Vacuum vs Manual Drainage During Unilateral Thoracentesis: A Randomized Trial
Phase: NA
Conditions: Pleural Effusion, Pleural Diseases, Thoracic Diseases
Sponsor: Yale University

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Vacuum vs Manual Drainage During Unilateral Thoracentesis 
 
Study Protocol 
 
NCT 03496987 
 
Original Document Date: 11/17/15 
 

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Title of Research Project: Thoracentesis using Manual Aspiration vs Vacuum Suction: A Study 
Comparing Pain and Complications 
Principal Investigator: Jonathan Puchalski, MD, 
MEd 
Yale Academic Appointment: Associate Professor 
Department: Department of Medicine 
Campus Address: LCI 100D, 15 York St., New Haven, CT 
Campus Phone: 737-5699 
Fax: 737-1666 
Pager: 370-6396 
E-mail: 
jonathan.puchalski@yale.edu 
Protocol Correspondent Name & Address (if different than PI): Michal Senitko, MD, LCI 100D, 15 York 
St, New Haven, CT 
Campus Phone: 737-5699 
Fax: 
E-mail: michal.senitko@yale.edu 
Yale Cancer Center CTO Protocol Correspondent Name & Address (if applicable): 
Campus Phone: 
Fax: 
E-mail: 
Business Manager: 
Campus Phone : 
Fax : 
E-mail 
 
Faculty Advisor:(required if PI is a student, 
resident, fellow or other trainee) 
 NA 
Yale Academic Appointment: 
Campus Address: 
Campus Phone: 
Fax: 
Pager: 
E-mail: 
 
Investigator Interests: 
Does the principal investigator, or do any research personnel who are responsible for the design, 
conduct or reporting of this project or any of their family members (spouse or dependent child) 
have an incentive or interest, financial or otherwise, that may affect the protection of the human 
subjects involved in this project, the scientific objectivity of the research or its integrity? Note: 
The Principal Investigator (Project Director), upon consideration of the individual’s role and 
degree of independence in carrying out the work, will determine who is responsible for the 
design, conduct, or reporting of the research. 
SECTION I: ADMINISTRATIVE INFORMATION 

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See Disclosures and Management of Personal Interests in Human Research 
http://www.yale.edu/hrpp/policies/index.html#COI 
ο Yes 
  No 
 
Do you or does anyone on the research team who is determined by you to be responsible for the 
design, conduct or reporting of this research have any patent (sole right to make, use or sell an 
invention) or copyright (exclusive rights to an original work) interests related to this research 
protocol? 
ο Yes 
 No 
 
If yes to either question above, list names of the investigator or responsible person: 
 
The Yale University Principal Investigator, all Yale University co-investigators, and all Yale 
University individuals who are responsible for the design, conduct or reporting of research must 
have a current financial disclosure form on file with the University’s Conflict of Interest Office. 
Yale New Haven Hospital personnel who are listed as co-investigators on a protocol with a Yale 
University Principal Investigator must also have a current financial disclosure form on file with 
the University’s Conflict of Interest Office. If this has not been done, the individual(s) should 
follow this link to the COI Office Website to complete the form: http://www.yale.edu/coi/ 
 
NOTE: The requirement for maintaining a current disclosure form on file with the University’s 
Conflict of Interest Office extends primarily to Yale University and Yale-New Haven Hospital 
personnel. Whether or not they are required to maintain a disclosure form with the 
University’s Conflict of Interest Office, all investigators and individuals deemed otherwise 
responsible by the PI who are listed on the protocol are required to disclose to the PI any 
interests that are specific to this protocol. 
 
 
1. Performing Organizations: Identify the hospital, in-patient or outpatient facility, school or 
other agency that will serve as the location of the research. Choose all that apply: 
 
a. Internal Location[s] of the Study: 
Magnetic Resonance Research Center 
Yale University PET Center 
(MR-TAC) 
YCCI/Church Street Research Unit (CSRU) 
Yale Cancer Center/Clinical Trials Office (CTO) 
YCCI/Hospital Research Unit (HRU) 
Yale Cancer Center/Smilow 
YCCI/Keck Laboratories 
Yale-New Haven Hospital 
Yale-New Haven Hospital—Saint Raphael Campus 
Cancer Data Repository/Tumor Registry 
Specify Other Yale Location: Thoracic Oncology Program (TOP) Clinic 
 
 
b. External Location[s]: N/A 
APT Foundation, Inc. 
Haskins Laboratories 
Connecticut Mental Health Center 
John B. Pierce Laboratory, Inc. 
Clinical Neuroscience Research Unit (CNRU) 
Veterans Affairs Hospital, West Haven 
Other Locations, Specify: 
 International Research Site 
SECTION II: GENERAL INFORMATION 

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(Specify location(s)): 
 
 
c. Additional Required Documents (check all that apply): 
 N/A 
*YCCI-Scientific and Safety Committee (YCCI-SSC) 
Approval Date: 
*Pediatric Protocol Review Committee (PPRC) 
Approval Date: 
*YCC Protocol Review Committee (YRC-PRC) 
Approval Date: 
*Dept. of Veterans Affairs, West Haven VA HSS 
Approval Date: 
*Radioactive Drug Research Committee (RDRC) 
Approval Date: 
YNHH-Radiation Safety Committee (YNHH-RSC) 
Approval Date: 
Magnetic Resonance Research Center PRC (MRRC-PRC) Approval Date: 
YSM/YNHH Cancer Data Repository (CaDR) 
Approval Date: 
Dept. of Lab Medicine request for services or specimens form 
Imaging on YNHH Diagnostic Radiology equipment request form (YDRCTO request) found 
at http://radiology.yale.edu/research/ClinTrials.aspx) 
*Approval from these committees is required before final HIC approval is granted. See instructions 
for documents required for initial submission and approval of the protocol. Allow sufficient time for 
these requests. Check with the oversight body for their time requirements. 
 
2. Probable Duration of Project: State the expected duration of the project, including all 
follow-up and data analysis activities. 
 
Expected duration of the project is approximately 1 (one) year from approval, which includes 
follow up and data analysis activities expected to end December 31, 2017. 
 
