---
title: "BY-COVID - WP5 - Baseline Use Case: COVID-19 vaccine effectiveness assessment"
subtitle: "Matching cases to controls (1:1) and assessing covariate balance after matching"
format: 
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---

```{r, metadata, results='hide', message=FALSE, warning=FALSE, error=FALSE}

################
### Metadata ###
################

# DATE LAST MODIFIED:
# 23/01/2024

# METADATA: 
if(FALSE) {
  title      <- 'BY-COVID WP5.2 Baseline Use Case: SARS-CoV-2 vaccine effectiveness - analytical pipeline - imputation of missing values'
  author     <- list('Marjan Meurisse','Javier González-Galindo','Francisco Estupiñán-Romero','Santiago Royo-Sierra','Nina Van Goethem','Enrique Bernal-Delgado')
  version    <- '1.0.2'
  maintainer <- 'Marjan Meurisse'
  email      <- 'Marjan.Meurisse@sciensano.be'
  input      <- list('cohort_data, cohort_data_imputed and imputation_methods (database tables in BY-COVID-WP5-BaselineUseCase-VE.duckdb)')
  output     <- list('4_matching.html (report)','group_similarity, result_matching_alg, matched_data (database tables in BY-COVID-WP5-BaselineUseCase-VE.duckdb)')
}

```

```{r, general settings, results='hide', message=FALSE, warning=FALSE, error=FALSE}

## Description: Load packages
source("./0_global.R")

```

```{r, logging, results='hide', message=FALSE, warning=FALSE, error=FALSE}

## Description: Log of 4_matching.QMD
    
info(logger, paste0("
========================================================================================
",
"4_matching.QDM","
",
"========================================================================================
 "))

```

```{r, matching, message=FALSE, warning=FALSE, error=FALSE}

## Description: execute matching

info(logger_simple, "EXECUTING MATCHING...")

tryCatch(
  {
    source("./4_matching.R")
  },
  finally={
    dbDisconnect(con, shutdown=TRUE)
  })

```

```{r, load data, results='hide', message=FALSE, warning=FALSE, error=FALSE}

## Description: Load the data into memory

info(logger_simple, "LOADING THE DATA INTO MEMORY...")

tryCatch(
  {
    ## Description: get database connection
    con = dbConnect(duckdb::duckdb(), dbdir=auxiliary_database_path, read_only=FALSE)
    
    ## Non-matched data
    df_nonmatched <- dbGetQuery(con,paste0("SELECT
                            a.person_id,
                            a.fully_vaccinated_dt,
                            a.fully_vaccinated_bl,
                            a.confirmed_case_dt,
                            a.exitus_dt, ",
                            ifelse("sex_cd" %in% v_matching_incl,"COALESCE(a.sex_cd,b.sex_cd) as sex_cd, ",""),
                            ifelse("age_cd" %in% v_matching_incl,"COALESCE(a.age_cd,b.age_cd) as age_cd, ",""),
                            ifelse("residence_area_cd" %in% v_matching_incl,"COALESCE(a.residence_area_cd,b.residence_area_cd) as residence_area_cd, ",""),
                            ifelse("pregnancy_bl" %in% v_matching_incl,"COALESCE(a.pregnancy_bl,b.pregnancy_bl) as pregnancy_bl, ",""),
                            ifelse("essential_worker_bl" %in% v_matching_incl,"COALESCE(a.essential_worker_bl,b.essential_worker_bl) as essential_worker_bl, ",""),
                            ifelse("institutionalized_bl" %in% v_matching_incl,"COALESCE(a.institutionalized_bl,b.institutionalized_bl) as institutionalized_bl, ",""), 
                            ifelse("foreign_bl" %in% v_matching_incl,"COALESCE(a.foreign_bl,b.foreign_bl) as foreign_bl, ",""),
                            ifelse("socecon_lvl_cd" %in% v_matching_incl,"COALESCE(a.socecon_lvl_cd,b.socecon_lvl_cd) as socecon_lvl_cd, ",""),
                            ifelse("comorbidities_bl" %in% v_matching_incl,"a.comorbidities_bl, ",""),
                            ifelse("immunestatus_bl" %in% v_matching_incl,"a.immunestatus_bl, ",""),
                    "FROM cohort_view a 
                    LEFT JOIN cohort_data_imputed b on a.person_id = b.person_id"))
    
    ## Matched data
    df_matched <- dbGetQuery(con,
      paste0("SELECT * FROM matched_data a
      LEFT JOIN (
        SELECT c.person_id, ",
               ifelse("sex_cd" %in% v_matching_incl, "COALESCE(c.sex_cd,d.sex_cd) AS sex_cd, ",""),
               ifelse("age_cd" %in% v_matching_incl, "COALESCE(c.age_cd,d.age_cd) AS age_cd, ",""),
               ifelse("residence_area_cd" %in% v_matching_incl, "COALESCE(c.residence_area_cd,d.residence_area_cd) AS residence_area_cd, ",""),
               ifelse("pregnancy_bl" %in% v_matching_incl, "COALESCE(c.pregnancy_bl,d.pregnancy_bl) AS pregnancy_bl, ",""),
               ifelse("essential_worker_bl" %in% v_matching_incl, "COALESCE(c.essential_worker_bl,d.essential_worker_bl) AS essential_worker_bl, ",""),
               ifelse("institutionalized_bl" %in% v_matching_incl, "COALESCE(c.institutionalized_bl,d.institutionalized_bl) AS institutionalized_bl, ",""),
               ifelse("foreign_bl" %in% v_matching_incl, "COALESCE(c.foreign_bl,d.foreign_bl) AS foreign_bl, ",""),
               ifelse("socecon_lvl_cd" %in% v_matching_incl, "COALESCE(c.socecon_lvl_cd,d.socecon_lvl_cd) AS socecon_lvl_cd, ",""),
               ifelse("comorbidities_bl" %in% v_matching_incl, "c.comorbidities_bl, ",""),
               ifelse("immunestatus_bl" %in% v_matching_incl, "c.immunestatus_bl ",""),
        " FROM cohort_data c
        LEFT JOIN cohort_data_imputed d on c.person_id = d.person_id
      ) b on a.person_id = b.person_id"
      )) %>% select(-c("person_id"))
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  },
  finally={
    dbDisconnect(con, shutdown=TRUE)
  })

