Generated Narrative: StructureDefinition m11-report Name Flags Card. Type Description & Constraints Composition 0..* EvidenceReport A set of resources composed into a single coherent clinical statement with clinical attestation #xD; type #xD; coding 1..1 Coding Code defined by a terminology system Required Pattern: At least the following #xD; system 1..1 uri Identity of the terminology system Fixed Value: http://loinc.org #xD; code 1..1 code Symbol in syntax defined by the system Fixed Value: 35528-9 #xD; display 1..1 string Representation defined by the system Fixed Value: Clinical trial protocol Clinical trial protocol #xD; text 0..1 string Plain text representation of the concept Required Pattern: CeSHarP Report #xD; Slices for section 15..* BackboneElement Composition is broken into sections Slice: Unordered, Open by value:code.text #xD; section:titlepage S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Title Page #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section0-title-page #xD; entry 0..* Reference(StudyDesign) A reference to data that supports this section #xD; section:summary S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Protocol Summary #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section1-protocol-summary #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:protocolSynopsis S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Protocol Synopsis #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section1.1-protocol-synopsis #xD; Slices for section 6..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:objectivesEndpoints S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Primary and Secondary Objectives and Estimands #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section1.1.1-objectives-estimands #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(Composition) A reference to data that supports this section #xD; section:overallDesign 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Overall Design #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section1.1.2-overall-design #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(Composition | ResearchStudy) A reference to data that supports this section #xD; section:numberOfArms 1..1 BackboneElement Nested Section #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: Number of Arms #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:blinding 1..1 BackboneElement Nested Section #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: Blinding #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:numberOfParticipants 1..1 BackboneElement Nested Section #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: Number of Participants #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:duration 0..1 BackboneElement Nested Section #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: Duration #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:committees 1..1 BackboneElement Nested Section #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: Committees #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:trialSchema S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Schema #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section1.2-trial-schema #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(SoaPlanDefinition) A reference to data that supports this section #xD; section:scheduleOfActivities S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Schedule of Activities #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section1.3-schedule-of-activities #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(SoaPlanDefinition) A reference to data that supports this section #xD; section:introduction S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Introduction #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2-introduction #xD; Slices for section 2..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:purposeOfTrial S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Purpose of Trial #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.1-trial-purpose #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:benefitsAndRisks S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Assessment of Risks and Benefits #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.2-benefits-risks #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:riskSummary 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Risk Summary and Mitigation Strategy #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.2.1-risk-summary #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:trialIntervention S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial-specific Intervention Risks and Mitigations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.2.1.1-trial-intervention-risk-summary #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:trialProcedures 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial-specific Procedure Risks and Mitigations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.2.1.2-trial-procedures-risk-summary #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:otherRisk 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial-specific Other Risks and Mitigations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.2.1.3-trial-other-risk-summary #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:benefitSummary S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Benefit Summary #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.2.2-benefit-summary #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:overallBenefitRisk 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Overall Risk-Benefit Assessment #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section2.2.3-overall-benefit-risk-conclusion #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:estimands S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Objectives and Associated Estimands #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section3-estimands #xD; entry 0..* Reference(StudyDesign) A reference to data that supports this section #xD; section:design S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Design #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4-trial-design #xD; Slices for section 4..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:description S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Description of Trial Design #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.1-description-of-trial-design #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:stakeholderInput S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Stakeholder Input into Design #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.1.1-stakeholder-input-into-design #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:rationale S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Trial Design #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2-rationale-for-trial-design #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:endpoints S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Estimand(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2.1-rationale-estimands #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:model S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Intervention Model #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2.2-rationale-intervention-model #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:comparator S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Control Type #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2.3-rationale-comparator #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:duration S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Duration #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2.4-rationale-duration #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:adaptive S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Adaptive or Novel Trial Design #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2.5-rationale-adaptive #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:interim S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Interim Analysis #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2.6-rationale-interim-analysis #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:otherAspects S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Other Trial Design Aspects #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.2.7-rationale-other-aspects #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:trialStoppingRules S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Stopping Rules #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.3-trial-stopping-rules #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:startEnd S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Start of Trial and End of Trial #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.4-start-and-end #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:access S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Access to Trial Intervention After End of Trial #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section4.5-access-after-trial #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:population S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Population #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5-trial-population #xD; Slices for section 6..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:description S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Description of Trial Population and Rationale #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.1-population-description #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(CohortDefinition) A reference to data that supports this section #xD; section:inclusionCriteria S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Inclusion Criteria #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.2-inclusion-criteria #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(CohortDefinition) A reference to data that supports this section #xD; section:exclusionCriteria S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Exclusion Criteria #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.3-exclusion-criteria #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(CohortDefinition) A reference to data that supports this section #xD; section:contraception S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Contraception #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.4-contraception #xD; Slices for section 2..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:contraceptionDefinitions S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Definitions Related to Childbearing Potential #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.4.1-contraception-definitions #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:contraceptionDetails S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Contraception Requirements #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.4.2-contraception-details #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:lifestyle S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Lifestyle Restrictions #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.5-lifestyle-restrictions #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:dietary S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Meals and Dietary Restrictions #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.5.1-dietary-restrictions #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:substances S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Caffeine, Alcohol, Tobacco, and Other Restrictions #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.5.2-substances-restrictions #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:activity S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Physical Activity Restrictions #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.5.3-activity-restrictions #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:other S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Other Activity Restrictions #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.5.4-other-restrictions #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:screenFailures S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Screen Failure and Rescreening #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section5.6-screen-failure #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:intervention S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Intervention and Concomitant Therapy #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6-trial-intervention #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 9..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:description S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Description of Investigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.1-description-of-trial-intervention #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(ConceptualExposureDefinition) A reference to data that supports this section #xD; section:rationale S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rationale for Investigational Trial Intervention Dose and Regimen #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.2-rationale-for-trial-intervention-regimen #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(ConceptualExposureDefinition) A reference to data that supports this section #xD; section:dosingAdministration S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Investigational Trial Intervention Administration #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.3-dosing-and-administration #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(ActivityDefinition) A reference to data that supports this section #xD; section:doseModification S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Investigational Trial Intervention Dose Modification #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.4-dose-modification #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(ActivityDefinition) A reference to data that supports this section #xD; section:treatmentOfOverdose S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Management of Investigational Trial Intervention Overdose #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.5-management-of-overdose #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(ActivityDefinition | PlanDefinition) A reference to data that supports this section #xD; section:preparation S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Preparation, Storage, Handling and Accountability of Investigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.6-preparation-storage-handling #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:preparationIntervention S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Preparation of Investigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.6.1-preparation #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:storageHandling S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Storage and Handling of Investigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.6.2-storage-handling #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:accountability S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Accountability of Investigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.6.3-accountability #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:assignmentAndBlinding S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Investigational Trial Intervention Assignment, Randomisation and Blinding #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.7-assignment-randomisation-blinding #xD; Slices for section 4..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:assignment S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Participant Assignment to Investigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.7.1-assignment #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:randomisation S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Randomisation #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.7.2-randomisation #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:blinding S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Measures to Maintain Blinding #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.7.3-blinding #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:unblinding S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Emergency Unblinding at the Site #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.7.4-unblinding #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:adherence S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Investigational Trial Intervention Adherence #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.8-intervention-adherence #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:noninvestigationalTherapy S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Non-Investigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.9-noninvestigational-interventions #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:background S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Background Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.9.1-background-intervention #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:rescue S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rescue Therapy #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.9.2-rescue-therapy #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:other S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Other Noninvestigational Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.9.3-other-therapy #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:concomitantTherapy S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Concomitant Therapy #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.10-concomitant-therapy #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:prohibited S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Prohibited Concomitant Therapy #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.10.1-prohibited-concomitant-therapy #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:permitted S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Permitted Concomitant Therapy #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section6.10.2-permitted-concomitant-therapy #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:dropout S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Participant Discontinuation of Trial Intervention and Discontinuation or Withdrawal from Trial #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section7-participant-discontinuation #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:discontinuation S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Discontinuation of Trial Intervention for Individual Participants #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section7.1-discontinuation-of-trial-intervention #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:permanent S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Permanent Discontinuation of Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section7.1.1-permanent-discontinuation-of-trial-intervention #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:temporary S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Temporary Discontinuation of Trial Intervention #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section7.1.2-temporary-discontinuation-of-trial-intervention #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:rechallenge S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Rechallenge #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section7.1.3-rechallenge #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:withdrawal S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Discontinuation or Withdrawal from the Trial #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section7.2-participant-withdrawal #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:lostToFollowUp S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Management of Loss to Follow-Up #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section7.3-lost-to-follow-up #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:assessments S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Assessments and Procedures #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8-assessments #xD; Slices for section 8..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:considerations S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Assessments and Procedures Considerations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.1-assessments-procedures #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:screeningBaseline S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Screening/Baseline Assessments and Procedures #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.2-screening-baseline-assessments #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:efficacy S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Efficacy Assessments and Procedures #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.3-efficacy-assessments #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:safety S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Safety Assessments and Procedures #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.4-safety-assessments #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:physical S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Physical Examination #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.4.1-physical-examination #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:vitals S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Vital Signs #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.4.2-vital-signs #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:ecg S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Electrocardiograms #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.4.3-electrocardiograms #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:laboratory S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Clinical Laboratory Assessments #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.4.4-clinical-laboratory-assessments #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:pregnancy S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Pregnancy Testing #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.4.5-pregnancy-testing #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:suicidal S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Suicidal Ideation and Behaviour Risk Monitoring #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.4.6-suicidal-ideation #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:pharmacokinetics S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Pharmacokinetics #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.5-pharmacokinetics #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:biomarkers S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Biomarkers #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.6-biomarkers #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 2..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:genetics S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Genetics and Pharmacogenomics #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.6.1-genetics-pharmacogenomics #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:pharmacodynamics S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Pharmacodynamic Biomarkers #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.6.2-pharmacodynamics #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:other S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Other Biomarkers #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.6.3-other-biomarkers #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:immunogenicity S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Immunogenicity Assessments #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.7-immunogenicity-assessments #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:economics S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Medical Resource Utilisation and Health Economics #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section8.8-economics #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:adverseEvents S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Adverse Events, Serious Adverse Events, Product Complaints, Pregnancy and Postpartum Information, and Special Safety Situations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9-adverse-events #xD; Slices for section 4..