportional hazards tests and diagnostics based on weighted residuals. Here is the syntax for CONTRAST statement. With appropriate data modification and weighting as described above, this baseline hazard function is exactly equal to the baseline subdistribution hazard function of a PSH model. controls the convergence criterion for the profile-likelihood confidence limits. For example, if \(\beta_x\) is 0.5, each unit increase in \(x\) will cause a ~65% increase in the hazard rate, whether X is increasing from 0 to 1 or from 99 to 100, as \(HR = exp(0.5(1)) = 1.6487\). However, the process of constructing CONTRAST statements is the same: write the hypothesis of interest in terms of the fitted model to determine the coefficients for the statement. specifies which differences to consider for the level comparisons of a CLASS variable. For observation \(j\), \(df\beta_j\) approximates the change in a coefficient when that observation is deleted. We, as researchers, might be interested in exploring the effects of being hospitalized on the hazard rate. run; proc corr data = whas500 plots(maxpoints=none)=matrix(histogram);
and what i need is the hard ratios for outcome on exposure. This study examined several factors, such as age, gender and BMI, that may influence survival time after heart attack. However, despite our knowledge that bmi is correlated with age, this method provides good insight into bmis functional form. Below we demonstrate use of the assess statement to the functional form of the covariates. However they lived much longer than expected when considering their bmi scores and age (95 and 87), which attenuates the effects of very low bmi. A solid line that falls significantly outside the boundaries set up collectively by the dotted lines suggest that our model residuals do not conform to the expected residuals under our model. Also notice that the distribution has been changed to Poisson, but the link function remains log. specifies the level of significance for the % confidence interval for each contrast when the ESTIMATE option is specified. For software releases that are not yet generally available, the Fixed The survival curves for females is slightly higher than the curve for males, suggesting that the survival experience is possibly slightly better (if significant) for females, after controlling for age. It is important to know how variable levels change within the set of parameter estimates for an effect. For these models, the response is no longer modeled directly. 51. Notice, however, that \(t\) does not appear in the formula for the hazard function, thus implying that in this parameterization, we do not model the hazard rates dependence on time. data example8_1; set sec1_5; group1 = group - 1; run; proc phreg data = example8_1; model time*death (0)=group1; run; run; proc phreg data = whas500;
then the procedure provides no results, either displaying Non-est in the table of results or issuing this message in the log: The estimate is declared nonestimable simply because the coefficients 1/3 and 1/6 are not represented precisely enough. | SAS FAQ We will use a data set called hsb2.sas7bdat to demonstrate. For this reason, it is known as a full-rank parameterization. Cox models are typically fitted by maximum likelihood methods, which estimate the regression parameters that maximize the probability of observing the given set of survival times. This test can be done using a CONTRAST statement to jointly test the interaction parameters. The default is DIFF=ALL. Partial Likelihood The partial likelihood function for one covariate is: where t i is the ith death time, x i is the associated covariate, and R i is the risk set at time t i, i.e., the set of subjects is still alive and uncensored just prior to time t i. The covariance matrix of the parameter estimator is computed as a sandwich estimate. The first 12 examples use the classical method of maximum likelihood, while the last two examples illustrate the Bayesian methodology. The next two elements are the parameter estimates for the levels of B, 1 and 2. run; proc phreg data = whas500;
You can specify nested-by-value effects in the MODEL statement to test the effect of one variable within a particular level of another variable. The following statements fit the model and compute the AB11 and AB12 cell means by using the LSMEANS statement and equivalent ESTIMATE statements: Suppose you want to test that the AB11 and AB12 cell means are equal.
