Clinical trial NCT01919411
Conditions: Sinusitis
Keywords: Chronic rhinosinusitis Sinus surgery Antibiotics
Sponsor: Massachusetts Eye and Ear Infirmary
Start date: 2013-02-01; Completion date: 2018-09-01
Enrollment: 134 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Surgeons commonly prescribe post operative prophylactic antibiotics after sinus surgery. There is minimal data to support this. The investigators' study will aim to demonstrate that patients' quality of life and rate of post operative infection is the same whether they receive or do not receive antibiotics post operatively. The investigators hypothesis is that the disease specific quality of life of patients taking post-operative antibiotics is not inferior to the quality of life of patients who do not take post-operative antibiotics, and the rate of post-operative infections are the same. The investigators' specific aim is to compare validated symptom scores between post-operative populations who are given or are not given antibiotics. Rates of infections in the first 10 days after surgery will be recorded. The investigators will also compare endoscopic grades of sinus cavities during the post-operative follow up exams as an additional outcome measure.

Detailed description:
Functional endoscopic sinus surgery (FESS) is a commonly performed procedure in the United States to treat chronic rhinosinusitis. Common practice is to prescribe prophylactic antibiotics postoperatively. This is similar to the long tradition of prophylactic antibiotics after tonsillectomy. The American Academy of Otolaryngology - Head and Neck Surgery recently strongly recommended against prophylactic antibiotics after tonsillectomy. In this light, this study would demonstrate the lack of need for antibiotics after FESS. Currently one surgeon does not prescribe antibiotics except when evidence of active infection was found during surgery. The other surgeon in the study currently prescribes antibiotics. This study would prospectively compare the two groups in a randomized fashion. The investigators' plan to use the Sinonasal outcomes test - 22 (SNOT-22) as the investigators' primary outcomes measure, which is a validated quality of life instrument in sinusitis.

Arms: arm 1: All patients in the study will undergo endoscopic sinus surgery. This arm will receive 7 days of augmentin (amoxicillin-clavulanate) 500mg orally twice a day after surgery. arm 2: All patients in the study will undergo endoscopic sinus surgery. This arm will receive 7 days of placebo orally twice a day after surgery.
Interventions: intervention 1: Amoxicillin-Potassium Clavulanate intervention 2: Placebo
Intervention descriptions: intervention 1: Patients in this arm will receive 500mg of Amoxicillin-Potassium Clavulanate Combination orally twice a day for 7 days after surgery. intervention 2: Patients in this arm will receive 7 days of placebo after surgery.

Protocol documents:
SAP_002.pdf: 
Protocol Title:  
Prophylactic Antibiotics After Functional Endoscopic Sinus Surgery: a 
Randomized, Double-blind Placebo Controlled Trial  
 
NCT:   
 
NCT01919411  
 
Date this document was last updated: 1/28/2020  
 
Statistical Analysis Plan 
 
The primary endpoint was the overall change in SNOT-22 scores from baseline to the final study 
visit. Secondary outcomes included the change in LK Endoscopic Score from the same time 
points, as well as rates of post-operative infection. Additional exploratory analyses included the 
effect of baseline clinical factors, including baseline sinus culture results, history of prior sinus 
surgery, comorbid asthma, and presence of nasal polyps.  
 
The primary outcome and secondary outcome were analyzed using a repeated-measures analysis 
of variance (ANOVA) to assess for a group x time interaction on clinical scores. For the 
secondary analysis of the primary outcome, this model was modified to include baseline clinical 
covariates in a repeated-measures analysis of covariance (ANCOVA).  
 
The achieved power for non-inferiority was calculated via the same methods as the prospective 
power analysis. Rather than an a priori estimate of standard deviation in scores, the achieved 
power was based on the actual number of randomized subjects and the actual pooled standard 
deviation of post-treatment SNOT-22 scores in the two groups. The non-inferiority margin was 9 
units on the SNOT-22. 

