ADAS-Cog (11) - Change from Baseline to Week 16 - LOCF

The same primary analysis read at Week 16 — the middle of the three scheduled reads.

Slug: t-eff-adas-wk16
Regulatory ID: EFT03
Type: Table
E3 position: §14.2
Status: evidenced
Current iteration: v002
Datasets: adqsadas d6ee9a3, adsl 70c7278
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: Clinical Study Report Table 14.2.5
Post-Text Display Package Table 14.2.5
Abbreviated Clinical Study Report (ICH E3) Table 14.2.5
Study model: Efficacy Analysis Set EFFFL · grouped by TRTP
Specification: 2 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

adsl254 rows · 70c7278
adqsadas12463 rows · d6ee9a3
analysis.yamlwhat to compute
display.yamlhow to show it
custom.Rthe display's own method
study modelEfficacy Analysis Set

Function

prepare_data()regenerate('t-eff-adas-wk16')
build_ard()one row per statistic
render_display()every variant
render_rtf()the same cells

Outputs

ard.jsonv002 · 95 rows · dd7d1cd
table.htmlthe rendered display
table.rtfsha256 74c3293
manifest.jsonwho, why, every hash

RTFFull display74c3293

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-wk16 · post_text variant · study CDISCPILOT01 · data cut-off 2015-02-17

	Placebo (N=79)	Xanomeline Low Dose (N=81)	Xanomeline High Dose (N=74)
ADAS-Cog (11) - Change from Baseline to Week 16 - LOCF
Study CDISCPILOT01 — Efficacy Analysis Set
Baseline
n	79	81	74
Mean (SD)	24.1 (12.19)	24.4 (12.92)	21.3 (11.74)
Median (Range)	21.0 (5;61)	21.0 (5;57)	18.0 (3;57)
Week 16
n	79	81	74
Mean (SD)	26.1 (14.16)	26.0 (13.05)	22.5 (12.33)
Median (Range)	23.0 (5;63)	25.0 (5;62)	20.0 (4;62)
Change from baseline
n	79	81	74
Mean (SD)	2.0 (5.89)	1.6 (4.10)	1.2 (4.33)
Median (Range)	2.0 (-17;23)	2.0 (-9;14)	1.0 (-11;13)
Statistical comparison of the change from baseline
p-value (dose response) [1][2]			0.412
p-value (Xanomeline - Placebo) [1][3]		0.724	0.392
Difference of LS means (SE)		-0.3 (0.77)	-0.7 (0.79)
95% CI		(-1.8;1.2)	(-2.2;0.9)
p-value (Xanomeline High - Xanomeline Low) [1][3]			0.606
Difference of LS means (SE)			-0.4 (0.78)
95% CI			(-1.9;1.1)
[1] Based on an analysis of covariance (ANCOVA) model with treatment and site group as factors and the baseline score as a covariate.
[2] Test for a non-zero coefficient for treatment (dose) as a continuous variable.
[3] Pairwise comparison with treatment as a categorical variable; p-values are not adjusted for multiple comparisons.
Missing post-baseline values are imputed by last observation carried forward, over assessments assigned to visit windows (CDISCPILOT01 statistical analysis plan, sections 8.1 and 8.2).
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). Analysis as specified in the CDISCPILOT01 statistical analysis plan, section 10.1.1. Reference report display: Table 14-3.05. Data cut-off: 2015-02-17.
open.csr display t-eff-adas-wk16 (post_text variant); generated from the committed ARD.