3. Research Type/Phase: (Check all that apply) 
a. Study Type 
Single Center Study 
Multi-Center Study 
Does the Yale PI serve as the PI of the multi-site study? Yes 
No 
N/A 
Coordinating Center/Data Management 
Other: 
 
b. Study Phase 
N/A 
Pilot 
Phase I 
Phase II 
Phase III 
Phase IV 
Other (Specify) Two arm, prospective, randomized study 
 
4. Area of Research: (Check all that apply) Note that these are overlapping definitions and 
more than one category may apply to your research protocol. Definitions for the following 
can be found in the instructions section 4c: 
Clinical Research: Patient-Oriented 
Clinical Research: Outcomes and 
Clinical Research: Epidemiologic and Behavioral 
 
Health Services 
Translational Research #1 (“Bench-to-Bedside”) 
Interdisciplinary Research 
Translational Research #2 (“Bedside-to-Community”) 
Community-Based Research 

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5. Is this study a clinical trial? Yes 
No 
 
NOTE the current ICMJE (International Committee of Medical Journal Editors) definition of a 
clinical trial: “any research study that prospectively assigns human participants or groups of humans 
to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related 
interventions include any intervention used to modify a biomedical or health-related outcome (for 
example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and 
process-of-care changes). Health outcomes include any biomedical or health-related measures 
obtained in patients or participants, including pharmacokinetic measures and adverse events” 
If yes, where is it registered? N/A 
Clinical Trials.gov registry 
Other (Specify) 
 
Registration of clinical trials at their initiation is required by the FDA, NIH and by the ICMJE. 
 
If this study is registered on clinicaltrials.gov, there is new language in the consent form and compound 
authorization that should be used. 
 
For more information on registering clinical trials, including whether your trial must be 
registered, see the YCCI webpage, http://ycci.yale.edu/researchers/ors/registerstudy.aspx 
or contact YCCI at 203.785.3482) 
 
 
1. Does the Clinical Trials Agreement (CTA) require compliance with ICH GCP (E6)? 
Yes 
No 
N/A 
 
 
7. Will this study have a billable service? A billable service is defined as any service rendered to 
a study subject that, if he/she was not on a study, would normally generate a bill from either 
Yale-New Haven Hospital or Yale Medical Group to the patient or the patient’s insurer. The 
service may or may not be performed by the research staff on your study, but may be provided by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include 
x-rays, MRIs, CT scans, specimens sent to central labs, or specimens sent to pathology). Notes: 
1. There is no distinction made whether the service is paid for by the subject or their insurance 
(Standard of Care) or by the study’s funding mechanism (Research Sponsored). 2. This generally 
includes new services or orders placed in EPIC for research subjects. 
 
Yes 
 
If answered, “yes”, this study will need to be set up in OnCore, Yale’s clinical research 
management system, for Epic to appropriately route research related charges. Please contact 
oncore.support@yale.edu 
8.. Are there any procedures involved in this protocol that will be performed at YNHH or one of 
its affiliated entities? Yes _x  No 
If Yes, please answer questions a through c and note 
instructions below. If No, proceed to Section III. 
a. Does your YNHH privilege delineation currently include the specific procedure that you will 
perform? Yes 

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b. Will you be using any new equipment or equipment that you have not used in the past for 
this procedure? No 
 
c. Will a novel approach using existing equipment be applied? No 
 
If you answered “no” to question 8a, or "yes" to question 8b or c, please contact the YNHH 
Department of Physician Services (688-2615) for prior approval before commencing with your 
research protocol. 
 
Please note that if this protocol includes Yale-New Haven Hospital patients, including patients at 
the HRU, the Principal Investigator and any co-investigators who are physicians or mid-level 
practitioners (includes PAs, APRNs, psychologists and speech pathologists) who may have direct 
patient contact with patients on YNHH premises must have medical staff appointment and 
appropriate clinical privileges at YNHH. If you are uncertain whether the study personnel meet 
the criteria, please telephone the Physician Services Department at 203-688-2615. By signing 
this protocol as a PI, you attest that you and any co-investigator who may have patient contact 
has a medical staff appointment and appropriate clinical privileges at YNHH. 
 
 
 
1. Funding Source: Indicate all of the funding source(s) for this study. Check all boxes that apply. 
Provide information regarding the external funding source. This information should include 
identification of the agency/sponsor, the funding mechanism (grant or contract), and whether 
the award is pending or has been awarded. Provide the M/C# and Agency name (if grant- 
funded). If the funding source associated with a protocol is “pending” at the time of the 
protocol submission to the HIC (as is the case for most NIH submissions), the PI should note 
“Pending” in the appropriate section of the protocol application, provide the M/C# and 
Agency name (if grant-funded) and further note that University (departmental) funds support 
the research (until such time that an award is made). 
 
 
PI 
Title of Grant 
Name of Funding Source 
Funding 
Funding Mechanism 
 
Jonathan 
Puchalski 
N/A 
None 
Federal 
State 
Non Profit 
Industry 
Other For 
Profit 
Other 
Grant-M# 
Contract# 
Contract Pending 
Investigator/Department 
Initiated 
Sponsor Initiated 
Other, Specify: 
Provide the Name and Address of the Sponsor Representative to whom the invoice should be 
sent. Note: the PI’s home department will be billed if this information is not provided. 
 
Send IRB Review Fee Invoice To: 
Name: 
SECTION III: FUNDING, RESEARCH TEAM AND TRAINING 

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Company: 
Address: 
 
2. Research Team: List all members of the research team. Indicate under the affiliation column whether 
the investigators or study personnel are part of the Yale faculty or staff, or part of the faculty or staff 
from a collaborating institution, or are not formally affiliated with any institution. ALL members of 
the research team MUST complete Human Subject Protection Training (HSPT) and Health 
Insurance Portability and Accountability Act (HIPAA) Training before they may be listed on the 
protocol. See NOTE below. 
 
NOTE: The HIC will remove from the protocol any personnel who have not completed required training. 
 