Prot_000.pdf: 
 
Human Studies Committee 
Tel: 617-573-3732 
Email: HSC@meei.harvard.edu 
 
HUMAN SUBJECT RESEARCH PROTOCOL-FORM I  
NOTE: For the purpose of this Form, Mass. Eye and Ear (MEE) include the Massachusetts Eye and Ear 
Infirmary (MEEI), and Schepens Eye Research Institute, Inc. (SERI). MEEI is a HIPAA-covered entity; SERI 
is not considered a covered entity.
DATE: 10/06/14 
TITLE OF PROJECT: Prophylactic antibiotics after functional endoscopic sinus surgery: a randomized, 
double-blind placebo controlled trial  
PRINCIPAL INVESTIGATOR: Eric Holbrook 
FUNDING SOURCE: Dr. Holbrook / Dr. Gray 
 
1)  
Does your research involve the following? Check all that apply: 
 
 Use of investigational drugs or biologics   
 Use of investigational devices  
 Use of human embryonic stem cells   
 Use of rDNA, microbiological agents, gene transfer, transplantation of animal tissues    
 
 2)  
Is this study a Clinical Trial?  
 YES       
 NO       
  
IF YES, submission of an industry-sponsored protocol or SUPP M is required. If no, SUPP N should be 
submitted. 
 
2b)  
Who will register the study with clinicaltrials.gov?  
 
 
 This is a Phase I or a pilot study-registration is not required    
 Sponsor     
 PI    
 
other:Already registered -  NCT01919411                                   
 
3)  
Provide a brief summary of the proposed research (in language that can be understood by a non-
 
scientist):   
RESPONSE: Functional endoscopic sinus surgery (FESS) is a commonly performed procedure in the United 
States to treat chronic rhinosinusitis.  Common practice is to prescribe prophylactic antibiotics postoperatively.  
This is similar to the long tradition of prophylactic antibiotics after tonsillectomy.  The American Academy of 
Otolaryngology - Head and Neck Surgery recently strongly recommended against prophylactic antibiotics after 
tonsillectomy.  In this light, this study would demonstrate the lack of need for antibiotics after FESS.  Currently 
Dr. Holbrook does not prescribe antibiotics except when evidence of active infection was found during surgery.  
Dr. Gray currently prescribes antibiotics.  This study would prospectively compare the two groups in a 
randomized fashion.  Two previous studies have been performed (Jiang et al. Postoperative antibiotic care after 
functional endoscopic sinus surgery. Am J Rhinol 22, 608-612, 2008); (Albu, et al.  Prophylactic antibiotics in 
endoscopic sinus surgery: A short follow-up study. Am J Rhinol 24 306-309, 2010.)  These studies were both 
randomized, placebo controlled prospective studies.  Albu et al found that amoxicillin/clavulanate improved the 
outcome in the "early blood crust healing" and the endoscopic score was improved.  Jiang et al. showed that 
amoxicillin/clavulanate did not not improve short term outcomes of FESS.  Both studies were limited by a lack 


 
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2
of a prospective instrument to evaluate symptoms.  We plan to use the Sinonasal outcomes test -22 (SNOT-22), 
which is a validated quality of life intrument in sinusitis.    
4)  
What is the estimated completion date? (MM/YYYY) 
RESPONSE: 06/2015 
5)   
Who specifically (name, title, and department) is going to perform the coordinator function? Discuss 
 
his/her relevant qualifications (training, education, experience):  
The PI, Dr. Holbrook, has assumed coordinator function.  He has had experience and training through the 
Harvard Catalyst education offerings in clinical studies. 
6a)  
Who is going to supervise the study coordinator(s)? When applicable, indicate if support and oversight 
 
will be provided by the Ophthalmology Clinical Research Office (OCRO). 
6b)  
Describe the PI’s plan to provide adequate training, and supervision (e.g., regular meetings, training 
 
opportunities):  
Dr. Holbrook will be supervising all aspects of the study and meets regularly (weekly) with Dr. Gray on matters 
of enrollment, patient compliance, and monitoring of adverse events.  
7)  
Delegation of Significant Study-Related Tasks-  If non-physicians are tasked to assess clinical response 
 
to an investigational therapy, provide medical care to subjects during the course of the study, assess 
 
inclusion/exclusion criteria, and evaluate adverse events, list their names in the table below and 
 
complete: 
Name 
Delegated  Tasks 
Qualifications- Licensing, or 
Certification  
Training  
Dr. Holbrook / Dr. Gray 
Enrollment, follow-up, 
evaluation for adverse 
reactions, data collection 
MD 
Residency and fellowship 
training in otolaryngology 
and rhinology 
Pharmacy staff 
(supervised by Dr. 
Christine Finn) 
Distribution of study drug 
Pharm D  
Doctorate in pharmacy  
 
 
 
 
 
 
 
 
 
8)  
Indicate all MEE sites where research activities occur:  
 
 Boston-MEEI 243 Charles Street  
 
 
 
 Boston Longwood Medical Area – 800 Huntington Ave 
 Boston-SERI 20 Staniford St.   
 Braintree - 250 Pond St 
 