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:definitions S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Definitions #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.1-definitions #xD; Slices for section 2..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:adverseEventsDefinitions S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Definitions of Adverse Events #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.1.1-definitions-adverse-events #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:seriousAdverseEventsDefinitions S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Definitions of Serious Adverse Events #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.1.2-definitions-serious-adverse-events #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:productComplaintsDefinitions S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Definitions of Product Complaints #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.1.3-definitions-product-complaints #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:collectionMethods S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Timing and Procedures for Collection and Reporting #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2-collection-methods #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 5..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:timing 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Timing #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.1-timing #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:procedures 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Collection Procedures #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.2-collection-procedures #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 5..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:identifying 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Identification #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.2.1-identification #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:intensity 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Severity #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.2.2-severity #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:causality 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Causality #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.2.3-causality #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:recording 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Recording #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.2.4-recording #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:followup 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Follow-up #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.2.5-followup #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:reporting 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Reporting #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.3-reporting-events #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 1..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:regulatoryRequirements 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Regulatory Reporting Requirements #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.3.1-regulatory-requirements #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:specialInterest 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Adverse Events of Special Interest #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.4-special-interest #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:diseaseRelatedEvents 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Disease-related Events or Outcomes Not Qualifying as AEs or SAEs #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.2.5-disease-related-events #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:pregnancy S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Pregnancy and Postpartum Information #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.3-pregnancy-postpartum #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:pregnant S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Participants Who Become Pregnant During the Trial #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.3.1-pregnant #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:pregnantPartner S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Participants Whose Partners Become Pregnant #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.3.2-pregnant-partner #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:special S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Special Safety Situations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section9.4-special-safety-situations #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:statistics S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Statistical Considerations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10-statistics #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 6..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:considerations S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: General Considerations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.1-general-considerations #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:analysisSets S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Analysis Sets #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.2-analysis-sets #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:analysisBaseline S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Analyses of Demographics and Other Baseline Variables #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.3-analyses-demographics #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:analysisPrimaryObjective S 1..* BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Analyses Associated with the Primary Objective(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.4-analysis-primary-objective #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 1..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:analysisPrimaryInstance S 1..* BackboneElement Nested Section #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.4.1-analysis-primary-objective-instance #xD; focus 0..1 Reference(VariableDefinition) Who/what the section is about, when it is not about the subject of composition #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:statisticalModel S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Statistical Analysis Method #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.4.1.1-statistical-method #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(EndpointAnalysisPlan) A reference to data that supports this section #xD; section:intercurrentEventHandling S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Handling of Data in Relation to Primary Estimand(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.4.1.2-data-handling #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:missingData S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Handling of Missing Data in Relation to Primary Estimand(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.4.1.3-missing-data-handling #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:sensitvityAnalysis S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Sensitivity Analysis #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.4.1.4-sensitivity-analysis #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(EndpointAnalysisPlan) A reference to data that supports this section #xD; section:supplementaryAnalysis S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Supplementary Analysis #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.4.1.5-supplementary-analysis #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:secondaryAnalysis S 0..* BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Analyses Associated with the Secondary Objective(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.5-analysis-secondary-objective #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 1..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:analysisSecondaryInstance S 1..* BackboneElement Nested Section #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.5.1-analysis-secondary-objective-instance #xD; focus 0..1 Reference(VariableDefinition) Who/what the section is about, when it is not about the subject of composition #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:statisticalModel S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Statistical Analysis Method #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.5.1.1-statistical-method #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(EndpointAnalysisPlan) A reference to data that supports this section #xD; section:intercurrentEventHandling S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Handling of Data in Relation to Secondary Estimand(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.5.1.2-data-handling #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:missingData S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Handling of Missing Data in Relation to Secondary Estimand(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.5.1.3-missing-data-handling #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:sensitvityAnalysis S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Sensitivity Analysis #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.5.1.4-sensitivity-analysis #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(EndpointAnalysisPlan) A reference to data that supports this section #xD; section:supplementaryAnalysis S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Supplementary Analysis #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.5.1.5-supplementary-analysis #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:exploratoryAnalysis S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Analyses Associated with the Exploratory Objective(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.6-analysis-exploratory-objective #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:safetyAnalyses S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Safety Analyses #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.7-safety-analyses #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:otherAnalyses S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Other Analyses #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.8-other-analyses #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:multiplicity S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Multiplicity Adjustments #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.10-multiplicity-adjustments #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:interimAnalyses S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Interim Analyses #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.9-interim-analyses #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:sampleSize S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Sample Size Determination #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section10.11-sample-size-determination #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(EndpointAnalysisPlan) A reference to data that supports this section #xD; section:oversight S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Oversight and Other General Considerations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11-oversight #xD; Slices for section 12..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:regulatory S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Regulatory and Ethical Considerations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.1-regulatory-considerations #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:trialOversight S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Trial Oversight #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.2-trial-oversight #xD; text 0..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 2..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:investigatorResponsibilities S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Investigator Responsibilities #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.2.1-investigator-responsibilities #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:sponsorResponsibilities S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Sponsor Responsibilities #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.2.2-sponsor-responsibilities #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:committees S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Committees #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.4-committees #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:informedConsent S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Informed Consent Process #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.3-informed-consent-process #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; Slices for section 0..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:assentProcess S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Assent Process #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.3.0-assent-process #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:emergency S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Emergency Consent Process #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.3.0-emergency-consent-process #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:rescreening S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Informed Consent for Rescreening #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.3.1-rescreening-consent-process #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:remainingSamples S 0..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Informed Consent for Remaining Samples in Exploratory Research #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.3.2-remaining-samples #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:insurance S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Insurance and Indemnity #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.5-insurance-and-indemnity #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:riskManagement S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Risk-Based Quality Management #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.6-risk-management #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:dataGovernance S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Data Governance #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.7-data-governance #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:dataProtection S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Data Protection #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.8-data-protection #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:sourceData S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Source Data #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.9-source-data #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:protcolDeviations S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Protocol Deviations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.10-protocol-deviations #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:earlySiteClosure S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Early Site Closure #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.11-early-site-closure #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:decisionRights S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Decision Rights for Site Closure #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.11-early-site-closure#decisionRights #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:criteria S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Crteria for Early Closure #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.11-early-site-closure#criteria #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:responsibilities S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Responsibilities Following Early Site Closure #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.11-early-site-closure#responsibilities #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:dataDissemination S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Data Dissemination #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section11.12-data-dissemination #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:definitions S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Appendix: Supporting Details #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section12-supporting-details #xD; Slices for section 3..* Nested Section Slice: Unordered, Open by value:code.text #xD; section:clinicalLaboratoryTests S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Clinical Laboratory Tests #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section12.1-clinical-laboratory-tests #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:regional S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Country/Region-Specific Differences #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section12.2-country-specific-differences #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:priorAmendments S 1..1 BackboneElement Nested Section #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Prior Protocol Amendment(s) #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section12.3-prior-protocol-amendments #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; section:glossary S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Appendix: Glossary of Terms and Abbreviations #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section13-glossary #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(ValueSet | CodeSystem) A reference to data that supports this section #xD; section:references S 1..1 BackboneElement Composition is broken into sections #xD; title 0..1 string Label for section (e.g. for ToC) Required Pattern: Appendix: References #xD; code #xD; text 1..1 string Plain text representation of the concept Required Pattern: section14-references #xD; text 1..1 Narrative Text summary of the section, for human interpretation #xD; entry 0..* Reference(Citation) A reference to data that supports this section #xD; Documentation for this format
HL7 International / Clinical Decision Support
Profile of Composition for Evidence Based Medicine IG. The M11Report Profile is used for the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Clinical Electronic Structured Harmonised Protocol (CeSHarP) M11 Technical Specification.
This Profile is developed to support the evolving draft of the M11 Template. The ICH is the copyright holder for the M11 template and has not endorsed or sponsored this Profile.
A set of resources composed into a single coherent clinical statement with clinical attestation
A set of healthcare-related information that is assembled together into a single logical package that provides a single coherent statement of meaning, establishes its own context and that has clinical attestation with regard to who is making the statement. A Composition defines the structure and narrative content necessary for a document. However, a Composition alone does not constitute a document. Rather, the Composition must be the first entry in a Bundle where Bundle.type=document, and any other resources referenced from Composition must be included as subsequent entries in the Bundle (for example Patient, Practitioner, Encounter, etc.).
While the focus of this specification is on patient-specific clinical statements, this resource can also apply to other healthcare-related statements such as study protocol designs, healthcare invoices and other activities that are not necessarily patient-specific or clinical.
If the resource is contained in another resource, it SHALL NOT contain nested Resources
If the resource is contained in another resource, it SHALL be referred to from elsewhere in the resource or SHALL refer to the containing resource
contained.where((('#'+id.trace('id') in %resource.descendants().select(reference | as(uri))) or descendants().where(reference='#' | as(uri)='#').exists()).not()).trace('unmatched', id).empty()
If a resource is contained in another resource, it SHALL NOT have a meta.versionId or a meta.lastUpdated
contained.meta.versionId.empty() and contained.meta.lastUpdated.empty()
If a resource is contained in another resource, it SHALL NOT have a security label
When a resource has no narrative, only systems that fully understand the data can display the resource to a human safely. Including a human readable representation in the resource makes for a much more robust eco-system and cheaper handling of resources by intermediary systems. Some ecosystems restrict distribution of resources to only those systems that do fully understand the resources, and as a consequence implementers may believe that the narrative is superfluous. However experience shows that such eco-systems often open up to new participants over time.
A resource should have narrative for robust management
Entity, Role, or Act,Document[classCode="DOC" and moodCode="EVN" and isNormalAct()]
The logical id of the resource, as used in the URL for the resource. Once assigned, this value never changes.
Within the context of the FHIR RESTful interactions, the resource has an id except for cases like the create and conditional update. Otherwise, the use of the resouce id depends on the given use case.
The metadata about the resource. This is content that is maintained by the infrastructure. Changes to the content might not always be associated with version changes to the resource.
All FHIR elements must have a @value or children
hasValue() or (children().count() > id.count())
A set of rules under which this content was created
A reference to a set of rules that were followed when the resource was constructed, and which must be understood when processing the content. Often, this is a reference to an implementation guide that defines the special rules along with other profiles etc.
Asserting this rule set restricts the content to be only understood by a limited set of trading partners. This inherently limits the usefulness of the data in the long term. However, the existing health eco-system is highly fractured, and not yet ready to define, collect, and exchange data in a generally computable sense. Wherever possible, implementers and/or specification writers should avoid using this element. Often, when used, the URL is a reference to an implementation guide that defines these special rules as part of its narrative along with other profiles, value sets, etc.
This element is labeled as a modifier because the implicit rules may provide additional knowledge about the resource that modifies its meaning or interpretation
The base language in which the resource is written.
Language is provided to support indexing and accessibility (typically, services such as text to speech use the language tag). The html language tag in the narrative applies to the narrative. The language tag on the resource may be used to specify the language of other presentations generated from the data in the resource. Not all the content has to be in the base language. The Resource.language should not be assumed to apply to the narrative automatically. If a language is specified, it should it also be specified on the div element in the html (see rules in HTML5 for information about the relationship between xml:lang and the html lang attribute).
