Measuring Antibiotic Solution Concentration at the Tympanic Membrane Following Self-administration by Patients With Chronic Suppurative Otitis Media
Conditions: Chronic Suppurative Otitis Media
Sponsor: Dartmouth-Hitchcock Medical Center

 
 
PROTOCOL TITLE: Antibiotic Concentration After Delivery to Middle Ear for Chronic 
Suppurative Otitis Media  
 
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PROTOCOL TITLE: 
Antibiotic concentration after delivery to middle ear for chronic suppurative otitis media 
 
STUDY IDENTIFIERS: 
 
NCT ID not yet assigned 
 
Unique Protocol ID: STUDY02001093 
 
PRINCIPAL INVESTIGATOR: 
James E. Saunders, MD, MS  
Department of Surgery, Section of Otolaryngology (Otology/Neuro-otology) 
(603) 650-8123 
James.E.Saunders@hitchcock.org 
VERSION NUMBER/DATE: 
Version 2 (updated as of August 14, 2021) 
*Dartmouth-Hitchcock (D-HH HRPP) IRB approval for this protocol is effective 
from July 7, 2021, until July 21, 2022.  
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
1 
July 2, 2021 
Responding to reviewer comments 
AL 
2 
August 14, 
2021 
Follow-up date changed to 3-10 days 
AL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Table of Contents 
1.0 
Study Summary ........................................................................................................ 3 
2.0 
Objectives* .............................................................................................................. 4 
3.0 
Background* ............................................................................................................ 4 
4.0 
Study Endpoints* ..................................................................................................... 7 
5.0 
Study Intervention/Investigational Agent ................................................................ 7 
6.0 
Procedures Involved*............................................................................................... 8 
7.0 
Data and Specimen Banking* .................................................................................. 9 
8.0 
Sharing of Results with Subjects* ........................................................................... 9 
9.0 
Study Timelines* ................................................................................................... 10 
10.0 Inclusion and Exclusion Criteria* .......................................................................... 10 
11.0 Vulnerable Populations* ........................................................................................ 11 
12.0 Local Number of Subjects ..................................................................................... 11 
13.0 Recruitment Methods ............................................................................................. 11 
14.0 Withdrawal of Subjects* ........................................................................................ 11 
15.0 Risks to Subjects* .................................................................................................. 11 
16.0 Potential Benefits to Subjects* .............................................................................. 11 
17.0 Data Management* and Confidentiality ................................................................ 11 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* ........................ 12 
19.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 12 
20.0 Compensation for Research-Related Injury ........................................................... 12 
21.0 Economic Burden to Subjects ................................................................................ 12 
22.0 Consent Process ..................................................................................................... 12 
23.0 Process to Document Consent in Writing .............................................................. 13 
24.0 Setting .................................................................................................................... 13 
25.0 Resources Available............................................................................................... 13 
26.0 Multi-Site Research* ............................................................................................. 13 
 
 
 

 
 
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1.0 
Study Summary 
 
Study Title 
Antibiotic concentration after delivery to middle ear for 
chronic suppurative otitis media   
Study Design 
Prospective observational study 
Primary Objective 
Investigate the reliability of ciprofloxacin concentration 
measurements from aspirates of middle ear fluid after self-
administration of otic drops in patients with chronic otorrhea 
and non-intact tympanic membrane 
Secondary 
Objective(s) 
Elucidate the role of antibiotic concentration in varying 
clinical outcomes in patients with chronic middle ear 
infections by using antibiotic concentration analysis of 
aspirates. 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Patients diagnosed with chronic suppurative otitis media 
prescribed with antibiotic drops (0.3% ciprofloxacin, 0.1% 
dexamethasone suspension) will apply drops 1-hour prior to 
visit. During visit, the ear will be cleaned of any debris and a 
microscopic aspirate of approximately 100 microliters will 
be collected with a modified Juhn Tym-Tap device.  
IND/IDE #  
N/A 
Study Population 
Adults in the community with diagnosed chronic middle ear 
infection 
Sample Size 
N=10 
Study Duration for 
individual 
participants 
An individual participant will be followed on a weekly basis 
until reaching either criteria of complete symptom 
resolution, new treatment prescription, or maximum duration 
of 3 months 
Study Specific 
Abbreviations/ 
Definitions  
Chronic suppurative otitis media (CSOM) 
 
 

 
 
