1
Confidential
Version 1.003-Jun-2014
Epidemiology and Inpatient Management of Patients Hospitalized for Acute Asthma: 37th Multicenter Airway Research Collaboration (MARC-37) Study
Author(s): / ______, MD (Site Investigator)Carlos A. Camargo, MD, DrPH (Principal Investigator; Emergency Medicine Network Coordinating Center, Massachusetts General Hospital)
Version number: / 1.0
Release date: / 03-Jun-2014
Number of pages: / 23pages + data collection instruments
Grant support / This study is supported by a grant from Novartis to the Massachusetts General Hospital.
Non-interventional study protocolProduct number/name/Study number
Table of contents
Table of contents......
List of abbreviations......
Protocol synopsis
1Background......
2Purpose and rationale......
3Objectives......
4Study design......
5Population and setting......
5.1Inclusion criteria......
5.2Exclusion criteria......
5.3Data sources......
5.4Study completion......
5.5Premature study discontinuation......
6Data collection/measurement......
6.1Patient demographics/characteristics......
6.2Site Survey......
6.3Medications of interest
6.4Outcomesof interest......
6.5Safety related measurements......
7Safety monitoring......
8Data analysis
8.1Patient demographics/other baseline characteristics......
8.2Drug exposure......
8.3Analysis of the main objectives......
8.3.1Primary Variables
8.3.2Handling of missing values/censoring/discontinuations......
8.3.3Other......
8.4Sample size/power calculation......
9Data monitoring and quality control......
9.1Sitemonitoring......
9.2Data recording and documentretention......
9.3Data qualityassurance......
10Limitations......
11Ethical considerations......
11.1Regulatory and ethical compliance......
11.2Informed consent procedures......
11.3Responsibilities of the site investigator and IRB......
11.4Early termination of study......
11.5Publication of study protocol and results......
11.6Protocol adherence and amendments......
12References
13Appendices......
13.1Appendix 1 Description of quality measures for inpatient acute asthma care.....
13.2 Appendix 2 Data collection instruments......
List of abbreviations
CRFCase Report/Record Form
eCRFelectronic Case Report/Record Form
EDEmergency Department
EMNetEmergency Medicine Network
ENCePPEuropean Network of Centres for Pharmacoepidemiology and Pharmacovigilance
EPR-3Expert Panel Report 3
GPPGood Pharmacoepidemiology Practices
ICD-9-CMInternational Classification of Diseases, Ninth Revision, Clinical Modification
IRBInstitutional Review Board
ISPEInternational Society for Pharmacoepidemiology
MARCMulticenter Airway Research Collaboration
NAEPPNational Asthma Education and Prevention Program
NIHNational Institutes of Health
NISNon-interventional Study
PEFPeak expiratory flow
PHIProtected health information
PIPrincipal Investigator
REDCapResearch Electronic Data Capture
SOPStandard Operating Procedure
STROBEStrengthening the Reporting of Observational Studies in Epidemiology
UHCUniversity HealthSystem Consortium
Protocol synopsis
Title of study: Epidemiology and Inpatient Management of Patients Hospitalized for Acute Asthma: 37thMulticenter Airway Research Collaboration (MARC-37) Study
Version and Date: Version 1.0. 31-May-2014
Name and affiliation of site investigator:______, MD; ______Hospital.
Background:Asthma hospitalizations represent a serious adverse outcome. In addition, the public health burden of asthma hospitalizations remains significant:385,000 asthma-related hospitalizations in 2011, with an estimated direct cost of $ 2.3 billion annually. In a prior 30-center inpatient study (the University HealthSystem Consortium [UHC] Asthma Clinical Benchmarking Project in 1999-2000), we demonstrated sex and racial/ethnic differences in asthma presentations and quality of inpatient care. However, current information on the epidemiology of patients hospitalized for acute asthma and the quality of inpatient asthma care is scarce. Furthermore, although the 2007 Expert Panel Report 3 (EPR-3) guidelines recommended referral to asthma specialist for patients with asthma hospitalization, there has been limited research on post-hospitalization asthma care.The current study will address these knowledge gaps and facilitate studies to implement preventive measures for this high-risk and costly population.
Purpose and rationale:To assist ongoing efforts to improve inpatient and post-hospitalization management of asthma and to reduce the burden of healthcare utilization and associated health care expenditures, the study will characterize today’s hospitalized asthma patients, to determine the concordance of their inpatient care with national asthma guidelines, and to characterize the post-hospitalization asthma care. The results will facilitate studies to implement preventive measures for this high-risk and costly population.
