Selection bias, death, and dying

Selection bias

Selection bias is used to refer to different concepts by different researchers (see this article by Haneuse or this one by Hernán et al for really nice discussions of these issues). The terminology doesn’t matter as much as understanding the underlying data generating processes that distinguish the different ideas.

The key issue is to understand what is being selected. In one case, the exposure or intervention is the focus. And in the second case, it is how the patients or subjects are selected into the study more generally that induces the bias. The first selection process is typically referred to by epidemiologists as confounding bias (though it is also called treatment-selection bias), while the second is actually selection bias.

When I’ve written about these issues before (for example, see here), I’ve described how DAGs can be useful to illuminate the potential biases. Below, I have drawn a diagram to represent a simple case of selection bias. Say we are interested in measuring the causal relationship between income and blood pressure in some population in which the two are actually not causally related. If people with higher income are more likely to visit a doctor, and if people with higher blood pressure are also more likely to visit a doctor, the underlying causal relationship might be well represented by the DAG on the left in the figure below.

Let’s say we recruit participants for our study right outside of a medical facility. Choosing this location (as opposed to, say, a shopping mall where the causal model on the left would not be relevant), we are inducing a relationship between income and blood pressure. This can be seen in the DAG on the right, where we have effectively “controlled” for medical facility access in our selection process. The induced statistical relationship can be described in this way: if someone is at the medical center and they have relatively low income, they are more likely to have relatively high blood pressure. Conversely, if someone is there and they have relatively low blood pressure, they are more likely to have relatively high income. Based on this logic, we would expect to see a negative relationship between income and blood pressure in our study sample drawn from patients visiting a medical facility.

To explore by simulation, we can generate a large population of individuals with uncorrelated income and blood pressure. Selection will be a function of both:

n = 5000
set.seed(748347)

income <- rnorm(n); 
bp <- rnorm(n)

logitSelect <- -2 + 2*income + 2*bp
pSelect <- 1/(1+exp(-logitSelect))
select <- rbinom(n, 1, pSelect)

dPop <- data.table(income, bp, select)
dSample <- dPop[select == 1]

The plot on the left below is the overall population of 5000; there is no obvious relationship between the income and blood pressure. The group that was recruited at the medical facility and enrolled in the study (a subset of the original population) is shown in purple in the plot on the right. In this subset, there does indeed appear to be a relationship between the two characteristics. An estimate of the association, which we know is zero, based on the sample would be biased; that bias is due to how we selected participants into the study.

Hospitalization before death

In the next simulation, let’s consider a somewhat more complex process, though with the same underlying structure and similar bias as the simpler case above. The next DAG (below) shows three different time periods. In this case there is an indicator of homecare by a nurse \(N_1\), \(N_2\), and \(N_3\). (In this particular example, an individual has home nursing care in all three periods or they don’t have any home nursing care in any period. This is not a requirement.) In each period, each patient has an underlying time-dependent health status, ranging from \(1\) (healthiest) to \(4\) (sickest). In this simulated study, the underlying health status \(U_1\), \(U_2\), and \(U_3\) are considered latent (i.e. unmeasured). The progression of health status is governed by a Markov process that is independent of any kind of treatment. (See here and here for a more detailed description of how this is done using simstudy.)

The probability of hospitalization is a solely a function of the underlying health status, and nothing else. (I could make hospitalization a function of palliative care as well, but this just simplifies matters. In both cases the estimates will be biased - you can try for yourself.)

Death is a function of underlying health status and palliative care. While it does not seem to be the case in practice, I am assuming that less aggressive care results in shorter survival times. And the sicker the patient is in a particular period, the greater risk of dying in that period. (There should be lines between death in various periods and all subsequent measures, but I have eliminated them for clarity sake.)

The code to generate the data starts with the definitions: first, I define an initial health state \(S_0\) that can range from 1 to 3 and the transition matrix \(P\) for the Markov process. Next, I define the hospitalization and death outcomes:

bDef <- defData(varname = "S0", formula = "0.4;0.4;0.2",
                     dist = "categorical")

P <- t(matrix(c( 0.7, 0.2, 0.1, 0.0,
                 0.0, 0.4, 0.4, 0.2,
                 0.0, 0.0, 0.6, 0.4,
                 0.0, 0.0, 0.0, 1.0),
              nrow = 4))

pDef <- defDataAdd(varname = "hospital", formula = "-2 + u",
                   dist = "binary", link = "logit")
pDef <- defDataAdd(pDef, varname = "death", 
                   formula = "-2 + u + homenurse * 1.5",
                   dist = "binary", link = "logit")

The data generation process randomizes individuals to nursing home care (or care as usual) in the first period, and creates all of the health status measures and outcomes. The last step removes any data for an individual that was generated after they died. (The function trimData is new and only available in simstudy 0.1.15, which is available on CRAN - as of 10/21/2019)

set.seed(272872)

dd <- genData(10000, bDef)
dd <- trtAssign(dd, grpName = "homenurse")

dp <- addMarkov(dd, transMat = P, 
                chainLen = 4, id = "id", 
                pername = "seq", start0lab = "S0",
                varname = "u")

dp <- addColumns(pDef, dp)
dp <- trimData(dp, seqvar = "seq", eventvar = "death")

d1 <- dp[seq == 1]

d1[, mean(death)]

## [1] 0.6109

fit1 <- glm(hospital ~ homenurse, data=d1[death==1], 
            family = "binomial")
fit2 <- glm(hospital ~ homenurse + u, data=d1[death==1], 
            family = "binomial")
fit3 <- glm(hospital ~ homenurse, data=d1, 
            family = "binomial")

library(stargazer)

stargazer(fit1, fit2, fit3, type = "text",
          column.labels = c("died", "died - adjusted", "all"), 
          omit.stat = "all", omit.table.layout = "-asn")

## 
## =============================================
##                   Dependent variable:        
##           -----------------------------------
##                        hospital              
##             died    died - adjusted    all   
##              (1)          (2)          (3)   
## homenurse -0.222***     -0.061       -0.049  
##            (0.053)      (0.057)      (0.040) 
##                                              
## u                      1.017***              
##                         (0.039)              
##                                              
## Constant   0.108**     -2.005***    -0.149***
##            (0.042)      (0.092)      (0.028) 
##                                              
## =============================================

dDied <- dp[death == 1]
nrow(dDied)/nrow(d1)

## [1] 0.9658

fit4 <- glm(hospital ~ homenurse, data=dDied, family = "binomial")
fit5 <- glm(hospital ~ homenurse + u, data=dDied, family = "binomial")

stargazer(fit4, fit5, type = "text",
          omit.stat = "all", omit.table.layout = "-asn")

## 
## ==============================
##           Dependent variable: 
##           --------------------
##                 hospital      
##              (1)        (2)   
## homenurse -0.383***   -0.048  
##            (0.041)    (0.045) 
##                               
## u                    1.020*** 
##                       (0.028) 
##                               
## Constant   0.296***  -2.028***
##            (0.030)    (0.070) 
##                               
## ==============================