Evidence Based Medicine on FHIR Implementation Guide
1.0.0-ballot - ballot
Evidence Based Medicine on FHIR Implementation Guide
1.0.0-ballot - ballot
This page is part of the Evidence Based Medicine on FHIR Implementation Guide (v1.0.0-ballot: STU1 Ballot 1) based on FHIR (HL7® FHIR® Standard) v5.0.0. . For a full list of available versions, see the Directory of published versions
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<div xmlns="http://www.w3.org/1999/xhtml"><p><b>Generated Narrative: Composition</b><a name="181448"> </a></p><div style="display: inline-block; background-color: #d9e0e7; padding: 6px; margin: 4px; border: 1px solid #8da1b4; border-radius: 5px; line-height: 60%"><p style="margin-bottom: 0px">Resource Composition "181448" Version "8" Updated "2023-12-05 20:20:35+0000" </p><p style="margin-bottom: 0px">Profile: <a href="StructureDefinition-m11-report.html">M11Report</a></p></div><p><b>Artifact Description</b>: This M11Report Profile of Composition includes the instructions in each section.text.div element for creating an M11Report instance.</p><p><b>url</b>: <a href="https://fevir.net/resources/Composition/181448">https://fevir.net/resources/Composition/181448</a></p><p><b>identifier</b>: FEvIR Object Identifier: 181448</p><p><b>status</b>: final</p><p><b>type</b>: EvidenceReport <span style="background: LightGoldenRodYellow; margin: 4px; border: 1px solid khaki"> (<a href="CodeSystem-179423.html">Evidence Based Medicine on FHIR Implementation Guide Code System</a>#EvidenceReport)</span></p><p><b>category</b>: CeSHarP Report <span style="background: LightGoldenRodYellow; margin: 4px; border: 1px solid khaki"> ()</span></p><p><b>date</b>: 2023-12-05 20:20:35+0000</p><p><b>author</b>: <span>: Brian S. Alper</span></p><p><b>title</b>: M11 Report Template Instructions</p><p><b>custodian</b>: <a href="Organization-118079.html">Organization/118079: Computable Publishing LLC</a> "Computable_Publishing_LLC"</p><h3>RelatesTos</h3><table class="grid"><tr><td style="display: none">-</td><td><b>Type</b></td><td><b>Citation</b></td></tr><tr><td style="display: none">*</td><td>cite-as</td><td>M11 Report Template Instructions [Composition]. Contributors: Brian S. Alper [Authors/Creators]. In: Fast Evidence Interoperability Resources (FEvIR) Platform, FOI 181448. Revised 2023-12-05. Available at: https://fevir.net/resources/Composition/181448. Computable resource at: https://fevir.net/resources/Composition/181448.</td></tr></table></div>
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<text value="CeSHarP Report"/>
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<date value="2023-12-05T20:20:35.182Z"/>
<author>
<display value="Brian S. Alper"/>
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<title value="M11 Report Template Instructions"/>
<custodian>🔗
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<section>
<title value="Protocol Summary"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section1-protocol-summary"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Protocol Synopsis"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section1.1-protocol-synopsis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Primary and Secondary Objectives and Endpoints"/>
<code>
<text value="section1.1.1-objectives-endpoints"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Include a copy of the Objectives/Endpoints Table including primary and secondary endpoints only from Section 3 of the protocol and follow all the same instructions. Not all trials will have a complete estimand. Do not include exploratory endpoints in the synopsis.]</div>
</text>
</section>
<section>
<title value="Overall Design"/>
<code>
<text value="section1.1.2-overall-design"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Key aspects of the trial design include Intervention Model, Control Type, Control Description, Intervention Assignment Method, Population Type, Population Diagnosis or Condition (use SNOMED or MedDRA), Population Age (Minimum, Maximum), and Site Distribution and Geographic Scope. Entries should Reference omposition Resource or ResearchStudy Resource.]</div>
</text>
</section>
<section>
<title value="Number of Arms"/>
<code>
<text value="Number of Arms"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Blinding"/>
<code>
<text value="Blinding"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 indictated will not be made aweare of the treatment group assignment during the trial:' [blinded roles] 'Not applicable (No blinding)' indicates an open-label trial.]</div>
</text>
</section>
<section>
<title value="Number of Participants"/>
<code>
<text value="Number of Participants"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Arms and Duration"/>
<code>
<text value="Arms and Duration"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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”.]</div>
</text>
</section>
<section>
<title value="Committees"/>
<code>
<text value="Committees"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 11.3.]</div>
</text>
</section>
</section>
<section>
<title value="Trial Schema"/>
<code>
<text value="section1.2-trial-schema"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 participants through the progression of trial period(s)/epochs (such as screening, washout/run-in, intervention, and key milestones [for example, randomisation, cross-over, end of treatment]). 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.]</div>
</text>
<entry>🔗
<reference value="PlanDefinition/181450"/>
<type value="PlanDefinition"/>
<display
value="SoaPlanDefinition: Follow-up assessment 3 months after study start"/>
</entry>
</section>
<section>
<title value="Schedule of Activities"/>
<code>
<text value="section1.3-schedule-of-activities"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. Entries should Reference SoaPlanDefinition Profile of PlanDefinition Resource.]</div>
</text>
<entry>🔗
<reference value="PlanDefinition/181450"/>
<type value="PlanDefinition"/>
<display
value="SoaPlanDefinition: Follow-up assessment 3 months after study start"/>
</entry>
</section>
</section>
<section>
<title value="Introduction"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section2-introduction"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Purpose of Trial"/>
<code>
<text value="section2.1-trial-purpose"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Explain why the trial is needed, why the research questions being asked are important. Do not restate the IB.]</div>
</text>
</section>
<section>
<title value="Summary of Benefits and Risks"/>
<code>
<text value="section2.2-benefits-risks"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Benefit Summary"/>
<code>
<text value="section2.2.1-benefit-summary"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[The benefit summary should be written from the perspective of an individual participant, and should describe any physical, psychological, social, legal, 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, 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.]</div>
</text>
</section>
<section>
<title value="Risk Summary and Mitigation Strategy"/>
<code>
<text value="section2.2.2-risk-summary"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Trial-specific Intervention Risks and Mitigations"/>
<code>
<text value="section2.2.2.1-trial-intervention-risk-summary"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. Include an assessment of known benefits and potential risks, including the basis of the risk (for example, preclinical studies or prior clinical trials).]</div>
</text>
</section>
<section>
<title value="Trial-specific Procedure Risks and Mitigations"/>
<code>
<text value="section2.2.2.2-trial-procedures-risk-summary"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Trial Procedures – Consider risks associated with the design (for example, placebo arm) and procedures specific to THIS trial (for example, biopsies), and any measures to control 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.]</div>
</text>
</section>
<section>
<title value="Trial-specific Other Risks and Mitigations"/>
<code>
<text value="section2.2.2.3-trial-other-risk-summary"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Other – Consider risks associated with other items (for example, comparators, challenge agents, imaging agents, medical devices). Insert a line for each, as needed.]</div>