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2.0 
Objectives* 
The purpose of this study is to develop methodology to better understand the potential 
effect of ototopical concentration on clinical outcomes in patients with chronic middle ear 
infections. The investigators will do so by measuring antibiotic concentration in aspirates 
from the middle ear of selected subjects with otorrhea due to Chronic Suppurative Otitis 
Media (CSOM) who are prescribed and instructed to self-administer ototopical 
ciprofloxacin.  
The primary specific aim of the study team is to investigate the reliability of measuring 
the concentration of ciprofloxacin from aspirates of middle ear fluid after self-
administration of otic drops in subjects with chronic otorrhea. A secondary aim is to 
correlate these concentrations with subject factors such as the extent of otorrhea and the 
anatomy of the ear. 
The investigators hypothesize that patient self-administration of ciprofloxacin drops 
results in variable concentrations delivered to the tissue level that are significantly below 
the in vitro concentration of the prescribed solution and that these concentrations are 
below the bactericidal concentration of ciprofloxacin-resistant bacteria as determine by 
our previous work.  Additionally, the investigators anticipate that the concentration levels 
of ciprofloxacin at the level of the tympanic membrane will correlate with specific patient 
factors and clinical outcomes. 
3.0 
Background* 
 
Chronic suppurative otitis media (CSOM) is characterized by chronic inflammation of 
the middle ear with persistent discharge from a non-intact tympanic membrane. CSOM is 
notably associated with a significant burden of disease worldwide (1). The most common 
pathogens are staphylococcus spp., klebsiella spp., pseudomonas aeruginosa, 
corynebacterium spp, and proteus spp. (2). Topical fluoroquinolones are first line therapy 
for CSOM and are advantageous as compared to oral or intravenous therapy in that these 
antibiotics avoid systemic side effects and have the potential to deliver high antibiotic 
concentrations directly to the middle ear mucosa (3-5). However, because of their 
widespread use, fluoroquinolone resistance has steadily risen (6-8), making management 
of CSOM challenging. 
 
A prior study by the study team confirmed 141 patients with ciprofloxacin-resistant otitis 
media had poor outcomes when using ciprofloxacin drops compared to alternative 
therapy options (9). Similarly, Jang et al. recovered ciprofloxacin-resistant P. aeruginosa 
from all patients (n=88) with unremitting CSOM in the context of topical ciprofloxacin 
therapy in a prospective population of 231 outpatients. Of these 88, over 40% required 
intravenous antibiotics (10). These findings contradict the previously accepted thought by 
many practicing otolaryngologists that the high concentrations (3000 mcg/ml) obtained 
with topical fluoroquinolone antibiotic preparations (3000 mcg/ml) would sufficiently 

 
 
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overcome all bacterial resistance to fluoroquinolones. This belief is based on the fact that 
minimum inhibitory concentration (MIC) levels are derived from available plasma 
concentrations. (4,11). 
 
To further investigate these relationships, the study team examined the actual MIC and 
minimal bactericidal concentrations (MBC).  In this study, Trinh et al. found that the 
actual MIC and MBC of ciprofloxacin-resistant ear pathogens are much higher than the 
plasma-derived MIC levels used to assign resistance, but generally still below the 
concentration of the ototopical solution (12). This study suggests elevated MIC or MBC 
levels alone do not explain the observed poor clinical outcomes in patients with 
ciprofloxacin-resistant infections. These findings have led to the hypothesis that poor 
clinical outcomes in fluoroquinolone resistance are due to multiple effects, including 
elevated MICs and poor drug delivery with failure to reach the necessary concentration at 
the tissue level (tympanic membrane or middle ear).  
  
The potential role of ineffective ototopical delivery of fluoroquinolones and antibiotic 
resistance in patient outcomes has yet to be elucidated.  As such, it is becoming 
increasingly clear that topical antibiotic delivery is more complex than previously 
considered. Understanding the complexities of drug delivery is critical to improving 
patient management and clinical outcomes. Only one study has reported on drug 
concentration of ototopical solutions at the level of the middle ear. Ohyama et al. studied 
clinician-administered ototopical fluoroquinolone after ear cleaning using high 
performance liquid chromatography to measure intratympanic ciprofloxacin 
concentration. This study demonstrated that commercially available preparations of 
ofloxacin (3000 mcg/ml) resulted in highly variable concentrations (1.2 to 602 mcg/g) in 
the middle ear mucosa in 11 patients, with undetectable levels in another five patients 
(13). These results allude to the variety of patient factors that can influence drug 
penetration and the availability in the middle ear, including volume of otorrhea, the 
narrowness of the ear canal, differences in surface tension affecting fluid dynamics, and 
size of the tympanic membrane. These patient related factors are ill defined within the 
literature and the magnitude of such individual effects is largely unknown. Furthermore, 
the delivery method employed in this prior study was not consistent with standard 
medical practice of patient self-administration. As such, the investigators are pressed to 
further examine the fundamentals of ototopical antibiotic delivery.  
One such avenue of examination is understanding what is happening at the tissue level. 
Many authors have advocated for a more complex assessment of fluoroquinolone 
resistance that includes both the relative resistance of the organism, the available 
concentration at the tissue level and duration of drug exposure to those tissues (14, 15). 
Matta et al. demonstrated the ability to measure concentrations of ciprofloxacin in the 
plasma, urine, kidney and bladder of mice using a high throughput liquid 
chromatography-tandem mass spectrometric (LC-MS/MS) method (16). The team hopes 
to use this as the basis for the development of our assay in order to measure the 
concentration of ciprofloxacin at the level of the tympanic membrane. In doing so, the 