Objectives: The study objective includes:
(1)To describe hospitalized patients with acute asthma.
(2)To quantify the proportion and characteristics of patients with at least one asthma hospitalization in the 12 months before their index hospitalization.
(3)To evaluate the concordance of current inpatient management of acute asthma with the 2007 EPR-3 guidelines.
(4)To describe post-hospitalization asthma care, including referral to an asthma specialist, allergy testing, and any adjustments to patients’ long-term controller medications.
Study design: We will conduct a multi-center chart review study examining a total of 1000 patients hospitalized with acute asthma to assess their current characteristics and inpatient management in 25 hospitals across the USA. MARC-37 study will be coordinated by EMNet (based at Massachusetts General Hospital), a research collaboration with >225 participating hospitals. EMNet will recruit the 25 hospitals by inviting all 30 sites that conducted the UHC study in 1999-2000.
Using a standardized protocol, investigators at each participating hospital will perform data abstraction from 40 randomly selected charts to collect information about patients hospitalized for acute asthma.
Population:MARC-37 sites will use hospital administrative records and the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)codes 493.xx, to identify all charts with a principal hospital discharge diagnosis of asthma during a 12-month period, between January 1, 2012 to December 31, 2013 (i.e., 24-month window). The hospital visit chosen for chart review will be selected at random from all asthma-related hospital visits over the 12-month period; the randomly-selected visit will not necessarily be the first visit by the patient during the 12-month period. Each site will randomly sample at least 40 visits for chart review (40 visits/site x 25 sites = 1000 visits).
Inclusion/Exclusion criteria:
1)Inclusion criteria are: 1) patients aged 2 to 54 years 2) a history of asthma before the index hospitalization
2)Exclusion criteria are: 1) hospitalizations made by patients with a history of cystic fibrosis or chronic obstructive pulmonary disease, 2) transfer hospitalizations, and 3) repeat hospitalizations by the same subject (i.e., each hospitalization in the study database will represent a unique patient).
Data sources:MARC-37 investigators will examine a total of 1000 patients. At each of the 25 sites, chart abstractors will review 40 charts that were randomly selected by the EMNet Coordinating Center at Massachusetts General Hospital.
Exposure to medication(s) of interest and comparator therapy: Medications of interest include:
1)Regular asthma medications (e.g., inhaled beta-agonists, inhaled corticosteroids, leukotriene modifiers, omalizumab, systemic corticosteroids) before the index hospitalization
2)Preadmission treatments (e.g., inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, intravenous magnesium)
3)Discharge medications (e.g., systemic corticosteroids, inhaled corticosteroids, leukotriene modifiers)
4)Post-hospitalizationlong-term controller treatment (e.g., inhaled corticosteroids, long-acting β2 agonists, and omalizumab)
Outcomes of interest:
(1)Outcomes for Aim 1 include patient demographics (e.g., socioeconomic factors, smoking), past asthma history (e.g., number of asthma emergency department visits in the past year), chronic asthma medications, and laboratory testing (e.g., total and specific IgE levels).
(2)The outcome for Aim 2 is the frequency of asthma hospitalizations in the past year.
(3)Outcomes for Aim 3 are guideline-concordance scores (calculated from inpatient asthma treatments and discharge factors).
(4)Outcomes for Aim 4 include referral to an asthma specialist, allergy testing, and any adjustments to long-term controller medications.
Safety related measurements: Not applicable
Data analysis: All analyses will be performed by the EMNet Coordinating Center at Massachusetts General Hospital (Boston, MA).
Summary statistics at both the patient- and site-levels will be presented as proportions (with 95% confidence intervals), means (with standard deviations), or medians (with interquartile ranges) (Aims 1 and 4). Then, patients will be classified into two inpatient utilization groups based on their number of asthma hospitalizations in the 12 months before their index hospitalization (Aim 2). Patients will be categorized as “no asthma hospitalization in past year” and one or more hospitalizations in the past 12 months. We will describe the summary statistics of the outcomes of interest in each stratum. The association between the number of hospitalizations and the outcomes of interest will be examined. Finally, we will calculate the 10 inpatient evidence-based process measures (Appendix 1) at the patient-level (Aim 3). These scores then will be averaged across patients at the hospital-level to obtain inpatient composite scores. Associations between hospital characteristics and composite concordance scores will be assessed by using multivariable linear regression, adjusting for aggregate patient mix at the hospital level.
