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TFL Gallery / t-eff-adas-mmrm

EFT08 · Table

ADAS-Cog (11) - Repeated Measures Analysis of Change from Baseline to Week 24

The supportive repeated-measures analysis: a mixed model with an unstructured within-subject covariance, which handles a missed visit through the covariance rather than by carrying a value forward. Its fit reproduces the reference report's own PROC MIXED output to six significant figures.

Slug
t-eff-adas-mmrm
Regulatory ID
EFT08
Type
Table
E3 position
§14.2
Status
evidenced
Current iteration
v004
Datasets
adqsadas d6ee9a3, adsl 1f6fa03
Evidence
26/26 passing
Requirements
DSP-ALL-001 DSP-ALL-002 DSP-EFF-001 DSP-EFF-002 DSP-EFF-003 DSP-EFF-004 DSP-EFF-005 DSP-EFF-006 DSP-EFF-007 DSP-EFF-008 DSP-EFF-009 DSP-INTXT-001 DSP-INTXT-002 DSP-INTXT-003 STD-GATE-001 STD-GATE-002 STD-GATE-003 STD-GATE-004 STD-GATE-005 STD-MODEL-001 STD-MODEL-002 STD-MODEL-003 STD-MODEL-004 STD-MODEL-005 STD-SRC-001 STD-SRC-002
Used in
Study model
Efficacy Analysis Set EFFFL · grouped by TRTP
Specification
4 iterations
Environment
R 4.3.3 Darwin 23.6.0
Bound by
No text block binds it
Values
No value is sourced from it
Inputs
Function
Outputs
RTFFull displayae5945a

Generated by the same pipeline run that wrote the ARD and the HTML above, from the same rendered cells; the short hash is the manifest's record of the file.

t-eff-adas-mmrm · post_text variant · study CDISCPILOT01 · data cut-off 2015-02-17

ADAS-Cog (11) - Repeated Measures Analysis of Change from Baseline to Week 24
Study CDISCPILOT01 — Efficacy Analysis Set
Placebo (N=79) Xanomeline Low Dose (N=81) Xanomeline High Dose (N=74)
LS means (SE) [1] 1.6 (0.49) 1.5 (0.52) 1.1 (0.55)
Comparison of least-squares means
   p-value (Xanomeline - Placebo) [1][2] 0.954 0.555
      Difference of LS means (SE) -0.0 (0.70) -0.4 (0.72)
      95% CI (-1.4;1.3) (-1.8;1.0)
   p-value (Xanomeline High - Xanomeline Low) [1][2] 0.605
      Difference of LS means (SE) -0.4 (0.75)
      95% CI (-1.9;1.1)
Kenward-Roger was tried (qc/mmrm-kenward-roger.R, 2 September 2026, mmrm 0.3.15): the refit reproduces the reference REML criterion to every printed digit and moves one of the five cells — the lower confidence limit of high dose against placebo prints -1.9 as the report does — but not the other four, so the model-based fit is kept and the four are stated here.
[1] Mixed model for repeated measures of the change from baseline, fitted by restricted maximum likelihood with an unstructured within-subject covariance matrix. Fixed effects: treatment, site group, visit, treatment by visit, the baseline score, and the baseline score by visit.
[2] Pairwise comparison of least-squares means; p-values are not adjusted for multiple comparisons.
Observed cases only: 539 assessments from 234 subjects at Weeks 8, 16 and 24. The model accounts for a missing visit through the covariance structure, so no value is carried forward.
WHAT THE LEAST-SQUARES MEANS ESTIMATE: they are the treatment main effect — the model's prediction averaged over all three post-baseline visits and over the eleven site groups equally, with the baseline score held at its mean. They are not the Week-24 visit conditioned on, which the title might suggest and which is a different and less precise quantity (for placebo, 2.3 with a standard error of 0.69 rather than 1.6 with 0.49). This display reproduces what the reference report computed; the distinction is stated here because the number cannot state it itself.
MEASURED, NOT ASSUMED: the fit reproduces the reference report's own PROC MIXED output to six significant figures on all six unstructured covariance parameters, and its REML criterion of 3087.84303515 to ten. It uses the same 539 observations from the same 234 subjects. Two programs can agree on a rounded least-squares mean by accident; they cannot agree on that by accident, so the model is identified far more sharply than the rounded cells above can show.
DIFFERS FROM THE REFERENCE, DELIBERATELY: standard errors and degrees of freedom here are the model-based ones, on 517 residual degrees of freedom. The reference used Kenward-Roger degrees of freedom with Prasad-Rao-Jeske-Kackar-Harville standard errors, which inflate both by roughly one per cent to allow for the covariance parameters having been estimated rather than known. That adjustment is not implemented here. Of the twelve cells above, seven are identical to the reference and five differ at the last digit shown: the three p-values, each 0.001 lower (0.954, 0.555 and 0.605 against 0.955, 0.556 and 0.606); the high-dose least-squares mean standard error (0.55 against 0.56); and one confidence-interval bound (-1.8 against -1.9). Every point estimate agrees. The difference is measured and recorded in quality/data/efficacy-agreement.json.
Treatment columns are planned treatment (TRTP), which is how the CDISCPILOT01 reference report presents them.
CDISCPILOT01 states no data cut-off date. The date shown is the latest ADAS-Cog assessment date present in the vendored ADaM package.
Source: adqsadas (ADAS-Cog (11) total score, PARAMCD ACTOT) and adsl, from the CDISC pilot's own ADaM package (phuse-org/phuse-scripts, MIT). Supportive analysis as specified in the CDISCPILOT01 statistical analysis plan, section 10.1.1. Reference report display: Table 14-3.11. Data cut-off: 2015-02-17.
open.csr display t-eff-adas-mmrm (post_text variant); generated from the committed ARD.

Rendered from outputs/t-eff-adas-mmrm/v004/table.html.

Every iteration is kept: outputs/t-eff-adas-mmrm/vNNN/ holds the spec snapshot, the ARD, the rendered output, and a manifest recording who regenerated it, why, and from which commit.