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JHSPH Institutional Review Board

RESEARCH PLAN

PI: William Checkley, MD, PhD

Study Title: Prevalence of Cardiopulmonary complications chronic mountain sickness and pulmonary
hypertension in among high-altitude urban dwellers in Peru

IRB No.:

PI Version Number/Date: Version 3- 31 May 2010

1. Aims/objectives/research question/hypotheses:

Aims:
1. Estimate the prevalence of chronic mountain sickness in a population living at 3800 meters
above sea level in two communities with and without varying levels of biomass fuel
exposureuse.
2. Estimate the prevalence of pulmonary hypertension in participants with chronic mountain
sickness in two communities with varying levels of biomass fuel use.with and without
biomass fuel exposure.
3. Determine if the degree of erythrocytosis correlates with the severity of symptoms among
participants with chronic mountain sickness.
4. Determine the prevalence of atherosclerosis through measurement of Characterize the
distribution of carotid intima-media thickness (cIMT) in participants with and without biomass
fuel exposure in high altitude dwellers and in participants at sea-level..
Determine the differences of prevalence from atherosclerosis through cIMT measurement
between populations from Puno and Lima

Hypotheses:
1. The prevalence of Chronic chronic mountain sickness and pulmonary hypertension
prevalence is greater in a high-altitude population that uses with biomass fuel combustion s
for cooking and heatingrelated varies among rural and urban population within high altitude
dwellers in Puno.
2. Pulmonary hypertension is associated with chronic mountain sickness in high altitude
dwellers in Puno.The distribution of values for carotid intima-media thickness is greater in a
high-altitude population that uses biomass fuels for cooking and heating than in a high-
altitude or low-altitude populations that do not.

