The hardware and bandwidth for this mirror is donated by METANET, the Webhosting and Full Service-Cloud Provider.
If you wish to report a bug, or if you are interested in having us mirror your free-software or open-source project, please feel free to contact us at mirror[@]metanet.ch.

library(psborrow2)
library(cmdstanr)

Propensity scores (PS) methods offer various ways to adjust analyses for differences in groups of patients. Austin (2013) discusses various approaches for using PS with survival analyses to obtain effect measures similar to randomized controlled trials. Wang et al. (2021) discuss using PS for IPTW, matching and stratification in combination with a Bayesian analysis. These methods allow for the separation of the design and analysis into two stages, which may be attractive in a regulatory setting. Another approach is the direct inclusion of the PS as a covariate in the outcome model.

Alternative PS Weights with WeightIt

The WeightIt package can calculate PS and other balancing weights with a number of different methods, such as generalized boosted modeling (method = "gbm"). In addition, weights can be calculated differently for different estimands. Here, we specifying estimand = "ATT", to calculate weights for estimating the average treatment effect among the treated (ATT).

library(WeightIt)

example_dataframe <- as.data.frame(example_matrix)
example_dataframe$int <- 1 - example_dataframe$ext

weightit_model <- weightit(
  int ~ cov1 + cov2 + cov3 + cov4,
  data = example_dataframe,
  method = "gbm",
  estimand = "ATT"
)
#> Warning: No `criterion` was provided. Using "smd.mean"FALSETRUE.
summary(weightit_model)
#>                  Summary of weights
#> 
#> - Weight ranges:
#> 
#>            Min                                  Max
#> treated 1.0000      ||                       1.0000
#> control 0.0826 |---------------------------| 5.8966
#> 
#> - Units with the 5 most extreme weights by group:
#>                                            
#>               5      4      3      2      1
#>  treated      1      1      1      1      1
#>             195    158    465    438    371
#>  control 2.7924 2.7924 5.8966 5.8966 5.8966
#> 
#> - Weight statistics:
#> 
#>         Coef of Var  MAD Entropy # Zeros
#> treated       0.000 0.00     0.0       0
#> control       1.582 0.82     0.6       0
#> 
#> - Effective Sample Sizes:
#> 
#>            Control Treated
#> Unweighted  350.       150
#> Weighted    100.09     150

Another useful package is cobalt, which provides tools for assessing balance between groups after weighting or matching. It is compatible with many matching and weighting packages. See the vignette for more details. We can use the cobalt package to assess balance with bal.plot().

library(cobalt)
bal.plot(weightit_model)
plot of chunk balplot

plot of chunk balplot

“Love plots” can also be generated that compare the populations before and after weighting:

love.plot(weightit_model, stars = "std")
plot of chunk loveplot

plot of chunk loveplot

The PS values can be copied into the data set and the analysis object can be constructed as before.

example_dataframe$att <- weightit_model$weights

example_matrix_att <- create_data_matrix(
  example_dataframe,
  ext_flag_col = "ext",
  outcome = c("time", "cnsr"),
  trt_flag_col = "trt",
  weight_var = "att"
)

analysis_att <- create_analysis_obj(
  data_matrix = example_matrix_att,
  outcome = outcome_surv_exponential("time", "cnsr", prior_normal(0, 10000), weight_var = "att"),
  borrowing = borrowing_full("ext"),
  treatment = treatment_details("trt", prior_normal(0, 10000)),
  quiet = TRUE
)

result_att <- mcmc_sample(analysis_att, seed = 123)

Matching with MatchIt

A variety of matching methods, including PS matching are implemented in the MatchIt package.

As described in the Getting Started vignette, it can be useful to check the imbalance before matching.

library(MatchIt)
#> 
#> Attaching package: 'MatchIt'
#> The following object is masked from 'package:cobalt':
#> 
#>     lalonde
# No matching; constructing a pre-match matchit object
no_match <- matchit(trt ~ cov1 + cov2 + cov3 + cov4,
  data = example_dataframe,
  method = NULL, distance = "glm"
)
summary(no_match)
#> 
#> Call:
#> matchit(formula = trt ~ cov1 + cov2 + cov3 + cov4, data = example_dataframe, 
#>     method = NULL, distance = "glm")
#> 
#> Summary of Balance for All Data:
#>          Means Treated Means Control Std. Mean Diff. Var. Ratio eCDF Mean
#> distance        0.2898        0.1776          0.7585     1.5831    0.2328
#> cov1            0.6300        0.7150         -0.1761          .    0.0850
#> cov2            0.3700        0.4625         -0.1916          .    0.0925
#> cov3            0.7600        0.4475          0.7317          .    0.3125
#> cov4            0.4600        0.2250          0.4715          .    0.2350
#>          eCDF Max
#> distance   0.3375
#> cov1       0.0850
#> cov2       0.0925
#> cov3       0.3125
#> cov4       0.2350
#> 
#> Sample Sizes:
#>           Control Treated
#> All           400     100
#> Matched       400     100
#> Unmatched       0       0
#> Discarded       0       0