</text>
</section>
</section>
<section>
<title value="Overall Benefit:Risk Conclusion"/>
<code>
<text value="section2.2.3-overall-benefit-risk-conclusion"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. Risks need to be assessed against the benefits for the individual participant at least once a year.]</div>
</text>
</section>
</section>
</section>
<section>
<title value="Trial Objectives, Endpoints and Estimands"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section3-endpoints"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Objective + Associated Endpoint (and Estimand)"/>
<code>
<text value="section3.1-objective-endpoint-estimand"/>
</code>
<focus>
<type value="EvidenceVariable"/>
<display
value="[Replace with OutcomeVariable Profile of EvidenceVariable Resource.]"/>
</focus>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Primary/Secondary/Exploratory Classification"/>
<code>
<text value="Primary/Secondary/Exploratory"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Replace with 'Primary' or 'Secondary' or 'Exploratory'.]</div>
</text>
</section>
<section>
<title value="Objective"/>
<code>
<text value="Objective"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[State each trial objective.]</div>
</text>
</section>
<section>
<title value="Endpoint"/>
<code>
<text value="Endpoint"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the endpoint.]</div>
</text>
</section>
<section>
<title value="Estimand"/>
<code>
<text value="Estimand"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the attributes that construct the estimand: the treatment condition of interest, the population of participants targeted by the clinical question of interest, other intercurrent events (if applicable), a population level summary, and the endpoint (or variable) specified above.]</div>
</text>
</section>
</section>
</section>
<section>
<title value="Trial Design"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section4-trial-design"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Description of Trial Design"/>
<code>
<text value="section4.1-description-of-trial-design"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the trial intervention model (for example, single group, parallel group, cross-over, factorial, sequential), the expected number of participants, and the control method (for example, placebo, active comparator, low dose, historical, standard of care, sham procedure, or none [uncontrolled]). If applicable, indicate other design characteristics (for example, superiority, non-inferiority, dose escalation, or equivalence). If the trial will have an adaptive or novel design (for example, the trial will be conducted under a master protocol), provide a summary of these design aspects. 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 (for example, 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 11.3, Committees. Describe the method of assignment to trial intervention (for example, stratified randomisation) with reference to Section 6.6. If assignment to trial intervention is by randomisation, describe when randomisation occurs relative to screening. Describe the level and method of blinding with reference to Section 6.6 (for example, single-blind, double-blind, [including sponsor unblinded], matching placebo, double-dummy, or open-label). Include mention of measures taken to minimise bias on the part of participants, investigators, and analysts. If applicable, describe within-trial transition rules, for example, transitions involving cohorts or trial parts. Dose escalation or dose-ranging details should also be described. Discuss any other important aspects of the design, including but not limited to the following, where applicable: • Geographic scope of trial (for example, 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 11.3, Committees, for details, • Whether an interim analysis is planned and, if so, refer to details in Section 10.7, Interim Analysis, and/or • 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.]</div>
</text>
<section>
<title value="Stakeholder Input into Design"/>
<code>
<text value="section4.1.1-stakeholder-input-into-design"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
</section>
<section>
<title value="Rationale for Trial Design"/>
<code>
<text value="section4.2-rationale-for-trial-design"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Rationale for Intervention Model"/>
<code>
<text value="section4.2.1-rationale-intervention-model"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Provide a rationale for the trial intervention model selected in Section 4.1, Description of Trial Design with a cross-reference to Section 6.2, Rationale for Investigational Intervention(s). Rationale for choice of comparator, if applicable, should be described separately in Section 4.2.5, Rationale for Comparator. A rationale for the choice of trial population should be described separately in Section 5.1, Description of Trial Population and Rationale.]</div>
</text>
</section>
<section>
<title value="Rationale for Duration"/>
<code>
<text value="section4.2.2-rationale-duration"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Provide a rationale that the trial duration is appropriate for a reliable and relevant evaluation of the trial intervention per the trial objective(s).]</div>
</text>
</section>
<section>
<title value="Rationale for Endpoints"/>
<code>
<text value="section4.2.3-rationale-endpoints"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Provide a rationale that the trial endpoint(s) described in Section 3, Trial Objectives, Endpoints, and Estimands, are clinically relevant and provide a reliable and valid measurement of the intended intervention effect.]</div>
</text>
</section>
<section>
<title value="Rationale for Interim Analysis"/>
<code>
<text value="section4.2.4-rationale-interim-analysis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Rationale for Comparator"/>
<code>
<text value="section4.2.5-rationale-comparator"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, provide a rationale for the type of control selected for the trial (for example, placebo, active drug, combination, historical). 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.]</div>
</text>
</section>
<section>
<title value="Rationale for Adaptive or Novel Trial Design"/>
<code>
<text value="section4.2.6-rationale-adaptive"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, provide a rationale for the use of an adaptive or novel design.]</div>
</text>
</section>
<section>
<title value="Rationale for Other Trial Design Aspects"/>
<code>
<text value="section4.2.7-rationale-other-aspects"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Discuss rationale for any additional aspects of the design not addressed above.]</div>
</text>
</section>
</section>
<section>
<title value="Trial Stopping Rules"/>
<code>
<text value="section4.3-trial-stopping-rules"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
<section>
<title value="Temporary Trial Halt"/>
<code>
<text value="section4.3.1-temporary-trial-halt"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe when any of the stopping rules may result in a temporary halt of enrollment into the trial and criteria for restarting enrollment.]</div>
</text>
</section>
</section>
<section>
<title value="Start of Trial and End of Trial"/>
<code>
<text value="section4.4-start-and-end"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Define key timepoints in the trial, including trial start and end dates. For example, 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 study assessment has occurred. If applicable, consider local regulatory requirements for these and other definitions (for example, the first act of recruitment). If appropriate, provide a cross-reference to Section 11.6]</div>
</text>
</section>
<section>
<title value="Access to Trial Intervention After End of Trial"/>
<code>
<text value="section4.5-access-after-trial"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe any possibilities for access to trial intervention, if any, beyond completion of the trial. Planned extension trials, if described above in Section 4.1 do not need to be repeated.]</div>
</text>
</section>
</section>
<section>