2. Background and rationale:

The study of altitude-related illnesses is a crucial an important area field of investigation and a field that
is relevant for the mmillions of people worldwide that currently live at more than above 2500 meters
above sea level. In South America alone, approximately 35 million people are estimated to live above
2500 meters1. Asian Asian countries such as China, India, Nepal, Afghanistan, Bhutan and Kyrgyzstan
are each each thought to have 2% to 45% of their populations living at high altitude1. The most
commonly and most ffatal of the altitude-related illnesses are Chronic Mountain Sickness (CMS) and
High Altitude Pulmonary Hypertension (HAPH). CMS, or also known as Monge Disease, was first
described by Carlos Monge in 19251. Since this original description by Monge, the definition and
diagnostic criteria has continued to evolve. The 2004 Consensus Statement on Chronic and Subacute
High Altitude Diseases defines CMS and HAPH as separate diseases caused by the chronic hypoxia
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found at high altitude. While the clinical symptoms often overlap, the pathophysiologic hallmark of CMS
is hypoxia induced polycythemia while in HAPH it is hypoxia- induced pulmonary hypertension.
Chronic hypoxemia due to CMS is further complicated by the high prevalence of biomass fuel
use in developing countries. In many areas of Peru biomass fuel remains the predominant form of fuel
for cooking and heating. While there has been a national program to address the risks of biomass fuel
exposure by replacing traditional stoves with more efficient stoves, the program has failed to be widely
accepted in these communities. As a consequence, high altitude populations continue to have high
levels of exposure to pollutants from biomass fuels. We seek to study the effect biomass fuel exposure
has on the risk of Chronic Mountain Sickness CMS and High Altitude Pulmonary HypertensionHAPH.
Previous studies have shown that worldwide the indoor air pollution that occurs with biomass
fuel exposure is associated with a higher incidence of respiratory infections, including pneumonia and
tuberculosis; chronic obstructive pulmonary disease, cardiovascular events, low birth weight and all-
cause mortality in both adults and children2. Few studies have examined the effect of biomass fuel
exposure specifically on high altitude populations. A study in the Himalayas found that regional
populations had a high prevalence of respiratory morbidity when exposed to biomass fuel3. In Bolivia
residents of two villages at high altitude were shown to have a higher prevalence of chronic bronchitis
secondary to domestic biomass fuel exposure4. Thus far, no studies have examined the effect of
biomass fuel exposure on Chronic Mountain Sickness CMS or High Altitude Pulmonary
HypertensionHAPH. Given that CMS and HAPH are purely diseases exclusively found of at high
altitude, it is vitally important that wwe seek to investigate the effects that better understand the
contribution of biomass fuel exposure use has on these on the development of these potentially fatal
illnesses.
Biomass fuel exposure may also increase the risk of cardiovascular disease. Since
cardiovascular diseases are associated with high mortality and generally undiagnosed before the onset
of clinical findings, there is a need for a reliable tool for early diagnosis. One such marker is the Carotid
carotid intima-media thickness (cIMT). is cIMT is a non-invasive surrogate marker of coronary artery
disease (CAD), measured at B mode ultrasound, is considered as a surrogate marker for and
atherosclerosis. It can be used to detect an accelerated process or subclinical disease.5,6 Specifically,
cIMT as a risk factor for myocardial infarction and stroke in older adultsCoronary artery disease (CAD)
increase in cIMT is associated with the presence and extent of CAD.7,8 Arterial wall thickness is
significantly increased by atherosclerotic plaques. Arterial wall thickness is significantly increased by
atherosclerotic plaques. A plaque defined by “The Mannheim Intima-media Thickness Consensus
Panel” is an isolated cIMT of ≥ 1.5 mm or < 50% of the surrounding IMT;9 however, some physicians
consider maximal thickness as little as 1 mm indicative of plaque10. Weil, et al.11 refers that high altitude
exposure is associated with significant erythropoiesis; oxygen saturation level below 95% stimulates
erythrocytosis from the resulting hypoxemia. As arterial oxygen partial pressure decreases below 67
mmHg, erythropoietin and transferrin plasma concentration increases, plasma volume decreases,
nonetheless plasma´s red blood cells increase has not been proven yet. Levine and colleagues12,13
suggested that intermittent high altitude exposure has a protective cardiovascular exercise factor, but
this has not been proven among chronic exposure yet. Since high altitude is associated with low oxygen
saturation and arterial oxygen partial pressure levels14, it may suggest that chronic exposure due to high
altitude levels may have a negative physiologic impact on the human body by decreasing plasma
volume, cardiac output and increasing erythrocytosis. Therefore changes in cIMT would be a valid may
be detected early diagnostic clinical instrument to prevent cardiovascular disease among high altitude
dwellers, particularly among those who manifest CMSchronic exposure.

3. Participants:
Puno is a city in southeastern Peru, located on the shore of Lake Titicaca at 3825 meters above sea
level. It is also the capital and largest city of the Puno Province and has a population of approximately
150,000 inhabitants. The city itself is currently in a state of rapid urbanization; hence, increasing levels
of ambient air pollution resulting primarily from automotive exhaust are an emerging threat. In contrast,
surrounding Puno city are many rural villages where the use of biomass fuels, particularly wood
burning, is either exclusive or highly prevalent in each village.

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We seek to enroll 400-450 participants in Puno, 200-225 from an urban area and 200-225 from a rural
area using data from a community census. We also seek to enroll 200-225 participants in a peri-urban
area in Lima that has no exposure to biomass fuels. To do so, we plan to screen approximately 600
800 participants. Our inclusion and exclusion criteria are as follows:

Inclusion criteria:
Full-time resident in the area
Capable of understanding procedures
Capable of providing informed consent and responding to a questionnaire

Exclusion criteria:
Lived in Puno for less than 6 months
Plans to move from the area within one year

Sample size:
We will identify potentially eligible subjects from the current census data using a simple random sample
of 400 450 subjects aged 30 35 years of age and older. Previous studies report that the prevalence of
CMS is approximately 10%. Therefore, to obtain a precision of 5% and a confidence level of 95%
(=0.05) we would require approximately 385 participants. Since we are asking participants to complete
several tests, we expect a 5%-10% drop-out loss to follow-up from the study. As a result, we will invite
400 450 subjects to participate in our study.

