Defining and Treating a New Pediatric Asthma Endotype: Depression-related Asthma Mediated by the Cholinergic Pathway
Phase: EARLY_PHASE1
Conditions: Asthma, Depression, Childhood Asthma
Sponsor: State University of New York at Buffalo

Page 1 of 42 
 
 
Cover Page for Protocol, Statistical Plan and ICF 
 
Official Title: 
Defining and treating a new pediatric asthma 
endotype: depression-related asthma mediated by the 
cholinergic pathway 
NCT number: 
NCT04617015 
Document Type: 
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
8/7/2018 
 
 
 
 

 
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IRB Version: JAN2016 
 
 
Complete Research Protocol (HRP-503) 
 
Table of Contents 
Template Instructions.......................................................................................................... 2 
1.0 
Objectives ................................................................................................................ 4 
2.0 
Scientific Endpoints ................................................................................................. 5 
3.0 
Background .............................................................................................................. 6 
4.0 
Study Design .......................................................................................................... 11 
5.0 
Local Number of Subjects ..................................................................................... 12 
6.0 
Inclusion and Exclusion Criteria ............................................................................ 13 
7.0 
Vulnerable Populations .......................................................................................... 15 
8.0 
Eligibility Screening .............................................................................................. 16 
9.0 
Recruitment Methods ............................................................................................. 16 
10.0 Procedures Involved............................................................................................... 18 
11.0 Study Timelines ..................................................................................................... 21 
12.0 Setting .................................................................................................................... 21 
13.0 Community-Based Participatory Research ............................................................ 22 
14.0 Resources and Qualifications ................................................................................. 23 
15.0 Other Approvals ..................................................................................................... 24 
16.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 24 
17.0 Data Management and Analysis ............................................................................ 25 
18.0 Confidentiality ....................................................................................................... 26 
A. 
Confidentiality of Study Data ............................................................................ 26 
B. 
Confidentiality of Study Specimens ................................................................... 27 
19.0 Provisions to Monitor the Data to Ensure the Safety of Subjects .......................... 28 
20.0 Withdrawal of Subjects .......................................................................................... 29 
21.0 Risks to Subjects .................................................................................................... 30 
22.0 Potential Benefits to Subjects ................................................................................ 32 
23.0 Compensation for Research-Related Injury ........................................................... 32 
24.0 Economic Burden to Subjects ................................................................................ 32 
25.0 Compensation for Participation ............................................................................. 33 
26.0 Consent Process ..................................................................................................... 33 
27.0 Waiver or Alteration of Consent Process............................................................... 38 
28.0 Process to Document Consent ............................................................................... 38 
29.0 Multi-Site Research (Multisite/Multicenter Only)................................................. 39 
30.0 Banking Data or Specimens for Future Use .......................................................... 40 
31.0 Drugs or Devices.................................................................................................... 41 
32.0 Humanitarian Use Devices .................................................................................... 42 
 
 
 

 
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IRB Version: JAN2016 
PROTOCOL TITLE: 
Include the full protocol title. 
Defining and treating a new pediatric asthma endotype: depression-related asthma 
mediated by the cholinergic pathway 
 
 
PRINCIPAL INVESTIGATOR: 
Name 
Department 
Telephone Number 
Email Address 
Heather Lehman 
Pediatrics 
716-323-0130 
hkm@buffalo.edu 
 
VERSION: 
Include the version date or number. 
Version 8/7/2018 
 
GRANT APPLICABILITY: 
Indicate whether this protocol is funded by a grant (e.g. NIH, foundation grant).  
For a grant with multiple aims, indicate which aims are covered by this research 
proposal. 
NOTE: This question does not apply to studies funded by a sponsor contract. 
Include a copy of the grant proposal with your submission.     
Response: This protocol is funded by a University at Buffalo CTSA Pilot Grant, 
under award Number UL1TR001412. 
 

 
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IRB Version: JAN2016 
RESEARCH REPOSITORY: 
Indicate where the research files will be kept, including when the study has been 
closed.  The repository should include, at minimum, copies of IRB 
correspondence (approval, determination letters) as well as signed consent 
documents.  This documentation should be maintained for 3 years after the study 
has been closed.   
Response:  
Location: UBMD Pediatrics Division of Allergy/Immunology  
Room 5454; 1001 Main Street, Buffalo NY 14203 
1.0 Objectives 
1.1 Describe the purpose, specific aims, or objectives of this research. 
Specific Aim 1: To compare the degree of cholinergically-mediated 
bronchoconstriction in depressed children with asthma vs 
nondepressed children with asthma.  
Response: Based upon studies of depressed asthmatic children showing 
increased parasympathetic/cholinergic reactivity  in response to laboratory 
based emotional stimuli, along with a recent study showing that depressed 
asthmatic adults have decreased bronchodilatory response to beta-agonists, 
we hypothesize  that asthmatic children with higher depressive indices will 
have more bronchodilatory response on spirometry following treatment 
with a short-acting inhaled anticholinergic, and less additional 
bronchodilation with an inhaled beta-agonist, compared to children with 
lower depressive indices.  
Specific Aim 2:  To define the inflammatory profile of depressed 
children with asthma, in contrast with non-depressed children with 
asthma. 
Child asthmatics are mainly “atopic” asthmatics, with disease driven by 
Th2-mediated inflammation. Markers of inflammation in these patients 
include peripheral blood eosinophilia, sputum eosinophilia, and elevated 
exhaled nitric oxide. Fractional exhaled nitric oxide (FeNO) has been 
shown to correlate with eosinophilic inflammation, specifically with 
bronchoalveolar lavage eosinophils, peripheral blood eosinophils, and 
serum eosinophil cationic protein (Strunk et al, 2003; Silkoff et al, 2005). 
We hypothesize that depressed pediatric asthmatics during an episode of 
bronchoconstriction will show less evidence of airway inflammation as 
measured by FeNO and peripheral blood eosinophilia, compared to non-
depressed child asthmatics during time of bronchoconstriction. 

 
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Specific Aim 3: To determine the atopic status of depressed children 
with asthma. 
It has been estimated that 78-88% of child asthmatics are atopic (Kattan et 
al, 1997; Nelson et al, 1999), with positive skin prick testing to 
environmental allergens and/or elevated total serum IgE. Using these 
objective measures, we will test the hypothesis that lower rates of atopic 
sensitization in depressed asthmatics with cholinergically-mediated 
bronchoconstriction. In addition, we hypothesize that patient-identified 
asthma triggers will be different in the depressed asthmatic group, with 
increased identification of emotions and cold weather as triggers, and less 
identification of allergens as triggers. 
1.2 
State the hypotheses to be tested, if applicable. 
NOTE:  A hypothesis is a specific, testable prediction about what you expect to 
happen in your study that corresponds with your above listed objectives. 
Response: We hypothesize that episodes of bronchoconstriction that occur 
in asthmatics with comorbid depression have an underlying cholinergic 
mechanism. Therefore, increased scores for depressive symptoms using 
standardized child depression scores will correlate with increased 
responsiveness (reversibility) of pulmonary function parameters with 
administration of inhaled ipratropium (an anticholinergic). 
We next predict that with excess cholinergic activation as a cause of 
bronchoconstriction in depressed pediatric asthmatics, there will be less 
atopic sensitization and Th2-mediated inflammation driving the airway 
disease in this subset of asthmatics. 
2.0 Scientific Endpoints 
 
2.1    Describe the scientific endpoint(s), the main result or occurrence under 
study.   
 
NOTE:  Scientific endpoints are outcomes defined before the study begins to determine 
whether the objectives of the study have been met and to draw conclusions from the data.  
Include primary and secondary endpoints.  Some example endpoints are:  reduction of 
symptoms, improvement in quality of life, or survival.  Your response should not be a 
date.   
Response: Scientific endpoints include a continuous variable of change in Forced 
Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and 
FEV1/FVC ratio following ipratropium; a continuous variable of Fractional 
Exhaled Nitric Oxide (FeNO); a continuous variable of serum IgE, and 
continuous variable of peripheral blood eosinophils, and positive vs negative skin 
testing to any environmental allergens. 

 
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3.0 Background 
3.1 Provide the scientific or scholarly background, rationale, and significance 
of the research based on the existing literature and how it will contribute to 
existing knowledge.  Describe any gaps in current knowledge.  Include 
relevant preliminary findings or prior research by the investigator.  
Response: Asthma is the most prevalent chronic disease of childhood, 
currently affecting 8.3% of children (NHIS, 2013). Disproportionately the 
burden of asthma falls on underserved populations. Black race, Puerto 
Rican Hispanic ethnicity, low socioeconomic status, and inner city 
residence are all associated with increased prevalence of asthma, but even 
more importantly, are also associated with increased morbidity and 
mortality of childhood asthma (Akinbami and Schoendorf, 2002). In 
Western New York, the highest rates of asthma-related emergency 
department visits and hospitalizations in children age 0-17 years are found 
in the zip codes of urban Buffalo and urban Niagara Falls. Subjects for this 
proposed study will be recruited from this high-risk asthma population, 
through the emergency department, primary care clinics, and Allergy and 
Pulmonology subspecialty clinics of )UBMD Pediatrics and Oishei 
Children’s Hospital.Adults and children with asthma have higher levels of 
depressive symptoms than controls and persons with most other medical 
illnesses (Zielinski and Brown, 2003). Rates of current depressive 
disorders in outpatients with asthma have been estimated to 14-25%, with 
31-47% of asthmatics estimated to have had depression at some point in 
their lifetime (Brown et al, 2000; Nejtek et al, 2001; Afari et al, 2001). 
Depression is associated with unfavorable asthma outcomes, including 
medication nonadherence, increased frequency of emergency room visits, 
hospitalizations, unscheduled visits for asthma (Eisner et al., 2005), and 
even asthma-related death (Mancuso et al., 2001). Morrison et al found 
that about 30% of children with asthma had scores on the Children’s 
Depression Rating Scale-Revised consistent with major depressive 
disorder (MDD), and depressive symptom severity in these children was 
associated with a greater number of hospitalizations (Morrison et al., 
2002). In a study of pediatric asthmatics residing in inner-city Buffalo, 
recruited through the WCHOB emergency room, 26% of children were in 
the clinical range for MDD and depression severity was associated with 
increased disease activity (Waxmonsky et al, 2006). 
Mediators of the relationship between child depression and asthma activity 
have been proposed.  One way in which stress and depression contribute 
to pediatric asthma morbidity is by causing compromised adherence to 
asthma controller therapy. (Bender et al. 1998)  However there is also 
evidence that stress and depression have direct psychobiologic impacts on 