<title value="Trial Population"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section5-trial-population"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Description of Trial Population and Rationale"/>
<code>
<text value="section5.1-population-description"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the population selected (for example, healthy participants, adult participants, paediatric participants) and how the enrollment criteria reflect the populations that are likely to use the drug if approved. Specify the population age range (for example, ≤3 months, ≥18 to ≤80 years old) including the time point at which qualification for age criteria is determined (for example, at time of screening vs randomization for paediatric trials). Specify any key diagnostic criteria for the population (for example, “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 reflects the targeted populations. 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 (for example, elderly, hepatic or renally impaired, or immunocompromised participants). Entries should Reference CohortDefinition (or StudyEligibilityCriteria) Profile of Group Resource.]</div>
</text>
</section>
<section>
<title value="Inclusion Criteria"/>
<code>
<text value="section5.2-inclusion-criteria"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Inclusion criteria are characteristics that define the trial population, for example, those criteria that every potential participant must satisfy, to qualify for trial entry. Add criteria as needed. Number sequentially. Entries should Reference CohortDefinition (or StudyEligibilityCriteria) Profile of Group Resource.]</div>
</text>
</section>
<section>
<title value="Exclusion Criteria"/>
<code>
<text value="section5.3-exclusion-criteria"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Exclusion criteria are characteristics that make an individual ineligible for participation. Add criteria as needed. Number the criteria sequentially. Entries should Reference CohortDefinition (or StudyEligibilityCriteria) Profile of Group Resource.]</div>
</text>
</section>
<section>
<title value="Lifestyle Restrictions"/>
<code>
<text value="section5.4-lifestyle-restrictions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
<section>
<title value="Meals and Dietary Restrictions"/>
<code>
<text value="section5.4.1-dietary-restrictions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe any restrictions on diet (for example, food and drink restrictions, timing of meals relative to dosing).]</div>
</text>
</section>
<section>
<title value="Caffeine, Alcohol, Tobacco, and Other Restrictions"/>
<code>
<text value="section5.4.2-substances-restrictions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe any restrictions on the intake of caffeine, alcohol, tobacco, or other restrictions.]</div>
</text>
</section>
<section>
<title value="Physical Activity Restrictions"/>
<code>
<text value="section5.4.3-activity-restrictions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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).]</div>
</text>
</section>
<section>
<title value="Other Activity Restrictions"/>
<code>
<text value="section5.4.4-other-restrictions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
</section>
<section>
<title value="Screen Failure and Rescreening"/>
<code>
<text value="section5.5-screen-failure"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
</section>
<section>
<title value="Trial Intervention"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section6-trial-intervention"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Description of Investigational Trial Intervention"/>
<code>
<text value="section6.1-description-of-trial-intervention"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[The investigational trial intervention(s) should be described concisely in a table. 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 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 ExposureDefinition Profile of Group Resource.]</div>
</text>
</section>
<section>
<title
value="Rationale for Investigational Trial Intervention Dose and Regimen"/>
<code>
<text value="section6.2-rationale-for-trial-intervention-regimen"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Provide a rationale for the selection of the dose(s) or dose range, the route of administration, and dosing regimen of the investigational trial intervention. This rationale should include relevant results from previous preclinical studies and clinical trials that support selection of the dose and regimen. Discuss impact of differences in study population characteristics (for example, age, sex and/or race) which could lead to differences in pharmacokinetics and pharmacodynamics in this study as compared to previous studies. 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 intervention. Include a rationale for prospective dose adjustments incorporated in the trial, if any. Entries should Reference ExposureDefinition Profile of Group Resource.]</div>
</text>
</section>
<section>
<title value="Investigational Trial Intervention Administration"/>
<code>
<text value="section6.3-dosing-and-administration"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the detailed procedures for administration of each participant’s dose of investigational trial intervention. This may include the timing of dosing (for example, time of day, interval), the duration (for example, the length of time participants will be administered the investigational trial intervention), the planned route of administration (for example, oral, nasal, intramuscular), and the timing of dosing relative to meals. Include any specific instructions to trial participants about when or how to prepare and take the dose(s) and how delayed or missed doses should be handled. 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.]</div>
</text>
<section>
<title value="Investigational Trial Intervention Dose Modification"/>
<code>
<text value="section6.3.1-dose-modification"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 an individua participant due to safety/other reasons should be detailed in Section 7, Participant Discontinuation of Trial Intervention and Withdrawal from Trial. Entries should Reference ActivityDefinition Resource.]</div>
</text>
</section>
</section>
<section>
<title
value="Management of Investigational Trial Intervention Overdose"/>
<code>
<text value="section6.4-management-of-overdose"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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-references these documents as applicable. Entries should Reference ActivityDefinition Resource or PlanDefinition Resource.]</div>
</text>
</section>
<section>
<title
value="Preparation, Storage, Handling and Accountability of Investigational Trial Intervention(s)"/>
<code>
<text value="section6.5-preparation-storage-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Preparation of Investigational Trial Intervention(s)"/>
<code>
<text value="section6.5.1-preparation"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe any preparation of the investigational trial intervention, and when necessary, by whom. When applicable, describe the maximum hold time once thawed/mixed before administration. Include thawing, diluting, mixing, and reconstitution/preparation instructions in this section. 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 a separate document(s) provided to the site (for example, a pharmacy manual). If the latter, reference the separate documents.]</div>
</text>
</section>
<section>
<title
value="Storage and Handling of Investigational Trial Intervention"/>
<code>
<text value="section6.5.2-storage-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe storage and handling requirements (for example, 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 (for example, the seal is broken). State how the investigational trial intervention(s) will be provided to the Investigator. If applicable, describe the 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 a separate document(s) provided to the site (for example, a pharmacy manual). If the latter, reference the separate documents.]</div>
</text>
</section>
<section>
<title value="Accountability of Investigational Trial Intervention"/>
<code>