Identifiers:
Personal information, including participant´s full names, household addresses, sex, personal
identification number, and contact phone numbers will be collected as part of the study. Each participant
will be provided a unique study identifier and personal information will be stored separately from any
results; both identifiers and data will be kept in a password-secured file so that only study administrators
will have access. . Patients will be assigned an ID number so data will not be directly linked to their
names. In a separate and secured file, we will have a list of patient names with their ID numbers in the
event that we need to contact them for future studies. This file will be accessible only by study
administrators. The addresses will be collected so that results from patients can be mapped to perform
a better epidemiologic analysis of asthma in these populations. Further issues with confidentiality are
subsequently discussed in this proposal.

4. Study procedures:
5.
As this is a cross-sectional study, we plan to recruit participants directly from the communities of
interest: the rural villages in Acora and Ilave, Puno and the urban center from Puno. For the sea-level
comparison group, we would plan to recruit participants from and semi urban from “Pampas”a peri-
urban shanty town located at in San Juan de Miraflores, in Lima (regarding the cIMT procedure).
Participants will be randomly sampled from a community census and approached regarding
participation into the study. We will obtain written informed consent or ask for a waiver of consent
among those who do not read or write. Only one adult per household will participate in the study. The
subject will only need to come to the study site only once as longitudinal data are not being collected for
this particular study. However, we will ask for consent to contact patients for future related studies. The
study is expected to require 12 to 18 months to complete.

Questionnaire
After informed consent is obtained, participants will respond to a face-to-face questionnaire by the
trained community health workers using paper-based formats. We will obtain data about several factors
related to Chronic Mountain Sickness CMS and High Altitude Pulmonary Hypertension HAPH including
age, sex, city of birth, number of years at high altitude, amount of time during the year spent at sea
level, chronic medical conditions (specifically coronary artery disease, OSA, COPD, interstitial lung
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disease), and smoking habits. To assess clinical symptoms patients will also respond to a CMS
questionnaire15.

Anthropometrics
After completing the questionnaire, each patient will have their height, weight, heart rate, systolic and
diastolic blood pressure, respiratory rate, and oxygen saturation measured.

Phlebotomy
After anthropometric measurements, up to 4 ml of venous blood will be taken by a trained technician
and refrigerated for later analysis of hemoglobin. The blood specimens will be labeled with the
participant ID number and stored in the local biospecimen storage laboratory. With patient consent,
these specimens will be stored for an indefinite period for future genetic and cytokine analyses for
further studies. Consent for indefinite storage is not required for participation in the study, nor is
consent for providing blood in the first place.

Clinical Quantitative Cardiovascular Measurements

Each patient will also undergo an electrocardiogram, transthoracic echocardiogram, and carotid intima-
media thickening measurement (cIMT) with a portatil portable ultrasound (Sonosite Micromaxxx
ultrasound, Sonosite Inc., Bothell, WA). Using electrocardography, we plan to detect signs of right heart
strain such as right atrial enlargement (P wave amplitude >2.5 mm in II and/or >1.5 mm in V1) or right
ventricular hypertrophy (right axis deviation > 90 degrees, R in aVR > 5 mm, R in aVR > Q in aVR; V1
findings consistent with: R/S ratio in > 1 and negative T wave, qR pattern, R > 6 mm, or S < 2mm, or
rSR' with R' >10 mm ; R in V1 + S in V5 or V6 >10 mm; R/S ratio in V5 or V6 < 1; R in V5 or V6 < 5 mm;
S in V5 or V6 > 7 mm). Using a transthoracic echocardiogram, we plan to measure right ventricular
systolic pressure (RVSP). .

3) Number of study contacts or visits required of participants.

Participants will be visited a maximum of 2 times. During the first visit, which will be done by home
visitation, we will ask for consent and we will administer a questionnaire. During the second visit, we
will ask participants to come to our offices for electrocardiogram, transthoracic echocardiogram, carotid
intima-media thickening measurements and venopunction.

4) Expected duration of the study.