Below, we show how to use the hazardratio statement to request that SAS estimate 3 hazard ratios at specific levels of our covariates. These statistics are provided in most procedures using maximum likelihood estimation. More than one HAZARDRATIO statement can be specified, and an optional label (specified as a quoted string) helps identify the output. Second, all three fit statistics, -2 LOG L, AIC and SBC, are each 20-30 points lower in the larger model, suggesting the including the extra parameters improve the fit of the model substantially. The first three parameters of the nested effect are the effects of treatments within the complicated diagnosis. But an equivalent representation of the model is: where Ai and Bj are sets of design variables that are defined as follows using dummy coding: For the medical example above, model 3b for the odds of being cured are: Estimating and Testing Odds Ratios with Dummy Coding. Standard nonparametric techniques do not typically estimate the hazard function directly. Hello. As time progresses, the Survival function proceeds towards it minimum, while the cumulative hazard function proceeds to its maximum. ESSENTIAL STEPS in using PROC PHREG. We see that the uncoditional probability of surviving beyond 382 days is .7220, since \(\hat S(382)=0.7220=p(surviving~ up~ to~ 382~ days)\times0.9971831\), we can solve for \(p(surviving~ up~ to~ 382~ days)=\frac{0.7220}{0.9972}=.7240\). model lenfol*fstat(0) = ;
First, write the model, being sure to verify its parameters and their order from the procedure's displayed results: Now write each part of the contrast in terms of the effects-coded model (3e). Density functions are essentially histograms comprised of bins of vanishingly small widths. The rows of are specified in order and are separated by commas. By default, is equal to the value of the ALPHA= option in the PROC PHREG statement, or 0.05 if that option is not specified. We also identify id=89 again and id=112 as influential on the linear bmi coefficient (\(\hat{\beta}_{bmi}=-0.23323\)), and their large positive dfbetas suggest they are pulling up the coefficient for bmi when they are included. However, if the nested models do not have identical fixed effects, then results from ML estimation must be used to construct a LR test. The PHREG procedure now fits frailty models with the addition of the RANDOM statement. Estimates are formed as linear estimable functions of the form . SAS provides easy ways to examine the \(df\beta\) values for all observations across all coefficients in the model. time lenfol*fstat(0);
From these equations we can see that the cumulative hazard function \(H(t)\) and the survival function \(S(t)\) have a simple monotonic relationship, such that when the Survival function is at its maximum at the beginning of analysis time, the cumulative hazard function is at its minimum. Had B preceded A in the CLASS statement, the levels of A would have changed before the levels of B, resulting in the second estimate being for 21. Checking the Cox model with cumulative sums of martingale-based residuals. We previously saw that the gender effect was modest, and it appears that for ages 40 and up, which are the ages of patients in our dataset, the hazard rates do not differ by gender. The EXPB option adds a column in the parameter estimates table that contains exponentiated values of the corresponding parameter estimates. 2009 by SAS Institute Inc., Cary, NC, USA. where \(d_i\) is the number who failed out of \(n_i\) at risk in interval \(t_i\). Example Suppose we wish to fit a PH model to the data from . By default, pis equal to the value of the ALPHA= option in the PROC PHREG statement, or 0.05 if that option is not specified. Because this seminar is focused on survival analysis, we provide code for each proc and example output from proc corr with only minimal explanation. Estimating and Testing Odds Ratios with Effects Coding. The CONTRAST statement provides a mechanism for obtaining customized hypothesis tests. Copyright Using model (1) above, the AB12 cell mean, 12, is: Because averages of the errors (ijk) are assumed to be zero: Similarly, the AB11 cell mean is written this way: So, to get an estimate of the AB12 mean, you need to add together the estimates of , 1, 2, and 12. The coefficients that are needed in the ESTIMATE statement are determined by writing what you want to estimate in terms of the fitted model. Because the observation with the longest follow-up is censored, the survival function will not reach 0. Consider a model for two factors: A with five levels and B with two levels: where i=1,2,,5, j=1,2, k=1, 2,,nij. We can remove the dependence of the hazard rate on time by expressing the hazard rate as a product of \(h_0(t)\), a baseline hazard rate which describes the hazard rates dependence on time alone, and \(r(x,\beta_x)\), which describes the hazard rates dependence on the other \(x\) covariates: In this parameterization, \(h(t)\) will equal \(h_0(t)\) when \(r(x,\beta_x) = 1\). To accomplish this smoothing, the hazard function estimate at any time interval is a weighted average of differences within a window of time that includes many differences, known as the bandwidth. to the coefficient for ses = 2. Example 1: One-way ANOVA The dependent variable is write and the factor variable is ses which has three levels. specifies the units of change in the continuous explanatory variable for which the customized hazard ratio is estimated. The same procedure could be repeated to check all covariates. Survival analysis models factors that influence the time to an event. 2009 by SAS Institute Inc., Cary, NC, USA. In this seminar we will be analyzing the data of 500 subjects of the Worcester Heart Attack Study (referred to henceforth as WHAS500, distributed with Hosmer & Lemeshow(2008)). The default is UNITS=1. As a consequence, you can test or estimate only homogeneous linear combinations (those with zero-intercept coefficients, such as contrasts that represent group differences) for the GLM parameterization. If you specify a CONTRAST statement involving A alone, the matrix contains nonzero terms for both A and A*B, since A*B contains A. Recall that when we introduce interactions into our model, each individual term comprising that interaction (such as GENDER and AGE) is no longer a main effect, but is instead the simple effect of that variable with the interacting variable held at 0. 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