10.1 Regulatory, Ethical, and Study Oversight Considerations
10.1.1 Informed Consent Process
Due to the nature of this study – conducted at the time of cardiac arrest - we will request a waiver or alteration of required elements of consent with 21 CFR 50.24, Exception from Informed Consent (EFIC) Requirements in Certain Emergency Research.
The study will use Exception from Informed Consent (EFIC). See the EFIC Protocol enclosed.
Consent groups:
Patients will be randomized into one of two groups:
Conventional ACLS (c-CPR)
Image guided ACLS (i-CPR)
The c-CPR group will initially be enrolled under the waiver of informed consent (WIC). These patients will receive standard of care including ACLS, CPR, and high-quality chest compressions and will not be exposed to greater than minimal risk interventions. Once an LAR is present or the patient is re-capacitated, consent for continued participation will be sought. Patients who survive will have chart review as well as neurological mRS screening performed according to the schedule described in the methods section. If the patient dies intra-arrest, no consent for continued participation will be sought because only intra-arrest data will be collected.
For the i-CPR group, the research cannot be practicably carried out without EFIC. Subjects will be provided with additional pertinent information after participation if they survive the code event and have neurological and psychological capacity for communication. We will pursue a EFIC section 21 CFR 50.24 from the IRB. The proposed research is on human subjects in a life-threatening situation. Patients will be enrolled after overhead cardiac code calls are placed throughout the hospital. The therapeutic window is 10 minutes and therefore obtaining consent from the LAR is impractical and not feasible.
Obtaining consent is not practical or feasible during cardiac arrest. Second, it is impractical to prospectively identify patients who will have an IHCA. Thus, it would be extremely challenging to consent every patient in the hospital who may experience in-hospital cardiac arrest and therefore participate in the study. If, however, at the time of cardiac arrest there are family members available to consent during the therapeutic window, consent will be obtained verbally and RescueTEE imaging completed. If, however there is no immediate family members available at the bedside during the code situation, efforts will be made immediately after the code to explain the risks and benefits of the RescueTEE study and consent for continued participation will be obtained. Furthermore, if family is not reachable directly or via the phone post-cardiac arrest, then a second attempt at contacting the family and updating them will be done at the time of admission to the ICU. Ongoing attempts at obtaining consent for continued participation will be done by the study team. Patient readable material will be given to the family after the use of RescueTEE and placed in the patient chart. Finally, in the event of the patient regaining consciousness, consent for continued participation directly from the patient will be performed by the study team. (See EFIC for details)
In the setting of an emergency situation, where the survival to neurologically intact discharge after in-hospital cardiac arrest is ~15-20%, and immediate mortality is greater than 50%. We submit that the benefits of lifesaving diagnosis outweigh the low risk of injury from intervention. In order to provide process review and quality assurance we have elected to provide independent oversight of this project to the University of Pennsylvania Code Committee. This committee comprising of over 40 members meets every month and discusses and reviews code events in the hospital. There are representatives from several disciplines including emergency medicine, internal medicine, advance practice nurses, etc.
Technical note
A verbal consent for refusal of participation mechanism has also been added to the study consent process. Verbal consent refusal is a mechanism, in the rare circumstance that a LAR or family member is immediately available at the bedside and also within the therapeutic window of 10 minutes when the RescueTEE team arrives. Practically speaking, most family members/LARs are ushered away from the bedside during a IHCA but this mechanism was added should the previously mentioned scenario arise. LARs consented with the verbal mechanism will educated about the study with the option for refusal for consent verbally, or with the long form consent. This verbal mechanism is an avenue for an LAR to object to the patient’s enrollment during IHCA if they so choose.
Summary:
The process is the following:
LAR at code – Can provide Verbal Refusal to participate
(Rare) LAR at code and consent is ethically possible – Traditional Consent Long Form
LAR after code – Conventional CPR – Waiver of Informed Consent for chart review and mRS screening
LAR after code – Intervention Echo-CPR – EFIC 21 CFR 50.24 for chart review and mRS screening
When patient regains capacity – reconsent patient directly for either arm for continued participation.
