C.3.10 Exemplar IRB Protocol LOI3-PHYS-01

ATTACHMENT C.3.10 Protocol Summary (Excerpted from Exemplar Local IRB Protocol)
LOI3-PHYS-01

OMB#: 0925-0593
EXPIRATION DATE: 07/31/2011

Risks/Benefits. Specific aims include hypotheses you will investigate.
HYPOTHESES:
1) Airway resistance and airway inflammation can be accurately measured and tracked in toddlers and
preschool children using methods such as airway resistance (Raw ) and exhaled nitric oxide levels
(FeNO);
2) These alternative methods correlate w ith validated spirometric values in older children;
OVERALL GOAL:
To assess the feasibility, the validity, and the reproducibility of different tools to measure pulmonary
function in children 1-8 years of age, and to evaluate w hether these tools are reproducible among tw o
different centers: the University of Miami, a currently active National Children’s Study, and St.
Christopher’s Hospital for Children in Philadelphia / Drexel University.
UTILITY AND RELEVANCE:
Raw and FeNO do not require patient cooperation beyond "normal" (tidal volume) breathing, and
therefore can be performed in toddlers and preschool children. Meaningful measurements have been
obtained in children as young as 2 years of age. These techniques should be easy to perform and
reproduce in the research field. Both Raw and FeNO can be performed across the ages including older
children and adolescents, and administering these tests requires relatively little expertise.
The relationship betw een measurements of resistance and flow s is not w ell established. Simultaneous
measurements of Raw, FeNO and subsequently spirometry (in children ~4-8yrs of age), w ill allow us to
establish correlations betw een all three methods.
As part of the National Children’s Study Vanguard phase, the current project will allow investigators to
assess whether measurements of Raw and FeNO a) Can be performed in children younger than
previously studied, b) Are correlated w ith each other, and c) Have a predictive value for lung function in
later childhood and adolescence (as measured by FEV1 and other spirometric values).
AIMS:
1) To measure lung function in toddlers and pre-school children using Raw and FeNO, novel
technologies that are accurate, reproducible, and easy to perform, and to assess w hether such
measurements are reproducible w ithin each child and between tw o centers;
2) To assess the correlation between Raw , FeNO, and spirometry in older children (~4-8 yrs old);
SPECIFIC OBJECTIVES:
We w ill utilize technologies that have recently been developed to measure pulmonary function and
airw ay resistance and to screen for airway inflammation; we w ill assess their correlation w ith standard
spirometry in older children; and w e will aim to extend their application to children of younger ages
than previously studied. The primary aim of our study will be to determine w hether airw ay resistance
and exhaled nitric oxide can be measured reliably in children as young as 1 year, and to assess
whether the results are comparable between different study centers. To this end, our study objectives
are:
1. To recruit ~60-70 healthy children ages 1-8 years at each center.
2. To obtain the following measurements of lung function:
a. Conventional spirometry in all children 5 years or older, and attempt it in younger children w ho
cooperate and can perform the required maneuvers (w e anticipate ~4-8yrs of age).
b. Airw ay resistance (Raw) by the random occlusion technique (Rocc) in all participating children.
c. Exhaled nitric oxide (FeNO) in all participating children.
3. To assess the reproducibility of these tools by evaluating repeated measurements for each
participating child during the study.
4. To assess the reliability of measurements by comparing the results betw een the two centers.
5. To assess the correlation between all three measures.
6. To assess parental perceptions of the testing and their likelihood to consent to the testing in the
main NCS.
7. To identify technical or other issues that may arise during the study, in regards to the feasibility of
using these technologies as a w ay to evaluate pulmonary function in young children.