<text value="section6.5.3-accountability"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the accountability method, including how the investigational trial intervention will be distributed and related details, including: • how and by whom the investigational trial intervention will be distributed • 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.]</div>
</text>
</section>
</section>
<section>
<title
value="Investigational Trial Intervention Assignment, Randomisation and Blinding"/>
<code>
<text value="section6.6-assignment-randomisation-blinding"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title
value="Participant Assignment to Investigational Trial Intervention"/>
<code>
<text value="section6.6.1-assignment"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. State that at enrollment, participant identification codes should be assigned. 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.]</div>
</text>
</section>
<section>
<title value="Randomisation"/>
<code>
<text value="section6.6.2-randomisation"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the randomisation procedures (for example, central randomisation procedures), the method used to generate the randomisation schedule (for example, computer generated), the source of the randomisation schedule (for example, sponsor, investigator, or other), and whether or not IxRS will be used. To maintain the integrity of the blinding, do not include the block size. Describe the use and validation of any computer systems and programmes used for randomisation.]</div>
</text>
</section>
<section>
<title value="Blinding"/>
<code>
<text value="section6.6.3-blinding"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe efforts to ensure that the investigational trial intervention(s) are as indistinguishable as possible. Plans for the maintenance of randomisation codes and appropriate blinding for the trial should be described. Procedures for planned and unplanned (for example, safety events) breaking of randomisation codes should be provided. If the trial allows for some investigators or other designated staff to remain unblinded (for example, 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.]</div>
</text>
</section>
<section>
<title value="Emergency Unblinding at the Site"/>
<code>
<text value="section6.6.4-unblinding"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
</section>
<section>
<title value="Investigational Trial Intervention Compliance"/>
<code>
<text value="section6.7-intervention-compliance"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe measures employed to ensure and document dosing information and investigational trial intervention compliance (for example, accountability records, diary cards, or concentration measurements). Include a description of what documents are mandatory to complete (for example, participant drug log) and what source data/records will be used to document investigational trial intervention compliance.]</div>
</text>
</section>
<section>
<title value="Non-Investigational Trial Intervention(s)"/>
<code>
<text value="section6.8-noninvestigational-interventions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Background Intervention"/>
<code>
<text value="section6.8.1-background-intervention"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe background interventions, including administration and any conditions for use.]</div>
</text>
</section>
<section>
<title value="Rescue Therapy"/>
<code>
<text value="section6.8.2-rescue-therapy"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[List all rescue medications, treatments, and/or procedures, including any relevant instructions about their administration and any conditions for their 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 Withdrawal from Trial.]</div>
</text>
</section>
<section>
<title value="Other Therapy"/>
<code>
<text value="section6.8.3-other-therapy"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe the use of other non-investigational or auxiliary therapy, for example, challenge agents or diagnostics.]</div>
</text>
</section>
</section>
<section>
<title value="Concomitant Therapy"/>
<code>
<text value="section6.9-concomitant-therapy"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the concomitant medications, supplements, complementary and alternative therapies, treatments, and/or procedures which are allowed or prohibited during the trial, and include details about when the information will be collected (for example, screening, all visits). This section should be consistent with the medication restrictions in the inclusion/exclusion criteria previously listed.]</div>
</text>
<section>
<title value="Prohibited Concomitant Therapy"/>
<code>
<text value="section6.9.1-prohibited-concomitant-therapy"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe any prohibited concomitant therapy.]</div>
</text>
</section>
<section>
<title value="Permitted Concomitant Therapy"/>
<code>
<text value="section6.9.2-permitted-concomitant-therapy"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe any permitted concomitant therapy.]</div>
</text>
</section>
</section>
</section>
<section>
<title
value="Participant Discontinuation of Trial Intervention and Withdrawal from Trial"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section7-participant-discontinuation"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title
value="Discontinuation of Trial Intervention for Individual Participants"/>
<code>
<text value="section7.1-discontinuation-of-trial-intervention"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Permanent Discontinuation of Trial Intervention"/>
<code>
<text
value="section7.1.1-permanent-discontinuation-of-trial-intervention"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. Specify whether participants who discontinue trial intervention can or cannot continue the trial (continue trial visits). Refer to the Section 1.3 Schedule of Activities for assessments to be performed at the time of and following discontinuation of trial intervention. Explain the process for collecting and recording the detailed reasons for discontinuing trial intervention(s).]</div>
</text>
</section>
<section>
<title value="Temporary Discontinuation of Trial Intervention"/>
<code>
<text
value="section7.1.2-temporary-discontinuation-of-trial-intervention"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 needs to temporarily discontinue or interrupt trial intervention • whether they will continue in the trial, and • whether all, or specify 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.]</div>
</text>
</section>
<section>
<title value="Rechallenge"/>
<code>
<text value="section7.1.3-rechallenge"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the criteria for rechallenge/restarting trial intervention, how 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.]</div>
</text>
</section>
</section>
<section>
<title value="Withdrawal from the Trial"/>
<code>
<text value="section7.2-participant-withdrawal"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the criteria for participant withdrawal from the trial. Describe the reason for withdrawal and the type and data to be collected for the final assessments with reference to the schedule of activities for the participant end of study visit unless provided in another section.]</div>
</text>
</section>
<section>
<title value="Lost to Follow-Up"/>
<code>
<text value="section7.3-lost-to-follow-up"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the measures to be taken to reduce the frequency of participants lost to follow up. Describe how the trial will define and address participants who are lost to follow-up to help limit the amount and impact of missing data. Describe the nature and duration of follow-up, as appropriate.]</div>
</text>
</section>
<section>
<title value="Participant Stopping Rules"/>
<code>
<text value="section7.4-participant-stopping-rules"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If applicable, describe any trial-specific stopping rules that would apply to individual participants such as treatment or study non-compliance or due to safety reasons. Address the procedure ensuring alignment with the intercurrent events and their handling strategies introduced in Section 3.]</div>
</text>
</section>
</section>
<section>
