Evidence Based Medicine on FHIR Implementation Guide
1.0.0-ballot3 - STU 1 ballot
Evidence Based Medicine on FHIR Implementation Guide
1.0.0-ballot3 - STU 1 ballot
Evidence Based Medicine on FHIR Implementation Guide, published by HL7 International / Clinical Decision Support. This guide is not an authorized publication; it is the continuous build for version 1.0.0-ballot3 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/ebm/ and changes regularly. See the Directory of published versions
| Page standards status: Informative |
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Alper, MD, MSPH</p><p><b>title</b>: M11 Report Section 8 (Trial Assessments) for A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example</p><p><b>custodian</b>: <a href=\"Organization-118079.html\">Computable Publishing LLC</a></p><blockquote><p><b>relatesTo</b></p><p><b>type</b>: Derived From</p><p><b>target</b>: <a href=\"ResearchStudy-267245.html\">A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example</a></p></blockquote><blockquote><p><b>relatesTo</b></p><p><b>type</b>: Cite As</p><p><b>target</b>: </p><div><p>M11 Report Section 8 (Trial Assessments) for A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example [Database Entry: FHIR Composition Resource]. Contributors: Brian S. Alper, MD, MSPH [Authors/Creators]. In: Fast Evidence Interoperability Resources (FEvIR) Platform, FOI 568065. Revised 2026-05-30. Available at: https://fevir.net/resources/Composition/568065. 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Alper, MD, MSPH" ] ] ) ; # fhir:title [ fhir:v "M11 Report Section 8 (Trial Assessments) for A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example"] ; # fhir:custodian [ fhir:l fhir:Organization/118079 ; fhir:reference [ fhir:v "Organization/118079" ] ; fhir:type [ fhir:v "Organization"^^xsd:anyURI ; fhir:l fhir:Organization ] ; fhir:display [ fhir:v "Computable Publishing LLC" ] ] ; # fhir:relatesTo ( [ fhir:type [ fhir:v "derived-from" ] ; fhir:target [ a fhir:Reference ; fhir:l fhir:ResearchStudy/267245 ; fhir:reference [ fhir:v "ResearchStudy/267245" ] ; fhir:type [ fhir:v "ResearchStudy"^^xsd:anyURI ; fhir:l fhir:ResearchStudy ] ; fhir:display [ fhir:v "A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example" ] ] ] [ fhir:type [ fhir:v "cite-as" ] ; fhir:target [ a fhir:Markdown ; fhir:v "M11 Report Section 8 (Trial Assessments) for A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example [Database Entry: FHIR Composition Resource]. Contributors: Brian S. Alper, MD, MSPH [Authors/Creators]. In: Fast Evidence Interoperability Resources (FEvIR) Platform, FOI 568065. Revised 2026-05-30. Available at: https://fevir.net/resources/Composition/568065. Computable resource at: https://fevir.net/resources/Composition/568065#json." ] ] ) ; # fhir:section ( [ fhir:title [ fhir:v "Trial Assessments and Procedures" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218590" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8 TRIAL ASSESSMENTS AND PROCEDURES" ] ] ) ; fhir:text [ fhir:v "section8-assessments" ] ] ; fhir:text [ fhir:status [ fhir:v "empty" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\">[No text is intended here (heading only).]</div>"^^rdf:XMLLiteral ] ] ; ( fhir:section [ fhir:title [ fhir:v "Trial Assessments and Procedures Considerations" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218591" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.1 Trial Assessments and Procedures Considerations" ] ] ) ; fhir:text [ fhir:v "section8.1-assessments-procedures" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Section 2 lists the Schedule of Activities, detailing the study procedures and their timing. Appendix 2 lists the laboratory tests that will be performed for this study. Appendix 5 provides a summary of the maximum number and volume of invasive samples, for all sampling, during the study. Unless otherwise stated in subsections below, all samples collected for specified laboratory tests will be destroyed within 60 days of receipt of confirmed test results. Certain samples may be retained for a longer period, if necessary, to comply with applicable laws, regulations, or laboratory certification standards</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Screening/Baseline Assessments and Procedures" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218592" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.2 Screening/Baseline Assessments and Procedures" ] ] ) ; fhir:text [ fhir:v "section8.2-screening-baseline-assessments" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>See Schedule of Activities Section 1.3 & Clinical Lab Tests.</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Efficacy Assessments and Procedures" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218593" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.3 Efficacy Assessments and Procedures" ] ] ) ; fhir:text [ fhir:v "section8.3-efficacy-assessments" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Plasma glucose levels will be measured as described in Section 9.2.3 and will be used to assess efficacy outcomes. 8.3.1 Primary Efficacy Assessments The primary efficacy measure is the proportion of patients achieving treatment success, defined as either an increase in PG to >70 mg/dL or an increase of >20 mg/dL from nadir within 30 minutes after administration of glucagon. 8.3.2 Secondary Efficacy Assessments Secondary efficacy measures will be determined from the pharmacodynamic (PD) characterization of PG profiles, including evaluation of change from baseline PG concentrations. 