TABLE 1.
Estimates of the First and Second Type of Estimand for the Time Points 7, 14, and 28 Days Since Randomization Using the Constructed Data Example (n = 200)
| Estimand | Treatment (n = 100) | Placebo (n = 100) | Difference (95% CI) | Treatment (n = 100) | Placebo (n = 100) | Difference (95% CI) | Treatment (n = 100) | Placebo (n = 100) | Difference (95% CI) |
|---|---|---|---|---|---|---|---|---|---|
| Probabilities (%) | At 7 d | At 14 d | At 28 d | ||||||
| Discharged alive | 31 | 16 | 15 (4–26) | 44 | 34 | 10 (–3 to 23) | 60 | 56 | 4 (–9 to 17) |
| Mortality | 5 | 9 | –4 (–11 to 3) | 15 | 15 | 0 (–1 to 10) | 19 | 23 | –4 (–15 to 7) |
| Hospitalized without MV | 61 | 72 | –11 (–23 to –2) | 36 | 47 | –11 (–24 to 2.4) | 16 | 20 | –4 (–14 to 6) |
| Hospitalized with MV | 3 | 3 | 0 (–4 to 4) | 5 | 4 | 1 (–4 to 6) | 5 | 1 | 4 (–0.03 to 8) |
| Mean time spent | At 7 d | At 14 d | At 28 d | ||||||
| Alive without MV (hospitalized or discharged alive) | 6.7 | 6.5 | 0.2 (–1 to 1) | 12.7 | 12.4 | 0.3 (–1.5 to 2) | 23.6 | 23.4 | 0.2 (–3 to 4) |
| Alive with MV | 0.2 | 0.2 | 0.0 (–0.2 to 0.2) | 0.4 | 0.4 | 0 (–0.5 to 0.5) | 1.0 | 0.8 | 0.2 (–0.5 to 1) |
| Hospitalized | 5.8 | 6.2 | –0.4 (–1 to 0.3) | 9.4 | 10.4 | –1.0 (–2.5 to 0.5) | 13.0 | 15.3 | –2.3 (–5 to 1) |
MV = mechanical ventilation.
The colors indicate how the estimates relate to the stacked probability plot. The probabilities can be read from the plot as distance between the curves. The mean time spent in each state can be read from the plot as the colored area between the curves. The mean time spent hospitalized is the sum of the time spent with and without ventilation in the hospital. The durations are restricted to the time points of interest; therefore, they are to be considered as the lower limits of the total durations spent in each state. If the multistate model is used for the primary analysis, the 95% CIs of the differences can be interpreted as treatment effects. If the primary analysis is based on a different endpoint, we do not recommend to estimate CIs and p values, as the confidence level may not be valid due to multiple testing.