<title value="Trial Assessments and Procedures"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section8-assessments"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Enter general trial assessments and procedures text, if needed.]</div>
</text>
<section>
<title value="Screening/Baseline Assessments and Procedures"/>
<code>
<text value="section8.1-screening-baseline-assessments"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe any assessments and procedures that are unique to screening/baseline (for example, 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 if screening and baseline are performed at different visits.]</div>
</text>
</section>
<section>
<title value="Efficacy Assessments and Procedures"/>
<code>
<text value="section8.2-efficacy-assessments"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe efficacy assessments and procedures in this section. Cross-refer to Section 8.7 if immunogenicity assessments are used in efficacy determination.]</div>
</text>
</section>
<section>
<title value="Safety Assessments and Procedures"/>
<code>
<text value="section8.3-safety-assessments"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Physical Examination"/>
<code>
<text value="section8.3.1-physical-examination"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Include any specific instructions for the collection and interpretation of physical examinations.]</div>
</text>
</section>
<section>
<title value="Vital Signs"/>
<code>
<text value="section8.3.2-vital-signs"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Include any specific instructions for the collection and interpretation of vital signs.]</div>
</text>
</section>
<section>
<title value="Electrocardiograms"/>
<code>
<text value="section8.3.3-electrocardiograms"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Include any specific instructions for the collection, interpretation, and archiving of ECGs.]</div>
</text>
</section>
<section>
<title value="Clinical Laboratory Assessments"/>
<code>
<text value="section8.3.4-clinical-laboratory-assessments"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Include any specific instructions for the collection and interpretation of clinical laboratory assessments. • 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 (for example, a pandemic or natural disaster) • treatment algorithms for results out of normal range • Cross-refer to Section 13.2 for lab assessment panels]</div>
</text>
</section>
<section>
<title value="Pregnancy Testing"/>
<code>
<text value="section8.3.5-pregnancy-testing"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Optional section to specify pregnancy testing requirements.]</div>
</text>
</section>
<section>
<title value="Suicidal Ideation and Behaviour Risk Monitoring"/>
<code>
<text value="section8.3.6-suicidal-ideation"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 will also need to be provided in the appropriate subsection of Section 9.4.]</div>
</text>
</section>
</section>
<section>
<title value="Pharmacokinetics"/>
<code>
<text value="section8.4-pharmacokinetics"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Include any specific instructions for the collection and assay of samples and interpretation of PK assessments. If pharmacokinetic testing is not included in the study, state “Not Applicable.” • Describe the biological sample(s) 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 that may be studied for each sample.]</div>
</text>
</section>
<section>
<title value="Genetic Testing"/>
<code>
<text value="section8.5-genetic-testing"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Include any specific instructions for the collection and assay of samples for genetic analysis. If genetic testing is not included in the study, state “Not Applicable.” • 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.]</div>
</text>
</section>
<section>
<title value="Biomarkers"/>
<code>
<text value="section8.6-biomarkers"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Immunogenicity Assessments"/>
<code>
<text value="section8.7-immunogenicity-assessments"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. If immunogenicity testing is not included in the study, state “Not Applicable.”]</div>
</text>
</section>
<section>
<title value="Medical Resource Utilisation and Health Economics"/>
<code>
<text value="section8.8-economics"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. If medical resource utilization and health economics assessment is not included in the study, state “Not Applicable.” Describe the health outcome measures, collection method (for example, diary, physician interview), and participant burden.]</div>
</text>
</section>
</section>
<section>
<title
value="Adverse Events, Serious Adverse Events, and Product Complaints"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section9-adverse-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Definitions"/>
<code>
<text value="section9.1-definitions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Definitions of Adverse Events"/>
<code>
<text value="section9.1.1-definitions-adverse-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. • The trial-specific definition for an overdose. • If applicable, any clarifications on the AE and SAE definitions for efficacy trials (for example, lack of efficacy or failure of pharmacological actions reporting).]</div>
</text>
</section>
<section>
<title value="Definitions of Serious Adverse Events"/>
<code>
<text value="section9.1.2-definitions-serious-adverse-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Definitions of Medical Device Product Complaints"/>
<code>
<text value="section9.1.3-definitions-product-complaints"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Enter Definition of Medical Device Product Complaints.]</div>
</text>
</section>
</section>
<section>
<title
value="Timing and Mechanism for Collection and Reporting of AEs, SAEs, Pregnancy, and Product Complaints"/>
<code>
<text value="section9.2-collection-methods"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the starting and ending time periods for and frequency of collecting AEs and SAEs. Cross refer to the Schedule of Assessments as appropriate.]</div>
</text>
</section>
<section>
<title
value="Recording and Follow-Up of AEs, SAEs, Pregnancy, and Product Complaints"/>
<code>
<text value="section9.3-recording-and-follow-up"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Identifying AEs, SAEs and Product Complaints"/>
<code>
<text value="section9.3.1-identifying-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify how AEs and SAEs will be identified (for example, spontaneous reporting, solicited questions).]</div>
</text>
</section>
<section>
<title value="Intensity"/>
<code>
<text value="section9.3.2-intensity"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the intensity rating categories/scale.]</div>
</text>
</section>
<section>
<title value="Causality"/>
<code>
<text value="section9.3.3-causality"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the causality categories/scale and the procedures for assessing causality.]</div>
</text>
</section>
<section>
<title
value="Recording of AEs, SAEs, Pregnancy and Product Complaints"/>
<code>
<text value="section9.3.4-recording-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the Investigator’s actions for recording AEs and SAEs, including severity, causality, and the final outcome.]</div>
</text>
</section>
<section>
<title value="Follow-up"/>
<code>
<text value="section9.3.5-followup"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the procedures for follow-up of AEs, SAEs, pregnancy and product complaints. Include the assessment tools that will be used to monitor the events and the duration of follow-up after appearance of the events. Specify any procedures to be used for trials in which death is not an endpoint.]</div>
</text>
</section>
</section>
<section>
<title
value="Reporting of AEs, SAEs, Pregnancy, and Product Complaints"/>
<code>
<text value="section9.4-reporting-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Reporting of SAEs"/>
<code>
<text value="section9.4.1-reporting-serious-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the SAE reporting method (for example, an electronic data collection tool or a paper CRF) and reporting timeline to the Sponsor.]</div>
</text>
</section>
<section>
<title