Here we are matching treated to untreated to select the most comparable control group, regardless of whether they are internal or external. For simplicity let’s try a 1:1 nearest matching approach.

match_11 <- matchit(trt ~ cov1 + cov2 + cov3 + cov4,
  data = example_dataframe,
  method = "nearest", distance = "glm"
)
summary(match_11)
#> 
#> Call:
#> matchit(formula = trt ~ cov1 + cov2 + cov3 + cov4, data = example_dataframe, 
#>     method = "nearest", distance = "glm")
#> 
#> Summary of Balance for All Data:
#>          Means Treated Means Control Std. Mean Diff. Var. Ratio eCDF Mean
#> distance        0.2898        0.1776          0.7585     1.5831    0.2328
#> cov1            0.6300        0.7150         -0.1761          .    0.0850
#> cov2            0.3700        0.4625         -0.1916          .    0.0925
#> cov3            0.7600        0.4475          0.7317          .    0.3125
#> cov4            0.4600        0.2250          0.4715          .    0.2350
#>          eCDF Max
#> distance   0.3375
#> cov1       0.0850
#> cov2       0.0925
#> cov3       0.3125
#> cov4       0.2350
#> 
#> Summary of Balance for Matched Data:
#>          Means Treated Means Control Std. Mean Diff. Var. Ratio eCDF Mean
#> distance        0.2898        0.2845          0.0355     1.1082    0.0075
#> cov1            0.6300        0.6800         -0.1036          .    0.0500
#> cov2            0.3700        0.3900         -0.0414          .    0.0200
#> cov3            0.7600        0.7600          0.0000          .    0.0000
#> cov4            0.4600        0.4600          0.0000          .    0.0000
#>          eCDF Max Std. Pair Dist.
#> distance     0.07          0.0355
#> cov1         0.05          0.1036
#> cov2         0.02          0.1243
#> cov3         0.00          0.0000
#> cov4         0.00          0.0000
#> 
#> Sample Sizes:
#>           Control Treated
#> All           400     100
#> Matched       100     100
#> Unmatched     300       0
#> Discarded       0       0
set.seed(123)
plot(match_11, type = "jitter", interactive = FALSE)
plot of chunk matchit_jitter

plot of chunk matchit_jitter

Determining whether the balance after matching is appropriate is beyond the scope of this vignette. You can read more in the MatchIt Assessing Balance vignette. Again the cobalt package can be useful here.

However, if you are happy with the results of the matching procedure, you can extract the data for use in psborrow2.

example_matrix_match <- create_data_matrix(
  data = example_dataframe[match_11$weights == 1, ],
  ext_flag_col = "ext",
  outcome = c("time", "cnsr"),
  trt_flag_col = "trt"
)
analysis_match <- create_analysis_obj(
  data_matrix = example_matrix_match,
  outcome = outcome_surv_exponential("time", "cnsr", prior_normal(0, 10000)),
  borrowing = borrowing_full("ext"),
  treatment = treatment_details("trt", prior_normal(0, 10000)),
  quiet = TRUE
)

result_match <- mcmc_sample(analysis_match, seed = 123)

Combined Weighting and Dynamic Borrowing

The models also support fixed weights on the likelihood contributions from each observation. This is equivalent to fixed power prior weights. This allows for the combination of models, such as an IPTW + commensurate prior approach.

analysis_iptw_bdb <- create_analysis_obj(
  data_matrix = example_matrix_att,
  outcome = outcome_surv_exponential("time", "cnsr", prior_normal(0, 10000), weight_var = "att"),
  borrowing = borrowing_hierarchical_commensurate("ext", prior_gamma(0.01, 0.01)),
  treatment = treatment_details("trt", prior_normal(0, 10000)),
  quiet = TRUE
)

result_iptw_bdb <- mcmc_sample(analysis_iptw_bdb, seed = 123)