8.3.3 Exploratory Efficacy Assessments Subjective hypoglycemia symptoms will be assessed using a self-reported assessment tool (Edinburgh Hypoglycemia Scale; Appendix 7) during the initiation of the hypoglycemia induction, as well as at various time points following the administration of either LY900018 or IMG (see Schedule of Activities; Section 2). The ability of the patient to identify hypoglycemic symptoms and describe their frequency will be captured at Period 1 Day -1 (see Schedule of Activities; Section 2). This self-report assessment will be done using the Clarke Hypoglycemia Awareness Survey (Appendix 8). 8.3.4 Insulin-induced Hypoglycemia A study investigator, or qualified designee, must be present at the bedside for clinical assessments of the patient during the insulin infusion and for the 120 minutes following the glucagon administration. The bedside PG level, measured using a glucose analyzer (Antsense Duo, HORIBA Ltd. or equivalent), must be 90 to 250 mg/dL to start the procedure. If the bedside PG is outside of this range, the hypoglycemia induction should be rescheduled. Hypoglycemia will be induced by IV infusion of diluted human regular insulin (0.3 U/mL) at a rate of 2 mU/kg/min. The infusion rate may be adjusted as necessary up to a rate of 3 mU/kg/min for T1DM or 4 mU/kg/min for T2DM to decrease bedside PG levels < 60 mg/dL; however, the rate of decrease in PG should not exceed 50 mg/dL per 30 minutes. When the bedside PG concentration reaches <90 mg/dL, the insulin infusion rate may be decreased to approximately 1.0 mU/kg/min at the investigator’s discretion. Once the bedside PG level is <60 mg/dL, the insulin infusion will be stopped. If the target bedside PG level cannot be achieved within 4 hours after the start of insulin infusion, the hypoglycemia induction procedure will be terminated before glucagon administration, and the patient may have a carbohydrate-rich meal and be discharged from the CRU after medical assessment. Additional safety assessments may be conducted at the investigator’s discretion. The patient may be rescheduled for a new dosing visit 1 to 7 days later. For safety monitoring during the hypoglycemia induction procedure, bedside PG levels will be measured using the glucose analyzer no more than 10 minutes apart while PG is ≥ 90 mg/dL, and no more than 5 minutes apart when PG is < 90 mg/dL. Blood samples will be collected at pre-hypoglycemia induction and end of insulin infusion (5 minutes prior to study treatment) for PG (PD, as measured by central laboratory) and/or glucagon (PK) measurements according to the Schedule of Activities (Section 2). 8.3.5 Glucagon Administration Approximately 5 minutes after the insulin infusion has stopped, glucagon (either 3 mg LY900018 or 1 mg IMG) will be administered according to randomization. Refer to Section 7 for details regarding treatments. 8.3.5.1 Nasal LY900018 Administration LY900018 will be administered by CRU staff with the patient lying in a fully reclined lateral position on the opposite side of the nostril being administered (ie, dose is given in the left nostril of a patient lying in right lateral recumbency). The tip of the drug product is gently entered in the nostril to the point where the index and middle finger of the administrator are just touching the external nare of the patient. At that point, the bottom of the drug product is pushed with the thumb until the device is engaged, the green band disappears, and powder is discharged into the nostril. The drug is absorbed from the nasal cavity; thus, the patient does not need to inhale after dosing and continues breathing normally throughout the process. If a patient sneezes immediately after administration, document using the Nasal and Non-nasal Score Questionnaire (see Appendix 6 for a copy of the questionnaire). 8.3.5.2 Intramuscular Glucagon Administration GlucaGen 1 mg for injection will be used as a comparator. The lyophilized 1 mg glucagon will be reconstituted with 1.1 mL diluent according to the instruction. A dose of 1 mg of glucagon in I8R-JE-IGBJ(a) Clinical Pharmacology Protocol Page 37 LY900018 a concentration of 1 mg/mL will be injected in the deltoid muscle of the patient’s nondominant arm with the patient lying in a fully reclined lateral position on the opposite side of the arm being administered (ie, dose is given in the left arm of a patient lying in right lateral recumbency if right arm is the dominant arm). 8.3.6 Post Glucagon Administration For 120 minutes after glucagon administration, bedside PG levels will be measured no more than 5 minutes apart when the PG is < 90 mg/dL, and no more than 10 minutes apart when PG is ≥ 90 mg/dL using a glucose analyzer (Antsense Duo, HORIBA Ltd. or equivalent). Blood samples will be collected at predose and various time points post glucagon administration for PG (PD, as measured by central laboratory) and/or glucagon (PK) measurements according to the Schedule of Activities (Section 2). To accurately capture the PG profile, the site should not give patients any calorie-containing food/drink within 90 minutes of glucagon administration unless there is a safety concern. 