 Concord - 54 Baker Ave Ext 
 Duxbury - 20 Tremont St, Route 3A 
 
 East Bridgewater - 400 N. Bedford St 


 
VERSION 1.0: 07/30/2013 
3
 Milton - 100 Highland St.  
. 
 Newton - 2000 Washington St 
 
 Quincy - 500 Congress St, Crown Colony Office Park 
 Stoneham - One Montvale Ave 
 Stoneham - Retina Consultants-3 Woodland Rd  
 
 Weymouth - 825 Main St             
9)   
Are there any non-MEE sites involved in this study?    
 YES      
 NO (If NO, skip to question 11) 
__________________________________________________________________________________________ 
 
IF YES, Is MEE the lead site or coordinating center?    
 YES       
 NO  
 
10)  
In the table below, list each non-MEE sites where research activities will occur, and the status of IRB 
 
review at each site (indicate if the intent is for MEE to serve as the IRB of record for all study sites (cede 
 
review) or if IRB review will be required at other sites:  
 
Non-MEE Sites 
IRB Review Status (i.e., review pending, approved, seeking cede 
review) 
 
 
 
 
 
 
SUBJECT INFORMATION
11)  
In the table below, please indicate age range, gender, total number of subjects to be enrolled at MEE, 
 
and if multi-site, total number for the study: 
 
 
Age Range  
Total Number at MEE 
Total Number for the Study  
(if multi-site) 
Adults (over 18) 
18- no limit 
140 
140 
Children  
(under 18) 
NA 
0 
 
 
12)  
Is a gender being excluded from this study?      
 YES   
   
 NO  
 
IF YES, provide scientific justification:  
Response:       
13)  
Select all populations that may/will be enrolled (will not be excluded from the study) below. For some 
 
populations you may be asked to provide additional information.   
  
Pregnant Women 
  
Employees/Staff of MEEI or SERI-please specify:       
  
Healthy Controls  


 
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4
  
Students/ Residents/ Fellows or other trainees  
  
Children  
  
Prisoner 
  
Non-English Speaking Subjects  
  
Adults with Decisional Impairment- If checked, please describe below the type and range of decisional 
impairment and a rationale for why it is necessary to include adults with decisional impairment:  
  
Other Populations with Potentially Diminished Capacity (i.e., socially, educationally, economically 
disadvantaged, elderly, terminally ill) - If checked, specify population below and describe what 
additional safeguards will be in place to protect the rights and welfare of these subjects: 
RESPONSE: We have enrolled approximately 25 patients so far.  We would prefer to enroll non-english 
speaking patients.  We are aware of the new IRB protocol regarding non English speaking patients’ consent.  
We would like to apply for the “short-form” consent process in order to continue to enroll non-English speaking 
patients. 
14)  
Explain how the Investigator has access to a population that would allow recruitment of the required 
 
number of subjects within the proposed timeframe: 
RESPONSE: Dr. Holbrook and Dr. Gray both have busy rhinology practices from which to enroll patients.   
15)  
If subjects are recruited from the investigator’s patient population or MEE/SERI employees will be 
 
recruited, describe what measures are taken to minimize coercion or undue influence: 
 
RESPONSE: The investigators discuss with the patient the voluntary nature of the study, and the fact that the 
subjects can withdraw at any time from the study.  Also it is discussed with the patient that by not enrolling they 
will not affect their clinical care at all.   
 
SUBJECT SCREENING/RECRUITMENT
16)  
Describe any screening methods used to determine eligible subjects (i.e., search of medical records or 
 
recruitment databases, completion of screening tests, response to interview questions, etc.): 
RESPONSE: Patients will be recruited by Dr. Gray and Dr. Holbrook in their clinics from patients that are 
determined to be candidates for endoscopic sinus surgery and have agreed to undergo surgery.  The patient will 
decide to undergo surgery first, and will then be asked to participate in the study.  A script to be used for oral 
invitation in the study is provided in the application packet. 
 
17)  
Is protected health information accessed during the screening process?    
 YES   
 
 NO 
 
IF YES, specify the information system(s) and the location of the database(s) you will be accessing during the 
screening process: 


 
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5
RESPONSE: LMR is accessed for patients’ clinical information.  This is accessed in the MEEI sinus center.   
18)  
Is protected health information recorded during the pre-screening process?  
 YES   
 
 NO  
 
IF YES, list the identifiers that are recorded prior to obtaining consent:  
RESPONSE:       
19)  
Describe the recruitment process (the process by which potential subjects are informed about the 
 
availability of the research), who is responsible for recruitment, and how (i.e., use of flyers, 
 
advertisements, letters, and oral scripts, etc.) and when subjects will be recruited: 
 
RESPONSE: Patients will be recruited by Dr. Gray and Dr. Holbrook in their clinics from patients that are 
determined to be candidates for endoscopic sinus surgery and have agreed to undergo surgery.  The patient will 
decide to undergo surgery first, and will then be asked to participate in the study.  A script to be used for oral 
invitation in the study is provided in the application packet. 
 
