PCORI contract # AS 1307-05420
11-24-2014
Study protocol, DSMB-approved
November 24, 2014
UIC PAF # 2014-01275
UIC IRB protocol #: pending
Clinicaltrials.gov registration #: pending
Patient Centered Outcomes Research Institute, contract # AS 1307-05420
Project period: March 1, 2014 - February 28, 2017
CHICAGO Trial Protocol, submitted to IRB, v1, 11-24-14
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TABLE OF CONTENTS
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
XII.
XIII.
XIV.
XV.
Executive summary
Overview of pragmatic trial
Primary and secondary aims
Study population
Interventions and comparators
Randomization
Data collection
A. Screening and enrollment (registration) into the study (in person)
B. 1-month follow-up visit after ED discharge (telephone)
C. 3-month follow-up visit after ED discharge (telephone)
D. 6-month follow-up visit after ED discharge (in person)
E. 12-month follow-up visit after ED discharge (telephone)
Outcomes
A. Co-primary outcomes
B. Secondary outcomes
Analysis plan
Identify barriers and facilitators of successfully implementing the intervention
(secondary aim)
Timeline / milestones
Protection of human subjects research
A. Risks to human subjects
B. Adequacy of protection against risks
C. Potential benefits of the proposed research to the subjects and others
D. Importance of the knowledge to be gained
E. Data safety monitoring plan
F. Clinicaltrials.gov requirements
G. Inclusion of women and minorities
Participating investigators, staff, and partnerships
References
Appendices
A. CAPE tool
B. Outline of home visit procedures
C. Chart review
D. Baseline questionnaire domains
E. 1-month follow-up questionnaire domains
F. 3-month follow-up questionnaire domains
G. 6-month follow-up questionnaire domains
H. 12-month follow-up questionnaire domains
I. Key performance indicators
J. PCORI approved milestones
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I. Executive summary
Background
Chicago is an epicenter for asthma health disparities in the United States, with African American children
5-11 years old bearing a disproportionate share of the burden.1-5 Among the most visible of these
disparities is the high rate of visits to the Emergency Department (ED) for uncontrolled asthma. Effective
strategies to implement national asthma guideline recommendations in this population are needed. As
part of a Patient Centered Outcomes Research Institute contract (AS 1307-05420; Coordinated
Healthcare Interventions for Childhood Asthma Gaps in Outcomes [CHICAGO] Trial), we conducted
qualitative interviews and user-centered observations of caregivers, physicians, nurses, and community
health workers to inform the development of interventions to implement asthma guidelines in the ED
and at home. We now propose to conduct a pragmatic trial to evaluate the effectiveness of ED and
home-based interventions on patient- and caregiver-centered endpoints.
Primary Aim
Conduct a 3-arm parallel group pragmatic clinical trial comparing the effectiveness of: 1) a patient /
caregiver-centered ED discharge education tool (CHICAGO trial Action Plan after Emergency department
discharge, “CAPE” prior to ED discharge); 2) CAPE prior to ED discharge followed by five home visits over
six months by a community-health worker (CHW) to promote asthma self-management skills, including a
reduction in environmental triggers (CAPE plus Home); and 3) Usual Care.
Methods
We will enroll 640 English or Spanish-speaking children ages 5-11 years who are being discharged to
home following treatment for uncontrolled asthma at one of six EDs in Chicago. Children will be
randomly allocated to one of three groups: CAPE, CAPE plus Home, or Usual Care. All groups will receive
asthma care as per the treating physicians and nurses, one-on-one instruction about the use of a
metered dose inhaler (MDI) with spacer, and two free MDI spacers. In the CAPE and CAPE plus Home
groups, an ED coordinator will use the CAPE to review ED discharge instructions with the patient /
caregiver (instructions about the use of corticosteroids, rescue medications, follow-up visits, and other
self-management instructions). In the CAPE plus Home group, a trained CHW will also conduct five
home visits over six months to review the use of CAPE (and subsequently updated asthma action plans),
asthma medications (including respiratory inhalers), safety of the child when at school, and approaches
to reduce exposure to environmental triggers at home. Secondary objectives include evaluating the
potential for heterogeneity of treatment effects, identifying barriers and facilitators of successfully
implementing the interventions, and assessing the durability of effects after the end of all study
interventions (six months) to inform later implementation studies. Outcomes will be assessed over 6
months by phone and in-person, and 50% of participants will be invited to continue the study for
another 6 months to evaluate the durability of interventions at 12 months. There will be two co-primary
outcomes: PROMIS Asthma Impact, parent proxy (child) and PROMIS Satisfaction with social roles
(caregiver). Secondary outcomes will examine other patient reported outcomes, including asthma
control measures, self-management skills, and patterns of acute care utilization.
Partnerships to facilitate study
Drawing on relationships that span nearly two decades, the CHICAGO Trial includes partners based in
Chicago, Illinois who are dedicated to eliminating asthma health disparities. This partnership includes
caregivers and patient advocacy groups, clinicians, the City of Chicago Department of Public Health,
health systems, and patient-centered outcomes researchers.
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II. Overview of the pragmatic trial
The study will employ a pragmatic clinical trial design using randomization and concurrent control
groups to provide a rigorous evidence base that is also applicable to routine clinical practice. Several
aspects of the study design are intended to reflect a priority to generate evidence closer to the
“effectiveness” end of the continuum between efficacy and effectiveness. Effectiveness studies are
generally considered to provide information more applicable to “real-world” clinical (rather than
research) settings. To ensure that interventions are tailored to the needs of end-users, we conducted
qualitative interviews and user-centered observations of caregivers, ED and ambulatory physicians, ED
nurses, and community health workers during the first six months of the project period for the Patient
Centered Outcomes Research Institute contract #AS 1307-05420 (Coordinated Healthcare Interventions
for Childhood Asthma Gaps in Outcomes [CHICAGO] Trial; March 1, 2014 - February 28, 2017). Based on
this input, eligibility criteria are intended to be clinically applicable and recruitment will take place in
multiple EDs serving underserved communities in Chicago (six Clinical Centers serving different
populations of children 5-11 yrs presenting with asthma; 53 to 94% African-Americans across Clinical
Centers). We will minimize interactions between research staff and participants to mimic the “realworld”. Data collection will employ validated approaches, but are also intended to minimize participant
burden: 1) an in-person enrollment and baseline visit in the ED, at the time children and caregivers
present for care; 2) telephone follow-up visits at 1 and 3 months; and 3) an in-person follow-up visit in
the participant’s home at 6 months (immediately after all study interventions are completed in the CAPE
plus Home group). In approximately 50% of study participants, we will also conduct a phone follow-up
visit at 12 months to assess the durability of the intervention. In-person visits are needed to reliably
evaluate some critical outcomes (some patient-reported asthma control measures that benefit from inperson administration, e.g., cACT) and evaluation of self-management skills, e.g., inhaler technique and
steps taken to reduce environmental triggers). Interventions and comparators were designed to be
easily implemented in clinical practice or represent clinical practice (Usual Care).
III. Primary and secondary aims
Primary aim
Conduct a 3-arm parallel group pragmatic clinical trial (Figure 1) comparing the effectiveness of: 1) a
patient / caregiver-centered ED discharge education tool (CHICAGO trial Action Plan after Emergency
department discharge, CAPE); 2) CAPE prior to ED discharge followed by five home visits over six months
by a community-health worker (CHW) to promote asthma self-management skills, including a reduction
in environmental triggers (CAPE plus Home); and 3) Usual Care. In secondary analyses, we will evaluate
a) the durability of effects after the intervention period and b) the potential for heterogeneity of
treatment effects.
Secondary aim
Identify barriers and facilitators of successfully implementing the interventions to inform subsequent
implementation studies.
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Figure 1: CHICAGO Trial study scheme: 640 children age 5-11 years presenting with uncontrolled
asthma to the ED will be randomized to one of three groups: Usual Care; CAPE; CAPE plus Home. The
CAPE intervention will take place prior to ED discharge. The CHW-led home visits will take place over 6
months (five home visits at 2-3 days, 14 days, 30 days, 90 days, and 180 days after ED discharge). The
assessment of outcomes will be performed at baseline (in-person on the day of ED discharge; 0 days), 1
month (via phone; 30 days), 3 months (via phone; 90 days), and 6 months (in-person; 180 days) after ED
discharge. The first 50% of study participants will be invited to continue the study for an additional 6
months to help us assess the durability at effects at 360 days after ED discharge (6 months after the end
of the intervention period in the CAPE plus Home group).
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IV. Study population
The following eligibility criteria will be used for the proposed CHICAGO trial.
Inclusion criteria (all of the following)
1. Children age 5-11 years;
2. Presenting to the ED at one of six CHICAGO Trial Clinical Centers (Ann and Robert H. Lurie
Children’s Hospital of Chicago; Cook County Health & Hospitals System; Rush University Medical
Center; Sinai Health System; The University of Chicago; or University of Illinois Hospital & Health
Sciences System);
3. Clinical diagnosis of asthma exacerbation by the Attending physician in the ED;
4. Receiving care in the ED (or an associated Observation Unit) for asthma exacerbation, defined as
at least 1 dose of inhaled short acting bronchodilator (beta-2 agonist or anticholinergic via
inhaler or nebulizer) and at least 1 dose of systemic corticosteroids (oral or intravenous or
intramuscular)
5. At least 1 hour since receiving the first dose of inhaled short acting bronchodilator and systemic
corticosteroids (at least 1 hour from whichever occurred last);
6. Attending physician in the ED indicates that the child is more than 75% likely to be discharged
home from the ED.
7. Preferred language at home is English or Spanish (per caregiver) and the child speaks English or
Spanish.
Exclusion criteria (none of the following):
1. Discharged from ED to location other than home (e.g., hospital; other acute care or chronic care
facility or died prior to ED discharge). If a patient is discharged to location other than home,
then the patient will be considered ineligible and terminated from the study (the potential for
post-enrollment termination will be explained during informed consent). The rationale for
approaching patients prior to the time a final decision is made about disposition on ED discharge
is to provide the time necessary to complete study procedures described below;
2. Caregiver declines to provide informed consent prior to ED discharge;
3. If child ≥7 years old, child declines to provide assent prior to ED discharge;
4. Child or another member of child’s primary household (defined as location where the child is
likely to sleep >50% of nights for next 6 months) is a current or previous participant in the
CHICAGO Trial;
5. Child is currently enrolled in another research study involving an intervention for any condition
(observational studies are not an exclusion criterion);
6. A community Health Worker (CHW) is expected to conduct 1 or more home visits over the next
6 months to the child’s primary household as part of any other CHW program;
7. Child expected to move out of Chicago within the next 6 months.
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Rationale for including systemic corticosteroids as an inclusion criterion:
Our clinical experience and that of ED clinicians suggest that some children may present to the ED
(proportion may vary across EDs) with relatively mild asthma symptoms or for a range of medical/social
issues at which time, they may also receive some asthma treatment (e.g., 1 nebulization treatment with
bronchodilators for asthma).We wanted to target a group with a greater level of uncontrolled asthma,
hence used the systemic corticosteroids inclusion criterion. We would like very much to standardize
use of systemic corticosteroids across all EDs, but our own work over the past 2 decades as part of the
Illinois Emergency Department Asthma Surveillance Project (IEDASP) indicates that use of systemic
corticosteroid varies across sites (dose and duration) and we were unable to define one dosing strategy
that would be acceptable to all ED clinicians. We worried that if we mandate a specific systemic
corticosteroid regimen, that we would lose support for enrollment in EDs and have limited numbers of
eligible participants; our study findings would also have limited external validity.
