Investigator Manual. What is the purpose of this manual? What is the Human Research Protection Program? What is Human Research? Exempt Human Research

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1 Investigator Manual What is the purpose of this manual? The 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 the Harvard Institutional Review Board (IRB) to which you are submitting. General information regarding Human Research protections and relevant federal regulations and guidance is incorporated into the required human protections training. See What training do investigators and study staff need to conduct Human Research? What is the Human Research Protection Program? The Human Research Protection Program (HRPP) at Harvard Longwood Medical Area (HLMA) is a comprehensive system to ensure the protection of the rights and welfare of participants in Human Research. It is comprised of the Harvard T.H. Chan School of Public Health (Harvard Chan School), Harvard Medical School (HMS), and Harvard School of Dental Medicine (HSDM) leadership, IRBs, HLMA Quality Improvement Program (QIP), investigators and their study staff, and relevant departments, centers, institutes and units. The document HUMAN RESEARCH PROTECTION PROGRAM PLAN describes the Schools overall plan to protect participants in Human Research, including: The mission of the Human Research Protection Program. The ethical principles that each IRB follows governing the conduct of Human Research. The applicable laws that govern Human Research. When Harvard becomes engaged in Human Research and when someone is acting as an agent of Harvard conducting Human Research. The types of Human Research that may not be conducted. The roles and responsibilities of individuals within Harvard. What is Human Research? The HMS/HSDM and Harvard Chan School IRBs follow the regulatory definitions of Human Subjects Research, which are described in the document HUMAN RESEARCH PROTECTION PROGRAM PLAN. An algorithm for determining whether an activity is Human Research can be found in WORKSHEET: Human Research Determination. Use this document for guidance as to whether an activity meets either the DHHS or FDA definition of Human Subjects Research. Each IRB will make the ultimate determination in questionable cases as to whether an activity constitutes Human Research. If an investigator would like a formal written Not Human Subjects Research determination, see How to submit new Human Research Application? Exempt Human Research Certain categories of Human Research may be exempt from HHS regulation but require IRB review. Investigators must obtain an IRB Exemption Determination prior to conducting exempt Investigator Manual HRP-103 Version date: October 9, 2015 Page 1 of 48

2 Human Research. An algorithm used by the IRB for determining whether an activity is exempt can be found in WORKSHEET: Exemption Determination. To request an exemption determination, see section entitled How to submit new Human Research Application? Who can be Principal Investigator (PI)? The Principal Investigator for any non-exempt Human Research must be a Harvard faculty member, e.g., professor, associate professor, assistant professor, instructor, lecturer, clinical assistant. The IRB may make an exception to this requirement on a case-by-case basis with appropriate justification. To request an exception, submit a cover memo with your application to the IRB outlining why this arrangement is appropriate and the qualifications of the proposed PI. Harvard students may serve as a PI for exempt protocols only. All student PIs are required to list their Faculty Advisor on the SmartForm Page: Study Team Members in ESTR. Faculty Advisor review and attestation is required, and will be obtained via ESTR. The Faculty Advisor is ultimately responsible for the conduct and oversight of the Human Research, and compliance by the student PI to the Principal Investigator responsibilities. For existing studies, if a PI fails to submit a continuing review application by the submission deadline and/or IRB approval lapses, the PI will be restricted from submitting new Human Research until the completed application has been received. What training do investigators and study staff need to conduct Human Research? All new investigators and study staff must review the HUMAN RESEARCH PROTECTION PROGRAM PLAN as part of their initial orientation. Anyone that will have (a) direct interaction with participants and/or (b) access to identifiable information must complete Harvard s online training curriculum available through the Collaborative Institutional Training Initiative (CITI) Program. The CITI site can be accessed at In addition, Principal Investigators, Co-Investigators, and those meeting the definition of NIH Key Personnel must complete human research training regardless of whether or not they have access to identifiable data/specimens or contact with human subjects. Human research training certification is valid for a three-year period from date of completion, after which time a refresher course or additional training is required. Refresher training can be achieved by taking the CITI refresher course or if the Investigator has a primary affiliation with Harvard Chan School, HMS and HSDM, and attends three QIP education series sessions (offerings can be found at IRB approval may not be granted for proposed research in which investigators have not completed human research protections training. To check the training status or obtain a copy of an individual s training certificate, contact the ORARC Coordinator at How to submit a new Human Research Application Online Complete an online application using the IRB s online e-submission system, ESTR (Electronic Submission, Tracking & Reporting), available at irb.harvard.edu, and submit it to the IRB along Investigator Manual HRP-103 Version date: October 9, 2015 Page 2 of 48