20)  
Does the recruitment strategy involve contacting individuals multiple times?   
 YES    
 NO  
 
IF YES, describe the frequency and in what manner individuals will be contacted:  
 
RESPONSE:       
 
21)  
Are you using email to recruit subjects?     
 YES       
 NO  
 
IF YES, describe the use of email and include a copy of the email text below: 
 
RESPONSE:       
22)  
Will fliers, letters and/or brochures be posted, mailed or otherwise distributed?    
 YES        
 NO 
  
IF YES, please describe how each document will be used:  
 
RESPONSE:       
NOTE: HIPAA does not permit non-MEE physicians to disclose patient information to Mass. Eye and Ear for research 
recruitment purposes other than for treatment purposes or pursuant to a HIPAA authorization.  Non-MEE physicians may 
inform their patients of a research study and allow the patients to self-disclose their interest to the study team. 
23)  
Describe whether physician referral is used and whether subjects healthcare providers be notified of 
 
their patients’ participation in the study?  
 


 
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6
RESPONSE: Dr. Gray and Holbrook are rhinology specialists.  They are referred patients from community 
otolaryngologists for management of chronic sinusitis.  This involves medical as well as surgical management.  
Referring otolaryngologists would not be notified of patient participation.    
COMPENSATION/COSTS 
24)  
Will subjects be paid/offered a recruitment incentive or reimbursed for participating in the research?    
 
 
 YES   
 NO  
 
IF YES, please describe the amount and type of payment or reimbursement (e.g. parking vouchers) and the 
proposed method and timing of disbursement and why this is reasonable and non-coercive: 
 
RESPONSE:       
 
25)  
Will there be any out-of-pocket costs to subjects and/or expenses likely to be covered by their insurance 
 
for participating in the study?   
 YES   
 NO  
 
IF YES, please specify in detail the costs to subjects and/or their insurance (e.g. co-pays): 
 
RESPONSE: The study drug is provided by the pharmacy free of charge.  The study medication supplies are 
charged to the study’s cost center by the pharmacy.   
 
26) 
If applicable, how will the cost of reasonably foreseeable medical care in the event of a research-related 
injury be covered (e.g., sponsor agreement, likely to be covered by insurance, grant, departmental 
funds)?  
 
RESPONSE: This would be covered by patients’ insurance.   
 
RISK
 
Risk is the probability and magnitude of harm or discomfort anticipated as a result of participation in the 
research. Any risks of harm to subjects and/or anticipated discomfort(s) that are reasonably foreseeable, even if 
unlikely, and the safeguards in place to minimize these risks and discomfort(s) must be identified and discussed 
below. Risks of harm and discomfort may include: physical harm/discomfort, psychological harm/discomfort, 
legal harm/discomfort, social harm discomfort, and economic harm. 
 
27)  
Describe any risks of harm to subjects that are reasonably foreseeable, even if unlikely:  
These are listed below: 
1. amoxicillin/clavulanate arm:  
From the FDA monograph 
Gastrointestinal 
 


 
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7
Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous 
candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis 
symptoms may occur during or after antibiotic treatment 
 
Hypersensitivity Reactions 
Skin rashes, pruritus, urticaria, angioedema, serum sickness−like reactions (urticaria or skin rash accompanied 
by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme (rarely Stevens-Johnson syndrome), 
acute generalized exanthematous pustulosis, and an occasional case of exfoliative dermatitis (including toxic 
epidermal necrolysis) have been reported. These reactions may be controlled with antihistamines and, if 
necessary, systemic corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the 
opinion of the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) 
reactions can occur with oral penicillin.  
 
Liver 
A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin-class 
antibiotics but the significance of these findings is unknown. Hepatic dysfunction, including increases in serum 
transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been infrequently reported 
with Augmentin. It has been reported more commonly in the elderly, in males, or in patients on prolonged 
treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, 
or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur 
during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is 
usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per estimated 4 
million prescriptions worldwide). These have generally been cases associated with serious underlying diseases 
or concomitant medications.  
 