Name 
Affiliation: Yale/Other 
Institution (Identify) 
NetID 
Principal Investigator 
Jonathan Puchalski, MD, 
MEd 
Yale Staff 
JTP2 
Role: Co-Investigator 
Michal Senitko, MD 
Yale Staff 
MS3383 
Role: Co-Investigator 
Kyle Bramley, MD 
Yale Staff 
KB449 
Role: Study Staff 
Kelsey Johnson, PA 
YNHH Staff 
KMJ39 
Role: Study Staff 
Rachel Southard, APRN 
YNHH Staff 
RCS72 
A personnel protocol amendment will need to be submitted when training is completed. 
 
SECTION IV: 
PRINCIPAL INVESTIGATOR/FACULTY ADVISOR/ DEPARTMENT CHAIR AGREEMENT 
As the principal investigator of this research project, I certify that: 
 The information provided in this application is complete and accurate. 
 I assume full responsibility for the protection of human subjects and the proper conduct of the 
research. 
 Subject safety will be of paramount concern, and every effort will be made to protect subjects’ 
rights and welfare. 
 The research will be performed according to ethical principles and in compliance with all federal, 
state and local laws, as well as institutional regulations and policies regarding the protection of 
human subjects. 
 All members of the research team will be kept apprised of research goals. 
 I will obtain approval for this research study and any subsequent revisions prior to my initiating the 
study or any change and I will obtain continuing approval of this study prior to the expiration date 
of any approval period. 
 I will report to the HIC any serious injuries and/or other unanticipated problems involving risk to 
participants. 
 I am in compliance with the requirements set by the University and qualify to serve as the 
principal investigator of this project or have acquired the appropriate approval from the 
Dean’s Office or Office of the Provost, or the Human Subject Protection Administrator at 
Yale-New Haven Hospital, or have a faculty advisor. 
 
I will identify a qualified successor should I cease my role as principal investigator and facilitate a 
smooth transfer of investigator responsibilities. 
PI Name (PRINT) and Signature 
Date 

Page 7 of 24 
 
As the faculty advisor of this research project, I certify that: 
 
The information provided in this application is complete and accurate. 
 
This project has scientific value and merit and that the student or trainee investigator has the necessary 
resources to complete the project and achieve the aims. 
 
I will train the student investigator in matters of appropriate research compliance, protection of human 
subjects and proper conduct of research. 
 
The research will be performed according to ethical principles and in compliance with all federal, state 
and local laws, as well as institutional regulations and policies regarding the protection of human 
subjects. 
 
The student investigator will obtain approval for this research study and any subsequent revisions prior 
to initiating the study or revision and will obtain continuing approval prior to the expiration of any 
approval period. 
 
The student investigator will report to the HIC any serious injuries and/or other unanticipated 
problems involving risk to participants. 
 
I am in compliance with the requirements set forth by the University and qualify to serve as 
the 
faculty advisor of this project. 
 
I assume all of the roles and responsibilities of a Principal Investigator even though the student may be 
called a PI. 
 
 
Advisor Name (PRINT) and Signature 
Date 
 
 
 
Department Chair’s Assurance Statement 
Do you know of any real or apparent institutional conflict of interest (e.g., Yale ownership of a 
sponsoring company, patents, licensure) associated with this research project? 
Yes (provide a description of that interest in a separate letter addressed to the HIC.) 
No 
 
As Chair, do you have any real or apparent protocol-specific conflict of interest between yourself and 
the sponsor of the research project, or its competitor or any interest in any intervention and/or method 
tested in the project that might compromise this research project? 
Yes (provide a description of that interest in a separate letter addressed to the HIC) 
No 
 
I assure the HIC that the principal investigator and all members of the research team are qualified by 
education, training, licensure and/or experience to assume participation in the conduct of this research 
trial. I also assure that the principal investigator has departmental support and sufficient resources to 
conduct this trial appropriately. 
 
 
 
_ 
_Gary V Desir, MD  
  
11/17/15 
 
Chair Name (PRINT) and Signature 
Date 
 
  
Department of Medicne  
 
Department 

Page 8 of 24 
 
 
YNHH Human Subjects Protection Administrator Assurance Statement 
Required when the study is conducted solely at YNHH by YNHH health care providers. 
 
 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested. 
 
The purpose of the study is to assess if there is a difference in pain and complication rate 
between using a manual drainage system vs vacuum containers during thoracenteis of pleural 
effusions. 
 
2. Background: Describe the background information that led to the plan for this project. 
Provide references to support the expectation of obtaining useful scientific data. 
 
Patients with pleural effusions routinely undergo thoracentesis in which a catheter is placed 
into the pleural space to remove the fluid. In this setting, large amounts (often liters) of fluid 
are removed to palliate the patient’s symptoms of breathlessness. 
 
Thoracentesis is standardly performed using Safe T-CentesisTM Catheter Drainage Tray. 
After insertion of catheter to pleural space operator has two drainage system options. 1. 
Manual drainage that connects to drainage bag (figure 1) or 2. Drainage to vacuum bottle 
(figure2). 
 
Pleural pressure (Ppl) is determined by the elastic recoil properties of the lung and chest wall. 
Normal pleural pressure is estimated to be -3 to -5 cm H20 at functional residual capacity. 
During drainage of pleural fluid, negative pressure is applied either via syringe during 
manual drainage or via vacuum using vacuum drainage bottle. Hypothetically more negative 
pressure can translate to increased perception of pain or visceral pleural injury. 
 
Two techniques (manual vs vacuum drainage) are used based on the operator preference and 
both are standard of care. To our knowledge there is no head to head comparison of two 
available systems of drainages during thoracentesis of pleural effusion. 
Date 
YNHH HSPA Name (PRINT) and Signature 
As Human Subject Protection Administrator (HSPA) for YNHH, I certify that: 
 I have read a copy of the protocol and approve it being conducted at YNHH. 
 I agree to notify the IRB if I am aware of any real or apparent institutional conflict of interest. 
 The principal investigator of this study is qualified to serve as P.I. and has the support of the hospital 
for this research project. 
SECTION V: RESEARCH PLAN 

Page 9 of 24 
 
Figure 1. 
Figure 2. 
3. Research Plan: Summarize the study design and research procedures using non-technical 
language that can be readily understood by someone outside the discipline. Be sure to 
distinguish between standard of care vs. research procedures when applicable, and 
include any flowcharts of visits specifying their individual times and lengths. Describe 
the setting in which the research will take place. 
 
