Greek gods: observed data

Only one of the two counterfactual outcomes is known: the one corresponding to the treatment level actually received

## # A tibble: 20 x 5
##    greek          A Y_obs  Y_a0  Y_a1
##    <chr>      <dbl> <dbl> <dbl> <dbl>
##  1 Rheia          0     0     0    NA
##  2 Kronos         0     1     1    NA
##  3 Demeter        0     0     0    NA
##  4 Hades          0     0     0    NA
##  5 Hestia         1     0    NA     0
##  6 Poseidon       1     0    NA     0
##  7 Hera           1     0    NA     0
##  8 Zeus           1     1    NA     1
##  9 Artemis        0     1     1    NA
## 10 Apollo         0     1     1    NA
## 11 Leto           0     0     0    NA
## 12 Ares           1     1    NA     1
## 13 Athena         1     1    NA     1
## 14 Hephaestus     1     1    NA     1
## 15 Aphrodite      1     1    NA     1
## 16 Cyclope        1     1    NA     1
## 17 Persephone     1     1    NA     1
## 18 Hermes         1     0    NA     0
## 19 Hebe           1     0    NA     0
## 20 Dionysus       1     0    NA     0

Randomized experiments

• Randomization ensures that the missing values on potential outcomes (PO) occurred by chance
• Effect measures can be consistently estimated

Hypothetical randomized experiment

• Flipping not a fair coin
  • if tails → assign treatment A=1/membership in a "white" group
  • otherwise → treatment A=0/membership in a "grey" group
  • probability of tossing tails is 0.6
• Associational risk ratio: Pr[Y=1|A=1] / Pr[Y=1|A=0] = 0.3/0.6 = 0.5
• Assumptions: no loss to follow-up, full adherence to the assigned treatment over the duration of the study, a single version of treatment, and double blind assignment
• Had we assigned the reverse treatment levels at random to this population, the association would be the same

Exchangeability

• When group membership is randomized, which particular group gets the treatment is irrelevant for the value of Pr[Y=1|A=1] (conditional probability of the outcome given the exposure level)

• The probability of the potential outcome Ya is the same under A=1 and A=0

  • Pr[Ya=1|A=1] = Pr[Ya=1|A=0], then
  • Pr[Ya=1|A=1] = Pr[Ya=1|A=0] = Pr[Ya=1] (in RCT)

• Ya⊥⊥ A for all a

• For the binary treatment variable scenario:

  • Ya⊥⊥ A=1
  • Ya⊥⊥ A=0

• The actual treatment level A does not predict PO Ya

  • Knowing the actual received treatment level does not tell you anything about the probability of the PO outcome in that group

In an ideal randomized experiment the association is causation

Under exchangeability:

• Pr[Ya=1] = Pr[Ya=1|A=a]- Pr[Ya=1=1] = Pr[Ya=1=1|A=1]
• Pr[Ya=0=1] = Pr[Ya=0=1|A=0]

Exchangeability is about PO outcome independence of actual treatment

• Exchangeability: Ya⊥⊥ A
• Conditional independence of two observed variables: Y⊥⊥ A

Hypothetical exchangeability assumption check

• In reality, exchangeability is untestable assumption
• To explore the concept of exchangeability, we go back to table 1.1, where we have hypothetical data on both potential outcomes under A=1 and under A=0

Greek gods, their actual treatment level and POs under actual and counterfactual levels of treatment

## # A tibble: 20 x 4
##    greek          A  Y_a0  Y_a1
##    <chr>      <dbl> <dbl> <dbl>
##  1 Rheia          0     0     1
##  2 Kronos         0     1     0
##  3 Demeter        0     0     0
##  4 Hades          0     0     0
##  5 Hestia         1     0     0
##  6 Poseidon       1     1     0
##  7 Hera           1     0     0
##  8 Zeus           1     0     1
##  9 Artemis        0     1     1
## 10 Apollo         0     1     0
## 11 Leto           0     0     1
## 12 Ares           1     1     1
## 13 Athena         1     1     1
## 14 Hephaestus     1     0     1
## 15 Aphrodite      1     0     1
## 16 Cyclope        1     0     1
## 17 Persephone     1     1     1
## 18 Hermes         1     1     0
## 19 Hebe           1     1     0
## 20 Dionysus       1     1     0