```

A sequence of nested (daily) trials are emulated with increasing time (t1, t2, ..., tn), iterating over the days in the enrollment period. At each eligible time during the enrollment period, the vaccination status of eligible individuals is assessed and every individual who has completed a primary vaccination schedule at that time (coded here as initiation of the intervention strategy when emulating a nested target trial) is matched to an individual who has not (yet) completed the primary vaccination schedule (coded here as the control strategy when emulating a nested target trial). Newly vaccinated individuals (completing a primary vaccination schedule) are eligible for inclusion in the study, even if they had previously been selected in the "no (or partial) vaccine group". Vaccinations have been administered in the context of national public health programs, without interference/manipulation of the research subjects.

We assess the covariate balance, which is the extent to which the distribution of covariates is similar across the intervention groups.

```{r, matchit prior, results='hide', message=FALSE, warning=FALSE, error=FALSE}

## Balance prior to matching

info(logger_simple, "ASSESSING BALANCE PRIOR TO MATCHING...")

tryCatch(
  {
    if("residence_area_cd" %in% v_matching_incl) {df_nonmatched$residence_area_cd <- as.factor(df_nonmatched$residence_area_cd)}
    if("sex_cd" %in% v_matching_incl) {df_nonmatched$sex_cd <- as.factor(df_nonmatched$sex_cd)}
    if("age_cd" %in% v_matching_incl) {df_nonmatched$age_cd <- as.factor(df_nonmatched$age_cd)}
    if("socecon_lvl_cd" %in% v_matching_incl) {df_nonmatched$socecon_lvl_cd <- as.factor(df_nonmatched$socecon_lvl_cd)}
    m.out0 <- matchit(as.formula(paste0("fully_vaccinated_bl ~ ", paste(v_matching_incl, sep="' '", collapse=" + "))), 
                      data = df_nonmatched,
                     method = NULL, distance = "glm")
    rm(df_nonmatched)
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })

```

```{r, matchit after, results='hide', message=FALSE, warning=FALSE, error=FALSE}

## Balance after matching

info(logger_simple, "ASSESSING BALANCE AFTER MATCHING...")

tryCatch(
  {
    if("residence_area_cd" %in% v_matching_incl) {df_matched$residence_area_cd <- as.factor(df_matched$residence_area_cd)}
    if("sex_cd" %in% v_matching_incl) {df_matched$sex_cd <- as.factor(df_matched$sex_cd)}
    if("age_cd" %in% v_matching_incl) {df_matched$age_cd <- as.factor(df_matched$age_cd)}
    if("socecon_lvl_cd" %in% v_matching_incl) {df_matched$socecon_lvl_cd <- as.factor(df_matched$socecon_lvl_cd)}
    m.out1 <- matchit(as.formula(paste0("fully_vaccinated_bl ~ ", paste(v_matching_incl, sep="' '", collapse=" + "))), 
                      data = df_matched,
                     method = NULL, distance = "glm")
    rm(df_matched)
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })

```

## Standardized Mean Differences {.tabset}

The Standardized Mean Difference (SMD) represents a standardized difference in mean between contrasted intervention groups for each covariate.

::: panel-tabset
##### Prior to matching

```{r, SMD prior matching, message=FALSE, warning=FALSE, error=FALSE}

## Standardized mean difference prior to matching

info(logger_simple, "ASSESSING STANDARDIZED MEAN DIFFERENCE PRIOR TO MATCHING...")

tryCatch(
  {
    smd_prior <- as.data.frame(summary(m.out0)$sum.all) %>% rename(`Means intervention group`=`Means Treated`,`Means control group`=`Means Control`, Std_Mean_Diff=`Std. Mean Diff.`)
    smd_prior <- cbind("Covariate" = rownames(smd_prior), smd_prior)
    formattable(
      smd_prior[,c("Means intervention group","Means control group","Std_Mean_Diff")],
      align = c("l","c","c","c"),
      list(
        Std_Mean_Diff = formatter("Std_Mean_Diff",
          style = ~style(display = "block", 
          padding = "0 4px", 
          `border-radius` = "4px", 
          `background-color` = case_when(
               Std_Mean_Diff > 0.01 ~"#F4A460"
        )))) 
      ) %>%  rename("Standardized mean difference" = Std_Mean_Diff)
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })
    
```

```{r, SMD prior matching plot, results='hide', message=FALSE, warning=FALSE, error=FALSE}
 
## Standardized mean difference plot prior to matching

info(logger_simple, "PLOTTING STANDARDIZED MEAN DIFFERENCE PRIOR TO MATCHING...")

tryCatch(
  {
    pl_prior <- ggplot(data = smd_prior %>% rename(`Std. Mean Diff.`=Std_Mean_Diff), mapping = aes(`Std. Mean Diff.`,Covariate)) +
      geom_point() +
      geom_vline(xintercept = 0.05, linetype="dashed", color = "#868181") +
      geom_vline(xintercept = -0.05, linetype="dashed", color = "#868181") +
      theme_minimal() +
      theme(axis.title.y = element_blank())
    ply_prior <- ggplotly(pl_prior)
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })

```

```{r, SMD prior matching plot 2, message=FALSE, warning=FALSE, error=FALSE}

## Balance prior to matching

tryCatch(
  {
    ply_prior
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })

```

##### After matching

```{r, SMD after matching, message=FALSE, warning=FALSE, error=FALSE}

## Standardized mean difference after matching

info(logger_simple, "ASSESSING STANDARDIZED MEAN DIFFERENCE AFTER MATCHING...")

tryCatch(
  {
    smd_after <- as.data.frame(summary(m.out1)$sum.all) %>% rename(`Means intervention group`=`Means Treated`,`Means control group`=`Means Control`,Std_Mean_Diff=`Std. Mean Diff.`)
    smd_after <- cbind("Covariate" = rownames(smd_after), smd_after)
    formattable(
      smd_after[,c("Means intervention group","Means control group","Std_Mean_Diff")],
      align = c("l","c","c","c"),
      list(
        Std_Mean_Diff = formatter("Std_Mean_Diff",
          style = ~style(display = "block", 
          padding = "0 4px", 
          `border-radius` = "4px", 
          `background-color` = case_when(
               Std_Mean_Diff > 0.01 ~"#F4A460"
        )))) 
      ) %>%  rename("Standardized mean difference" = Std_Mean_Diff)
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })

```

```{r, SMD after matching plot, results='hide', message=FALSE, warning=FALSE, error=FALSE}
 
## Standardized mean difference plot after matching

info(logger_simple, "PLOTTING STANDARDIZED MEAN DIFFERENCE AFTER MATCHING...")

tryCatch(
  {
    pl_after <- ggplot(data = smd_after %>% rename(`Std. Mean Diff.`=Std_Mean_Diff), mapping = aes(`Std. Mean Diff.`,Covariate)) +
      geom_point() +
      geom_vline(xintercept = 0.05, linetype="dashed", color = "#868181") +
      geom_vline(xintercept = -0.05, linetype="dashed", color = "#868181") +
      theme_minimal() +
      theme(axis.title.y = element_blank()) 
    ply_after <- ggplotly(pl_after)
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })

```

```{r, SMD after matching plot 2, message=FALSE, warning=FALSE, error=FALSE}

## Standardized mean difference plot after matching

tryCatch(
  {
    ply_after
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })

```
:::

## Propensity score distribution {.tabset}

::: panel-tabset
##### Before matching

```{r, plot ps before, message=FALSE, warning=FALSE, error=FALSE}

## Propensity score distribution prior to matching

info(logger_simple, "ASSISSING PROPENSITY SCORE DISTRIBUTION PRIOR TO MATCHING...")

tryCatch(
  {
    pl_ps_prior <- ggplot(data.frame(ps=m.out0$distance,Intervention=as.factor(ifelse(m.out0$treat==0,"No","Yes"))), 
                          aes(x = ps, group=Intervention, colour=Intervention,fill=Intervention)) +
                  geom_density(alpha = 0.4) +
                  theme_minimal() +
                  xlab("Propensity score") +
                  theme(axis.title.y=element_blank())
    ply <- ggplotly(pl_ps_prior)
    ply$x$data[[1]]$text <- paste0("Density: ", round(as.numeric(gsub('.*density: ','',gsub("<br.*$","",ply$x$data[[1]]$text))),3), "<br />",
                                   "Propensity score: ", round(ply$x$data[[1]]$x,3), "<br />",
                                   ifelse(ply$x$data[[1]]$legendgroup=="Yes","Yes","No"))
    ply$x$data[[2]]$text <- paste0("Density: ", round(as.numeric(gsub('.*density: ','',gsub("<br.*$","",ply$x$data[[2]]$text))),3), "<br />",
                                   "Propensity score: ", round(ply$x$data[[2]]$x,3), "<br />",
                                   ifelse(ply$x$data[[2]]$legendgroup=="Yes","Yes","No"))
    ply
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })  

```

##### After matching

```{r, plot ps after, message=FALSE, warning=FALSE, error=FALSE}

## Propensity score distribution after matching

info(logger_simple, "ASSISSING PROPENSITY SCORE DISTRIBUTION AFTER MATCHING...
     ")

tryCatch(
  {
    pl_ps_after <- ggplot(data.frame(ps=m.out1$distance,Intervention=as.factor(ifelse(m.out1$treat==0,"No","Yes"))), 
                          aes(x = ps, group=Intervention, colour=Intervention,fill=Intervention)) +
                  geom_density(alpha = 0.4) +
                  theme_minimal() +
                  xlab("Propensity score") +
                  theme(axis.title.y=element_blank())
    ply <- ggplotly(pl_ps_after)
    ply$x$data[[1]]$text <- paste0("Density: ", round(as.numeric(gsub('.*density: ','',gsub("<br.*$","",ply$x$data[[1]]$text))),3), "<br />",
                                   "Propensity score: ", round(ply$x$data[[1]]$x,3), "<br />",
                                   "Intervention: ",ifelse(ply$x$data[[1]]$legendgroup=="Yes","Yes","No"))
    ply$x$data[[2]]$text <- paste0("Density: ", round(as.numeric(gsub('.*density: ','',gsub("<br.*$","",ply$x$data[[2]]$text))),3), "<br />",
                                   "Propensity score: ", round(ply$x$data[[2]]$x,3), "<br />",
                                   "Intervention: ",ifelse(ply$x$data[[2]]$legendgroup=="Yes","Yes","No"))
    ply
  },
  error=function(cond) {
    ## Log info
    warn(logger, paste0("MY ERROR: 
                        ", cond))
    return(stop(cond))
  })
    
```
:::