Rendered from outputs/t-eff-adas-wk16/v002/table.html.

analysis	group1	group1_level	group2	group2_level	variable	variable_level	context	stat_name	stat_label	warning	error	stat
population	TRTP	Placebo	—	—	USUBJID	—	population	N	N	—	—	79
population	TRTP	Xanomeline High Dose	—	—	USUBJID	—	population	N	N	—	—	74
population	TRTP	Xanomeline Low Dose	—	—	USUBJID	—	population	N	N	—	—	81
summary	TRTP	Placebo	—	—	BASE	—	continuous	N	N	—	—	79
summary	TRTP	Placebo	—	—	BASE	—	continuous	mean	Mean	—	—	24.121780881711
summary	TRTP	Placebo	—	—	BASE	—	continuous	sd	SD	—	—	12.1863695136042
summary	TRTP	Placebo	—	—	BASE	—	continuous	median	Median	—	—	21
summary	TRTP	Placebo	—	—	BASE	—	continuous	p25	Q1	—	—	15
summary	TRTP	Placebo	—	—	BASE	—	continuous	p75	Q3	—	—	31
summary	TRTP	Placebo	—	—	BASE	—	continuous	min	Min	—	—	5
summary	TRTP	Placebo	—	—	BASE	—	continuous	max	Max	—	—	61
summary	TRTP	Placebo	—	—	AVAL	—	continuous	N	N	—	—	79
summary	TRTP	Placebo	—	—	AVAL	—	continuous	mean	Mean	—	—	26.0839240506329
summary	TRTP	Placebo	—	—	AVAL	—	continuous	sd	SD	—	—	14.1550253390723
summary	TRTP	Placebo	—	—	AVAL	—	continuous	median	Median	—	—	23
summary	TRTP	Placebo	—	—	AVAL	—	continuous	p25	Q1	—	—	16
summary	TRTP	Placebo	—	—	AVAL	—	continuous	p75	Q3	—	—	33
summary	TRTP	Placebo	—	—	AVAL	—	continuous	min	Min	—	—	5
summary	TRTP	Placebo	—	—	AVAL	—	continuous	max	Max	—	—	63
summary	TRTP	Placebo	—	—	CHG	—	continuous	N	N	—	—	79
summary	TRTP	Placebo	—	—	CHG	—	continuous	mean	Mean	—	—	1.96214316892187
summary	TRTP	Placebo	—	—	CHG	—	continuous	sd	SD	—	—	5.89327999384544
summary	TRTP	Placebo	—	—	CHG	—	continuous	median	Median	—	—	2
summary	TRTP	Placebo	—	—	CHG	—	continuous	p25	Q1	—	—	-2
summary	TRTP	Placebo	—	—	CHG	—	continuous	p75	Q3	—	—	6
summary	TRTP	Placebo	—	—	CHG	—	continuous	min	Min	—	—	-17
summary	TRTP	Placebo	—	—	CHG	—	continuous	max	Max	—	—	23
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	N	N	—	—	74
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	mean	Mean	—	—	21.2972972972973
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	sd	SD	—	—	11.7365250390648
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	median	Median	—	—	18
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	p25	Q1	—	—	13
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	p75	Q3	—	—	27
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	min	Min	—	—	3
summary	TRTP	Xanomeline High Dose	—	—	BASE	—	continuous	max	Max	—	—	57
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	N	N	—	—	74
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	mean	Mean	—	—	22.4902143522833
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	sd	SD	—	—	12.3282523185932
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	median	Median	—	—	20
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	p25	Q1	—	—	13
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	p75	Q3	—	—	31
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	min	Min	—	—	4
summary	TRTP	Xanomeline High Dose	—	—	AVAL	—	continuous	max	Max	—	—	61.551724137931
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	N	N	—	—	74
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	mean	Mean	—	—	1.19291705498602
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	sd	SD	—	—	4.33045631759373
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	median	Median	—	—	1
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	p25	Q1	—	—	-1
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	p75	Q3	—	—	3
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	min	Min	—	—	-11
summary	TRTP	Xanomeline High Dose	—	—	CHG	—	continuous	max	Max	—	—	13