Renal 
Interstitial nephritis and hematuria have been reported rarely. Crystalluria has also been reported  
 
Hemic and Lymphatic Systems 
Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, 
and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible 
on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was 
noted in less than 1% of the patients treated with Augmentin. There have been reports of increased prothrombin 
time in patients receiving Augmentin and anticoagulant therapy concomitantly. 
  
Central Nervous System 
Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible 
hyperactivity have been reported rarely.  
 
Miscellaneous 
Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in 
pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases. 
 
2. Placebo Arm:  
The main theoretical risk from not giving antibiotics post operatively would be  a risk of postoperative 
infection.  This would manifest as sinusitis-like symptoms.  Worst case scenario would result in complications 
of sinusitis (orbital infection, meningitis, brain abscess).  These complications are rare, and Dr. Holbrook has 
not experienced them while not giving routine postoperative antibiotics as is his usual practice. 
 
3. Privacy: 


 
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8
Personal data will be collected from subjects.  The data will be saved under a unique subject number, which will 
remove personal identifying information from the research data.  Data will be secured under a password 
protected computer in a locked office of the PI.  
 
 
28)  
If applicable, describe any group harms (i.e., research that focuses on a specific group or population):  
 
 
RESPONSE: NA 
 
29)  
Do you anticipate any circumstances in which a “breach of confidence” associated with a mandated 
disclosure (e.g. reporting abuse to authorities) may occur as part of this study? 
 
RESPONSE: No we do not anticipate a breach of confidence 
 
30)  
In the view of the PI, what risk classification (taking into consideration the probability and magnitude of 
 
harm) is appropriate for the proposed research?  
 
      
 Minimal Risk 
 
 
 Greater than Minimal Risk  
 
 
 Unknown  
 
Minimal risk means the probability and magnitude of harm or discomfort anticipated in the research are not 
greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine 
physical or psychological examinations or tests. 
 
31)  
Please explain why you feel this category is appropriate based on the definition above (when more than 
 
minimal risk describe the likelihood and seriousness of such risks): 
 
RESPONSE: In patients that are randomized to receive post operative antibiotics, there is a risk of adverse 
reaction to augmentin as detailed above.  For patients that are randomized to placebo, there is a risk of post 
operative infection as detailed above as well.   We believe the study is low risk to participants, however as 
defined above, it is more than the risk encountered in daily life.    
 
32)  
What provisions are in place to minimize harm or discomfort? 
 
RESPONSE: Patients are seen one week after surgery to undergo endoscopic evaluation to ensure that the 
patient is healing well without evidence of infection.  At all times during the day they can call the sinus center 
to speak to a nurse if they have any concerns.  At night there is a resident on call to answer questions and the 
MEEI ED is always open.   
 
ALTERNATIVES  
 
33)  
Describe any alternatives, especially other treatment(s) that are available to potential patients outside of 
the research:  
 


 
VERSION 1.0: 07/30/2013 
9
RESPONSE: If patients do not elect to enroll in the study, they would receive standard post-operative care.  
They would be prescribed antibiotics at the discretion of the surgeon.   
 
BENEFITS
 
34)  
Are there any potential direct benefits to individual subjects related to the research?    
 
 
 YES   
 
 NO    
 
IF YES, please explain (address whether these benefits (e.g., clinical, therapeutic) would be available to 
subjects outside of the research): 
 
RESPONSE:       
 
35)  
Explain the potential benefits to science, and/or society (indirect benefits) which may accrue as a result 
 
of this research: 
 
RESPONSE: Antibiotic resistance is growing in the world, and this study may provide prospective, randomized 
data that antibiotics do not result in a benefit to patients.  Hopefully surgeons would stop giving postoperative 
antibiotics, and decrease the risk of side-effects from antibiotics (allergic reactions, clostridium dificile 
infection, GI upset, etc) to future patients.  Also health care costs would be decreased by reducing antibiotic 
prescriptions.    
 
36)  
If more than minimal risk, address how risks relate to benefits:  
 
RESPONSE: While not “minimal risk”, the risk to patients is low, as detailed above.  Many patients have 
adverse reactions to antibiotics, and if this study shows that the outcomes of patients undergoing sinus surgery 
without antibiotics are not worse, then hopefully less patients will be prescribed antibiotics.   
 