One year.

5) A brief data analysis plan and description of the nature of the variables to be derived.
Following double data-entry and careful data cleaning and consistency checking, descriptive statistics
using tabulations and graphical methods will be performed. Standard methods will be used to calculate
95% confidence intervals for prevalence estimates. Multivariable logistic (for binary outcomes) and
linear regressions (for continuous, normally distributed outcomes) will be used to assess the
relationship between urbanization and CMS, pulmonary hypertension and carotid-intima media
thickness.

6) If human biospecimens (blood, urine, saliva, etc.) will be collected, provide details about collection,
volume (ml) or number, use, storage, identification, and disposal.
Biospecimens will consist of 4 ml samples of blood obtained from each willing participant. They will be
stripped of all identifying data except for each participant’s study ID, which will be on the labeled tube.
As before mentioned, access to the study results with identifiers is limited to the study physicians and
PI. The tube will also be labeled with date of collection. The biospecimens will be stored at -20oC in the
sites’ respective storage facilities. In Lima, they will be stored in the lab of Dr. Gilman at the Universidad
Peruana Cayetano Heredia. Biospecimens will be disposed of after completion of study and future
related cytokine assays and genetic studies.

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7) Describe how subjects will be screened for eligibility and assigned to to

study/intervention and comparison/control groups.
Participants will be drawn from census data for the communities under study. Subjects will be randomly
selected from each of the two study areas (an urban community in Puno city and two outlying rural
communities in Puno).

8) Explain and justify whether there will be blinding.

Not applicable.

9) Explain and justify whether participants will not receive routine care or will have current therapy
stopped.
Not applicable.

10) Explain and justify the use of a placebo or non-treatment group.

Not applicable.

11) Provide a definition of treatment failure or participant removal criteria.

Not applicable.

12) Describe what happens to participants receiving therapy when the study ends or if a subject’s
participation ends prematurely.
Not applicable.

13) Describe the process for referring subjects to care outside the study, if needed.
Not applicable.Participants who are identified to have CMS or HAPH will be referred to the reference
hospital in Puno city. Participants who are found to have any signs of ischemia by electrocardiography
or during clinical questioning will be referred to the reference in Puno city.

14) For studies that evaluate interventions, have a randomized study design, and/or are a clinical trial,
provide power calculations for projected sample size.
Not applicable.

15) Describe any plan for reporting test results to participants. For medical tests, describe how results
will be validated (e.g., conducted in a CLIA certified laboratory).
Not applicable.We will report values of hemoglobin, oxygen saturation by pulse oximetry, blood pressure
and presence or absence of high-altitude related illnesses (CMS or HAPH) that needs further evaluation
by a physician. cIMT is still a research tool, thus we will not report these values for any clinical
interventions.

5. Data Security and Protection of Subject Confidentiality

a. Are you applying for a Certificate of Confidentiality? Yes.

b. Identify the data security plan below that best describes how you will minimize the risk of a
breach of confidentiality by checking one of the boxes on the left side of this chart. If your
study includes sequential phases that require different procedures, or does not fit these
categories, explain in “Other”.

Note: Identifiers include name, address, SSN, hospital record number, etc., and other indirect identifiers
(e.g., date of birth) that, when combined with other variables, may make a subject identifiable. These
categories reflect minimal standards; you may impose more stringent protections. See the JHSPH Data
Security Guidance at www.jhsph.edu/irb > Policies & Guidance > Guidance for additional information
regarding best practices.