 
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asthma morbidity and mortality. Compared with nondepressed children, 
depressed children demonstrate increased impairment in pulmonary 
function when exposed to emotional stressors. Depression has been shown 
to cause an imbalance in parasympathetic activation versus sympathetic 
activation, (specifically the predominance of parasympathetic over 
sympathetic activation) (Reite et al, 1978) and this has formed the basis of 
a proposed parasympathetic/cholinergic mechanism for the airway 
constriction seen in depressed asthmatic children (Miller and Wood, 
2003). 
Basal airway smooth muscle contraction (“tone”) is under autonomic 
nervous regulation, with cholinergic activity as the predominant driver of 
bronchoconstriction. Asthmatics have higher basal smooth muscle tone in 
the airways. In addition to airway smooth muscles, cholinergic activity is 
also believed to regulate other cell types within the lungs, including 
inflammatory cells and mucus-secreting goblet cells. While short-acting 
anticholinergics are in general poorer bronchodilators than beta-agonists, a 
very recent study of depressed adult asthmatics demonstrated poorer 
bronchodilatory effect of beta-agonists compared to non-depressed 
asthmatics (Han et al, 2016). This study suggests that depressed asthmatics 
are not receiving full benefit from at least one conventional asthma 
therapy. Our study has a potential for significant impact in the field of 
asthma research by determining the response of depressed asthmatics to 
anticholinergic bronchodilators, and guiding development of therapy for 
this subset of asthmatics in the future. 
Currently, the main controller therapies for asthmatic patients are inhaled 
corticosteroids (ICS). While ICS have broad anti-inflammatory properties, 
and are very effective in many patients, it is becoming increasingly 
evident that certain subsets of asthmatic patients do not receive benefit 
from ICS; these patients need to have alternative therapies identified based 
on the underlying pathophysiology of their asthma. Patients with non-
eosinophilic sputum profiles or neutrophilic inflammation do not gain the 
same benefit from inhaled corticosteroids (ICS) as those with eosinophilic 
inflammation, and hence may be candidates for anticholinergic therapy 
(Berry et al, 2007; Pavord et al, 1999). Anticholinergics are being 
investigated as adjunctive asthma therapy or as alternative asthma therapy 
for patients not well-controlled with traditional asthma medications. A 
small study has suggested that a short acting anticholinergic produced a 
better bronchodilatory response in non-allergic asthmatic compared to 
allergic asthmatics (Partridge et al, 1981). Phase II and III trials with 
tiotropium (a long-acting anticholinergic), as add-on therapy, have 
demonstrated improvements in lung function and a reduction in 
exacerbation risk in patients with poorly-controlled asthma despite the use 

 
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of ICS, or ICS plus a long-acting beta-agonist (LABA) (Kerstjens et al, 
2012). As tiotropium specifically was beneficial for adults with severe 
asthma who had poor response to ICS, this suggests that the airway 
disease in these asthmatics is mediated by mechanisms alternative to the 
eosinophilic inflammation that is typically seen in asthmatics with good 
response to inhaled steroids. Indeed, earlier studies with tiotropium 
identified asthmatics lacking eosinophilic inflammation as good 
candidates for tiotropium therapy (Iwamoto, 2008).  
Clinical trials for asthma controller therapies, including the trials of the 
long-acting anticholinergic, tiotropium, do not evaluate depression or 
anxiety as a possible comorbid state in study subjects. Therefore, there is 
no insight into whether depressed asthmatics were overrepresented in the 
tiotropium responder group. If depressed asthmatics, as we hypothesize, 
have airway disease that is not driven by atopy, and lack high levels of 
eosinophilic inflammation in their airways, they are likely to be less 
responsive to ICS, and may be an important subset of asthmatics for which 
a response to long-acting anticholinergics like tiotropium can be 
anticipated. 
3.2 Include complete citations or references.  
Response:  
Afari N, Schmaling KB, Barnhart S, Buchwald D. Psychiatric comorbidity 
and functional status in adult patients with asthma. J Clin Psychology 
Medical Settings 2001; 8:245-252. 
Akinbami LJ, Schoendorf KC. Trends in childhood asthma: prevalence, 
health care utilization, and mortality. Pediatrics 2002; 110(2):315-22. 
Bender B, Milgrom H, Rand C, Ackerson L. Psychological factors 
associated with medication nonadherence in asthmatic children. J Asthma 
1998; 35:347-53. 
Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C et al. 
Pathological features and inhaled corticosteroid response of eosinophilic 
and non-eosinophilic asthma. Thorax 2007; 62:1043–1049. 
Brown ES, Khan DA, Nejtek VA, Thomas NR, Mahadi SF. Depressive 
symptoms and functioning in asthma patients. Primary Care Psychiatry 
2000; 6:155-161. 
Gao YH, Zhao HS, Zhang FR et al. The relationship between depression 
and asthma: a meta-analysis of prospective studies. PLoS One 
2015;10:e0132424 

 
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Han Y-Y, Forno E, Marsland AL, Miller GE, Celedon JC. Depression, 
asthma and bronchodilator response in a nationwide study of US adults. J 
Allergy Clin Immunol Pract 2016;4:68–73. 
Information on Asthma in New York State. 
https://www.health.ny.gov/statistics/ny_asthma/ Accessed February 15, 
2016. 
Iwamoto H, Yokoyama A, Shiota N, Shoda H, Haruta Y, Hattori N, 
Kohno N. Tiotropium bromide is effective for severe asthma with 
noneosinophilic phenotype. European Respiratory Journal. 2008; 
31(6):1379-1380. 
Kattan M, Mitchell H, Eggleston P, Gergen P, Crain E, Redline S et al. 
Characteristics of inner-city children with asthma: The National 
Cooperative Inner-City Asthma Study. Pediatr Pulmonol 1997; 24:253–
262. 
Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, 
Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED. Tiotropium in 
asthma poorly controlled with standard combination therapy. New 
England Journal of Medicine. 2012; 367(13):1198-1207. 
Liu AH, Zeiger R, Sorkness C, Mahr T, Ostrom N, Burgess S et al. 
Development and cross-sectional validation of the Childhood Asthma 
Control Test. J Allergy Clin Immunol 2007; 119(4):817-825. 
Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A et 
al. Asthma endotypes: A new approach to classification of disease entities 
within the asthma syndrome. J Allergy Clin Immunol 2011;127(2):355-60. 
Mancuso CA, Rincon M, Mcculloch CE, Charlson ME. Self-efficacy, 
depressive symptoms, and patients' expectations predict outcomes in 
asthma. Medical Care 2001; 39:1326-1338. 
Miller BD, Wood BL. Emotions and family factors in childhood asthma: 
Psychobiologic mechanisms and pathways of effect. In: Brown ES, editor. 
Social and psychological factors and psychosomatic syndromes. 24th. 
Basel: Karger; 2003. p. 131-160. 
Miller BD, Wood BL, Lim J, Ballow M, Hsu C. Depressed children with 
asthma evidence increased airway resistance: "vagal bias" as a 
mechanism? J Allergy Clin Immunol 2009 Jul;124(1):66-73. 
Morrison KM, Goli A, Van Wagoner J, Brown ES, Khan DA. Depressive 
symptoms in inner-city children with asthma. Prim Care Companion J 
Clin Psychiatry 2002; 4:174-177. 

 
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Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, 
Pendergraft TB. Development of the asthma control test: a survey for 
assessing asthma control. J Allergy Clin Immunol 2004; 113(1):59-65. 
(NHIS) National Health Institute Survey, 2013. 
http://www.cdc.gov/asthma/nhis/2013/table4-1.htm Accessed February 
15, 2016. 
Nejtek VA, Brown ES, Khan DA, Moore JJ, van Wagner J, Perantie DC. 
Prevalence of mood disorders and relationship to asthma severity in 
patients at an inner-city asthma clinic. Ann Allergy Asthma Immunol 
2001; 87:129-133. 
Nelson HS, Szefler SJ, Jacobs J, Huss K, Shapiro G, Sternberg AL. The 
relationships among environmental allergen sensitization, allergen 
exposure, pulmonary function, and bronchial hyperresponsiveness in the 
childhood asthma management program. J Allergy Clin Immunol 
1999;104:775-785.  
Omari-Asor L, Stewart R, Artero S, Ritchie K. 5-HTTLPR genotype, 
asthma, diabetes and late-life depression in an older French population. Int 
J Geriatric Psychiatry 2015; 30:1017-1022. 
Partridge MR, Saunders KB. Site of action of ipratropium bromide and 
clinical and physiological determinants of response in patients with 
asthma. Thorax 1981; 36:530–533. 
Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic 
corticosteroid unresponsive asthma. Lancet 1999; 353:2213–2214. 
Reite M, Short R, Kaufman IC, Stynes AJ, Pauley JD. Heart rate and body 
temperature in separated monkey infants. Biol Psychiatry 1978; 13:91-
105. 
Ritz T, Steptoe A, Bobb C, Harris AH, Edwards M. The asthma trigger 
inventory: validation of a questionnaire for perceived triggers of asthma. 
Psychosomatic Med 2006; 68(6):956-965. 
Silkoff PE, Lent AM, Busacker AA, et al. Exhaled nitric oxide identifies 
the persistent eosinophilic phenotype in severe refractory asthma. J 
Allergy Clin Immunol 2005; 116:1249-1255. 
Strunk RC, Szefler SJ, Phillips BR, et al, Childhood Asthma Research and 
Education Network of the National Heart, Lung, and Blood Institute. 
Relationship of exhaled nitric oxide to clinical and inflammatory markers 
of persistent asthma in children. J Allergy Clin Immunol 2003; 112:883-
892. 