10.1.1.1 Consent/assent and Other Informational Documents Provided to participants
A procedure for prospective informed consent has been developed as is required by the regulations, in the unlikely event that a LAR can be identified within the therapeutic time window for the intervention and is able to provide a meaningful prospective surrogate consent for patient enrollment. However, it will not likely be possible in the ReTEECA trial for the reasons summarized in the scientific protocol, to delay treatment for most of the eligible patients long enough to identify and contact either a LAR or other family members. In circumstances in which is it impossible to identify a LAR within the therapeutic time frame, EFIC will be applied for the interventional group and waiver of consent for the conventional arm.
Prior to enrolling an eligible patient into the proposed trial with EFIC Waiver, the physician will see if the eligible patient has refused study participation by checking if the patient is wearing an opt-out bracelet with the phrase “ReTEECA declined.” If the words “ReTEECA declined” are listed on the bracelet or known to the patient care team or code team, the patient will not be enrolled in the clinical investigation. If no “opt out” is identified, the patient will be entered into the study.
Subjects who are enrolled in ReTEECA trial with EFIC Waiver, or their LAR/family, will be informed of the subject’s inclusion in the clinical investigation at the earliest possible opportunity. This will be done in person, after the patient is coherent and informed consent can be obtained as medically determined. An on-call study team member will speak with the senior clinician to determine the stability of the subject and the appropriate time for speaking with the subject, or if not alert or capable of making informed decisions, a LAR or family member. The study team member will approach the subject (or LAR/family) to notify the subject or LAR/family about the subject’s enrollment under EFIC or WIC, provide information about the study, about the subject’s rights, the responsibilities of the investigators, and answer any questions about the study. At that time, the patient or the LAR will be asked to provide consent for continued participation in the study. A verbal objection to the study is acceptable. A written informed consent document will be used to document the subject’s (or LAR/family’s) decision to either continue in the study or to not participate any further. A copy of this form will be provided to the subject and another copy will be placed in the research record. Subjects who do not wish to continue to participate will be excluded from all further aspects of the study except for the use of data required by the federal agencies and permitted by the IRB to determine safety and efficacy. All data must remain in the study until such time as the subject or family/LAR decides to object to further participation in the study (i.e., withdrawal from the study). No further treatment is provided, and no further data is collected, however, all data up to the point of withdrawal remains in the study per FDA policy.
10.1.1.2 Consent Procedures and Documentation
Informed consent
is a process that is initiated prior to the participant or the individual’s legally authorized representative agreeing to continue to participate in the study and continues throughout the individual’s study participation. Extensive discussion of risks and possible benefits of continued participation will be provided to the participants and their families along with a description of what has occurred so far given initial enrollment under EFIC. Consent forms will be IRB-approved and the participant will be asked to read and review the document. The investigator will explain the research study to the participant and answer any questions that may arise. All participants will receive a verbal explanation in terms suited to their comprehension of the purposes, procedures, and potential risks of the study and of their rights as research participants. Participants will have the opportunity to carefully review the written consent form and ask questions prior to signing. The participants should have the opportunity to discuss the study with their surrogates or think about it prior to agreeing to participate. The participants may withdraw consent at any time throughout the course of the trial. A copy of the informed consent document will be given to the participants for their records. The rights and welfare of the participants will be protected by emphasizing to them that the quality of their medical care will not be adversely affected if they decline to continue to participate in this study
10.1.2 Study Discontinuation and Closure
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. Written notification, documenting the reason for study suspension or termination, will be provided by the suspending or terminating party to study participants, investigator, funding agency, the Investigational Device Exemption (IDE) sponsor and regulatory authorities. If the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform study participants, the Institutional Review Board (IRB), and sponsor and will provide the reason(s) for the termination or suspension. Study participants will be contacted, as applicable, and be informed of changes to study visit schedule.
Circumstances that may warrant termination or suspension include, but are not limited to:
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Determination of unexpected, significant, or unacceptable risk to participants
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Demonstration of efficacy that would warrant stopping
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Insufficient compliance to protocol requirements
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Data that are not sufficiently complete and/or evaluable
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Determination that the primary endpoint has been met
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Determination of futility
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA).]