As a compromise, we elected to stratify by site and then randomize within each site to minimize the
opportunity for confounding by systemic corticosteroid regimen post-ED discharge. We will also collect
data on what systemic corticosteroid regimen was prescribed for use post-ED discharge, providing the
opportunity for statistically “controlling” these site-specific variables. We recognize that our study
design “gives” a little on the internal validity aspects of the study design, but believe it is a compromise
between the benefits of rigor (efficacy design) and the need to generate findings that are applicable to a
range of clinical practices (effectiveness design).
Our study design is the result of what is feasible when embedding of research in multiple delivery
systems when the priority is to test a tool to promote use of discharge instructions rather than the
efficacy of specific corticosteroid regimens.
V. Interventions and comparators
The study will include two active comparators and a usual care condition. The Clinical Center PI and coinvestigator will present at department grand rounds and at faculty and staff meetings to explain the
rational and significance of the CHICAGO Trial and to obtain local support from clinicians, staff, and
administrators for the successful conduct of the CHICAGO Trial at their Clinical Center. All participants
(regardless of treatment group) will receive asthma care per their ED physician and nurse. In addition,
the CHICAGO Trial will provide education about the use of a metered dose inhaler (MDI) using teach-togoal methodology, and two MDI spacers free-of-charge (see Usual Care below for rationale).
1. CAPE. This intervention occurs prior to ED discharge and is intended to promote adherence to
guideline-recommended care after ED discharge (corticosteroids [systemic and inhaled], arrange
follow-up visit, rescue medications, self-management skills instruction; APPENDIX A [English
version]).6-9 A Spanish version of the CAPE is in development. An ED coordinator from each Clinical
Center will use teach-back to address the core content areas. These include the child’s / caregiver’s
ability to (a) understand what medications to use after discharge (systemic corticosteroids, rescue
medications; inhaled corticosteroids or another controller medication); (b) use appropriate MDI
technique with a spacer; (c) attend a post-ED discharge follow-up appointment; (d) recognize the
difference between controlled (green zone) and uncontrolled (yellow and red zones) asthma, and
when to seek additional medical care (yellow or red zones); (e) avoid known environmental triggers.
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The CAPE tool is intended to be a patient- and caregiver-centered approach to facilitating
communication and education prior to ED discharge. The CAPE tool was designed based on
caregiver, physician, and nurse input from all six Clinical Centers. The CHICAGO Trial ED coordinator
will complete the CAPE discharge tool, based on ED physician and nurse discharge instructions. The
ED and asthma site PIs will serve as opinion leaders to promote use of the CAPE for patients
randomized to CAPE in the CHICAGO Trial.
2. CAPE plus Home. Participants allocated to this active comparator will receive the same CAPE
intervention prior to ED discharge. In addition, a CHW trained by the CHICAGO Trial CHW
Coordinating Center will conduct five home visits over 180 days (6 months) to further promote
asthma self-management skills.10-12 These visits will occur 2-3, 14, 30, 90, and 180 days after ED
discharge. Each home visit will take 60 to 90 minutes to complete. The CAPE will be reviewed at
each home visit and updated as appropriate. Core content areas will be the same as in the CAPEonly intervention, and also include instructions about how to establish a plan with the child’s school
for managing asthma during school hours and implement a specific and feasible plan to reduce
environmental triggers at home.
Cigarette smoke, roach and mice were selected as the primary focus for interventions to reduce
environmental triggers based on the prevalence of exposures in the urban environment, scientific
literature linking these exposures to asthma health, and the availability of effective evidence-based
interventions to reduce exposure and improve asthma health.13-19
In terms of exposure, in inner city homes there are a variety of allergen exposures as follows:15,20,21
• Roach was , 55.1% of Chicago homes have Bla G1 levels >2 U/ g
• Dust mite was present at a level of >2ug/g in 15%
• Cat at Fel d1 >8ug/g of dust and dog can f1 at >10 ug/g of dust were present at <10 percent of
homes, and
• 95% of homes had mouse allergen levels with detectable allergen.17
As such, roach and mouse are very common exposures in inner city homes.
Of the common perennial allergens to which these inner city subjects are exposed, roach was a
sensitizer in over 60% of subjects with dust mite in 60%, and mouse in 18%.15,17,21 However, while
dust mite was a common sensitizer, a number of well performed studies have not supported the use
of dust mite encasements or dust mite abatement strategies.22-26
In this population, maximum symptom days, nocturnal symptoms and rates of hospital admission
were all highest in the exposed and sensitized groups for mouse allergen.15 Similarly for roach,
sensitized individuals exposed at levels greater than 8 U/g experienced greater morbidity, including
hospitalizations, urgent visits, and reported symptoms.21
Integrated pest management (which is a form of extermination using bait traps and insecticide) is an
approach which has been studied by a number of groups and found to be effective in improving
asthma symptoms including the NCICAS study,27 the ICAS study,13,15,28 as well as other groups
studies.29-31
We agree with the DSMB that smoking is an actionable target, but would respectively submit that
roach and mouse allergens are important sensitizations in our population, are present in a high
proportion of homes at levels associated with symptoms, and that approaches such as integrated
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pest management are effective in decreasing exposures and result in improvements in asthma
outcomes. The burden of evidence has resulted in our focus on integrated pest management
strategies in the inner city environment as being relevant to disease morbidity.16
We are aware that we will sometimes encounter situations that are beyond the scope or
responsibility of the CHW and parent to address without additional support. Fortunately, we have
recently received permission from the study sponsor (PCORI) to bring in another partner, the
Metropolitan Tenants Organization (MTO). MTO offers us additional support in better addressing
complex environmental issues, including those that might require extermination. Since 1985, MTO
has educated, organized and empowered tenants to have a voice in decisions that affect housing.
MTO serves more than 15,000 tenants annually, and is Chicago’s largest organizer of tenants. MTO
brings extensive expertise in housing, including local, state and national Healthy Homes efforts.
MTO and one the CHICAGO Trial’s current participating sites, the Sinai Urban Health Institute (SUHI),
have worked together on asthma healthy homes projects since 2008, with MTO serving as an
environmental expert, participating in the training of CHWs, assisting on cases with more complex
housing needs, assisting residents to eliminate environmental issues in their home environment,
and working with landlords to resolve cases while protecting tenant’s rights. On one such CDCfunded translational research study, SUHI referred 240 complex environmental cases to MTO, and
MTO was able to successfully resolve 160 (66.7%) of those cases. When considering specific
triggers, MTO resolved 68% of roach infestations, 68% of mold issues, and 62% of rodent issues.
These are high proportions given the severity of the situations encountered.
We have developed an expanded environmental protocol, which relies heavily on the two CHW
Supervisors who will be employed by SUHI, to act as housing advocates in addressing complex
environmental situations, including those that require extermination. MTO will provide training and
consultation services to the CHICAGO Trial. All CHWs will be trained by MTO in Integrated Pest
Management (IPM). IPM has been found to effectively reduce allergen levels, which in turn
improves asthma control. The CHW Supervisors will be further trained by MTO to address more
complex situations that require more extensive environmental remediation, housing advocacy,
protecting tenant’s rights, and navigating the landlord/tenant relationship. When extermination is
required, we will work with the landlord to identify an exterminator that uses IPM and to advocate
for extermination.
The CHICAGO Trial will provide supplies specific to these triggers (e.g., roach baits) free-of-charge.
We will also provide, as time allows, assistance with developing specific strategies to reduce
exposure to other possible asthma triggers identified by the CHW during the home visits conducted
at 14 and 90 days post-ED discharge (e.g., mold, dust, pets, irritants/strong odors, cold/flu, extremes
in weather, exercise, and emotions). An outline of procedures at each home visit is listed in
APPENDIX B.
The CHW Coordinating Center for the CHICAGO Trial is located at Sinai Urban Health Institute (SUHI),
an organization that is widely acknowledged to be a leader in the training, supervising, and
deployment of CHWs as members of the healthcare team. SUHI will train and supervise all CHWs for
the CHICAGO Trial. CHWs will be trained to promote the child’s and caregiver’s self-efficacy for
asthma self-management using interpretation, modeling, and performance mastery.32 This
approach will be used for assessing and improving asthma symptom control, as well as other selfmanagement skills described above. To illustrate the approach, we describe below the approach for
symptoms.
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Interpretation of symptoms begins first with knowledge of symptoms, followed by monitoring
changes in those symptoms (self-monitoring), then interpreting and reinterpreting causes of
symptoms, leading to the self-management skills of problem solving and decision making. An
example of this is a CHW helping a child to take their controller medication daily. The CHW teaches
the caregiver (e.g., mother) to monitor how often the child takes the medication over one week, as
a baseline. If necessary, the CHW then encourages the mother to set a goal of increasing the
frequency of controller use to once per day every day. Another component to increase self-efficacy
is modeling. This is accomplished through the shared life experience that CHWs bring to the
CHICAGO Trial program. It is also facilitated by the exploratory and guided discovery approaches
provided by popular education.33 A third component of self-efficacy enhancement is performance
mastery. When a person feels as though he or she accomplishes a goal, a sense of mastery is
experienced. The more goals are accomplished, the greater the sense of mastery and subsequent
self-efficacy.
To obtain performance mastery, CHWs will use action planning (“Behavior Change Plans” in the
CHICAGO Trial). Behavior Change Plans involve identifying one behavior the person would like to
change and developing a very specific plan to accomplish that change. Behavior Change Plans are
not the goal but rather small steps toward that goal. Therefore, to increase the sense of mastery,
Behavior Change Plans need to be specific, something the person wants to do and small enough to
be realistic and achievable within a short timeframe. After developing the Behavior Change Plan, the
CHW assesses the caregiver’s self-efficacy by asking: “How confident are you that you can complete
this behavior change plan?” On a scale of 1 to 10, a rating of 7 and below indicates that the plan is
unrealistic and needs to be narrowed down to something feasible. Problem solving and decision
making are the relevant self-management skills taught and reinforced with action planning.
3. Usual Care. The Usual Care group provides the basis to evaluate the effectiveness of each active
intervention versus current practice. Comparisons with Usual Care will also help to interpret results
if there is no observed difference in outcomes between the active comparators (i.e., are both active
comparators similarly effective or is neither effective relative to Usual Care). Focus groups with
caregivers and clinicians, as well as discussions with investigators indicate support for having a usual
care group in the study, but there was interest in having: (a) the CAPE tool available for use by ED
physicians and ED nurses in children assigned to the Usual Care group; and (b) the ED coordinator
providing education about appropriate MDI technique to the Usual Care group.