 
 
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investigators can begin to better define the variables that contribute to drug penetration 
and effectiveness of ototopical antibiotics in the context of CSOM. 
 
1.      Mofatteh, M. R., Shahabian Moghaddam, F., Yousefi, M., & Namaei, M. 
H. (2018). A study of bacterial pathogens and antibiotic susceptibility patterns in 
chronic suppurative otitis media. Journal of Laryngology and Otology, 132(1), 
41–45. 
2.      Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, 
Bavcar A, Grasso D, Barbiero C, Tamburlini G. Burden of disease caused by 
otitis media: systematic review and global estimates. PLoS One. 
2012;7(4):e36226. doi: 10.1371/journal.pone.0036226. Epub 2012 Apr 30. PMID: 
22558393; PMCID: PMC3340347. 
3.      Klein JO. Strategies for decreasing multidrug antibiotic resistance: role of 
ototopical agents for treatment of middle ear infections. Am J Manag Care 2002 
Oct; 8:S345-352. 
4.      Koulich E, Roland PS, Pawlowski KS. Comparison of systemic and otic 
administration of ofloxacin. Laryngoscope 2010 Oct; 120:2083-2088. 
5.      Ohyama M, Furuta S, Ueno K, Katsuda K, Nobori T, Kiyota R, Miyazaki 
Y. Ofloxacin otic solution in patients with otitis media: an analysis of drug 
concentrations. Arch Otolaryngol Head Neck Surg. 1999 Mar;125(3):337-40. doi: 
10.1001/archotol.125.3.337. PMID: 10190808 
6.      Correia S, Poeta P, Hebraud M, Capelo JL, Igrejas G. Mechanisms of 
quinolone action and resistance: where do we stand? J Med Microbiol 
2017;66:551-559. 
7.      Dalhoff A. Global fluoroquinolone resistance epidemiology and 
implications for clinical use. Interdiscip Perspect Infect Dis 2012; 2012:976273. 
8.      Kim ES, Hooper DC. Clinical importance and epidemiology of quinolone 
resistance. Infect Chemother 2014; 46:226-238. 
9.      Noonan KY, Kim SY, Wong LY, Martin IW, Schwartzman JD, Saunders 
JE. Treatment of Ciprofloxacin-resistant Ear Infections. Otol Neurotol. 2018 
Oct;39(9):e837-e842. 
10. Jang CH, Park SY. Emergence of ciprofloxacin-resistant Pseudomonas in 
chronic suppurative otitis media. Clin Otolaryngol Allied Sci 2004; 29:321- 323. 
11.  Weber PC, Roland PS, Hannley M, Friedman R, Manolidis S, Matz G, 
Owens F, Rybak L, Stewart MG. The development of antibiotic resistant 
organisms with the use of ototopical medications. Otolaryngol Head Neck Surg. 
2004 Mar;130(3 Suppl):S89-94. doi: 10.1016/j.otohns.2003.12.009. PMID: 
15054367. 
12.  Trinh KV, Ruoff KL, Rees CA, Ponukumati AS, Martin IW, O’Toole GA, 
Saunders JE. Characterization of Ciprofloxacin Resistance Levels: Implications 
for Ototopical Therapy. Otol Neurotol [Manuscript accepted for publication] 

 
 