The interventional pulmonary team at Yale performs hundreds of thoracenteses per year. We 
have arbitrarily used the manual evacuation technique. However, use of a vacuum container 
could potentially save time for the patient and practitioner. Both methods of drainage are 
considered standard of care. 
 
There are no research procedures performed in this study. During this study, we will simply 
methodically document which technique is performed, the patient’s assessment of pain 
during the procedure, and complications (namely pneumothorax) based on randomization of 
which technique is performed. 
 
Randomization will be done by block randomization to ensure an equal number of subjects in 
each group using a predefined key. (see Appendix 1: Research Randomizer Key). 
 
Pain prior the initiation of the procedure and during the procedure will be assessed using The 
Numeric Pain Rating Scale (NPRS see Appendix 2). Patients’ demographics (sex and age), 
the presumed etiology of pleural effusions, effusion laterality, volume removed, duration of 
procedure, reason for termination and complications will be recorded. 
 
Investigators, study staff and patients will not be blinded to type of drainage system used. 
 
4. Genetic Testing N/A 
 
A. Describe 
i. the types of future research to be conducted using the materials, specifying if 
immortalization of cell lines, whole exome or genome sequencing, genome wide 
association studies, or animal studies are planned 

Page 10 of 24 
 
ii. the plan for the collection of material or the conditions under which material will 
be received 
iii. the types of information about the donor/individual contributors that will be 
entered into a database 
iv. the methods to uphold confidentiality 
 
B. What are the conditions or procedures for sharing of materials and/or distributing for 
future research projects? 
C. Is widespread sharing of materials planned? 
D. When and under what conditions will materials be stripped of all identifiers? 
E. Can donor-subjects withdraw their materials at any time, and/or withdraw the identifiers 
that connect them to their materials? 
i. How will requests to withdraw materials be handled (e.g., material no longer 
identified: that is, anonymized) or material destroyed)? 
 
F. Describe the provisions for protection of participant privacy 
G. Describe the methods for the security of storage and sharing of materials 
 
5. Subject Population: Provide a detailed description of the types of human subjects who will 
be recruited into this study. 
 
Patients with unilateral or bilateral pleural effusions who undergo thoracentesis by the 
Interventional Pulmonary team will be enrolled. These patients may be inpatient or  
outpatient and the procedure is performed throughout the hospital and clinic locations. 
Patients will be enrolled between Janaury 1st 2015 through December 31st 2017. 
 
6. Subject classification: Check off all classifications of subjects that will be specifically 
recruited for enrollment in the research project. Will subjects who may require additional 
safeguards or other considerations be enrolled in the study? If so, identify the population of 
subjects requiring special safeguards and provide a justification for their involvement. N/A 
 
Children 
Healthy 
Fetal material, placenta, or dead fetus 
Non-English Speaking 
Prisoners 
 Economically disadvantaged persons 
Decisionally Impaired 
Employees 
 Pregnant women and/or fetuses 
Yale Students 
Females of childbearing potential 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as 
potential subjects? 
Yes  
 No (If yes, see Instructions section VII #4 for further 
requirements) 
 
Subjects who may require additional safeguards or other considerations will not be enrolled in 
the study. 
 
7. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or 
exclusion? 

Page 11 of 24 
 
 
Inclusion criteria: 
 
1. Age > 18 y/o 
2. Unilateral or bilateral pleural effusion 
 
Exclusion criteria: 
 
1. Patients with pleural effusions unable to be drained by thoracentesis 
2. Adults who refuse to provide consent. 
3. Patients unable to provide verbal feedback of their pain during the procedure. 
These include patients with an altered mental status and non-English speaking 
patients. 
 
8. How will eligibility be determined, and by whom? 
 
Once the consult for thoracentesis is received, the chart will be reviewed as part of standard 
practice. Eligibility for the study will be determined by the Interventional Pulmonary attending 
or fellow. 
 
9. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, 
discomforts, or inconveniences associated with subjects participating in the research. 
 
There is minimal to no risk for the study participant. The thoracentesis is standard of care. 
We will only be collecting data about pain (no risk to the patient) and complications of the 
procedure (no risk from study participation). 
 
10. Minimizing Risks: Describe the manner in which the above-mentioned risks will be 
minimized. 
 
Subject privacy risk will be minimized by using data collection tool where each subject will 
have a random number assigned. The medical record number will be available only to the 
Interventional Pulmonary Team involved in patient care and data will be de-identified as soon 
as the research data are entered to the data collection tool. 
 
To protect against breaches of confidentiality, we will store all data on password protected 
computers and in locked file cabinets in key-card restricted areas. Data will be entered in 
computers associated with the Yale Program on Aging database. 
 
 
11. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan 
(DSMP) based on the investigator’s risk assessment stated below. (Note: the HIC will make 
the final determination of the risk to subjects.) For more information, see the Instructions, 
page 24. 
a. 
What is the investigator’s assessment of the overall risk level for subjects 
participating in this study? No risk 

Page 12 of 24 
 
b. 
If children are involved, what is the investigator’s assessment of the overall risk 
level for the children participating in this study? N/A 
c. 
Include an appropriate Data and Safety Monitoring Plan. Examples of DSMPs are 
available here http://www.yale.edu/hrpp/forms-templates/biomedical.html for 
i. Minimal risk 
ii. Greater than minimal 
 
d. For multi-site studies for which the Yale PI serves as the lead investigator: N/A 
i. How will adverse events and unanticipated problems involving risks to subjects or 
others be reported, reviewed and managed? 
ii. What provisions are in place for management of interim results? 
iii. What will the multi-site process be for protocol modifications? 
 
The principal investigator is responsible for monitoring the data, assuring protocol compliance, 
and conducting the safety reviews quarterly. During the review process the principal investigator 
will evaluate whether the study should continue unchanged, require modification/amendment, or 
close to enrollment. 
 