We acknowledge that both 3(a) and 3(b) could result in contamination between the Usual Care
group and the two CAPE groups. However, as we previously demonstrated in the Illinois Emergency
Department Asthma Surveillance Project (IEDASP), efforts to improve guideline consistent care by
relying on existing front-line clinicians is far from sufficient.34 Despite audit and feedback to
clinicians, adherence to guideline recommended care remained highly variable (e.g., use of inhaled
corticosteroids, mean 52% (range 38 to 65%); arranging a follow-up visit, mean 74% [range 55 to
100%]). A prescription for rescue medications was the only indicator of care that happened
consistently (100%). Moreover, clinical experience among CHICAGO Trial investigators indicates that
the availability of an education tool in the ED (e.g., CAPE) does not necessarily indicate that the tool
will be used due to limited staff time (this was the motivation for not relying on the treating ED
physicians or nurses to administer the CAPE intervention). After considerable discussion, the
CHICAGO Trial Steering Committee voted to proceed with 3(a) and 3(b) above because the benefits
of obtaining ED nurse/physician support for the CHICAGO Trial outweighed the theoretical risk of
contamination.
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To describe “usual care” at each site, to assess the extent to which there was contamination between
the Usual Care group and the CAPE groups, and to assess fidelity of implementing the study protocol at
each site, the site project manager will conduct chart abstractions (masked to treatment assignment;
see APPENDIX C). This chart abstraction will be performed within 3 business days of enrolling the
participant in the study. Involvement of the site project manager will help to ensure they are involved in
the audit and feedback of study activities with their staff (ED coordinator). We will review these findings
with the investigators and with the DSMB on a regular basis.
The lack of an attention control group in the design of the Usual Care and the CAPE only groups was
intended to mimic real-world clinical practice (Usual Care group) and the effectiveness of an
intervention limited to the ED only (CAPE only group).
VI. Randomization
The randomization will be at level of the patient, with permuted block sizes stratified by site and race
(black vs. non-black). Based on data from the Clinical Centers, we expect about 448/640 (70%) of
enrolled participants will be black, 148/640 (23%) will be white, and that the remainder will mostly be
Asian. Of the 640 children, 96 (15%) will be Hispanic/Latino; of the Hispanic/Latino, only about 10%, or
10 are expected to be Puerto Rican.
While the prevalence, morbidity, and intervention effect may vary by ethnicity, the number and
distribution of patients within each Clinical Center will make any additional stratification upfront
challenging. We therefore modified the study protocol (originally proposed as stratified randomization
based on site and six race/ethnicity strata), as recommended by the DCC, to employ site and two racebased strata.
The DSMB raised questions about how multi-race or multi-ethnicity will be handled. Consistent with the
approach used in most studies that collect demographic data using questionnaires, race will be asked
first and then ethnicity; caregivers will be allowed to choose as many categories as they wish to report.
We acknowledge that some individuals will report as identifying themselves with more than 1 race or
ethnicity (multi-race or multi-ethnicity, respectively). Thus, stratification by race for the purposes of
randomization will be “Black” (those who select “Black” (includes multi-race if at least one race is
“Black”) vs. “non-Black” (else).
We considered a cluster randomized trial (rather than randomization at the level of the individual child).
However, each site wanted the possibility of beginning to offer improved care for its ED patients. In our
design (not cluster randomized) each site gets to study the effect of the interventions in its own ED with
its own clinicians with its own particular patient population. Lacking that, few major medical centers
with EDs would be interested in participating.
The crucial question about cluster vs. individual-level randomization is the tradeoff between complexity
of implementation versus contamination. Here the medical centers were willing to accept the burdens
of additional complexity if they could see the effects of the interventions in their own EDs, not only at
other institutions. The risks of contamination were judged to be manageable. Patients are seldom
present in the ED at the same time, and are rarely acquainted, so the risk of communication among
patients is minor. There is some risk of CAPE materials being mistakenly provided to Usual Care
patients, but we will develop training materials that will minimize this risk.
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The CHICAGO Trial intranet for study personnel (available 24X7) will provide the random treatment
assignment: CAPE, CAPE plus CHW home visit, or Usual Care.
VII. Data collection
A. Screening and enrollment (registration) into the study (in person; ~40 minutes)
The ED coordinator at each Clinical Center will screen patients in the ED or Observation Unit after
treatment initiation for asthma exacerbation and before the time of discharge. The timing of screening
(at least 1 hour after treatment initiation for asthma exacerbation, as defined in eligibility criteria) is
based on ED physician and nurse stakeholder input about the importance of not delaying the discharge
process. Stakeholder input indicates that patients receive ED treatment for 2 to 6 hours, providing
ample time for screening / enrollment activities, as compared to the time available after the decision to
discharge the child to home has been made (approximately 30 minutes, during which time the ED
physician and nurse may be busy with the patient to expedite discharge). ED physicians who serve as
investigators in the project believe that in most cases, a physician evaluation about 1 hour after
treatment can help to identify children who are likely to be discharged to home (even if that discharge
occurs several hours later).
The ED coordinator will obtain verbal assent from the clinical team prior to approaching the
child/caregiver for informed consent (see details in Protection of Human Subjects). Following informed
consent, the ED coordinator will obtain Baseline data (APPENDIX D), then “register” the patient in a
customized, secure, on-line CHICAGO Trial REDCap portal developed by the DCC, then obtain treatment
assignment (CAPE, CAPE plus Home, or Usual Care). The ED Coordinator will arrange date/time of the 1month follow-up visit (see below).
B. 1-month Follow-up contact after ED discharge (telephone; ~15 minutes).
Post-baseline data collection will be performed by the DCC Research Assistant, masked to treatment
assignment. The research assistant will be trained by the DCC team in the conduct of research, and by
the Sinai team on home assessment.
The Research Assistant will conduct a telephone interview to assess outcomes at 1 month after ED
discharge (APPENDIX E). The interview is also designed to collect / update contact information and to
promote retention in the CHICAGO Trial. The DCC Research Assistant will arrange date/time of the 3month follow-up visit (see below), or inquire about when to call again to schedule (date/time to be
arranged no later than 3 weeks prior to visit).
C. 3-month Follow-up contact after ED discharge (telephone; ~15 minutes). The DCC Research
Assistant, masked to treatment assignment will conduct a telephone interview to assess outcomes at 3
months after ED discharge (APPENDIX F). The interview is also designed to collect / update contact
information and to promote retention in the CHICAGO Trial. The DCC Research Assistant will arrange
date/time of the 6-month in-person follow-up visit (see below), or inquire about when to call again to
schedule (date/time to be arranged no later than 3 weeks prior to visit).
D. 6-month Follow-up contact after ED discharge (in person; ~40 minutes). The DCC Research
Assistant, masked to treatment assignment will conduct an in-person study visit to assess outcomes at 6
months after ED discharge (APPENDIX G). The interview is also designed to collect / update contact
information and to promote retention in the CHICAGO Trial. The DCC Research Assistant will arrange
date/time of the 12-month telephone follow-up visit in selected patients (patients enrolled within first 9
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months of project, estimated 50% of participants). Only participants who were enrolled within the first
9 months of the trial will have sufficient observation time to complete a 12-month study visit. The inperson visit affords the ability to conduct an assessment of home trigger avoidance; review inhaler
technique; and assess cACT (child) and PACQLQ, which are more easily collected during in-person visits.
E. 12-month Follow-up contact after ED discharge (telephone; ~15 minutes). The DCC Research
Assistant, masked to treatment assignment will conduct a telephone interview to assess outcomes at 12
months after ED discharge in participants enrolled during the first 9 months of the trial (APPENDIX H).
This will be the final study visit.
VIII. Outcomes
The selection of primary outcomes was based on several criteria: 1) patient-centeredness, defined as
domains identified as important by caregivers; 2) availability of validated measures in English and in
Spanish that could be administered in person and by phone; 3) biologic plausibility that such measures
could be responsive to an effective intervention in the target population; and 4) limited burden (e.g.,
time) for study participants. Based on these criteria and extensive discussions by the CHICAGO Trial
Steering Committee, the following were identified as the co-primary and secondary outcomes. The
primary analysis will be conducted at 6 months, at the end of the intervention period.
A. Co-primary outcomes
 Asthma impact in children, as assessed by the NIH PROMIS-Asthma Impact Scale (parent proxy
for children ages 5-7 years; pediatric version for children 8-11 years).
 Caregiver of child with asthma: NIH PROMIS- Satisfaction with social roles
We will use two National Institutes of Health (NIH) Patient Reported Outcomes Measurement
Information System (PROMIS) measures for our co-primary outcomes: (1) NIH PROMIS-Asthma Impact
Scale (8 items) will be used to assess the impact of asthma on the child in the past 7 days; and (2) NIH
PROMIS-Satisfaction with Social Role Scale (4 items) will be used to assess the effects of the intervention
on the caregiver in the past 7 days. We had originally proposed to use the parent proxy for asthma
impact for all children in the study (ages 5-11 yrs), but one of the DSMB members recommended we
obtain data from the child directly if they are old enough to provide answers. The PROMIS asthma
Impact Instrument has two versions for pediatric populations: pediatric short form (8 items; 8-17 yrs)
and parent proxy short from (8 items; for use ages 5-17 yrs). Based on this DSMB comments during
Meeting #1 and the availability of pediatric and parent proxy versions for assessing asthma impact in
children, we will use the parent proxy for children 5- 7 yrs and pediatric version for children 8-11 yrs.
The final scores for each measure are represented by a T-score, with a mean of 50 and standard
deviation of 10. More information about PROMIS measures and analyses can be found at:
http://www.nihpromis.org/, http://www.assessmentcenter.net/manuals.aspx
There is considerable interest in use of PROMIS measures by the study sponsor (Patient-Centered
Outcomes Research Institute, PCORI). The NIH Patient Reported Outcomes Measurement Information
System (PROMIS) measures confer several distinct advantages for the conduct of a pragmatic trial: (1)
Comparability: measures have been standardized so there are common domains and metrics across
conditions, allowing for comparisons across domains and diseases, and with the general population. For
the CHICAGO Trial study, this permits comparisons of effectiveness across patient racial and ethnic
subgroups; (2) Reliability and Validity: metrics for each domain have been rigorously reviewed and
tested; (3) Flexibility: PROMIS can be administered in a variety of ways (in person, telephone, or via
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computer adaptive testing; some measures, such as the c-ACT is not validated for use by phone); and (4)
Inclusiveness: PROMIS encompasses all people, regardless of literacy, language (including both English or
Spanish preferences), physical function or life course.
The selection of these outcomes was based on some key considerations:
(1) We sought a measure to assess the impact of asthma on the child that could be collected in person
or by phone (since 2 of the visits are in person and two are by phone) and in English or in Spanish in this
5-11 yrs age group. The study was designed as a large simple trial and is budgeted that way too; so we
can only do 1 follow-up visit in person (the other 2 are by phone). We are also enrolling Spanish
speaking caregivers, so needed to take this into account (need for a tool that could be used in Spanish
and by phone) and could be combined with data in the same person collected in person or by phone.
None of the other asthma-specific measures (e.g., cACT) meet all these criteria.