4.2. * Research Background
Provide background and previous studies supporting the study rationale. Include a brief summary
of existing knowledge relevant to the research. Explain how the research may contribute to the
advancement of knowledge.
BACKGROUND AND SIGNIFICANCE:
Lung development continues at a remarkable pace from birth to about 6-7 years of age, and the lungs
continue to grow until late adolescence. Understanding patterns of the progression of normal lung /2011

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function in young children w ould allow clinicians to identify those with early changes in pulmonary
function. Early changes in pulmonary function may indicate an increased risk of pulmonary disorders
such as asthma or others. There are, how ever, limited longitudinal studies defining the range of normal
development of the lungs from infancy.
One of the reasons for the paucity of studies and normative data on lung function in early childhood is
that preschool children cannot perform conventional spirometry, the accepted standard for pulmonary
function testing (PFT), w hich requires significant cooperation and coordination. Alternative techniques
have gained popularity in recent years, such as studies of airw ay resistance (Raw) by the random
occlusion technique (Rocc). Other techniques, such as exhaled nitric oxide (FeNO), measure the degree
of inflammation in the airw ays.

4.3. If you have cited references above, please attach a bibliography, including title, full

author list, journal, date and pages. This bibliography should include only those articles
referenced above.
Name
Description
There are no items to display

Version

4a. Description of Study (cont'd)
Rationale and Methodology
4.4. * In non-technical, lay language, describe the study design and all study procedures, in order of
sequence and timing. Include length of subject participation, what tasks are involved in the study,
what tests or procedures subjects will be asked to complete or undergo, specific measures to be
used, etc. If applicable, include frequency of visits, duration of visits, and study procedure
calendar.
This is a 2-center study (UM being the main site and Drexel/Philadelphia the secondary site). Each
center w ill recruit ~60-70 children ages 1-8 years. Study visits will be as follows:
Visit 1: After consent/assent and initial evaluation by one of the study investigators, the
parent/guardian w ill fill in a general health and respiratory questionnaire. Three different tools for
pulmonary function tests (PFT) w ill be attempted with the child:
1) Airway resistance (Raw ) by random occlusion technique (Rocc)
2) Exhaled nitric oxide (FeNO)
3) Conventional spirometry (for children approximately 4-8 years, if developmentally capable).
All three types of tests (Raw , FeNO, and spirometry) are standard approved techniques and
procedures. Prior research on lung function testing has been done in children as young as 2-3 years of
age. Raw and FeNO require only that the child breathe into a disposable mouthpiece for ~10 seconds
(FeNO) or ~30 seconds (Raw ). Conventional spirometry w ill only be attempted in children as young as
~4-5 years of age who can cooperate, as it involves following specific instructions such as taking a
deep breath and exhaling quickly. None of these procedures are experimental, painful, or put their
health or safety at risk. All instruments that w ill be utilized are FDA 501(k) cleared.
Visit 2 (approximately 1 week after visit 1): Attempts at Raw , FeNO, and if possible, spirometry (for
children age ~4-8) will be repeated.
Visit 3 (approximately 1 month after visit 1): Raw , FeNO, and if possible, spirometry w ill be repeated. At
this final visit there will be a survey regarding the family's perception of the ease of performing PFTs
and their opinion on whether these are tools that could be used routinely in young children.
Follow -up: After finishing the study, we w ill perform one follow -up call at ~6 and at ~12 months from
the initial study, using the follow-up questionnaire, to assess w hether any of the study participants
has developed asthma or other respiratory symptoms. There w ill be no study visits or procedures other
than the phone call.
4.4.A.

Standard Measures: Click the "Add" button to open the search window , then click the "Find"

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button to brow se and select measures.
Name of Measure
Brief Description
There are no items to display

OMB#: 0925-0593
EXPIRATION DATE: 07/31/2011

Type of Measure

NO TE: A copy of the first page of e a ch sta ndard m e a sure is pro vide d in the Library of Standard Me asures for
ve rification. Ensure that the ve rsion be ing use d in this study is the sam e as the ve rsion that has be e n
se le cte d.

