Prophylactic Efficacy of Relenza Against Influenza A and B

Study Overview
=================
Brief Summary
-----------------
In response to the European regulatory authorities, GSK is conducting a post-marketing observational study to assess the efficacy of Relenza when used as prophylaxis against influenza. SPECIFIC AIMS Determine the frequency of patients who received Relenza from October 2006 through April 2009, and among them the number who have no concurrent diagnosis of influenza, i.e., those receiving Relenza for prophylaxis, and among these the number who have a family member with a medical visit for influenza within three days preceding the above indentified patient's dispensing of Relenza. This is to determine the feasibility of conducting detailed analysis. If analysis is feasible then tabulate the frequency of influenza-like-illness and respiratory outcomes in users of prophylactic Relenza and their family members and in family members of persons using Relenza for the treatment of influenza (i.e., index cases). If analysis is feasible then estimate the direct effect of prophylactic Relenza on the occurrence of influenza-like-illness and respiratory outcomes, the secondary effect of Relenza treatment of influenza on susceptible family members, and the total effect of Relenza (treatment plus prophylaxis). METHODS Overview of Study Design This is an analysis of the 30-day risk of influenza-like illness and respiratory outcomes in persons for whom some household members (index cases) have had a medical visit associated with a diagnosis of influenza. The exposed individuals to the index case will be categorized into one of four cohorts according to whether the exposed person received prophylactic Relenza or no antiviral treatment and by whether the index family member with a diagnosis of influenza received antiviral treatment. Estimates of the direct effect of Relenza prophylaxis, the indirect effectof preventing disease in susceptible family members, and the total effect of disease reduction when both index cases and susceptible family members are treated will be obtained from different comparisons between cohorts, as outlined below. The research will cover the first three influenza seasons during which Relenza has been indicated for prophylactic use in the United States. These will be from October through April of 2006-2009.

Detailed Description
-----------------
***Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.*** This analysis will use the i3 Ingenix proprietary National Health Information (NHI) database, containing claims and enrollment data back to 1993, with the opportunity to link patient and physician survey data to pharmacy and medical claims, and clinical laboratory results. These data are use for a wide range of pharmacoepidemiologic, healthcare utilization, and economic analyses. In addition to data derived from affiliated health plans, data from large, national employer groups are also stored in the database. The data undergo regular audits and quality control procedures. The accessible information includes demographics, pharmacy use, and all medical and facilities claims, which provide data on services, procedures, and their accompanying diagnoses. Underlying information is geographically diverse across the US, and is updated frequently. The insured population from which the database draws the data comprises approximately 4 percent of the US population. The data used for analysis is de-identified. Study Cohorts From October 2006 through April 2009, we will count patients receiving prophylactic Relenza, defined as a dispensing of Relenza to a person who meets two criteria: (1) not having had a diagnosis of influenza associated with medical care on the day of dispensing or in the preceding three days, and (2) a household member has had a diagnosis of influenza associated with medical care on the day of the index dispensing or within the preceding three days. Household members will be defined operationally as persons within the RDM sharing a common family identifier and address. We will assemble the study cohorts for the 3 influenza seasons running from October 2006 through April 2009. Cohort membership is based on the treatment an individual receives and the nature of household exposure. Exclusion criteria include: Sex unknown Year of birth is missing or where the date of dispensing or service date preceded the year of birth Age at index date is less than 5 years Not enrolled in the health plan for 6 months prior to the study entry date Observation begins for the prophylaxis and treated patients on the day following Relenza dispensing and for the non-prophylaxis and untreated patients on the third day following their medical visit, and continues for a total of 30 days. Covariates For each individual we will identify age, sex, medical conditions requiring care in the six months preceding cohort entry from insurance claims for health services. Medical conditions requiring care will be defined at the 3-digit ICD9 diagnostic level. Outcomes We will identify medical visits and hospitalizations with influenza-like illness and respiratory disease in the 30 days following cohort entry. Analysis Within categories of age of 5-14, 15-44, 45-64 and 65+ years, we will tabulate: the number of individuals in each of four cohorts (cohorts defined below) the number of medical visits for influenza-like illness and respiratory illness in the 30-day follow-up period For each outcome we will estimate the following antiviral efficacy measures detailed in Halloran's analysis of clinical trials data [Halloran, 2007]. The first two effects below will be standardization to the age distribution of all persons receiving prophylactic Relenza; Direct Effect of Relenza Prophylaxis: Risk in Cohort 1 is less than Risk in Cohort 3 Prophylaxis patient with untreated index case vs patient without prophylaxis with untreated index Total Effect of Relenza Prophylaxis and Treatment: Risk in Cohort 2 is less than Risk in Cohort 3 Prophylaxis patient with treated index case vs. patient without prophylaxis with untreated index We will calculate the following effect estimate with standardization to the age distribution of untreated persons. Protective Effect of Relenza Prophylaxis on Susceptible: Risk in Cohort 2 is less than Risk in Cohort 4 Prophylaxis patient with treated index case vs. patient without prophylaxis with treated index Using binomial regression and a linear risk model, we will obtain adjusted estimates for Direct Effect, Total Effect, and Protective Effect, defined as above, adjusted for age group, sex, and any diagnosis with a prevalence of at least 10 percent in the cohorts combined.

