There were 232 subjects randomized to the maintenance group cohort, and 63 still at risk of relapse after 1 year of follow-up. In other words, 27% of this cohort was still being followed in the study at the end of the study period. However, the corresponding Kaplan- Meier curve estimate of the percentage of subjects in the cohort who had not relapsed as of one-year after randomization is 61%. How could this have happened?

1. There was very little censoring, if any, prior to one-year among the observations in the maintenance group.

2. The researchers deleted all of the censored observations in the maintenance group prior to estimating the given Kaplan-Meier curve.

3. Some of the observations in the maintenance group were censored before one- year (lost to follow-up)

4. The Kaplan-Meier curve estimate at one-year is the risk of relapse among only those still at risk of relapse one-year after randomization.

The p-value given by the log-rank test comparing the two survival curves is 0.001. Assuming a rejection level (alpha level) of 0.05, what conclusion is consistent with this

result?

1. The observed differences in Kaplan-Meier curves between the two groups are relatively likely if there is no population-level difference in the time-to-event curves for the maintenance and discontinuation groups

2. The observed differences in Kaplan-Meier curves between the two groups are relatively unlikely if there is no population-level difference in the time-to-event curves for the maintenance and discontinuation groups

3. The observed differences in Kaplan-Meier curves between the two groups are relatively likely if there is a population-level difference in the time-to-event curves for the maintenance and discontinuation groups

4. The observed differences in Kaplan-Meier curves between the two groups are relatively unlikely if there is a population-level difference in the time-to-event curves for the maintenance and discontinuation groups

The following information is referenced in questions 13 - 17. A 2021 article in The New England Journal of Medicine details the results of a randomized clinical trial designed to the effects of maintaining or discontinuing antidepressant therapy for persons being treated with this medication(s). As per the authors: "Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting." "We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. The following Kaplan-Meier curves show the percentage of subjects in each group remaining relapse free beyond the corresponding time on the horizontal axis. The incidence rate ratio (and 95% confidence interval) of relapse in the one-year follow-up for the discontinuation group compared to the maintenance group is 2.06 (1.56 -2.70). After one-year of follow-up, an estimated 61% of the maintenance group had not relapsed, as compared to an estimated 44% who had not yet relapsed in the discontinuation group. 1.00 0.75 Maintenance Probability of Freedom from Relapse 0.50- Discontinuation 0.25 Hazard ratio, 2.06 (95% CI, 1.56-2.70) P