10.1.3 Confidentiality and Privacy
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover imaging acquisition as well as to the clinical information relating to participants. Therefore, the study protocol, documentation, data, and all other information generated will be held in strict confidence. No information concerning the study or the data will be released to any unauthorized third party without prior written approval of the sponsor-investigator.
All research activities will be conducted in as private a setting as possible.
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may inspect all documents and records required to be maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. The clinical study site will permit access to such records.
The study participant’s contact information will be securely stored at each clinical site for internal use during the study. At the end of the study, all records will continue to be kept in a secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements.
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted to and stored at the University of Pennsylvania CTMS as well as Penn Redcap. This will not include the participant’s contact or identifying information. Rather, individual participants and their research data will be identified by a unique study identification number. The study data entry and study management systems used by clinical sites and by University of Pennsylvania research staff will be secured and password protected. At the end of the study, all study databases will be de-identified and archived at the University of Pennsylvania CTMS as well as Penn Redcap.
10.1.4 Future Use of Stored Specimens and Data
Patient information will be de-identified by software-based imaging techniques when imaging is analyzed. This encryption tool is available in all imaging-based storage systems. Imaging will be erased 5 years after the end of the study period. All data are anonymized, with records indexed by alphanumeric IDs; no names, SSNs, hospital record numbers, phone numbers, addresses or other identifiers will be stored.
Clinical data from patients will also be stored for the 5 years following the study conclusion. This includes code data, echocardiography reports, follow up data and survival data. This will all be stored electronically.
10.1.5 Key Roles and Study Governance
Principal Investigator
Jacob Gutsche MD
Associate Professor
Department of Anesthesiology and Critical Care
Asad Usman MD, MPH
Instructor
Department of Anesthesiology and Critical Care
Co-investigators
Justin Clapp PhD, MPH
Assistant Professor
Department of Anesthesiology and Critical Care, Anthropology
Benjamin Abella MD, MPhil
Professor
Department of Emergency Medicine
Cameron Baston MD
Associate Professor
Department of Pulmonary Medicine and Critical Care
Research Coordinators
Samantha Stein (PhD in process)
Department of Anesthesiology
Nathan Sands, BA
Emergency Medicine
Alikesei Basataski, MA
Department of Anesthesiology and Critical Care
DSMB
Scot Falk, MD
Department of Anesthesiology and Critical Care
Kristen Welsh, NP
Department of Cardiac Surgery
Kelly Hoesnich, BSN
Department of Anesthesiology and Critical Care
10.1.6 Safety Oversight
Safety oversight will be under the direction of a Data and Safety Monitoring Board (DSMB) composed of individuals with the appropriate expertise, including Head of the clinical emergencies committee and Kristen Welsh NP. Members of the DSMB should be independent from the study conduct and free of conflict of interest, or measures should be in place to minimize perceived conflict of interest. The DSMB will meet at least semiannually to assess safety and efficacy data on each arm of the study.
The ReTEECA data safety monitoring process is intended to review the events surrounding the code, the ability or inability to place TEE probes, patient safety, and image quality for every one in ten RescueTEE – randomized patients enrolled in the trial. This will include image review, image quality, ability to obtain all rescue views intended, review the events of the code, and review the probe placement attempts. This is not intended to address autonomy of the patient but the actual safety and monitoring of data and data acquisition. If there are concerns with regards to the RescueTEE ReTEECA trial and the collaboration with the hospital code teams the study will be halted until further review.
There will be a team of three reviewers for the safety monitoring of the study from outside the Department of Anesthesiology and Critical Care who will provide independent review alongside the clinical emergencies committee at HUP which is a team of 40 staff members independent to the study. We will use the office of clinical research to ensure that this is an independent process and also report biannually our progress to the clinical emergencies committee which oversees safety during all rapid responses and codes in the hospital. We will utilize the support from the Department of Medicine, Pulmonary and Critical Care and from the Department of Emergency Medicine for this task. In addition to this, Kelly Hoesnich RN, the nurse supervisor for the CTICU founder 5 will be a point person ensuring that TEE probes are housed in a sterile environment, cleaned after each exam and sterilized appropriately. A TEE probe cleaning mechanism has been approved by the clinical processing division (CPD) department at the University of Pennsylvania and will be housed in a sterile cabinet provided by the respiratory therapy (RT) department in the CTICU.