 
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Waxmonsky J, Wood BL, Stern T, Ballow M, Lillis K, Cramer-Benjamin 
D et al. Association of depressive symptoms and disease activity in 
children with asthma: Methodological and clinical implications. J Am 
Acad Child Adolesc Psychiatry 2006; 45: 945-954. 
Wood BL, Cheah PA, Lim J, Ritz T, Miller BD, Stern T, Ballow M. 
Reliability and Validity of the Asthma Trigger Inventory Applied to a 
Pediatric Population. J Ped Psychology 2007; 32(5):552–560. 
Zielinski TA, Brown ES. Depression in patients with asthma. Advances 
Psychosomatic Medicine 2003; 24:42-50. 
4.0 Study Design 
4.1 Describe and explain the study design (e.g. case-control, cross-sectional, 
ethnographic, experimental, interventional, longitudinal, observational). 
Response: This is a cross-sectional study designed to compare depressed and non-
depressed asthmatics in their response to anticholinergics and the presence of 
atopic inflammation. 
After informed consent and screening baseline spirometry described in Section 
8.1, patients with decreased lung volumes for age/height/race (FEV1 <=80% 
predicted or FEV1/FVC <=85%) or significantly decreased compared to personal 
best lung volumes (FEV1 or FEV1/FVC >12% below the subject’s personal best 
spirometry results for those with old spirometry results available) will continue to 
the study intervention. They will receive 2 puffs of ipratropium HFA (42mcg 
ipratropium total dose) administered through a disposable spacer device. They 
will have spirometry repeated 30 minutes after ipratropium is given.  
Because some participants may not achieve maximum reversibility of their 
bronchoconstriction using ipratropium, all participants will receive 2 puffs of 
albuterol HFA after their second spirometry, which is the standard clinical 
practice to reverse airway obstruction of asthma, and spirometry will again be 
checked 15 minutes after albuterol. 
During the study visit, participants will undergo standardized assessments with 
validated instruments to assess depressive/anxiety symptoms, asthma triggers, and 
asthma control. 
 Components of the assessment include: 
1) 
Children’s Depression Inventory will be used to classify depressed versus 
nondepressed subjects (CDI; a 27-item self-report for depression in children. 
Scale is validated in children 7-17 years. A parent’s version of the CDI is a 
complementary tool to assess parent’s perception of child’s depressive 
symptoms). If a score on the depression inventory is suggestive of major 
depressive disorder (MDD), the guardian will be informed of this score, and 

 
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offered evaluation by the clinical child psychiatrist on our research team, who will 
make appropriate referrals if indicated. 
2) 
Asthma Control Test (ACT) will be administered to children ages 12+ and 
the Childhood Asthma Control Test (cACT) will be administered to children ages 
7-11. (Nathan et al, 2004; Liu et al, 2007) The ACT and cACT tools represent a 
continuum of asthma control assessment tools across childhood age ranges. In 
both tools, a score of >19 signifies controlled disease and scores of ≤19 signifies 
uncontrolled asthma. 
3) 
Asthma Trigger Inventory (ATI) will be used to assess perceived asthma 
triggers for subjects (ATI contains 32 items comprising six trigger-type subscales: 
(a) emotions (e.g., angry, feeling alone, home stress, tense, depressed, worried, 
unhappy, arguments, excited, weak), (b) animal allergens, (c) pollen, (d) physical 
activity, (e) air pollution/irritants, and (f) infections. Patients rate on a 5-point 
scale (0=never, 1=rarely, 2=sometimes, 3=most of the time, 4=always) how often 
a particular trigger is related to their asthma symptoms (Wood et al, 2007). 
4) 
Skin prick testing will be used to assess atopic sensitization. Children will 
undergo skin prick testing to seasonal (tree, grass, weed pollens) and perennial 
(mites, roach, animal dander, mold) allergens. Allergens eliciting a skin wheal of 
3mm greater than the saline control will indicate positive sensitization. 
5) 
Fractional exhaled nitric oxide (FeNO) will be used to assess lung 
inflammation. Subjects exhale into a FeNO analyzer for 60 seconds, and an 
exhaled nitric oxide reading measured in parts-per-million is obtained; this test 
can successfully be performed in individuals ages 5 and up. 
6) 
Subjects will have peripheral blood draw in Kaleida lab adjacent to study 
clinic. 5ml of blood will be drawn, and CBC with differential and serum IgE will 
be measured. For those children who do not meet safety qualifications for skin 
prick testing, an additional 2ml of blood will be drawn for environmental allergy 
IgEs (“Region 1 Respiratory Panel”). 
 
5.0 Local Number of Subjects 
5.1 Indicate the total number of subjects that will be enrolled or records that 
will be reviewed locally. 
Response:  50 subjects 
5.2 If applicable, indicate how many subjects you expect to screen to reach your 
target sample (i.e. your screen failure rate).  
Response: 100-200 subjects (expect 50-75% screen failure rate) 

 
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5.3 Justify the feasibility of recruiting the proposed number of eligible subjects 
within the anticipated recruitment period. For example, how many potential 
subjects do you have access to? What percentage of those potential subjects 
do you need to recruit? 
Response: In the UBMD Pediatric Allergy clinic, 752 unique patients with asthma 
diagnosis, age 7-17 years were seen in the last year. Because we would need to 
have 13-26% of these patients screened for our study to enroll 6.5% of these 
patients, we are also recruiting through flyers in the Kaleida primary care 
pediatric clinics and in the Oishei Children’s Hospital emergency department, to 
make our recruitment feasible within the study period of 1 year. 
 
6.0 Inclusion and Exclusion Criteria 
6.1 Describe the criteria that define who will be included in your final study 
sample.  
NOTE:  This may be done in bullet point fashion. 
Response: Inclusion criterion:  
1. Patients with an established diagnosis of asthma between the ages of 7-
17 years, and: 
2. Decreased lung volumes for age/height/race (FEV1 80% predicted or 
FEV1/FVC 85%) on day of study visit assessed by portable spirometry.  
6.2 Describe the criteria that define who will be excluded from your final study 
sample.   
NOTE:  This may be done in bullet point fashion.  
Response:  Exclusion criterion:  
1. Patients/parents who do not give written informed consent.  
2. Patients who are unable to perform pulmonary function testing.  
3. Patients who, on the day of study enrollment, require pulmonary 
function tests pre/post-albuterol bronchodilator, as part of their routine 
clinical care. These patients can be enrolled in the study at future visits 
when they are not receiving albuterol with pulmonary function testing. 
4. Severely developmentally delayed patients, or those who suffer from 
other severe cognitive impairment not allowing them to perform 
spirometry or participate in study instruments.  
5. Patients who are pregnant or nursing. 

 
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6. Patients that carry a diagnosis of significant cardiopulmonary disease 
other than asthma, including cystic fibrosis, alpha-1-antitrypsin deficiency, 
interstitial lung disease, tracheo-/broncheomalacia, or cyanotic congenital 
cardiac defect. 
7. Patients with glaucoma, myasthenia gravis, or bladder neck obstruction 
(anticholinergics can worsen these conditions). 
8. Patients currently taking another anticholinergic medication 
9. Non-English speaking caregivers who cannot complete study 
instruments. 
10. Patients otherwise eligible for study who have normal lung volumes 
for age/height/race (FEV1 >80% predicted and FEV1/FVC >85%, or 
<12% below the subject’s personal best spirometry results for those with 
old spirometry results available) upon screening spirometry. 
6.3 Indicate specifically whether you will include any of the following special 
populations in your study using the checkboxes below.   
 
NOTE:  Members of special populations may not be targeted for enrollment in 
your study unless you indicate this in your inclusion criteria. 
Response:   
☐ 
Adults unable to consent 
 
Individuals who are not yet adults (infants, children, teenagers) 
☐ 
Pregnant women 
☐ 
Prisoners 
6.4 Indicate whether you will include non-English speaking individuals in your 
study.  Provide justification if you will exclude non-English speaking 
individuals.  
In order to meet one of the primary ethical principles of equitable selection 
of subjects, non-English speaking individuals may not be routinely excluded 
from research as a matter of convenience. 
In cases where the research is of therapeutic intent or is designed to 
investigate areas that would necessarily require certain populations who 
may not speak English, the researcher is required to make efforts to recruit 
and include non-English speaking individuals.  However, there are studies 
in which it would be reasonable to limit subjects to those who speak 
English.  Some examples include pilot studies, small unfunded studies with 
validated instruments not available in other languages, studies with 

 
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numerous questionnaires, and some non-therapeutic studies which offer no 
direct benefit. 
Response: This pilot study will be limited to subjects with English-speaking 
parents/guardians and English-speaking children. Children and/or parents or legal 
guardians who cannot speak or read English will be encountered infrequently, and 
would represent diverse language groups. Of the 3 instruments used in this study 
(ACT, CDI, ATI), the ATI is only available in English and the CDI is only 
available in English and Spanish. The inability to use all 3 instruments on non-
English speaking participants would make our results uninterpretable for those 
subjects. 
7.0 Vulnerable Populations 
If the research involves special populations that are considered vulnerable, 
describe the safeguards included to protect their rights and welfare.   
NOTE: You should refer to the appropriate checklists, referenced below, to ensure you 
have provided adequate detail regarding safeguards and protections. You do not, 
however, need to provide these checklists to the IRB. 
7.1 For research that involves pregnant women, safeguards include: 
NOTE CHECKLIST: Pregnant Women (HRP-412) 
Response: 
  