Text summary of the resource, for human interpretation
A human-readable narrative that contains a summary of the resource and can be used to represent the content of the resource to a human. The narrative need not encode all the structured data, but is required to contain sufficient detail to make it "clinically safe" for a human to just read the narrative. Resource definitions may define what content should be represented in the narrative to ensure clinical safety.
Contained resources do not have a narrative. Resources that are not contained SHOULD have a narrative. In some cases, a resource may only have text with little or no additional discrete data (as long as all minOccurs=1 elements are satisfied). This may be necessary for data from legacy systems where information is captured as a "text blob" or where text is additionally entered raw or narrated and encoded information is added later.
These resources do not have an independent existence apart from the resource that contains them - they cannot be identified independently, nor can they have their own independent transaction scope. This is allowed to be a Parameters resource if and only if it is referenced by a resource that provides context/meaning.
This should never be done when the content can be identified properly, as once identification is lost, it is extremely difficult (and context dependent) to restore it again. Contained resources may have profiles and tags in their meta elements, but SHALL NOT have security labels. Contained resources may be a resource type defined in the FHIR specification, or an [additional resource](http://build.fhir.org/resource.html#additional).
Indicates the mechanism used to compare versions to determine which is more current.
If set as a string, this is a FHIRPath expression that has two additional context variables passed in - %version1 and %version2 and will return a negative number if version1 is newer, a positive number if version2 and a 0 if the version ordering can't be successfully be determined.
Must have either extensions or value[x], not both
A Boolean value to indicate that this artifact is authored for testing purposes (or education/evaluation/marketing) and is not intended to be used for genuine usage.
Natural language description of the artifact
A free text natural language description of the artifact from a consumer's perspective.
This description can be used to capture details such as comments about misuse, instructions for clinical use and interpretation, literature references, examples from the paper world, etc. It is not a rendering of the artifact as conveyed in the 'text' field of the resource itself. This item SHOULD be populated unless the information is available from context (e.g. the language of the artifact is presumed to be the predominant language in the place the artifact was created).
Explanation of why this artifact is needed and why it has been designed as it has.
This element does not describe the usage of the artifact. Instead, it provides traceability of ''why'' the resource is either needed or ''why'' it is defined as it is. This may be used to point to source materials or specifications that drove the structure of this artifact.
A copyright statement relating to the artifact and/or its contents. Copyright statements are generally legal restrictions on the use and publishing of the artifact.
The short copyright declaration (e.g. (c) '2015+ xyz organization' should be sent in the copyrightLabel element.
A short string (<50 characters), suitable for inclusion in a page footer that identifies the copyright holder, effective period, and optionally whether rights are resctricted. (e.g. 'All rights reserved', 'Some rights reserved').
Defines the content expected to be rendered in all representations of the artifact. The (c) symbol should NOT be included in this string. It is expected to be added by software when rendering the notation. Full details about licensing, restrictions, warrantees, etc. goes in the more general 'copyright' element.
When the artifact was approved by publisher
The date on which the artifact content was approved by the publisher. Approval happens once when the content is officially approved for usage.
The 'date' element may be more recent than the approval date because of minor changes or editorial corrections.
The date on which the resource content was last reviewed. Review happens periodically after approval but does not change the original approval date.
If specified, this date follows the original approval date.
When the artifact is expected to be used
The period during which the artifact content was or is planned to be in active use.
The effective period for an artifact determines when the content is applicable for usage and is independent of publication and review dates. For example, an artifact intended to be used for the year 2016 might be published in 2015.
The Resource contains content in a language additional to the one in the language element.
Contact details to assist a user in finding and communicating with the publisher.
May be a web site, an email address, a physical address, a telephone number, etc.
Specifies the publication date of the Resource.
The status of the processing for making the artifact publicly available, not necessarily the same as artifact status (Resource.status).
May be used to represent additional information that is not part of the basic definition of the resource and that modifies the understanding of the element that contains it and/or the understanding of the containing element's descendants. Usually modifier elements provide negation or qualification. To make the use of extensions safe and managable, there is a strict set of governance applied to the definition and use of extensions. Though any implementer is allowed to define an extension, there is a set of requirements that SHALL be met as part of the definition of the extension. Applications processing a resource are required to check for modifier extensions. Modifier extensions SHALL NOT change the meaning of any elements on Resource or DomainResource (including cannot change the meaning of modifierExtension itself).
There can be no stigma associated with the use of extensions by any application, project, or standard - regardless of the institution or jurisdiction that uses or defines the extensions. The use of extensions is what allows the FHIR specification to retain a core level of simplicity for everyone.
Modifier extensions allow for extensions that *cannot* be safely ignored to be clearly distinguished from the vast majority of extensions which can be safely ignored. This promotes interoperability by eliminating the need for implementers to prohibit the presence of extensions. For further information, see the [definition of modifier extensions](http://build.fhir.org/extensibility.html#modifierExtension).
Modifier extensions are expected to modify the meaning or interpretation of the resource that contains them
Canonical identifier for this Composition, represented as a URI (globally unique)
An absolute URI that is used to identify this Composition when it is referenced in a specification, model, design or an instance; also called its canonical identifier. This SHOULD be globally unique and SHOULD be a literal address at which an authoritative instance of this Composition is (or will be) published. This URL can be the target of a canonical reference. It SHALL remain the same when the Composition is stored on different servers.
Can be a urn:uuid: or a urn:oid: but real http: addresses are preferred. Multiple instances may share the same URL if they have a distinct version.
Allows the Composition to be referenced by a single globally unique identifier.
Version-independent identifier for the Composition
A version-independent identifier for the Composition. This identifier stays constant as the composition is changed over time.
Similar to ClinicalDocument/setId in CDA. See discussion in resource definition for how these relate.
An explicitly assigned identifier of a variation of the content in the Composition
While each resource, including the composition itself, has its own version identifier, this is a formal identifier for the logical version of the Composition as a whole. It would remain constant if the resources were moved to a new server, and all got new individual resource versions, for example.
registered | partial | preliminary | final | amended | corrected | appended | cancelled | entered-in-error | deprecated | unknown
The workflow/clinical status of this composition. The status is a marker for the clinical standing of the document.
If a composition is marked as withdrawn, the compositions/documents in the series, or data from the composition or document series, should never be displayed to a user without being clearly marked as untrustworthy. The flag "entered-in-error" is why this element is labeled as a modifier of other elements. Some reporting work flows require that the original narrative of a final document never be altered; instead, only new narrative can be added. The composition resource has no explicit status for explicitly noting whether this business rule is in effect. This would be handled by an extension if required.
Need to be able to mark interim, amended, or withdrawn compositions or documents.
This element is labelled as a modifier because it is a status element that contains status entered-in-error which means that the resource should not be treated as valid
The workflow/clinical status of the composition.
interim: .completionCode="IN" & ./statusCode[isNormalDatatype()]="active"; final: .completionCode="AU" && ./statusCode[isNormalDatatype()]="complete" and not(./inboundRelationship[typeCode="SUBJ" and isNormalActRelationship()]/source[subsumesCode("ActClass#CACT") and moodCode="EVN" and domainMember("ReviseComposition", code) and isNormalAct()]); amended: .completionCode="AU" && ./statusCode[isNormalDatatype()]="complete" and ./inboundRelationship[typeCode="SUBJ" and isNormalActRelationship()]/source[subsumesCode("ActClass#CACT") and moodCode="EVN" and domainMember("ReviseComposition", code) and isNormalAct() and statusCode="completed"]; withdrawn : .completionCode=NI && ./statusCode[isNormalDatatype()]="obsolete"
Specifies the particular kind of composition (e.g. History and Physical, Discharge Summary, Progress Note). This usually equates to the purpose of making the composition.
For Composition type, LOINC is ubiquitous and strongly endorsed by HL7. Most implementation guides will require a specific LOINC code, or use LOINC as an extensible binding.
Key metadata element describing the composition, used in searching/filtering.
Unique id for the element within a resource (for internal references). This may be any string value that does not contain spaces.
Extensions are always sliced by (at least) url
Additional content defined by implementations
May be used to represent additional information that is not part of the basic definition of the element. To make the use of extensions safe and managable, there is a strict set of governance applied to the definition and use of extensions. Though any implementer can define an extension, there is a set of requirements that SHALL be met as part of the definition of the extension.
A reference to a code defined by a terminology system.
Codes may be defined very casually in enumerations, or code lists, up to very formal definitions such as SNOMED CT - see the HL7 v3 Core Principles for more information. Ordering of codings is undefined and SHALL NOT be used to infer meaning. Generally, at most only one of the coding values will be labeled as UserSelected = true.
Allows for alternative encodings within a code system, and translations to other code systems.
Clinical trial protocol Clinical trial protocol
fhir:CodeableConcept.coding rdfs:subPropertyOf dt:CD.coding
Plain text representation of the concept
A human language representation of the concept as seen/selected/uttered by the user who entered the data and/or which represents the intended meaning of the user.
Very often the text is the same as a displayName of one of the codings.
The codes from the terminologies do not always capture the correct meaning with all the nuances of the human using them, or sometimes there is no appropriate code at all. In these cases, the text is used to capture the full meaning of the source.
C*E.9. But note many systems use C*E.2 for this
fhir:CodeableConcept.text rdfs:subPropertyOf dt:CD.originalText
A categorization for the type of the composition - helps for indexing and searching. This may be implied by or derived from the code specified in the Composition Type.
Helps humans to assess whether the composition is of interest when viewing an index of compositions or documents.
High-level kind of a clinical document at a macro level.
.outboundRelationship[typeCode="COMP].target[classCode="LIST", moodCode="EVN"].code
Who and/or what the composition is about
Who or what the composition is about. The composition can be about a person, (patient or healthcare practitioner), a device (e.g. a machine) or even a group of subjects (such as a document about a herd of livestock, or a set of patients that share a common exposure).
Reference a Citation Resource, ArtifactAssessment Resource (Classification Profile), Group Resource (EvidenceReportSubject Profile), ReserchStudy Resource, or any Resource to define a subject of this EvidenceReport.
Essential metadata for searching for the composition. Identifies who and/or what the composition/document is about.
Describes the clinical encounter or type of care this documentation is associated with.
Provides context for the composition and supports searching.
unique(highest(./outboundRelationship[typeCode="SUBJ" and isNormalActRelationship()], priorityNumber)/target[moodCode="EVN" and classCode=("ENC", "PCPR") and isNormalAct])
The composition editing time, when the composition was last logically changed by the author.
The Last Modified Date on the composition may be after the date of the document was attested without being changed. This means that the date on an amended document is the date of the amendment, not the date of original authorship.
dateTime is used for tracking, organizing versions and searching. Note that this is the time of authoring this version of the Composition. When packaged in a document, [Bundle.timestamp](http://hl7.org/fhir/R5/bundle-definitions.html#Bundle.timestamp) is the date of packaging.