In addition to data monitoring and collection review the two PIs of the study will review and provide continuous process improvement in study processes. If any items are found that need to be updated, the IRB will be notified immediately.
10.1.7 Clinical Monitoring
The study PI and Co-PI will be responsible for ensuring the ongoing quality and integrity of the research study. Independent monitors will be assigned to conduct routine data safety and quality monitoring procedures.
The sponsor-investigator Dr. Usman and Dr. Gutsche will permit direct access for the study monitors and appropriate regulatory authorities to the study data and to the corresponding source data and documents to verify the accuracy of these data. Independent monitoring of the clinical study for clinical protocol and IDE application compliance will be conducted by University of Pennsylvania pre-identified data safety monitoring board (DSMB)
Our local DSMB will confirm that study activities are in compliance with the approved protocol and applicable regulatory authorities (FDA, IRB, local and State regulations).
The DSMB as well as the clinical emergencies committee will include Anesthesiology Associate professor and head of the Clinical Emergencies Committee (CEC) and nurse practitioner Kristen Welsh NP as well as code team nurse practitioner Stacie Neecfie NP. They will review and adjudicate serious and unexpected adverse events independently from the PI and co investigators.
Frequency of safety checks will occur:
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After IRB approval
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As soon as possible after the first subject is enrolled
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During the study data collection phase
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After the last subject has completed his/her participation in the study
This monitoring schedule may be revised based on the following considerations:
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Accrual rate
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Protocol deviations or non-compliance with regulatory authorities
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Magnitude of data corrections required
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Study stage (e.g. start-up or follow-up)
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Complexity of the trial
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Request (IRB, Investigator, other etc.)
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DSMB recommendation
The DSMB will evaluate the study quarterly, at a minimum, in a targeted on-site fashion. The sponsor-investigator will permit direct access to the study monitors and appropriate regulatory authorities to the study data and to the corresponding source data and documents to verify the accuracy of these data.
Primary responsibilities of the monitors will include verifying the following:
- Investigator qualifications
- Facilities and equipment
- Storage, dispensing and disposition of investigational products
- Protocol compliance
- Informed consent
- Training and delegation of authority
- Subject eligibility
- Recruitment, screening and enrollment
- Verification of data and data clarification
- Adverse event reporting
- FDA correspondence – Provided quarterly as minutes
- Deviations
10.1.8 Quality Assurance and Quality Control
This study will be performed at a single center. We will perform internal quality management of study conduct, data and biological specimen collection, documentation and completion. An individualized quality management plan will be developed to describe a site’s quality management.
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC checks that will be run on the database will be generated. Any missing data or data anomalies will be communicated to the site(s) for clarification/resolution. In this particular study we will run quality control metrics on the Redcap data form to ensure timely entry of code data, echocardiographic data and imaging upload. Data entry beyond 14 days will be noted and reported to the study PI.
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is conducted and data are generated and neurological screening scores are collected, documented (recorded), and reported in compliance with the protocol, International Conference on Harmonization Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)).
The investigational site will provide direct access to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. The study PI and co investigators will screen data for quality control and quality assurance. Key areas include timely and accurate data entry in echocardiography reports, timely and accurate data entry for code sheets from the medical record, and timely and accurate follow up data for survival. This granular data will be collected and maintained by the research coordinators of the study.
10.1.9 Data Handling and Record Keeping
10.1.9.1 Data Collection and Management Responsibilities
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported.