value="Regulatory Reporting Requirements for SAEs and Product Complaints"/>
<code>
<text value="section9.4.2-regulatory-requirements"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify: • The investigators’ responsibilities for reporting SAEs and Medical Device Product Complaints 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 SAEs to regulatory authorities, ethics committees, and investigators • Serious and unexpected adverse reaction reporting]</div>
</text>
</section>
<section>
<title value="Adverse Events of Special Interest"/>
<code>
<text value="section9.4.3-special-interest"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify any Adverse Events of Special Interest (AESI): • Other events that merit reporting to the Sponsor, trial leadership, IRB, and regulatory agencies (for example, secondary malignancies in oncology trials). • Other reportable events not already included in the previous sections, such as cardiovascular events, medical device incidents (including malfunctions), laboratory test abnormalities, and trial intervention overdose. Include the following for each AESI: • The definition of the event. Specify the MedDRA preferred terms to use to report the AESI. • If it is a measurable quantity, specify how will the measurement be done. • If it is a clinical event, specify how will it be confirmed.]</div>
</text>
</section>
<section>
<title
value="Disease-related Events or Outcomes Not Qualifying as AEs or SAEs"/>
<code>
<text value="section9.4.4-disease-related-events"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify any Disease-Related Events (DREs), disease-related outcomes (DROs), or both that will not be reported as AEs or SAEs (for example, seizures in anticonvulsant trials) or state not applicable.]</div>
</text>
</section>
</section>
<section>
<title
value="Timing and Mechanism for Collection and Reporting of AEs, SAEs, Pregnancy, and Product Complaints"/>
<code>
<text value="section9.5-collection-methods"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Participants Who Become Pregnant During the Trial"/>
<code>
<text value="section9.5.1-pregnant"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify • the assessments to be performed, • type and duration of monitoring, • whether participants who become pregnant during the trial must be discontinued from trial intervention (refer to Section 7 as applicable), and • what information will be collected about a participant who becomes pregnant during the trial (for example, 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 (for example, 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, and • what information will be collected for both the participant and child. While pregnancy itself is not considered to be an AE or SAE, if negative or consequential outcome occurs in the participant or child/foetus, it will be reported as an AE or SAE. Refer to Section 9 for AE and SAE related procedures as applicable. If the negative event meets the seriousness criteria, then this is considered an SAE (for example, spontaneous abortion, foetal death, stillbirth, congenital anomalies, ectopic pregnancy, or pre-eclampsia) and reported per Section 9.4.]</div>
</text>
</section>
<section>
<title value="Participants Whose Partners Become Pregnant"/>
<code>
<text value="section9.5.2-pregnant-partner"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 as applicable), and • The assessments to be performed, type and duration of monitoring, and what information will be collected.]</div>
</text>
</section>
</section>
</section>
<section>
<title value="Statistical Considerations"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section10-statistics"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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 statistical considerations section. Provide a statement with regard to when the primary analyses will be conducted. For example: The analysis will be conducted on all participant data at the time the trial ends.]</div>
</text>
<section>
<title value="Analysis Sets"/>
<code>
<text value="section10.1-analysis-sets"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Analysis sets to support each analysis will be specified here and described in the Statistical Analysis Plan.]</div>
</text>
</section>
<section>
<title value="Analysis Supporting Primary Objective"/>
<code>
<text value="section10.2-analysis-primary-objective"/>
</code>
<focus>
<type value="EvidenceVariable"/>
<display
value="[Replace with OutcomeVariable Profile of EvidenceVariable Resource.]"/>
</focus>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[This section introduces the Statistical Analysis Plan, with the detail to be provided in the subsequent subsections. This includes describing the methods of estimation (analytic approach) in alignment with how the estimands are defined. Sensitivity analyses should be aligned with how the estimands and estimators are defined.]</div>
</text>
<section>
<title value="Statistical Model, Hypothesis, and Method of Analysis"/>
<code>
<text value="section10.2.1-statistical-model"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Ensure that the statistical hypothesis/model (and corresponding assumptions)/analysis is aligned with the primary estimand(s). For all applicable objectives (for example, primary, secondary), under the appropriate header, state the null and alternative hypotheses, including the pre-planned type 1 error, or alternative criteria to define trial success 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 (for example, pooling of centres). If applicable, state and describe any adjustments to account for multiplicity. If modelling and simulation methods are to be used, please describe the model (inputs and outputs), the underlying assumptions, and the method of model fitting. Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.]</div>
</text>
</section>
<section>
<title value="Handling of Intercurrent Events of Primary Estimand"/>
<code>
<text value="section10.2.2-intercurrent-events-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[For each intercurrent event of the primary estimand(s) (Section 3.1, Estimand[s] for the Primary Objective[s]), explain how data will be handled for the statistical analysis in line with the primary estimand. The handling of intercurrent events in statistical analysis should be aligned with the specific estimand strategies being used. This section should describe with more detail the rationale and handling of the data rather than repeating the guidance from the preceding sections.]</div>
</text>
</section>
<section>
<title value="Handling of Missing Data"/>
<code>
<text value="section10.2.3-missing-data-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[This section should describe how missing data will be dealt with. Refer to the E9(R1) addendum when estimand framework is used. The protocol should describe how missing data will be handled (for example, type of imputation technique, if any, and provide justification). In cases where the Primary Objective is related to safety, this section should also be completed. It may also be helpful to include additional statements regarding handling of missing data in general for other important efficacy or safety endpoints or this information can be included in the analysis of secondary endpoint section below.]</div>
</text>
</section>
<section>
<title value="Sensitivity Analysis"/>
<code>
<text value="section10.2.4-sensitivity-analysis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Supplementary Analysis"/>
<code>
<text value="section10.2.5-supplementary-analysis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe any supplementary analysis if applicable.]</div>
</text>
</section>
</section>
<section>
<title value="Analysis Supporting Secondary Objective"/>
<code>
<text value="section10.3-analysis-secondary-objective"/>
</code>
<focus>
<type value="EvidenceVariable"/>
<display
value="[Replace with OutcomeVariable Profile of EvidenceVariable Resource.]"/>
</focus>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[This section should focus on estimands for Secondary Objectives. In this section describe the statistical analysis, handling of intercurrent events, handling of missing data, and if applicable, sensitivity analysis corresponding to each secondary estimand.]</div>
</text>