The principal investigator, the Institutional Review Board (IRB) or, Yale Cancer Center Data 
and Safety Monitoring Committee (DSMC)] have the authority to stop or suspend the study or 
require modifications. 
 
This protocol presents minimal risks to the subjects and Unanticipated Problems Involving Risks 
to Subjects or Others (UPIRSOs), including adverse events, are not anticipated. In the unlikely 
event that such events occur, Reportable Events (which are events that are serious or life- 
threatening and unanticipated (or anticipated but occurring with a greater frequency than 
expected) and possibly, probably, or definitely related) or Unanticipated Problems Involving 
Risks to Subjects or Others that may require a temporary or permanent interruption of study 
activities will be reported immediately (if possible), followed by a written report within 5 
calendar days of the Principal Investigator becoming aware of the event to the IRB (using the 
appropriate forms from the website) and any appropriate funding and regulatory agencies. The 
investigator will apprise fellow investigators and study personnel of all UPIRSOs and adverse 
events that occur during the conduct of this research project. Investigator will meet this 
obligation though the study meetings. The protocol’s research monitor(s), Yale Cancer Center 
Data and Safety Monitoring Committee (DSMC), DSMBs, and regulatory agencies, and 
regulatory and decision-making bodies will be informed of any serious or life-threatening and 
unanticipated adverse events within 5 days of the event becoming known to the principal 
investigator. 
 
 
12. Statistical Considerations: Describe the statistical analyses that support the study design. 
 
The t-test will be used to analyze the difference in pneumothorax rate and pain assessment 
scales. 

Page 13 of 24 
 
 
 
If this section (or one of its parts, A or B) is not applicable, state N/A and delete the rest of the 
section. 
 
A. DRUGS, BIOLOGICS and RADIOTRACERS 
N/A 
1. Identification of Drug, Biologic or Radiotracer: What is (are) the name(s) of the drug(s) 
biologic(s) or radiotracer(s) being used? Identify whether FDA approval has been granted and for 
what indication(s). 
 
 
All protocols which utilize a drug, biologic or radiotracer not approved by, but regulated by, the FDA, 
or a radiotracer regulated by the RDRC, must provide the following information: 
a. What is the Investigational New Drug (IND) number assigned by the FDA? 
b. Who holds the IND? 
c. All protocols which utilize a radiotracer not approved by, but regulated by the FDA must 
provide the IND number:   
 
Alternatively, use of the investigational radiotracer may be under RDRC/RSC oversight: (check 
if appropriate)  
 
 
For all investigational radiotracers, attach a copy of the RDRC/RSC application (for 
radioisotopes used in the PET Center, PET Center personnel may complete this step) 
Go to http://rsc.med.yale.edu/login.asp?url=myApps.asp. When you have logged in, complete 
the application and attach a copy to this submission. 
 
Alternatively, an exemption from IND filing requirements may be sought for a clinical 
investigation of a drug product that is lawfully marketed in the United States. If there is no IND and 
an exemption is being sought, review the following categories and complete the category that applies 
(and delete the inapplicable categories): 
 
Exempt Category 1 
The clinical investigation of a drug product that is lawfully marketed in the United States can be 
exempt from IND regulations if all of the following are yes: 
 
i. The intention of the investigation is NOT to report to the FDA as a well-controlled study in support 
of a new indication for use or to be used to support any other significant change in the labeling for 
the drug. 
Yes 
No 
ii. The drug that is undergoing investigation is lawfully marketed as a prescription drug product, and 
the intention of the investigation is NOT to support a significant change in the advertising for the 
product. 
Yes 
No 
iii. The investigation does NOT involve a route of administration or dosage level or use in populations 
or other factor that significantly increases the risks (or decreases the acceptability of the risks) 
SECTION VI: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND 
DEVICES 

Page 14 of 24 
 
associated with the use of the drug product. 
Yes 
No 
iv. The investigation will be conducted in compliance with the requirements for institutional (HIC) 
review and with the requirements for informed consent of the FDA regulations (21 CFR Part 50 
and 21 CFR Part 56). Yes No 
v. The investigation will be conducted in compliance with the requirements regarding promotion and 
charging for investigational drugs. 
Yes 
No 
 
Exempt Category 2 (all items i, ii, and iii must be checked to grant a category 2 exemption) 
 
i. The clinical investigation is for an in vitro diagnostic biological product that involves one or 
more of the following (check all that apply): 
Blood grouping serum 
Reagent red blood cells 
Anti-human globulin 
 
ii. The diagnostic test is intended to be used in a diagnostic procedure that confirms the 
diagnosis made by another, medically established, diagnostic product or procedure; and 
 
iii. The diagnostic test is shipped in compliance with 21 CFR §312.160. 
 
Exempt Category 3 
 
The drug is intended solely for tests in vitro or in laboratory research animals if shipped in 
accordance with 21 CFR 312.60 
 
Exempt Category 4 
 
A clinical investigation involving use of a placebo if the investigation does not otherwise 
require submission of an IND. 
 
 
2. Background Information: Provide a description of previous human use, known risks, and data 
addressing dosage(s), interval(s), route(s) of administration, and any other factors that might 
influence risks. If this is the first time this drug is being administered to humans, include relevant 
data on animal models. 
 
 
3. Source: a) Identify the source of the drug or biologic to be used. 
 
b) Is the drug provided free of charge to subjects? 
Yes 
No 
If yes, by whom? 
 
4. Storage, Preparation and Use: Describe the method of storage, preparation, stability information, 
and for parenteral products, method of sterilization and method of testing sterility and 
pyrogenicity. 

Page 15 of 24 
 
Check applicable Investigational Drug Service utilized: 
YNHH IDS 
Yale Cancer Center 
CMHC Pharmacy 
West Haven VA 
PET Center 
None 
Other: 
Note: If the YNHH IDS (or comparable service at CMHC or WHVA) will not be utilized, explain in 
detail how the PI will oversee these aspects of drug accountability, storage, and preparation. 
 