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13.  Ohyama M, Furuta S, Ueno Ket al. Ofloxacin otic solution in patients with 
otitis media: an analysis of drug concentrations. Arch Otolaryngol Head Neck 
Surg 1999 Mar; 125:337-340. 
14.  Brauner A, Fridman O, Gefen O, Balaban NQ. Distinguishing between 
resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol 
2016; 14:320-330. 
15.  Perea JRA. The pharmacodynamic bases of the prescription of antimicrobials. 
Rev Esp Quimioter 2019; 32:35-37. 
16.  Matta, M.K.; Chockalingam, A.; Gandhi, A.; Stewart, S.; Xu, L.; Shea, K. 
LC-MS/MS based quantitation of ciprofloxacin and its application to 
antimicrobial resistance study in Balb/c mouse plasma, urine, bladder and 
kidneys. Anal. Methods 2018, 10, 1237–1246 
 
 
4.0 
Study Endpoints* 
The specific aim is to investigate the reliability of accurately measuring the concentration 
of ciprofloxacin from aspirates of middle ear fluid after self-administration of otic drops 
in subjects with chronic otorrhea. A secondary aim is to correlate these concentrations 
with patient factors such as the extent of otorrhea and the anatomy of the ear. 
 
Objective 
Study Endpoint 
Safety 
Endpoint 
Investigate the reliability of 
measuring concentration of 
ciprofloxacin from middle 
ear aspirates 
Precise sampling of a known aspirate 
volume (100 microliters) and performance 
of LC-MS/MS ciprofloxacin assay 
development for middle ear aspirate 
analysis 
 
Correlate the concentrations 
with patient factors 
Correlate ciprofloxacin concentration of 
middle ear aspirate to symptom resolution 
time, patient demographics, patient 
anatomy and clinical outcomes (infection 
resolution). 
 
5.0 
Study Intervention/Investigational Agent 
The standard of care for CSOM involves ototopical quinolone therapy such as 
ciprofloxacin or ofloxacin. The affected ear is routinely cleaned of any debris, and 
a Juhn Tym-Tap® device will be used to aspirate fluid for culture samples. The 
patient will be provided the standard course of treatment, which is a prescription 

 
 
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for antibiotic drops of ciprofloxacin 0.3% and dexamethasone 0.1% suspension 
with specific written instructions. The frequency of treatment is three times daily 
for ten days.  
 
For this study, patients who meet inclusion-exclusion criteria will be offered an 
opportunity to participate by the prescribing provider. Informed consent will be 
obtained. Enrolled subjects will be asked to return 3 to 10 days after the initial 
visit. Additionally, the subject will be asked to keep a log of their medication use 
and to administer the ototopical medication one hour prior to their appointment. 
During the follow-up appointment, the ear will be cleaned of any wax or purulent 
debris. A microscopic aspirate (~100 L) will then be collected of fluid at the 
level of the non-intact tympanic membrane will be collected using with a 
modified Juhn Tym-Tap®. This type of sampling of middle ear aspirates is 
commonly performed in the ENT clinic (performed more than 120 times in the 
Dartmouth-Hitchcock ENT clinic in the past year). After sampling, the volume of 
the aspirate will then be precisely measured with a device developed specifically 
for this study. The color and consistency of the sample will be noted. The sample 
will then be diluted with a known volume of water to an acceptable volume for 
the LC-MS/MS assay.   Furthermore, other data beyond ciprofloxacin 
concentration such as otologic diagnosis, bacteria culture results, presenting 
symptoms, specific site of infection, external ear canal volume estimates (based 
upon tympanometry and physical exam), configuration of external auditory canal, 
prescribed treatment, treatment outcome, and duration of infection will be noted 
for each subject.   
 
6.0 
Procedures Involved* 
 
Specimen collection: This will be a prospective observational study of adult subjects 
being diagnosed with chronic otorrhea at a tertiary care hospital, Dartmouth-Hitchcock 
Medical Center. To test our hypothesis, we will identify subjects with chronic otorrhea in 
clinic. Informed consent will be obtained. Subjects will be given a prescription for 
antibiotic drops containing ciprofloxacin 0.3% and dexamethasone 0.1% suspension from 
a pharmacy of their choice with specific written instructions for self-administration. A 
compliance card will be given to record adherence to three-time daily regiment for ten 
days.  Drops will be dosed three times daily for ten days, and no other non-prescribed 
ototopical antibiotic therapy nor additional over the counter treatments should be used 
during this period. Subjects will return for a follow up visit between 3 to 10 days after 
their initial visit and will be asked to administer the drops in the affected ear one hour 
prior to their appointment. At that time, the ear will once again be cleaned of any debris 
and a microscopic aspirate (~100 L) of fluid at the level of the tympanic membrane or 
middle ear will be collected using an aseptic technique with a Juhn Tym-Tap specimen 
trap to collect micro aspirates.  This specimen will be analyzed, precisely measured for 

 
 
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volume, diluted, and sent for analysis using mass spectrometry (description below). Data 
collected will include patient demographics, otologic diagnosis, bacteria culture results, 
presenting symptoms, amount and type of drainage, specific site of infection, external ear 
canal volume estimates, configuration of the external auditory canal based on physical 
exam, prescribed treatment, treatment outcome, and duration of infection. 
 
