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
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<div xmlns="http://www.w3.org/1999/xhtml"><p class="res-header-id"><b>Generated Narrative: Composition 568059</b></p><a name="568059"> </a><a name="hc568059"> </a><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">version: 2; Last updated: 2026-05-30 21:43:11+0000</p><p style="margin-bottom: 0px">Profile: <a href="StructureDefinition-m11-report-section-02.html">M11ReportSection02</a></p></div><p><b>ArtifactPublicationStatus</b>: <span title="Codes:{http://terminology.hl7.org/CodeSystem/cited-artifact-status-type active}">Active</span></p><p><b>url</b>: <a href="https://fevir.net/resources/Composition/568059">https://fevir.net/resources/Composition/568059</a></p><p><b>identifier</b>: FEvIR Object Identifier/568059</p><p><b>status</b>: Final</p><p><b>type</b>: <span title="Codes:{http://loinc.org 35528-9}">CeSHarP Report</span></p><p><b>category</b>: <span title="Codes:{http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl C218520}">section2-introduction</span></p><p><b>date</b>: 2026-05-30 21:43:11+0000</p><p><b>author</b>: Brian S. Alper, MD, MSPH</p><p><b>title</b>: M11 Report Section 2 (Introduction) 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 2 (Introduction) 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 568059. Revised 2026-05-30. Available at: https://fevir.net/resources/Composition/568059. Computable resource at: https://fevir.net/resources/Composition/568059#json.</p>
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<div xmlns="http://www.w3.org/1999/xhtml"><p>Nasal glucagon (LY900018) is a powder formulation of human glucagon for the rescue treatment of hypoglycemia packaged in a user-friendly, single-use, nasal dosing device that delivers 3 mg glucagon powder for absorption through the nasal mucosa. The glucagon component of LY900018 is a synthetic single-chain, 29-amino-acid polypeptide identical to human glucagon. LY900018 is being developed for the rescue treatment of hypoglycemia. Currently, glucagon in a liquid form lacks physical and chemical stability; thus, marketed products require reconstitution of glucagon powder before the product can be administered through intramuscular (IM) injection. LY900018 combines stable, synthetic glucagon and a nasal dosing device that for effective use obviates reconstitution, injection, and moreover, patient inhalation. Because of these advantages, LY900018 may offer a significant improvement in the treatment of severe hypoglycemia occurring outside of the hospital setting. The aim of this study is to compare LY900018 with IM glucagon (IMG), a currently approved product that requires reconstitution prior to administration through IM injection, in Japanese patients with type 1 diabetes mellitus (T1DM) and patients with type 2 diabetes mellitus (T2DM) who achieve treatment success during controlled insulin-induced hypoglycemia. Treatment success is defined as an increase in plasma glucose (PG) to ≥70 mg/dL or an increase of ≥20 mg/dL from the PG nadir within 30 minutes after receiving glucagon, without the patient receiving additional treatments to increase PG. The nadir is defined as the minimum PG measurement at the time of or within 10 minutes following glucagon administration. The design and conduct of Study IGBJ are similar to the completed Phase 3 Study I8R-MC-IGBC (IGBC) (Rickels et al. 2016) and the planned Phase 1 Study I8R-MC-IGBI.</p></div>
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<div xmlns="http://www.w3.org/1999/xhtml"><p>2.2.1 Risk Summary and Mitigation Strategy </p><p>This study will expose patients to an insulin-induced hypoglycemia meant to simulate hypoglycemia in a controlled setting. The procedure of insulin-induced hypoglycemia targeting nadir glucose around 50 mg/dL is adopted from a previously completed trial, specifically Study IGBC, which demonstrated the safe use of this method. This is an inpatient procedure in which the patients will be under constant supervision of the clinical research unit (CRU) staff with frequent glucose monitoring. Safety provisions have been considered in that IV glucose will be administered if the patient experiences signs and symptoms of severe hypoglycemia and gauged to require intervention during the experimental procedure, at the discretion of the investigator. Potential risks associated with LY900018, derived from the known risks of currently existing injected glucagon therapy and from the safety profile observed from clinical trials conducted for LY900018, include nausea, vomiting, allergic reactions, increased blood pressure (BP) and heart rate, headache, dysgeusia, and nasal or ocular events (Glucagon G Novo for Injection Package Insert, 2016; Glucagon G Novo for Injection Interview Form, 2015; GLUCAGON for Injection ITO Package Insert, 2016; GLUCAGON for Injection ITO Interview Form, 2016). Nausea and Vomiting: Glucagon therapy, including LY900018, may cause nausea and vomiting. Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with glucagon therapy, including LY900018. Patients who have had hypersensitivity reactions to injectable glucagon, or LY900018 or any of its excipients will be excluded from all clinical studies. Increased Blood Pressure and Heart Rate: Glucagon exerts positive inotropic and chronotropic effects. A temporary increase in both BP and heart rate may occur after the administration of glucagon, including LY900018. Headache and Dysgeusia: Use of LY900018 may cause headache and altered taste. Nasal Symptoms: Use of LY900018 may cause a variety of nasal symptoms, such as runny nose, stuffy nose, nasal discomfort, cough, and sneezing. Ocular Symptoms: Use of LY900018 may cause a variety of ocular symptoms, such as watery eyes, redness of eyes, and itchy eyes. No additional potential risks of LY900018 were identified in preclinical safety pharmacology and toxicity studies (Reno et al. 2015).</p></div>