(2) We wanted to examine a patient-centered (not disease specific outcome) in the caregiver because
clinical experience and information during our planning period (focus groups and interviews conducted
in the EDs, homes) indicate that a child with uncontrolled asthma affects the caregiver in many ways,
including the caregiver's ability to meet their other obligations in life. This aspect of our study is novel
and reflects a 'shift' in priorities for us to examine impact on caregivers using a holistic (patientcentered) approach, rather than a disease-specific approach. We acknowledge that there are trade-offs
and that patient-centered outcomes may not be as responsive as disease-specific outcomes. We
therefore also assess the impact of our intervention on asthma-specific patient—reported outcomes
(childhood Asthma Control Test (cACT) for the child; Pediatric Asthma Caregiver Quality of Life
Questionnaire (PACQLQ) for the caregiver) and healthcare utilization as secondary measures; this will
also provide an opportunity for us to compare our results with those of other studies.
B. Secondary outcomes
1. For the Child: The Childhood Asthma Control Test (cACT, validated as interviewer administered
surveys in –person in English and in Spanish);35 Acute care visits at 6 mos (number of all-cause and
respiratory-related UC visits, ED visits, hospitalizations, using self-report);
2. For Caregiver: Pediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ);36 NIH PROMIS
measures not identified by patient as their primary measure (Anxiety, Depression, Fatigue, Sleep
disturbance);37-39 MDI technique (misuse, defined as <75% steps correct, yes/no);40 filled prescriptions
for systemic corticosteroids provided at ED discharge within 7 days (pharmacy data; yes/no); filled
prescription for inhaled corticosteroids at ED discharge within 7 days (pharmacy data; yes/no);
environmental checklist indicating adherence to recommendations for reducing exposure to smoking,
roach, and mice (to work with other PCORI-funded asthma centers in identifying a practical checklist;
pending).
IX. Analysis plan
The proposed study employs a split-plot factorial repeated measures design, in which three parallel
randomized groups of children with uncontrolled asthma and their caregivers (CAPE; CAPE plus Home
visit; Usual care) are recruited in the ED and followed for up to 12 months (observations collected at 0,
1, 3, 6, and (in about half the sample at 12 months).41 The primary analysis will be conducted at 6
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months (all study participants); durability of effects will be examined in a secondary analysis in which
further data from 12-month observations are included (participants enrolled in the first 9 months of the
trial, estimated to be about 50% of the overall trial population). For the whole sample we have a 3
group x 4 times design, but for half the sample there is a follow up, yielding a 3 group x 5 times design.
Since the 3 x 4 design includes all patients, that was the basis for the power calculation described
below.42,43 The analyses will be according to the intent-to-treat principle (primary analysis),
supplemented by more informative analyses of the sensitivity of results to different missing data
processes.44In addition to the linear mixed models relying on the normality assumption (appropriate for
continuously scaled PROMIS measures), we anticipate using generalized linear mixed models and in
particular generalized estimating equations for the between-groups (marginal) analysis of categorical
responses, such as pharmacy dispensations.
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The following are the Null and alternate hypotheses that will be examined.
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For Asthma Impact Scale (primary outcome for child):
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Null Hypothesis 1: Six-month change in the Asthma Impact Scale in the CAPE-only group will not differ
from six-month change in the Asthma Impact Scale in the Usual Care group. Alternative Hypothesis 1:
Six-month change in the Asthma Impact Scale in the CAPE-only group will differ from six-month change
in the Asthma Impact Scale in the Usual Care group.
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Null Hypothesis 2: Six-month change in the Asthma Impact Scale in the CAPE+CHW group will not differ
from six-month change in the Asthma Impact Scale in the Usual Care group. Alternative Hypothesis 2:
Six-month change in the Asthma Impact Scale in the CAPE+CHW group will differ from six-month change
in the Asthma Impact Scale in the Usual Care group.
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Null Hypothesis 3: Six-month change in the Asthma Impact Scale in the CAPE+CHW group will not differ
from six-month change in the Asthma Impact Scale in the CAPE-only group. Alternative Hypothesis 4:
Six-month change in the Asthma Impact Scale in the CAPE+CHW group will differ from six-month change
in the Asthma Impact Scale in the CAPE-only group.
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For Satisfaction with Social Roles (primary outcome for caregiver):
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Null Hypothesis 4: Six-month change in caregiver Satisfaction with Social Roles in the CAPE-only group
will not differ from six-month change in caregiver Satisfaction with social Roles in the Usual Care group.
Alternative Hypothesis 4: Six-month change in caregiver Satisfaction with Social Roles in the CAPE-only
group will differ from six-month change in caregiver Satisfaction with Social Roles in the Usual Care
group.
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Null Hypothesis 5: Six-month change in caregiver Satisfaction with Social Roles in the CAPE+CHW group
will not differ from six-month change in caregiver Satisfaction with social Roles in the Usual Care group.
Alternative Hypothesis 5: Six-month change in caregiver Satisfaction with Social Roles in the CAPE+CHW
group will differ from six-month change in caregiver Satisfaction with Social Roles in the Usual Care
group.
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Null Hypothesis 6: Six-month change in caregiver Satisfaction with Social Roles in the CAPE+CHW group
will not differ from six-month change in caregiver Satisfaction with social Roles in the CAPE-only group.
Alternative Hypothesis 6: Six-month change in caregiver Satisfaction with Social Roles in the CAPE+CHW
group will differ from six-month change in caregiver Satisfaction with Social Roles in the CAPE-only
group.
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The analysis will additionally include examination of the heterogeneity of treatment effects as
exploratory analyses, as specified in the PCORI Methodology Standards and relevant guidance.33 The
subgroups examined will include standard demographics such as race/ethnicity and gender, and allcause acute care use (# visits to urgent care or emergency department in the past 12 months, #
hospitalizations past 12 months; less than median vs. at least median).
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X. Identify barriers and facilitators of successfully implementing the intervention (Secondary aim)
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A limitation of research directed at improving healthcare is that there is often inadequate attention
devoted to understanding why the intervention was successful or not successful. Thus, when outcomes
are not improved, it is unclear if barriers to implementation or lack of efficacy is the reason. Similarly,
when a multi-dimensional intervention is successful, it is helpful to know whether all dimensions of the
intervention were necessary. We therefore propose a mixed methods approach to examine the barriers
and facilitators of successfully implementing the CHICAGO Trial.
Power / sample size calculation. We propose to enroll and randomize 640 participants over 15 months
(~200-215 per group), representing ~25% of the expected pool of children 5-11 yrs presenting to the EDs
across the CHICAGO Trial Clinical Centers with uncontrolled asthma. Assuming evaluable data in 80% of
enrolled participants (n=512) at 6 mos, sample size calculations suggest ample power for two co-primary
outcomes. Our approach is based on the methods of Rochon,46 with a Bonferroni adjustment for 3 pairwise comparisons (2-sided α =.05/3 =.0167; usual care and two active intervention groups), power 80%,
4 measurements / individual (0, 30, 90, and 180 days), within individual correlation 0.80, correction for
within ED clustering (design effect of 2), and a coefficient of determination (R2) for control of individuallevel demographics = 0.15. Based on these considerations, a sample size of 426 (well within the
expected sample size of 512) is sufficient for a minimum detectable difference (MDD) of 0.35 SD units
(midway between Cohen’s “small” (0.20) and “medium” (0.50) effect size)47 for two co-primary
continuous outcomes compared pairwise across the three treatment groups. The MDD of 0.35 SD units
corresponds (based on published SDs for the various outcome measures) to sufficient power to detect a
minimum important difference [MID] in any two of the PROMIS measures (MID = 5, which is 0.5 SD).37-40
Analyses to examine heterogeneity of treatment effects have more limited power (e.g., 71% power in
African-Americans) for two co-primary outcomes, but results may be suggestive for further research and
can be incorporated in later meta-analyses.
The power analyses do not incorporate adjustment for the presence of two "co-primary" outcomes.
Such an adjustment is not commonly made in biomedical trials, as multivariate (viz. MANOVA) analyses
are not commonly conducted. A further hurdle in undertaking an adjustment was that patient and
caregiver input on the selection of outcome measures was not available at the proposal stage. The
power analysis for single outcomes employed the Rochon (1991) method based on Hotelling's Tsquared, which was adapted to a 3-group comparison by adjusting the alpha level using a Bonferronistyle technique. This approach tends toward a conservative (larger) sample size.
The target recruitment of 640 children will take place over 15 months (~200-215 per group, 3 groups),
representing approximately 25-35% of children 5-11 yrs presenting to the Clinical Center EDs. The
recruitment period is from 3/1/2015 to 5/30/2016, so we have planned for a mean of 7-8 enrolled per
site per month (7.1 enrolled X 6 sites X 15 months = 640 children).
(1) Intervention fidelity: We will use a scoring system (0 – not performed; 1 – incompletely performed;
2 – performed fully) to measure the extent to which each patient received each component of the
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CHICAGO Trial intervention, based on their allocation to the three treatment groups. For patients
randomized to CAPE plus Home, we will also review home visit logs completed by CHWs to measure
completion rates (target = minimum 4 of 5 home visits completed in the pre-specified visit window).
(2) Focus groups: We will invite a random 5% sample of caregivers who did vs. did not complete the
interventions in the two active treatment groups to participate in a focus group to determine if they
were satisfied with the content, comprehension, and relevance of the intervention material. We will
also ask about the satisfaction with the interventions provided by the ED coordinator and CHWs, and
any other comments the patient or caregiver would like to offer about how to improve the CHICAGO
Trial. We will inform the participants that their responses will be anonymous and are being used to help
determine how to improve the CHICAGO Trial intervention.
(3) Interviews of ED Coordinators and CHWs personnel: We will invite the study staff to understand if
there were barriers to completing the study (e.g., space or time constraints when providing ED-based
instruction; availability of participants at scheduled home visit times). These interviews will help identify
suggestions to improve the feasibility of interventions;
Information from #1 to #3 will be used to determine if there are consistent patterns in the barriers and
facilitators for successfully implementing the interventions. We will also determine if specific
components of the CHICAGO Trial interventions were more consistently present in patients who had
improvements in the co-primary endpoints for the child and for the caregiver. Such information could
help to suggest the necessity of some or all components of the multi-component CHICAGO Trial
intervention.
A list is key performance indicators at the ED, home, and data collection procedures is provided in
APPENDIX I. We will make such assessments for all 3 groups to understand barriers and facilitators
related to implementing study procedures and how that varied across groups. These assessments will be
made at the “end of the trial” to avoid the assessments becoming another “intervention”. End of trial is
12 months after the ED visit in participants randomized during the first half of the recruitment period,
and 6 months after the ED visit in those randomized during the second half of the recruitment period
(given the total duration of the study period). We will conduct these assessments at the end of the trial
in a 5% sample of participants assigned to each of the 3 treatment groups (about half at 6 months, and
half at 12 months, whichever is appropriate). We will also interview all ED coordinators and CHWs near
the end of the project period (end of year 3).
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XI. Timeline / milestones
We propose to enroll and randomize 640 participants over 15 months (~200-215 per group),
representing ~25% of the expected pool of children presenting to the EDs across the Clinical Centers
with uncontrolled asthma.