CONSENT PROCESS 
 
37)  
Describe the consent process in detail. Include who specifically will be obtaining consent, describe their 
knowledge/experience in obtaining consent from research subjects, and include the location where study 
information will be exchanged, how (consent form, orally, information sheet, etc.) information is being 
conveyed to subjects, and when the consent will be obtained (e.g. during pre-surgical visit, about one 
week before the screening visit): 
 
RESPONSE: Consent will be obtained by Dr. Gray, Dr. Meier or Dr. Holbrook in the clinic during the subject's 
preoperative visit in the MEEI sinus center.  There is a formal consent form that is signed by patients and an 
oral script (these are on IRBNET).  Subjects can think about the study and opt out of randomization at the time 
of surgery (usually 2-4 weeks elapse between preoperative visit and surgery).   
38)  
Indicate which of the following consent procedures you are contemplating for this research: 
 
 
  
Written consent form  


 
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10
 
 
 
  
 Short form process (only appropriate for minimal risk studies) 
 
 
 
* If checked, answer question 42 below. 
 
 
 
  
Assent from adults with diminished decision-making capacity 
 
 
 
*If checked, provide justification below: 
 
            
  
Assent from children and parental permission 
 
 
  
Oral consent or implied consent (e.g. completing a survey)  
 
 
*If checked, provide justification based on 45 CFR 46.117(c) below: 
 
 
  
Requesting a waiver of informed consent from the HSC    
 
 
*If checked, provide justification based on 45 CFR 46.116(c) and (d) below: 
 
RESPONSE:       
 
39)  
Describe any foreseeable circumstances and/or reasons under which the subject’s participation in the 
 
research may be terminated:  
 
RESPONSE: If the patient does not want to participate further then they may opt out at any time during the 
study.   
 
40)  
How is subject comprehension assessed initially and throughout the consent process? Is the manner in 
 
which information is presented appropriate for the population? In cases where subject comprehension is 
 
severely limited what special provisions have been made (is there a third party involved in the consent 
 
process)? Discuss below:  
 
RESPONSE: The investigators will describe the study according to the oral script and ask the patient if they 
understand everything that has been explained to them.  We will ask them if they have any questions and 
answer them to their satisfaction.  If the patients’ comprehension is severely limited then we will not include 
them in the study.   
 
 
41)  
If the research-related intervention or interaction will occur on the same day that the subject initially 
 
receives information about the study, justify why this is appropriate/necessary:  
 
RESPONSE:  It will not be on the same day, patients will be enrolled at their post operative visit.      
 
42)  
Describe additional provisions in place for non-English speaking subjects (view guidance), including 
 
the availability/presence of translators (fluent in both English and the subject’s spoken language) during 
 
the consent process and the translation of consent documents in a language understandable to them 
 
(when consent documents are translated all translated versions must be accompanied by an attestation 
 
from the translator) OR justify why non-English speaking subject are being excluded from the research: 
 
RESPONSE: We would like to apply for use of the short form consent process for patients that do not speak 
English.  We have used translators for patients that are not English speakers previously.   


 
VERSION 1.0: 07/30/2013 
11
 
43)  
How will literacy be assessed? If subjects cannot read the consent form, describe the process for 
 
providing information to these subjects (i.e., reading the information aloud) and for documenting 
 
consent, including whether or not the short form (45 CFR 46.117(b) (2)) process will be utilized:  
 
RESPONSE: This has not come up in the year of our trial.  We would ask subjects if they understand the 
written consent form.  If they are not literate, then we would use the oral script and document their 
understanding.   
 
44)  
For Ophthalmology related studies, describe if the cohort is capable of reading the consent form and if 
 
not, describe exacerbating factors (visual impairment, eyes dilated at the onset of the study, etc.).  In 
 
these cases, describe additional measures you will take to ensure comprehension of study-related 
 
information to promote informed decision-making by the subject: 
 
RESPONSE: NA 
 
45)  
For Otology related studies, describe if the cohort is capable of comfortably hearing the Investigator 
 
during the consent process and if not, describe exacerbating factors (hearing aid, cochlear implant, 
 
hearing impaired, etc.).  In these cases, describe additional measures you will take to ensure 
 
comprehension of study-related information to promote informed decision- making by the subject: 
 
RESPONSE: NA  
INCIDENTAL FINDINGS 
46)  
Is there a possibility of clinically significant incidental findings (information relating to previously 
 
undiagnosed medical or psychiatric conditions) being discovered during research procedures?  
 
 YES 
   
 NO    
 
IF YES, please outline the plan for addressing incidental findings (i.e., contacting the subject’s primary care 
provider, referral etc.) including if and how subjects will be informed:  
 
RESPONSE:       
 
DISSEMINATION OF RESULTS 
 
47)  
Describe any plans to share research results with subjects, this may include sharing individual results 
and/or aggregate results and may also serve as an opportunity to follow-up with subjects and thank 
them for participating in the research, particularly in cases where there is no direct benefit to the subject. 
If there are no plans to share results explain why this is not feasible, appropriate or applicable to this 
research:  
 
RESPONSE: We would plan on disseminating the final publication paper to the subjects with a note of thanks 
when the research is completed.   
 