DocumentReference.content.attachment.date, DocumentReference.date
The context that the content is intended to support
The content was developed with a focus and intent of supporting the contexts that are listed. These contexts may be general categories (gender, age, ...) or may be references to specific programs (insurance plans, studies, ...) and may be used to assist with indexing and searching for appropriate Composition instances.
When multiple useContexts are specified, there is no expectation that all or any of the contexts apply.
Assist in searching for appropriate content.
Who and/or what authored the composition
Identifies who is responsible for the information in the composition, not necessarily who typed it in.
Identifies who is responsible for the content.
Name for this Composition (computer friendly)
A natural language name identifying the {{title}}. This name should be usable as an identifier for the module by machine processing applications such as code generation.
The name is not expected to be globally unique. The name should be a simple alphanumeric type name to ensure that it is machine-processing friendly.
Support human navigation and code generation.
Official human-readable label for the composition.
For many compositions, the title is the same as the text or a display name of Composition.type (e.g. a "consultation" or "progress note"). Note that CDA does not make title mandatory, but there are no known cases where it is useful for title to be omitted, so it is mandatory here. Feedback on this requirement is welcome during the trial use period.
DocumentReference.description, DocumentReference.content.attachment.title
A comment, general note or annotation not coded elsewhere.
A participant who has attested to the accuracy of the composition/document.
Identifies responsibility for the accuracy of the composition content.
All FHIR elements must have a @value or children or both
Extensions that cannot be ignored even if unrecognized
May be used to represent additional information that is not part of the basic definition of the element and that modifies the understanding of the element in which it is contained and/or the understanding of the containing element's descendants. Usually modifier elements provide negation or qualification. To make the use of extensions safe and managable, there is a strict set of governance applied to the definition and use of extensions. Though any implementer can define an extension, there is a set of requirements that SHALL be met as part of the definition of the extension. Applications processing a resource are required to check for modifier extensions. Modifier extensions SHALL NOT change the meaning of any elements on Resource or DomainResource (including cannot change the meaning of modifierExtension itself).
Modifier extensions are expected to modify the meaning or interpretation of the element that contains them
reviewer | editor | endorser | informant | recorder
The type of attestation the authenticator offers.
Indicates the level of authority of the attestation.
implied by .authenticator/.legalAuthenticator
When the composition was attested by the party.
Identifies when the information in the composition was deemed accurate. (Things may have changed since then.).
./time[type="TS" and isNormalDatatype()]
Who attested the composition in the specified way.
Identifies who has taken on the responsibility for accuracy of the composition content.
./role[classCode="ASSIGNED" and isNormalRole]/player[determinerCode="INST" and classCode=("DEV", "PSN") and isNormalEntity()] or ./role[classCode="ASSIGNED" and isNormalRole and not(player)]/scoper[determinerCode="INST" and classCode="ORG" and isNormalEntity()]
Organization which maintains the composition
Identifies the organization or group who is responsible for ongoing maintenance of and access to the composition/document information.
This is useful when documents are derived from a composition - provides guidance for how to get the latest version of the document. This is optional because this is sometimes not known by the authoring system, and can be inferred by context. However, it is important that this information be known when working with a derived document, so providing a custodian is encouraged.
Identifies where to go to find the current version, where to report issues, etc.
.participation[typeCode="RCV"].role[classCode="CUST"].scoper[classCode="ORG" and determinerCode="INST"]
Relationships to other compositions/documents
Relationships that this composition has with other compositions or documents (FHIR or non-FHIR resources) that already exist.
To reference (using relatesTo) a Bundle of type "document" or another Composition where you only have the identifier, use a targetReference with an identifier.\ When a Composition is an alternate representation of another type of document e.g. CDA, the other document could be referenced in a DocumentReference resource. Here is an example of using relatesTo to reference another Bundle of type "document" or Composition where you only have the identifier: ``` "relatesTo": [{ "type": "replaces", "targetReference": { "identifier": { "system": "...", "value": "..." } } }] ```
Additional classifiers for RelatedArtifacts
Provides additional classifiers of the related artifact.
documentation | justification | predecessor | successor | derived-from | depends-on | composed-of | part-of | amends | amended-with | appends | appended-with | cites | cited-by | comments-on | comment-in | contains | contained-in | corrects | correction-in | replaces | replaced-with | retracts | retracted-by | signs | similar-to | supports | supported-with | transforms | transformed-into | transformed-with | specification-of | created-with | cite-as | summarizes
The type of relationship to the related artifact.
The artifact that is related to this Composition
The artifact that is related to this Composition Resource.
The clinical service(s) being documented
The clinical service, such as a colonoscopy or an appendectomy, being documented.
The event needs to be consistent with the type element, though can provide further information if desired.
Provides context for the composition and creates a linkage between a resource describing an event and the composition created describing the event.
The period of time covered by the documentation. There is no assertion that the documentation is a complete representation for this period, only that it documents events during this time.
The event(s) being documented, as code(s), reference(s), or both
Represents the main clinical acts, such as a colonoscopy or an appendectomy, being documented. In some cases, the event is inherent in the typeCode, such as a "History and Physical Report" in which case the procedure being documented is necessarily a "History and Physical" act. The events may be included as a code or as a reference to an other resource.
An event can further specialize the act inherent in the typeCode, such as where it is simply "Procedure Report" and the procedure was a "colonoscopy". If one or more events are included, they SHALL NOT conflict with the values inherent in the classCode, practiceSettingCode or typeCode, as such a conflict would create an ambiguous situation. This short list of codes is provided to be used as key words for certain types of queries.
This list of codes represents the main clinical acts being documented.
The root of the sections that make up the composition.
A section must contain at least one of text, entries, or sub-sections
text.exists() or entry.exists() or section.exists()
A section can only have an emptyReason if no entries are included
./outboundRelationship[typeCode="COMP" and isNormalActRelationship()]/target[moodCode="EVN" and classCode="DOCSECT" and isNormalAct]
The label for this particular section. This will be part of the rendered content for the document, and is often used to build a table of contents.
The title identifies the section for a human reader. The title must be consistent with the narrative of the resource that is the target of the section.content reference. Generally, sections SHOULD have titles, but in some documents, it is unnecessary or inappropriate. Typically, this is where a section has subsections that have their own adequately distinguishing title, or documents that only have a single section. Most Implementation Guides will make section title to be a required element.
Section headings are often standardized for different types of documents. They give guidance to humans on how the document is organized.
A code identifying the kind of content contained within the section. This must be consistent with the section title.
The code identifies the section for an automated processor of the document. This is particularly relevant when using profiles to control the structure of the document. If the section has content (instead of sub-sections), the section.code does not change the meaning or interpretation of the resource that is the content of the section in the comments for the section.code.
Provides computable standardized labels to topics within the document.
Who and/or what authored the section, when the section is authored by someone other than the composition.author
Identifies who is responsible for the information in this section, not necessarily who typed it in. The actual author of the section when it is not the author of the composition. If author is not specified, the author is assumed to be the author of the parent section or the author of the composition.
Who/what the section is about, when it is not about the subject of composition
The actual focus of the section when it is not the subject of the composition, but instead represents something or someone associated with the subject such as (for a patient subject) a spouse, parent, fetus, or donor. If not focus is specified, the focus is assumed to be focus of the parent section, or, for a section in the Composition itself, the subject of the composition. Sections with a focus SHALL only include resources where the logical subject (patient, subject, focus, etc.) matches the section focus, or the resources have no logical subject (few resources).
Typically, sections in a doument are about the subject of the document, whether that is a patient, or group of patients, location, or device, or whatever. For some kind of documents, some sections actually contain data about related entities. Typical examples are a section in a newborn discharge summary concerning the mother, or family history documents, with a section about each family member, though there are many other examples.
.subject? (CDA did not differentiate between subject and focus)
Text summary of the section, for human interpretation
A human-readable narrative that contains the attested content of the section, used to represent the content of the resource to a human. The narrative need not encode all the structured data, but is required to contain sufficient detail to make it "clinically safe" for a human to just read the narrative.
Document profiles may define what content should be represented in the narrative to ensure clinical safety.
Specifies the order applied to the items in the section entries.
Applications SHOULD render ordered lists in the order provided, but MAY allow users to re-order based on their own preferences as well. If there is no order specified, the order is unknown, though there may still be some order.
Important for presentation and rendering. Lists may be sorted to place more important information first or to group related entries.
What order applies to the items in the entry.
.outboundRelationship[typeCode=COMP].sequenceNumber > 1
A reference to data that supports this section
A reference to the actual resource from which the narrative in the section is derived.
If there are no entries in the list, an emptyReason SHOULD be provided.
.outboundRelationship[typeCode=COMP] or .participation[typeCode=SBJ]
If the section is empty, why the list is empty. An empty section typically has some text explaining the empty reason.
The various reasons for an empty section make a significant interpretation to its interpretation. Note that this code is for use when the entire section content has been suppressed, and not for when individual items are omitted - implementers may consider using a text note or a flag on an entry in these cases.
Allows capturing things like "none exist" or "not asked" which can be important for most lists.
A nested sub-section within this section.
Nested sections are primarily used to help human readers navigate to particular portions of the document.
Modifier extensions allow for extensions that *cannot* be safely ignored to be clearly distinguished from the vast majority of extensions which can be safely ignored. This promotes interoperability by eliminating the need for implementers to prohibit the presence of extensions. For further information, see the [definition of modifier extensions](extensibility.html#modifierExtension).
Classification of a section of a composition/document.
Primary and Secondary Objectives and Estimands
Summarise the primary and secondary objectives and any associated estimands in natural, nontechnical (layperson) language. For trials intended to estimate a treatment effect or test a hypothesis related to a treatment effect, include the primary and secondary objectives and any associated estimands using a nontechnical summary describing the objective and treatment effect of interest (estimand). For other types of trials not intended to estimate a treatment effect or test a hypothesis related to a treatment effect, define trial objectives and describe additional information relevant to the clinical question(s) of interest (e.g., the endpoint(s) associated with each objective). For trials with numerous objectives in which the description of objectives will exceed half a page, consider including the most important objectives and estimands in the synopsis and refer to Section 3 Trial Objectives and Associated Estimands, which covers the objectives and estimands in technical detail. For considerations on estimands, refer to ICH E9(R1).
Key aspects of the trial design include Intervention, Intervention Model, Control Type, Control Description, Intervention Assignment Method, Drug/Device Combination Product Indicator, Population Type, Population Diagnosis or Condition, Population Age (Minimum, Maximum), Site Distribution and Geographic Scope, Master Protocol, and Adaptive Trial Design. Entries should Reference Composition Resource or ResearchStudy Resource.
Enter the numeric value for the number of arms in the trial. For trials with a different number of arms in different periods, populate this field based on the total number of arms.
For designs in which these details may differ in one or more trial periods, answer according to the portion of the trial in which the highest number of blinded roles occurs. More details can be provided in Section 6.6 of the protocol. State: Blinded roles: The following roles indicated will not be made aware of the treatment group assignment during the trial: [blinded roles]. Not applicable (No blinding) indicates an open-label trial.