Ciprofloxacin concentration measurements: A reverse-phase liquid chromatography with 
tandem mass spectrometry (LC-MS/MS) assay will be developed to measure 
concentrations of ciprofloxacin in the auricular aspirate. The assay is based on that 
published by Matta et al (16). In brief, a C18 stationary phase column will be used with a 
gradient elution of 5mM ammonium formate in 0.1% formic acid buffer and acetonitrile 
for the mobile phase. External standards using a ciprofloxacin stock solution at low, 
medium, and high concentrations will be used to create a calibration curve of instrument 
response to known concentrations. For sample analysis, a 30-µL aliquot of the auricular 
aspirate sample will be combined with a 60-µL water and 100-µL acetonitrile, which 
would be spiked with a single standardized amount of the internal standard, deuterated 8 
ciprofloxacin. By using this internal standard method of calibration, a precise 
quantification of the ciprofloxacin concentration in the auricular aspirate will be 
determined.  This assay will be developed and validated by the staff of the Clinical 
Pharmacology Shared Resource directed by Dr. Lionel D. Lewis. 
 
7.0 
Data and Specimen Banking* 
 
The electronic data will be managed in an excel file of a local computer drive with 
frequent electronic backups in a securely encrypted cloud storage service (ShareFile). 
The stored data will include date of birth, medical record number, assigned sex at birth, 
BMI, otologic diagnosis, degree of anatomic involvement, bacteria culture results, 
presenting symptoms, amount and type of drainage, specific site of infection, external ear 
canal volume estimates, configuration of the external auditory canal, prescribed 
treatment, treatment outcome, and duration of infection.   
 
All specimens will not be stored longer than necessary to complete analysis and will be 
discarded through proper DHMC lab protocols. 
 
8.0 
Sharing of Results with Subjects* 
 
The subjects will be asked whether they would like to receive the study results, which 
would be released in the form of a manuscript or journal article over email at the 
conclusion of the study. Furthermore, a form to share (or not share) any incidental 
findings and investigational diagnostic tests such as bacterial culture results will be 
provided as an option to the subject.  
 

 
 
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9.0 
Study Timelines* 
 
Proposal 
Timeline 
AUG SEP OCT NOV DEC JAN FEB MAR 
Funding 
Acquisition 
& IRB 
Process 
X 
X 
X 
 
 
 
 
 
Assay  
Development 
 
X 
X 
X 
X 
 
 
 
Patient 
Recruitment 
& Sample 
Collection 
 
 
 
 
X 
X 
X 
 
Statistical 
Data 
Analysis 
 
 
 
 
 
X 
X 
X 
Concluding 
Analysis, 
Article 
Submission 
 
 
 
 
 
 
X 
X 
 
Subject enrollment is anticipated from December 2021 to January 2022 with subsequent 
data collection and analysis happening immediately afterwards. The subjects will be 
followed up with weekly until infection is resolved (for a maximum of 3 months). The 
study is anticipated to end in December 2021.  
10.0 Inclusion and Exclusion Criteria* 
 
Inclusion criteria include: 
 
• 
Adult patients greater than or equal to 18 years of age 
• 
Diagnosis of CSOM 
 
 
Exclusion criteria include: 
• 
Atypical presentation of CSOM or atypical anatomy of the ear 
• 
Presence of additional ear pathophysiology beyond CSOM 
• 
Adults unable to consent 
• 
Individuals who are not yet adults (infants, children, teenagers) 
• 
Pregnant women 
• 
Prisoners 

 
 
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• 
Non-English speaking 
 
 
11.0 Vulnerable Populations* 
 
This is not applicable to this study.  
 
12.0 Local Number of Subjects 
Ten subjects will be accrued locally in the ENT clinic on 4F at DHMC in Lebanon, NH.  
 
13.0 Recruitment Methods  
The potential subjects will be recruited in the ENT clinic from July to September 2021 
during otology clinic hours. Provider will screen using inclusion-exclusion criteria 
described above in conjunction with clinical presentation aligned with CSOM diagnosis.   
 
