http://hl7.org/fhir/uv/ebm/Evidence/179691
type: Evidence
node role: treeRoot
id:
  v: 179691
meta:
  version id:
    v: 16
  last updated:
    v: 2025-11-04T13:17:05.088Z
  profile:
    v: http://hl7.org/fhir/uv/ebm/StructureDefinition/endpoint-analysis-plan
    l: endpoint-analysis-plan
language:
  v: en
text:
  status:
    v: empty
  div:
    v: [No data.]
extension:
  url:
    v: http://hl7.org/fhir/uv/ebm/StructureDefinition/artifact-publication-status
    l: artifact-publication-status
  value: CodeableConcept
    coding:
      system:
        v: http://terminology.hl7.org/CodeSystem/cited-artifact-status-type
        l: cited-artifact-status-type
      code:
        v: active
      display:
        v: Active
url:
  v: https://fevir.net/resources/Evidence/179691
  l: https://fevir.net/resources/Evidence/179691
identifier:
  type:
    coding:
      system:
        v: http://terminology.hl7.org/CodeSystem/v2-0203
        l: v2-0203
      code:
        v: ACSN
      display:
        v: Accession ID
    text:
      v: FEvIR Object Identifier
  system:
    v: https://fevir.net/FOI
    l: FOI
  value:
    v: 179691
  assigner:
    display:
      v: Computable Publishing LLC
name:
  v: Example_EndpointAnalysisPlan_from_PHUSE_Lilly_Redacted_Protocol_EBMonFHIR_IG_Version
title:
  v: Example EndpointAnalysisPlan from PHUSE Lilly Redacted Protocol - EBMonFHIR IG Version
cite as:
  v: Example EndpointAnalysisPlan from PHUSE Lilly Redacted Protocol - EBMonFHIR IG Version [Database Entry: FHIR Evidence Resource]. Contributors: Brian S. Alper [Authors/Creators]. In: Fast Evidence Interoperability Resources (FEvIR) Platform, FOI 179691. Revised 2025-11-04. Available at: https://fevir.net/resources/Evidence/179691. Computable resource at: https://fevir.net/resources/Evidence/179691#json.
status:
  v: active
author:
  name:
    v: Brian S. Alper
publisher:
  v: Computable Publishing LLC
contact:
  telecom:
    system:
      v: email
use context:
  code:
    system:
      v: https://fevir.net/resources/CodeSystem/179423
      l: https://fevir.net/resources/CodeSystem/179423
    code:
      v: evidence-communication
    display:
      v: Evidence Communication
  value: CodeableConcept
    coding:
      system:
        v: https://fevir.net/resources/CodeSystem/179423
        l: https://fevir.net/resources/CodeSystem/179423
      code:
        v: EndpointAnalysisPlan
      display:
        v: EndpointAnalysisPlan
copyright:
  v: https://creativecommons.org/licenses/by-nc-sa/4.0/
relates to:
  type:
    v: specification-of
  target: Attachment
    content type:
      v: application/pdf
    size:
      v: 240785
    title:
      v: PHUSE.Lilly.Redacted.Protocol
description:
  v: An example of an EndpointAnalysisPlan Profile which uses intended='true' and include-if extensions within Evidence.statistic.modelCharacteristic elements.
note:
  text:
    v: The statistic element will show an example of an endpoint analysis plan. To determine if there is a statistically significant relationship (overall Type 1 error rate, α=.05) between the change in both ADAS-Cog (see Attachment LZZT.2) and CIBIC+ (see Attachment LZZT.3) scores, and drug dose (0, 50 cm2 [54 mg], and 75 cm2 [81 mg]). 4.3.1. Efficacy Variables to be Analyzed Efficacy measures are described in Section 3.9.1.1. As stated in Section 3.9.1.2, the primary outcome measures are the ADAS-Cog (11) and CIBIC+ instruments. Because both of these variables must reach statistical significance, an adjustment to the nominal p-values is necessary in order to maintain a .05 Type I error rate for this study. This adjustment is described in detail in Section 4.3.5. 