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	N	N	—	—	81
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	mean	Mean	—	—	24.4074074074074
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	sd	SD	—	—	12.9224478515241
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	median	Median	—	—	21
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	p25	Q1	—	—	15
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	p75	Q3	—	—	30
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	min	Min	—	—	5
summary	TRTP	Xanomeline Low Dose	—	—	BASE	—	continuous	max	Max	—	—	56.7241379310345
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	N	N	—	—	81
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	mean	Mean	—	—	26.017454235845
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	sd	SD	—	—	13.0469450133446
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	median	Median	—	—	25
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	p25	Q1	—	—	17
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	p75	Q3	—	—	32
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	min	Min	—	—	5
summary	TRTP	Xanomeline Low Dose	—	—	AVAL	—	continuous	max	Max	—	—	62
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	N	N	—	—	81
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	mean	Mean	—	—	1.61004682843763
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	sd	SD	—	—	4.10011688145552
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	median	Median	—	—	2
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	p25	Q1	—	—	-1
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	p75	Q3	—	—	4
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	min	Min	—	—	-9
summary	TRTP	Xanomeline Low Dose	—	—	CHG	—	continuous	max	Max	—	—	14
ancova	TRTP	Xanomeline High Dose	—	—	CHG	dose_response	ancova	pvalue	pvalue	—	—	0.411525392150486
ancova	TRTP	Xanomeline High Dose	—	—	CHG	dose_response	ancova	n_model	n_model	—	—	234
ancova	TRTP	Xanomeline Low Dose	—	—	CHG	xan_vs_placebo	ancova	estimate	estimate	—	—	-0.271559730434118
ancova	TRTP	Xanomeline Low Dose	—	—	CHG	xan_vs_placebo	ancova	se	se	—	—	0.766731510960597
ancova	TRTP	Xanomeline Low Dose	—	—	CHG	xan_vs_placebo	ancova	pvalue	pvalue	—	—	0.723544425248927
ancova	TRTP	Xanomeline Low Dose	—	—	CHG	xan_vs_placebo	ancova	lcl	lcl	—	—	-1.78263848009299
ancova	TRTP	Xanomeline Low Dose	—	—	CHG	xan_vs_placebo	ancova	ucl	ucl	—	—	1.23951901922475
ancova	TRTP	Xanomeline Low Dose	—	—	CHG	xan_vs_placebo	ancova	n_model	n_model	—	—	234
ancova	TRTP	Xanomeline High Dose	—	—	CHG	xan_vs_placebo	ancova	estimate	estimate	—	—	-0.676182860148953
ancova	TRTP	Xanomeline High Dose	—	—	CHG	xan_vs_placebo	ancova	se	se	—	—	0.787808167051367
ancova	TRTP	Xanomeline High Dose	—	—	CHG	xan_vs_placebo	ancova	pvalue	pvalue	—	—	0.391655988836574
ancova	TRTP	Xanomeline High Dose	—	—	CHG	xan_vs_placebo	ancova	lcl	lcl	—	—	-2.22879960150029
ancova	TRTP	Xanomeline High Dose	—	—	CHG	xan_vs_placebo	ancova	ucl	ucl	—	—	0.87643388120238
ancova	TRTP	Xanomeline High Dose	—	—	CHG	xan_vs_placebo	ancova	n_model	n_model	—	—	234
ancova	TRTP	Xanomeline High Dose	—	—	CHG	high_vs_low	ancova	estimate	estimate	—	—	-0.404623129714835
ancova	TRTP	Xanomeline High Dose	—	—	CHG	high_vs_low	ancova	se	se	—	—	0.783664979571014
ancova	TRTP	Xanomeline High Dose	—	—	CHG	high_vs_low	ancova	pvalue	pvalue	—	—	0.606148412711407
ancova	TRTP	Xanomeline High Dose	—	—	CHG	high_vs_low	ancova	lcl	lcl	—	—	-1.94907445400959
ancova	TRTP	Xanomeline High Dose	—	—	CHG	high_vs_low	ancova	ucl	ucl	—	—	1.13982819457992
ancova	TRTP	Xanomeline High Dose	—	—	CHG	high_vs_low	ancova	n_model	n_model	—	—	234