3 with any relevant attachments. The IRB must review and approve all Human Research prior to the initiation of any research activities. Log in to irb.harvard.edu; on the left side of the screen, select Create New Study. Details about how to navigate the IRB online submission system and complete an application are available separately, via the Study Submission Guide. Who has access to my ESTR record and submission to the IRB? The individual listed as the Principal Investigator has full access to the entire ESTR record and all of the SmartForm Pages. The PI can make edits, create Modifications and Continuing Review applications, and will receive all notifications generated via ESTR. If needed, one additional contact person may be identified in the system by completing the Assign Primary Contact activity. In addition to the PI, this person will receive a copy of all notifications related to the protocol. There can only be one individual assigned as Primary Contact. The Principal Investigator may designate proxy permissions so that system activities that are only available to the Principal Investigator can be completed by another member of the study team. A proxy can be assigned by the Principal Investigator only after initial study approval has been granted by the IRB. Anyone assigned as a system-based proxy can assist with IRB follow-on submissions (modifications and continuing review) and the management of the ESTR record. However, being assigned as proxy does not imply that the named proxy has Principal Investigator responsibilities, those are still unique to the Principal Investigator. As part of the process to assign proxy, the system will record the name, date, and time that the Principal Investigator completed the activity, serving as a record that the Principal Investigator assured their compliance with IRB policies on PI responsibilities (see What are the Investigator s obligations after IRB approval? section of this document). The PI, Primary Contact, and any listed Proxy will receive all system notifications. If more than one individual should have access to the ESTR record and submission documents, they should be added as a member of the guest list by completing the Manage Guest List activity in the main study workspace. This will allow any Harvard-affiliated individual read-only access to the ESTR record. If the study is being conducted by a student, and the Faculty Advisor has been listed on the SmartForm Page: Study Team Members, the IRB will forward the application for Faculty Advisor review and attestation. If the study is non-exempt, the IRB will forward the application to the responsible Department Chair for review and approval. How to write a Research Protocol? The purpose of the research protocol is to provide IRB members and reviewers with sufficient information to conduct a substantive review. If a separate sponsor s protocol exists, please submit it in addition to this document. Complete all sections of the Research Protocol (check a Yes/No box or provide an answer). Investigator Manual HRP-103 Version date: October 9, 2015 Page 3 of 48

4 The IRB encourages investigators to maintain electronic Word documents of all information (specifically, any supporting documents uploaded in ESTR) submitted to the IRB in case revisions are required. In addition, an investigator must retain a hard copy or electronic version of the submission, as well as the IRB notification letters, as part of their regulatory documentation. These materials may be maintained through ESTR (all final and validated versions are on the Documents tab of the main study workspace), on a secured drive, or via hard copy binder or filing system. The Quality Improvement Program can provide guidance on what other regulatory documentation is required as part of PI files and how best to maintain it. Template Regulatory Binders are also available here. General Information: Provide the version number/date, principal investigator, the student/instructor/course instructor investigator (in the space provided for Student Investigator ), complete protocol title, and funding agency/sponsor (if applicable). In addition to the information provided in this manual, a number of checklists are available on the IRB website to guide investigators in drafting the Research Protocol. Individual checklists are referenced throughout this section when appropriate. 1. Specific Aims. Describe the specific aims, purpose and/or objectives of the Human Research. State the hypotheses to be tested if applicable. 2. Background. Provide the scientific or scholarly background and rationale for the Human Research based on the existing literature. Describe the relevant prior experience, gaps in current knowledge, and any relevant preliminary data. Explain the significance of the Human Research and how will it add to or enhance existing knowledge. Describe the importance of the knowledge expected to result. 3. Study Setting. Describe the study site(s), setting and location in which the Human Research will occur. Outline the Principal Investigator s experience working in this setting and the study population(s) as well as his/her familiarly with the local culture. For research conducted outside of the United States, describe any site-specific regulations or customs, e.g., local age of majority; the local ethical review structure, i.e., national, regional, institution-based model, and/or engagement of a community advisory board (CAB). Describe how local implementation of the research will be supervised to ensure compliance with the IRB-approved protocol. 4. Study Design. 4.1 Describe the type of study planned, e.g., ethnography, randomized trial, doubleblind, parallel, etc. If an observational study, specify cross-sectional, cohort, case-control, etc. 4.2 Indicate the study duration for participant involvement from study initiation to closure. Provide an anticipated date of study completion. 4.3 Indicate the total number of participants (differentiate between those who are screened versus enrolled, i.e., signed a consent form). For non-exempt secondary analysis research, indicate the number of data, documents, records, and/or specimens that will be utilized for analysis. 4.4 Inclusion Criteria. Describe the criteria that define who will be included in the protocol. Investigator Manual HRP-103 Version date: October 9, 2015 Page 4 of 48