 
5. Use of Placebo: 
Not applicable to this research project 
If use of a placebo is planned, provide a justification which addresses the following: 
1.  
Describe the safety and efficacy of other available therapies. If there are no other 
available therapies, state this. 
b. State the maximum total length of time a participant may receive placebo while on the study. 
c. Address the greatest potential harm that may come to a participant as a result of receiving 
placebo. 
d. Describe the procedures that are in place to safeguard participants receiving placebo. 
 
6. Use of Controlled Substances: 
Will this research project involve the use of controlled substances in human subjects? 
Yes 
No See HIC Application Instructions to view controlled substance listings. 
 
If yes, is the use of the controlled substance considered: 
Therapeutic: The use of the controlled substance, within the context of the research, has the 
potential to benefit the research participant. 
Non-Therapeutic: Note, the use of a controlled substance in a non-therapeutic research study 
involving human subjects may require that the investigator obtain a Laboratory Research License. 
Examples include controlled substances used for basic imaging, observation or biochemical 
studies or other non-therapeutic purposes. See Instructions for further information. 
 
7. Continuation of Drug Therapy After Study Closure 
Not applicable to this project 
Are subjects provided the opportunity to continue to receive the study drug(s) after the study has 
ended? 
Yes If yes, describe the conditions under which continued access to study drug(s) may apply 
as well as conditions for termination of such access. 
 
No If no, explain why this is acceptable. 
B. DEVICES 
N/A 
1. 
Are there any investigational devices used or investigational procedures performed at Yale- 
New Haven Hospital (YNHH) (e.g., in the YNHH Operating Room or YNHH Heart and 
Vascular Center)? ☐Yes  ☒No If Yes, please be aware of the following requirements: 

Page 16 of 24 
 
a. A YNHH New Product/Trial Request Form must be completed via EPIC: Pull down the 
Tools tab in the EPIC Banner, Click on Lawson, Click on “Add new” under the New 
Technology Request Summary and fill out the forms requested including the “Initial 
Request Form,” “Clinical Evidence Summary, “ and attach any other pertinent 
documents. Then select “save and submit” to submit your request; and 
 
b. Your request must be reviewed and approved in writing by the appropriate YNHH 
committee before patients/subjects may be scheduled to receive the investigational device 
or investigational procedure. 
 
 
2. What is the name of the device to be studied in this protocol? 
 
Has this device been FDA approved? 
Yes 
No 
If yes, state for what indication. 
 
 
3. Background Information: Provide a description of previous human use, known risks, and 
any other factors that might influence risks. If this is the first time this device is being used in 
humans, include relevant data on animal models. 
 
 
4. Source: 
a) Identify the source of the device to be used. 
 
b) Is the device provided free of charge to subjects? 
Yes 
No 
 
5. What is the PI’s assessment of risk level (significant or non-significant) associated with the 
use of the device? 
 
Significant Risk (SR) Device Study: A study of a device that presents a potential for serious 
risk to the health, safety, or welfare of a participant and 1) is intended as an implant; 2) is used in 
supporting or sustaining human life; or otherwise prevents impairment of human health; 3) is of 
substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents 
impairment of human health; or 4) otherwise presents a potential for serious risk to the health, 
safety, or welfare of a participant. 
 
Significant Risk Devices require an Investigational Device Exemption (IDE) issued by the FDA. 
What is the IDE number assigned by the FDA? 
Did the FDA approve this IDE as Category A (experimental/investigational) or as Category B 
(non-experimental/investigational)? 
Who holds the IDE? 

Page 17 of 24 
 
Non-Significant Risk (NSR) Device Study: A study of a device that does not meet the 
definition for a significant risk device and does not present a potential for serious risk to the health, 
safety, or welfare of participants. Note that if the HIC concurs with this determination, an IDE is 
not required. 
 
6. Abbreviated IDE or Exempt IDE: There are abbreviated requirements for an IDE and 
there also are exemptions to the requirement for an IDE. See the criteria in the HIC 
Application Instructions, Section VI.B.4 at 
http://www.yale.edu/hrpp/resources/docs/100FR1aHICProtocol_Application_Instructions5- 
25-11.pdf to determine if these pertain to this study. 
 
Abbreviated IDE or Exempt IDE – If criteria set forth in the HIC Application Instructions 
are met, copy and paste the completed relevant section from the Instructions into this application. 
 
 
7. 
Investigational device accountability: 
a. State how the PI, or named designee, ensures that an investigational device is used only in 
accordance with the research protocol approved by the HIC, and maintains control of the 
investigational device as follows: 
Maintains appropriate records, including receipt of shipment, inventory at the site, 
dispensation or use by each participant, and final disposition and/or the return of the 
investigational device (or other disposal if applicable): 
Documents pertinent information assigned to the investigational device (e.g., date, quantity, batch 
or serial number, expiration date if applicable, and unique code number): 
Stores the investigational device according to the manufacturer's recommendations with respect to 
temperature, humidity, lighting, and other environmental considerations: 
Ensures that the device is stored in a secure area with limited access in accordance with applicable 
regulatory requirements: 
Distributes the investigational device to subjects enrolled in the IRB-approved protocol: 
1. Targeted Enrollment: Give the number of subjects: 
a. Targeted for enrollment at Yale for this protocol 100_ 
b. If this is a multi-site study, give the total number of subjects targeted across all sites 
N/A 
 
2. Indicate recruitment methods below. Attach copies of any recruitment materials that will be used. 
 
Flyers 
Internet/Web Postings 
Radio 
Posters 
Mass E-mail Solicitation 
Telephone 
Letter 
Departmental/Center Website 
Television 
Medical Record Review 
Departmental/Center Research Boards 
Newspaper 
Departmental/Center Newsletters 
YCCI Recruitment database 
Web-Based Clinical Trial Registries 
Clinicaltrials.gov Registry (do not send materials to HIC) 
SECTION VII: RECRUITMENT/CONSENT AND ASSENT PROCEDURES 

Page 18 of 24 
 
  Other (describe): Patients with pleural effusion referred for thoracentesis will be invited to 
participate in this study. There is no specific advertising. 
 