N/A:  This research does not involve pregnant women. 
7.2 For research that involves neonates of uncertain viability or non-viable 
neonates, safeguards include: 
NOTE CHECKLISTS: Non-Viable Neonates (HRP-413), or Neonates of Uncertain 
Viability (HRP-414) 
Response:  
 
N/A:  This research does not involve non-viable neonates or neonates of 
uncertain viability. 
7.3 
For research that involves prisoners, safeguards include: 
NOTE CHECKLIST: Prisoners (HRP-415) 
Response:  
 
N/A:  This research does not involve prisoners. 
7.4 For research that involves persons who have not attained the legal age for 
consent to treatments or procedures involved in the research (“children”), 
safeguards include:   
NOTE CHECKLIST: Children (HRP-416) 
Response:  

 
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☐ 
N/A:  This research does not involve persons who have not attained the 
legal age for consent to treatments or procedures (“children”). 
7.5 For research that involves cognitively impaired adults, safeguards include: 
NOTE CHECKLIST: Cognitively Impaired Adults (HRP-417) 
Response:  
 
N/A:  This research does not involve cognitively impaired adults. 
7.6 Consider if other specifically targeted populations such as students, 
employees of a specific firm, or educationally or economically 
disadvantaged persons are vulnerable.  Provide information regarding 
their safeguards and protections, including safeguards to eliminate 
coercion or undue influence. 
Response:  
N/A 
8.0 Eligibility Screening  
8.1 
Describe screening procedures for determining subjects’ eligibility.  
Screening refers to determining if prospective participants meet inclusion and 
exclusion criteria.  
Include all relevant screening documents with your submission (e.g. screening 
protocol, script, questionnaire).  
Response: 
Informed consent will be obtained. In a private room in the UBMD Allergy clinic, 
study investigators will screen interested subjects for eligibility criteria using 
questions 1-9 on the “Pediatric Cholinergic Study Data Sheet”, and if patient is 
not screened out by history of exclusion criteria 1-9, they will have baseline 
spirometry performed by study investigator, to assess FEV1, FVC, FEV1/FVC 
ratio. Patients with normal lung volumes for age/height/race (FEV1 >80% 
predicted and FEV1/FVC >85%) will screen out of the study.  
Patients with decreased lung volumes for age/height/race (FEV1 <=80% predicted 
or FEV1/FVC <=85%) will be eligible to continue to the study intervention. 
☐ 
N/A:  There is no screening as part of this protocol. 
9.0 Recruitment Methods 
☐ 
N/A:  This is a records review only, and subjects will not be 
recruited.  NOTE:  If you select this option, please make sure that 
all records review procedures and inclusion/exclusion screening 
are adequately described in other sections. 
9.1 
Describe when, where, and how potential subjects will be recruited.  

 
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NOTE:  Recruitment refers to how you are identifying potential participants and 
introducing them to the study.  Include specific methods you will use (e.g. 
searching charts for specific ICD code numbers, Research Participant Groups, 
posted advertisements, etc.). 
Response: Potential subjects will be recruited through flyers posted in waiting 
areas of OCH ED and Hodge and Towne Garden clinics, or through a mailed 
letter explaining study which will be mailed to potential subjects who are already 
patients of UBMD Pediatrics Allergy/Immunology or Pulmonology clinics. 
Subjects from the Allergy/Immunology and Pulmonology clinics will be 
identified through chart query for ICD-9 diagnosis code 493.*/ ICD-10 code 
J45.*, and age 7-17 years. Interested prospective subjects will call the UBMD 
Pediatrics Allergy office to state they are interested in the trial, and may either 
make a study appointment, or ask to speak to the PI or study nurse to hear more 
information about the study. We will also use the i2b2 database through UB’s 
Institute for Healthcare Informatics (IHI) to recruit participants from the UBMD 
medical data base. 
9.2 Describe how you will protect the privacy interests of prospective subjects 
during the recruitment process.   
NOTE:  Privacy refers to an individual’s right to control access to him or herself.   
Response: Potential subjects will either respond to a posted flyer or letter to home. 
The list of potential subjects identified through chart query (based on age and 
ICD-9/-10 code) will be shredded once study information letters are sent out to 
those on the list. Interested prospective subjects will call the office to state they 
are interested in the trial, and may either make a study appointment, or ask to 
speak to the PI or study nurse to hear more information about the study. The PI or 
study nurse will explain the personal information that would be shared if they 
agree to be in the study. If they agree, they will be scheduled for an in person 
study visit, and they will hear fully about the study and undergo informed consent 
in a private clinic room with closed door, and interact with the study enroller and 
study nurse, who will administer questionnaires, FeNO, skin testing and 
spirometry. The privacy of patients recruited using the i2b2 data will be protected 
by following the UB IRB-approved procedure. A letter will be sent to the eligible 
patient’s physician (see attached). After one week, if the physician doesn’t contact 
the research team to refuse, a recruitment letter will be sent to participants via 
mail (see attached). If we don’t hear from the patients within two weeks, one 
follow-up call will be made (see attached phone script). If at any point the 
physician or the patient declines, the patient will be removed from the contact list. 
 
9.3 Identify any materials that will be used to recruit subjects.  

 
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NOTE:  Examples include scripts for telephone calls, in person announcements / 
presentations, email invitations.  
For advertisements, include the final copy of printed advertisements with your 
submission. When advertisements are taped for broadcast, attach the final 
audio/video tape.  NOTE:  You may submit the wording of the advertisement prior 
to taping to ensure there will be no IRB-required revisions, provided the IRB also 
reviews and approves the final version. 
 Response:  A study informational flyer with tear-off tabs will be posted in 
waiting areas of OCH ED and Hodge and Towne Garden Pediatric clinics. A 
mailed letter explaining study will be mailed to potential subjects who are already 
patients of UBMD Pediatrics Allergy/Immunology and Pulmonology clinics. 
 
10.0 
Procedures Involved 
10.1 Provide a description of all research procedures or activities being 
performed and when they are performed once a subject is screened and 
determined to be eligible. Provide as much detail as possible.   
NOTE:  This should serve as a blueprint for your study and include enough detail 
so that another investigator could pick up your protocol and replicate the research.  
For studies that have multiple or complex visits or procedures, consider the 
addition of a schedule of events table in in your response. 
Response: The entire research procedure will occur in a single study visit. 
After informed consent and screening baseline spirometry described in 
Section 8.1, patients with decreased lung volumes for age/height/race 
(FEV1 <=80% predicted or FEV1/FVC <=85%) will continue to the study 
intervention. They will receive 2 puffs of ipratropium HFA (42mcg 
ipratropium total dose) administered through a disposable spacer device. 
They will have spirometry repeated 30 minutes after ipratropium is given.  
Because some participants may not achieve maximum reversibility of their 
bronchoconstriction using ipratropium, all participants will receive 2 puffs 
of albuterol HFA after their second spirometry, which is the standard 
clinical practice to reverse airway obstruction of asthma, and spirometry 
will again be checked 15 minutes after albuterol. 
Participants will undergo standardized assessments with validated 
instruments to assess depressive/anxiety symptoms, asthma triggers, and 
asthma control. 
 Components of the assessment include: 
1) 
Children’s Depression Inventory will be used to classify depressed 
versus nondepressed subjects (CDI; a 27-item self-report for depression in 
children. Scale is validated in children 7-17 years. A parent’s version of 

 
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the CDI  (Parental CDI) is a complementary tool to assess parent’s 
perception of child’s depressive symptoms) which the parent will 
complete at the same time the child is completing the CDI. If a score on 
the depression inventory is suggestive of major depressive disorder 
(MDD), the guardian will be informed of this score, and offered 
evaluation by the clinical child psychiatrist on our research team, who will 
make appropriate referrals if indicatedMcG. 
2) 
Asthma Control Test (ACT) will be administered to children ages 
12+ and the Childhood Asthma Control Test (cACT) will be administered 
to children ages 7-11. (Nathan et al, 2004; Liu et al, 2007) The ACT and 
cACT tools represent a continuum of asthma control assessment tools 
across childhood age ranges. In both tools, a score of >19 signifies 
controlled disease and scores of ≤19 signifies uncontrolled asthma. 
3) 
Asthma Trigger Inventory (ATI) will be used to assess perceived 
asthma triggers for subjects (ATI contains 32 items comprising six trigger-
type subscales: (a) emotions (e.g., angry, feeling alone, home stress, tense, 
depressed, worried, unhappy, arguments, excited, weak), (b) animal 
allergens, (c) pollen, (d) physical activity, (e) air pollution/irritants, and (f) 
infections. Patients rate on a 5-point scale (0=never, 1=rarely, 
2=sometimes, 3=most of the time, 4=always) how often a particular 
trigger is related to their asthma symptoms (Wood et al, 2007). 
4) 
Skin prick testing will be used to assess atopic sensitization. 
Children will undergo skin prick testing to seasonal (tree, grass, weed 
pollens) and perennial (mites, roach, animal dander, mold) allergens. 
Allergens eliciting a skin wheal of 3mm greater than the saline control will 
indicate positive sensitization. 
5) 
Fractional exhaled nitric oxide (FeNO) will be used to assess lung 
inflammation. Subjects exhale into a FeNO analyzer for 60 seconds, and 
an exhaled nitric oxide reading measured in parts-per-million is obtained; 
this test can successfully be performed in individuals ages 5 and up. 
6) 
Subjects will have peripheral blood draw by our study nurse, 
labeled only with a study ID, and the nurse will transfer this blood sample 
to the OCH Kaleida lab. 5ml of blood will be drawn, and CBC with 
differential and serum IgE will be measured. For those children who do 
not meet safety qualifications for skin prick testing, an additional 2ml of 
blood will be drawn for environmental allergy IgEs (“Region 1 
Respiratory Panel”). 
 