<section>
<title value="Statistical Model, Hypothesis, and Method of Analysis"/>
<code>
<text value="section10.3.1-statistical-model"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[For all applicable objectives (for example, primary, secondary), under the appropriate header, state the null and alternative hypotheses, including the pre-planned type 1 error, or alternative criteria to define trial success 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 (for example, pooling of centres). If applicable, state and describe any adjustments to account for multiplicity. Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.]</div>
</text>
</section>
<section>
<title value="Handling of Intercurrent Events of Secondary Estimand"/>
<code>
<text value="section10.3.2-intercurrent-events-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[For each intercurrent event of the primary estimand(s) (Section 3.1, Estimand[s] for the Primary Objective[s]), explain how data will be handled for the statistical analysis in line with the primary estimand. The handling of intercurrent events in statistical analysis should be aligned with the specific estimand strategies being used.]</div>
</text>
</section>
<section>
<title value="Handling of Missing Data"/>
<code>
<text value="section10.3.3-missing-data-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[The protocol should describe how missing data will be handled (for example, type of imputation technique, if any, and provide justification).]</div>
</text>
</section>
<section>
<title value="Sensitivity Analysis"/>
<code>
<text value="section10.3.4-sensitivity-analysis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Supplementary Analysis"/>
<code>
<text value="section10.3.5-supplementary-analysis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe any supplementary analysis if applicable.]</div>
</text>
</section>
</section>
<section>
<title value="Analysis of Exploratory Objective"/>
<code>
<text value="section10.4-analysis-exploratory-objective"/>
</code>
<focus>
<type value="EvidenceVariable"/>
<display
value="[Replace with OutcomeVariable Profile of EvidenceVariable Resource.]"/>
</focus>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Enter Analyses Supporting Tertiary/Exploratory Objective(s)].]</div>
</text>
<section>
<title value="Statistical Model, Hypothesis, and Method of Analysis"/>
<code>
<text value="section10.4.1-statistical-model"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[For all applicable objectives (for example, primary, secondary), under the appropriate header, state the null and alternative hypotheses, including the pre-planned type 1 error, or alternative criteria to define trial success 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 (for example, pooling of centres). If applicable, state and describe any adjustments to account for multiplicity. Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.]</div>
</text>
</section>
<section>
<title
value="Handling of Intercurrent Events of Exploratory Estimand"/>
<code>
<text value="section10.4.2-intercurrent-events-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[For each intercurrent event of the primary estimand(s) (Section 3.1, Estimand[s] for the Primary Objective[s]), explain how data will be handled for the statistical analysis in line with the primary estimand. The handling of intercurrent events in statistical analysis should be aligned with the specific estimand strategies being used.]</div>
</text>
</section>
<section>
<title value="Handling of Missing Data"/>
<code>
<text value="section10.4.3-missing-data-handling"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[The protocol should describe how missing data will be handled (for example, type of imputation technique, if any, and provide justification).]</div>
</text>
</section>
<section>
<title value="Sensitivity Analysis"/>
<code>
<text value="section10.4.4-sensitivity-analysis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Supplementary Analysis"/>
<code>
<text value="section10.4.5-supplementary-analysis"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe any supplementary analysis if applicable.]</div>
</text>
</section>
</section>
<section>
<title value="Safety Analyses"/>
<code>
<text value="section10.5-safety-analyses"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If safety is a primary and/or secondary objective, describe the corresponding safety analyses in the appropriate section above (Section 10.2 or Section 10.3).]</div>
</text>
</section>
<section>
<title value="Other Analyses"/>
<code>
<text value="section10.6-other-analyses"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe Other Analyses such as Subgroup analyses, Adjusted analysis if needed.]</div>
</text>
</section>
<section>
<title value="Interim Analyses"/>
<code>
<text value="section10.7-interim-analyses"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe any interim analysis and criteria for stopping or adapting the trial. The description should include, but is not limited to, the following: • Any interim analysis plan, even if it is only to be performed at the request of an oversight body (for example, DMC). • Describe (briefly and concisely) and reference the applied statistical method, for example, group sequential test and spending function (for example, O’Brien-Fleming), as applicable. • Who will perform the analyses. • When they 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 (for example, maintaining blinding) when any adaptations to the trial are made. • Who has the ultimate authority to stop or modify the trial, for example, investigator, principal investigator, Data Monitoring Committee, or sponsor. • The stopping guidelines. • If pre-specified interim analyses are to be used for other trial adaptations such as sample size re-estimation, alteration to the proportion of participants allocated to each trial group, and changes to eligibility criteria.]</div>
</text>
</section>
<section>
<title value="Sample Size Determination"/>
<code>
<text value="section10.8-sample-size-determination"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[This section should detail the methods used for the determination of the sample size and a reference to tables or statistical software used to carry out the calculation. Sufficient information should be provided so that the sample size calculation can be reproduced or described. If the planned sample size is not derived statistically, then this should be explicitly stated along with a rationale for the intended sample size (for example, exploratory nature of pilot trials; pragmatic considerations for trials in rare diseases). Entries should Reference EndpointAnalysisPlan Profile of Evidence Resource.]</div>
</text>
</section>
<section>
<title value="Protocol Deviations"/>
<code>
<text value="section10.9-protocol-deviations"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Plans for detecting, reviewing, and reporting any deviations from the protocol should be described.]</div>
</text>
</section>
</section>
<section>
<title
value="General Considerations: Regulatory, Ethical, and Trial Oversight"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section11-oversight"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Regulatory and Ethical Considerations"/>
<code>
<text value="section11.1-regulatory-considerations"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[List 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: • World Medical Association Declaration of Helsinki ethical principles 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]</div>
</text>
</section>
<section>
<title value="Trial Oversight"/>
<code>
<text value="section11.2-trial-oversight"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe 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.]</div>
</text>
<section>
<title value="Investigator Responsibilities"/>
<code>
<text value="section11.2.1-investigator-responsibilities"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Enter Investigator Responsibilities.]</div>
</text>
</section>
<section>
<title value="Sponsor Responsibilities"/>
<code>
<text value="section11.2.2-sponsor-responsibilities"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the sponsor duties to be delegated to a third party that may impact the investigators sites, if applicable.]</div>
