. 2023 Feb 14;192(6):987–994. doi: 10.1093/aje/kwad036

Table 4.

Understanding What Treatment Effects Represent Based on Reported Statistical Methods Versus Estimands in a Trial of Baricitinib for Atopic Dermatitis^a

Statistical Methods	Estimand
“The analysis population comprised all randomised patients, regardless of whether they received the correct treatment” (3, p. 1545). “Mean change from baseline for continuous measures (PROMIS^b and WPAI-AD^c) was evaluated using a restricted maximum likelihood-based mixed model repeated measures (MMRM), where the model includes treatment, region, baseline disease severity [validated Investigator Global Assessment for AD (vIGA-AD)^d], visit and treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects” (3, p. 1546).	The treatment effect is the difference between mean values in the WPAI:AD change from baseline score (at 16 weeks) for baricitinib 4 mg or 2 mg versus placebo daily, plus topical corticosteroids for adults with atopic dermatitis (meeting the trial eligibility criteria), regardless of whether participants received the correct treatment, in the hypothetical scenario where treatment discontinuation did not occur regardless of side effects or other adverse effects and rescue therapy was not provided, even if medically indicated.
“Data collected after first rescue therapy or permanent study drug discontinuation were considered missing… No explicit imputations were conducted for continuous measures; MMRM analysis was performed to mitigate the impact of missing data because it yields valid inferences assuming that missing observations are missing-at-random” (3, p. 1546).

Statistical Methods

Estimand

“The analysis population comprised all randomised patients, regardless of whether they received the correct treatment” (3, p. 1545). “Mean change from baseline for continuous measures (PROMIS^b and WPAI-AD^c) was evaluated using a restricted maximum likelihood-based mixed model repeated measures (MMRM), where the model includes treatment, region, baseline disease severity [validated Investigator Global Assessment for AD (vIGA-AD)^d], visit and treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects” (3, p. 1546).

The treatment effect is the difference between mean values in the WPAI:AD change from baseline score (at 16 weeks) for baricitinib 4 mg or 2 mg versus placebo daily, plus topical corticosteroids for adults with atopic dermatitis (meeting the trial eligibility criteria), regardless of whether participants received the correct treatment, in the hypothetical scenario where treatment discontinuation did not occur regardless of side effects or other adverse effects and rescue therapy was not provided, even if medically indicated.

“Data collected after first rescue therapy or permanent study drug discontinuation were considered missing… No explicit imputations were conducted for continuous measures; MMRM analysis was performed to mitigate the impact of missing data because it yields valid inferences assuming that missing observations are missing-at-random” (3, p. 1546).

Abbreviations: AD, atopic dermatitis; MMRM, mixed-model repeated measures; PROMIS, Patient-Reported Outcomes Measurement Information System; vIGA-AD, Validated Investigator Global Assessment Scale for Atopic Dermatitis; WPAI:AD, Work Productivity and Activity Impairment Questionnaire: Atopic Dermatitis.

^a Based on the study by Wollenberg et al. (3).

^b PROMIS Health Organization, River Forest, Illinois.

^c Created by Reilly et al. (41).

^d Eli Lily and Company, Indianapolis, Indiana.