State the expected number of participants to be assigned to trial intervention/enrolled. Indicate whether the number provided is the target or maximum number of individuals to be randomly assigned to trial intervention/enrolled. A [Target/ Maximum] of Enter Number of Participants participants will be [randomly assigned to trial intervention/ enrolled].
See Template instructions. Select one of the two options for total planned duration of trial intervention and trial participation for each participant. Note that the total duration of trial participation should include any washout and any follow-up periods in which the participant is not receiving trial intervention. When duration will vary, provide a short explanation (for example, “event-driven” or “adaptive design”.
Indicate whether any committee(s) will be reviewing data while the trial is ongoing, and the type of committee. Common examples include Data Monitoring Committee, Dose Escalation Committee, or Endpoint Adjudication Committee; describe others, if applicable. List independent committees in the space indicated. Other committees may be included at the Sponsor’s discretion in the separate space provided. Committees listed here should be fully described in Section 11.4 Committees.
The purpose of this section is to provide a visual depiction of the trial design, orienting users of the protocol to the key features of the design. The schema depicts the trial arms, the flow of individual participant through the progression of trial period(s)/epochs (such as screening, washout/run-in, intervention, and key milestones [e.g., randomisation, cross-over, end of treatment, end of study, post-treatment follow-up]). For complex trials, additional schemas may be added to describe activities or trial periods in greater detail. Entries should Reference SoaPlanDefinition Profile of PlanDefinition Resource.
The schedule of activities must capture the procedures that will be accomplished at each trial visit, and all contact with participants, for example, telephone contacts. This includes any tests that are used for eligibility, participant randomisation or stratification, or decisions on trial intervention discontinuation. Allowable windows should be stated for all visits and procedures. A tabular format is recommended. When applicable for studies with extensive sampling (e.g., serial PK sampling) a separate table may be added. Entries should Reference SoaPlanDefinition Profile of PlanDefinition Resource.
Explain why the trial is needed, and why the research questions being asked are important. Do not restate the objectives or estimands. Do not restate the IB; rather, cross reference to the IB as applicable to the description.
Include an assessment of known and potential risks and benefits, if any, as a result of participating in the trial from the perspective of an individual participant, including the basis of the risk (e.g., nonclinical trials or prior clinical trials). This section may be structured under one single heading 2.2 Assessment of Risks and Benefits, or if applicable under 3 subheadings as 2.2.1 Risk Summary and Mitigation Strategy, 2.2.2 Benefit Assessment and 2.2.3 Overall Risk-Benefit Assessment
You may enter the entire risk summary here or use the subsections for Trial Intervention, Trial Procedures, and Other as noted below.
Trial-specific Intervention Risks and Mitigations
Trial Intervention - Describe risks related to trial-specific treatments and interventions. For the protocol, focus only on the relevant key risks for THIS trial. Provide a brief description of strategies to mitigate identified risks or provide a cross-reference to the relevant protocol section.
Trial-specific Procedure Risks and Mitigations
Trial Procedures - Describe risks associated with the design (e.g., placebo arm) and procedures specific to this trial (e.g., biopsies), and any measures to control or mitigate the risks. Provide a brief description of strategies to mitigate identified risks or provide a cross reference to the relevant protocol section. This is not intended to be an exhaustive list of all possible risks associated with trial procedures but should focus on the unique risks inherent in the design or less common or high-risk procedures. As above, provide a brief description of strategies to mitigate identified risks or provide a cross reference to the relevant protocol section.
Trial-specific Other Risks and Mitigations
Other - Consider risks associated with other items (for example, comparators, challenge agents, imaging agents, medical devices). This could include discussion of risk mitigation for special populations, if not described elsewhere. Insert a line for each, as needed.
The benefit summary should describe any physical, psychological, social, or any other potential benefits to individual participants as a result of participating in the trial, addressing immediate potential benefits and/or long-range potential benefits. Clearly state if no benefits to an individual participant can be anticipated, or if potential benefits are unknown. For early clinical trials such as Phase 1 or trials in healthy participants, benefits for an individual participant (other than those of altruism) are expected to be minimal. Benefits to society in general may also be included but should be described separately from the individual participant perspective.
Provide a succinct, concluding statement on the perceived balance between risks that have been identified from cumulative safety data, protocol procedures, and anticipated efficacy/benefits within the context of the proposed trial.
Trial Objectives and Associated Estimands
Describe the overall trial design and intervention model (e.g., single group, parallel group, cross-over, factorial, sequential), the expected number of participants, and the control method (e.g., placebo, active comparator, low dose, external, standard of care, sham procedure, or none [uncontrolled]). If there are any key aspects of the investigational trial intervention that inform the selection of the intervention model, this should be described. If applicable, indicate other design characteristics (e.g., superiority, noninferiority, dose escalation, or equivalence). If the trial will have an adaptive or novel design (e.g., the trial will be conducted under a master protocol), provide a summary of these design aspects. If applicable, describe within-trial transition rules, e.g., transitions involving cohorts or trial parts. Dose escalation or dose-ranging details should also be described. Describe the trial duration with reference to Section 1.2 Trial Schema. Explain what the overall duration for an individual participant is anticipated to be and why, including the sequence and duration of trial periods (e.g., screening, run-in, randomisation, treatment [fixed dose/titration], follow-up/washout periods). Where applicable, include discussion of sentinel dosing (or lack thereof), dose escalation, and cohort expansion. If dose modification decisions are dependent upon review by a committee, include details in Section 11.4 Committees. State the method of assignment to trial intervention the level and method of blinding that will be used with reference to Section 6.7 Investigational Trial Intervention Assignment, Randomisation and Blinding. Describe any other important aspects of the design, e.g.: • geographic scope of trial (e.g., single-centre, multi-centre, or multi-centre and multi-national) • use of decentralised processes, tools, or features in the trial • planned use of a Data Monitoring Committee, or similar review group and cross reference Section 11.4 Committees, for details • whether an interim analysis is planned; if so, refer to details in Section 10.9 Interim Analyses • any planned extension trial, long-term follow-up/registry, planned future use of samples or data, or post-trial sample analysis or other data-related activities
If applicable, describe any stakeholder (for example, patient, healthcare professional and patient advocacy groups) involvement in the design of the trial and any suggestions implemented.
Enter Overall Rationale for Trial Design if not using below optional subheadings.
When estimands are associated with the Primary and Secondary Objectives described in Section 3 Trial Objectives and Associated Estimands, provide a rationale for the estimand(s) not described elsewhere in the document. This should include a rationale that the selected endpoint(s) are clinically relevant and provide a reliable and valid measurement of the intended intervention effect. It should also include a rationale for the selected strategies for handling intercurrent events.
Provide a rationale for the trial intervention model described in Section 4.1 Description of Trial Design with a cross reference to Section 6.2 Rationale for Investigational Intervention Dose and Regimen. Rationale for choice of comparator, if applicable, should be described separately in Section 4.2.5 Rationale for Control Type. A rationale for the choice of trial population should be described separately in Section 5.1 Description of Trial Population and Rationale.
If applicable, provide a rationale for the type and choice of control selected for the trial (e.g., placebo, active drug, combination, external). Describe any known or potential problems associated with the control group selected in light of the specific disease and intervention(s) being studied. If comparators will differ by region, describe. The rationale for dose/dose regimen is explained in Section 6.2 Rationale for Investigational Trial Intervention Dose and Regimen.
Provide a rationale that the trial duration is appropriate for a reliable and relevant evaluation of the trial intervention per the trial objective(s).
Rationale for Adaptive or Novel Trial Design
If applicable, provide a rationale for the use of an adaptive or novel design.
If applicable, provide a rationale for any interim analysis planned with respect to its purpose (for example, stopping the trial early for efficacy or futility) and timing.
Rationale for Other Trial Design Aspects
Discuss rationale for any additional aspects of the design not addressed above.
If applicable, describe any trial-specific stopping rules, including guidance on when the trial should be stopped for safety reasons, when a cohort or dose escalation should be terminated, and/or when a given treatment arm should be terminated. If applicable, describe any rules that may result in a temporary pause of dosing and/or enrollment into the trial and criteria for restarting enrollment. Ensure that the trials stopping rules are aligned with the specifications that are described in Section 10.9 for Interim Analyses.
Define key timepoints in the trial, including trial start and end definitions (e.g., a key timepoint definition for start of trial might be when the informed consent is signed by the first participant and a key timepoint definition for end of trial might be when participants are no longer being examined or the last participant’s last trial assessment has occurred). Consider local regulatory requirements for these and other definitions (e.g., the first act of recruitment). If appropriate, provide a cross reference to Section 11.11 Early Site Closure.
Access to Trial Intervention After End of Trial
If applicable, describe any possibilities for access to trial intervention, if any, beyond completion of the trial. Planned extension trials, if described in Section 4.1 Description of Trial Design, do not need to be repeated in this section.
Description of Trial Population and Rationale
Describe the population selected (e.g., healthy participants, adult participants, paediatric participants, pregnant participants, or breastfeeding participants) and how the enrollment criteria reflect the populations that are likely to use the drug if approved. Specify the population age range (e.g., ≤3 months, ≥18 to ≤80 years old) including the time point at which qualification for age criteria is determined (e.g., at time of screening vs randomisation for paediatric trials). Specify any key diagnostic criteria for the population (e.g., “acute lung injury”, or a specific biomarker profile). If applicable, describe similar conditions or diseases and their differential diagnosis. Provide a rationale for the trial population ensuring that the population selected is well defined and clinically recognisable. Describe how the selected population can meet the trial objectives and how the enrollment criteria reflect the population of interest. If the population targeted by a clinical question is based on a subset of the entire trial population, e.g., defined by a particular characteristic measured at baseline (e.g., a specific biomarker), this subset should be justified in this section. Justify whether the trial intervention is to be evaluated in paediatric participants, in adults unable to consent for themselves, other vulnerable participant populations, or those that may respond to the trial intervention differently (e.g., elderly, hepatic or renally impaired, or immunocompromised participants). Entries should Reference CohortDefinition (or StudyEligibilityCriteria) Profile of Group Resource.
Inclusion criteria are characteristics that define the trial population, for example, those criteria that every potential participant must satisfy to qualify for trial enrollment. Entries should Reference CohortDefinition (or StudyEligibilityCriteria) Profile of Group Resource.
Exclusion criteria are characteristics that make an individual ineligible for participation. Entries should Reference CohortDefinition (or StudyEligibilityCriteria) Profile of Group Resource.
Definitions Related to Childbearing Potential
Specify the definitions of: • participant of childbearing potential, and • participant of nonchildbearing potential.
Specify the: • contraceptive methods required, and • duration of use.
In the following subsections, describe any restrictions during the trial pertaining to lifestyle and/or diet, intake of caffeine, alcohol, or tobacco, or physical and other activities. If not applicable, include a statement that no restrictions are required.