10.2 Describe what data will be collected.   

 
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NOTE:  For studies with multiple data collection points or long-term follow up, 
consider the addition of a schedule or table in your response. 
Response: Subjects with scores above CDI clinical cutoff for depression 
will be compared to the response of those below the cutoff for depression 
in the following areas: 
a. The response (% change in volume) of lung volumes to anticholinergic 
(ipratropium) 
b. The response (% change in volume) of lung volumes to beta agonist 
(albuterol)  
c. Airway inflammation as measured by the FeNO 
d. Peripheral blood eosinophilia (eos/uL) as a measure of Th2-mediated 
inflammation 
e. Total serum IgE as a measure of atopy 
f. Atopic sensitization to perennial and seasonal allergens as measured 
by skin prick test 
g. Current asthma control per ACT tool 
h. Perceived asthma triggers per ATI tool  
In addition, the CDI depressive symptom score will also be examined as a 
continuous variable versus the above measures. 
10.3 List any instruments or measurement tools used to collect data 
(e.g. questionnaire, interview guide, validated instrument, data collection 
form).   
 
Include copies of these documents with your submission. 
Response:  
1. Child Depression Inventory (CDI) and Parental CDI 
2. Asthma Control Test 
3. Asthma Trigger Inventory 
4. Skin testing result sheet 
5. Screening history questionnaire 
 
10.4 Describe any source records that will be used to collect data about subjects 
(e.g. school records, electronic medical records). 

 
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Response: Electronic Medical Records from Kaleida Health and/or UBMD 
Pediatrics. 
 
10.5 Indicate whether or not individual subject results, such as results of 
investigational diagnostic tests, genetic tests, or incidental findings will be 
shared with subjects or others (e.g., the subject’s primary care physician) 
and if so, describe how these will be shared. 
Response: Subjects/guardians will be informed at time of visit of their initial 
spirometry results, skin testing results, and if they experience responsiveness of 
their bronchoconstriction to ipratropium. 
If a score on the depression inventory is suggestive of major depressive disorder 
(MDD), the caregiver will be informed of this score, and offered evaluation by the 
clinical child psychiatrist that is part of our research team, who will make 
appropriate referrals if he deems that it is indicated. 
10.6 Indicate whether or not study results will be shared with subjects or others, 
and if so, describe how these will be shared. 
Response: The study results will not be shared with others aside from at time of 
publication in peer-reviewed journal. 
11.0 
Study Timelines 
11.1 Describe the anticipated duration needed to enroll all study subjects. 
Response: one year is anticipated to enroll all study subjects 
 
11.2 Describe the duration of an individual subject’s participation in the study. 
Include length of study visits, and overall study follow-up time. 
Response: Individual subjects will only participate in the study during a single 
visit day, lasting approximately 2 hours. 
 
11.3 Describe the estimated duration for the investigators to complete this study 
(i.e. all data is collected and all analyses have been completed). 
Response: 14 months (12 months for data collection and 2 months for final 
analysis. 
 
12.0 
Setting 
12.1 Describe all facilities/sites where you will be conducting research 
procedures.  Include a description of the security and privacy of the 

 
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facilities (e.g. locked facility, limited access, privacy barriers).  Facility, 
department, and type of room are relevant.  Do not abbreviate facility 
names.   
NOTE:  Examples of acceptable response may be:  “A classroom setting in the 
Department of Psychology equipped with a computer with relevant survey 
administration software,” “The angiogram suite at Buffalo General Medical 
Center, a fully accredited tertiary care institution within New York State with 
badge access,” or, “Community Center meeting hall.” 
Response: The clinic settings of UBMD Pediatrics, in the Sweethome Road 
office, the Southwestern Boulevard office, and the Conventus building 4th floor 
subspecialty clinic at 1001 Main Street will be the settings for conducting this 
study. All of these clinic sites have private patient rooms where subjects will be 
consented, enrolled, and participate in study. 
 
12.2 For research conducted outside of UB and its affiliates, describe: 
• Site-specific regulations or customs affecting the research 
• Local scientific and ethical review structure 
NOTE:  This question is referring to UB affiliated research taking place outside 
UB, i.e. research conducted in the community, school-based research, 
international research, etc.  It is not referring to multi-site research.  UB affiliated 
institutions include Kaleida Health, ECMC, and Roswell Park Cancer Institute.   
Response:  
 
N/A:  This study is not conducted outside of UB or its affiliates. 
13.0 
Community-Based Participatory Research 
13.1 Describe involvement of the community in the design and conduct of the 
research.  
NOTE:  Community-Based Participatory Research (CBPR) is a collaborative 
approach to research that equitably involves all partners in the research process 
and recognizes the unique strengths that each brings.  CBPR begins with a 
research topic of importance to the community, has the aim of combining 
knowledge with action and achieving social change to improve health outcomes 
and eliminate health disparities. 
Response:  
 
N/A:  This study does not utilize CBPR. 
13.2 
Describe the composition and involvement of a community advisory 
board. 

 
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Response:  
 
N/A:  This study does not have a community advisory board. 
14.0 
Resources and Qualifications 
14.1 Describe the qualifications (e.g., education, training, experience, expertise, 
or certifications) of the Principal Investigator and staff to perform the 
research.  When applicable describe their knowledge of the local study sites, 
culture, and society.  Provide enough information to convince the IRB that 
you have qualified staff for the proposed research.  
NOTE:  If you specify a person by name, a change to that person will require prior 
approval by the IRB.  If you specify a person by role (e.g., coordinator, research 
assistant, co-investigator, or pharmacist), a change to that person will not usually 
require prior approval by the IRB, provided that the person meets the 
qualifications described to fulfill their roles. 
Response:  
Dr. Heather Lehman is board certified in Allergy/Immunology and is the Clinical 
Director of the UBMD Pediatrics Allergy/Immunology service (clinic sites of this 
service will be the study recruitment sites). She has trained multiple personnel on 
spirometry techniques. 
Dr. Wood is a developmental and family psychologist who focuses on childhood 
physical and emotional illness as influenced by specifically modeled family and 
parent-child relational patterns. 
Dr. Miller is a child psychiatrist whose research examines psychobiologic 
mechanisms (autonomic dysregulation) by which stress and depression impact 
asthma in children and adolescents.  
Over the last 20 years Drs. Miller and Wood have collaborated in examining how 
caregiver depression, family stress, and negative parenting affects the child’s 
asthma control, and pulmonary function. Drs. Miller and Wood are co-directors of 
the Center for Child and Family Asthma Studies (Women and Children’s Hospital 
of Buffalo). 
Rachel Reid is a clinical LPN who works in the UBMD Pediatric 
Allergy/Immunology clinic and the Severe Asthma Clinic. She is trained in 
performing spirometry, skin testing, phlebotomy, and FeNO measurement, and is 
able to administer medications. 
Describe other resources available to conduct the research.  
14.2 Describe the time and effort that the Principal Investigator and research 
staff will devote to conducting and completing the research. 

 
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NOTE:  Examples include the percentage of Full Time Equivalents (FTE), hours 
per week.  The question will elicit whether there are appropriate resources to 
conduct the research. 
Response:  Dr. Lehman will spend 0.1 FTE or 4 hours per week on this study. 
Rachel Reid is the study nurse and will spend 8 hours per week conducting this 
study.  
14.3 Describe the availability of medical or psychological resources that subjects 
might need as a result of anticipated consequences of the human research, if 
applicable. 
NOTE:  One example includes: on-call availability of a counselor or psychologist 
for a study that screens subjects for depression. 
Response:  Because we will be assessing participant’s emotional state in this 
study, if a score on the depression inventory is suggestive of major depressive 
disorder (MDD), the caregiver will be offered evaluation by the clinical child 
psychiatrist that is part of our research team, who will make appropriate referrals 
if he deems that it is indicated. 
14.4 Describe your process to ensure that all persons assisting with the research 
are adequately informed about the protocol, the research procedures, and 
their duties and functions. 
Response: All subjects and families will be informed about the study in detail by 
the enroller, and given adequate time to review the study consent/assent forms 
and ask any questions they may have about the study. Other Approvals 
14.5 Describe any approvals that will be obtained prior to commencing the 
research (e.g., school, external site, funding agency, laboratory, radiation 
safety, or biosafety). 
Response: Approval was already obtained from National Center for Advancing 
Translational Sciences (NCATS), as required for CTSA pilot studies. 
☐ 
N/A:  This study does not require any other approvals. 
15.0 
Provisions to Protect the Privacy Interests of Subjects 
 
15.1 Describe how you will protect subjects’ privacy interests during the course 
of this research. 
NOTE:  Privacy refers to an individual’s right to control access to him or herself.  
Privacy applies to the person.  Confidentiality refers to how data collected about 
individuals for the research will be protected by the researcher from release.  
Confidentiality applies to the data.   
Examples of appropriate responses include:  “participant only meets with a study 
coordinator in a classroom setting where no one can overhear”, or “the 