Fixed Weights

We can also use weights to specify a fixed power prior model. Here we set the power parameter \(\alpha = 0.1\) for the external controls.

example_matrix_pp01 <- cbind(example_matrix, pp_alpha = ifelse(example_matrix[, "ext"] == 1, 0.1, 1))

analysis_pp01 <- create_analysis_obj(
  data_matrix = example_matrix_pp01,
  outcome = outcome_surv_exponential("time", "cnsr", prior_normal(0, 10000), weight_var = "pp_alpha"),
  borrowing = borrowing_full("ext"),
  treatment = treatment_details("trt", prior_normal(0, 10000)),
  quiet = TRUE
)

result_pp01 <- mcmc_sample(analysis_pp01, seed = 123)

Reference Models

For comparison, we also fit a full borrowing, a no borrowing, and a BDB model without weights.

result_full <- mcmc_sample(
  create_analysis_obj(
    data_matrix = example_matrix,
    outcome = outcome_surv_exponential("time", "cnsr", prior_normal(0, 10000)),
    borrowing = borrowing_full("ext"),
    treatment = treatment_details("trt", prior_normal(0, 10000)),
    quiet = TRUE
  ),
  seed = 123
)

result_none <- mcmc_sample(
  create_analysis_obj(
    data_matrix = example_matrix,
    outcome = outcome_surv_exponential("time", "cnsr", prior_normal(0, 10000)),
    borrowing = borrowing_none("ext"),
    treatment = treatment_details("trt", prior_normal(0, 10000)),
    quiet = TRUE
  ),
  seed = 123
)

result_bdb <- mcmc_sample(
  create_analysis_obj(
    data_matrix = example_matrix_att,
    outcome = outcome_surv_exponential("time", "cnsr", prior_normal(0, 10000)),
    borrowing = borrowing_hierarchical_commensurate("ext", prior_gamma(0.01, 0.01)),
    treatment = treatment_details("trt", prior_normal(0, 10000)),
    quiet = TRUE
  ),
  seed = 123
)

Comparison of Results

models <- list(
  "No borrowing" = result_none,
  "Full borrowing" = result_full,
  "Power Prior 01" = result_pp01,
  "ATT Weights" = result_att,
  "IPTW + BDB" = result_iptw_bdb,
  "Matching 1:1" = result_match,
  "BDB" = result_bdb
)

We can use summary() to extract the variable of interest and specify summary statistics.

results_table <- do.call(rbind, lapply(
  models,
  function(i) i$summary("HR_trt", c("mean", "median", "sd", "quantile2"))
))
knitr::kable(cbind(models = names(models), results_table), digits = 3)
models variable mean median sd q5 q95
No borrowing HR_trt 0.896 0.879 0.179 0.635 1.214
Full borrowing HR_trt 0.387 0.385 0.049 0.311 0.471
Power Prior 01 HR_trt 0.633 0.625 0.106 0.475 0.819
ATT Weights HR_trt 0.893 0.884 0.127 0.700 1.114
IPTW + BDB HR_trt 0.893 0.877 0.164 0.654 1.186
Matching 1:1 HR_trt 0.796 0.785 0.130 0.601 1.028
BDB HR_trt 0.873 0.855 0.176 0.620 1.190

We can extract a draws object from each model and plot the posterior distribution of the treatment hazard ratio.

plot(density(models[[1]]$draws("HR_trt")),
  col = 1, xlim = c(0, 2), ylim = c(0, 9), lwd = 2,
  xlab = "HR_trt",
  main = "Posterior Hazard Ratio"
)
for (i in 2:7) {
  lines(density(models[[i]]$draws("HR_trt")), col = i, lty = i, lwd = 2)
}
legend("topright", col = seq_along(models), lty = seq_along(models), legend = names(models))
plot of chunk plots

plot of chunk plots

Here we see no borrowing and full borrowing at the extremes and the other methods in between.

References

Austin, Peter C. 2013. “The Use of Propensity Score Methods with Survival or Time-to-Event Outcomes: Reporting Measures of Effect Similar to Those Used in Randomized Experiments.” Statistics in Medicine 33 (7): 1242–58. https://doi.org/10.1002/sim.5984.
Wang, Xi, Leah Suttner, Thomas Jemielita, and Xiaoyun Li. 2021. “Propensity Score-Integrated Bayesian Prior Approaches for Augmented Control Designs: A Simulation Study.” Journal of Biopharmaceutical Statistics 32 (1): 170–90. https://doi.org/10.1080/10543406.2021.2011743.

These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.