Key dates relevant to the trial
March 1, 2015: Expected start of enrollment
May 31, 2016: End of enrollment period
November 30, 2016: End of study visits/data collection
February 28, 2017: End of project period
Other PCORI milestones (see APPENDIX J)
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XII. PROTECTION OF HUMAN SUBJECTS RESEARCH
A. Risks to Human Subjects
Human Subjects Involvement and Characteristics
The trial will include approximately 640 children ages 5-11 yrs and their caregivers. The eligibility
criteria are discussed in an earlier section of this protocol. Children and caregivers will be randomly
allocated to 1) CAPE; 2) CAPE plus Home; or 3) Usual Care. All participants will be enrolled for a
maximum of 12 months, regardless of the group they are assigned to; a research assistant from the DCC
will conduct assessment visits (masked to treatment group) at months 0 (baseline before
randomization), 1, 3, 6, and 12. Only the participants enrolled during the first 9 months of the
enrollment period will be invited to participate in the 12 month study visit.
Sources of Materials
Questionnaires administered by the ED coordinator (baseline data), and those administered by the
research assistant (follow-up data); Pharmacy dispensation data and electronic health records (EHR);
Direct observation (e.g., home inspection / completion of environmental assessment checklist; review of
inhaler technique using checklist).
Potential Risk
Participants and caregivers will be subject only to minimal risks through this research; we are testing
two different approaches to promoting guideline recommended care (CAPE in the ED; CAPE in the ED
plus home visits by a CHW) compared to usual ED care. Risks may include inconvenience or
embarrassment involved in completing questionnaires or demonstrating self-management skills, or
permitting the CHW (or research assistant) to conduct home visits for interventions (or for assessments),
or in allowing the DCC to obtain pharmacy dispensation records (used for measuring adherence). The
caregiver will not be required to answer any questions (or conduct any part of the study) that he/she is
reluctant to discuss/conduct. There is also a risk of loss of confidentiality. The CHW will not provide
patients/caregivers with any type of medical advice, but will have direct access to health care providers
to address any patient/caregiver clinical questions or concerns. If the CHW is accidentally contacted with
clinical questions, the CHW will connect the participant/caregiver with a health care provider familiar
with the participant’s medical condition immediately. On enrollment, caregivers will be instructed to call
their health care provider or seek emergency services in case of worsening symptoms, as opposed to
directing questions to the CHW. All participants will be informed in advance that they may withdraw
from the study at any time without negatively affecting their medical care or any other benefits they
might receive.
B. Adequacy of Protection Against Risks
Recruitment and Informed Consent/Assent
We will seek informed assent in all children that are capable of providing assent (age ≥7 years old) and
permission of their caregiver in the ED. In children < 7 years old, consent will obtained from the
caregiver in the ED. As this study is no greater than minimal risk, the permission of only one parent or
guardian will be sufficient for research to be conducted under the Additional Protections for Children
Involved as Subjects in Research (45 CFR Part 46.404). Assent from the child and permission or consent
from the parent/guardian will be obtained by the ED coordinator at each participating clinical site. All
staff will be trained in informed consent/assent procedures and will be available to read the
consent/assent forms to individual with low literacy levels. The consent/assent form will be available in
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English and Spanish.
All caregiver/family information, including contact information, questionnaires, pharmacy dispensation
and clinical information will be monitored by study staff and only available to them. Case report forms
will be locked in cabinets and electronic data will be stored on password-protected files. Only authorized
study staff will have access to study data. Study reports will not contain any identifiable information and
will present findings in aggregate (or by treatment group).
Incomplete Disclosure
As participants in this trial will be aware of which treatment group they are assigned to, there is a risk
for Hawthorne effect (change in behavior as a result of monitoring alone) and information bias as it
relates to answering questions for the patient-reported outcomes (the co-primary outcomes and several
secondary outcomes). Although there may be changes in behavior (e.g., improved adherence to
corticosteroids), our studies and those of others have shown that monitoring does not itself result in
sustained adherence.48 To minimize this risk, however, there will be incomplete disclosure of the
interventions in the CHICAGO study during informed consent. The study will be described as testing
different communication strategies combining written and verbal instructions to all participants. We
will also embark on procedures to mask the participants, using doorknob hangers, as was successfully
performed in a recent study. Regardless of the arm the participant is randomized in, children and
caregiver/families will receive an opaque envelope containing a different color doorknob hanger in the
form of a plasticized document, depicting one or more facts about asthma unrelated to the study
interventions (e.g., recommendations for influenza vaccinations) along with community events (e.g.,
upcoming health fairs, resources in the community such as community health center hours, or pharmacy
or grocery store openings). Each doorknob will be marked with a unique identifier to confirm
possession by the DCC research assistant at 1 month, 3 months, 6 months, and 12 months; as well as the
study logo and contact information. To minimize the risk of bias, the DCC research assistant who will
collect outcome data will be masked to the treatment group.
Incomplete disclosure is generally necessary in studies of bias or social desirability (such as monitoring
of adherence) and is considered acceptable by medical ethicists, the American Psychological Association,
and IRBs when certain strict criteria are met. In designing this study, as with previous studies conducted
by Dr. Krishnan, we have been guided by the American Psychological Association (APA) Ethics Code for
conducting research. Specifically, we believe that incomplete disclosure is minimal risk to participants
and is unavoidable since we are proposing to monitor behavior while minimizing the risk of Hawthorne
effect. Moreover, we will follow the recommendations of the APA and Bersoff et al. that call for a full
debriefing of participants at the conclusion of the study.49,50
C. Potential Benefits of the Proposed Research to the Subjects and Others
It is difficult to know if the participants will benefit from the research. All study participants/caregivers
will receive instruction about appropriate MDI use with the teach-to-back methodology; they will also
receive two MDI spacers for their use. Other than these specific benefits, we will not indicate that there
may not be a benefit from participating.
D. Importance of the Knowledge to be Gained
African American and Hispanic children suffer disproportionate asthma outcomes compared to nonHispanic whites, as evidenced by emergency department (ED) visits for uncontrolled asthma. This study
aims to evaluate the effectiveness of using multi-level interventions to increase self-management skills
and patient-centered outcomes in a minority pediatric ED population with uncontrolled asthma. If this
intervention proves successful, it could make a significant impact in adherence to the asthma guidelines
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and equalize asthma care and health care utilization, among African American and Hispanic children
with asthma. Risks to participants and their caregivers involved in the research are minimal.
E. Data Safety Monitoring Plan
The study will be reviewed by the IRB at each participating institution and approval will be sought before
study activities begin. We will also submit IRB continuing reviews annually and adverse event reports as
specified by each IRB. This study will use a Data Safety Monitoring Board (DSMB) that will include 5
individuals who are not affiliated with any of the participating institutions. There will be 1 chairperson
(senior researcher with experience in community-based asthma interventions), at least 1 clinical trialist,
1 statistician, and at least 1 physician who cares for children with asthma, at least 1 caregiver with a
child with asthma. The DSMB will convene once in Y1 (review/approve final study protocol) and twice
per year in Y2 and 3. The DSMB will make an affirmative decision at each meeting whether to continue
or terminate the study. Early termination is an option for the DSMB, particularly if there are serious
concerns about patient safety or there is evidence of futility or sufficient evidence of efficacy; decisions
regarding early termination will be made by the DSMB. No interim analyses of outcomes for efficacy or
futility are planned. In general, the DSMB will be provided data grouped by treatment without
identified treatment groups (i.e., masked to treatment assignment). If the DSMB requests, for the
purpose of competent deliberation, to see the treatment assignments (by group or individual), these will
be provided by the DCC biostatistician from this research program. Insofar as possible, the investigators
will remain masked to the treatment assignments of individual patients unless it is judged that it is in the
best interests of an individual patient.
F. ClinicalTrials.gov Requirements
Registration of this clinical trial in ClinicalTrials.gov is required. This trial will be registered in
ClinicalTrials.gov prior to start of enrollment of participants. The results of the trial will be reported
within the required timeframe. The registration will be updated and results be made available according
to the requirements.
G. Inclusion of Women and Minorities
The proportion of girls included in the study will mirror the prevalence of this condition in the
community and the patient population of the medical centers in which the study will take place. The
study will take place at different medical centers but all serve a large number of racial or ethnic
minorities. The investigators anticipate that approximately 70% of participants will be African American,
15% Hispanic, 8% Caucasian and 7% other (Asian, Native American, Pacific Islander) reflecting the racial
and ethnic background of our patient populations. Minorities will be enrolled as they present to
enrollment sites, and participants whose primary language is Spanish will be included.
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805
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807
XIII. Participating investigators, staff, and partnerships
Institution
University of Illinois
Hospital & Health Sciences
System/University of
Illinois at Chicago
Sinai Health System
Ann and Robert H. Lurie
Children’s Hospital of
Chicago
University of Chicago
Rush University Medical
Center
John H. Stroger, Jr.,
Hospital of Cook County
Illinois Institute of
Technology - Institute of
Design
Chicago Asthma
Consortium
Respiratory Health
Association
City of Chicago
Department of Public
Health
Investigators
Jerry Krishnan
Michael Berbaum
Sharmilee Nyenhuis
Trevonne Thompson
Molly Martin
Hélène Gussin
Sara Heinert
Nina Bracken
Amy Franco
Hajwa Kim
Yi-Fan Chen
Helen Margellos-Anast
Leslie Zun
Jessica Ramsay
Rajesh Kumar
Zachary Pittsenbarger
Michael Miller
Janet Flores
Valerie Press
Margaret Paik
Julian Solway
Nicole Twu
Nicole Woodrick
Giselle Mosnaim
Jane Kramer
Kenneth Soyemi
Tom Senko
Tom MacTavish
Kim Erwin
Jaime Rivera
Sarah Norell
Tara Flippin
Jaime Rivera
Stacy Ignoffo
Role
Working Group
SC, DCC
DCC
SC, Ast
ED
SC, Stk, CHW
SC (PM), reg
reg
ED
DCC
DCC
DCC
SC, CHW, DCC
ED
Reg, CHW
Ast (chair), SC
Reg, ED
DCC
CHW
SC, Stk, Ast, CHW
Ast, ED, DCC
Contact PI
Co-PI (DCC)
Site PI (Clin)
Co-I (ED)
Co-I
PM
ED coordinator
RN coordinator
DCC manager
Biostatistician
Biostatistician
Site PI
Co-I (ED)
coordinator
Site PI
Co-I
Research Informatics
coordinator
Site PI
Co-I (ED)
Co-I
Project mgr
Coordinator
Site PI
Co-I (ED)
Site PI
Co-I (ED)
Co-PI
Co-PI
Student/RA
Student/RA
Student/RA
RA
Site PI
Kate Sheridan
Site PI
SC, Stk
Cortland Lohff
Site PI
SC, reg, Ast
reg
SC, Ast, DCC
ED
SC, DCC, CHW
ED
SC, Stk
SC, Stk
Stk
Stk
Stk
Reg.