If applicable, describe any restrictions on diet (for example, food and drink restrictions, timing of meals relative to dosing).
Caffeine, Alcohol, Tobacco, and Other Restrictions
If applicable, describe any restrictions on the intake of caffeine, alcohol, tobacco, or other restrictions.
If applicable, describe any restrictions on activity (for example, in first-in-human trials, activity may be restricted by ensuring participants remain in bed for 4 to 6 hours after dosing).
If applicable, describe restrictions on any other activity (for example, blood or tissue donation); or any other activity restrictions, such as on driving, heavy machinery use, or sun exposure.
Describe screen failure and indicate how screen failure will be handled in the trial, including conditions and criteria upon which rescreening is acceptable. If applicable, indicate the circumstances and time window under which a repeat procedure is allowed for screen failure relating to specific inclusion/exclusion criteria for the trial.
Trial Intervention and Concomitant Therapy
Trial interventions are all pre-specified investigational and noninvestigational medicinal products, medical devices or other interventions intended for the participants during the trial. The investigational trial intervention is the product used in the trial as part of trial objectives. Description of the investigational trial intervention is provided in Section 6.1 Description of Trial Intervention. Other trial interventions that are not part of trial objectives or do not have an investigational role in this trial are described in Section 6.9 Description of Noninvestigational Trial Interventions. Any regional requirements should be noted in the appropriate subsections. Provide an overview of investigational and noninvestigational trial interventions. Classify the trial intervention as IMP, NIMP/AxMP designations based on trial design and regional requirements. Consider an optional table with 12 columns (Arm Name, Arm Type, Intervention Name, Intervention Type, Pharmaceutical Dose Form, Dosage Strength(s), Dosage Level(s), Route of Administration, Regimen/Treatment Period/Vaccination Regimen, Use, IMP/NIMP, Sourcing).
Description of Investigational Trial Intervention
Describe the investigational trial intervention to be administered in each arm of the trial and for each period of the trial including route and mode of administration, dose, dosage regimen, duration of intervention, use, packaging and labelling. Refer to approved regional labelling, as appropriate. For investigational drug/device combination products, include details on the configuration and use of the device and device manufacturer. A device user manual may be referenced in this section. Entries should Reference ConceptualExposureDefinition Profile of Group Resource.
Rationale for Investigational Trial Intervention Dose and Regimen
Provide a rationale for the selection of the dose(s) or dose range, pharmaceutical dose form, route of administration, and dosing regimen of the investigational trial intervention, as applicable. This rationale should include relevant results from nonclinical studies and clinical trials that support selection of the dose and regimen. Discuss impact of differences in trial population characteristics (e.g., age, sex, race) which could lead to differences in pharmacokinetics and pharmacodynamics in this trial as compared to previous trials. If applicable, justify any differences in dose regimen or therapeutic use relative to approved labelling. Describe prior trials and other information that support the dose and/or dose regimen of the investigational trial intervention. Include a rationale for prospective dose adjustments incorporated in the trial, if any. Entries should Reference ConceptualExposureDefinition Profile of Group Resource.
Investigational Trial Intervention Administration
Describe the detailed procedures for administration of each participant’s dose of each investigational trial intervention. This may include the timing of dosing (e.g., time of day, interval), the duration (e.g., the length of time participants will be administered the investigational trial intervention), and the timing of dosing relative to meals. Include any specific instructions on who, when or how to prepare and take the dose(s) and how to handle any delayed or missed doses. Dose escalation or cohort expansion as part of the overall design should be covered in Section 4.1 Description of Trial Design. Entries should Reference ActivityDefinition Resource.
Investigational Trial Intervention Dose Modification
For each participant, describe any dose modifications allowed, including conditions for such dose modifications, particularly regarding failure to respond or safety concerns. State any minimum period required before a participant’s dose might be raised to the next higher dose or dose range. Include whether it is permissible to start and stop treatment and how dose reductions (if permitted) are to be managed. Information on stopping investigational trial intervention for participants due to safety/other reasons should be described in Section 7 Participant Discontinuation of Trial Intervention and Discontinuation or Withdrawal from Trial. Entries should Reference ActivityDefinition Resource.
Management of Investigational Trial Intervention Overdose
Describe what is meant by investigational trial intervention overdose. Provide any available information on managing the overdose and ensure it is consistent with the Investigator’s Brochure or product labelling. Cross reference these documents as applicable. Entries should Reference ActivityDefinition Resource or PlanDefinition Resource.
Preparation, Storage, Handling and Accountability of Investigational Trial Intervention
Preparation of Investigational Trial Intervention
Describe any preparation of the investigational trial intervention, and when necessary, who should prepare it. When applicable, describe the maximum hold time once thawed/mixed before administration. Include thawing, diluting, mixing, and reconstitution/preparation instructions. For drug/device combination products, include any relevant assembly or use instructions and reference the package insert that is provided separately. If the instructions are lengthy or complicated, it is acceptable to reference the package insert (if applicable) or include instructions in separate documents provided to the site (e.g., a pharmacy manual and reference the separate documents.
Storage and Handling of Investigational Trial Intervention
Describe storage and handling requirements (e.g., protection from light, temperature, humidity) for the investigational trial intervention(s). For trials in which multi-dose vials are utilised, provide additional information regarding stability and expiration time after initial use (e.g., if the seal is broken). Explain how the investigational trial intervention will be provided to the Investigator. If applicable, include details about kits, packaging, or other material of the investigational trial intervention for blinding purposes. If the instructions are lengthy or complicated, it is acceptable to reference the package insert (if applicable) or include instructions in separate documents provided to the site (e.g., a pharmacy manual) and reference the separate documents.
Accountability of Investigational Trial Intervention
Describe the accountability method, including: • how the investigational trial intervention will be distributed • who will distribute the investigational trial intervention • participation of a drug storage repository or pharmacy, if applicable • plans for disposal or return of unused product • if applicable, plans for reconciliation of investigational trial intervention
Investigational Trial Intervention Assignment, Randomisation and Blinding
Participant Assignment to Investigational Trial Intervention
State that at enrollment, participant identification codes should be assigned. Describe the method of assigning participants to investigational trial intervention without being so specific that blinding or randomisation might be compromised. If assignment to investigational trial intervention is by randomisation, describe when randomisation occurs relative to screening. If adaptive randomisation or other methods of covariate balancing/minimisation are employed, include a cross reference to the methods of analysis in Section 10 Statistical Considerations. As applicable, details regarding the implementation of procedures to minimise bias should be described.
Describe the randomisation procedures (e.g., central randomisation procedures), the method used to generate the randomisation schedule (e.g., computer generated), the source of the randomisation schedule (e.g., sponsor, investigator, or other), and whether IxRS will be used. To maintain the integrity of the blinding, do not include the block size.
Describe efforts to maintain blinding: • The investigational trial interventions are as indistinguishable as possible • Plans for the maintenance of randomisation codes and appropriate blinding for the trial • Procedures for planned (e.g., interim analysis), and unintentional (e.g., breach of procedure) breaking of randomisation codes. For unplanned but intentional actions (e.g., safety events), refer to Section 6.7.4 Emergency Unblinding at the Site. If the trial allows for some investigators or other designated staff to remain unblinded (e.g., to allow them to adjust investigational trial intervention), the means of maintaining the blinding for other investigators or staff should be explained. Measures to prevent unblinding by laboratory measurements or while performing study assessments, if used, should be described.
Describe the criteria for breaking the trial blind or participant code. Describe the circumstances in which the blinding would be broken for an individual or for all participants and who has responsibility. Include the procedure for emergency unblinding such as via IxRS or code envelopes as well as documentation of unblinding. Indicate to whom the intentional and unintentional unblinding should be reported.
Investigational Trial Intervention Adherence
Describe the measures to monitor and document participants’ adherence with investigational trial intervention (e.g., trial intervention accountability records, diary cards, or investigational trial intervention concentration measurements). List what documents are mandatory to complete (e.g., participant drug log) and what source data/records will be used to document investigational trial intervention adherence.
As stated in Section 6 Trial Intervention and Concomitant Therapy, noninvestigational interventions are pre-specified products used in the trial but are not part of trial objectives and hence, are not investigational trial interventions.
Describe any background intervention(s), including administration and any conditions for use.
List all permitted rescue medications, treatments, and/or procedures, including any relevant instructions on administration and any conditions of use. If administration of rescue therapy leads to the temporary discontinuation of trial intervention or a participant’s withdrawal from the trial, refer to Section 7 Participant Discontinuation of Trial Intervention and Discontinuation or Withdrawal from Trial.
Other Noninvestigational Trial Intervention
If applicable, describe the use of any other noninvestigational trial intervention, e.g., challenge agents or diagnostics.
Specify the concomitant medications, supplements, complementary and alternative therapies, treatments, and/or procedures which are prohibited or permitted during the trial and include details about when the information will be collected (e.g., during screening, at each visit). When appropriate to separate the content, subheadings may be used.
If applicable, describe any prohibited concomitant therapy.
If applicable, describe any permitted concomitant therapy.
Participant Discontinuation of Trial Intervention and Discontinuation or Withdrawal from Trial
Discontinuation of Trial Intervention for Individual Participants
Permanent Discontinuation of Trial Intervention
Describe: • the criteria for discontinuation of a participant from any trial intervention, carefully evaluating which are appropriate for the trial population and therapy being studied • how participants who discontinue trial intervention will be followed after discontinuation. Depending on the chosen intercurrent event handling strategy, it will be important to continue to follow and ascertain outcomes in participants who discontinue treatment through the end of the trial to prevent missing data in important analyses. Refer to Section 1.3 Schedule of Activities for assessments to be performed at the time of and following discontinuation of trial intervention • the process for collecting and recording the detailed reasons for discontinuing trial intervention if not described elsewhere
Temporary Discontinuation of Trial Intervention
Describe: • the criteria for temporary discontinuation or interruption of trial intervention for an individual participant • what to do and which restrictions still apply if the participant has to temporarily discontinue or interrupt trial intervention • whether the participant will continue in the trial • which assessments will be performed for the stated duration of the trial. Details of any rechallenge or restart after a safety-related event should be included in Section 7.1.3 Rechallenge.
Describe the criteria for rechallenge/restarting trial intervention, how and when to perform rechallenge, number of rechallenges allowed during the trial, and whether all, or specify which, assessments will be performed for the stated duration of the trial. If rechallenge is not allowed, state this.
Discontinuation or Withdrawal from the Trial
Describe the criteria for participant discontinuation or withdrawal from the trial. Describe the reason for withdrawal and the type of data to be collected for the final assessments with reference to the schedule of activities for the participant’s end of study visit unless provided in another section. In many cases, the only reason for a participant being considered withdrawn from the trial should be a participant’s withdrawal of consent to continue to participate in the trial. All other participants, including those who discontinue treatment, should remain in the trial and continue to be followed to prevent missing data in important analyses. Refer to Section 10 Statistical Considerations for the data that must be collected for the trial estimands.