8.3.7 Procedures for Insufficient Response to Glucagon Administration If the patient loses consciousness or the bedside PG is declining too fast or symptoms consistent with the progression to severe hypoglycemia occur, the investigator may decide to start a glucose infusion to prevent a deterioration of the situation. Following the administration of glucagon, if a patient’s bedside PG concentration remains < 55 mg/dL at 30 minutes or < 60 mg/dL at 45 minutes postdose, IV glucose may be given as deemed clinically necessary. If IV glucose is given, the time and amount of glucose infusion will be recorded in the CRF. 8.3.8 End of Admission Before discharge from the CRU, the glucose and insulin dosing and stability of the patient will be evaluated by the investigator to ensure patient safety. Patients will remain at the CRU for at least 6 hours following glucagon administration, during which time a carbohydrate-rich meal will be provided. The patient may stay at the CRU longer, at the discretion of the investigator</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Safety Assessments and Procedures" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218594" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.4 Safety Assessments and Procedures" ] ] ) ; fhir:text [ fhir:v "section8.4-safety-assessments" ] ] ; fhir:text [ fhir:status [ fhir:v "empty" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\">[Describe safety assessments and procedures utilizing the following subsections as applicable. Add level 3 headings as needed. • Identify any noninvestigator party responsible for evaluation of laboratory or other safety assessments (e.g., Sponsor or external Independent Data Monitoring Committee; cross refer to Section 11.4 Committees for details as applicable). • Include guidelines for the medical management of relevant laboratory or other safety assessment abnormalities.]</div>"^^rdf:XMLLiteral ] ] ; ( fhir:section [ fhir:title [ fhir:v "Physical Examination" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218595" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.4.1 Physical Examination" ] ] ) ; fhir:text [ fhir:v "section8.4.1-physical-examination" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Nasal inspections with nasal speculum and injection-site assessments will be conducted according to the Schedule of Activities (Section 2). This inspection will ascertain whether sites are normal in appearance prior to and after drug administration</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Vital Signs" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218596" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.4.2 Vital Signs" ] ] ) ; fhir:text [ fhir:v "section8.4.2-vital-signs" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>For each patient, vital sign measurements should be conducted according to the Schedule of Activities (Section 1.3). Body temperature will be measured as specified in the Schedule of Activities (Section 1.3) and as clinically indicated. Blood pressure and pulse rate should be measured after at least 5 minutes supine. Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or posture-induced symptoms. If orthostatic measurements are required, patients should be supine for at least 5 minutes and stand for at least 2 minutes. If the patient feels unable to stand, supine vital signs only will be recorded. Additional vital signs may be measured during each study period if warranted.</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Electrocardiograms" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218597" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.4.3 Electrocardiograms" ] ] ) ; fhir:text [ fhir:v "section8.4.3-electrocardiograms" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>For each patient, single and triplicate ECGs should be collected according to the Schedule of Activities (Section 1.3). Any clinically significant findings from ECGs that result in a diagnosis and that occur after the patient receives the first dose of the investigational product should be reported to Lilly, or its designee, as an AE via CRF. Single ECGs will be collected and stored locally at the investigator’s site. Triplicate ECGs will be electronically transmitted to a central ECG laboratory designated by Lilly. The central ECG laboratory will perform a basic quality control check (for example, demographics and study details) then store the ECGs in a database. At a future time, the stored ECG data may be overread at the central ECG laboratory for further evaluation of machine-read measurements or to meet regulatory requirements. Triplicate ECGs collected 30 and 15 minutes prior to the start of insulin-induced hypoglycemia on Day 1 of each period will be used to I8R- establish a baseline. The consecutive triplicate ECGs will be obtained at approximately 1-minute intervals. When scheduled at the same time point, ECGs must be recorded before collecting any blood samples. Patients must be supine for at least 5 minutes before ECG collection and remain supine but awake during ECG collection. Electrocardiograms may be obtained at additional times, when deemed clinically necessary. Single ECGs will be interpreted by a qualified physician (the investigator or qualified designee) at the site as soon after the time of ECG collection as possible, and ideally while the patient is still present, to determine whether the patient meets entry criteria at the relevant visit(s) and for immediate patient management, should any clinically relevant findings be identified. If a clinically significant finding is identified (including, but not limited to, changes in QT/corrected QT interval from baseline) after enrollment, the investigator will determine if the patient can continue in the study. The investigator, or qualified designee, is responsible for determining if any change in patient management is needed, and must document his/her review of the ECG printed at the time of collection. Any new clinically relevant finding should be reported as an AE. The machine-read ECG intervals and heart rate may be used for data analysis and report writing purposes unless a cardiologist overread of the ECGs is conducted prior to completion of the final study report (in which case the overread data would be used).