Heterogeneity & Demographic Analysis

2020-04-08

Introduction

Heterogeneity analysis is a way to explore how the results of a model can vary depending on the characteristics of individuals in a population, and demographic analysis estimates the average values of a model over an entire population.

In practice these two analyses naturally complement each other: heterogeneity analysis runs the model on multiple sets of parameters (reflecting differents characteristics found in the target population), and demographic analysis combines the results.

For this example we will use the result from the assessment of a new total hip replacement previously described in vignette("d-non-homogeneous", "heemod").

Population characteristics

The characteristics of the population are input from a table, with one column per parameter and one row per individual. Those may be for example the characteristics of the indiviuals included in the original trial data.

For this example we will use the characteristics of 100 individuals, with varying sex and age, specified in the data frame tab_indiv:

tab_indiv
## # A tibble: 100 x 2
##      age   sex
##    <dbl> <int>
##  1    87     0
##  2    60     1
##  3    52     1
##  4    65     1
##  5    65     0
##  6    65     1
##  7    34     0
##  8    79     0
##  9    32     1
## 10    67     1
## # … with 90 more rows
library(ggplot2)
ggplot(tab_indiv, aes(x = age)) +
  geom_histogram(binwidth = 2)

Running the analysis

res_mod, the result we obtained from run_model() in the Time-varying Markov models vignette, can be passed to update() to update the model with the new data and perform the heterogeneity analysis.

res_h <- update(res_mod, newdata = tab_indiv)
## No weights specified in update, using equal weights.
## Updating strategy 'standard'...
## Updating strategy 'np1'...

Interpreting results

The summary() method reports summary statistics for cost, effect and ICER, as well as the result from the combined model.

summary(res_h)
## An analysis re-run on 100 parameter sets.
## 
## * Unweighted analysis.
## 
## * Values distribution:
## 
##                                  Min.     1st Qu.       Median        Mean
## standard - Cost          450.15881156  613.836464  761.4317051 721.6313517
## standard - Effect          7.47256790   25.569643   27.3769142  26.1326792
## standard - Cost Diff.               -           -            -           -
## standard - Effect Diff.             -           -            -           -
## standard - Icer                     -           -            -           -
## np1 - Cost               593.80297968  637.950820  680.0145801 668.7386332
## np1 - Effect               7.49009703   25.829934   27.7656911  26.4202297
## np1 - Cost Diff.        -167.83433856 -129.482909  -81.4171250 -52.8927186
## np1 - Effect Diff.         0.01752913    0.208543    0.2918287   0.2875505
## np1 - Icer              -355.65308588 -333.051997 -278.9894047  -5.9314266
##                             3rd Qu.         Max.
## standard - Cost         828.5434528  882.1752204
## standard - Effect        29.0749005   31.7692206
## standard - Cost Diff.             -            -
## standard - Effect Diff.           -            -
## standard - Icer                   -            -
## np1 - Cost              699.0605439  714.3408818
## np1 - Effect             29.5008365   32.0078346
## np1 - Cost Diff.         24.1143568  143.6441681
## np1 - Effect Diff.        0.3887769    0.4719046
## np1 - Icer              115.6325465 8194.5991768
## 
## * Combined result:
## 
## 2 strategies run for 60 cycles.
## 
## Initial state counts:
## 
## PrimaryTHR = 1000L
## SuccessP = 0L
## RevisionTHR = 0L
## SuccessR = 0L
## Death = 0L
## 
## Counting method: 'end'.
## 
## Values:
## 
##           utility     cost
## standard 26132.68 721631.4
## np1      26420.23 668738.6
## 
## Efficiency frontier:
## 
## np1
## 
## Differences:
## 
##     Cost Diff. Effect Diff.      ICER     Ref.
## np1  -52.89272    0.2875505 -183.9424 standard

The variation of cost or effect can then be plotted.

plot(res_h, result = "effect", binwidth = 5)

plot(res_h, result = "cost", binwidth = 50)

plot(res_h, result = "icer", type = "difference",
     binwidth = 500)

plot(res_h, result = "effect", type = "difference",
     binwidth = .1)

plot(res_h, result = "cost", type = "difference",
     binwidth = 30)

The results from the combined model can be plotted similarly to the results from run_model().

plot(res_h, type = "counts")

Weighted results

Weights can be used in the analysis by including an optional column .weights in the new data to specify the respective weights of each strata in the target population.

tab_indiv_w
## # A tibble: 100 x 3
##      age   sex .weights
##    <dbl> <int>    <dbl>
##  1    56     0    0.723
##  2    60     0    0.622
##  3    62     0    0.980
##  4    54     1    0.934
##  5    61     1    0.135
##  6    69     0    0.198
##  7    51     1    0.321
##  8    50     0    0.435
##  9    73     1    0.216
## 10    54     0    0.399
## # … with 90 more rows
res_w <- update(res_mod, newdata = tab_indiv_w)
## Updating strategy 'standard'...
## Updating strategy 'np1'...
res_w
## An analysis re-run on 100 parameter sets.
## 
## * Weigths distribution:
## 
##    Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
## 0.01442 0.24555 0.44433 0.48456 0.72400 0.99424 
## 
## Total weight: 48.4558
## 
## * Values distribution:
## 
##                                   Min.      1st Qu.      Median        Mean
## standard - Cost          426.799283002  605.0062810 628.9121661 703.5302567
## standard - Effect          2.546855139   25.6294657  27.3769142  26.4760642
## standard - Cost Diff.                -            -           -           -
## standard - Effect Diff.              -            -           -           -
## standard - Icer                      -            -           -           -
## np1 - Cost               587.614226251  635.5509751 642.0508188 663.6040782
## np1 - Effect               2.551285038   25.8299343  27.7656911  26.7509535
## np1 - Cost Diff.        -164.881373261 -129.4829089  13.0247725 -39.9261785
## np1 - Effect Diff.         0.004429899    0.1948185   0.2294328   0.2748893
## np1 - Icer              -354.324313745 -333.0519971  58.3249840 271.4961764
##                             3rd Qu.          Max.
## standard - Cost         828.5434528   878.0433890
## standard - Effect        29.0749005    31.3071020
## standard - Cost Diff.             -             -
## standard - Effect Diff.           -             -
## standard - Icer                   -             -
## np1 - Cost              699.0605439   713.1620157
## np1 - Effect             29.5008365    31.5405654
## np1 - Cost Diff.         30.5446941   160.8149432
## np1 - Effect Diff.        0.3887769     0.4653403
## np1 - Icer              156.7853582 36302.1702601
## 
## * Combined result:
## 
## 2 strategies run for 60 cycles.
## 
## Initial state counts:
## 
## PrimaryTHR = 1000L
## SuccessP = 0L
## RevisionTHR = 0L
## SuccessR = 0L
## Death = 0L
## 
## Counting method: 'end'.
## 
## Values:
## 
##           utility     cost
## standard 26476.06 703530.3
## np1      26750.95 663604.1
## 
## Efficiency frontier:
## 
## np1
## 
## Differences:
## 
##     Cost Diff. Effect Diff.      ICER     Ref.
## np1  -39.92618    0.2748893 -145.2446 standard

Parallel computing

Updating can be significantly sped up by using parallel computing. This can be done in the following way:

Results may vary depending on the machine, but we found speed gains to be quite limited beyond 4 cores.