Describe how the trial will define how participants are lost to follow-up. In general, participants should be considered lost to follow-up only if they cannot be reached despite multiple attempts to contact. Also describe approaches that will be used to minimise loss to follow-up, such as multiple, diverse methods to remain in contact with participants (e.g., telephone calls, texts, and emails to the participant) and how contacts will be recorded.
Trial Assessments and Procedures Considerations
Describe general considerations applicable across trial assessments and procedures.
Screening/Baseline Assessments and Procedures
Describe any assessments and procedures that are unique to screening/baseline (e.g., collection of data on participant characteristics, assessments/procedures performed for the purpose of determining eligibility or for stratification) in this section. Describe screening and baseline assessments and procedures separately when screening and baseline are different or performed at different visits.
Describe efficacy assessments and procedures in this section. Cross reference Section 8.7 Immunogenicity Assessments if immunogenicity assessments are used in efficacy determination.
Describe safety assessments and procedures utilizing the following subsections as applicable. Add level 3 headings as needed. • Identify any noninvestigator party responsible for evaluation of laboratory or other safety assessments (e.g., Sponsor or external Independent Data Monitoring Committee; cross refer to Section 11.4 Committees for details as applicable). • Include guidelines for the medical management of relevant laboratory or other safety assessment abnormalities.
Include any specific instructions for the collection and interpretation of physical examinations.
Include any specific instructions for the collection and interpretation of vital signs.
Include any specific instructions for the collection, interpretation, and archiving of ECGs.
Describe any specific instructions for the collection and interpretation of clinical laboratory assessments, including: • type of laboratory (central/local/hybrid) • acceptability of additional tests deemed necessary by the investigator or local regulations • instructions for situations in which central laboratory results are not available in time for trial intervention and/or response evaluation, or in the event of a severe disruption (e.g., a pandemic or natural disaster) • treatment algorithms for results out of normal range • cross reference Section 12.1 Clinical Laboratory Tests for laboratory assessment panels
Include any specific instructions for the collection and interpretation of pregnancy testing.
Suicidal Ideation and Behaviour Risk Monitoring
If the trial meets any of the criteria requiring suicidal ideation and behaviour risk monitoring by the guidance/guideline in each region, include justification for the need for suicidal ideation and behaviour risk monitoring in the study and add any specific instructions for the collection and interpretation of the assessment. In case this is an AESI in the study, justification should also be provided in Section 9.2.4 Adverse Events of Special Interest.
Include any specific instructions for the collection and assay of samples and interpretation of PK assessments. • Describe the biological samples collected, the handling of samples, and the assay method. o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of analyses for each sample. • Define the PK parameters to be calculated and the calculation methods.
No text is intended here (header only). Include any specific instructions for the collection of samples and assessment of biomarkers, including pharmacodynamics. If biomarker or pharmacodynamic testing is not included in the study, state “Not Applicable.” • Describe the biological samples that will be collected (for example, tissue, serum, plasma, etc.). o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross-referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of biomarkers that will be studied for each sample. • Specify whether each sample is optional or required. Required samples must be based on a protocol objective.
Include any specific instructions for the collection and assay of samples for genetic and/or pharmacogenomic analysis. • Describe the biological samples that will be collected (for example, tissue, serum, plasma, etc.), handling of samples, and the assay method. o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross-referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of analyses that may be studied for each sample.
Include any specific instructions for the collection of samples and assessment of pharmacodynamic biomarkers. • Describe the biological samples that will be collected (for example, tissue, serum, plasma, etc.). o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross-referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of biomarkers that will be studied for each sample. • Specify whether each sample is optional or required. Required samples must be based on a protocol objective.
Include any specific instructions for the collection of samples and assessment of other biomarkers. • Describe the biological samples that will be collected (for example, tissue, serum, plasma, etc.). o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross-referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of biomarkers that will be studied for each sample. • Specify whether each sample is optional or required. Required samples must be based on a protocol objective.
Include any specific instructions for the collection of samples and interpretation of immunogenicity. If immunogenicity assessments are included within Efficacy Assessments or Safety Assessments, cross-reference to that section. • Describe the biological samples that will be collected (e.g., tissue, serum, plasma). o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of biomarkers that will be studied for each sample. • Specify whether each sample is optional or required. Required samples must be based on a protocol objective.
Medical Resource Utilisation and Health Economics
This section does not apply to COAs. Include this section only for any value evidence and outcomes assessments not included in either the efficacy or safety sections. Describe the health outcome measures, collection method (e.g., diary, physician interview), and participant burden.
Adverse Events, Serious Adverse Events, Product Complaints, Pregnancy and Postpartum Information, and Special Safety Situations
Specify the AE definitions, including: • any relevant regional AE requirements • any events that meet and do not meet the AE definition • any trial-specific AE clarifications • if applicable, any clarifications on the AE and SAE definitions for efficacy trials (e.g., lack of efficacy or failure of pharmacological actions reporting)
Specify the SAE definitions, including: • Any relevant regional SAE requirements. • Any events that meet and do not meet the SAE definition. • Any trial-specific SAE clarifications.
Specify the definition of product complaints in the context of the trial. If appropriate, include 9.1.3.1 Definition of Medical Device Product Complaints.
Timing and Procedures for Collection and Reporting
Specify timing and procedures for collection and reporting of AEs, SAEs, product complaints (including medical device product complaints if applicable) and pregnancy and postpartum information in the sections below. This information may be summarized in a tabular format with 7 columns: Event Type, Situational Scope, Reportable Period Start, Reportable Period End, Timing for Reporting to Sponsor or Designee, Method for Reporting, Back-up Method for Reporting.
Specify timing for collection and reporting, including: • start and end dates for collection and reporting • frequency of collection and reporting • cross reference to the Schedule of Assessments as appropriate
Specify procedures for collection and recording of AEs, SAEs, product complaints (including medical device product complaints if applicable) and pregnancy and postpartum information in the sections below.
Specify how information will be identified (e.g., spontaneous reporting, solicited questions).
Specify the intensity rating categories/scale.
Specify the causality categories/scale and the procedures for assessing causality.
Specify the procedures for follow-up. Include the assessment tools that will be used to monitor the events and the duration of follow-up after appearance of the events.
Specify the reporting method (e.g., an electronic data collection tool or a paper CRF), backup reporting method if applicable and reporting timeline to the Sponsor
Specify: • the Investigator’s responsibilities for reporting to the Sponsor (and to Ethics Committees, where required), specifying timing of reporting to allow the Sponsor to meet their responsibilities • the Sponsor’s legal/regulatory responsibilities to report to regulatory authorities, ethics committees, and investigators • serious and unexpected adverse reaction reporting
Specify any AESI: • any event (serious or nonserious) of scientific and medical concern relative to the trial intervention, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate • other events that merit reporting to the Sponsor, trial leadership, IRB, and regulatory agencies. Include the following for each AESI: • the definition • the approach for ascertaining information • if applicable, any approach to confirm or adjudicate the occurrence
Disease-related Events or Outcomes Not Qualifying as AEs or SAEs
Specify any DREs, DROs, or both that will not be reported as AEs or SAEs (e.g., seizures in anticonvulsant trials) or state “Not applicable.”
Participants Who Become Pregnant During the Trial
Specify: • the assessments to be performed • type and duration of monitoring • whether participants who become pregnant during the trial may continue with trial intervention or must be discontinued from trial intervention (refer to Section 7 Participant Discontinuation of Trial Intervention and Discontinuation or Withdrawal from Trial as applicable) • any trial modifications that need to be made for participants who become pregnant • what information will be collected about a participant who becomes pregnant during the trial (e.g., recording and reporting to the Sponsor, postpartum follow-up, trial intervention discontinuation or continuation, or trial withdrawal). For postpartum follow-up, include the time period (e.g., initial child development) with the justification. If exposure to trial intervention during breastfeeding is applicable, specify: • the assessments to be performed • type and duration of monitoring • what information will be collected for both the participant and child
Participants Whose Partners Become Pregnant
Specify: • if the investigator will attempt to collect pregnancy information about a participant’s partner, who becomes pregnant during the specified period in the trial • whether the participant whose partner becomes pregnant should be discontinued from trial intervention (refer to Section 7 Participant Discontinuation of Trial Intervention and Discontinuation or Withdrawal from Trial as applicable) • the assessments to be performed, type and duration of monitoring, and the information to be collected
Specify special safety situations associated with the trial intervention(s) that do not qualify as an AE or SAE, but require regulatory reporting. Examples include: • misuse or abuse • off-label use (if applicable) • medication error (prescription or dispensing error) • occupational exposure • use outside of what is foreseen in the protocol • unintended exposure of embryo, foetus, or child via maternal exposure (pregnancy or breastfeeding) or via paternal exposure (semen) • lack of therapeutic efficacy; this is not applicable for studies that measure efficacy as a study endpoint • suspected transmission of an infectious agent; this is only applicable for injected or biologic medicinal products • product complaint, including falsified or counterfeit products • suspected drug-food or drug-drug interaction
Ensure that the data analysis complies with ICH E9 Guideline and ICH E9(R1) Guideline. In general, all relevant data collected in the trial should be considered in this section. No text is intended here (header only).
Provide general statements related to statistical considerations, such as whether a separate statistical analysis plan exists, which summary statistics will be provided, and the timing of analyses (e.g., “The analysis will include all participant data at trial completion”).
Describe analysis sets to be considered at the trial level, i.e., the set of participants whose data are to be included in the analyses, aligned with estimands. Clearly specify the analysis set to be used for each analysis described in Section 10 Statistical Considerations.
Analyses of Demographics and Other Baseline Variables
Describe the summary statistics that will be used to characterize the distribution of demographic and other relevant variables at baseline. Specify when the variables are measured (e.g., at trial inclusion, prior to randomisation, or at the time of randomisation). Relevant variables include but are not limited to: stratification variables specified in Section 6.7 Investigational Trial Intervention Assignment, Randomisation and Blinding, covariates for the statistical models specified in Section 10.4 Analyses Associated with the Primary Objective(s), other suspected predictive or prognostic variables, and variables used for planned subgroup analyses.
Analyses Associated with the Primary Objective(s)
No content here. Create a new section for each estimand.
Describe the statistical analysis methods that will be used to evaluate the primary objective(s) and associated estimand(s) in Section 3.1 Primary Objective(s) and Associated Estimands. Ensure that the statistical hypothesis/model/analysis (and corresponding assumptions) is aligned with the primary estimand(s). For each objective, when applicable, state the null and alternative hypotheses, including the pre-planned type 1 error rate, or alternative criteria for evaluating whether the objective has been met, and relevant operating characteristics if appropriate. Describe the statistical model used and the factors that will be included (covariates and interactions) and any rules for handling these factors (e.g., pooling of centres). If modelling and simulation methods are to be used, describe the model (inputs and outputs), the underlying assumptions, and the method of model fitting. Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.