The investigator-sponsor will maintain records in accordance with Good Clinical Practice guidelines; to include:
- FDA correspondence related to the IDE application and investigational plan; including copies of submitted Form FDA 3500 A, supplemental IDE applications, current investigator lists, progress reports, notice of device recall or disposition, and failure to obtain informed consent reports;
- IRB correspondence (including approval notifications) related to the clinical protocol; including copies of adverse event reports and annual or interim reports;
- Current and past versions of the IRB-approved clinical protocol and corresponding IRB-approved consent form(s)
- Signed Investigator’s Agreements and Certifications of Financial Interests of Clinical Investigators;
- Curriculum vitae (investigator-sponsor and clinical protocol sub-investigators);
- Certificates of required training (e.g., human subject protections, Good Clinical Practice, etc.) for investigator-sponsor and listed sub-investigators;
- Normal value(s)/range(s) for medical/laboratory/technical procedures or tests included in the clinical protocol;
- Instructions for on-site preparation and handling of the investigational device and/or study treatment or diagnostic product(s), and other study-related materials (i.e., if not addressed in the clinical protocol);
- Decoding procedures for blinding of month
- Consent forms
- Code sheets
- Subject enrollments
- EFIC documentation and data analysis
- Public disclosure forms
- Interim results
- Follow up forms
- Audio files
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of data. Data recorded in the electronic case report form (eCRF) derived from source documents should be consistent with the data recorded on the source documents.
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions data) and clinical laboratory data will be entered into Penn Redcap, a 21 CFR Part 11-compliant data capture system provided by the PennVault and PennCTMS as well as Penn EPIC integrated Redcap. The data system includes password protection and internal quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source documents.
Data analyses will be carried out using SAS (version 9.3 or later), Stata (version 11 or higher), Microsoft Excel (2021) or R (version 3.2 or later).
All data files are backed up to a remote location on a daily basis, and can be restored by designated data management personnel in case of system failures or power outages. Access to our system by unauthorized entities is closely monitored. The RedCap system automatically includes a data dictionary and complete specifications with regard to data type (e.g., numeric, character, dates, ICD-10 codes, other).
Data will be collected through Penn Redcap forms. Data will also be uploaded to a secure site that is maintained by the University of Pennsylvania called the clinical trials management software (CTMS) and the PennVault. The PennVault is a location where secure documents can be stored. External and internal audit mechanisms are built in to allow for reviewers to check the progress of the study and monitor SAE and AE. All IHCA codes at HUP have a nurse documenting on a live code sheet. This sheet is subsequently uploaded into the EPIC chart. The RescueTEE report will be completed by the clinician performing the examination and then will be transferred over after the event. A master list containing PHI and subject ID numbers separate from any data forms, electronically. This account will be restricted to IRB approved researchers only.
Other forms that will be collected in the Redcap will be regarding survival information, demographic information, and also if “Visit 1” which refers to follow up formal TEE/TTE if completed in the ICU for those patients surviving the initial cardiac arrest. Direct responsibility for IDE documentation and handling will be done by Alieksei Basatiski research coordinator in the Department of Anesthesiology, as well as the clinical research coordinator for the trial Samantha Stein. Ultimately, all records will be held through the study investigator-sponsors Dr. Asad Usman and Dr. Jacob Gutsche.
Study participation will be documented in plain generic terms through as statement that will be placed in the EPIC electronic medical record. This will read “Patient XX has been randomized and placed in the Rescue Transesophageal Echocardiography for in-Hospital Cardiac Arrest (ReTEECA) trial and placed into one of two arms: Conventional CPR or Echo CPR. Randomization disclosure is possible if clinically necessary. Please contact study PI Asad Usman for this information. Any complications will be recorded and disclosed to the care team immediately.”
10.1.9.2 Study Records Retention
Study documents should be retained for a minimum of 2 years after the last approval of a marketing application in an International Conference on Harmonization (ICH) region and until there are no pending or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical development of the study intervention. These documents should be retained for a longer period, however, if required by local regulations. No records will be destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform the investigator when these documents no longer need to be retained.
Screening records for all IHCA subjects will be maintained. Patient information will be de-identified by software-based imaging techniques when imaging is analyzed. This encryption tool is available in all imaging-based storage systems. Imaging will be erased 5 years after the end of the study period.
10.1.10 Protocol Deviations
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on Harmonization Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a result of deviations, corrective actions are to be developed by the site and implemented promptly.
These practices are consistent with ICH GCP:
- 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3
- 5.1 Quality Assurance and Quality Control, section 5.1.1
- 5.20 Noncompliance, sections 5.20.1, and 5.20.2.