Upload any questionnaires and/or assessment tools to be used that are not listed
Name
Description
Contact info sheet
Contact information. Detachable.
Health screen
To be used before each visit.
Main questionnaire
Main questionnaire. Visit 1.
Parental exit survey
Exit survey. Visit 3.
Phone follow-up questionnaire
Screening questionnaire
Study checklist

above:
Version
0.04
0.03
0.03
0.04
0.01
0.03
0.01

4.5. Identify and distinguish between those procedures that are standard treatment versus those that
are experimental/research-specific.
Not applicable
All three types of PFT (Raw, FeNO, and spirometry) are considered standard approved techniques and
procedures. Prior research has been done in children as young as 2-3 years of age. We will be
evaluating whether children as young as 1 year of age are able to cooperate and perform these
studies. No experimental procedures w ill be utilized. All devices are FDA 501(k) cleared.
4.6. Describe any therapeutic alternatives that may exist for the study population.
Not applicable

4b. Description of Study (cont'd)
Risk/Benefit Assessm ent
4.7. * Describe the nature, degree, and if available, expected frequency of all potential
economic/financial, legal, physical, psychological, social or other risks to which research
participants may be exposed as a result of their participation in this research. If applicable,
please describe the risk of investigational agents or devices (side effects).
None of the 3 types of PFT utilized are invasive, nor do they pose any risk of physical harm to the
participants. Two of them (Raw and FeNO) only involve the child breathing into the mouthpiece or face
mask of the device for approximately 30 seconds. The third (spirometry) requires more collaboration in
performing specific maneuvers and will be reserved to children over ~4-5 yrs of age (the standard age
for clinical use of spirometry); of note, spirometry is standard of care in the diagnosis and
management of pediatric respiratory diseases such as asthma, and both FeNO and Raw are
increasingly utilized in clinical settings.
4.8. * Are there potential direct benefits of this research to the subjects?
Y es

No

4.8.A. If yes, provide a description of the potential direct benefits and indicate if all, or only
some, of the subject groups may derive this potential benefit.
While we w ill recruit healthy children, w e do anticipate w e might detect certain children with
abnormal measurements. These children may have un-diagnosed asthma or other conditions
and the detection of such conditions would be a direct benefit for the child. Additionally all
families will meet w ith one of the study investigators, all pediatric pulmonologists, and will have
the opportunity to ask questions about their child's respiratory health. Finally, families w ith
identified smokers w ill be given information on the dangers of smoking and smoking cessation
resources.
4.9. * Are there potential benefits of this research to society?

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Y es

Tools for screening of pulmonary funct…

OMB#: 0925-0593
EXPIRATION DATE: 07/31/2011

No

4.9.A. * Please explain:
The National Children Study (w w w.nationalchildrensstudy.gov) is an ambitious prospective
cohort study that w ill examine the effects of environmental influences on the health and
development of 100,000 children across the United States, following them from before birth
until age 21. The goal of the Study is to improve the health and well-being of children.
Our project is one of the studies in the Vanguard or formative phase of the NCS. We aim to
determine w hether lung function can be measured much earlier (as early as 1 year of age)
than conventional methods (usually 5 yrs of age). If these tools w ork we w ill be able to
monitor lung function during the NCS and hopefully learn how to identify children at risk for
respiratory disease much earlier in life than w e currently are able to.
4.10. * Explain why the risk/benefit ratio supports conducting this research.
Risks from study procedures are minimal, and involve basically the child being unw illing to cooperate.
All the child has to do is breathe into the instrument's mouthpiece for 20-30 seconds. Risks to privacy
w ill be minimized by study protocol.
Direct benefits include education and possible detection of undiagnosed lung disease in some of the
participating children. Indirect benefits w ill arise from the NCS, which will be the largest birth cohort
study of children ever undertaken.