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Hard Copy of data collection form: Indicate your choice but typing an X in the appropriate box
on the left:
Hard copies of data collection materials have identifiers and are locked in a secure cabinet or room
with limited access by specified individuals. When possible, redacted (de-identified) versions of the
data collection sheets will be used for coding and analysis.
X Hard copies of data collection materials include an ID code and do not have personal identifiers.
However, a code linking the data to the subject’s personal information is stored separately from the
data collection sheets, and is locked in a secure cabinet or room with limited access by authorized
individuals.
Data are not collected on paper.
Other (describe):

Electronic Databases: Indicate your choice but typing an X in the appropriate box on the left: :
Note: A de-identified version of the database should be used for data analysis except in instances in
which identifying information is prerequisite for coding or analysis. Databases that retain identifying
information require a higher degree of electronic security.
The study is minimal risk and data collected are not sensitive in nature. No personal identifiers are
included in the electronic database. Any electronic documents that link IDs to identifying
information are stored on a computer in accordance with JHSPH Data Security guidance.
X Personal identifiers are included in the database. The data are stored on a computer that is
password protected with a secure server. Transfer or storage on portable devices (e.g., laptops,
flashdrives) is encrypted. The devices on which this information is stored are accessible only to
individuals who need access to these data.
No personal identifiers are included in the database but linkable identifiers exist separately and the
data are sensitive in nature (e.g., substance use, mental health, genetic propensities, sexual
practices or activities) such that disclosure could provide a risk to the individual. The codes are
stored on a computer that is password protected with a secure server. Transfer or storage on
portable devices (e.g., laptops, flashdrives) is encrypted. The devices on which this information is
stored are accessible only to individuals who need access to these data.
Other (describe):

c. If you are using participants’ personal identifiers, describe any plans for disposing of
identifiers including if, when and how that will be done.
All individuals will be assigned study identification (ID) number and only the ID number will
be linked to the data. Data will be recorded, stored, and backed up electronically in
password protected files. The data that could be used as identifiers – participant addresses
and ages/birthdates – will be securely stored in these files. Joao Da Silva, MD, Mary
Elmasri, MD, and William Checkley, M.D., Ph.D. will be responsible for the confidentiality
of study documents and personal identities of participants. Access to the study results
with identifiers is limited to the field workers, data entry personnel, Joao Da Silva, Mary
Elmasri on-site physicians, and Drs. Checkley and Gilman.

d. Describe any plans for destroying data including if, when and how that will be done.
Data will not be destroyed.

6. Recruitment process:
a. Describe how participants will be recruited.
We will identify potential subjects using current census data using random sampling within
each study location (Puno city: --urban, surrounding and rural communities—rural and semi
urban from Pampas at SJM in Lima: Pampas de San Juan de Miraflores city). These
potential participants will be approached at their homes by the investigators or fieldworkers
and asked if they would be willing to participate in our study if eligible.

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b.Explain how your recruitment materials will be used.

Subjects will be selected using the most recent census available for this study. Subjects will
be asked a series of questions to determine eligibility. If eligible, the investigator or
fieldworker will explain the study purpose and protocol. If they agree to participate the
investigator or fieldworker will explain the risks of participation and explain that subjects are
free to leave the study at any time without penalty.
c. If relevant, address any privacy concerns associated with the recruitment process.
Not relevant.
7. Consent process and documentation:
a. Describe who will obtain informed consent from participants, and how, when and where
consent will be obtained.
b. This consent form will be read to the participant before commencing participation. Before
providing consent, participants will be given the opportunity to ask questions until they fully
understand the study. Eligible persons willing to participate will be asked to give written
informed consent. The participant as well as the interviewer will sign the consent process
guide, stating that consent was given. If the participant does not read or write, we will ask
the participant to provide informed verbal consent for participation. A waiver of consent will
be requested in these instances.
c. If the study will involve vulnerable populations (e.g., children, prisoners, cognitively impaired
adults, non-English-speakers, etc.) describe efforts to ensure their understanding of the
research and the extra protections that will be in place to ensure their voluntary
participation.
No vulnerable populations will be involved in this study. However, in the event that a
participant is illiterate, the signature of a witness will be required for consent.
d. If a waiver of consent or a waiver or alteration of signed consent is requested, provide a
justification for the waiver/alteration, and describe any alternate procedures for informing
participants about the research.
Not applicable.