SC, Stk
808
809
Page 22 of 46
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810
Consultants
Institution
Northshore University Health System
Northwestern University
Illinois Emergency Department Asthma
Surveillance Project (IEDASP)
811
812
813
814
815
816
817
818
819
820
Name
Madeleine Shalowitz
Pedro Avila
Michael McDermott
WG
SC, Stk
SC, Ast
SC, ED
Abbreviations:
SC: Steering Committee
DCC: Data Coordinating Center
Reg: Regulatory and Contracts
Stk: Stakeholder and Patient engagement
Ast: Asthma
ED: Emergency Medicine
CHW: Community Health workers
Page 23 of 46
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XIV. References
825
826
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828
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Wallace D, Sublett J, Bernstein J, Grimes C, Miller JD, Seltzer J; Joint Task Force on Practice
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18. Krieger J, Jacobs DE, Ashley PJ, Baeder A, Chew GL, Dearborn D, Hynes HP, Miller JD, Morley R,
Rabito F, Zeldin DC. Housing interventions and control of asthma-related indoor biologic agents: a
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20. Rosenstreich DL, Eggleston P, Kattan M, Baker D, Slavin RG, Gergen P, Mitchell H, McNiff-Mortimer
K, Lynn H, Ownby D, Malveaux F, for the National Cooperative Inner-City Asthma Study. The Role of
Cockroach Allergy and Exposure to Cockroach Allergen in Causing Morbidity among Inner-City
Children with Asthma. N Engl J Med 1997; 336:1356-1363.
21. Gruchalla RS, Pongracic J, Plaut M, Evans R, Visness CM, Walter M, Crain EF, Kattan M, Morgan WJ,
Steinback S, Stout J, Malindzak G, Smartt E, Mitchell H. The Inner City Asthma Study: Relationships
between sensitivity, exposure and morbidity. J Allergy Clinical Immunol. 2005 115 584-91.
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and tertiary prevention of allergic disease: a meta-analysis. Ann Allergy Asthma Immunol. 2014;
112(3):237-48.
23. Gehring U, de Jongste JC, Kerkhof M, Oldewening M, Postma D, van Strien RT, Wijga AH, Willers SM,
Wolse A, Gerritsen J, Smit HA, Brunekreef B. The 8-year follow-up of the PIAMA intervention study
assessing the effect of mite-impermeable mattress covers. Allergy. 2012 Feb;67(2):248-56.
24. Gøtzsche PC, Johansen HK. House dust mite control measures for asthma: systematic review.
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HJ, de Jongste JC. House dust mite allergen reduction and allergy at 4 yr: follow up of the PIAMAstudy. Pediatr Allergy Immunol. 2006 Aug;17(5):329-36.
26. de Vries MP, van den Bemt L, Aretz K, Thoonen BP, Muris JW, Kester AD, Cloosterman S, van Schayck
CP. House dust mite allergen avoidance and self-management in allergic patients with asthma:
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27. Gergen PJ, Mortimer KM, Eggleston PA, Rosenstreich D, Mitchell H, Ownby D, Kattan M, Baker D,
Wright EC, Slavin R, Malveaux F. Results of the National Cooperative Inner-City Asthma Study
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Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):501-6.
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Smartt E, Plaut M, Walter M, Vaughn B, Mitchell H; Inner-City Asthma Study Group. Results of a
home-based environmental intervention among urban children with asthma. N Engl J Med. 2004 Sep
9;351(11):1068-80.
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extermination and sodium hypochlorite cleaning in inner-city homes. Ann Allergy Asthma Immunol.
2001 Jul;87(1):60-4.
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cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: month 12 continuation
results. J Allergy Clin Immunol. 2004 Jan;113(1):109-14.
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Illinois Emergency Department Asthma Surveillance Program, Illinois Department of Public Health,
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September 7, 2013).
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of respiratory inhalers to hospitalized patients with asthma or COPD: a randomized trial. J Gen
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41. Kirk RE. Experimental design: Procedures for the behavioral sciences (4th ed.). Thousand Oaks, CA:
Sage Publications, Inc., 2013.
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42. Hedeker D, Gibbons RD. Longitudinal data analysis. Hoboken, NJ: John Wiley & Sons, Inc., 2006.
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43. Diggle PJ, Heagerty P, Kung-Yee L, Zeger SL. Analysis of longitudinal data (2nd ed.). New York:
Oxford University Press, Inc., 2002.
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44. Little, Roderick J. A., and Yau, L. (1996). Intent-to-treat analysis in longitudinal studies with dropouts. Biometrics, 52, 1324-1333.
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45. Varadhan, Ravi, and Segal, Jodi (June 25, 2013). Methodology Standards for the Analysis of
Heterogeneity of Treatment Effect. Presentation at the AcademyHealth Conference, Baltimore, MD.
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46. Rochon, J. Sample size calculations for two-group repeated-measures experiments. Biometrics
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47. Cohen, J. Statistical power analysis for the social sciences. 2nd ed. New York: Routledge; 1988.
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48. Krishnan JA, Bender BG, Wamboldt FS, Szefler SJ, Adkinson NF Jr, Zeiger RS, Wise RA, Bilderback AL,
Rand CS. Adherence Ancillary Study Group Adherence to inhaled corticosteroids: an ancillary study
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49. Bersoff DM, Bersoff DN. Ethics and self-report data. In: Stone A, Turkkan JS, Bachrach CA, Jobe JB,
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XV. Appendices
975
B. Outline of home visit procedures
976
C. Chart review
977
D. Baseline questionnaire domains
978
E. 1-month follow-up questionnaire domains
979
F. 3-month follow-up questionnaire domains
980
G. 6-month follow-up questionnaire domains
981
H. 12-month follow-up questionnaire domains
982
I.
Key performance indicators
983
J.
PCORI approved milestones
A. CAPE tool
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APPENDIX A. CAPE Tool (Version 3.3-2014.10.07)
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APPENDIX B: Outline of home visit procedures
Competency
#
Days after ED discharge
Time for each
element
(estimate)
1
Introductions and explanation of CHICAGO Trial
Program and role of CHW
Review and confirm understanding of asthma
action plan (meds, when to seek care; attend
follow-up);
10 min
Asthma basics: What is asthma? How does it
affect the airways?
Symptom recognition and understanding
controlled vs. uncontrolled asthma
Teach-back regarding appropriate use of
medications, including MDI
Identification of major triggers (cigarette smoke,
roach, mouse) in home and strategies to reduce
exposure;
Identification of other triggers (mold, dust, pets,
pollen, food, strong odors, cold/flu, extreme
weather, exercise, emotions) in home and
strategies to reduce/avoid them;
Educate about 504 plan and how to submit
paperwork (school nursing and administrative
support )
Assess progress towards Behavior Change Plan
from last visit; Develop plan until next visit.
2
3
4
5
6
7
8
9
Visit #1
2-3 days
60-90
min
Priority
Visit #2
14 days
60-90 min
Visit #3
30 days
60-90 min
Visit #4
90 days
60-90 min
Visit #5
180 days
60-90 min
Up to 10 min
Priority;
(CAPE)
Priority
(updated
asthma
action plan)
Priority
(updated
asthma
action plan)
Priority
(updated
asthma
action plan)
Up to 5 min
Priority
Priority
(CAPE OR
updated
asthma action
plan)
Priority
If time allows
If time allows
If time allows
Up to 10 min
Priority
Priority
If time allows
If time allows
If time allows
Up to 15 min
Priority
Priority
Priority
Priority
Priority
Up to 30 min
Priority
Priority
Priority
Priority
Up to 30 min
If time allows
If time allows
If time allows
If time allows
Up to 5 min
If time
allows
Priority
Priority
Priority
Priority
Up to 10 min
Priority
Priority
Priority
Priority
Priority
994
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996
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
APPENDIX C: Chart review to be completed 3-4 business days after ED discharge
Personnel: Site project manager to review EHR and document for each enrolled patient whether the
following occurred prior to ED discharge. At the time of review the site project manager will be masked
to treatment group. Based on enrollment targets, there will be 1.25 patients enrolled / week / site (6-7
participants / month / site). Involvement of the site project manager will help to ensure they are
involved in the audit and feedback of study activities with their staff (ED coordinator).