1Background
Asthma hospitalizations represent a serious adverse outcome that is theoretically preventable with optimal management of asthma. Although several cost-effective preventive measures are available,1 the public health burden of asthma hospitalizations remains significant: 385,000 asthma-related hospitalizations in 2011, with an estimated direct cost of $ 2.3 billion annually (and an estimated charge of $ 8 billion).2 In this context, the US government identified the reduction of hospitalizations for acute asthma as a national objective in Healthy People 2020 through better prevention, treatment, and education efforts. In a prior 30-center inpatient study (the University HealthSystem Consortium [UHC] Asthma Clinical Benchmarking Project in 1999-2000),3we demonstrated sex and racial/ethnic differences in asthma presentations and quality of inpatient care.4-6 However, current information on the epidemiology of patients hospitalized for acute asthma and the quality of inpatient asthma care is scarce. Furthermore, although the 2007 Expert Panel Report 3 (EPR-3) guidelines recommended referral to an asthma specialist for patients with asthma hospitalization, there has been limited research on post-hospitalization asthma care.
2Purpose and rationale
To assist ongoing efforts to improve inpatient and post-hospitalization management of asthma and to reduce the burden of healthcare utilization and associated health care expenditures, the study will characterize today’s hospitalized asthma patients, to determine the concordance of their inpatient care with national asthma guidelines, and to characterize the post-hospitalization asthma care. The results will facilitate studies to implement preventive measures for this high-risk and costly population.
3Objectives
The study objectives include:
Aim 1: To describe hospitalized patients with acute asthma.
Aim 2: To quantify the proportion and characteristics of patients with at least one asthma hospitalization in the 12 months before their index hospitalization.
Aim 3: To evaluate the concordance of current inpatient management of acute asthma with the 2007 EPR-3 guidelines.
Aim 4: To describe post-hospitalization asthma care, including referral to an asthma specialist, allergy testing, and any adjustments to patients’ long-term controller medications.
4Study design
We will conduct a multi-center chart review study of 1000 patients hospitalized with acute asthma in 25 hospitals across the USA.MARC-37 study will be coordinated by EMNet (based at Massachusetts General Hospital), a research collaboration with >225 participating hospitals.It will build on the success of the UHC study in 1999-2000,3 by updating observational data from 25 general and children’s hospitals in that prior study. Using a standardized protocol, investigators at each participating hospital will perform data abstraction from 40 randomly selected charts to collect information about patients hospitalized for acute asthma.
Before data collection, each MARC-37 site will obtain Institutional Review Board (IRB) approval of the protocol, with waiver of informed consent for the chart review study and informed consent implied through voluntary completion of the online site survey. Copies of all IRB approvals will be retained by EMNet Coordinating Center.
5Population and setting
We will identify hospitalizations duringa 24-month period to facilitate implementation of the study across the 25 sites. Although we will encourage all sites to start with calendar year 2013 (i.e., January 2013 to December 2013), some sites will not be able to run a calendar year 2013 search until later in 2014. Others will prefer to work within their fiscal year (e.g., July 2012-June 2013; Oct 2012-Sep 2013) because data are more readily available for that time period.
Each site will identify hospitalizations with a principal hospital discharge diagnosis of asthma during a 12-month period. The EMNet Coordinating Center will randomly select at least 40 hospitalizations for chart review. The exclusion criteria will require that some sites sample >40 to yield 40 eligible hospitalizations. For example, random sampling may yield two hospitalizations by the same person; the hospitalization that was sampled first will be retained for chart review, unless it is otherwise ineligible (e.g., transfer). We will avoid systematic retention of the earlier hospitalization during the 12-month period (e.g., choosing January hospitalization before May hospitalization) to avoid over-representation of hospitalizations that occurred earlier in the 12-month period, which often will be based on calendar year. The review of 40 hospitalizations per site, at 25 sites, will yield a database with 1000 hospitalizations. Each hospitalization will represent a unique patient.