8. Risks:
a. Describe the risks associated with the study and its procedures, including physical,
psychological, emotional, social, legal, or economic risks.
There is minimal risk associated with participation in this study. TThere is a small risk of
psychological distress if one becomes aware that he or she is living with CMS or pulmonary
hypertensionHAPH or if severe cardiac disease is identified..
b. Describe steps to be taken to minimize those risks.
Information regarding chronic illness due to high-altitude (CMS or pulmonary hypertension
HAPH) will be given to participants., and how those values compare against study
populations in an urban (low biomass fuel use) and rural setting (high biomass fuel use). We
will review with each participant the benefits of decreasing their CMS or High Altitude
Pulmonary Hypertension symptoms to their health if it is 1 SD greater than those
experienced in the urban setting.
c. Describe the research burden for participants, including time, inconvenience, out-of pocket
ccosts, etc.
Answering the questionnaire will take no longer than 30 minutes. Visits to the home for vital
functions and anthropometry measures will take no longer than one hour.
Electrocardiography, Echocardio echocardiography and cIMT would take no longer than 45
minutes. No out-of-pocket costs will be required of the participants.
d. Describe how participant privacy will be protected during data collection if sensitive
questions are included in interviews.
No sensitive questions are included in interviews.

9. Benefits:

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a. Describe any potential direct benefits to participants from participating in the research (not
including payment for participation).
Participants will be given information regarding the chronic diseases related to high altitude
(CMS and HAPH) findings during this study. They will also be informed of potential
measures that can be taken to reduce this exposure. This may prompt participants to make
certain changes to their daily basis activities or behaviors that will improve their quality of
life.
b. Describe potential societal benefits likely to derive from the research.
The data collected from this study will give us insights on new theories that could help
prevent or implement interventions to reduce high altitude diseases within these
communities, also the behavioral and household factors associated with different levels of
exposure.

10. Payment:
a. Describe the form, amount, and schedule of payment to participants.
Not applicable.
b. Include the possible total remuneration and any consequences for not completing all
phases of the research.
Not applicable.

11. FDA regulated studies: (not applicable)

a. Drug products:
1) Provide the rationale for the drug, dose, and route of administration chosen.
2) If FDA-approved drugs will be administered for non-FDA approved indications, or
if doses or routes of administration or participant populations will be different from those
approved by the FDA, justify the choices and provide safety information for the method
or population.
3) Provide a justification and safety information if the study will administer non-FDA
approved drugs without an IND.
b. Devices:
1) Provide the rationale for the device chosen.
2) If you are using an investigational device, clarify whether it has an IDE or provide
information to support a determination that it is a Non-Significant Risk device (NSR).
3) If the device is NSR, explain whether it is exempt from the IDE requirements.

12. Safety monitoring:

a. Describe how safety will be monitored, by whom, and how often.
All study-related information will be stored securely. All participant information will be stored
in password-protected databases at computers accessible only to study investigators. All
reports, study data collection, process, and administrative forms will be identified by a coded
number to maintain participant confidentiality. Names or other personal identifiers from the
participants will be recorded and stored safely under supervision of study investigators.
All information from this study will be held with strict confidentiality, and only researchers
listed above, local regulatory authorities, Institutional review board/ethics Committee (UPCH
and Johns Hopkins University), the Office of Human Research Protection (OHRP), and their
designees may have access to this information.
b. If a DSMB (or equivalent) will be established, describe the following:
i. The DSMB membership, affiliation and expertise.
Not applicable.
ii. The charge or charter to the DSMB.
Not applicable.
iii. Plans for providing DSMB reports to the IRB.
Not applicable.
c. Describe plans for interim analysis and stopping rules.
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Not applicable.

13. Plan for reporting unanticipated problems/adverse events: Describe plan for reporting to the
IRB and (if applicable) to the sponsor. Include plan for government-mandated reporting of abuse
or illegal activity.
As health outcomes are being assessed, reporting of adverse events is relevant to this study. If
any serious adverse event (SAE) occurs, they will be identified by the investigators who will
generate electronic reports within 24 hours after the event. Patients would be assessed by Drs.
Elmasri and Da Silva during this particular adverse event redirecting them towards the nearest
emergency health facility for them proper care.