4.3.5. Nominal P-value Adjustments When there are multiple outcomes, and the study drug is declared to be effective when at least one of these outcomes achieves statistical significance in comparison with a placebo control, a downward adjustment to the nominal α-level is necessary. A well-known simple method is the Bonferroni method, that divides the overall Type I error rate, usually .05, by the number of multiple outcomes. So, for example, if there are two multiple outcomes, the study drug is declared to be effective if at least one of the two outcomes is significant at the .05/2 or .025 level. However, when one has the situation that is present in this study, where there are 2 (or 3 for Europe) outcome variables, each of which must be statistically significant, then the adjustment of the nominal levels is in the opposite direction, that is upwards, in order to maintain an overall Type 1 error rate of .05. In the case of two outcomes, ADAS-Cog (11) and CIBIC+, if the two variables were completely independent, then each variable should be tested at the nominal α-level of .051/2 = .2236 level. So if both variables resulted in a nominal p-value less than or equal to .2236, then we would declare the study drug to b…
variable definition:
  description:
    v: random permutation of treatment assignments matching the actual trial distribution of treatment assignment counts and keeping all other observed variables fixed
  variable role:
    v: population
variable definition:
  description:
    v: high dose xanomeline vs. low dose xanomeline vs. placebo
  variable role:
    v: exposure
  comparator category:
    v: placebo
  observed:
    l: http://hl7.org/fhir/uv/ebm/EvidenceVariable/179689
    reference:
      v: EvidenceVariable/179689
    type:
      v: EvidenceVariable
      l: EvidenceVariable
    display:
      v: GroupAssignment: high dose xanomeline vs. low dose xanomeline vs. placebo
variable definition:
  description:
    v: whether the permuted sample is more extreme than the observed data (ANCOVA-derived ADAS-Cog(11) effect estimate > observed effect estimate AND ANOVA-derived CIBIC+ effect estimate > observed effect estimate)
  variable role:
    v: outcome
synthesis type:
  coding:
    system:
      v: http://terminology.hl7.org/CodeSystem/synthesis-type
      l: synthesis-type
    code:
      v: NotApplicable
    display:
      v: not applicable
study design:
  coding:
    system:
      v: https://fevir.net/sevco
      l: sevco
    code:
      v: SEVCO:01003
    display:
      v: randomized assignment
statistic:
  statistic type:
    coding:
      system:
        v: https://fevir.net/sevco
        l: sevco
      code:
        v: STATO:0000607
      display:
        v: Proportion
    text:
      v: reported as an empirical p-value
  sample size:
    number of participants:
      v: 10000
    known data count:
      v: 10000
  model characteristic:
    code:
      text:
        v: prospective sample permutation testing
    intended:
      v: true
  model characteristic:
    code:
      text:
        v: nominal Type I error rate
    value: Quantity
      value:
        v: 0.025
    intended:
      v: true
  model characteristic:
    code:
      text:
        v: threshold for marginal statistical significance
    value: Quantity
      value:
        v: 0.05
    intended:
      v: true
  model characteristic:
    code:
      text:
        v: null hypothesis (STATO:0000057)
    value: CodeableConcept
      text:
        v: xanomeline is equal or worse than placebo
    intended:
      v: true

v: defined-in-text

v: defined in text

v: defined-in-text

v: defined in text

code:
  text:
    v: alternative hypothesis (STATO:0000208)
value: CodeableConcept
  text:
    v: xanomeline has greater efficacy than placebo
intended:
  v: true

code:
  text:
    v: statistical software package
value: CodeableConcept
  text:
    v: SAS
intended:
  v: true

code:
  text:
    v: Sample Size/Power Calculation
value: CodeableConcept
  text:
    v: Rationale: Because there will be roughly 300!/(3 * 100!) possible permutations of the data, random data permutations will be sampled (10,000 random permutations).
intended:
  v: true