Handling of Data in Relation to Primary Estimand(s)
For each intercurrent event of the primary estimand(s) (Section 3.1 Primary Objective(s) and Associated Estimands), explain how data will be handled for the statistical analysis in line with the primary estimand. The handling of intercurrent events in the statistical analysis should be aligned with the specific estimand strategies being used. This section should describe in more detail the rationale and handling of the data rather than repeating information from the preceding sections.
Handling of Missing Data in Relation to Primary Estimand(s)
Describe how missing data will be addressed (e.g., imputation method and model), state the underlying assumptions, and provide a rationale for the approach.
Describe any sensitivity analyses and how their assumptions changed from the assumptions of the main statistical analysis. Sensitivity analyses are a series of analyses conducted with the intent to explore the robustness of inferences from the main estimator to deviations from its underlying modelling assumptions and limitations in the data. Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.
Describe any supplementary analysis, if applicable. Supplementary analyses are conducted in addition to the main and sensitivity analysis with the intent to provide additional insights into the understanding of the treatment effect.
Analyses Associated with the Secondary Objective(s)
No content here. Create a new section for each estimand. Unless there is no secondary objective, in which case indicate 'Not applicable.'
Clearly specify any secondary hypotheses that will be tested for confirmatory purposes. Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.
Handling of Data in Relation to Secondary Estimand(s)
Enter Handling of Data in Relation to Secondary Estimand(s)
Handling of Missing Data in Relation to Secondary Estimand(s)
Describe how missing data will be addressed (e.g., imputation method and model), state the underlying assumptions, and provide a rationale for the approach. Refer to the E9(R1) addendum when the estimand framework is used.
Describe sensitivity analyses. Sensitivity analyses are a series of analyses conducted with the intent to explore the robustness of inferences from the main estimator to deviations from its underlying modelling assumptions and limitations in the data. Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.
Describe any supplementary analysis if applicable. Supplementary analyses are conducted in addition to the main and sensitivity analysis with the intent to provide additional insights into the understanding of the treatment effect.
Analyses Associated with the Exploratory Objective(s)
Describe any exploratory analyses, if applicable. Additional subsections may be created to describe the analyses for each exploratory objective, as needed. If there is no exploratory objective, indicate “Not applicable”.
If safety is a primary and/or secondary objective, describe the corresponding safety analyses in the appropriate section above (Section 10.4 Analyses Associated with the Primary Objective(s) or Section 10.5 Analyses Associated with the Secondary Objective[s]). In this section, describe statistical methods that will be used to analyse relevant safety outcomes, including any AESI. This should typically include specification of a measure to estimate risk within treatment arms, a measure to compare risks across treatment arms, and a measure of statistical uncertainty around the comparison such as a confidence interval.
Describe other analyses not included in Sections 10.3-10.7, such as subgroup analyses.
Multiple testing procedures may be needed to limit the probability of false positive findings in a trial. Reasons for carrying out multiple statistical tests include - but are not restricted to - multiple endpoints, multiple treatment groups, multiple hypotheses, subgroups, multiple timepoints. Describe any approaches to multiplicity control for the trial. This description might go beyond the analysis of primary objectives. Specify the statistical approach to control the overall type I error rate as well as the (adjusted) significance levels to test specific hypotheses, as applicable. Clarify whether the tests/confidence intervals are one- or two-sided. State the circumstances under which a trial will be considered to have met its primary objective(s). For example, in a study with two primary efficacy endpoints, this section should state whether the study would be expected to provide statistical evidence on at least one or on both of the endpoints in order to confirm the efficacy of the treatment. For some statistical approaches it might be helpful to include a graphical depiction, as visualisation will be helpful for understanding, coupled with the clinical translation of the mathematical choices. Details regarding interim analyses should be provided in Section 10.9 Interim Analyses.
Describe any interim analyses and criteria for stopping or adapting the trial. Ensure alignment with Section 4.3 Trial Stopping Rules. The description should include, but is not limited to, the following. Under circumstances where interim analysis details could impede the integrity of the trial, some of the information can be added in other documents outside of the protocol. • any planned interim analysis, even if it is only to be performed at the request of an oversight body (for example, DMC) • the purpose of the interim analysis, including whether the interim analysis may be used for stopping and/or for other trial adaptations such as sample size re-estimation, alteration to the proportion of participants allocated to each trial group, or changes to eligibility criteria • the applied statistical method; e.g., group sequential test and spending function (e.g., O’Brien-Fleming), as applicable • the parties responsible for performing and reviewing the results of the analyses (e.g., DMC, independent statistician) • when the analyses will be conducted (timing and/or triggers) • the decision criteria—statistical or other—that will be adopted to judge the interim results as part of a guideline for early stopping or other adaptations • who will see the outcome data while the trial is ongoing • whether these individuals will remain blinded to trial groups • how the integrity of the trial implementation will be protected (e.g., maintaining blinding) when decisions are made after interim analyses (e.g., a decision to continue the trial or implement a specific adaptation)
This section should detail the methods used for the determination of the sample size. The sample size calculation should be aligned with the primary estimand and the primary analysis, otherwise a justification is needed. Details of sample size calculation should include all relevant information to enable reproduction of the sample size, e.g.,: • referencing any prior studies on which assumptions were based • significance level (including information on the choice of one- or two-sided level) • power • assumed treatment effect and variability • how dropout rate and intercurrent events have been incorporated into sample size calculation • precision of estimator/length of confidence interval. Any assumptions made should be stated and justified. Further analysis of how deviations from the assumptions will affect the sample size should be included. If complex simulations were used to calculate the sample size, consider including details in a separate simulation report as an appendix to the protocol. If the planned sample size is not derived statistically, then this should be explicitly stated along with a rationale for the intended sample size (e.g., exploratory nature of pilot trials; pragmatic considerations for trials in rare diseases). Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.
Trial Oversight and Other General Considerations
Provide a high-level statement on the prevailing ethical, legal, and regulatory guidelines that will be applied throughout the trial. For example, This trial will be conducted in accordance with the protocol and with the following: • Ethical principles that have their origin in the Declaration of Helsinki for medical research involving human subjects • Consensus ethical principles derived from international guidelines including the Declaration of Helsinki and the Council for International Organisations of Medical Sciences (CIOMS) International Ethical Guidelines • ICH Good Clinical Practice (GCP) Guidelines • Applicable laws and regulations
Concisely summarize the trial oversight listing the investigator and sponsor responsibilities not covered in other sections of the protocol which are essential for the operations of the trial, specifying the ones related to quality assurance.
Describe the investigator duties, including the oversight of duties delegated to a third party that may impact the trial conduct at sites, if applicable and if not addressed elsewhere.
Describe the sponsor duties, including those to be transferred to a third party that may impact the investigators sites, if applicable.
Briefly describe the administrative structure of committees that will be reviewing data while the trial is ongoing, and the type of committee (e.g., Dose Escalation Committee, Data Monitoring Committee or Data Safety Monitoring Board). Note that specific details may be required depending on local law or regulation. If applicable, Committee Charters may be cross referenced. If no committees are involved, state “Not applicable.”
Specify the key elements of the informed consent process, including any special needs and how these are addressed (for example, assent, capacity, legally acceptable representative, adolescents who may reach age of majority during the trial, pregnant participants and pregnant partners of participants)
If enrollment in the trial may occur during an emergency in which the participant or their legally acceptable representative is not able or available to give consent, describe the consent process.
If participants can be rescreened as described in Section 5.6, state whether the participant needs to complete a new consent. Screen failure and rescreening should be clearly defined in the protocol, with cross reference to those definitions.
Informed Consent for Remaining Samples in Exploratory Research
If participants will be asked to consent to optional exploratory research using the remainder of mandatory samples, describe the use of remaining samples for optional exploratory research. If any exploratory research is planned and additional written consent regarding the use of remaining samples for exploratory research will be obtained, describe the consent process.
Concisely summarize the arrangements for participants insurance and indemnity if not addressed in a separate agreement, if required by the applicable regulatory requirements.
Describe the identified critical to quality factors, associated risks and risk mitigation strategies in the trial or refer to a separate document where this is described.
Describe the key processes for critical trial integrity, traceability and security including a summary of the monitoring approaches enabling accurate collection, reporting, monitoring, transfer, retention, and access if not addressed in separate agreement(s).
Describe the measures to protect the privacy and confidentiality of personal information of trial participants in accordance with applicable regulatory requirements on personal data protection and any measures that should be taken in case of a data security breach.
Establish the importance of source data and expectation for traceability of transcribed information back to source. Delineate expectations for investigators (e.g., maintain source data at the site, ensure availability of current records) and trial monitors (e.g., verify CRF data relative to source, ensure that safety of participants is being protected and that conduct is in accordance with GCP). Identify what constitutes source data and its origin or provide a reference to the location of this information, if contained in a separate document, such as a monitoring guideline or source data acknowledgement). Describe the provision for direct access to source data and documents enabling clinical trial-related monitoring, audits and regulatory inspections, if not included in separate agreement(s).
Describe plans for detecting, reviewing, and reporting any deviations from the protocol or include reference to a separate document.
List the sponsor's rights to close a site. Likewise, list the investigator's rights to initiate early site closure.
List the criteria for early closure of a site by the sponsor or investigator.
Responsibilities Following Early Site Closure
List the responsibilities of the sponsor and investigator following early site closure, such as informing the ethics committee(s), and prompt notification of the participant and transition to appropriate therapy and/or follow-up.
Describe whether the clinical trial will be registered in public databases, including reporting of results, if applicable.
Specify which laboratory parameters should be included in each clinical laboratory assessment panel (for example, for haematology, chemistry, urinalysis). A tabular presentation for such information is common. If applicable, include equations and references for locally calculated laboratory results. If not applicable, retain header and enter Not Applicable.
Although global clinical trial practices are increasingly harmonised, some country/ region-specific differences in requirements do exist (for example, document retention periods, contraception requirements). Where differences in requirements cannot be reconciled, sponsors should explain how they will document and communicate country/region-specific differences (for example, by country/region-specific amendments or addenda). An alternative to country/region-specific amendments is to list the specific differences by country or countries in this section, including a reference to the relevant section of the protocol where the differing requirement applies. If not applicable, retain header and enter Not Applicable.
Either enter value of {Not applicable. The protocol has not been amended.} or {Not applicable. This is the first protocol amendment.} or SEE TEMPLATE INSTRUCTIONS.
Appendix: Glossary of Terms and Abbreviations
Define abbreviations and other terms used in the protocol. A tabular presentation is common and may serve as the definition at first use.
References should be listed in a common format that includes all relevant information to identify the source and date published. If not published, this should be clearly indicated.