Time of data collection: 3-4 business days after ED discharge
CORTICOSTEROIDS prior to ED discharge
 Prescription for systemic corticosteroids (record: yes/no; and dose, route, frequency, duration)
 Prescription for inhaled corticosteroids (record: yes/no; and dose, frequency, duration)
ARRANGE FOLLOW-UP VISIT prior to ED discharge
 Follow-up visit scheduled (record: yes/no; timeline for follow-up)
RESCUE MEDICATION prescribed prior to ED discharge
 Prescription for rescue medication (record: yes/no; and dose, frequency, and duration)
SELF-MANAGEMENT SKILLS instruction prior to ED discharge
 Review of discharge medications (record: yes/no)
 Review of inhaler technique (record: yes/no; which inhalers were reviewed and whether there
was documentation that caregiver / child achieved mastery prior to ED discharge)
 Provide action plan about when to seek additional medical care (record: yes/no)
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1023
APPENDIX D: Baseline questionnaire domains (in-person data collection by ED coordinator)
Domain / items
Source/measure
Interview (INT)
Electronic health record
review (EHR)
Estimated time (min)
INT and EHR; From NHLBI
AsthmaNet case report
forms
5
INT; From AsthmaNet
3
INT; From AsthmaNet
5
INT; To be determined (TBD)
2
Demographics
Gender, race/ethnicity, date of birth of child;
caregiver marital status, highest level of
education achieved, employment, health
insurance; number / ages of children
Contact information: phone (x3),
primary household address
Name/contact information
primary asthma provider
Preferred language at home
Medical history
Weight/height of child ED EHR
Comorbidity ED EHR
Medication prescribed ED EHR
----
Self-management skills
MDI plus spacer Inhaler technique INT; MDI checklist28
Asthma health (caregiver and child)
5
Asthma Impact (child) INT; PROMIS Asthma Impact
Scale; (PROMIS AIS proxy)
INT; Childhood Asthma
Asthma control (child) Control Test (cACT)
Anxiety (caregiver), depressive INT; PROMIS-20 (short
symptoms (caregiver), sleep forms)
disturbance (caregiver),
fatigue (caregiver), satisfaction with
social role (caregiver);
Asthma Caregiver Quality of Life INT; PACQLQ
Acute care visits past 12 months INT; CDC asthma
(Urgent care, ED, hospitalizations) questionnaire
Date / time of 1-month follow-up visit
INT
(phone)
TOTAL TIME
4
2
4
5
3
1
39 min
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PCORI contract # AS 1307-05420
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1024
APPENDIX E: 1-month Follow-up questionnaire domains (via telephone by DCC research assistant)
Domain / items
Source/measure
Interview (INT)
Electronic health record
review (EHR)
Estimated time (min)
Demographics
Contact information (x3) INT; From AsthmaNet
Name/contact information INT; From AsthmaNet
primary asthma provider
Self-management skills
Pharmacy dispensation for child after ED
discharge
Attending follow-up appointment
arranged at ED discharge
3
1
Pharmacy records (fax from
pharmacy used by patient)
EHR (if at index institution),
fax of clinic note (else)
--
Asthma Impact (child) INT; PROMIS Asthma Impact
Scale; (PROMIS AIS proxy)
Anxiety (caregiver), depressive INT; PROMIS-20 (short
symptoms (caregiver), sleep forms)
disturbance (caregiver),
fatigue (caregiver), satisfaction with
social role (caregiver);
Acute care visits since ED discharge INT; modified CDC asthma
(All cause and respiratory-related questionnaire
urgent care, ED, hospitalizations)
Date / time of 3 month follow-up visit
INT
(phone)
TOTAL TIME
4
--
Asthma health (caregiver and child)
4
3
1
16 min
1025
1026
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PCORI contract # AS 1307-05420
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1027
APPENDIX F: 3-month Follow-up questionnaire domains (via telephone by DCC research assistant)
Domain / items
Source/measure
Interview (INT)
Electronic health record
review (EHR)
Estimated time (min)
Demographics
Contact information (x3) INT; From AsthmaNet
Name/contact information INT; From AsthmaNet
primary asthma provider
Self-management skills
3
1
Pharmacy dispensation for child after ED Pharmacy records (fax from
discharge pharmacy used by patient)
Asthma health (caregiver and child)
--
Asthma Impact (child) INT; PROMIS Asthma Impact
Scale; (PROMIS AIS proxy)
Anxiety (caregiver), depressive INT; PROMIS-20 (short
symptoms (caregiver), sleep forms)
disturbance (caregiver),
fatigue (caregiver), satisfaction with
social role (caregiver);
Acute care visits past 3 months INT; modified CDC asthma
(All cause and respiratory-related questionnaire
urgent care, ED, hospitalizations)
Date / time of 6 month follow-up visit (inINT
person )
TOTAL TIME
4
4
3
1
16 min
1028
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1029
APPENDIX G: 6-month Follow-up questionnaire domains (in-person by DCC research assistant)
Domain / items
Source/measure
Interview (INT)
Electronic health record
review (EHR)
Estimated time (min)
Demographics
Contact information (x3) INT; From AsthmaNet
Name/contact information INT; From AsthmaNet
primary asthma provider
Self-management skills
3
1
Pharmacy dispensation for child after ED
discharge
MDI plus spacer Inhaler technique
Environmental trigger avoidance for cigarette
smoke, roach, and mouse
Asthma health (caregiver and child)
--
Pharmacy records (fax from
pharmacy used by patient)
INT; MDI checklist28
Inspection; TBD
Asthma Impact (child) INT; PROMIS Asthma Impact
Scale; (PROMIS AIS proxy)
INT; Childhood Asthma
Asthma control (child) Control Test (cACT)
Anxiety (caregiver), depressive INT; PROMIS-20 (short
symptoms (caregiver), sleep forms)
disturbance (caregiver),
fatigue (caregiver), satisfaction with
social role (caregiver);
Asthma Caregiver Quality of Life INT; PACQLQ
Acute care visits past 3 months INT; modified CDC asthma
(Urgent care, ED, hospitalizations) questionnaire
Date / time of 12-month follow-up visit
INT
(participants enrolled first 9 months)
TOTAL TIME
5
10
4
2
4
5
3
1
38 min
1030
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PCORI contract # AS 1307-05420
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1031
APPENDIX H: 12-month Follow-up questionnaire domains (via telephone by DCC research assistant)
Domain / items
Source/measure
Interview (INT)
Electronic health record
review (EHR)
Estimated time (min)
Demographics
Contact information (x3) INT; From AsthmaNet
Name/contact information INT; From AsthmaNet
primary asthma provider
Self-management skills
3
1
Pharmacy dispensation for child after ED Pharmacy records (fax from
discharge pharmacy used by patient)
Asthma health (caregiver and child)
--
Asthma Impact (child) INT; PROMIS Asthma Impact
Scale; (PROMIS AIS proxy)
Anxiety (caregiver), depressive INT; PROMIS-20 (short
symptoms (caregiver), sleep forms)
disturbance (caregiver),
fatigue (caregiver), satisfaction with
social role (caregiver);
Acute care visits past 3 months INT; modified CDC asthma
(All cause and respiratory-related questionnaire
urgent care, ED, hospitalizations)
4
TOTAL TIME
4
3
15 min
1032
1033
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PCORI contract # AS 1307-05420
11-24-2014
1034
APPENDIX I: Key performance indicators
1035
1036
1037
1038
We propose the following performance DRAFT metrics for each site (will require review and approval by
the External Advisory Committee and Steering Committee). For each, we will monitor the % completion
on a monthly basis at our Steering Committee meetings and provide these key performance metrics to
the DSMB prior to the scheduled meetings.
1039
1040
A. Emergency Department (ED)-level intervention performance metrics
1041
1042
1043
(1)
Randomize 7.1 children/caregivers per month per site X 15 months (hereafter referred to as
participants)
1044
(2)
% of participants who meet study eligibility criteria
1045
1046
(3)
% of participants who have appropriate documentation of informed consent (written informed
consent)
1047
1048
1049
1050
1051
1052
1053
(4)
% of participants who receive the intervention as per randomized treatment assignment: (a)
for the Usual Care group, the ED coordinator provides MDI instruction and Doorknob hanger;
(b) for CAPE group, ED coordinator provides MDI instructions, Doorknob hanger, and completes
the CAPE with the participants prior to ED discharge; (c) for CAPE plus Home group, ED
coordinator provides MDI instructions, Doorknob hanger, completes the CAPE with the
participants prior to ED discharge, and arranges appointment for the first home visit by the
community health worker).
1054
1055
1056
Additional ED-level performance indicators for participants assigned to CAPE groups (CAPE only or CAPE
plus Home):
1057
1058
(5)
% of participants who received a prescription for systemic corticosteroids,
1059
1060
(6)
% of participants who received a prescription for inhaled corticosteroids (or other controller) for
a minimum of 30 days,
1061
1062
(7)
% of participants who received a post-ED follow-up appointment with the child’s provider
(date/time/name),
1063
(8)
% of participants who received a prescription for a rescue medication,
1064
1065
1066
(9)
% of participants who received instruction using teach-to-goal methodology to (a) increase
comprehension about (5) to (8), (b) green/yellow/red zones of the asthma action plan, and (c)
need to avoid known environmental triggers;
1067
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PCORI contract # AS 1307-05420
11-24-2014
1068
1069
1070
1071
1072
1073
The site project manager will conduct ED chart reviews (masked to treatment group) within 3-4 business
days of all study participants to assess (2) to (9). These data will be used to assess performance and to
also evaluate the extent to which there is contamination across treatment groups . The site project
manager will record performance on each metric as: 0 – not performed; 1 – incompletely performed; 2
– performed as per study protocol. Training or re-training will be performed and documented on a caseby-case basis.
1074
1075
1076
B. Home visit-level intervention performance metrics (for participants randomized to CAPE plus
Home)
1077
1078
1079
Performance metrics for completion of home visits by community health worker (CHW) within study
window:
1080
1081
(10)
% of participants who receive Home Visit #1 within 3 business days of ED discharge (window
ends 3 business days after ED discharge)
1082
1083
(11)
% of participants who receive Home Visit #2 within 17 calendar days of ED discharge (window is
14 days +/- 3 calendar days)
1084
1085
(12)
% of participants who receive Home Visit #3 within 37 calendar days of ED discharge (window is
30 days +/- 7 calendar days)
1086
1087
(13)
% of participants who receive Home Visit #4 within 97 calendar days of ED discharge (window is
90 days +/- 7 calendar days)
1088
1089
(14)
% of participants who receive Home Visit #5 within 187 calendar days of ED discharge (window
is 180 days +/- 7 calendar days)
1090
1091
Performance metrics for completion of all elements of each home visit:
1092
1093
1094
1095
1096
1097
(15)
% of participants who receive each of the following elements by the CHW during Home Visit #1:
introduction and explanation of the CHICAGO Trial; review asthma action plan developed in ED
(ED CAPE); review of asthma basics; review of symptom recognition and understanding of
controlled (green zone) vs. uncontrolled asthma (yellow/red zones): teach-to-goal instruction
about use of MDIs; assistance to develop a behavior change plan (related to preceding
elements)
1098
1099
1100
1101
1102
1103
1104
(16)
% of participants who receive each of the following elements by the CHW during Home Visit #2:
review asthma action plan updated since ED discharge in collaboration with patient’s provider
(updated CAPE); review of asthma basics; review of symptom recognition and understanding of
controlled (green zone) vs. uncontrolled asthma (yellow/red zones): teach-to-goal instruction
about use of MDIs; identification of and help with strategies to reduce the 3 major triggers;
assess progress towards behavior change plan developed during home visit #1 and assistance to
develop updated plan (related to preceding elements)
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PCORI contract # AS 1307-05420
11-24-2014
1105
1106
1107
1108
1109
1110
1111
(17)
% of participants who receive each of the following elements by the CHW during Home Visit #3:
review asthma action plan updated since ED discharge in collaboration with patient’s provider
(updated CAPE); teach-to-goal instruction about use of MDIs; identification of and help with
strategies to reduce the 3 major triggers; assess progress towards behavior change plan
developed during home visit #2 and assistance to develop updated plan (related to preceding
elements)
1112
1113
1114
1115
1116
1117
(18)
% of participants who receive each of the following elements by the CHW during Home Visit #4:
review asthma action plan updated since ED discharge in collaboration with patient’s provider
(updated CAPE); teach-to-goal instruction about use of MDIs; identification of and help with
strategies to reduce the 3 major triggers; assess progress towards behavior change plan
developed during home visit #3 and assistance to develop updated plan (related to preceding
elements)
1118
1119
1120
1121
1122
1123
(19)
% of participants who receive each of the following elements by the CHW during Home Visit #5:
review asthma action plan updated since ED discharge in collaboration with patient’s provider
(updated CAPE); teach-to-goal instruction about use of MDIs; identification of and help with
strategies to reduce the 3 major triggers; assess progress towards behavior change plan
developed during home visit #4 and assistance to develop updated plan (related to preceding
elements).
1124
1125
1126
1127
1128
1129
1130
The Data Coordinating Center will collect these data in the REDcap datqbase, which will be used by the
CHW to document attempted and completed home visits. The Supervising CHWs (from the Sinai CHW
Coordinator Center) will accompany site-specific CHWs during home visits in a random 25% sample of
home visits to review in-person site-specific CHW performance. The Supervising CHW will record
performance on each metric as: 0 – not performed; 1 – incompletely performed; 2 – performed as per
study protocol. Training or re-training will be performed and documented on a case-by-case basis.
1131
1132
C. DCC data collection performance metrics (for all participants)
1133
Performance metrics for data collection within study window:
1134
1135
(20)
% of participants with in-person BASELINE data collection prior to ED discharge
1136
1137
(21)
% of participants with 1-month phone FOLLOW-UP data within 37 calendar days of ED discharge
(window is 30 days +/- 7 calendar days)
1138
1139
(22)
% of participants with 3-month phone FOLLOW-UP data within 97 calendar days of ED discharge
(window is 90 days +/- 7 calendar days)
1140
1141
(23)
% of participants with 6-month in-person FOLLOW-UP data within 187 calendar days of ED
discharge (window is 180 days +/- 7 calendar days)
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PCORI contract # AS 1307-05420
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1142
1143
1144
1145
(24)
% of participants with 12-month in-person FOLLOW-UP data within 367 calendar days of ED
discharge (window is 360 days +/- 7 calendar days); this data collection time-point is only for
those participants enrolled within first 7.5 months of enrollment period (50% of enrollment
period) to ensure there is adequate observation time for data collection at 12 months.