95 rows, one per computed statistic.

Schema: opencsr/ard/v1
Generated: 2026-09-02T15:23:23Z
Spec hash: sha256:304b61611c0d38a88607ebf107374d9b6e04b4aa9c5b324c222dbf7702766ab5
Display hash: sha256:6bbf55b2944d9534095e19a472253bb469d28ddc53b157c64c730eea73a03c9b
ARD file: outputs/t-eff-adas-wk16/v002/ard.json
ARD hash: sha256:dd7d1cd49f32843776209689cc9e83ed7388b258afcbb74eb0c969bdc66b1fbc

Source datasets

Dataset	Rows	Package	Hash
adsl	254	phuse-org/phuse-scripts:data/adam 398a6d33ced9359ffb58c46650a6d488811176b1	sha256:70c7278e83e571a7d4a94fd864c98bf8ca243c7c2cc9eec8b99a40fa7bc98e35
adqsadas	12463	phuse-org/phuse-scripts:data/adam 398a6d33ced9359ffb58c46650a6d488811176b1	sha256:d6ee9a321a2a9d338285cc702d750624eefd6da11b0da0ae260a4133a492215f

Environment

R 4.3.3 · Darwin 23.6.0 · cards 0.6.1 · cardx 0.2.5 · gtsummary 2.3.0 · gt 1.0.0 · dplyr 1.1.4 · pharmaverseadam 1.1.0 · jsonlite 2.0.0 · yaml 2.3.10 · digest 0.6.37

library/tfl/t-eff-adas-wk16/analysis.yaml

id: t-eff-adas-wk16
title: "ADAS-Cog (11) - Change from Baseline to Week 16 - LOCF"
regulatory_id: EFT03
type: table
dataset: adqsadas
analysis_set: efficacy
denominator: adsl
sources: phuse
group:
  - TRTP
total: false
analyses:
  - name: population
    method: continuous
    custom: population_n
    label: "Subjects in the analysis population"
    filter: "PARAMCD == 'ACTOT'"
  - name: summary
    method: continuous
    label: "ADAS-Cog (11) total score at baseline, at Week 16, and its change"
    variables: [BASE, AVAL, CHG]
    filter: "PARAMCD == 'ACTOT' & ANL01FL == 'Y' & AVISIT == 'Week 16'"
  - name: ancova
    method: continuous
    custom: ancova_change
    label: "ANCOVA of the change from baseline to Week 16"
    variables: [CHG]
    filter: "PARAMCD == 'ACTOT' & ANL01FL == 'Y' & AVISIT == 'Week 16'"
    response: CHG
    covariates: [BASE]
    factors: [SITEGR1]
    treatment: TRTP
    treatment_levels: ["Placebo", "Xanomeline Low Dose", "Xanomeline High Dose"]
    dose: TRTPN
    conf_level: 0.95
    contrasts:
      - { name: dose_response, type: dose, column: "Xanomeline High Dose" }
      - { name: xan_vs_placebo, type: pairwise, test: "Xanomeline Low Dose",
          reference: "Placebo", column: "Xanomeline Low Dose" }
      - { name: xan_vs_placebo, type: pairwise, test: "Xanomeline High Dose",
          reference: "Placebo", column: "Xanomeline High Dose" }
      - { name: high_vs_low, type: pairwise, test: "Xanomeline High Dose",
          reference: "Xanomeline Low Dose", column: "Xanomeline High Dose" }

