Adverse Event Clinical Research R4 Backport
1.0.1 - STU1

Adverse Event Clinical Research R4 Backport, published by HL7 International / Biomedical Research and Regulation. This guide is not an authorized publication; it is the continuous build for version 1.0.1 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/fhir-ae-research-backport-ig/ and changes regularly. See the Directory of published versions

## Real World examples

### Introduction

The following use cases are exemplified with FHIR instances in this guide. Every effort has been made to be accurate, especially with regards to the AdverseEvent Clinical Research Profile instances, but these are intended as examples and may not include referenced data such as an Encounter. They are from real world examples and show how the AdverseEvent Clinical Research Profile is intended to be generally used. Keep in mind that it is intended that the profile in this guide be derived from to produce use case specific guidance. The examples are demonstrative of using FHIR in adverse event reporting but not prescriptive. As the use of adverse event reporting with FHIR matures, the examples could become outdated. Note the Patient resource was referenced as appropriate; however, in clinical research the data would go to the sponsor as a research subject identifier. Depending on the use case implementers will want to be aware of the ResearchSubject resource which points to the Patient resource.

### Clinical trial: significant adverse event

(Link to Example AdverseEvent Clinical Research Profile)

This scenario involves a phase 2, clinical study evaluating the safety and efficacy of a new oral agent administered daily for treatment of severe psoriasis unresponsive to FDA-approved treatments. There are two arms of the study – subjects receiving the new oral agent or a placebo. Only the research pharmacist is aware of the arm assignment. The fifth subject enrolled in the trial develops severe hepatic failure complicated by encephalopathy one month after starting the study.

The known risk profile of the new oral agent prior to this event included mild elevation of serum liver enzymes in 10% of subjects receiving the agent during previous clinical studies, but there was no other history of subjects developing clinically significant liver disease. The IRB approved protocol and informed consent document for the study identifies mild liver injury as a risk of the research.

The study sponsors determined that is an unanticipated problem that must be reported because although the risk of mild liver injury was foreseen, severe liver injury resulting in hepatic failure was unexpected in severity; possibly related to participation in the research; and serious.

### FDA MedWatch 3500A Form being used during a clinical trial

(Link to Example AdverseEvent Clinical Research Profile)

A 64-year-old woman (Janet) is participating in a breast cancer clinical trial and taking an investigational drug. As part of her participation in the study, she was instructed to use a patient reported outcomes (ePRO) application to report an adverse event that resulted in any of the following: hospitalization, required help to prevent permanent harm, disability or health problem, birth defect, life-threatening, death, other serious/important medical incident (this list identifies the event as being “serious events”). The application is designed to capture data elements found on the 3500A Form.

The Clinical Investigator (CI) receives a notification that Janet has an adverse event and reviews the event in Janet’s EHR system. The adverse event form is pre-populated from EHR data for the clinical investigator. The CI assesses causality for Janet’s adverse event and submits the serious adverse event to the sponsor. The sponsor reviews the received adverse event and performs its own causality assessment. Since this event is a Suspected Unexpected Serious Adverse Reaction (SUSAR) within FDA’s regulation. If the Suspected Unexpected Serious Adverse Reaction (SUSAR) was life threating or death, it is submitted within 7 calendar days.

Any other types of seriousness are submitted within 15 calendar days.

### Serious Adverse Event Research Study

(Link to Example AdverseEvent Clinical Research Profile)

Patient SCHJO on Research Study XYZ, Study ID XYZ-123, Subject number XYZ-123-002. SCHJO was enrolled in the study on 12-Jun-2021 taking Study Medication ABC 10 mg orally daily every morning for atrial fibrillation to prevent thromboembolism. On 2-Dec-2021, the subject XYZ-123-002 was hospitalized with a Gastrointestinal (GI) bleed. The investigator was notified of the event on the day of admission when the patient presented with vomiting a large amount of coffee-ground like hematemesis. The investigator stopped the study drug because the event was “Possibly related” to the study drug. The patient’s hemoglobin dropped to 6.5 g/dL and received 2 units of PRBCs. The patient had an upper endoscopy that showed a moderate amount of bleeding from the esophagus. The site was cauterized, and the patient had no further bleeding after the procedure. The GI bleed resolved within one week after discontinuation of study drug and the patient was discharged on 9-Dec-2021 in good condition.

### Non-Serious Adverse Event Research Study Medication

(Link to Example AdverseEvent Clinical Research Profile)

Patient MOUMIC on Research Study DISNEY, Study ID DUCK-828, Subject number DUCK-828-012. MOUMIC was enrolled in the study on 21-Jan-2022 taking Study Medication 20 mg subcutaneously daily every morning for diabetes. At visit 3 on 21-Feb-2022, the patient stated that he had started to experience intermittent headaches on 1-Feb-2022 that were mild. They occurred once a week and resolved with Tylenol but were still ongoing. The investigator said the headaches were “UNLIKELY RELATED” to study drug. The action taken with the study treatment was the “DOSE NOT CHANGED” and the outcome was noted to be “NOT RECOVERED/NOT RESOLVED”.

### Non-Serious Adverse Event Related to Study Procedure (not study drug)

(Link to Example AdverseEvent Clinical Research Profile)

Patient SLP on Research Study ACME, Study ID ACME-789, Subject number ACME-789-100. SLP was enrolled in the study on 2-Jan-2021, taking Study Medication WBY 10 mg orally daily every morning for moderate asthma.
On 15-Jan-2021, the subject has the protocol-prescribed procedure of a Lung CT Scan, with contrast dye. As a result of the contrast dye, the subject experiences moderate hives and itching from the contrast dye. This is reported as an Adverse Event, related to study procedure. He is treated with a Benadryl injection and recovers the same day.

The investigator said the reaction to the contrast dye was “UNLIKELY RELATED” to study drug. The action taken with the study treatment was the “DOSE NOT CHANGED” and the outcome was noted to be “RECOVERED/RESOLVED”.

### Cancer Clinical Trial with Non-serious Adverse Events

This use case persona describes a hypothetical cancer patient on a cancer clinical trial with example instances to demonstrate how the adverse event profile can be used to guide the creation of resources representing a clinically realistic scenario.

### Device Example

Exemplification of referencing a device in an adverse event, Device Example. The example has a device as the suspected entity, but the AdverseEvent Clinical Research Profile also has a reference for Device as a participant, contributingFactor, mitigatingAction, and supportingInfo.