5 4.5 Exclusion Criteria. Describe the criteria that define who will be excluded in the protocol. 4.6 Study procedures. Provide a timeline of all procedures being performed, including procedures being performed to monitor participants for safety or minimize risks. Describe procedures taken to lessen the probability or magnitude of risks. Describe what data will be collected, including long-term follow-up data. If study includes qualitative data collection, describe all procedures and information collected. Identify documents that will be used to collect data (e.g., questionnaires, surveys, interview guides) and be sure to include these documents with your application. Source documents, (e.g., case report forms), need not be submitted, but should be identified. If applicable, specify whether or not deception or incomplete disclosure will be employed, and if so, describe why it is necessary. Describe provisions in place to debrief participants after study procedures conclude. Specify whether participants will be audio or video recorded, and when or if these recordings will be destroyed. Differentiate routine clinical care from research procedures, if applicable. Differentiate procedures conducted by Harvard staff from those conducted by non-harvard members of the research team. Identify any drugs/devices to be used, their purpose, and regulatory status. Study Intervention. Describe primary and secondary study endpoints (i.e. events or outcomes that can be measured to determine effect of research intervention), as well as any primary and secondary safety endpoints (for qualitative research, study endpoint may include completion of 6-month survey). 4.7 Collection of Samples or Existing Data. Indicate how, when, where and from whom samples or data will be obtained. 4.8 Data and safety monitoring plan (required when Human Research involves more than minimal risk to participants). Describe the plans to periodically evaluate the data collected regarding both harms and benefits to determine whether participants remain safe. Describe; what data will be reviewed, including safety and efficacy data, how safety information will be collected (e.g., with case report forms, at study visits, by telephone), the frequency of data collection, including when safety data collection begins, the person or entity (e.g., a Data and Safety Monitoring Board) responsible for reviewing the data, the frequency or periodicity of cumulative data review, statistical measures for analyzing safety data to determine whether harm is occurring, and any conditions that would trigger an immediate suspension of the research. 4.9 Describe anticipated circumstances, if any, under which participants will be withdrawn from the research without their consent. Describe any procedures for orderly termination. Describe procedures that will be followed when Investigator Manual HRP-103 Version date: October 9, 2015 Page 5 of 48

6 participants withdraw from the research, including partial withdrawal from procedures with continued data collection. 5. Data/Statistical Analysis Plan. Describe the statistical method and analysis plan. Describe the sample size and its scientific rationale, by site and key characteristics, e.g., participant demographics, which is also applicable to studies posing greater than minimal risk or incurring a high societal cost. 6. Recruitment Methods. Describe the source of participants for all study groups (intervention/case and control); when, where, how, and by who these potential participants will be recruited. Describe the methods employed to identify potential participants, and the materials used to recruit participants, including the use of and text messaging. If this is a multi-center study in which participants are recruited by methods not under the control of the local site, e.g., call center or national advertisements, describe those methods. Of note, the IRB must review and approve the content of all recruitment and advertisement materials, including oral communications, before implementation. For advertisements, submit the final copy of printed advertisements. When advertisements are taped for broadcast, provide the final audio/video tape. To avoid re-taping due to inappropriate wording, submit the proposed (draft) wording of the advertisement to the IRB. Otherwise, provide the final English copy of these materials and include a version number and/or date within each document. For guidance on what to include in an advertisement, refer to WORKSHEET: Advertisements. When community based participatory research is involved, define the term community as it relates to this protocol and describe provisions to engage this community in design and study conduct. Identify any community partners. 7. Available Resources. Demonstrate (based on retrospective data) a potential for recruiting the required number of eligible participants within the set recruitment period and the time frame necessary to implement and complete the protocol. Describe the process to ensure that all persons assisting with the protocol are adequately informed about the protocol and study-related duties. Describe the qualifications of the study personnel, their experience in conducting research, their knowledge of the local study site(s), culture, and society. Describe the facilities and the available equipment required to conduct the protocol. Describe the availability of medical and/or psychological resources that participants might need as a consequence of their participation in the Human Research. Describe the time allocated to complete the study. 8. Vulnerable Populations. Identify all potential vulnerable populations regardless of whether the Human Research is focused on or targets such individuals. These may include, but are not limited to children, human fetuses, neonates, pregnant women, prisoners, non-english speakers, low/literate individuals, cognitively impaired persons, and persons with a stigmatizing disease or condition, e.g., HIV/AIDS. Describe safeguards implemented to protect their rights and welfare. Adults Unable to Consent. If the Human Research involves adults unable to consent refer to CHECKLIST: Cognitively Impaired Adults and address each of the criteria for approval. Investigator Manual HRP-103 Version date: October 9, 2015 Page 6 of 48

