A Study of the Burden of Illness and Treatment Patterns in Teenagers and Adults With Hereditary Angioedema

Study Overview
=================
Brief Summary
-----------------
This study is about teenagers and adults with hereditary angioedema (HAE) type I and type II. In this study, the burden of illness means the impact of HAE in terms of long-term health outcomes and the financial cost. The main aims of this study are as follows: to learn how often, how severe and where on the body HAE attacks occur. to describe how HAE prophylaxis and on-demand medicines are prescribed and used. (Prophylaxis medicines prevent a bleed from happening and on-demand medicines treat a bleed when it occurs.) This study is about collecting data only; participants will not receive treatment as part of this study. Existing data available in the participant's medical records will be collected. Participants will be asked to complete an electronic questionnaire either on a website or by using an app on their mobile phone; data from this questionnaire will also be collected. Participants do not need to visit their doctor in addition to their normal visits.

Official Title
-----------------
A Retrospective Observational Chart Review Study Evaluating the Burden of Illness and Treatment Patterns in Hereditary Angioedema Type I and II

Conditions
-----------------
Hereditary Angioedema

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant aged >= 12 years at the time of the last documented HAE attack in the eligibility period. Physician-confirmed diagnosis (or confirmation in medical records) of HAE type I or type II. Participant had at least one documented HAE attack during the eligibility period. Participant is not adequately or sub-optimally controlled according to treating physician. Participant (or parent/legal guardian) is willing and able to comply with the study requirements and provides informed consent or assent. Exclusion Criteria: Participant enrolled in a therapeutic investigational drug or device trial during the observation period. Participant initiated long-term prophylaxis with Takhzyro® at any time since diagnosis.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with HAE<br>Participants' data will be collected retrospectively from electronic medical records using chart review of de-identified data on participant demographics, HAE medical history and information on diagnostics, treatments and disease course assessments that are routinely performed in accordance with current guidelines and/or local standard of care which are entered into an Electronic data capture (EDC) system over multiple data collection waves up to 6 months. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HAE Attacks Occurrence During Study Period | HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of participants with HAE attacks occurrence (start and end date of each HAE attack) during study period will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Categorized Based on Characteristics of HAE Attacks During Study Period | HAE attack characteristics will be based on prodromal symptoms, severity and location, whether attack was life-threatening will be reported. | Throughout the study period (up to 6 months) | 
| Time Interval Between HAE Attacks During Study Period | Time interval between HAE attacks during the study period will be reported. | Throughout the study period (up to 6 months) | 
| Duration of Each HAE Attacks During Study Period | Duration of each HAE attacks during study period will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Based on Type of HAE Prophylactic Treatments | Number of participants based on type of HAE prophylactic treatment will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Based on Long-term or Short-term HAE Prophylactic Treatment | Number of participants based on long-term or short-term HAE prophylactic treatment will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Categorized Based on Reasons for HAE Prophylactic Treatment Initiation | Number of participants categorized based on reasons for HAE prophylactic treatment initiation will be reported. | Throughout the study period (up to 6 months) | 
| Duration of HAE Prophylactic Treatment | Duration of HAE prophylactic treatment includes treatment start and end dates will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Categorized Based on Dose and Route of Administration for HAE Prophylactic Treatment | Number of participants categorized based on dose and route of administration for HAE prophylactic treatment will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Categorized Based on Reasons for HAE Prophylactic Treatment Discontinuation | Number of participants categorized based on reasons for HAE prophylactic treatment discontinuation will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Based on Type of HAE On-demand Treatment | Number of participants based on type of HAE on-demand treatment will be reported. | Throughout the study period (up to 6 months) | 
| Duration of HAE On-demand Treatment | Duration of HAE on-demand treatment includes treatment start and end dates will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Categorized Based on Dose and Route of Administration for HAE On-demand Treatment | Number of participants categorized based on dose, route of administration and setting of administration for HAE on-demand treatment will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Associated Between Prescriptions Patterns and HAE Attacks | Number of participants with association between prescriptions patterns and HAE attacks related to frequency or severity. Generalized linear models (GLM) will be used to evaluate the association of outcomes of interest with relevant covariates between prescription pattern, HAE attacks, frequency and severity of HAE attacks will be reported. | Throughout the study period (up to 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthcare Resource Utilization (HRU): Number of Visits to Healthcare Professionals (HCP) | HRU is measured by the number of visits to HCP will be reported. | Throughout the study period (up to 6 months) | 
| HRU: Number of Participants With Emergency Room/Emergency Departments (ER/ED) Visits due to HAE Attacks | Number of participants with ER/ED visits due to HAE attacks will be reported. | Throughout the study period (up to 6 months) | 
| HRU: Number of Participants With Hospitalizations due to HAE Attacks | Number of participants with hospitalizations due to HAE attacks will be reported. | Throughout the study period (up to 6 months) | 
| Health-related Quality of Life (HRQoL): Angioedema Quality of Life (AE-QoL) Questionnaire | The AE-QoL was developed to measure HRQoL in participants with recurrent angioedema. It is a self-administered patient-reported outcome instrument with a recall period of four weeks. There are 17 items across four domains: functioning (four items), fatigue/mood (five items), fears/shame (six items), and food (two items). Responses use a 5-point Likert scale ranging from 1 (Never) to 5 (Very Often). Global scores range from 0 to 100 and scores by domains range from 0 to 100. An overall score is calculated and a higher score indicates lower quality of life. | Throughout the study period (up to 6 months) | 
| HRQoL: EuroQoL Group 5-Dimension 5-Level (EQ-5D-5L) Questionnaire | The EQ-5D-5L descriptive system assesses health in five dimensions (Mobility, Self-Care, Usual Activities, Pain / Discomfort, Anxiety / Depression), each of which has five levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems/unable to). This part of the EQ-5D questionnaire provides a descriptive profile that can be used to generate a health state profile. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The second part of the questionnaire consists of a visual analogue scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). | Throughout the study period (up to 6 months) | 
| HRQoL: EuroQoL-five Dimensions, Youth Version (EQ-5D-Y) | The EQ-5D-Y is composed of two sections. The first section contains one question for each of the five dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. Participants select from three response levels (no problems, some problems, a lot of problems) for each dimension. A health state profile score can be calculated from the responses on these five questions. The second section includes the same visual analogue scale as the EQ-5D-5L. The scale is scored from 0-100. The reference to a high score indicates a better outcome of quality of life. | Throughout the study period (up to 6 months) | 
| Number of Participants With HAE Attacks Occurrence in Relevant Subgroups | HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE). Number of participants with HAE attacks occurrence (start and end date of each HAE attack) in relevant subgroups will be reported. | Throughout the study period (up to 6 months) | 
| Number of Participants Categorized Based on Characteristics of HAE Attacks in Relevant Subgroups | HAE attack characteristics will be based on prodromal symptoms, severity and location, whether attack was life-threatening in relevant subgroups will be reported. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE). | Throughout the study period (up to 6 months) | 
| Time Interval Between HAE Attacks in Relevant Subgroups | Time interval between HAE attacks in relevant subgroups will be reported. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE). | Throughout the study period (up to 6 months) | 
| Duration of Each HAE Attacks in Relevant Subgroups | Duration of each HAE attacks in relevant subgroups will be reported. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE). | Throughout the study period (up to 6 months) | 
| HAE Attacks Prescription Pattern in Relevant Subgroups | Prescription pattern of HAE attacks medication by drug class in relevant participant subgroups during study period. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE). | Throughout the study period (up to 6 months) |