Official Title
-----------------
Prophylactic Efficacy of Relenza Against Influenza A and B

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive, Bronchospasm, Influenza, Human, Asthma, Respiratory Disease, Exacerbation of COPD, Bronchitis, Otitis Maedia, Pneumonia, Sinusitis

Intervention / Treatment
-----------------
* Drug: Receiving a prescription of Relenza for prophylaxis
* Other: No prophylaxis with Relenza


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 5 years or older At least 6 months of continuous follow up time Received Relenza without a diagnosis of influenza Exclusion Criteria: Sex unknown Year of birth is missing Date of dispensing or service date preceded the year of birth Age at index date is less than 5 years Not enrolled in the health plan for 6 months prior to the study entry date
Sexes Eligible for Study
-----------------
All

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort1: Prophylaxis with untreated index<br>Individuals are eligible to be included in the prophylaxis with untreated index cohort if they are at least 5 years old and have at least 6 months of continuous enrollment, and Received a dispensing of Relenza (HICL=020398 or HCPCS = G9018 or G9034), and Have no diagnosis of influenza (ICD-9 487.xx) on the day of Relenza dispensing or in the 3 preceding days, and A household member (index case) with the same family identifier code has had a medical visit (outpatient, inpatient or emergency room (ER) visit) in the 3 days preceding or the day of the Relenza dispensing with a diagnosis of influenza (ICD-9 487.xx), and The household member (index case) has not received any antiviral therapy (oseltamivir (Tamiflu), rimantadine, amantadine, and zanamivir (Relenza)) on the day of or the day after the index case's medical visit associated with a diagnosis of influenza. | Drug: Receiving a prescription of Relenza for prophylaxis<br>* Receiving a prescription of Relenza for prophylaxis<br>|
| Cohort2: Prophylaxis with treated index<br>Individuals are eligible to be included in the prophylaxis with treated index cohort if they are at least 5 years old, have 6 months continuous enrollment and Received a dispensing of Relenza (HICL=020398 or HCPCS = G9018 or G9034), and Have no diagnosis of influenza (ICD-9 487.xx) on the day of Relenza dispensing or in the 3 preceding days, and A household member (index case) with the same family ID variable has had a medical visit (outpatient, inpatient or ER visit) in the 3 days preceding or the day of the Relenza dispensing with a diagnosis of influenza (ICD-9 487.xx), and The household member (index case) has received any antiviral therapy (oseltamivir (Tamiflu), rimantadine, amantadine, and zanamivir (Relenza)) on the day of or the day after the index case's medical visit associated with a diagnosis of influenza. | Drug: Receiving a prescription of Relenza for prophylaxis<br>* Receiving a prescription of Relenza for prophylaxis<br>|
| Cohort3: No prophylaxis with untreated index<br>Individuals are eligible to be included in the no prophylaxis with untreated index cohort if they are at least 5 years old, have 6 months continuous enrollment and Have not received a dispensing of Relenza (HICL=020398 or HCPCS = G9018 or G9034) within 3 days following the date on which A household member (index case) with the same family ID variable has had a medical visit (outpatient, inpatient or ER visit) with a diagnosis of influenza (ICD-9 487.xx), and The household member (index case) has not received any antiviral therapy (oseltamivir (Tamiflu), rimantadine, amantadine, and zanamivir (Relenza)) on the day of or the day after the index case's medical visit associated with a diagnosis of influenza. | Other: No prophylaxis with Relenza<br>* No prophylaxis with Relenza<br>|
| Cohort4: No prophylaxis with treated index<br>Individuals are eligible to be included in the no prophylaxis with treated index cohort if they are at least 5 years old, have 6 months continuous enrollment and Have not received a dispensing of Relenza(HICL=020398 or HCPCS = G9018 or G9034) within 3 days following the date on which A household member (index case) with the same family ID variable has had a medical visit (outpatient, inpatient or ER visit) with a diagnosis of influenza (ICD-9 487.xx), and The household member (index case) has received zanamivir (Relenza) on the day of or the day after the index case's medical visit associated with a diagnosis of influenza | Other: No prophylaxis with Relenza<br>* No prophylaxis with Relenza<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Influenza | The frequency of influenza among the four cohorts was measured. | 2006-2009 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Asthma | The frequency of asthma among the four cohorts was measured. | 2006-2009 | 
| Number of Patients With Pneumonia | The frequency of pneumonia among the four cohorts was measured.. | 2006-2009 | 
| Number of Patients With Bronchitis | The frequency of bronchitis among the four cohorts was measured. | 2006-2009 | 
| Number of Patients With Any Respiratory Diagnosis | The frequency of any respiratory diagnosis among the four cohorts was measured. | 2006-2009 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza, Zanamivir, Influenza prophylaxis, Relenza