</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Clinical Laboratory Assessments" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218598" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.4.4 Clinical Laboratory Assessments" ] ] ) ; fhir:text [ fhir:v "section8.4.4-clinical-laboratory-assessments" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>For each patient, laboratory tests detailed in Section 13.1 should be conducted according to the Schedule of Activities (Section 1.3). Lilly or its designee will provide the investigator with the results of laboratory tests analyzed by a central vendor, if a central vendor is used for the study.</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Pregnancy Testing" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218599" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.4.5 Pregnancy Testing" ] ] ) ; fhir:text [ fhir:v "section8.4.5-pregnancy-testing" ] ] ; fhir:text [ fhir:status [ fhir:v "empty" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\">[Include any specific instructions for the collection and interpretation of pregnancy testing.]</div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Suicidal Ideation and Behaviour Risk Monitoring" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218600" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.4.6 Suicidal Ideation and Behaviour Risk Monitoring" ] ] ) ; fhir:text [ fhir:v "section8.4.6-suicidal-ideation" ] ] ; fhir:text [ fhir:status [ fhir:v "empty" ] ; fhir:div [ fhir:v "<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 should also be provided in Section 9.2.4 Adverse Events of Special Interest.]</div>"^^rdf:XMLLiteral ] ] ] ) ] [ fhir:title [ fhir:v "Pharmacokinetics" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218601" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.5 Pharmacokinetics" ] ] ) ; fhir:text [ fhir:v "section8.5-pharmacokinetics" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>At the visits and times specified in the Schedule of Activities (see Section 1.3), venous blood samples of approximately 4 mL each will be collected to determine the plasma concentrations of glucagon. Three samples may be collected per patient at additional time points during the study if warranted and agreed upon between both the investigator and sponsor. Instructions for the collection and handling of blood samples will be provided by the sponsor. The actual date and time (24-hour clock) of each sampling will be recorded. 8.5.1 Bioanalysis Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility designated by the sponsor. Concentrations of glucagon will be assayed using a validated liquid chromatography with tandem mass spectrometry method. Bioanalytical samples collected to measure investigational product concentrations will be retained for a maximum of 1 year following last patient visit for the study.</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Biomarkers" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218602" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.6 Biomarkers" ] ] ) ; fhir:text [ fhir:v "section8.6-biomarkers" ] ] ; fhir:text [ fhir:status [ fhir:v "empty" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\">[No text is intended here (heading only). Include any specific instructions for the collection of samples and assessment of biomarkers, including pharmacodynamics. If biomarker or pharmacodynamic testing is not included in the study, state “Not Applicable.” • Describe the biological samples that will be collected (for example, tissue, serum, plasma, etc.). o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross-referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of biomarkers that will be studied for each sample. • Specify whether each sample is optional or required. Required samples must be based on a protocol objective.]</div>"^^rdf:XMLLiteral ] ] ; ( fhir:section [ fhir:title [ fhir:v "Genetics, Genomics, Pharmacogenetics, and Pharmacogenomics" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218603" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.6.1 Genetics, Genomics, Pharmacogenetics and Pharmacogenomics" ] ] ) ; fhir:text [ fhir:v "section8.6.1-genetics-pharmacogenomics" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>A blood sample will be collected for pharmacogenetic analysis as specified in the Schedule of Activities (Section 1.3), where local regulations allow. Samples will not be used to conduct unspecified disease or population genetic research either now or in the future. Samples will be used to investigate variable exposure or response to nasal glucagon (LY900018) and to investigate genetic variants thought to play a role in diabetes mellitus and related complications. Assessment of variable response may include evaluation of AEs or differences in efficacy. All samples will be coded with the patient number. These samples and any data generated can be linked back to the patient only by the investigative site personnel. Samples will be retained for a maximum of 15 years after the last patient visit, or for a shorter period if local regulations and/or ERBs impose shorter time limits, for the study at a facility selected by Lilly or its designee. This retention period enables use of new technologies, response to regulatory questions, and investigation of variable response that may not be observed until later in the development of LY900018 or after LY900018 is commercially available. Molecular technologies are expected to improve during the 15-year storage period and therefore cannot be specifically named. However, existing approaches include whole genome or exome sequencing, genome wide association studies, multiplex assays, and candidate gene studies. Regardless of technology utilized, data generated will be used only for the specific research scope described in this section.