 
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participant is reminded that they are free to refuse to answer any questions that 
they do not feel comfortable answering.”   
Response: Potential subjects will either respond to a posted flyer or letter to home, 
Interested prospective subjects will call the UBMD Pediatrics Allergy office to 
state they are interested in the trial, and may either make a study appointment, or 
ask to speak to the PI or study nurse to hear more information about the study. If 
they agree, a study appointment is made in which they will hear about the study in 
a private room with closed door, and interact with that study enroller and study 
nurse, who will administer questionnaires, FeNO, skin testing and spirometry. 
15.2 Indicate how the research team is permitted to access any sources of 
information about the subjects.   
NOTE:  Examples of appropriate responses include:  school permission for review 
of records, consent of the subject, HIPAA waiver.  This question does apply to 
records reviews. 
Response: The research team will be permitted to access information about 
subjects in the Kaleida Health and UBMD EMRs, through consent of the subject 
and HIPAA waiver. 
16.0 
Data Management and Analysis 
16.1 Describe the data analysis plan, including any statistical procedures.  This 
section applies to both quantitative and qualitative analysis.  
Response: For Primary Study End Point we will conduct Repeated Measures 
Analysis of Variance (RM-ANOVA) statistical procedures, with depression vs 
non-depression as independent variables and % predicted of FEV1, FVC,  
FEV1/FVC ratio, and % reversibility as dependent variables.  For the Secondary 
Study End Point we will conduct liner regression analyses. We will correlate the 
continuous depression severity score (CDI) with % predicted of FEV1, FVC,  
FEV1/FVC ratio, and % reversibility. We will set 0.05 as the cut off p value for 
significance. 
16.2 If applicable, provide a power analysis.   
NOTE:  This may not apply to certain types of studies, including chart/records 
reviews, survey studies, or observational studies.  This question is asked to elicit 
whether the investigator has an adequate sample size to achieve the study 
objectives and justify a conclusion.  
Response: There have been no studies testing the particular relationships between 
the specific variables hypothesized in the proposed study, so it is impossible to 
conduct a reliable and valid power analysis. One of the objectives of this pilot 
study is to obtain information on distribution, variance and effect sizes necessary 
to conduct an accurate power analysis, which will be necessary to properly design 
and justify sample size for an application for funding for the larger study. 

 
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16.3 Describe any procedures that will be used for quality control of collected 
data. 
Response: The completed data collection forms and study instruments will be 
checked by the PI regularly for completeness and quality control; weekly for the 
first 4 weeks of the study and then monthly thereafter. 
 
17.0 
Confidentiality 
 
A. Confidentiality of Study Data 
 
Describe the local procedures for maintenance of confidentiality of study data 
and any records that will be reviewed for data collection.   
 
17.1 
A.  Where and how will all data and records be stored?  Include 
information about:  password protection, encryption, physical controls, 
authorization of access, and separation of identifiers and data, as applicable.  
Include physical (e.g. paper) and electronic files. 
Response: Information related to each subject will be treated with confidentiality 
to the extent provided by law. Each subject will be assigned with a single unique 
study identification number (study ID number). The medical record number, 
patient’s date of birth, and their date of office visit will not appear on the actual 
data collection form or completed study instruments; instead, only the study ID 
number will appear on the data collection form/instruments, and a separate 
identifier form will be stored in a separate locked cabinet with the original signed 
consent forms. All paper data forms/consent forms and study log will be stored in 
locked cabinets in the PI’s office, Room 5454 of the 1001 Main Street/Conventus 
Building. Data will be entered in a password-guarded spreadsheet on a password-
guarded computer. Verbal or written communications among study team members 
will only include study identification numbers, if needed, for reference. When the 
results of the study are presented and/or published, only group data will be 
provided such that no individual study participant will be identifiable. 
17.2 
A.  How long will the data be stored? 
Response:  3 years following study completion. 
 
17.3 
A.  Who will have access to the data? 
Response: Only study investigators (all CITI-trained) will have access to the data. 

 
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17.4 
A.  Who is responsible for receipt or transmission of the data? 
Response: Only study investigators (all CITI-trained) will be responsible for the 
receipt or transmission of the data. 
17.5 
A.  How will the data be transported? 
Response: Data forms will be transported only by study investigators, bringing 
them immediately to the PI’s office/locked cabinet after subject enrollment. 
B. Confidentiality of Study Specimens 
 
Describe the local procedures for maintenance of confidentiality of study 
specimens.   
 
☐ 
N/A:  No specimens will be collected or analyzed in this research.   
(Skip to Section 19.0) 
17.6 
B.  Where and how will all specimens be stored?  Include information 
about:  physical controls, authorization of access, and labeling of specimens, as 
applicable.   
Response: Samples will be labeled with a study ID number only, and 
ordered/resulted through a special study account set up with the Kaleida 
laboratory. No data will go into patient clinical charts.  
 
17.7 
B.  How long will the specimens be stored? 
Response: The blood samples will be processed immediately for CBC/diff and 
IgE. Excess blood will be discarded. No blood will be stored long-term. 
 
17.8 
B.  Who will have access to the specimens? 
Response: The study nurse will have access to the specimens, followed by the 
Kaleida laboratory staff, who will only have a study ID label on the specimens, 
with no identifiable patient information attached. 
 
17.9 
B.  Who is responsible for receipt or transmission of the specimens? 
Response: The study nurse is responsible for transmission of the specimens to the 
laboratory. 
 
17.10 B.  How will the specimens be transported? 

 
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Response: Specimens will be drawn by study nurse and transported directly to 
OCH Kaleida Core lab for processing. 
 
 
18.0 
Provisions to Monitor the Data to Ensure the Safety of 
Subjects 
☐ 
N/A:  This study is not enrolling subjects, or is limited to records review 
procedures only.  This section does not apply. 
 
NOTE:  Minimal risk studies may be required to monitor subject safety if the research 
procedures include procedures that present unique risks to subjects that require 
monitoring.  Some examples include:  exercising to exertion, or instruments that elicit 
suicidality or substance abuse behavior.  In such cases, N/A is not an acceptable 
response. 
 
18.1 Describe the plan to periodically evaluate the data collected regarding both 
harms and benefits to determine whether subjects remain safe. 
Response: All research personnel will be trained on all study procedures (protocol 
and consenting procedures) and the Principle Investigator will monitor and 
document the training and the conduct of the study on a regular basis, including 
weekly for the first 4 weeks of the study, and then monthly thereafter.  The PI will 
also monitor recruitment, enrollment rates, and events and problems involving 
risks to subjects. The i2b2 data will be protected by only accessing identifiable 
contact information remotely on IHI’s “virtual machine”, so the identifiable data 
never leaves their secure encrypted server. All use of identifiable data is done 
behind the firewall on IHI’s secure system. Although this study presents minimal 
risk to the subjects and serious events/problems (SEPs) are unlikely to occur, 
SEPs will be monitored and reported to the IRB.  In addition to reporting serious 
adverse events, protocol deviations and data integrity issues will be reported to 
the IRB. 
18.2 Describe what data are reviewed, including safety data, untoward events, 
and efficacy data. 
Response: Case reports of safety concerns will be reviewed immediately by the 
PI.  
18.3 Describe any safety endpoints. 
Response: There are no safety endpoints in this study. 
18.4 Describe how the safety information will be collected (e.g., with case report 
forms, at study visits, by telephone calls with participants). 

 
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Response: Safety information will be collected during the study visit. If a safety 
concern arises, after addressing acute safety concerns, a case report will be 
generated in writing, for immediate review by the PI. 
18.5 Describe the frequency of safety data collection. 
Response: Data collection will only occur on the single timepoint of study 
recruitment. 
18.6 Describe who will review the safety data. 
Response: The PI will review the data. 
18.7 Describe the frequency or periodicity of review of cumulative safety data. 
Response: The cumulative data will be reviewed when the entire sample size has 
been recruited, or if continuing review is required by IRB prior to the time that we 
recruit our entire sample size. Throughout the study, however, the PI will monitor 
enrollment rates and safety case reports. 
18.8 Describe the statistical tests for analyzing the safety data to determine 
whether harm is occurring. 
Response: N/A 
18.9 Describe any conditions that trigger an immediate suspension of the 
research. 
Response: Any adverse events not immediately reversible with in office treatment 
will trigger research suspension and a report to the IRB. 
19.0 
Withdrawal of Subjects 
☐ 
N/A:  This study is not enrolling subjects.  This section does not apply. 
 
19.1 Describe anticipated circumstances under which subjects may be withdrawn 
from the research without their consent. 
Response: If a subject is unable to adequately perform spirometry maneuvers or 
complete the study instruments/questionnaires, they will be withdrawn.  
19.2 Describe any procedures for orderly termination.   
NOTE:  Examples may include return of study drug, exit interview with clinician.  
Include whether additional follow up is recommended for safety reasons for 
physical or emotional health. 
Response: None. Each subject will only be involved for a single study visit, so 
this would be done in person with the study investigator at that visit. 

 
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19.3 Describe procedures that will be followed when subjects withdraw from the 
research, including retention of already collected data, and partial 
withdrawal from procedures with continued data collection, as applicable. 
Response: Participants that ask to be withdrawn from the study before completing 
all instruments or spirometry tests at study visit will be withdrawn and no data 
will be collected after withdrawal.  Data collected prior to timepoint of 
withdrawal from the study will be used in the data analysis. 
20.0 
Risks to Subjects 
20.1 List the reasonably foreseeable risks, discomforts, hazards, or 
inconveniences to the subjects related to their participation in the research. 
Consider physical, psychological, social, legal, and economic risks.  Include 
a description of the probability, magnitude, duration, and reversibility of the 
risks.  
NOTE:  Breach of confidentiality is always a risk for identifiable subject data. 
Response:  
Ipratropium is an inhaled anticholinergic agent with low risk of anticholinergic 
side effects. We will be excluding patients with disease states or medications 
which can be worsened by anticholinergic therapy (see exclusions). As an 
anticholinergic drug, cases of precipitation or worsening of narrow-angle 
glaucoma, glaucoma, halo vision, conjunctival hyperemia, corneal edema, 
mydriasis, acute eye pain, dry throat, hypotension, palpitations, urinary retention, 
tachycardia, constipation, bronchospasm, including paradoxical bronchospasm 
have been reported with the use of ipratropium. We will only be giving a one-time 
dose of ipratropium in the study so significant or long-term side effects are not 
anticipated. 
Spirometry is considered a safe procedure that can occasionally may make a 
subject cough or feel lightheaded, and rarely can cause transient bronchospasm 
which can be treated with bronchodilator. 
Allergy skin testing is a routine clinical procedure in an allergy office. Local skin 
reactions are common at positive testing sites. These positive reactions will 
gradually disappear over about 30-60 minutes, and usually no treatment is 
necessary.  Occasionally, local swelling will appear 4-6 hours after testing, and 
will gradually disappear over the next week or so. Skin testing will infrequently 
cause systemic allergic reactions. These reactions may consist of any or all of the 
following symptoms: itchy eyes, nose, or throat; stuffy nose; runny nose; 
tightness in the throat or chest; wheezing; lightheadedness; faintness; nausea and 
vomiting; hives; generalized itching; and shock, the latter under extreme 
circumstances.  