14. Other IRBs:

If the research will require review by other IRBs, provide the name and contact information for
each IRB and its FWA (available on OHRP’s website at http://www.hhs.gov/ohrp/assurances).

This proposal will be also reviewed by the IRB at Universidad Peruana Cayetano Heredia
(UPCH) in Lima, Peru (IORG0000671) and NGO ASOCIACION BENEFICA PRISMA IRB (IORG
0001304). The UPCH Ethical Institutional Committee has the code IRB00001014 and its Federal
Wide Assurance is FWA00000525, whereas the PRISMA Ethical Institutional Committee has the
code IRB00001304 and its FWA is FWA00001413.

UPCH Contact information:

Ethical Committee at Universidad Peruana Cayetano Heredia
Av. Honorio Delgado 430, Urb. Ingeniería, S.M.P. Lima – Perú.
Teléfono: (51-1)319-0005, (51-1)482-4541
Email: duiictinv@upch.edu.pe

PRISMA Contact information

Sra. Mónica Mateo
Asociación Benéfica Prisma
Calle Carlos Gonzales 251 .Urb. Maranga San Miguel, Perú
mmateo@prisma.org.pe
Tel. 6165500 anexo 246
Fax. 6165501

15. Outside collaborations:

The study is to be implemented in collaboration with the Universidad Peruana Cayetano Heredia
and Asociación Benéfica PRISMA; a Peruvian NGO with over 15 years of experience conducting
NIH funded research studies. UPCH will provide laboratory support and A.B. PRISMA will provide
administrative support. Joao Da Silva, MD; Mary Elmasri, MD; Robert Gilman, MD and William
Checkley, MD; are responsible for protocol design, implementation, and quality control.

16. Oversight plan for student studies:

For student-initiated studies, explain how the PI will monitor the student’s adherence to the IRB-
approved research plan, such as communication frequency and form, training, reporting requirements,
anticipated time frame for the research, and who will have direct oversight of the student if the study site
is not local.

This student study will take place under the auspices of the Fogarty International Clinical Research
Scholars program, academic year 2009-10, and will likely continue after Joao Da Silva and Mary
Elmasri completes his year of scholarship. During this upcoming year, Joao Da Silva and Mary Elmasri
will be in continual contact with Drs. William Checkley (JHSPH) and Robert Gilman (JHSPH). Both
mentors visit UPCH on a monthly basis and are present from one to several weeks at a time. During
these visits, they will meet with Joao both Fogarty Scholars and the field workers to address any issues,
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as well as observe data collection to ensure that the protocol is followed. In addition, the two mentors
will be in contact via scheduled telephone or Skype conversations on at least a weekly basis, and they
will also remain in contact via email. The study is expected to be completed by July of 2011.

17. Oversight plan for studies conducted at non-JHSPH sites, including international venues,
for which the JHSPH investigator is the responsible PI:
Explain how the study will be managed, the qualifications of study personnel managing the project, and
how personnel involved with the data collection and analysis will be trained in human subjects research
protections. If the PI will not personally be on-site during the data collection process, provide details
about the supervision of the data collection and the communication plan between the PI and study team
to assure adherence to the IRB-approved research plan.

This study will be managed primarily by William Checkley, MD, PhD. Dr. Checkley is Assistant
Professor of Pulmonary and Critical Care, has a joint appointment in International Health, and is a
research scientist at A.B. PRISMA, Lima, Peru. He is the Principal Investigator for the project and
will be providing close guidance and supervision to the team on all phases of the study. Dr.
Checkley is a pulmonary physician and epidemiologist by training. He has extensive experience in
the conduct of field research in developing countries, particularly in longitudinal field studies.
Relevant to this project, Dr. Checkley has participated in a variety of research endeavors over a 16-
year period in the field sites in Peru and is the project leader for pulmonary research activities of the
UPCH Center of Excellence.