 
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12
48)  
How will results be published, and in what form (i.e., subjects will not be individually identifiable in 
publications):  
 
RESPONSE: Results will be published in an otolaryngology peer-reviewed journal.  There will be no 
identifiable information in the publication.   
 
PRIVACY/CONFIDENTIALITY 
 
Insofar as they apply, investigators are required to adhere to MEE Information Security Policies and 
Procedures. Therefore, research protocols must be designed in accordance with these requirements. On 
occasion the HSC may require additional provisions related to the use and security of research data. The HSC 
evaluates the collection and use of data based on the minimum necessary standard, the data necessary to satisfy 
the purposes of the research to carry out research-related activities. The HSC may require that when a research 
project collects personally identifiable, sensitive information that the PI obtain a Certificate of Confidentiality.   
 
 
49)  
Describe the provisions in place to respect the privacy of subjects throughout the research: 
 
RESPONSE: For each subject in the study, a unique identification number will be generated, this number will 
be used with their study responses and all results from the study.  A list linking patients’ names, MRN and 
unique ID will be created and stored on a password-protected computer only accessible by the PI.  The survey 
responses with the unique identifiers will be locked in the PI’s office.  Only the PI will have access to this list. 
Pharmacy will have access only to the unique ID, and will be in charge of randomization.       
 
50)  
Check all identifiers that will be obtained by investigators for the purposes of this study.   
 
 Name 
 
 
 
 
 
 
 
 Telephone Number 
 Social Security Number   
 
 
 
 
 Fax Number 
 Medical Record Number    
 
 
 
 
 Email Address 
 Address by Street Location 
 
 
 
 
 Web URLs 
 Address by Town/City/Zip Code  
 
 
 
 Internet Protocol (IP) Address 
 Health Plan Beneficiary Number  
 
 
 
 Account Number 
 Certificate/License Number 
 
 
 
 
 Ages over 89 
 Full Face Photographic Image 
 
 Elements of Dates except Year (Admission/Discharge Date, Procedure Date, Date of Birth or Death) 
 Vehicle ID Number and Serial Number Including License Plate Number 
 Medical Device Identifiers and Serial Number 
 Biometric Identifiers (e.g. finger or voice prints, retinal images) 
 None of the listed identifiers will be recorded as part of this study.   
 Other unique identifiers or code that can be used to identify the participant:       
 
51)  
Investigators should only obtain the minimum data necessary to achieve research goals. Please justify 
 
why the data you are obtaining is the minimum necessary:  
 
RESPONSE: We need the patients’ names, date of birth, and MRN to identify patients.  A unique number will 
be generated that will deidentify the patients to the pharmacy.   


 
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52)  
Will data about individual subjects be collected from sources outside of Mass. Eye and Ear?    
 
 YES  
  
 NO   
 
IF YES, list each source (include if the source is considered a covered entity), the data collected, and any 
agreements in place to allow transfer of this data:  
 
RESPONSE:       
53)  
Sensitive information includes (but is not limited to) information relating to sexual attitudes, preferences, 
 
or practices; information relating to the use of alcohol, drugs, or other addictive products; information 
 
pertaining to illegal conduct; information that, if released, might be damaging to an individual’s 
 
financial standing, employability, or reputation within the community or might lead to social 
 
stigmatization or discrimination; information pertaining to an individual’s psychological well-being or 
 
mental health; and genetic information or tissue samples.  
  
 
Will this research collect sensitive information?  
 YES         
 NO (If NO, skip to question 55)  
 
IF YES, list the data that will be collected and provide a rationale under the minimum necessary standard: 
 
RESPONSE:       
 
54)  
Has a Certificate of Confidentiality been sought for this research?    
 YES     
 NO  
__________________________________________________________________________________________ 
 
IF YES, include a copy of the certificate at the time of submission or provide information related to the status 
 
of your application 
 
IF NO, justify your response below: 
 
55)  
Please indicate the specific safeguards in place to protect the confidentiality of subject data: 
 
Administrative Safeguards: 
 
 YES   
 NO 
Each member of the study team has completed Mass. Eye and Ear Privacy Training and 
Information Security Awareness Training and this training is up to date.  
 