 
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Risks with a simple venous stick for a blood drawn include bleeding from the site, 
bruising or hematoma formation, temporary dizziness, and a low risk of infection 
being introduced at the blood draw site.  
Risks from psychological screening include possible embarrassment or discomfort 
secondary to the identification of possible depressive symptoms of which the 
child and guardian were not aware of; however, scores from our testing would not 
be sufficient to make a clinical diagnosis of psychological illness. Risks will be 
minimized by administering the psychological questionnaires privately (child 
undergoes CDI separate from parent who undergoes Parental CDI). 
There is a small but present risk of breach of confidentiality in the study. All 
efforts will be taken to minimize this risk by conducting research in a private 
room, using study IDs only for all questionnaires/study samples, and storing study 
identifier sheet and signed informed consents in a separate locked area away from 
the locked area where all study results are stored. 
20.2 Describe procedures performed to lessen the probability or magnitude of 
risks, including procedures being performed to monitor subjects for safety. 
Response: To lessen the risk of allergic reaction to skin testing, this will not be 
performed on subjects with active wheezing, upper respiratory infection, or need 
for albuterol for active asthma symptoms in the prior 24 hours. These subjects that 
are not eligible for skin testing will have an extra 2ml of blood drawn to look for 
environmental allergen IgEs through a blood test. 
20.3 If applicable, indicate which procedures may have risks to the subjects that 
are currently unforeseeable. 
Response: Allergy skin testing, phlebotomy, exhaled nitric oxide measurement, 
and spirometry are the procedures involved in the study, and while they are 
common procedures routinely used in clinical practice, could have a potentially 
unforeseeable risks. 
20.4 If applicable, indicate which research procedures may have risks to an 
embryo or fetus should the subject be or become pregnant. 
Response: Skin testing is not recommended during pregnancy because an allergic 
reaction during pregnancy can include uterine contractions as a symptom. This is 
therefore a risk on day of study. Spirometry should be performed with caution 
during third trimester of pregnancy because of the mechanical stress on the gravid 
abdomen during a spirometry breathing maneuver, but is not contraindicated 
during the first or second trimester. 
20.5 If applicable, describe risks to others who are not subjects. 
Response: N/A 
 

 
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21.0 
Potential Benefits to Subjects 
21.1 Describe the potential benefits that individual subjects may experience by 
taking part in the research.  Include the probability, magnitude, and 
duration of the potential benefits.  Indicate if there is no direct benefit.   
NOTE:  Compensation cannot be stated as a benefit. 
Response: Subjects have the potential to benefit by determining if they have 
significant responsiveness of their asthma to ipratropium therapy. As 
anticholinergic therapy emerges as an option for asthmatics, information on their 
ipratropium-responsiveness will help to guide whether an anticholinergic agent 
should be considered in their asthma regimen. 
They also have the potential benefit of finding out what they are allergic to by 
skin testing at study visit. 
22.0 
Compensation for Research-Related Injury 
☐ 
N/A:  The research procedures for this study do not present risk of 
research related injury (e.g. survey studies, records review studies).  This 
section does not apply.   
22.1 
If the research procedures carry a risk of research related injury, 
describe the available compensation to subjects in the event that such injury 
should occur.   
Response: none 
 
22.2 
Provide a copy of contract language, if any, relevant to compensation for 
research related injury. 
NOTE:  If the contract is not yet approved at the time of this submission, submit the 
current version here.  If the contract is later approved with different language regarding 
research related injury, you must modify your response here and submit an amendment 
to the IRB for review and approval. 
Response: N/A 
 
23.0 
Economic Burden to Subjects 
23.1 Describe any costs that subjects may be responsible for because of 
participation in the research.   
NOTE:  Some examples include transportation or parking. 
Response: Transportation to the study site and parking at the study site are the 
potential costs to subjects. 

 
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☐ 
N/A:  This study is not enrolling subjects, or is limited to records review 
procedures only.  This section does not apply. 
24.0 
Compensation for Participation 
25.1 
Describe the amount and timing of any compensation to subjects, 
including monetary, course credit, or gift card compensation. 
Response: We will reimburse families with a $10 gift card for going through the 
baseline spirometry only (if they screen out due to normal spirometry), or with a 
$100 gift card if they qualify for and complete the entire study (spirometry post-
ipratropium/post-albuterol, exhaled nitric oxide, skin testing, blood draw and 3 
study instruments). Gift cards will be provided at the time of study visit. 
Subjects receiving the $100 gift card will be asked to complete and submit an IRS 
W-9 form, which will be held confidentially by the PI in locked cabinets in the 
PI’s office, Room 5454 of the 1001 Main Street/Conventus Building. 
☐ 
N/A:  This study is not enrolling subjects, or is limited to records 
review procedures only.  This section does not apply. 
☐ 
N/A:  There is no compensation for participation.  This section 
does not apply. 
25.0 
Consent Process 
25.1 Indicate whether you will be obtaining consent.   
NOTE:  This does not refer to consent documentation, but rather whether you will 
be obtaining permission from subjects to participate in a research study.   
Consent documentation is addressed in Section 27.0. 
 
Yes 
(If yes, Provide responses to each question in this Section) 
☐ 
No 
(If no, Skip to Section 27.0) 
 
25.2 Describe where the consent process will take place.  Include steps to 
maximize subjects’ privacy. 
Response: Consent will be obtained in a private room in the UBMD 
Pediatric outpatient clinics. 
25.3 Describe how you will ensure that subjects are provided with a sufficient 
period of time to consider taking part in the research study.   
NOTE:  It is always a requirement that a prospective subject is given sufficient 
time to have their questions answered and consider their participation.  See “SOP: 
Informed Consent Process for Research (HRP-090)” Sections 5.5 and 5.6. 

 
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Response: The parent/guardian can take as much time as they would like to 
review the informed consent at the time of enrollment, and if desired, could even 
postpone study involvement until a future date. 
25.4 Describe any process to ensure ongoing consent, defined as a subject’s 
willingness to continue participation for the duration of the research study.   
Response: The enroller and nurse will communicate verbally with the 
subject/guardian throughout the study visit to ensure ongoing consent through the 
single study visit. 
25.5 Indicate whether you will be following “SOP: Informed Consent Process for 
Research (HRP-090).” If not, or if there are any exceptions or additional 
details to what is covered in the SOP, describe: 
• 
The role of the individuals listed in the application who are involved in 
the consent process 
• 
The time that will be devoted to the consent discussion 
• 
Steps that will be taken to minimize the possibility of coercion or 
undue influence 
• 
Steps that will be taken to ensure the subjects’ understanding 
Response:  
 
We have reviewed and will be following “SOP: Informed Consent Process 
for Research (HRP-090).” 
 
Non-English Speaking Subjects  
 
N/A:  This study will not enroll Non-English speaking subjects.   
(Skip to Section 26.8) 
25.6 Indicate which language(s) other than English are likely to be 
spoken/understood by your prospective study population or their legally 
authorized representatives. 
 
NOTE: The response to this Section should correspond with your response to 
Section 6.4 of this protocol. 
Response:  
 
25.7 If subjects who do not speak English will be enrolled, describe the process 
to ensure that the oral and written information provided to those subjects 
will be in that language.  Indicate the language that will be used by those 
obtaining consent. 

 
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NOTE:  Guidance is provided on “SOP:  Informed Consent Process for Research 
(HRP-090).” 
Response:  
 
 
Cognitively Impaired Adults 
 N/A:  This study will not enroll cognitively impaired adults.   
(Skip to Section 26.9) 
25.8   Describe the process to determine whether an individual is capable of 
consent.  
Response:  
 
 
Adults Unable to Consent 
 
N/A:  This study will not enroll adults unable to consent.  
(Skip to Section 26.13) 
When a person is not capable of consent due to cognitive impairment, a legally 
authorized representative should be used to provide consent (Sections 26.9 and 
26.10) and, where possible, assent of the individual should also be solicited 
(Sections 26.11 and 26.12). 
25.9  Describe how you will identify a Legally Authorized Representative (LAR).  
Indicate that you have reviewed the “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013)” for research in New 
York State.  
NOTE:  Examples of acceptable response includes: verifying the electronic 
medical record to determine if an LAR is recorded. 
Response:  
☐ 
We have reviewed and will be following “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013).”  
25.10 For research conducted outside of New York State, provide information 
that describes which individuals are authorized under applicable law to 
consent on behalf of a prospective subject to their participation in the 
research.  One method of obtaining this information is to have a legal 
counsel or authority review your protocol along with the definition of 

 
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“legally authorized representative” in “SOP: Legally Authorized 
Representatives, Children, and Guardians (HRP-013).” 
Response:  
 
25.11 Describe the process for assent of the adults: 
• 
Indicate whether assent will be obtained from all, some, or none of the 
subjects.  If some, indicate which adults will be required to assent and 
which will not. 
Response:  
 
• 
If assent will not be obtained from some or all subjects, provide an 
explanation of why not. 
Response:  
 
25.12 Describe whether assent of the adult subjects will be documented and the 
process to document assent.   
NOTE:  The IRB allows the person obtaining assent to document assent on the 
consent document using the “Template Consent Document (HRP-502)” Signature 
Block for Assent of Adults who are Legally Unable to Consent. 
Response:  
 
 
Subjects who are not yet Adults (Infants, Children, and Teenagers) 
☐ 
N/A:  This study will not enroll subjects who are not yet adults.   
(Skip to Section 27.0) 
25.13 Describe the criteria that will be used to determine whether a prospective 
subject has not attained the legal age for consent to treatments or 
procedures involved in the research under the applicable law of the 
jurisdiction in which the research will be conducted (e.g., individuals under 
the age of 18 years).  For research conducted in NYS, review “SOP: 
Legally Authorized Representatives, Children, and Guardians (HRP-013)” 
to be aware of which individuals in the state meet the definition of 
“children.”  
NOTE:  Examples of acceptable responses include: verification via electronic 
medical record, driver’s license or state-issued ID, screening questionnaire. 