Student investigators and fieldworkers will be trained before the beginning of field activities. In
addition to training in selection of study participants and the appropriate completion of the study
questionnaire, the training will include modules on ethical issues including appropriate consent
procedures granting confidentiality and avoiding any form of coercion. All course participants will
receive a copy of an Interviewer’s Manual for the study.

The student investigators or field coordinators on site will communicate regularly with Dr. Checkley
regarding the progress of the study.

18. Creation of a biospecimen repository: (not applicable)

a. Explain the source of the biospecimens, if not described above.
b. Describe where the biospecimens will be stored and who will be responsible for them.
c. Describe how long the biospecimens will be stored, and what will happen at the end of
that period.
d. Explain whether the biospecimens will be shared with other investigators, inside and
outside of JHU, how the decision to share will be made, and by whom. Also explain how
downstream use of the specimen will be managed, and what will happen to left-over
specimens.
e. Explain whether the specimens will be identifiable, and if so, how they will be coded, who
will have access to the code, and whether the biospecimens will be shared in linked
(identifiable) form.
f. Explain whether the repository will have Certificate of Confidentiality protections.
g. Explain whether a participant will be able to withdraw consent to use a biospecimen, and
how the repository will handle a consent withdrawal request.
h. Describe data and/or specimen use agreements that will be required of users.

19. Data Coordinating Center: Note: Complete section 14 for each participating site. (Not
applicable)
a. How will the study procedures be developed? Who is responsible for considering the
feasibility of the study intervention, and the risks the intervention poses to subjects?
b. How will the study documents that require IRB approval at each local site be developed?
Will there be some sort of steering or equivalent committee that will provide central review
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and approval of study documents, or will template consent forms, recruitment materials, data
collection forms, etc. be developed by and provided to the local sites by the coordinating
center without external review?
c. Will each local clinical site have its own IRB, and will the institution have an FWA with the
federal government? State whether the coordinating center will collect IRB approvals and
renewals from the clinical centers or not; if not, explain why not.
d. How will the coordinating center provide each local site with the most recent version of
the protocol and other study documents? What will be the process for requesting that these
updates be approved by local clinical center IRBs?
e. What is the plan for collecting data, managing the data, and protecting the data at the
coordinating center?
f. What is the process for reporting and evaluating protocol events and deviations from the
local sites? Who has overall responsibility for overseeing subject safety: the investigators at
the recruitment site, Coordinating Center, the Steering Committee, or a data and safety
monitoring board (DSMB)? Is there a DSMB that will evaluate these reports and provide
summaries of safety information to all the reviewing IRBs, including the coordinating center
IRB? Please note that if there is a DSMB for the overall study, then the coordinating center
PI does not have to report to the coordinating center IRB each individual adverse
event/problem event that is submitted by the local site PIs.
g. Who is responsible for compliance with the study protocol and procedures and how will
the compliance of the local sites be monitored and reviewed? How will issues with
compliance be remedied, if there are issues?

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APPENDIX A. PERSONNEL AND ROLES

Institution and personnel Roles and responsibilities

Johns Hopkins University Schools of Public Health and Medicine

William Checkley, MD, PhD Principal Investigator, study coordinator, liaison to

additional collaborations

Robert Gilman, M.D. Co-Investigator, study coordinator, liaison to

additional collaborations, provision of storage

Universidad Peruana Cayetano Heredia

Fabiola León-Velarde, Dr.Sc Co-Investigator, liaison to additional collaborations

María Rivera Chira, Dr.Sc Co-Investigator, liaison to additional collaborations

Fogarty International Center, Johns Hopkins University Bloomberg School of Public Health

Joao Da Silva, MD Student Researcher, study coordinator, training of

field personnel, development of manuals and
protocol, echocardio, cIMT, patient monitoring

Mary Elmasri, MD Student Researcher, study coordinator, training of

field personnel, development of manuals and
protocol, echocardio, cIMT, patient monitoring

A.B. PRISMA, Lima, Perú

Field worker TBD Field coordinator/worker, data collection, exercise

testing, phlebotomy, patient monitoring

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 Page 13 of 14

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