 YES   
 NO 
Paper files, electronic data, computing devices and storage media will be safeguarded in 
accordance with Mass. Eye and Ear Privacy and Information Security policies and 
procedures, including, but not limited to the safeguards more specifically identified 
below: 
 
Physical Safeguards: 
 
 YES   
 NO   
 N/A 
 
Paper files will be locked in cabinets when not in use 
 
 YES   
 NO   
 N/A 
 
Paper files will be protected from inappropriate access when in use 
 


 
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 YES   
 NO   
 N/A 
 
Mobile computing devices and storage media will be locked in cabinets  
 
 
when not in use 
 
 YES   
 NO   
 N/A 
 
Computing devices will be protected from inappropriate access when in  
 
 
use 
 
 Yes   
 No     
 N/A 
 
Research data will be coded using a subject identification number that  
 
 
 
 
 
does not include the subject’s initials and is not derived from the subject’s  
 
 
 
 
 
identifiable information.   
 
                                       
 IF YES: The key linking the subject identification number to the   
 
 
 
 
 
subject’s identifiable information is available only to the following study  
 
 
 
 
 
team members:  
 
 
 
 
 
 Mass. Eye and Ear PI 
 
 
 
 
 Other Mass. Eye and Ear study team members 
 
 
 
 
 External investigator 
 
 
 
 
 External sponsor 
 
 Yes   
 No                        The key will be stored separately and in a locked cabinet (if paper)  
 
 Yes   
 No 
 
The key will be stored separately and on a password protected network drive with 
 
access limited to those people identified above  
 
Technical Safeguards: 
 
 YES   
 NO 
 
Electronic data will be stored on Mass. Eye and Ear network folders for which 
 
access is limited to authorized members of the study team only 
 
 YES   
 NO 
 
To the extent that electronic data is collected on the hard drive of a computing 
 
device, it will be promptly and securely transferred to a secure folder within 
 
the Mass. Eye and Ear network 
 
 YES   
 NO 
 
Mobile devices (including but not limited to laptops, tablet computers, smart 
 
phones, external hard drives and USB drives) containing electronic data will be 
 
encrypted 
 
 YES   
 NO 
 
Remote access to electronic data will be gained through Information Systems 
 
 YES   
 NO 
 
Electronic data will be encrypted when transmitted outside of Mass. Eye and Ear 
 
 
Please describe any additional safeguards that will be used to protect the study data and explain any “No” 
responses: 
RESPONSE: We will not use remote access, and we will not send data outside of MEEI.  
 
56)  
Will data that identifies individual subjects be disclosed to parties outside of Mass. Eye and Ear (e.g. 
 
sponsor and/or coordinating center, research registry) for purposes of the research?   
 YES    
 NO    
 


 
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IF YES, list the parties and explain how and what information will be shared: 
 
RESPONSE:       
 
57)  
Where will research data, including the signed informed consent form and assent be stored (e.g., MEEI 
 
medical record, research record, etc.). 
 
RESPONSE: In the MEEI Sinus center under lock and key.   
 
58)  
Please provide the plan for destroying identifiers (at the earliest opportunity as consistent with the 
 
research plan) or provide a health or research justification for retaining identifiers. For protocols subject 
 
to future and secondary data analysis, provide justification for not destroying identifiers permanently 
 
and explain plans for future use (i.e., establishment of a data or specimen repository):  
 
RESPONSE: When the research is complete, we will destroy all identifiable information by following 
MEEI protocols.  
 
CONFLICTS OF INTEREST 
If the research involves any of the following: 1) for-profit sponsor or funding source; 2) a marketed drug, 
device, or other technology; or a drug, device, or other technology in development; or 3) a new 
technology, software, or therapeutic approach, all investigators are required to complete and submit (at the 
time of initial submission and thereafter in accordance with the policy) a Conflict of Interest in Research: 
Project-Specific Disclosure (SUPP L) in accordance with the HSC Conflicts of Interest: Clinical Research 
policy. Please refer to the policy and SUPP L for further guidance on disclosure and submission requirements. 
FAQ guidance on this topic is also available.  
 
59)  
Does the research involve (check all that apply):  
 
 
For-profit sponsor or funding source?   
 YES   
 NO 
 
 
Marketed drug, device, or other technology; or a drug or device, or other technology in development? 
 
 YES   
 NO  
 
We are using amoxicillin / clavulinate as the study drug.  This drug is generically available in the US.  We 
are not seeking a new indication for this already FDA approved medication.   
 
 
New technology, software, or therapeutic approach?   
 YES   
 NO 
 
 
 
 
 
 
 
 


 
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