</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Pharmacodynamic Biomarkers" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218604" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.6.2 Pharmacodynamic Biomarkers" ] ] ) ; fhir:text [ fhir:v "section8.6.2-pharmacodynamics" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>At times specified in the Schedule of Activities (see Section 2), venous blood samples will be collected and used to determine PG concentrations. The samples will be stored for up to a maximum of 1 year after last patient visit for the study at a facility selected by the sponsor.</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Other Biomarkers" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218605" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.6.3 Other Biomarkers" ] ] ) ; fhir:text [ fhir:v "section8.6.3-other" ] ] ; fhir:text [ fhir:status [ fhir:v "empty" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\">[Include any specific instructions for the collection of samples and assessment of other biomarkers. • Describe the biological samples that will be collected (for example, tissue, serum, plasma, etc.). o Specific sample collection and processing instructions can be described in an appendix or a separate document and cross-referenced. • Describe the retention time for the samples (ensuring alignment with the ICF). • Indicate the types of biomarkers that will be studied for each sample. • Specify whether each sample is optional or required. Required samples must be based on a protocol objective.]</div>"^^rdf:XMLLiteral ] ] ] ) ] [ fhir:title [ fhir:v "Immunogenicity Assessments" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218606" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.7 Immunogenicity Assessments" ] ] ) ; fhir:text [ fhir:v "section8.7-immunogenicity-assessments" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples will be collected to determine antibody production against glucagon. To interpret the results of immunogenicity, a venous blood sample may be collected at the same time points to determine the concentrations of glucagon. All samples for immunogenicity should be taken predose when applicable. In the event of drug hypersensitivity reactions (immediate or non-immediate), additional immunogenicity samples will be collected as close to the onset of the event as possible, at the resolution of the event, and 30 days following the event. A PK sample may be collected at these same time points(s) if warranted and agreed upon between both the investigator and sponsor. Treatment-emergent antidrug antibodies (TE ADA) are defined in Section 10.3.6. If the immunogenicity titer at the last scheduled assessment or discontinuation visit meets the definition of treatment emergent, then, at the discretion of the sponsor, patients should be called back to the site for follow-up immunogenicity assessment(s). Samples for immunogenicity should be collected every 12 weeks until the titer returns to baseline (ie, returns to within a single 2-fold dilution of the baseline titer) or until 1 year after the last dose of study treatment. A PK sample may be collected at the follow-up immunogenicity assessment(s) if warranted and agreed upon between both the investigator and sponsor. Every attempt should be made to contact patients for the follow-up immunogenicity assessment; however, if patients are unwilling or unable to return for the visit, this is not considered a protocol violation. Instructions for the collection and handling of blood samples will be provided by the sponsor. The actual date and time (24-hour clock time) of each sampling will be recorded. Immunogenicity will be assessed by a validated assay designed to detect antidrug antibodies (ADA) in the presence of glucagon at a laboratory approved by the sponsor. Antibodies may be further characterized and/or evaluated for their ability to neutralize the activity of glucagon. Samples will be retained for a maximum of 15 years after the last patient visit, or for a shorter period if local regulations and ethical review boards (ERBs) allow, at a facility selected by the sponsor. The duration allows the sponsor to respond to future regulatory requests related to LY900018. Any samples remaining after 15 years will be destroyed.</p></div>"^^rdf:XMLLiteral ] ] ] [ fhir:title [ fhir:v "Medical Resource Utilisation and Health Economics" ] ; fhir:code [ ( fhir:coding [ fhir:system [ fhir:v "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl"^^xsd:anyURI ; fhir:l <http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl> ] ; fhir:code [ fhir:v "C218607" ] ; fhir:display [ fhir:v "ICH M11 Protocol Section 8.8 Medical Resource Utilisation and Health Economics" ] ] ) ; fhir:text [ fhir:v "section8.8-economics" ] ] ; fhir:text [ fhir:status [ fhir:v "additional" ] ; fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Not applicable..</p></div>"^^rdf:XMLLiteral ] ] ] ) ] ) . #
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2026-06-02
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