Explore exchangeability assumption among greek gods

• Ya=0
  • Had the treated and untreated gods were exchangeable, Ya⊥⊥ A and Pr[Ya=1|A=1] = Pr[Ya=1|A=0]
  • Is Ya⊥⊥ A for a=0 → Pr[Ya=0=1|A=0] = Pr[Ya=0=1|A=1]?

greek_gods_potential_outcomes %>% 
  group_by(A) %>% 
  count(Y_a0) %>% 
  mutate(
    denominator = sum(n),
    pr_of_Y_a0 = round(n / denominator, 2)
  ) %>% 
  filter(Y_a0 == 1)

## # A tibble: 2 x 5
## # Groups:   A [2]
##       A  Y_a0     n denominator pr_of_Y_a0
##   <dbl> <dbl> <int>       <int>      <dbl>
## 1     0     1     3           7       0.43
## 2     1     1     7          13       0.54

• Pr[Ya=0=1|A=0] = 0.43 and Pr[Ya=0=1|A=1] = 0.54, then
  • Pr[Ya=0=1|A=0] < Pr[Ya=0=1|A=1]
  • Under consistency: Pr[Ya=0=1|A=0] = Pr[Y=1|A=0]
  • In words, treated individuals had they been untreated (A=0) had a higher probability of dying
  • Exchangeability does not hold for the greek gods

Explore exchangeability assumption among greek gods

• Ya=1
  • Is Ya⊥⊥ A for a=1 → Pr[Ya=1=1|A=0] = Pr[Ya=1=1|A=1]?

greek_gods_potential_outcomes %>% 
  group_by(A) %>% 
  count(Y_a1) %>% 
  mutate(
    denominator = sum(n),
    pr_of_Y_a1 = round(n / denominator, 2)
  ) %>% 
  filter(Y_a1 == 1)

## # A tibble: 2 x 5
## # Groups:   A [2]
##       A  Y_a1     n denominator pr_of_Y_a1
##   <dbl> <dbl> <int>       <int>      <dbl>
## 1     0     1     3           7       0.43
## 2     1     1     7          13       0.54

• Pr[Ya=1=1|A=0] = 0.43 and Pr[Ya=1=1|A=1] = 0.54, then
  • Pr[Ya=1=1|A=0] < Pr[Ya=1=1|A=1]
  • Under consistency: Pr[Ya=1=1|A=1] = Pr[Y=1|A=1]
  • In words, actually treated individuals had a higher probability of dying than untreated had they been treated (A=1)
  • Exchangeability does not hold for the greek gods
  • Knowing the actual received treatment level tells us something about the probability of the PO → being treated means having a higher probability of potential death

Marginal randomization vs. conditional randomization

• Marginal randomization (RCT): unconditional assignment of treatment probability

• Introducing prognostic factor L

## # A tibble: 20 x 6
##    greek          L     A Y_obs  Y_a0  Y_a1
##    <chr>      <dbl> <dbl> <dbl> <dbl> <dbl>
##  1 Rheia          0     0     0     0    NA
##  2 Kronos         0     0     1     1    NA
##  3 Demeter        0     0     0     0    NA
##  4 Hades          0     0     0     0    NA
##  5 Hestia         0     1     0    NA     0
##  6 Poseidon       0     1     0    NA     0
##  7 Hera           0     1     0    NA     0
##  8 Zeus           0     1     1    NA     1
##  9 Artemis        1     0     1     1    NA
## 10 Apollo         1     0     1     1    NA
## 11 Leto           1     0     0     0    NA
## 12 Ares           1     1     1    NA     1
## 13 Athena         1     1     1    NA     1
## 14 Hephaestus     1     1     1    NA     1
## 15 Aphrodite      1     1     1    NA     1
## 16 Cyclope        1     1     1    NA     1
## 17 Persephone     1     1     1    NA     1
## 18 Hermes         1     1     0    NA     0
## 19 Hebe           1     1     0    NA     0
## 20 Dionysus       1     1     0    NA     0