4c. Description of Study (cont'd)
Data
4.11. * Describe follow-up, data storage methods, data security, authorized access to records and
record retention, including site name and address.
At each center, all study data (questionnaires and PFTs) w ill be collected using passw ord-protected,
FISMA-compliant laptops during study visits.
Data collected at UM w ill then be transferred to the password-protected desktop in the PI's office and
entered into a database system w ith the capability to export files to statistical programs such as SAS
or SPSS.
Data collected from the Drexel site w ill be uploaded to the PI's study desktop via a secure, FISMAcompliant VPN connection, and/or w ill be brought personally by that site's main investigator during
site visits to UM, and will be merged w ith the main database.
All study forms and instruments w ill contain only the participant's Study ID. The only link betw een the
patient's PHI (name and contact information) and the Study ID w ill be the Contact Information Sheet
(CIS, attached, section 4.4.A). The CIS w ill not be duplicated or digitally backed up in any manner (ex.
photocopies, digital scans, faxes, etc.) and w ill be stored in a secure, locked storage area or draw er
w ithin a secure location. CIS from the Philadelphia site w ill be either physically mailed to UM or w ill be
handed to the PI in person during one of the study visits to UM.
Only the PI, co-investigators, and RA will have access to the study computers. These computers w ill
be FISMA-compliant and located in the badge-accessible study/PI office. The master database w ill be
only accessible to the PI until the end of the study. At that time, after de-identification has been
verified and after data cleaning and verification, it will be accessible to the study co-investigators and
the sponsoring institution. All original records w ill be kept according to UM's institutional policies.
4.12. * Support the study validity by describing the statistical design, including quantitative and
qualitative methods used to analyze data.
This w ill be primarily a feasibility study to evaluate whether these PFT tools can be used in children
younger than previously studied. We w ill assess this in the following ways:
1) Completion rate: Description of the rate of success in obtaining reliable measurements for each of
the three tools (Rint, FeNO, spirometry).
2) Reproducibility: For each PFT, we w ill assess w ithin-subject correlation among the 3 study visits
(day 1, day ~5-10, day ~25-35).
3) Reliability: We will compare completion rates, reproducibility measures, and results betw een the

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EXPIRATION DATE: 07/31/2011

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tw o centers, to assess w hether these are measure that can be compared among multiple centers in
the larger NCS.
4) Correlation: We w ill evaluate w hether the results from three tools correlate w ith each other, to
assess w hether they can be used as 'surrogates' for each other in the larger NCS.
Priv acy/Confidentiality Agreem ents
4.13. Describe any privacy agreements or certificates of confidentiality, if applicable.

4d. Description of Study (cont'd)
Deception
4.14. * Is the use of deception part of the study design?
Yes

No

If yes, please answer the following 3 questions:
4.14.A. Describe in detail the nature of the deception and explain why this is necessary for the
research.
4.14.B. State how, when, and by whom the research subjects will be debriefed.
4.14.C. Upload a copy of the debriefing script.

5. Study Participants
Per 45 CFR 46, human subjects (participants) means a living individual about w hom an investigator (w hether
professional or student) conducting research obtains:
1. data through intervention or interaction w ith the individual; or
2. identifiable private information (i.e. pathological specimens, medical records, etc.)
5.1. * Participant Age:
Check all that
apply

Notes

0-6

Parent Permission/Consent required for each participant

7-17

Parent Permission/Consent & Child Assent required for each participant

18-65
65+

Consent required for each participant unless a waiver of consent is approved by the
IRB
Consent required for each participant unless a waiver of consent is approved by the
IRB

5.2. For the following questions, please use integers for your responses. For any question that is not
applicable, please enter the number 0.
(Do not enter commas, decimal points or special characters)
5.2.A. * Maximum number of subjects in the Protocol to be screened at all sites (regardless of
PI):
500
5.2.B. * Total number of subjects in the Protocol to be studied at all sites(regardless of PI):
200
Univ ersity of Miam i
5.2.C. * Maximum number of subjects to be screened by this PI at UM:
250
* Maximum number of subjects to be enrolled by this PI at UM:
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EXPIRATION DATE: 07/31/2011

