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 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?
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, Institutional Review Boards (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 a 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 Participant 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 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 all non-exempt studies must be a Harvard faculty member. 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 outlining why this arrangement is appropriate and the qualifications of the proposed PI.
Harvard students may serve as a PI for exempt protocols only. Student PIs are required to obtain their Faculty Advisor’s review and assurance for each submission to the IRB.
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 http://www.citiprogram.org/. 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 http://www.hsph.harvard.edu/research/human-research-administration/education/).
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 617-432-2157.
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 with any relevant attachments. The IRB must review and approve all Human Research activities 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. They 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.
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 more than one individual should receive the email notifications generated via ESTR (submission reminders, approval notifications, requests for clarifications, expiration notices, etc.), they should be added as email recipients by completing the “Edit Email List” activity in the main study workspace.
If the study is being conducted by a student Principal Investigator, and the Faculty Advisor has been listed in item 5 on the SmartForm Page: Basic Information, the IRB will forward the application for Faculty Advisor review and assurance.
If the study is non-exempt, the IRB will forward the application for Department Chair 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).
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 on the IRB websites (linked below).
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, double-blind, 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).
4.4 Inclusion Criteria. Describe the criteria that define who will be included in the protocol.
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.
· 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 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 email 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 and Payments”. 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.