7 Children. If the Human Research involves persons who have not attained the legal age for consent to treatments or procedures involved in the research ( children ): Refer to CHECKLIST: Children and address each of the criteria for approval. Neonates of Uncertain Viability. If the Human Research involves neonates of uncertain viability, refer to CHECKLIST: Neonates of Uncertain Viability and address each of the criteria for approval. o Non-viable Neonates. If the Human Research involves non-viable neonates, refer to CHECKLIST: Non-viable Neonates and address the criteria for approval in this section. o Pregnant Women: If the Human Research involves pregnant women, refer to CHECKLIST: Pregnant Women and address each of the criteria for approval. Prisoners. If the Human Research involves prisoners, refer to CHECKLIST: Prisoners and/or CHECKLIST: Unexpected Incarceration and address the criteria for approval in this section. Note: The checklists are not required to be submitted as part of the application process. However, the criteria for approval outlined within the checklists should be addressed within the IRB submission application. 9. Consent Process Describe the setting of the consent process; identify who will be responsible for obtaining consent, and how consent will be obtained, e.g., written or oral consent. Avoid naming specific individuals, but rather study roles, e.g., research coordinators or nurses vs. John Doe. Describe the time that will be devoted to the initial consent discussion. Describe any waiting periods between (a) informing the prospective participant and obtaining consent and (b) obtaining consent and carrying out the study procedures. Describe any steps that will be taken to minimize the possibility of coercion or undue influence. Describe the process to ensure ongoing consent. Indicate that study staff will continue to ensure participants understand what the research is about and what their participation involves. Confirm that any new information which might influence a participant s decision to continue participation will be provided to participants, including re-consent where applicable. Indicate what language(s), if any, other than English are understood by prospective participants or their representatives. If non-english speaking participants will be enrolled describe the process to ensure that the oral and written information provided to those participants will be in that language and submit FORM: Translation Attestation. Provide an English copy of the consent document(s), as well as a copy of the local language translation when it becomes available. Include version number and/or version date within each document. Back-translation of foreign language consent forms is not required. Investigator Manual HRP-103 Version date: October 9, 2015 Page 7 of 48

8 9.2. If the Human Research involves any special population, describe the process to obtain consent, permission or assent, including: Persons who have not attained the legal age for consent to treatments or procedures involved in the research ( children ): i. Describe whether parental permission will be obtained from: 1. Both parents unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child. 2. One parent even if the other parent is alive, known, competent, reasonably available, and shares legal responsibility for the care and custody of the child. ii. Describe whether permission will be obtained from individuals other than parents, and if so, who will be allowed to provide permission. Describe the process used to determine these individuals authority to consent to each child s general medical care. iii. Describe whether assent will be obtained from all, some, or none of the children, and if some children, which children will be required to provide assent. Customarily, the IRB requires that investigators obtain assent from individuals ages 7 years or older; however, if this is not appropriate for the specific target population, please describe. iv. When assent of children is obtained, describe whether and how it will be documented. v. Describe the procedures in place to obtain consent when, if any, children reach the local age of majority during the course of the protocol. If the Human Research involves adults who may be unable to consent describe the process to determine whether an individual is capable of consent and address the following, if applicable: i. If permission of a legally authorized representative will be obtained: ii. 1. List the individuals from whom permission will be obtained in order of priority, e.g., durable power of attorney for health care, court appointed guardian for health care decisions, spouse, and adult child. 2. Determine which individuals are authorized under applicable law to consent on behalf of a prospective participant to their participation in the research procedure(s). 3. To make this determination, contact the IRB who will consult with the Office of the General Counsel to review the definition of legally authorized representative in 45 CFR (c) or 21 CFR 50(l). Describe the process for assent of the participants. Indicate whether: Investigator Manual HRP-103 Version date: October 9, 2015 Page 8 of 48

9 1. Assent will be required of all, some, or none of the participants. If some, indicated, which participants will be required to assent and which will not. 2. If assent will not be obtained from some or all participants, include an explanation of why not. 3. Describe whether assent of the participants will be documented and the process to document assent. iii. Describe how consent of the participant will be documented in writing and indicate that participants will be provided with a copy of their signed consent form. If there are extenuating circumstances that make it impossible or inappropriate to meet this requirement, please describe. If the consent process will not be documented in writing, i.e., consent will be obtained, but the participant or representative will not sign a consent document, refer to CHECKLIST: Waiver of Written Documentation of Consent and address each of the following criteria for approval within this section: (1) That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or (2) That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context 9.3. (through 9.5) If the Human Research involves a waiver or alteration of the consent process (consent will not be obtained, required information will not be disclosed, or the research involves deception) review CHECKLIST: Waiver or Alteration of the Consent Process and address each of the following criteria for approval in this section. (1) The research involves no more than minimal risk to the subjects; (2) The waiver or alteration will not adversely affect the rights and welfare of the subjects; (3) The research could not practicably be carried out without the waiver or alteration; and (4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation. 10. Risks. List the foreseeable risks, discomforts, hazards or inconveniences to participants. For each indicate the probability, magnitude, and duration. Consider physical, psychological, social, legal and/or economic risks. Outline the provisions in place to minimize each identified risk, discomfort, hazard, and inconvenience. Investigator Manual HRP-103 Version date: October 9, 2015 Page 9 of 48

10 11. Benefits. Describe the potential benefits that individual participants may experience; otherwise, indicate that there is no direct benefit to participants. Describe any potential benefit to the local community, population, country and/or society. Of note, compensation is not a benefit and should not be addressed in this section. 12. Reportable Events. Outline plans for communicating reportable events, e.g. adverse events, unanticipated problems involving risks to participants or others. Indicate that reportable events will be reported to the IRB in accordance with IRB policies (refer to Appendix A for prompt reporting requirements and report categories), i.e., reporting to the IRB within 5 business days from the time the study team becomes aware of the information. 13. Research Related Injuries. If the research involves greater than minimal risk to participants, describe the provisions for medical care and what, if any, compensation will be available in the event of a research-related injury. Describe how participants will report research-related injuries should they occur. Although Harvard s policy is not to provide compensation for physical injuries that result from study participation, medical treatment should be available including first aid, emergency treatment and follow-up care as needed. If the research plan deviates from this policy, provide appropriate justification. 14. Participant Privacy. Describe the provisions implemented to protect participants privacy interests. Privacy interest refers to a person s desire to control access of others to themselves. It involves consideration of whether the participants will be comfortable with the research procedures. For example, conducting interviews in a private room or visiting a participants home in an unidentifiable manner, such as in an unmarked car, wearing plain street clothing. Describe steps that will be taken to reduce any sense of intrusiveness that may be caused by study questions or procedures. 15. Data Confidentiality. Describe the provisions implemented to limit dissemination of identifiable data. Describe where data will be stored, how it will be transmitted, who will have access, how long it will be stored, and when applicable, how it will be archived and/or destroyed. Indicate how research team members are permitted access to information about study participants. If future open access (i.e., free availability and unrestricted use) is planned, describe such plans. If data is subject to NIH Genomic Data Sharing policy or data will be voluntarily submitted to an NIHdesignated repository, include a description of all data fields to be submitted to the repository; a copy of the consent form(s) used to enroll participants and collect underlying data; a description of the PI s plan for de-identifying datasets for transmission to the data repository, how the key linking the identity of each study participant will be maintained, and who will have access. Data security plans must comply with protection requirements described in the Harvard Research Data Security Policy (HRDSP) which can be found on the University security website The recommended location for all research data is a secure Harvard file server. Harvard has school-specific, and sometimes department-specific, resources so please contact your local IT Security Officer to confirm which secure server is available for your use. should not be used to transmit any research data. If files need to be sent via , please use Harvard's Accellion Secure File Transfer server. Research Investigator Manual HRP-103 Version date: October 9, 2015 Page 10 of 48

11 data can only be kept on portable or handheld devices if they are configured and managed appropriately (i.e. password protected, up-to-date operating system, antivirus protection, active firewall, etc.). Please check with IT before using any of these kinds of devices. USB/flash drives, CDs, or external hard drives should only be used if those devices are encrypted and preferably remote wipeable. You can request a secure flash drive known as IronKey from IT, which will be provided on loan at no cost. Per the Harvard Research Data Security Policy, research data of any security level can be stored electronically, however there are level-specific requirements and investigators must consult with IT for level 3 and higher before implementing. IT at Harvard is school-specific however; all data security inquiries should be sent to itsecec@harvard.edu. 16. Costs and Payments. Describe any costs that participants may incur, e.g., transportation, meals, or other out-of-pocket expenses, or payment that participants may receive through their participation in this study. Payment plans must comply with Harvard University Financial Policy on Human Participants Payment, which can be found at For additional guidance on what appropriate payment plans, refer to WORKSHEET: Advertisements and Payments. 17. Multi-site Study Management. Describe the management of information if the study involves more than one study site, e.g., results, new information, adverse events, unanticipated problems involving risk to participants or others, and protocol modifications, among sites. 18. Investigational Drug/Biologic/Device. Identify and describe the drug/biologic/device, e.g. classification of a device as significant vs. non-significant risk. Refer to WORKSHEET: Devices and/or CHECKLIST: Non-Significant Risk Device and address the criteria for approval in this section. 19. HIPAA Privacy Protections. Harvard University Health Services and Harvard School of Dental Medicine are covered entities at Harvard. Harvard is otherwise not a HIPAA covered entity as defined by the HIPAA Privacy Rule. If, however, protected health information (PHI) is derived from a Covered Entity, e.g. a hospital or community health center, for purposes of this protocol, describe the plans to obtain authorization to access protected health information or provide a rationale for requesting a waiver of authorization. If requesting the latter, address why it is not practical to obtain an authorization and why the research cannot be conducted without obtaining PHI. Refer to CHECKLIST: HIPAA Waiver of Authorization. 20. Data and Specimen Banking. Describe what data/specimens will be collected and stored, what information will be associated with the data/specimens, where and how long the data/specimens will be stored, who will have access to data/specimens, plans for destroying or returning the data/specimens, whether participants can withdraw their specimens/data and how they would do so, i.e., is written request required. Address whether data/specimens will be stored for future uses not described in the protocol. Describe plans to send data/specimens to collaborators outside of Harvard, e.g., dbgap or other NIH-designated repository, and/or receive data/specimens from collaborators outside of Harvard. Indicate who will send and/or receive the data/specimens, how data/specimens will be shared, and whether the data/specimens will contain identifiers Investigator Manual HRP-103 Version date: October 9, 2015 Page 11 of 48

12 (direct or indirect). Describe any plans to receive data/specimens from collaborators outside of Harvard, include: from where data/specimens will be obtained and if the data/specimens will contain identifiers that would enable Harvard Investigators to link them to individual participants. When appropriate, submit documentation of IRB approval and a copy of the IRB approved consent form from the external institution. 21. Sharing Study Results. Consider whether it is appropriate to share study results and how best to do so. Specifically, describe the plans to share individual results of the research with participants when appropriate, e.g., results letter. Include plans to disseminate aggregate results to the larger community, e.g. journal publication. 22. Regulatory Compliance. Describe plans for monitoring regulatory compliance, in order to ensure proper record keeping, e.g. appropriate consent documentation, and retention of required regulatory documents. Plans may include conducting internal checks using the Quality Improvement Program s CHECKLIST: Investigator Quality Improvement Assessment. Alternatively, QIP staff members are available to conduct periodic onsite review or assist in drafting an appropriate monitoring plan to meet the needs of your protocol. What financial interests have to be reported to the IRB? In order to minimize the actual or potential conflicts of interest in human research, the IRBs require all individuals involved in the design, conduct, or reporting of the research to report all financial interests related to the research. Of note, all individuals involved in the design, conduct, or reporting of the research is broader than principal investigators and co-investigators and may include study coordinators, research nurses, data coordinators, and other support staff possibly not captured on the Study Team Members Page SmartForm. To disclose, submit FORM: Financial Interest Disclosure Form at the time of initial review and each subsequent continuing review. In addition, investigators must report any change(s) to this disclosure to the IRB within 30 business days of discovering or acquiring (e.g., through purchase, marriage, or inheritance) a new financial interest. The definitions of important terms are as follows: Financial Interest Related to the Research means any of the following interests in the sponsor, product or service being tested, or competitor of the sponsor held by the individual or the individual s immediate family: Ownership interest of any value including, but not limited to stocks and options. Compensation of any amount including, but not limited to honoraria, consultant fees, royalties, or other income. Proprietary interest of any value including, but not limited to, patents, trademarks, copyrights, and licensing agreements. Board or executive relationship, regardless of compensation. Reimbursed or sponsored travel by an entity other than a federal, state, or local government agency, higher education institution or affiliated research institute, academic teaching hospital, or medical center. Immediate Family means spouse, domestic partner, and dependent children. Investigator Manual HRP-103 Version date: October 9, 2015 Page 12 of 48

13 Additional details can be found in Harvard University Policy and Individual Financial Conflicts of Interest for Persons Holding Faculty and Teaching Appointments, and HMS: HMS Policy on Financial Conflicts of Interest in Sponsored Research Harvard Chan School: SOP: Financial Conflicts of Interests (HRP-055) and the Harvard Chan School Implementation Plan for the Harvard University Policy on Individual Financial Conflicts of Interest for Persons Holding Faculty and Teaching Appointments and/or Conducting Work on School Sponsored Grants How to create a consent/assent document? The IRB strongly recommends that investigators use TEMPLATE: Consent Document and/or TEMPLATE: Assent Document to create consent/assent documents for Human Research. If an alternative format is preferred or required, i.e., by the Sponsor or local Ethical Review Committee, include a cover memo with the submission justifying its use. Note that all consent documents must contain all of the required and additional appropriate elements of informed consent. No informed consent (oral or written) should include exculpatory language whereby the participant or their representative is made to waive or appear to waive any of the participant s legal rights, or releases or appears to release the Investigator, the sponsor, the Institution or its agents from liability for negligence. Additional suggestions for inclusion in Consent Form: If applicable, include the following under Purpose of the Research : Describe the current therapies for their disease/condition and why they are not satisfactory. For non-therapeutic studies, explain the scientific problem. Describe how this research will attempt to solve the problem. Information about the drug/device, including current regulatory status, e.g., The drug/device is/is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of If applicable, include the following under Risk or possible Discomforts : In the case of participants who are patients, indicate procedures being performed as standard of care and which are part study procedures. Information about the study design, e.g., randomization, placebo, blinding. Special requirements, e.g., stopping current medications, fasting before tests. Reasons and procedures for early withdrawal from the study, e.g., tapering medications, final study visit. Sending data/specimens to research collaborators. Storage of data/specimens for future use. Sponsor use of identifiable study information for additional research. The sponsor may request to use identifiable study information for additional research related to the study. Unforeseeable risks that may result from study drugs, devices, procedures, e.g., There may be other risks or side effects that are not known at this time. Investigator Manual HRP-103 Version date: October 9, 2015 Page 13 of 48

14 Group the risks into those that are expected, occasional, or rate and describe them as such. List all expected and occasional side effects. If the research involves an investigational product or procedures whose risk profile is not well known, add: In addition to these risks, this research may hurt you in ways that are unknown. If the research involves pregnant women or women of child-bearing potential and procedures that involve risks to an embryo or fetus, add: The procedures in this research are known to hurt a pregnancy or fetus in the following ways: If the research involves pregnant women or women of child-bearing potential and procedures whose risk profile in pregnancy is not well known, add: The research may also hurt a pregnancy or fetus in ways that are unknown. These may be a minor inconvenience or may be so severe as to cause death. You should not be or become pregnant [include as applicable or father a baby ] while on this research study. If applicable, include the following under Benefits from being in the Research : If the study is likely to lead to the development of a commercial product, then state this fact. You may also add, if true, that there are no plans to provide financial compensation to the participant in the event a commercial product is developed. For studies involving prisoners include the following statement: Taking part in this research study will not improve your housing or correctional program assignments. Further, taking part in this research study will not improve your chance of parole or release. Please note: Do not include compensation as a benefit. If applicable, include in the section on Compensation: Will I be compensated for participating in this research? Include the following information in this section: Money or other forms of compensation or reimbursement, e.g., gift certificate, meal voucher, parking voucher, and travel expenses. Include the method and timing of the compensation or compensation Include how the amount of compensation is calculated if the participant does not complete the entire study for any reason, e.g., If you do not complete all of the study visits, we will give you $25 for each study visit you completed. Refer to Harvard University Financial Policy on Human Participants Payment, which can be found at Note: If participants will not be paid or will not receive other forms of compensation for participation, please state so. Other Considerations: Investigator Manual HRP-103 Version date: October 9, 2015 Page 14 of 48

15 a. In the section What will I have to pay for if I participate in this research? Describe any costs the participant may incur. If participants will not incur any costs, please state so. Include the following information in this section: Usually, There will be no cost to you for participating in this research. If applicable, research procedures that will be provided at no cost to the participant, e.g., The study drug and all of the tests and procedures that will be done only for the research will be paid for by study funds. If applicable, include the following: A statement indicating that the cost of research procedures that may be billed to the participant or his/her Health Insurance Company. A statement indicating that the cost of the participant s routine medical care will be billed to the participant s or his/her Health Insurance Company in the usual way, e.g., The cost of your routine medical care will be billed to you or to your health insurance company in the usual way. b. What happens if I am injured as a result of participating in this research study? This section must be included in all consent forms under review. The IRB r may determine that the information is unnecessary if the project is determined to be no more than minimal risk and the information is not relevant. c. Can my taking part in the research end early? Unless there are adverse consequences to withdrawing from the research, say: You may decide not to continue in the research at any time without it being held against you. The person in charge of the research [or the sponsor if applicable] can remove you from the research at any time without your approval for any reason. If appropriate, include: Possible reasons for removal include (reasons why the participant may be withdrawn, such as if it is in your best interest or if you do not follow study directions ). If there are adverse consequences, say: You may decide not to continue in the research at any time without it being held against you. If you decide to leave the research (describe adverse consequences). If you decide to leave the research, contact the investigator so that the investigator can (Describe the procedures for orderly termination by the subject.) Otherwise: The person in charge of the research or the sponsor can remove you from the research at any time without your approval. If appropriate, include Possible reasons for removal include (any reasons why the participant may be withdrawn). Include for FDA-regulated research: If you stop being in the research, already collected data may not be removed from the study database. You will be asked whether the investigator can collect data from your routine medical care. (Note: The consent document cannot give the subject the option of having data removed.) If you agree, this data will be handled the same as research data. (Note: If a subject withdraws from the interventional portion of a study and does not consent to continued follow-up of associated clinical outcome information, the investigator must not access for purposes related to the study the subject s medical record or other confidential records requiring the subject s consent. However, an investigator may review study data related to the subject collected prior to the subject s withdrawal Investigator Manual HRP-103 Version date: October 9, 2015 Page 15 of 48

16 from the study, and may consult public records, such as those establishing survival status.) (For research that is not FDA-regulated, describe what will happen to data collected to the point of withdrawal. Describe whether subjects will be asked to explain the extent of their withdrawal and whether they will be asked for permission to collect data through interaction or collection of private identifiable information. For example, a subject may wish to withdraw from the experimental procedure because of unacceptable side effects, but may agree to undergo follow-up procedures and data collection.) Include for research where this is a possibility: We will tell you about any new information that may affect your health, welfare, or choice to stay in the research. d. If I take part in this research, how will my privacy be protected? What happens to the information you collect? Describe confidentiality protections. Include the following information in this section, if applicable: If the researcher does not know the identity of participants, you may say, Your participation is anonymous, and your responses cannot be linked to your identity. If the researcher will know the identity of participants, you may say, Your responses will be kept confidential, and then go on to describe measures such as a. Conducting interviews in a private place (if appropriate to minimize coercion, state The person who gave me your name to contact you won t know whether you agreed to participate or not ). b. Replacing names with a code and keeping the key in a secure location separate from the data. c. Using encrypted and password-protected electronic files; storing paper data in locked cabinets in locked offices. d. Destroying identifying raw data and erasing recordings at appropriate times e. Describing the publication protections, such as I won t use your name or information that would identify you in any publications or presentations. Or, if you are requesting permission to identify and/or quote participants, say that instead. f. Indicate that the Harvard IRB office may review study records. g. If additional offices or agencies will collaborate on or oversee the research, indicate the possibility that information may be shared with these groups. e. Statement of Consent. This section should be included in the consent form, if applicable. Indicate if the study involves the possibility of re-contacting the participant and provide a yes/no option for the participant to complete. If data or specimens will be stored for future use, describe how the information or materials will be stored and for how long. Provide a yes/no option for the participant to complete. Investigator Manual HRP-103 Version date: October 9, 2015 Page 16 of 48

17 f. Signature. There are multiple signature pages, appropriate for different types of studies. Create a separate consent document for each signature block type that will be used. Make any necessary alterations to the signature blocks, as instructed on the TEMPALTE: CONSENT DOCUMENT. If signature will not be obtained as part of the consent process, remove this section and provide the rational in the Research Protocol. What are the different regulatory classifications that research activities may fall under? Submitted activities may fall under one of the following four regulatory classifications: Not Human Research : Activities must meet the organizational definition of Human Research to fall under IRB oversight. Activities that do not meet this definition are not subject to IRB oversight or review. Review the IRB Office s WORKSHEET: Human Research for reference. Contact the IRB Office in cases where it is unclear whether an activity is Human Research, or if you would like the IRB office s written confirmation that your project is not Human Research. Exempt: Certain categories of Human Research may be exempt from regulation but require IRB review. It is the responsibility of the IRB, not the investigator, to determine whether Human Research is exempt. The IRB uses WORKSHEET: Exemption when determine whether a particular study meets one or more exempt criteria. Review Using the Expedited Procedure: Certain categories of non-exempt Human Research may qualify for review using the expedited procedure, meaning that the project may be approved by a single designated IRB reviewer, rather than the convened board. Review the IRB Administration s WORKSHEET: Expedited Review for reference on the categories of research that may be reviewed using the expedited procedure. 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. How does the IRB decide whether to approve Human Research? The criteria for IRB approval of non-exempt Human Research can be found in WORKSHEET: Criteria for Approval. Additional checklists may be applicable depending on the nature of the proposed Human Research, e.g., inclusion of children will prompt the use of CHECKLIST: Children. All checklists can be found on the IRB website. These checklists are used by IRB members and reviewers at the time of initial review, continuing review, and review of modifications to previously approved Human Research. Investigators are also encouraged to use the checklists as a reference or guide when writing the Research Protocol in a way that addresses the criteria for approval. Review Using the Expedited Procedure Certain categories of non-exempt Human Research may qualify for review using the expedited procedure. Review WORKSHEET: Expedited Review for reference on applicable categories of research. Protocols eligible for review using the expedited procedure are reviewed on a firstcome, first-served, rolling basis. Investigator Manual HRP-103 Version date: October 9, 2015 Page 17 of 48