100
* From the above, how many are expected to com plete this study (participate in the study
beyond initial enrollment?
80
Jackson Health System s
5.2.D. * Maximum number of subjects to be screened by this PI at Jackson Health System s
(JHS):
0
* Maximum number of subjects to be enrolled by this PI at Jackson Health System s (JHS):
0
* From the above, how many are expected to com plete this study (participate in the study
beyond initial enrollment)?
0
Miam i VA Medical Center
5.2.E. * Maximum number of subjects to be screened by this PI at Miam i VA Medical Center:
0
* Maximum number of subjects to be enrolled by this PI at Miam i VA Medical Center:
0
* From the above, how many are expected to com plete this study (participate in the study
beyond initial enrollment)?
0

5a. Study Populations
5.3. * Study populations to be included in this study where PI will be conducting research and those
sites where the UM IRB will have oversight responsibility:
Check all that apply
Notes
Normal, healthy volunteers
Children/minors (under 18 years of age)

5.3.A. If other, please specify:

5.3.B. Describe below any additional safeguards that have been included to protect vulnerable
subjects:
None of the study procedures involve more than minimal risk for the participating children.
Written informed consent w ill be obtained from the parents and assent from the children w hen
age-appropriate.

5b. Inclusions/Exclusions
5.4. * Is the population being enrolled in this study at high risk for incarceration?
Yes

No

5.4.A. If yes, will the subjects be withdrawn from the study once they are incarcerated?
Yes

No

5.4.A.(i) If the above answer (question 5.4.A.) is no, describe how re-contacting/reconsenting, treatment, and/or follow-up will occur:
NOTE: If a subject becomes incarcerated while enrolled in a study, all research interactions and
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funct…
NOTE: If a subject becomes incarcerated
enrolled
in a study,
all research interactions and
interventions with that subject, and the obtaining of identifiable private information about the subject, must
cease until the requirements of subpart C have been satisfied with respect to the relevant protocol.
If notified that a previously enrolled research subject has become a prisoner, the principal investigator must
promptly seek IRB re-review of the protocol in accordance with the requirements of subpart C if the principal
investigator wishes to have the prisoner-subject continue to participate in the research. In special
circum stances in which the principal inv estigator asserts that it is in the best interests of the
subject to rem ain in the research study while incarcerated, the IRB Chairperson m ay determ ine
that the subject m ay continue to participate in the research until the requirem ents of subpart C
are satisfied.

5.5. * What are the criteria for exclusion of participants from the research?
1) Diagnosed asthma
2) History of preterm birth before 34 w eeks gestational age
3) Cystic fibrosis, chronic lung disease or other significant pulmonary disease
4) Recent acute respiratory tract infection (<2 weeks)*
5) Other acute or chronic disease at the discretion of the investigators
[*May be re-approached at a later time]
5.6. * Will any population be systematically excluded in this study?
Yes

No

5.6.A. If yes, provide rationale/justification for this exclusion:

5.7. * What are the criteria for inclusion of participants in the research?
1) Ages 12 months to 8 years (inclusive)
2) Ability to understand and follow instructions
3) Willingness to participate and sign informed consent
4) Ability and w illingness to participate in all 3 study visits

5.8. * Will only one group of individuals be systematically selected and recruited for this study (e.g.,
welfare patients, racial and/or ethnic minorities, persons confined to institutions or persons
determined to be incapacitated)?
Yes

No

5.8.A. If yes, please state how this participant group will benefit from the results of the research
and provide the reasons and justifications to target this group:

5f. Research Involving Minors
* Pick ONE category below:
Select one
§46.404 Research not involving greater than minimal risk.
HHS w ill conduct or fund research in which the IRB finds that no greater than minimal risk to children is
presented, only if the IRB finds that adequate provisions are made for soliciting the assent of the
children and the permission of their parents or guardians.
§46.405 Research involving greater than minimal risk but presenting the prospect of direct benefit
to the individual subjects.
HHS w ill conduct or fund research in which the IRB finds that more than minimal risk to children is
presented by an intervention or procedure that holds out the prospect of direct benefit for the
individual subject, or by a monitoring procedure that is likely to contribute to the subject's w ell-being,
only if the IRB finds that:

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