Conditional randomization

• Assigning the probability of treatment based on the value of prognostic factor L
• Conditional exchangeability: Ya⊥⊥ A|L for all a and all l (A and L being variables and a and l being values of these variables)
  • Conditional exchangeability given L guarantees the exchangeability within the levels of L

Risk ratio in a conditionally randomized study (observational study)

• Associations risk ratio

# broke
greek_gods_condrand %>% 
  group_by(A) %>% 
  count(Y_obs) %>% 
  mutate(
    denominator = sum(n),
    risk = round(n/sum(n), digits = 2)
  ) %>% 
  filter(Y_obs == 1)

## # A tibble: 2 x 5
## # Groups:   A [2]
##       A Y_obs     n denominator  risk
##   <dbl> <dbl> <int>       <int> <dbl>
## 1     0     1     3           7  0.43
## 2     1     1     7          13  0.54

0.54/0.43

## [1] 1.255814

# woke
greek_gods_condrand %>% 
  glm(formula = Y_obs ~ A, family = binomial(link = "log")) %>% 
  broom::tidy(exponentiate = T) %>% 
  filter(term == "A") %>% 
  select(term, estimate)

## # A tibble: 1 x 2
##   term  estimate
##   <chr>    <dbl>
## 1 A         1.26

Risk ratio in a conditionally randomized study (e.g., observational study)

• L-stratum specific causal risk ratios

  1. Pr[Ya=1=1|L=1]Pr[Ya=0=1|L=1]

  2. Pr[Ya=1=1|L=0]Pr[Ya=0=1|L=0]

• Average causal effect in the entire population:

  • Pr[Ya=1=1]Pr[Ya=0=1]

Standardization

• Pr[Ya=1=1|L=1]Pr[Ya=0=1|L=1]

  • under conditional exchangeability = Pr[Ya=1=1|L=1,A=1]Pr[Ya=0=1|L=1,A=0]
  • under consistency = Pr[Y=1|L=1,A=1]Pr[Y=1|L=1,A=0]

• Same for the stratum L=0

  • Pr[Ya=1=1|L=0]Pr[Ya=0=1|L=0] = Pr[Y=1|L=0,A=1]Pr[Y=1|L=0,A=0]

Strata L=0

greek_gods_condrand %>% 
  filter(L == 0) %>% 
  group_by(A) %>% 
  count(Y_obs) %>% 
  mutate(
    denominator = sum(n),
    risk = round(n/sum(n), digits = 2)
  ) %>% 
  filter(Y_obs == 1)

## # A tibble: 2 x 5
## # Groups:   A [2]
##       A Y_obs     n denominator  risk
##   <dbl> <dbl> <int>       <int> <dbl>
## 1     0     1     1           4  0.25
## 2     1     1     1           4  0.25

Strata L=1

greek_gods_condrand %>% 
  filter(L == 1) %>% 
  group_by(A) %>% 
  count(Y_obs) %>% 
  mutate(
    denominator = sum(n),
    risk = round(n/sum(n), digits = 2)
  ) %>% 
  filter(Y_obs == 1)

## # A tibble: 2 x 5
## # Groups:   A [2]
##       A Y_obs     n denominator  risk
##   <dbl> <dbl> <int>       <int> <dbl>
## 1     0     1     2           3  0.67
## 2     1     1     6           9  0.67

Standardiazation

Average causal effect for the whole population:

• Weighted average of the effects in L=1 and L=0
• Weights are proportional to the size of L-strata

mean(greek_gods_condrand$L)

## [1] 0.6

Pr[Ya=1=1]Pr[Ya=0=1]

• = ΣlPr[Ya=1=1|L,A=1]∗Pr(L)ΣlPr[Ya=0=1|L,A=0]∗Pr(L) (under conditional exchangeability)
• = ΣlPr[Y=1|L,A=1]∗Pr(L)ΣlPr[Y=1|L,A=0]∗Pr(L) for all L=l (under consistency)
• = Pr[Y=1|L=0,A=1]∗Pr(L=0)+Pr[Y=1|L=1,A=1]∗Pr(L=1)Pr[Y=1|L=0,A=0]∗Pr(L=0)+Pr[Y=1|L=1,A=0]∗Pr(L=1)
• = 0.25∗0.4+0.67∗0.60.25∗0.4+0.67∗0.6
• = 0.5020.502
• = 1.0