library/tfl/t-eff-adas-wk16/display.yaml

id: t-eff-adas-wk16
title: "ADAS-Cog (11) - Change from Baseline to Week 16 - LOCF"
study: CDISCPILOT01
population_label: "Efficacy Analysis Set"
cutoff: "2015-02-17"
source: "Source: adqsadas (ADAS-Cog (11) total score, PARAMCD ACTOT) and adsl, from the CDISC pilot's own ADaM package (phuse-org/phuse-scripts, MIT). Analysis as specified in the CDISCPILOT01 statistical analysis plan, section 10.1.1. Reference report display: Table 14-3.05. Data cut-off: 2015-02-17."
footnotes:
  - "[1] Based on an analysis of covariance (ANCOVA) model with treatment and site group as factors and the baseline score as a covariate."
  - "[2] Test for a non-zero coefficient for treatment (dose) as a continuous variable."
  - "[3] Pairwise comparison with treatment as a categorical variable; p-values are not adjusted for multiple comparisons."
  - "Missing post-baseline values are imputed by last observation carried forward, over assessments assigned to visit windows (CDISCPILOT01 statistical analysis plan, sections 8.1 and 8.2)."
  - "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."
columns:
  order: ["Placebo", "Xanomeline Low Dose", "Xanomeline High Dose"]
format:
  mean_sd: "{mean} ({sd})"
  median_range: "{median} ({min};{max})"
  est_se: "{estimate} ({se})"
  ci: "({lcl};{ucl})"
  p_value: "{pvalue}"
  digits:
    mean: 1
    sd: 2
    median: 1
    min: 0
    max: 0
    estimate: 1
    se: 2
    lcl: 1
    ucl: 1
    pvalue: 3
rows:
  - { label: "Baseline", section: true }
  - { analysis: summary, variable: BASE, pattern: "N", label: "n", indent: 1 }
  - { analysis: summary, variable: BASE, pattern: mean_sd, label: "Mean (SD)", indent: 1 }
  - { analysis: summary, variable: BASE, pattern: median_range, label: "Median (Range)", indent: 1 }
  - { label: "Week 16", section: true }
  - { analysis: summary, variable: AVAL, pattern: "N", label: "n", indent: 1 }
  - { analysis: summary, variable: AVAL, pattern: mean_sd, label: "Mean (SD)", indent: 1 }
  - { analysis: summary, variable: AVAL, pattern: median_range, label: "Median (Range)", indent: 1 }
  - { label: "Change from baseline", section: true }
  - { analysis: summary, variable: CHG, pattern: "N", label: "n", indent: 1 }
  - { analysis: summary, variable: CHG, pattern: mean_sd, label: "Mean (SD)", indent: 1 }
  - { analysis: summary, variable: CHG, pattern: median_range, label: "Median (Range)", indent: 1 }
  - { label: "Statistical comparison of the change from baseline", section: true }
  - { analysis: ancova, variable: CHG, level: dose_response, pattern: p_value,
      label: "p-value (dose response) [1][2]", indent: 1 }
  - { analysis: ancova, variable: CHG, level: xan_vs_placebo, pattern: p_value,
      label: "p-value (Xanomeline - Placebo) [1][3]", indent: 1 }
  - { analysis: ancova, variable: CHG, level: xan_vs_placebo, pattern: est_se,
      label: "Difference of LS means (SE)", indent: 2 }
  - { analysis: ancova, variable: CHG, level: xan_vs_placebo, pattern: ci,
      label: "95% CI", indent: 2 }
  - { analysis: ancova, variable: CHG, level: high_vs_low, pattern: p_value,
      label: "p-value (Xanomeline High - Xanomeline Low) [1][3]", indent: 1 }
  - { analysis: ancova, variable: CHG, level: high_vs_low, pattern: est_se,
      label: "Difference of LS means (SE)", indent: 2 }
  - { analysis: ancova, variable: CHG, level: high_vs_low, pattern: ci,
      label: "95% CI", indent: 2 }
variants:
  post_text: {}

library/tfl/t-eff-adas-wk16/custom.R

# Display-specific statistics (contract section 2).
#
# Both functions are thin wrappers: the statistics themselves live in
# {opencsr} so that the seven ADAS-Cog displays share one tested
# implementation, and every model term is declared in this display's
# analysis.yaml rather than written in code.

ancova_change <- function(data, spec, denominator = NULL) {
  opencsr::ard_ancova(data, spec, denominator)
}

population_n <- function(data, spec, denominator = NULL) {
  opencsr::ard_population_n(data, spec, denominator)
}

Every iteration is kept: outputs/t-eff-adas-wk16/vNNN/ holds the spec snapshot, the ARD, the rendered output, and a manifest recording who regenerated it, why, and from which commit.