 
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Response: It will be determined whether a prospective subject has not attained 
legal age of consent by verification via electronic medical record. 
 
25.14For research conducted outside of New York State, provide information 
that describes which persons have not attained the legal age for consent to 
treatments or procedures involved the research, under the applicable law of 
the jurisdiction in which research will be conducted.  One method of 
obtaining this information is to have a legal counsel or authority review 
your protocol along the definition of “children” in “SOP: Legally 
Authorized Representatives, Children, and Guardians (HRP-013).” 
Response:  N/A 
 
25.15 Describe whether parental permission will be obtained from: 
Response:  
  One parent even if the other parent is alive, known, competent, reasonably 
available, and shares legal responsibility for the care and custody of the 
child. 
☐ 
Both parents unless one parent is deceased, unknown, incompetent, or not 
reasonably available, or when only one parent has legal responsibility for 
the care and custody of the child. 
☐ 
Parent permission will not be obtained.  A waiver of parent permission is 
being requested. 
NOTE:  The requirement for parent permission is a protocol-specific determination 
made by the IRB based on the risk level of the research.  For guidance, review the 
“CHECKLIST: Children (HRP-416).”  
25.16Describe whether permission will be obtained from individuals other than 
parents, and if so, who will be allowed to provide permission.  Describe 
your procedure for determining an individual’s authority to consent to the 
child’s general medical care. 
Response: Legal guardians may provide consent. They must provide legal 
documentation of their status at the time of informed consent, or this 
documentation must be readily available in the electronic medical record. 
 

 
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25.17 Indicate whether assent will be obtained from all, some, or none of the 
children.  If assent will be obtained from some children, indicate which 
children will be required to assent. 
Response: Assent will be obtained for all children age 7 and greater. 
 
25.18 When assent of children is obtained, describe how it will be documented. 
Response: Children age 7-13 will have a separate Assent Document to review and 
sign, and children ages 14-17 will have a separate Assent Document to review and 
sign. 
26.0 
Waiver or Alteration of Consent Process 
Consent will not be obtained, required information will not be disclosed, or the 
research involves deception. 
 
N/A:  A waiver or alteration of consent is not being requested. 
26.1 If the research involves a waiver or alteration of the consent process, please 
review the “CHECKLIST: Waiver or Alteration of Consent Process (HRP-
410)” to ensure that you have provided sufficient information for the IRB to 
make the determination that a waiver or alteration can be granted.   
NOTE:  For records review studies, the first set of criteria on the “CHECKLIST: 
Waiver or Alteration of Consent Process (HRP-410)” applies.  
Response:  
 
26.2 If the research involves a waiver of the consent process for planned 
emergency research, please review the “CHECKLIST: Waiver of Consent 
for Emergency Research (HRP-419)” to ensure you have provided sufficient 
information for the IRB to make these determinations.  Provide any 
additional information necessary here: 
Response:  
 
27.0 
Process to Document Consent 
☐ 
N/A:  A Waiver of Consent is being requested.   
(Skip to Section 29.0) 
27.1 Indicate whether you will be following “SOP: Written Documentation of 
Consent (HRP-091).” If not or if there are any exceptions, describe whether 
and how consent of the subject will be obtained including whether or not it 
will be documented in writing.   

 
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NOTE:  If your research presents no more than minimal risk of harm to subjects 
and involves no procedures for which written documentation of consent is normally 
required outside of the research context, the IRB will generally waive the 
requirement to obtain written documentation of consent.  This is sometimes 
referred to as ‘verbal consent.’  Review “CHECKLIST: Waiver of Written 
Documentation of Consent (HRP-411)” to ensure that you have provided sufficient 
information.  
If you will document consent in writing, attach a consent document with your 
submission.  You may use “TEMPLATE CONSENT DOCUMENT (HRP-
502)”.  If you will obtain consent, but not document consent in writing, attach the 
script of the information to be provided orally or in writing (i.e. consent script or 
Information Sheet).   
Response:  
 
We will be following “SOP:  Written Documentation of Consent” 
(HRP-091). 
28.0 
Multi-Site Research (Multisite/Multicenter Only) 
 
N/A:  This study is not an investigator-initiated multi-site study.  This 
section does not apply. 
 
28.1 If this is a multi-site study where you are the lead investigator, describe the 
processes to ensure communication among sites, such as: 
• 
All sites have the most current version of the IRB documents, including 
the protocol, consent document, and HIPAA authorization. 
• 
All required approvals have been obtained at each site (including 
approval by the site’s IRB of record). 
• 
All modifications have been communicated to sites, and approved 
(including approval by the site’s IRB of record) before the 
modification is implemented. 
• 
All engaged participating sites will safeguard data as required by 
local information security policies. 
• 
All local site investigators conduct the study appropriately. 
• 
All non-compliance with the study protocol or applicable requirements 
will be reported in accordance with local policy. 
Response:  
 
28.2 Describe the method for communicating to engaged participating sites: 
• 
Problems 

 
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• 
Interim results 
• 
Study closure 
Response:  
 
28.3 
Indicate the total number of subjects that will be enrolled or records that 
will be reviewed across all sites. 
Response:  
 
28.4 
If this is a multicenter study for which UB will serve as the IRB of record, 
and subjects will be recruited by methods not under the control of the local site 
(e.g., call centers, national advertisements) describe those methods.  
Response:  
 
29.0 
Banking Data or Specimens for Future Use 
 
N/A:  This study is not banking data or specimens for future use or 
research outside the scope of the present protocol.  This section does not 
apply. 
29.1 If data or specimens will be banked (stored) for future use, that is, use or 
research outside of the scope of the present protocol, describe where the 
data/specimens will be stored, how long they will be stored, how the 
data/specimens will be accessed, and who will have access to the 
data/specimens.  
NOTE:  Your response here must be consistent with your response at the “What 
happens if I say yes, I want to be in this research?” Section of the Template 
Consent Document (HRP-502). 
Response:  
 
29.2 List the data to be stored or associated with each specimen. 
Response:  
 
29.3 Describe the procedures to release banked data or specimens for future 
uses, including: the process to request a release, approvals required for 
release, who can obtain data or specimens, and the data to be provided with 
specimens. 
Response:  

 
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30.0 
Drugs or Devices 
☐ 
N/A:  This study does not involve drugs or devices.  This section does not 
apply. 
30.1 If the research involves drugs or devices, list and describe all drugs and 
devices used in the research, the purpose of their use, and their regulatory 
approval status.  
Response:  
Ipratropium (Atrovent) HFA Inhalational Device – will be used to assess 
responsiveness of subject asthma to cholinergic bronchodilator. FDA-approved 
for bronchoconstriction related to COPD. Used “off-label” for asthma. We 
requested clarification from the FDA whether IND was required for this study and 
it was determined that an IND is not required. 
Albuterol HFA Inhalational Device – will be used to assess responsiveness of 
subject asthma to beta-adrenergic bronchodilator. FDA-approved for treatment or 
prevention of bronchospasm in patients 4 years of age and older with reversible 
obstructive airway disease 
30.2 Describe your plans to store, handle, and administer those drugs or devices 
so that they will be used only on subjects and be used only by authorized 
investigators. 
Response: The ipratropium HFA, albuterol HFA and portable spirometer used in 
this study will be stored in a locked cabinet in the PI’s office (Rm 5454 of 1001 
Main Street) and removed only by study personnel during study recruitment 
sessions. 
If the drug is investigational (has an IND) or the device has an IDE or a claim 
of abbreviated IDE (non-significant risk device), include the following 
information: 
30.3 Identify the holder of the IND/IDE/Abbreviated IDE. 
Response:  N/A; FDA has determined that no IND is required for this study. 
 
30.4 Explain procedures followed to comply with FDA sponsor requirements for 
the following:   
 

 
University at Buffalo Institutional Review Board (UBIRB) 
Office of Research Compliance | Clinical and Translational Research Center Room 5018 
875 Ellicott St. | Buffalo, NY 14203 
UB Federalwide Assurance ID#: FWA00008824 
 
 
Page 42 of 42 
IRB Version: JAN2016 
 
Applicable to: 
FDA Regulation 
IND Studies 
IDE studies 
Abbreviated 
IDE studies 
21 CFR 11 
X 
X 
 
21 CFR 54 
X 
X 
 
21 CFR 210 
X 
 
 
21 CFR 211 
X 
 
 
21 CFR 312 
X 
 
 
21 CFR 812 
 
X 
X 
21 CFR 820 
 
X 
 
Response:  N/A 
 
31.0 
Humanitarian Use Devices 
 
N/A:  This study does not involve humanitarian use devices.  This does 
not apply. 
31.1 
For Humanitarian Use Device (HUD) uses provide a description of the 
device, a summary of how you propose to use the device, including a description 
of any screening procedures, the HUD procedure, and any patient follow-up 
visits, tests or procedures. 
Response:  
 
31.2 
 For HUD uses provide a description of how the patient will be informed 
of the potential risks and benefits of the HUD and any procedures associated with 
its use. 
Response: