Investigator Manual January 23, 2014

Transcription

1 Investigator Manual January 23, 2014

2 Investigator Manual Page 2 of 60 Table of Contents What is the purpose of this manual?... 4 What is Human Research?... 4 What is the Human Research Protection Program?... 4 What is Exempt Human Research?... 5 What training do my staff and I need to conduct Human Research?... 5 Who can be listed as a Principal Investigator?... 7 What financial interests do my staff and I need to disclose in order to conduct Human Research?... 8 How do I submit new Human Research to the IRB?... 9 How do I complete the AEHN-211- FORM: Application for Human Research? How do I write a Human Research Protocol? How do I complete the AEHN FORM: AEHN Protocol/ Summary? How do I create a consent/assent document? How do I submit a Humanitarian Use Device application to the IRB for review? Non-AEHN researchers who want access to AEHN resources What other organizational approvals may be needed in addition to IRB approval? Is there an application fee for IRB submissions? What are the different regulatory classifications that research activities may fall under? What is the typical turnaround time on IRB review? What are the decisions the IRB can make when reviewing a protocol? How does the IRB decide whether to approve Human Research? What will happen after IRB review? What are my obligations as an investigator after IRB approval? How do I conduct the informed consent process? How do I document consent? When is a witness required for informed consent for research? How do I obtain consent for adults who are unable to consent for themselves? How do I obtain parental/legal guardian consent for children? When can minors give legally effective informed consent? What types of changes to an approved study require submission of a modification request to the IRB? How do I submit for continuing review? What problems or events need to be promptly reported to the IRB? How do I close out a study? How long do I keep records? What if I need to use an unapproved drug or device in a life-threatening situation and there is no time for prior IRB review? What if I plan to conduct research with or at another site which has an IRB? Do I have to submit to both the AEHN IRB and the IRB where the research is being conducted? Does the IRB conduct audits? How do I get additional information and answers to questions? Appendix A-1 Additional Requirements for DHHS-Regulated Research

3 Investigator Manual Page 3 of 60 Appendix A-2 Additional Requirements for FDA-Regulated Research Appendix A-3 Additional Requirements for Clinical Trials (ICH-GCP) Appendix A-4 Additional Requirements for Department of Defense (DoD) supported research Appendix A-5 Additional Requirements under Department of Education for Projects Involving Student Records... 58

4 Investigator Manual Page 4 of 60 What is the purpose of this manual? This Investigator Manual is designed to guide investigators and study staff through policies and procedures related to the conduct of Human Research that are specific to Albert Einstein Healthcare Network (AEHN). General information regarding Human Research protections and relevant federal regulations and guidance is incorporated into the required human protections training. For additional information see page 5: What training do my staff and I need in order to conduct Human Research?. What is Human Research? AEHN follows the regulatory definitions of Human Subject Research that are defined in DHHS regulations at 45 CFR (d) and 45 CFR (f) and as defined in FDA regulations at 21 CFR (c), 21 CFR (e), and 21 CFR 812.3(p) and described in the Human Research Protection Program Plan located in the IRB Documents section of the IRB Forms folder on the shared drive. An algorithm for determining whether an activity is Human Research can be found in the HRP WORKSHEET: Human Research Determination, located in the IRB Forms folder on the shared drive. Use this document for guidance as to whether an activity meets either the DHHS or FDA definition of Human Research, keeping in mind that the IRB makes the ultimate determination in questionable cases as to whether an activity constitutes Human Research subject to IRB oversight. Human Research must not be conducted without prior IRB review and approval (or an IRB determination that the Human Research is Exempt). If you have questions about whether an activity is Human Research, contact the IRB office and they will provide you with a determination. If you wish to have written determination of the IRB decision, provide a written request to the IRB office. Investigators are strongly encouraged to maintain electronic Word documents of all information submitted to the IRB in case revisions are required. In addition, an investigator must retain a hard copy or electronic version of the signed and dated submission as well as the IRB s notification letters as part of the regulatory documentation. What is the Human Research Protection Program? The HUMAN RESEARCH PROTECTION PROGRAM PLAN located in the IRB Forms folder on the shared drive provides an outline of AEHN s comprehensive system to ensure the protection of the rights and welfare of participants in Human Research. It includes the following: The mission of the Human Research Protection Program. The ethical principles that the organization follows governing the conduct of Human Research. The applicable laws that govern Human Research.

5 Investigator Manual Page 5 of 60 Definition of when the organization becomes engaged in Human Research and when someone is acting as an agent of the organization conducting Human Research. The roles and responsibilities of individuals within the organization. This system is comprised of AEHN leadership, the staff of the Office of Research and Technology Development (ORTD), the Institutional Review Board (IRB), investigators and their study staff and relevant departments and units. The document defines the activities that this organization considers to be Human Research and describes the roles and responsibilities of each of the above-named parties as well as AEHN s overall plan to protect participants in Human Research. What is Exempt Human Research? Certain categories of Human Research (e.g. many retrospective chart reviews) may be exempt from regulation but require an initial IRB review to make this determination. Investigators must obtain an IRB Exemption Determination letter prior to conducting Exempt Human Research. An algorithm to determining whether an activity is exempt from IRB approval can be found in HRP WORKSHEET: Exemption Determination. What training do my staff and I need to conduct Human Research? All investigators and study staff are responsible for reviewing the HUMAN RESEARCH PROTECTION PROGRAM PLAN as part of their initial orientation to human subject research at AEHN. Investigators, research staff and others who are involved in the design, conduct, or reporting of the Human Research, and have (a) direct interaction with participants and/or (b) access to identifiable data must complete the online Collaborative Institutional Training Initiative (CITI) human subjects research online training program. The CITI site can be accessed at This training is valid for a two-year period, after which time a refresher CITI course must be completed. Please note that all members of the research team are required to complete this training and achieve an overall score of 80% or greater. Upon completing the course, a notice of completion and the cumulative score will be sent electronically by CITI administration to the Research Compliance Officer. It is recommended that you print and retain a paper copy of the certificate of completion for your records. If you have completed the CITI course at another institution, you will need to log in to the CITI website and affiliate yourself with Albert Einstein Healthcare Network. For additional information on registering and affiliating in CITI, please contact the Research Compliance Officer, Roberta Costello at or bcostell@einstein.edu.

6 Investigator Manual Page 6 of 60 Who is considered research personnel required to complete human research subject protection CITI training? Refer to your own institution s HRPP for requirements. NO Are you an AEHN employee/authorized volunteer or in direct contact with AEHN patients and/or patient medical information OR using the AEHN IRB as your IRB of record for the proposed research study? Complete CITI training YES YES Are you listed as the Principal Investigator, Co- Investigator, Sub-Investigator, Study Coordinator or Research Assistant on the proposed research study? Complete CITI training YES NO Will you be directly involved in the screening, consenting and/or enrolling of potential research subjects? Complete CITI training YES NO Will you be involved in the abstracting of medical data from identifiable patient medical records for the proposed research study? NO Complete CITI training YES Will you be conducting an experimental medical procedure (i.e. a procedure not considered standard practice for this patient population at this institution) for the proposed research study (e.g. validating a new assessment tool, implanting an experimental device)? NO Clinical Informant training recommended* YES Are you a treating clinician whose involvement in research is limited to providing data on your opinion regarding clinical encounters involving standard of care tests and procedures only and whose role does not warrant professional recognition on publications or presentations related to the research? NO No CITI training required.

7 Investigator Manual Page 7 of 60 Please note: IRB approval will not be granted for protocols in which one or more research team members have not completed human research protections training. Ancillary support staff: Clinicians such as phlebotomists, unit nurses, radiology technicians, medical technologists, therapists, etc. typically are not considered part of the research team if their role is limited to performing routine/standard medical procedures on a research subject. Therefore, they would not be required to complete the CITI training Medical Residents and Students: If conducting a research study, residents and/or medical students are required to complete CITI training if one of the criteria on the chart above is met. * Clinical Informants: In some cases, a treating clinician may be asked to provide data for research that is limited to their opinions of clinical encounters with their own patients. These clinicians would not be listed on the protocol as a member of the research team. However, since they are contributing to the collection of data for research, it is recommended that they become familiar with the basic principles governing Human Research. Clinical Informant training is available through the CITI website at It is recommended that all clinicians who meet the criteria for Clinical Informant indicated in the chart above complete this training prior to participating in any Human Research and achieve an overall score of 80% or greater. Upon completing the course, a notice of completion and the cumulative score will be sent electronically by CITI administration to the Research Compliance Officer. It is recommended that you print and retain a paper copy of the certificate of completion for your records. For additional information on registering and affiliating in CITI, please contact the Research Compliance Officer, Roberta Costello at or bcostell@einstein.edu. The Office of Research and Technology Development is available to answer questions and provide specific training for investigators and study staff upon request. Please contact the Research Compliance Officer at (215) for more information on how to obtain additional education/training. Who can be listed as a Principal Investigator? The principal investigator must be one of the following: 1) a member of the medical or professional staff (salaried or voluntary) or 2) an allied professional of any of the entities of Albert Einstein Healthcare Network. If the principal investigator is a medical student, fellow, resident, courtesy, or associate medical staff member, a co-investigator who meets the criteria in the paragraph above must be included on the protocol.

8 Investigator Manual Page 8 of 60 What financial interests do my staff and I need to disclose in order to conduct Human Research? Individuals involved in the design, conduct, or reporting of research are required to disclose the financial interests listed in the Conflict of Interest Screening Form available in the IRB Forms folder on the shared drive (under Financial Disclosure Policies and Forms/non-PHS regulated research) for each study, unless you are involved in a study that is funded through a grant or cooperative agreement from a Public Health Service (PHS) agency (e.g. NIH, SAMHSA, OPHS, HIS, HRSA, FDA, CDC and AHRQ) or other agency that has adopted the PHS disclosure requirements (e.g. American Heart Association and American Cancer Society). The Conflict of Interest Screening Form must be submitted: On submission of a protocol for initial IRB review When a new staff member is added to a study At least annually as part of continuing IRB review Within 30 days of discovering or acquiring (e.g. through purchase, marriage, or inheritance) a new financial interest. Investigators and their staff involved in PHS-regulated research must complete the Financial Disclosure Form available on the shared drive in the IRB Forms folder (under Financial Disclosure Policies and Forms/PHS-regulated research). This form must be submitted: Upon submission of a grant application to any agency covered under PHS regulations or AEHN s execution of a PHS-funded cooperative agreement/ sub award agreement or other agreement for PHSregulated Research if a current form is not already on file in the IRB office Annually thereafter Whenever circumstances arise that either constitutes a new Financial Interest or changes the facts applicable to a previously disclosed Financial Interest. Such a report must be submitted within 30 days of the change in circumstance. Addition of a new research staff member to an ongoing project who does not have a Financial Disclosure Form on file During the course of a given year, individuals who have an up-to-date Financial Interest Disclosure Form on file with the IRB office are required to either verify that the disclosures are up to date using a Verification Form or submit an updated Financial Disclosure Form under the following circumstances: Submission of a new PHS- regulated application or acceptance of a new PHS-regulated grant award Submission of a new non-phs regulated research application to the

9 Investigator Manual Page 9 of 60 Institutional Review Board (IRB) Within 30 days of obtaining a new Financial Interest or change to a previously disclosed Financial Interest Addition of a new Investigator to ongoing research studies It is the responsibility of the Principal Investigator to ensure that each individual working on the research project submits the Verification Form and timely updates to a previously-submitted Financial Disclosure Form as required. Conflict of interest training must be completed as part of the human subjects training prior to initiating any human research activity, at least every two years, and immediately when: Financial conflict of interest policies are revised in a manner that changes investigator requirements. Non-compliant with financial conflict of interest policies and procedures Additional details can be found in the following policies: A Financial Disclosure Policy for Research and A0283 Financial Disclosure Policy for Investigators Involved in Research Subject to Public Health Service Regulations located in the policy and procedure database on E-net. How do I submit new Human Research to the IRB? Complete the AEHN FORM: Application for Human Research and the AEHN FORM: AEHN Protocol Summary located in the IRB Forms folder on the shared drive. Attach all requested supplemental and supporting documents (e.g. AEHN-201 -FORM: Contact Information and the appropriate financial disclosure form (see section above) for all research staff members, protocol, informed consent form, etc.), have the Application signed by the individuals listed in the form, and provide one original of all study documents to the IRB office. All financial disclosure forms should have been signed within 45 days of submission to the IRB. PLEASE NOTE: IRB approval letters will not be released if the required CITI human subjects research training for the investigator or any member of the research team has expired or will expire within 30 days of IRB approval. Investigators are strongly encouraged to maintain electronic Word documents of all information submitted to the IRB in case revisions are required. In addition, an investigator must retain a hard copy or electronic version of the signed and dated submission as well as the IRB s notification letters as part of the regulatory documentation.

10 Investigator Manual Page 10 of 60 How do I complete the AEHN-211- FORM: Application for Human Research? 1) Protocol Name Enter the full protocol name. If available, append in parentheses the cooperative group, sponsor protocol code or protocol number. 2) Investigator Provide the name and address for the person with overall responsibility for the conduct of the Human Research. There can only be one investigator with this overall responsibility. 3) Primary Contact Provide the name and address of the person who should receive a copy of all communications related to the Human Research. Leave blank if there is no contact other than the investigator. There can only be one contact. 4) Check whether the Human Research involves any of the following a) Appendix A: Check this box if the research involves departments other than the principal investigator s department For example, you are an investigator in the Department of Pediatrics and you are collaborating with someone in the Department of Medicine. Please note: the IRB expects the principal investigator to secure approval from ancillary departments prior to IRB submission. b) Appendix B: Check this box if the research involves external (non-aehn) sites and the research activities that are occurring at these sites are under the responsibility of the AEHN investigator For example, you are conducting research in a school, nursing home, or other external facility or site. c) Appendix C: Check this box if the research involves minors under the age of 18 years. d) Appendix D: Check this box if the research involves the use of drugs other than the use of approved drugs in the course of medical practice OR the use of approved drug(s) is the focus of the study. e) Appendix E: Check this box if the research involves the evaluation of the safety or effectiveness of a device OR a new use of an approved device. f) Humanitarian Use Device (HUD): Check this box if you and/or the sponsor are conducting a research study on the safety and effectiveness of a HUD. Otherwise, STOP completing this application and complete the FORM: Application for Humanitarian Use Device.

11 Investigator Manual Page 11 of 60 5) Approvals Required Prior to Initiating Research Check all additional approvals that are required and obtain the appropriate signature(s) if one or more of the following are included in your research: a) Use of drugs other than the use of approved drug(s) in the course of standard medical practice OR use of approved drug(s) is the focus of the study b) Therapeutic radiation OR diagnostic radiation being provided for research only and not as part of standard clinical care. c) The use of any biohazards (i.e. biological, chemical or recombinant DNA agents). d) Study will be initiated at MossRehab or involve resources from MossRehab (including staff, patients, equipment, etc.) 6) Funding Sources Select the appropriate funding type(s) and list all funding sources. For each, list the associated grant number, protocol number or award ID if known. 7) Names of all research personnel involved in the design, conduct, or reporting of the research List all personnel involved in the design, conduct, or reporting of the Human Research and their roles. This includes all co-investigators, sub-investigators, study coordinators, research assistants, residents, fellows, and collaborators who have a role in the design, conduct, or reporting of the Human Research and who have (a) contact with human participants or (b) access to identifiable data. Include external (non-aehn) collaborators only in the absence of local IRB review at the collaborating site. For each individual, complete the AEHN FORM: Contact Information if an individual does not already have a copy on file with the IRB and the appropriate financial disclosure form and include with the submission materials. Check the appropriate box(es) if the person will have contact with subjects or access to private identifiable data and/or whether the person will be involved in the consent process. REMINDER: All research personnel listed on the application form must have completed the required human subject protections online training (CITI). Research will not be approved if any members of the research team do not have current training. Approval letters will not be released if training expires within 30 days of IRB approval. 8) Departmental Review and Approval Have your department chairman review, sign and date the application.

12 Investigator Manual Page 12 of 60 9) Investigator Signature Personally sign and date the application. 10) Appendices a. Appendix A: Internal Departmental/Unit Approvals List all departments/units involved or affected by the Human Research other than the Principal Investigator s department/unit. This may include departments/units whose facilities, equipment, or personnel will be required during the conduct of the research. Provide the IRB with an acknowledgement from each listed department/unit stating that the department/unit (or affected personnel) is willing and able to contribute to the research. This acknowledgement may be in the form of an , letter or memo correspondence between the investigator and the affected department/unit or individual. b. Appendix B: External Site Approvals This appendix only applies if you are an investigator sponsoring your own multi-site research or the lead investigator overseeing multiple sites. List all external sites where the Human Research will be conducted (e.g. medical offices/clinics not part of AEHN) where the AEHN investigator is responsible for overseeing activities at that site. For each list name and contact information for the site. Provide the IRB with an acknowledgement from an authorized representative from each site stating that they have granted permission for you to conduct the Human Research. Indicate whether the site is/will be receiving federal funding from your grant. Also, indicate whether the site has an IRB, and if so, whether the site s IRB will review the Human Research or the site will rely on our IRB. Provide a copy of the written approval, e.g. IRB approval letter, from each site. If local approval is not available at the time of submission, a copy must be submitted to the IRB prior to implementing any study procedures at the external site(s). c. Appendix C: Children Have the investigator assess the risk/benefit information. Indicate if your research will include any children considered wards of the state. This would include children in the foster care system. d. Appendix D: Drugs List all drugs being used in the Human Research (FDA approved and non-fda approved). For each, indicate whether it has an IND number. For each drug with an IND number, ensure that the application includes one of the following: Sponsor protocol with the IND number; Communication from the sponsor with the IND number; or Communication from the FDA with the IND number.

13 Investigator Manual Page 13 of 60 If the study is IND exempt, provide either communication from the FDA or an explanation of how the IND exemption criteria are met (21 CFR 321.2). Submit a current package insert for each marketed drug involved in the Human Research if the drug is: 1) used off-label for research purposes; 2) used in combination with an investigational drug; OR 3) being studied as part of the research. e. Appendix E: Devices List all devices being evaluated for safety or effectiveness (FDA approved and non- FDA approved) or being used in a study inconsistent with FDA approved labeling (i.e. for a new use). For each device, indicate whether it has an IDE number or if the device is claimed to be a non-significant risk (NSR) and being submitted under the Abbreviated IDE requirements in 21 CFR 812.2(b). For each device with an IDE number, ensure that the application includes one of the following: Sponsor protocol with the IDE number; Communication from the sponsor with the IDE number; or Communication from the FDA with the IDE number If you are claiming your study involves a non-significant risk (NSR) device, provide either communication from the FDA or an explanation of how the IDE exemption criteria are met (21 CFR 812.2(b)). PLEASE NOTE: The AEHN FORM: Application for Human Research is considered a supplemental document to your protocol and may require updating during the course of the study. If human subjects protections items change during the course of the study (e.g. adding new research personnel), you will be to submit an updated AEHN FORM: Application for Human Research. For this reason, it is expected that you will maintain an electronic version of this document and submit a revised version with any of the following forms when applicable: modifications and/or modifications to secure approval. Further information on how to submit a modification of approved Human Research is addressed in the section titled How do I submit a modification?. 11) Documents Include any of the listed supporting documents with the corresponding version date or indicate N/A if not applicable for the Human Research. You are not required to submit copies of case report forms for industry-sponsored studies. For any research that includes a waiver of written informed consent, you will need to submit the data collection forms that will be used by the research staff for collecting or abstracting data. All data collection and educational materials must include a version date and/or version number. ADVERTISEMENT REMINDER: The final versions (including site contact information) of any material that will be seen, heard, or provided to potential subjects

14 Investigator Manual Page 14 of 60 must receive IRB review and approval prior to use. This includes, but is not limited to, video/audio recordings of radio/tv ads, flyers and website postings advertising the study, subject education materials/brochures on the study, information sheets, etc. All advertising and recruitment material must include a version date and/or version number. CONSENT REMINDER: Consent documents must include a version date and/or version number. Include any foreign translations of informed consent documents. If foreign language consents will be provided to AEHN patients to read, the foreign translation must include a signed certification of translation by a certified translator. The staff from Language and Cultural Services can provide certifications of translations for AEHN departments if needed. PHONE SCRIPTS REMINDER: If you are conducting consent over the phone and do not have a corresponding written consent form that the potential subject will have to review and sign for study enrollment, a copy of the phone script must be submitted to the IRB for review and approval. How do I write a Human Research Protocol? If you are an investigator designing your own Human Research study, you will be expected to create and submit a protocol for the IRB to review. The TEMPLATE: Human Research Protocol is available in the IRB Forms folder (under Human Research Protection Program IRB Documents) to assist you in protocol development and writing. This template includes the sections the IRB reviewer(s) expect to see included as a minimum in every protocol. Here are some key points to remember when developing a protocol: The AEHN FORM: AEHN Protocol/Summary serves as the protocol document for investigators who need to develop their own Human Research Protocol for submission to the IRB. If you are a new investigator, it is recommended that you work with a faculty advisor or mentor in developing your protocol. When writing a protocol, always keep an electronic copy. You may need to modify this copy and submit it to the IRB with tracked changes, if future amendments/changes need to be made to the protocol. Modify the version date with each modification to the protocol. Note that, depending on the nature of your research (e.g. retrospective chart review), certain sections of the protocol template (e.g. data safety monitoring) may not be applicable. Mark N/A in any sections in the protocol form that are not applicable to your type of Human Research. If you are conducting community-based participatory research, you may contact the IRB Office for information about: o Research studies using a community-based participatory research design o Use of community advisory boards

15 Investigator Manual Page 15 of 60 o Use of participant advocates o Partnerships with community-based organizations If you believe your activity may not be Human Research, contact the IRB Office prior to developing your protocol. Examples of activities that may not qualify as research include: o Quality Improvement Activities - Routine Quality Improvement (QI) means systematic, data-guided activities designed to bring about immediate, positive changes in the delivery of health care in particular settings. QI involves deliberate actions to improve care, guided by data reflecting the effects (e.g., types of practical problem solving; an evidence-based management style; the application of science of how to bring about system change; review of aggregate data at the patient/ provider/unit/ organizational level to identify a clinical or management change that can be expected to improve care). QI is generally not considered research however, QI activities can be research if they are also intended to contribute to generalizable knowledge. For more information on what types of activities may qualify as QI please contact the Chief Quality Officer or designate at o Program Evaluation Activities When data are gathered on a clinical program for the sole purpose of improving its operation over time and not to address a more general issue, it falls within the category of program evaluation. This activity is not considered research and does not require review and approval by the IRB. How do I complete the AEHN FORM: AEHN Protocol/ Summary? This form must include the entire study plan. Its purpose is to provide IRB members with sufficient information about the research in order to conduct a substantive review. If a separate protocol document already exists, reference the section and page number where the information can be found. DO NOT DUPLICATE INFORMATION THAT ALREADY EXISTS IN OTHER FORMS. For multi-site research, keep in mind that many of the questions on this form are looking specifically for what will be happening locally to protect AEHN participants. 1) Project Objectives and Hypotheses: Describe the purpose, specific aims or objectives of the Human Research. State the hypotheses to be tested. 2) Background/Significance of Research: Provide the scientific or scholarly background and rationale for the Human Research based on the existing literature. Describe the gaps in current knowledge and any relevant preliminary data. Explain the significance of the Human Research and how

16 Investigator Manual Page 16 of 60 it will add to or enhance existing knowledge. Describe the importance of the knowledge expected to result. 3) Setting of the Human Research Select the AEHN locations where the Human Research will be conducted. Indicate if the investigator will be overseeing the research at a non-aehn site. 4) Resources available Indicate total number of participants that are planned to be enrolled by the AEHN investigator. The IRB defines a participant as enrolled when any of the following conditions apply: 1) the participant or legally authorized representative gives consent to participate and signs a consent document 2) in cases where written consent is waived, the participant gives verbal consent to participate in the study OR completes a research task (e.g., completion of a questionnaire, interview, survey, etc.) 3) data on participant is collected as part of chart review for use in data analyses (Note: when reviewing charts for screening purposes prior to enrollment, data should not be collected from chart, only viewed to determine eligibility for research). Complete the other sections on the form by checking the appropriate boxes, filling in the information requested or referencing the page numbers in the protocol or other supporting documents where the relevant information can be found if appropriate. If a section is not appropriate to your protocol, indicate N/A. If you are unsure which information the IRB is requesting when completing the form, you are encouraged to contact the IRB office for assistance at (215) How do I create a consent/assent document? Typically, the sponsor of the Human Research will provide a sample informed consent/assent documents which provide the potential subject with important information to consider before deciding whether or not to participate in the Human Research. You are expected to ensure the sponsor-provided informed consent/assent documents have the required elements per regulations, has local contact information, includes the AEHN IRB required language and, for clinical trials, includes Good Clinical Practice required items. Prior to submitting the informed consent document to the IRB, refer to Section 7 of the IRB s HRP WORKSHEET: Criteria for Approval and Additional Considerations, located in the IRB Forms folder on the shared drive (under Human Research Protection Program IRB Documents/IRB Review Worksheets and Checklists) to ensure that all of the required and all additional appropriate elements of informed consent disclosure are present. If you are not working with a sponsor or a sample informed consent/assent document is not provided, you will need to create your own forms. Use the TEMPLATE: Consent Form to create a consent document and/or the TEMPLATE: Assent Form to create

17 Investigator Manual Page 17 of 60 an assent document for Human Research. These templates are located in the IRB Forms folder on the shared drive (under Human Research Protection Program IRB documents). You must include a local version (AEHN/Belmont/Moss/MRRI) date in the header/footer on your informed consent/assent document to ensure that you always use the most recent version approved by the IRB when consenting subjects and/or getting assent from children. The local version date must be updated each time the consent is modified. Always keep an electronic copy of the final IRB approved consent/assent documents. You may need to modify these documents and submit them to the IRB with tracked changes if future amendments/changes need to be made to either document. If you have questions on creating your informed consent/assent document or other related consent documents such as short forms, information sheets, or telephone scripts, please contact the IRB office for assistance at (215) How do I submit a Humanitarian Use Device application to the IRB for review? The definition of a Humanitarian Use Device (HUD) is a device that is intended to benefit patients in the treatment and diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year. The use of a HUD under an approved use for medical treatment only is not research. However, the FDA requires that the HUD be used under IRB approval. Full board review is required for the initial review. Continuing review by the IRB is also required for HUD activities. If you are using the HUD consistent with FDA approved labeling and indication(s) to treat or diagnose patients only then submit the FORM: Application for Humanitarian Use Device, located under the IRB Forms folder on the shared drive. For continuing review you will use the FORM: Continuing Review Progress Report for Humanitarian Use Device (HUD) and for submitting modifications the FORM: Modification of Approved Humanitarian Use Device (HUD). These forms are located under the IRB Forms folder on the shared drive. If you are using a Humanitarian Use Device (HUD) consistent with FDA approved labeling and indication(s) to treat or diagnose patients only, you are NOT required to submit a research informed consent document with your application for IRB review. However, you are expected to include a copy of the patient information sheet or brochure that will be provided to the patient describing the device and the potential risks and benefits. Physicians using a HUD are required to submit medical device reports to the IRB (21 CFR , , and (a)). Among these requirements, manufacturers must submit reports to FDA and the IRB whenever a HUD may have caused or contributed to a death or serious injury, or has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur (21 CFR and

18 Investigator Manual Page 18 of (a)). Physicians must submit reports to the FDA, the IRB, and the manufacturer whenever a HUD may have caused or contributed to a death, and must submit reports to the manufacturer (or to FDA and the IRB if the manufacturer is unknown) whenever a HUD may have caused or contributed to a serious injury (21 CFR and (a)). Serious injury means an injury or illness that (1) is life-threatening, (2) results in permanent impairment of a body function or permanent damage to a body structure, or (3) necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure (21 CFR 803.3). PLEASE NOTE: Just because the IRB has approved the use of a HUD to treat or diagnose patients does not mean that the IRB has approved investigational use of the HUD. When a HUD is used in a clinical investigation (i.e. collection of safety and effectiveness data) whether for its FDA-approved indication(s) or for a different indication, this is considered research. You must complete the FORM: Application for Human Research and all other research requirements will apply. Physicians and any other staff involved in the use of a HUD are encouraged to watch a video produced by the FDA that is specific to HUD requirements. The link to the training is as follows: Presentation: Institutional Review Board: Humanitarian Use Devices (HUDs) Non-AEHN researchers who want access to AEHN resources Albert Einstein Healthcare Network (AEHN) has an interest in supporting collaborative research with other institutions. In the interest of supporting this activity, the following is a standard method for external researchers to petition AEHN for access to AEHN faculty, staff, and/or patients as research participants in the absence of a formal subcontract or subaward agreement. External researchers are defined as researchers who are not employed at an AEHN facility or are not members of the AEHN Medical Staff. Please note: some AEHN departments have an internal review process for any research involving their department and/or patients. The external researcher is responsible for contacting the department(s) involved to get more information on any departmental review/approval procedures that may be required. External researchers must also request permission from the Director of the Office of Research and Technology Development (ORTD) to conduct research involving human participants at AEHN. The decision to approve the request will be balanced against the potential benefit of the study, AEHN s ongoing research needs and activities, and the quality of the research. In order to initiate this review, external researchers must submit a one to two page proposal to the Director, ORTD. Proposals should include: Purpose of study

19 Investigator Manual Page 19 of 60 Proposed study subject specifications and sampling plan (this sampling plan must not conflict with any ongoing projects at AEHN) Timing of study Method of recruitment and data collection Description of how results will be used Reason why AEHN facility should be a study/recruitment site including any potential benefits to AEHN and/or AEHN subjects Description of activities that will take place at an AEHN facility CV s of principal investigator and any other non-aehn individuals who would have contact with AEHN subjects Source of funds for study For external researchers on studies where AEHN s involvement is limited to posting a recruitment flyer or handout at an AEHN facility must provide a copy of the flyer/handout to be used along with a copy of the IRB approval letter from their home institution and a copy of the protocol. These documents must be reviewed and accepted by the Director, ORTD and the chairman/administrator for the area where the documents will be posted/distributed prior to use at AEHN. For studies where research activities such as approaching patients for recruitment, consenting and/or data collection will occur at an AEHN facility, permission to conduct the research at AEHN will be granted contingent on approval from the department chairman for the area where the patients will be recruited. In addition, the external researcher must identify an AEHN faculty or staff member who can serve as the AEHN investigator for the duration of the research project. The external researcher will be responsible for coordinating submission of a proposal to AEHN s Institutional Review Board (IRB) for review and approval through the AEHN investigator. The AEHN investigator must be a full time, regular status employee with relevant experience. Medical students, residents, fellows and/or visiting faculty are not eligible to serve as AEHN investigators unless they have a full-time faculty member as a co-investigator. Due to potential conflicts of interest, the AEHN IRB chair and ORTD staff members are not eligible to serve as AEHN investigators. Potential AEHN investigators must receive permission from their department chairman before agreeing to participate. The AEHN investigator should be able to answer questions about the project, serve as the contact for questions or concerns about the research, be responsible for submitting the proposal to the AEHN IRB, and if approved, oversee all research activities occurring at AEHN related to the project to ensure compliance with applicable policies and procedures. For research activities that qualify as exempt from IRB review, documentation must be provided from the home institution that exempt status has been granted along with a copy of the study proposal and the required AEHN IRB forms. For such activities, the chair of the AEHN IRB shall review the appropriateness of the exempt status prior to approval to conduct the research at AEHN.

20 Investigator Manual Page 20 of 60 For research activities that require expedited or full-board IRB review, documentation must be provided from the home institution that IRB approval to conduct the research has been granted. In addition, IRB review at AEHN is required. The AEHN investigator is responsible for submitting the proposal to the AEHN IRB using the forms required per AEHN IRB policy. The external researcher is responsible for collaborating with the AEHN investigator to address any concerns the AEHN IRB has about the research. Approval must be granted by the AEHN IRB prior to conducting any research activities at an AEHN facility. The AEHN IRB has the option to accept the IRB approval from the external researcher s home institution. However, this decision will be made on a caseby-case basis. Research activities that require access to patients personal health information (PHI) prior to consent must receive a partial waiver of authorization from the Privacy Officer. In addition, all studies that require a waiver of consent/authorization must also be reviewed and approved by the AEHN Privacy Officer prior to initiation of any study activities. External researchers who will be coming on-site to conduct study activities at an AEHN facility, including subject recruitment, consenting, and/or data collection, must go through the AEHN Volunteer Office to become an authorized volunteer and provide documentation of current human subjects training prior to participating in any research activities at an AEHN facility. Whenever possible, any costs incurred by AEHN due participation in an approved project should be reimbursed. Additionally, AEHN requires that copies of the data collected at an AEHN facility as well as any written products of approved research activities, including reports including a summary of the results and publications be provided to ORTD. What other organizational approvals may be needed in addition to IRB approval? Depending on the nature of the research, certain additional reviews and approvals may be required in addition to any department-level approvals. These additional approvals may include: Biosafety Committee Radiation Safety Committee Research Conflict of Interest Committee Privacy Officer Is there an application fee for IRB submissions? The IRB office will invoice a fee for all industry-sponsored (research sponsored by forprofit organizations) study submissions requiring convened IRB review. There is also a fee for continuing review and protocol modifications for these studies. The initial

21 Investigator Manual Page 21 of 60 submission fee for convened review is $1750. All continuing reviews and protocol modifications are $500. These fees are charged to the sponsor or their designate. Invoices are sent to the appropriate party following the IRB review. As an investigator, you are responsible for ensuring that these fees are covered in your Clinical Trial Agreement with the sponsor. What are the different regulatory classifications that research activities may fall under? Submitted activities may fall under one of the following five regulatory classifications: Not Engaged : DHHS Office of Human Research Protections (OHRP) defines an Institution as engaged in Human Research when its employees or agents for the purposes of the research obtain: (1) data about the subjects of the research through intervention or interaction with them; (2) identifiable private information about the subjects of the research; or (3) the informed consent of human subjects for the research. For example, if an AEHN physician collects a blood sample for a genetic research study being conducted at another institution and has the informed consent obtained by the other institution and does not collect data about the subject for research then AEHN would not be considered engaged in the Human Research. Contact the IRB office in cases where it is unclear whether or not you are engaged in Human Research. Not Human Research : Activities must meet the DHHS or FDA definition of research involving human subjects for the activity to fall under IRB oversight. Review the HRP WORKSHEET: Human Research Determination in the IRB Forms folder on the shared drive for reference. Contact the IRB office in cases where it is unclear whether an activity meets the regulatory definition of Human Research. Exempt: Certain categories of Human Research may be exempt from regulation but still require IRB review. It is the responsibility of the IRB, not the investigator, to determine whether Human Research is exempt from IRB review. Review the HRP-319 WORKSHEET: Exemption Determination in the IRB Forms folder on the shared drive for reference on the categories of research that may be exempt. Human Research determined to be exempt does not require continuing review by the IRB once the initial review and determination are complete. Review Using the Expedited Procedure: Certain categories of non-exempt Human Research may qualify for review using the expedited procedure. Review the HRP WORKSHEET: Eligibility for Review Using the Expedited Procedure in the IRB Forms folder on the shared drive for reference on the categories of research that may be reviewed using the expedited procedure.

22 Investigator Manual Page 22 of 60 Review by the Convened IRB: Non-Exempt Human Research that does not qualify for review using the expedited procedure must be reviewed by the convened IRB. The IRB is scheduled to meet on the third Friday of every month. Deadlines for submission are posted on the bulletin board outside the IRB office in Korman 100 and also can be found in the IRB Forms folder on the shared drive (under IRB Roster - Meeting Information). What is the typical turnaround time on IRB review? Turnaround time on a submission varies depending on the: 1) the type of submission (e.g. initial reviews typically take longer to review than modifications to previously approved research); 2) the completeness and accuracy of the submission (e.g. missing information and forms delay processing); 3) if the submission requirements are met (e.g. CITI training completed for listed research personnel); 4) the complexity of the request; and 5) the current IRB office workload at the time of submission. The IRB generally convenes for meetings once a month, on the third Friday of the month. Expedited reviews occur on an ongoing basis. The IRB office processes hundreds of requests each year. Their goal is to process these requests in a timely manner. If three weeks or more have passed since your submission, and you have not received any correspondence from the IRB office, please feel free to contact the IRB office for a status update at (215) Be sure to have the investigator s last name, protocol title/irb number, type of submission (e.g. initial vs. continuing review vs. modification) and the approximate date of submission available when you call. What are the decisions the IRB can make when reviewing a protocol? The IRB may approve research, require modifications to secure approval, table research, defer or disapprove research: Approval: Made when all criteria for approval are met. The Human Research may commence once all other organizational and/or local approvals have been secured. IRB approval is granted for a limited period of time, not exceeding one year, which is noted in the approval notification letter. See How does the IRB decide whether to approve Human Research? below. Modifications Required to Secure Approval: Made when IRB members require specific modifications to a protocol or other study documents before approval can be finalized. Such changes may be reviewed administratively and do not require re-review by the convened IRB. Tabled: Made when the IRB cannot approve the research at a meeting for reasons unrelated to the protocol, such as loss of quorum. When taking this action, the IRB automatically schedules the protocol for the next meeting. Deferred: Made when the IRB determines that the board is unable to approve a protocol and the IRB suggests modifications that might make the research