</text>
</section>
</section>
<section>
<title value="Committees"/>
<code>
<text value="section11.3-committees"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Briefly describe the administrative structure of committees that will be reviewing data while the trial is ongoing, and the type of committee (for example, 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 applicable, state “Not Applicable.”]</div>
</text>
</section>
<section>
<title value="Informed Consent Process"/>
<code>
<text value="section11.4-informed-consent-process"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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).]</div>
</text>
<section>
<title value="Assent Process"/>
<code>
<text value="section11.4.0-assent-process"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Enter Description of Assent Process.]</div>
</text>
</section>
<section>
<title value="Emergency Consent Process"/>
<code>
<text value="section11.4.0-emergency-consent-process"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
<section>
<title value="Informed Consent for Rescreening"/>
<code>
<text value="section11.4.1-rescreening-consent-process"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[If participants can be rescreened, add the text to 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.]</div>
</text>
</section>
<section>
<title
value="Informed Consent for Remaining Samples in Exploratory Research"/>
<code>
<text value="section11.4.2-remaining-samples"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
</section>
<section>
<title value="Insurance and Indemnity"/>
<code>
<text value="section11.5-insurance-and-indemnity"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the arrangements for participants insurance and indemnity if not addressed in a separate agreement.]</div>
</text>
</section>
<section>
<title value="Early Site Closure"/>
<code>
<text value="section11.6-early-site-closure"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Decision Rights for Site Closure"/>
<code>
<text value="section11.6-early-site-closure#decisionRights"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[List the sponsor’s rights to close a site. Likewise, list the investigator’s rights to initiate early site closure.]</div>
</text>
</section>
<section>
<title value="Crteria for Early Closure"/>
<code>
<text value="section11.6-early-site-closure#criteria"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[List the criteria for early closure of a site by the sponsor or investigator.]</div>
</text>
</section>
<section>
<title value="Responsibilities Following Early Site Closure"/>
<code>
<text value="section11.6-early-site-closure#responsibilities"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.]</div>
</text>
</section>
</section>
</section>
<section>
<title
value="General Considerations: Risk Management and Data Governance"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section12-risk-management-and-data-governance"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Risk Management"/>
<code>
<text value="section12.1-risk-management"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe how the critical to quality factors will be mitigated. It is important to determine the risks that threaten their integrity and decide whether they can be accepted or should be mitigated, based on their probability, detectability and impact. Where it is decided that risks should be mitigated, the necessary control processes should be put in place and communicated, and the necessary actions taken to mitigate the risks.]</div>
</text>
</section>
<section>
<title value="Data Governance"/>
<code>
<text value="section12.2-data-governance"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Describe the key processes for critical trial integrity, traceability and security enabling accurate collection, reporting, monitoring, transfer, retention, access and publication 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.]</div>
</text>
</section>
<section>
<title value="Source Data"/>
<code>
<text value="section12.3-source-data"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Establish the importance of source data and expectation for traceability of transcribed information back to source. Delineate expectations for investigators (for example, maintain source data at the site, ensure availability of current records) and trial monitors (for example, verify CRF data relative to source, safety of participants is being protected, conduct is in accordance with GCP). Define what constitutes source data and its origin or provide a reference to the location of these definitions, 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).]</div>
</text>
</section>
</section>
<section>
<title value="Appendix: Definitions and Supporting Operational Details"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section13-definitions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Contraception"/>
<code>
<text value="section13.1-contraception"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[No text is intended here (header only).]</div>
</text>
<section>
<title value="Definitions Related to Childbearing Potential"/>
<code>
<text value="section13.1.1-contraception-definitions"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the definitions of • Participant of childbearing potential, and • Participant of non-childbearing potential]</div>
</text>
</section>
<section>
<title value="Contraception"/>
<code>
<text value="section13.1.2-contraception-details"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Specify the: • Contraceptive methods required, and • Duration of use]</div>
</text>
</section>
</section>
<section>
<title value="Clinical Laboratory Tests"/>
<code>
<text value="section13.2-clinical-laboratory-tests"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.”]</div>
</text>
<emptyReason>
<coding>
<system
value="http://terminology.hl7.org/CodeSystem/list-empty-reason"/>
<code value="notstarted"/>
<display value="Not Started"/>
</coding>
</emptyReason>
</section>
<section>
<title value="Country/Region-Specific Differences"/>
<code>
<text value="section13.3-country-specific-differences"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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.”]</div>
</text>
<emptyReason>
<coding>
<system
value="http://terminology.hl7.org/CodeSystem/list-empty-reason"/>
<code value="notstarted"/>
<display value="Not Started"/>
</coding>
</emptyReason>
</section>
<section>
<title value="Prior Protocol Amendment(s)"/>
<code>
<text value="section13.4-prior-protocol-amendments"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[See M11 for specific guidance if not able to simply state {Not applicable. This protocol has not been amended.} or {Not applicable. This is the first protocol amendment.}.]</div>
</text>
<emptyReason>
<coding>
<system
value="http://terminology.hl7.org/CodeSystem/list-empty-reason"/>
<code value="notstarted"/>
<display value="Not Started"/>
</coding>
</emptyReason>
</section>
</section>
<section>
<title value="Appendix: Glossary of Terms and Abbreviations"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section14-glossary"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[Define abbreviations and other terms used in the protocol. A tabular presentation is common and may serve as the definition at first use. Entries should Reference ValueSet Resource or CodeSystem Resource.]</div>
</text>
</section>
<section>
<title value="Appendix: References"/>
<code>
<coding>
<system value="https://fevir.net/resources/CodeSystem/179423"/>
<code value="regulatory-report"/>
<display value="Regulatory Report"/>
</coding>
<text value="section15-references"/>
</code>
<text>
<status value="empty"/>
<div xmlns ="http://www.w3.org/1999/xhtml">[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. Entries should Reference Citation Resource.]</div>
</text>
<emptyReason>
<coding>
<system
value="http://terminology.hl7.org/CodeSystem/list-empty-reason"/>
<code value="notstarted"/>
<display value="Not Started"/>
</coding>
</emptyReason>
</section>
</Composition>
IG © 2022+ HL7 International / Clinical Decision Support. Package hl7.fhir.uv.ebm#1.0.0-ballot based on FHIR 5.0.0. Generated 2023-12-17
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