1146
Performance metrics for completeness of outcome data:
1147
1148
1149
(25)
Among those with BASELINE data, we will assess % items with missing data and time needed to
complete BASELINE data collection (compare with estimate of <40 minutes). Data collection to
be completed by ED coordinator prior to randomization.
1150
1151
1152
(26)
Among those with 1-month phone FOLLOW-UP data, we will assess % items with missing data
and time needed to complete BASELINE data collection (compare with estimate of <20 minutes).
Data collection to be completed by DCC research assistant, masked to treatment assignment.
1153
1154
1155
(27)
Among those with 3-month phone FOLLOW-UP data, we will assess % items with missing data
and time needed to complete BASELINE data collection (compare with estimate of <20 minutes).
Data collection to be completed by DCC research assistant, masked to treatment assignment.
1156
1157
1158
1159
(28)
Among those with 6-month in-person FOLLOW-UP data, we will assess % items with missing
data and time needed to complete BASELINE data collection (compare with estimate of <40
minutes). Data collection to be completed by DCC research assistant, masked to treatment
assignment.
1160
1161
1162
(29)
Among those with 12-month phone FOLLOW-UP data, we will assess % items with missing data
and time needed to complete BASELINE data collection (compare with estimate of <20 minutes).
Data collection to be completed by DCC research assistant, masked to treatment assignment.
1163
1164
1165
1166
1167
1168
The Data Coordinating Center will collect these data in the REDcap datqbase, which will be used by the
DCC research assistants to document attempted and completed outcome assessments. The CHICAGO
Trial project manager will record performance on each metric as: 0 – not performed; 1 – incompletely
performed; 2 – performed as per study protocol. Training or re-training will be performed and
documented on a case-by-case basis.
1169
1170
1171
1172
1173
1174
1175
1176
1177
1178
1179
The study design employs the “large simple trial” or “pragmatic trial” format, rather than an efficacy
design. The target performance varies by metric. For elements linked to human subjects protection
(e.g., obtaining written informed consent from the caregiver; assent from the child >7yrs), the definition
for major protocol deviation is <100%. For elements linked to implementing the interventions or data
collection linked to specific time points, the definition for major protocol deviation is <50%. The goal is
100% performance on all metrics; we will ask site PIs to develop a written corrective action plan if sitelevel performance for implementing the protocol is <80% (<100% if there are deviations linked to human
subjects protection). We will report major protocol deviations to the DSMB within 14 days after the
event has been discovered by the contact PI. Depending on the site-specific reporting requirements, we
may also report major deviations to the site’s Institutional Review Board (IRB); for example, we will
Page 42 of 46
PCORI contract # AS 1307-05420
11-24-2014
1180
1181
1182
report all instances where informed consent was not obtained, but, depending on the institution may
not need to report completion rates of study visits prior to the annual continuing review date for that
institution’s IRB.
Page 43 of 46
PCORI contract # AS 1307-05420
11-24-2014
1183
1184
APPENDIX J: PCORI-approved milestones (Modification 002, October 22, 2014)
Milestone Name
Description
A
Contract Execution
-
B1
IRB compliance
Approval of IRB documents.
B2
Focus Groups with
Patients
(Engagement)
B3
Key Informant Interviews
(Engagement)
Convene 2 focus groups with caregivers of children with
asthma: 1 in English (6 caregivers); 1 in Spanish (6
caregivers).
Conduct 12 key informant interviews with ED-based
providers (6 physicians and 6 nurses) and ambulatory
providers (6 providers) to review asthma guideline
recommendations for care on ED discharge.
B4
B5
Focus Groups with
CHWs
(Engagement)
User-centered
Observations and
Interviews
(Engagement)
B6
Convene Steering
Committee
(Engagement)
B7
Develop Spanish Version
of Tool
B9
Patient/Stakeholder
Engagement Update
(Engagement)
B
Report Submission
C1
DSMB
C2
Submit study protocol
(Engagement)
C3
C4
C5
C6
Finalize intervention,
study design, and
materials
Hire and train CHWs and
Train Study Personnel
Obtain IRB Approval
from Each Clinical Center
Steering Committee
(Engagement)
Conduct one focus group with 6 CHWs about the barriers
and facilitators of completing home visits.
Conduct 8-12 user centered observations and interviews with
caregivers of children discharged from the ED following a
visit for uncontrolled asthma to address how the caregiver is
presently managing the child’s asthma.
Convene Steering Committee which includes CAC and RHA
to provide input, review study performance, and participate in
decision-making and dissemination activities. Describe the
role of patients, caregivers, and/or stakeholders and their
contribution.
Use key informant interviews to adapt the WAP-P tool to a
Spanish version.
Describe other patient, caregiver, and/or stakeholder
involvement, engagement, and contribution in the study, such
as decision-making at the various stages in the research
process (e.g., study design, development of study tools and
materials) and role in dissemination of research findings.
Submit Progress Report, Using Interim Progress Report
Template
Convene DSMB meeting to review and approve draft
CHICAGO Trial protocol. Submission of DSMB report to
PCORI.
Submit study protocol, which should include documentation
of how research team will address recruitment, potential
barriers, and ways to overcome barriers. Study protocol will
be submitted for presentation (conference) and/or publication
(peer-reviewed). Register protocol in clinicaltrials.gov.
Describe patient, caregiver, and/or stakeholder contribution
in the dissemination of the study protocol.
Finalize the manual of procedures, case report forms,
associated handouts for providers and children and
caregivers in English and Spanish.
Hire and train community health workers (CHWs) and
conduct training sessions for all study personnel together.
Obtain IRB approval from each clinical center participating in
recruitment.
Update on Steering Committee which includes CAC and
RHA to provide input, review study performance, and
participate in decision-making and dissemination activities.
Describe the role of patients, caregivers, and/or stakeholders
Projected
Completion
Date
03/1/2014
05/1/2014
07/1/2014
07/1/2014
07/1/2014
07/1/2014
08/1/2014
08/1/2014
08/31/2014
08/31/2014
11/30/2014
11/30/2014
11/30/2014
12/31/2014
02/28/15
01/31/2015
Page 44 of 46
PCORI contract # AS 1307-05420
11-24-2014
and their contribution.
C7
Begin Enrollment in
Trial^
C8
Patient/Stakeholder
Engagement Update
(Engagement)
C
Stage 1
Report Submission^
D1
DSMB
D2
Patient/Stakeholder
Engagement Update
(Engagement)
D
Report Submission
E1
Midpoint for Enrollment
Enroll approximately 320 participants.
11/30/2015
E2
DSMB
Convene DSMB meeting. Submission of biannual DSMB
report.
02/29/2016
E3
Mid-point for Intervention
and Follow-up
Mid-point for intervention and follow-up.
E4
Steering Committee
(Engagement)
E5
Patient/Stakeholder
Engagement Update
(Engagement)
E
Report Submission
F1
Complete Enrollment
F2
DSMB
F3
Patient/Stakeholder
Engagement Update
(Engagement)
F
Report Submission
G1
Complete Intervention
and Follow-up
G2
Completion of analysis
Initiate enrollment of participants in trial.
Describe other patient, caregiver, and/or stakeholder
involvement, engagement, and contribution in the study, such
as decision-making at the various stages in the research
process (e.g., study design, development of study tools and
materials) and role in dissemination of research findings.
Submit Stage 1 Interim Progress Report, Using Interim
Progress Report Template
Be sure to include in the Interim Progress Report
statements regarding adherence to the following PCORI
Methodology Standards*:

Formulating Research Questions (RQ-2)

Data Integrity and Rigorous analysis (IR-1)

Handling Missing Data (MD-1, MD-2)

Heterogeneity of Treatment Effects (HT-1, HT-2)
Convene DSMB meeting. Submission of biannual DSMB
report.
Describe other patient, caregiver, and/or stakeholder
involvement, engagement, and contribution in the study, such
as decision-making at the various stages in the research
process (e.g., study design, development of study tools and
materials) and role in dissemination of research findings.
Submit Progress Report, Using Interim Progress Report
Template
Steering Committee which includes CAC and RHA to provide
input, review study performance, and participate in decisionmaking and dissemination activities. Describe the role of
patients, caregivers, and/or stakeholders and their
contribution.
Describe other patient, caregiver, and/or stakeholder
involvement, engagement, and contribution in the study, such
as decision-making at the various stages in the research
process (e.g., study design, development of study tools and
materials) and role in dissemination of research findings.
Submit Progress Report, Using Interim Progress Report
Template
Complete enrollment of participants in trial.
Convene DSMB meeting. Submission of biannual DSMB
report.
Describe other patient, caregiver, and/or stakeholder
involvement, engagement, and contribution in the study, such
as decision-making at the various stages in the research
process (e.g., study design, development of study tools and
materials) and role in dissemination of research findings.
Submit Progress Report, Using Interim Progress Report
Template
Complete intervention and 6 month and 12 month follow-up
for up to 640 and 384 participants, respectively.
Completion of primary analysis and secondary analysis in
which further data from 12-month observations are included.
03/1/2015
02/28/2015
02/28/2015
08/31/2015
08/31/2015
08/31/2015
2/29/2016
02/29/2016
02/29/2016
02/29/2016
05/31/2016
08/31/2016
08/31/2016
08/31/2016
11/30/2016
12/31/2016
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PCORI contract # AS 1307-05420
11-24-2014
G3
Dissemination
G4
Replication/dissemination
(Engagement)
G5
Steering Committee
(Engagement)
G6
Patient/Stakeholder
Engagement Update
(Engagement)
G7
DSMB
Publication of results on advocacy groups' websites.
Develop and finalize study reports. Submission of results for
presentation (conference) and/or publication (peer-reviewed).
Describe patient, caregiver, and/or stakeholder contribution
in the dissemination of study findings.
Steering Committee which includes CAC and RHA to provide
input, review study performance, and participate in decisionmaking and dissemination activities. Describe the role of
patients, caregivers, and/or stakeholders and their
contribution.
Describe other patient, caregiver, and/or stakeholder
involvement, engagement, and contribution in the study, such
as decision-making at the various stages in the research
process (e.g., study design, development of study tools and
materials) and role in dissemination of research findings.
01/31/2017
Convene DSMB meeting. Submission of final DSMB report.
02/28/2017
01/31/2017
01/31/2017
02/28/2017
Submit Stage 2 Final Progress Report, Using Final
Progress Report Template
G
Stage 2 Final Report
Submission
Be sure to include in the Final Progress Report
statements regarding adherence to the following PCORI
Methodology Standards*:

Data Integrity and Rigorous analysis (IR-5, IR-6)

Handling Missing Data (MD-3, MD-4, MD-5)

Heterogeneity of Treatment Effects (HT-3, HT-4)
02/28/2017
Submit Expenditure Report (See Contract for
Instructions)
H
I
Notification of Public
Acceptance
Notification of Peer
Review Rejections
See Contract for Instructions
See Contract for Instructions
Within 30 Days
of Acceptance
Annually by
MM/DD
1185
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