5.1Inclusion criteria
Inclusion criteria are:
1) Patients aged 2 to 54 years with a history of asthma before the index hospitalization, and
2) Patients with a principal hospital discharge diagnosis of asthma during a 12-month period between January 1, 2012 to December 31, 2013 (i.e., 24-month window)
5.2Exclusion criteria
Exclusion criteria are:
1) Hospitalizations made by patients with a history of cystic fibrosis or chronic obstructive pulmonary disease
2) Transfer hospitalizations, and
3) Repeat hospitalizations by the same subject
5.3Data sources
MARC-37 investigators will examine a total of 1000 hospitalized patients. At each of the 25 sites, chart abstractors will review 40 charts randomly selected by the EMNet Coordinating Center using a random numbers table. All sites will have >40 acute asthma charts in the preceding 12-month period. Chart abstractors will have some medical training, with the vast majority being physicians, nurses, or respiratory therapists. Abstractors will be trained by the EMNet Coordinating Center, and then the abstractors will complete two practice charts, which will be assessed versus a ‘‘criterion standard.’’ If an abstractor’s accuracy is less than 80% per chart, the individual will be retrained. Online tools (e.g. an extensive Manual of Procedures) will be available for abstractors. Since all forms already have been adapted from forms used in prior successful studies,3-21 we are confident that the forms will function well across the 25 sites in the MARC-37 study.
Data will be entered directly into an online database, using the National Institutes of Health (NIH)-sponsored Research Electronic Data Capture (REDCap).22 REDCap is a secure, web-based, electronic database hosted at Massachusetts General Hospital, and is being used in several ongoing EMNet studies. All data entered into REDCap by site investigators will undergo further review by the MARC-37 Project Coordinator and trigger specific data queries, as needed. Access to the REDCap database will be limited to study personnel only and require an individual assigned username and password. The REDCap database will be exported into Microsoft Excel and then imported into Stata for statistical analysis. All files will be kept on secure, password-protected servers at Massachusetts General Hospital.
5.4Study completion
Each site will complete the study when they complete their site survey, submit data from 40 randomly-selected charts, and have answered any queries about their submitted chart review data.
5.5Premature study discontinuation
Not applicable.
6Data collection/measurement
This is a non-interventional study and does not impose a therapy protocol, diagnostic/therapeutic procedure, or a visit schedule. Patients will be treated according to the local prescribing information, and routine medical practice in terms of visit frequency and types of assessments performed and only these data will be collected as part of the study.
6.1Patient demographics/characteristics
Data abstracted from charts will include:
- Baseline patient characteristics (e.g., age, sex, race/ethnicity, home ZIP code [to assign median household income], primary care physician status, primary insurance, pregnancy status, smoking history, obesity, other comorbid conditions)
- Past asthma history (e.g., age of diagnosis, history of hospitalization and/or intubation secondary to asthma, frequency of asthma-related hospitalizations and ED visits during the 12 months before the index hospitalization, outpatient management by an asthma specialist)
- Laboratory testing at each study site over the 12 months before the index hospitalization (e.g., total IgE, specific IgE, skin-prick testing)
- Regular asthma medications (e.g., inhaled beta-agonists, inhaled corticosteroids, leukotriene modifiers, omalizumab, systemic corticosteroids) and medication adherence before the index hospitalization
- Location of preadmission assessment (e.g., ED, clinic/office)
- Preadmission presentation (e.g., season, time of arrival, vital signs, peak expiratory flow)
- Preadmission treatments (e.g., inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, intravenous magnesium) and their timing relative to the patient’s ED/clinic arrival time
- Initial hospital admission location (e.g., observation unit, hospital ward, intensive care unit)
- Inpatient management (e.g., laboratory testing [e.g., total IgE] and treatment)
- Disposition (home, died in hospital, other)
- Length of stay (inpatient, intensive care unit)
- Discharge medications (e.g., systemic corticosteroids, inhaled corticosteroids, leukotriene modifiers)
- Discharge plan (e.g., asthma action plan at discharge, follow-up appointment.
- Post-hospitalization asthma care (e.g., referral to an asthma specialist, allergy testing, and any adjustments to long-term controller treatment [e.g., inhaled corticosteroids, long-acting β2 agonists, and omalizumab]).
To avoid privacy concerns, sites will not send any protected health information (PHI) to the EMNet Coordinating Center. Specifically, patient date of birth, date of hospitalization, date of hospital discharge, and ZIP code will be collected on the Chart Review Log and converted, as necessary, to non-PHI data. For example, date of birth will yield age in years. Likewise, ZIP code will be used to look up specific information of interest (e.g., median household income).
Peak expiratory flow (PEF) is recorded in liters per minute and expressed as the absolute value. Severity of acute asthma will be classified according to the initial PEF as follows: mild, 300 L/min or greater for women and 400 L/min or greater for men; moderate, 200 to 299 L/min for women and 250 to 399 L/min for men; severe, 120 to 199 L/min for women and 150 to 249 L/min for men; and very severe, less than 120 L/min for women and less than 150 L/min for men. The absolute PEF values represent approximately 70%, 40%, and 25% of predicted value, respectively, for a typical adult woman and man.23