14.0 Withdrawal of Subjects* 
Circumstances for subject withdrawal from research may include non-compliance with 
prescribed antibiotic regiment or any additional necessary medical intervention beyond 
that prescribed for CSOM. The study team does not plan to collect survival data from 
subjects that withdraw from the study. The subject always has the option to voluntarily 
withdraw from the study.  
 
15.0 Risks to Subjects* 
Participation for the subject may cause: 
• 
Mild physical discomfort with an additional study-related sample 
collection using a Juhn Tym-Tap device 
• 
Psychological stress via social pressure to comply to medication regiment 
and research protocol 
• 
Time and potential indirect financial expense, especially for subjects who 
may have higher reliance on hourly wage 
 
16.0 Potential Benefits to Subjects* 
The subject may benefit from the additional examination and cleaning 3 to 10 days after 
the follow up appointment as well as higher social pressure to comply to prescribed 
medication regiment.  
 
17.0 Data Management* and Confidentiality 
Given the small sample size (n=10) and expected variability of results, a Fisher’s exact 
test will be used to describe and compare the measured concentration of ciprofloxacin at 
the tympanic membrane to subject demographics as well as extent of perforation, amount 
of aural drainage and treatment outcomes.  
 

 
 
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The data will be managed on a locally encrypted device in an Excel file while stored on 
the encrypted cloud storage service called ShareFile. Access will be provided to those on 
the research team on a need-to-know basis with particular caution to ensure separation of 
identifiers and data. Any communication in a non-encrypted platform will not contain 
any protected health information.   
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
This is not applicable to our study as our study does not involve more than minimal risk 
to the subject. 
 
19.0 Provisions to Protect the Privacy Interests of Subjects 
 
The subjects’ privacy interests will be conserved in this study as the subject will 
primarily see the physician and will only be exposed to one more interaction should they 
give informed consent.  
 
At every encounter between the subject and research team, the subjects will be offered a 
time to ask questions as well as an email and cell-phone number to call for any forgotten 
questions.  
 
The research team will have access to the subjects’ electronic medical records as well as 
the master data file stored onto the encrypted cloud storage. The excel data file will only 
be shared with people directly involved in the data entry and analysis. 
 
20.0 Compensation for Research-Related Injury 
This research does not involve more than minimal risk to subjects.  
 
21.0 Economic Burden to Subjects 
The subject will have direct time cost by participating in this research including the travel 
and clinic time associated with the additional ear sampling needed to obtain the study-
related middle aspirate. This may have an indirect financial cost with time possibly taken 
off from work. Furthermore, the subjects will be expected to complete a medication 
compliance / symptoms log. To offset this economic burden, subjects will be 
compensated $50 for their participation.   
 
22.0 Consent Process 
Subjects who meet inclusion-exclusion criteria will be given the option to enroll into our 
study during their first visit for CSOM to the ENT clinic at DHMC in Lebanon, NH. The 
subjects will have the opportunity to read through the consent form in the clinic room 
without any medical staff present to remove possibility of coercion or undue influence. 

 
 
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After five to ten minutes, a member of the research team will talk to the subject as per 
HRP-090. Non-English speaking, cognitively impaired, pregnant, prisoners, and pediatric 
subjects are not included in this study. 
 
The “SOP: Informed Consent Process for Research (HRP-090)” will be followed.  
 
23.0 Process to Document Consent in Writing 
 
The “SOP: Written Documentation of Consent (HRP-091)” will be followed.  
 
24.0 Setting 
The setting of this research project is at Dartmouth-Hitchcock Medical Center (DHMC) 
in Lebanon, NH. The potential subjects will be recruited from the ENT clinic on 4F. 
Laboratory analyses will be completed in the labs at DHMC.  
 
25.0 Resources Available 
The feasibility of recruiting ten suitable subjects is high given the prevalence of CSOM. I 
will be dedicating full-time commitment during the summer months of July and August 
with additional part-time commitment until the conclusion of this project. This research 
will be conducted in the ENT clinic at DHMC with the support of Dr. Galit Almosnino 
and Dr. James Saunders. Furthermore, Dr. Lionel Lewis of the Section of Clinical 
Pharmacology and his lab have agreed to develop and operate the ciprofloxacin assays.  
 
Prior to the formal initiation of the study, all members of the research team will be 
presented with the protocol as well as a specific delineation of each member’s role.  
 
  
26.0 Multi-Site Research* 
 
This is not currently applicable to this study.