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<div xmlns="http://www.w3.org/1999/xhtml"><p>2.2.2 Benefit Assessment </p><p>Hypoglycemia is a common complication in all patients with T1DM and some patients with T2DM who use insulin to reduce blood glucose levels. Use of sulfonylurea and glinide by patients with T2DM may also cause hypoglycemia. Depending on the severity, hypoglycemia causes physical symptoms ranging from weakness, dizziness, and sweating progressing to blurred vision, behavioral changes, progressing to unconsciousness, seizures, and coma, and possibly to death (American Diabetes Association 2017). When emergency services are available in a timely manner, intravenous (IV) glucose supplementation is also an effective treatment. Glucagon for injection is a globally available product currently indicated for the treatment of severe hypoglycemia, and is another important treatment option outside of a clinical setting for people who try to rescue patients with severe hypoglycemia. However, for people without enough medical training, the multi-step reconstitution of glucagon and injection procedure would be complex and daunting with substantial risk of errors (Polonsky et al. 2016). Therefore the needle-free and easy-to-administer formulation of glucagon is desired for patients who have a risk of severe hypoglycemia related to anti-diabetes treatments. LY900018 is a powder formulation of synthetic human glucagon in a user-friendly, single-use, nasal dosing device which delivers 3 mg glucagon powder. Patients do not need to inhale, as the drug is absorbed from the nasal cavity. Three clinical trials using LY900018 have been completed in non-Japanese adults with T1DM and T2DM: Study IGBC, Study I8R-MC-IGBA (IGBA), and an actual use study (Study I8R-MC-B002 [B002]). Studies IGBC and IGBA demonstrated comparable safety and efficacy between 3 mg LY900018 and 1 mg injectable glucagon in reversing insulin-induced hypoglycemia in adult patients with T1DM only (Study IGBA) or patients with T2DM and T1DM (IGBC). Study B002 was an actual use study that evaluated the effectiveness of 3 mg LY900018 administered by a trained caregiver to patients with T1DM experiencing moderate to severe hypoglycemia in a real-world environment of work and home. Study B002 demonstrated that 96% of moderate to severe hypoglycemic events were resolved within 30 minutes. Finally, 2 trials were conducted in pediatric patients with T1DM: Study I8R-MC-IGBB (IGBB) and Study I8R-MC-B001 (B001). Studies IGBB and B001 demonstrated effectiveness in rescuing pediatric patients from hypoglycemia. All adult diabetic patients in the 2 inpatient clinical trials (Studies IGBA and IGBC) underwent hypoglycemia induction through IV insulin under close clinical supervision and were administered either LY900018 or injectable glucagon. Patients fully recovered from hypoglycemia without additional actions to increase glucose level. Specifically, in Study IGBC, at 30 minutes after glucagon dosing, 98.7% (74 out of 75 patients) of LY900018 and 100% (75 out of 75) of IMG-treated patients achieved treatment success (defined as an increase in PG to >70 mg/dL or an increase of >20 mg/dL from nadir). The nadir is defined as the minimum glucose measurement at the time of or within 10 minutes following glucagon administration. The LY900018-treated patient who did not meet the above criteria did achieve both PG >70 mg/dL and an increase of >20 mg/dL from nadir at 40 minutes after dosing. Furthermore, the mean time to treatment success in participants with nadir glucose <50 mg/dL were 16 minutes in the LY900018 treatment arm and 13 minutes in the IMG treatment arm, respectively (Rickels et al. 2016) 2.2.1 Benefit Summary There is no anticipated therapeutic benefit for the patients participating in this study</p></div>
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<div xmlns="http://www.w3.org/1999/xhtml"><p> 2.2.3 Overall Risk-Benefit Assessment</p><p>More information about the known and expected benefits, risks, serious adverse events (SAEs), and reasonably anticipated adverse events (AEs) of LY900018 are to be found in the Investigator’s Brochure (IB). More detailed information about the known and expected benefits and risks of GlucaGen® may be found in the Summary of Product Characteristics (GlucaGen Summary of Product Characteristics, 2015). <</p></div>
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Package hl7.fhir.uv.ebm#1.0.0-ballot3 based on FHIR 6.0.0-ballot3.
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2026-06-02
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