It is the responsibility of the site investigator to use continuous vigilance to identify and report deviations within 7 working days of identification of the protocol deviation, or within 7 working days of the scheduled protocol-required activity. Protocol deviations must be sent to the reviewing Institutional Review Board (IRB) per their policies. The site investigator is responsible for knowing and adhering to the reviewing IRB requirements. Further details about the handling of protocol deviations will be included in the MOP.
10.1.11 Publication and Data Sharing Policy
This study will be conducted in accordance with the following publication and data sharing policies and regulations: National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the published results of the ReTEECA trial research. It requires scientists to submit final peer-reviewed journal manuscripts to the digital archive PubMed central upon acceptance for publication. At the time of submission for this protocol there currently no NIH funding for this project. However, in the event of NIH funding, compliance with NIH funding publication policy will be followed.
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial has been registered at ClinicalTrials.gov as trial NCT04220619 and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.
This study will be used for several journal article publication and also help drive departmental policy in the Department of Anesthesiology and Critical Care – Cardiovascular Anesthesiology and cardiothoracic ICU section for POC TEE. We intend to submit separate work on the EFIC results including de-identified results from the clinician interviews and surveys, de-identified results from the patient and family interviews and surveys, and also bioethics works on EFIC and consent related topics in cardiac arrest. We intend to also submit for several research grants both through the NIH and also through the AHA.
After the conclusion of the ReTEECA trial period of 3 years the data is expected to be analyzed and published in various medical journals. We also intended to distribute the results of our study on the Penn Anesthesiology webpage. We will revisit community consultation both in the healthcare worker and non-medical layperson cohort with disclosure of the results of the ReTEECA trial. Public dissemination will occur through local and national broadcast (e.g., presentations, press releases). In particular we will post our results online including the Anesthesiology website and will follow up with our audio blog interviews and the Resuscitative TEE working group. Individuals who participated and have contact information will be informed of the results by a study coordinator.
10.1.12 Conflict of Interest Policy
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be required to have such conflicts managed in a way that is appropriate to their participation in the design and conduct of this trial.
10.2 Abbreviations
AE
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Adverse Event
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ANCOVA
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Analysis of Covariance
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CFR
|
Code of Federal Regulations
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CLIA
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Clinical Laboratory Improvement Amendments
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CMP
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Clinical Monitoring Plan
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COC
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Certificate of Confidentiality
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CONSORT
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Consolidated Standards of Reporting Trials
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CRF
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Case Report Form
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DCC
|
Data Coordinating Center
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DHHS
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Department of Health and Human Services
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DSMB
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Data Safety Monitoring Board
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DRE
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Disease-Related Event
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EC
|
Ethics Committee
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eCRF
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Electronic Case Report Forms
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FDA
|
Food and Drug Administration
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FDAAA
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Food and Drug Administration Amendments Act of 2007
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FFR
|
Federal Financial Report
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GCP
|
Good Clinical Practice
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GLP
|
Good Laboratory Practices
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GMP
|
Good Manufacturing Practices
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GWAS
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Genome-Wide Association Studies
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HIPAA
|
Health Insurance Portability and Accountability Act
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IB
|
Investigator’s Brochure
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ICH
|
International Conference on Harmonisation
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ICMJE
|
International Committee of Medical Journal Editors
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IDE
|
Investigational Device Exemption
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IND
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Investigational New Drug Application
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IRB
|
Institutional Review Board
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ISM
|
Independent Safety Monitor
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ISO
|
International Organization for Standardization
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ITT
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Intention-To-Treat
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LSMEANS
|
Least-squares Means
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MedDRA
|
Medical Dictionary for Regulatory Activities
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MOP
|
Manual of Procedures
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MSDS
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Material Safety Data Sheet
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NCT
|
National Clinical Trial
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NIH
|
National Institutes of Health
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NIH IC
|
NIH Institute or Center
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OHRP
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Office for Human Research Protections
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PI
|
Principal Investigator
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QA
|
Quality Assurance
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QC
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Quality Control
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SAE
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Serious Adverse Event
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SAP
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Statistical Analysis Plan
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SMC
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Safety Monitoring Committee
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SOA
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Schedule of Activities
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SOC
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System Organ Class
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SOP
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Standard Operating Procedure
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UP
|
Unanticipated Problem
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US
|
United States
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