3. Recruitment Procedures: 
a. Describe how potential subjects will be identified. 
Any patient who needs thoracentesis as part of their routine medical care is eligible for this study. 
 
b. Describe how potential subjects are contacted. 
The study will be described to each patient at the time of the consent for the procedure. 
 
c. Who is recruiting potential subjects? 
Recruitment will be performed by Jonathan Puchalski, MD; Michal Senitko, MD; Kyle Bramley, MD; 
Kelsey Johnson PA and Rachel Southard APRN. All persons obtaining consent have experience with 
procedural consent. 
 
4. Screening Procedures 
a. Will email or telephone correspondence be used to screen potential subjects for 
eligibility prior to the potential subject coming to the research office? 
Yes  
 No 
b. If yes, identify below all health information to be collected as part of screening and 
check off any of the following HIPAA identifiers to be collected and retained by the 
research team during this screening process. 
 
HEALTH INFORMATION TO BE COLLECTED: 
 
HIPAA identifiers: 
Names 
All geographic subdivisions smaller than a State, including: street address, city, county, precinct, zip codes and their 
equivalent geocodes, except for the initial three digits of a zip code if, according to the current publicly-available data from 
the Bureau of the Census: (1) the geographic unit formed by combining all zip codes with the same three initial digits 
contains more than 20,000 people, and (2) the initial three digits of a zip code for all such geographic units containing 
20,000 or fewer people is changed to 000. 
Telephone numbers 
Fax numbers 
E-mail addresses 
Social Security numbers 
Medical record numbers 
Health plan beneficiary numbers 
Account numbers 
All elements of dates (except year) for dates related to an individual, including: birth date, admission date, discharge 
date, date of death, all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages 
and elements may be aggregated into a single category of age 90 or older 
Certificate/license numbers 
Vehicle identifiers and serial numbers, including license plate numbers 
Device identifiers and serial numbers 
Web Universal Resource Locators (URLs) 
Internet Protocol (IP) address numbers 
Biometric identifiers, including finger and voice prints 
Full face photographic images and any comparable images 
Any other unique identifying numbers, characteristics, or codes 

Page 19 of 24 
 
5. Assessment of Current Health Provider Relationship for HIPAA Consideration: 
Does the Investigator or any member of the research team have a direct existing clinical 
relationship with any potential subject? 
Yes, all subjects 
Yes, some of the subjects 
No 
 
If yes, describe the nature of this relationship. 
 
The patients scheduled for thoracentesis will be asked to participate in this study. The PI and 
research staff will have a medical history of all patients based on the inherent relationship 
required for medical procedures 
 
6. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization 
for either the entire study, or for recruitment purposes only. Note: if you are collecting PHI as part of 
a phone or email screen, you must request a HIPAA waiver for recruitment purposes.) 
 
Choose one: 
☐ For entire study 
☐ For recruitment purposes only 
☐ For inclusion of non-English speaking subject if short form is being used 
 
i. Describe why it would be impracticable to obtain the subject’s authorization for 
use/disclosure of this data; 
ii. If requesting a waiver of signed authorization, describe why it would be 
impracticable to obtain the subject’s signed authorization for use/disclosure of this 
data; 
 
By signing this protocol application, the investigator assures that the protected 
health information for which a Waiver of Authorization has been requested will not 
be reused or disclosed to any person or entity other than those listed in this 
application, except as required by law, for authorized oversight of this research 
study, or as specifically approved for use in another study by an IRB. 
 
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale 
HIPAA-Covered entity must be accounted for in the “accounting for disclosures log”, by subject 
name, purpose, date, recipients, and a description of information provided. Logs are to be 
forwarded to the Deputy HIPAA Privacy Officer. 
 
7. Required HIPAA Authorization: If the research involves the creation, use or disclosure of 
protected health information (PHI), separate subject authorization is required under the 
HIPAA Privacy Rule. Indicate which of the following forms are being provided: 
Compound Consent and Authorization form 
HIPAA Research Authorization Form 

Page 20 of 24 
 
8. Consent Personnel: List the names of all members of the research team who will be obtaining 
consent/assent. 
 
Consent will be obtained by Jonathan Puchalski, MD; Michal Senitko, MD; Kyle Bramley, MD; Kelsey 
Johnson PA and Rachel Southard, APRN. All persons obtaining consent have experience with procedural 
consent. 
 
9. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will 
be obtained, including parental permission or surrogate permission and the steps taken to ensure 
subjects’ independent decision-making. 
 
At the time of outpatient or inpatient consult visit for thoracentesis, the study will be described to 
each patient. Only English speaking patients with a normal mental status will be enrolled. 
 
Thoracentesis will be offered regardless to subjects’ participation in the study. The procedure will 
be done in a standardized way. 
 
10. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the 
personnel obtaining consent will assess the potential subject’s ability and capacity to consent to the 
research being proposed. 
 
All persons obtaining consent have experience with procedural consent and are trained to 
evaluate decision making capacity of the patients. 
 
11. Documentation of Consent/Assent: Specify the documents that will be used during the 
consent/assent process. Copies of all documents should be appended to the protocol, in the same 
format that they will be given to subjects. 
 
The consent form as appended in Appendix 3 will be used to consent patients to participate in the 
study. 
 
12. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for 
research involving non-English speaking subjects. If enrollment of these subjects is anticipated, 
translated copies of all consent materials must be submitted for approval prior to use. 
 
N/A 
 
 
12(a) As a limited alternative to the above requirement, will you use the short form* for 
consenting process if you unexpectedly encounter a non-English speaking individual interested 
in study participation and the translation of the long form is not possible prior to intended 
enrollment? 
 
Note* If more than 2 study participants are enrolled using a short form translated into the same 
language, then the full consent form should be translated into that language for use the next time 
a subject speaking that language is to be enrolled. 

Page 21 of 24 
 
Several translated short form templates are found on our website 
at: http://www.yale.edu/hrpp/forms-templates/biomedical.html. If the translation of the short 
form is not available on our website, then the translated short form needs to be submitted to the 
IRB office for approval via amendment prior to enrolling the subject. Please review the 
guidance and presentation on use of the short form available on the HRPP website. 
 
If using a short form without a translated HIPAA Research Authorization Form, please 
request a HIPAA waiver in the section above. 
 
 
13. Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or 
a full waiver of consent, depending on the study. If you will request either a waiver of consent, 
or a waiver of signed consent for this study, complete the appropriate section below. 
Not Requesting a consent waiver 
Requesting a waiver of signed consent 
Requesting a full waiver of consent 
 
 
A. Waiver of signed consent: (Verbal consent from subjects will be obtained. If PHI is 
collected, information in this section must match Section VII, Question 6) 
Requesting a waiver of signed consent for Recruitment/Screening only 
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
Yes 
No 
b. Does a breach of confidentiality constitute the principal risk to subjects? 
Yes 
No 
 
OR 
 
c. Does the research activity pose greater than minimal risk? 
Yes If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity 
No 
AND 
d. Does the research include any activities that would require signed consent in a non- 
research context? 
Yes 
No 
 
Requesting a waiver of signed consent for the Entire Study (Note that an information 
sheet may be required.) 
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
Yes 
No 
b. Does a breach of confidentiality constitute the principal risk to subjects? 
Yes 
No 
 
OR 

Page 22 of 24 
 
 
c. Does the research pose greater than minimal risk? 
Yes If you answered yes, stop. A 
waiver cannot be granted. 
No 
AND 
d. Does the research include any activities that would require signed consent in a non- 
research context? 
Yes 
No 
 
B. Full waiver of consent: (No consent from subjects will be obtained for the activity.) 
Requesting a waiver of consent for Recruitment/Screening only 
a. Does the research activity pose greater than minimal risk to subjects? 
Yes If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity 
No 
b. Will the waiver adversely affect subjects’ rights and welfare? 
Yes 
No 
c. Why would the research be impracticable to conduct without the waiver? 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date? 
 
 
Requesting a full waiver of consent for the Entire Study (Note: If PHI is 
collected, information here must match Section VII, question 6.) 
 
If requesting a full waiver of consent, please address the following: 
 
a. Does the research pose greater than minimal risk to subjects? 
Yes If you answered yes, stop. A waiver cannot be granted. 
No 
b. Will the waiver adversely affect subjects’ rights and welfare? 
Yes 
No 
c. Why would the research be impracticable to conduct without the waiver? 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date? 
 
 
Confidentiality & Security of Data: 
a. 
What protected health information (medical information along with the HIPAA identifiers) 
about subjects will be collected and used for the research? 
 
Medical information as outlined in the Data Collection Tool (Apendix 3) will be collected. Data 
will be collected by interview and medical record abstraction. Medical record abstraction data will 
be directly entered into the data management software. All data will be entered with an ID code 
and no personal identifiers will be stored on computers. Consent Forms and contact information 
will be stored separately in locked file cabinets that will only be accessible by study staff. 
SECTION VIII: PROTECTION OF RESEARCH SUBJECTS 

Page 23 of 24 
 
b. 
How will the research data be collected, recorded and stored? Data will be collected from 
the patient’s chart by investigators and research staff and will be recorded in Data Collection 
Tool. Data will be stored in secured server. 
c. How will the digital data be stored? 
CD 
DVD 
Flash Drive 
Portable Hard 
Drive   
 Secured Server  
 Laptop Computer 
 Desktop Computer 
 Other 
d. What methods and procedures will be used to safeguard the confidentiality and security of 
the identifiable study data and the storage media indicated above during and after the 
subject’s participation in the study? 
Do all portable devices contain encryption software? 
 Yes 
No 
If no, see http://hipaa.yale.edu/guidance/policy.html 
 
e. What will be done with the data when the research is completed? Are there plans to destroy 
the identifiable data? If yes, describe how, by whom and when identifiers will be destroyed. 
If no, describe how the data and/or identifiers will be secured. 
 
Data will be stored in Secured Server. 
 
f. Who will have access to the protected health information (such as the research sponsor, the 
investigator, the research staff, all research monitors, FDA, Yale Cancer Center Data and Safety 
Monitoring Committee (DSMC), SSC, etc.)? (please distinguish between PHI and de-identified 
data) 
 
Only investigators and research staff will have access to the protected health information. 
 
g. If appropriate, has a Certificate of Confidentiality been obtained? N/A 
 
h. Are any of the study procedures likely to yield information subject to mandatory reporting 
requirements? (e.g. HIV testing – reporting of communicable diseases; parent interview - 
incidents of child abuse, elderly abuse, etc.). Please verify to whom such instances will need to 
be reported. 
 
No. 
 
 
Potential Benefits: Identify any benefits that may be reasonably expected to result from the 
research, either to the subject(s) or to society at large. (Payment of subjects is not considered a 
benefit in this context of the risk benefit assessment.) 
 
The potential benefit we expect from the study is to determine if there is a population of patients 
with pleural effusion who would benefit from using manual drainage rather than vacuum 
drainage. 
 
 
SECTION IX: POTENTIAL BENEFITS 
SECTION X: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS 

Page 24 of 24 
 
1. 
Alternatives: What other alternatives are available to the study subjects outside of the research? 
 
Patient will have thoracentesis done regardless of participating in the study. 
 
2. 
Payments for Participation (Economic Considerations): Describe any payments that will be 
made to subjects, the amount and schedule of payments, and the conditions for receiving this 
compensation. 
 
No payments will be made to participating subjects. 
 
3. 
Costs for Participation (Economic Considerations): Clearly describe the subject’s costs 
associated with participation in the research, and the interventions or procedures of the study that 
will be provided at no cost to subjects. 
There will be no extra cost to subjects participating in the study. 
 
4. 
In Case of Injury: This section is required for any research involving more than minimal risk. 
a. 
Will medical treatment be available if research-related injury occurs? N/A 
b. 
Where and from whom may treatment be obtained? N/A 
c. 
Are there any limits to the treatment being provided? N/A 
d. 
Who will pay for this treatment? N/A 
e. 
How will the medical treatment be accessed by subjects? N/A