Standardization formula: Pr(Ya=1)=ΣlPr(Y=1|A=a,L=l)∗Pr(L=l)

Inverse probability weighting

pr_a <- glm(data = greek_gods_condrand, formula = A~1, family = binomial("logit"))
pr_a_l <- glm(data = greek_gods_condrand, formula = A~L, family = binomial("logit"))
greek_gods_condrand %<>% mutate(
  p_a = predict(object = pr_a, type = "response"),
  p_a_l = predict(object = pr_a_l, type = "response"),
  # average treatment effect
  iptw = if_else(A==1, 1/p_a_l, 1/(1-p_a_l)), # unstabilized weights
  sw_iptw = if_else(A==1, p_a/p_a_l, (1-p_a)/(1-p_a_l)) # stabilized weights
)

greek_gods_condrand %>% 
  select(iptw, sw_iptw) %>% 
  skimr::skim()

Table: Data summary

Variable type: numeric

Figure 2.3

greek_gods_condrand %>% 
  distinct(A, Y_obs, L, iptw, sw_iptw)

## # A tibble: 8 x 5
##       L     A Y_obs  iptw sw_iptw
##   <dbl> <dbl> <dbl> <dbl>   <dbl>
## 1     0     0     0  2.00   0.7  
## 2     0     0     1  2.00   0.7  
## 3     0     1     0  2.     1.30 
## 4     0     1     1  2.     1.30 
## 5     1     0     1  4.00   1.40 
## 6     1     0     0  4.00   1.40 
## 7     1     1     1  1.33   0.867
## 8     1     1     0  1.33   0.867

glm(data = greek_gods_condrand, formula = Y_obs~A, family = binomial("log"), weights = iptw) %>% 
  broom::tidy(exponentiate = T) %>% 
  filter(term == "A") %>% 
  select(term, estimate)

## Warning in eval(family$initialize): non-integer #successes in a binomial glm!

## # A tibble: 1 x 2
##   term  estimate
##   <chr>    <dbl>
## 1 A         1.00

glm(data = greek_gods_condrand, formula = Y_obs~A, family = binomial("log"), weights = sw_iptw) %>% 
  broom::tidy(exponentiate = T) %>% 
  filter(term == "A") %>% 
  select(term, estimate)

## Warning in eval(family$initialize): non-integer #successes in a binomial glm!

## # A tibble: 1 x 2
##   term  estimate
##   <chr>    <dbl>
## 1 A         1.00

# crude 2x2 table
greek_gods_condrand  %>% 
  group_by(A) %>% 
  count(Y_obs) %>% 
  mutate(
    denominator = sum(n)
  ) %>% 
  filter(Y_obs == 1)

## # A tibble: 2 x 4
## # Groups:   A [2]
##       A Y_obs     n denominator
##   <dbl> <dbl> <int>       <int>
## 1     0     1     3           7
## 2     1     1     7          13

# unstabilized weights doubled the size of the population
greek_gods_condrand  %>% 
  group_by(A) %>% 
  count(Y_obs, wt = iptw) %>% 
  mutate(
    denominator = sum(n)
  ) %>%
  filter(Y_obs == 1)

## # A tibble: 2 x 4
## # Groups:   A [2]
##       A Y_obs     n denominator
##   <dbl> <dbl> <dbl>       <dbl>
## 1     0     1  10.0        20.0
## 2     1     1  10.         20.

# stabilized weights kept the original size of the population
greek_gods_condrand  %>% 
  group_by(A) %>% 
  count(Y_obs, wt = sw_iptw) %>% 
  mutate(
    denominator = sum(n)
  ) %>%
  filter(Y_obs == 1)

## # A tibble: 2 x 4
## # Groups:   A [2]
##       A Y_obs     n denominator
##   <dbl> <dbl> <dbl>       <dbl>
## 1     0     1  3.50        7.00
## 2     1     1  6.5        13.