. Author manuscript; available in PMC: 2022 Jun 25.

Published in final edited form as: Clin Trials. 2022 Mar 8;19(3):285–291. doi: 10.1177/17407745221080463

Table 2.

Estimand-to-Analysis Table Example for a Safety Objective

ESTIMAND	ANALYSIS
Objective: To assess the safety of ARVTRT once daily for 24 weeks.
Estimand: Probability of at least one severe or life-threatening adverse event occurring up to 24 weeks after initiation of ARVTRT in a pediatric population with controlled HIV-1
Treatment: ARVTRT # mg once daily for 24 weeks
Target population	Analysis set
Individuals aged 13 – 18 years on combination ART regimen with controlled HIV-1 (HIV-1 RNA < 50 copies/ml for at least 6 months) who initiate ARVTRT as a replacement for one of the drugs.	All participants who meet trial eligibility criteria and initiate treatment.
Variable	Outcome measure
Occurrence of at least one severe or life-threatening adverse event up to 24 weeks after treatment initiation	Grade ≥3 adverse event (graded according to the NIAID DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events²⁰) occurring after initiation of treatment and up to and including Week 24 study visit, per protocol-defined visit window.
Handling of intercurrent events	Handling of missing data
Death is the most serious adverse event and is included in the variable (Composite Variable Strategy). Premature treatment discontinuation for any reason, including pregnancy: Events through 24 weeks used to determine the variable irrespective of ARVTRT discontinuation for any reason (Treatment Policy Strategy).	For participants discontinuing study prior to Week 24, assume no additional adverse events occur. Sensitivity analysis: For participants discontinuing study prior to Week 24, censor follow-up at the last study visit.
Population-level summary measure	Analysis approach
Proportion of individuals with at least one adverse event as specified in the variable	Proportion calculated with a two-sided 95% confidence interval (CI) using Clopper-Pearson exact method for binomial data. Sensitivity analysis: Proportion calculated using the Kaplan-Meier method with Greenwood’s formula for the variance to calculate two-sided 95% CI.