IRB Determinations for Beginners (and Students) Alyssa Speier, MS, CIP Assistant Director, Regulatory Affairs & Research Compliance Harvard T.H. Chan School of Public Health

So you need to conduct research with Human Subjects? Don’t panic!

 Non-Committee Review  Not Human Subjects Research determination  Exemption determination  Expedited  Committee/Convened/Full Board Review  Possible outcomes: Approved; Requires Modifications; Deferred; Disapproved 3 Types of IRB Review

Types of IRB Review (cont.) Non-Committee Review  Occurs on a rolling basis  No submission deadlines  Performed by one or more designated & experienced IRB members  department-assigned IRB Review Specialist Committee Review  Occurs at scheduled meetings (Harvard LMA IRB meets monthly)  Submission deadlines approx. 30 days prior to meeting Submission deadlines  Performed by committee, which must achieve quorum 4

 Research is defined as a… “systematic investigation including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge”  Human Subject is defined as a… “living individual about whom an investigator (whether professional or student) conducting research obtains:  data through intervention or interaction with the individual or  private identifiable information” 5 Human Subjects Research

A computer science student plans to develop automated computer methods to summarize the contents of medical texts. In order to do this, he needs examples of real clinical texts from a variety of sources, including clinical and research databases from Pathology and Radiology. None of the texts will contain any individually identifiable information. 6 Case Study #1

A researcher in Bioengineering plans to examine spine tissue to determine the mechanical properties that help protect the spine from inadvertent damage. All of the spine tissues will be obtained from postmortem specimens. 7 Case Study #2

An investigator obtains coded information on the treatment outcomes of patients treated for arthritis with Drug A versus Drug B from the patients’ treating physician. The only involvement of the treating physician is to provide coded information to the investigator. The investigator and the treating physician enter into an agreement prohibiting the release of the key to decipher the code to the investigator under any circumstances, until the individuals are deceased. 8 Case Study #3

 IRB review is not required but recommended  Investigators may obtain a formal not HSR determination  Submit a Not Human Subjects Research Request FormNot Human Subjects Research Request Form  Any Harvard LMA agent can serve as PI, including students  Human Subjects Training, e.g., CITI, not required 9 How to obtain a not Human Subjects Research determination

1.Research conducted in established or commonly accepted educational settings, involving normal educational practices 2.Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior  Not recorded in an identifiable manner OR  Does not increase risk to participant 3.Surveys, interviews, observation of public behavior if participants are public officials 4.Collection of existing data, documents, specimens  If publicly available OR  If no identifiers are recorded 5.Evaluation of public benefit or service programs, etc. subject to approval of Department or Agency heads 6.Taste and food quality evaluation and consumer acceptance 10 Exempt Human Research

Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior Caveats:  Sensitive information collected must be anonymous  Doesn’t apply to research with minors unless activities are limited to observation of public behavior and investigator doesn’t manipulate the environment  Doesn’t apply to research with prisoners 11 Category #2 Up Close

Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects. Caveats:  Data must be existing, on the shelf, at the time of submission to the IRB  “Publicly available” means anyone could access it  Identifiers cannot be recorded if not publicly available 12 Category #4 Up Close

An investigator wishes to analyze data on 5,000 patients with ICU admissions from to compare statistical models of risk adjustment and mortality prediction. To this end, she will review medical records at BIDMC. No identifiers will be recorded/moved off site for the analyses. 13 Case Study #4

a.A survey on substance abuse administered to adults with subject identifiers maintained. b.A survey administered to children asking about their favorite television shows. c.Evaluation of the effectiveness of a sex education course in a high school curriculum. d.Detailed personality and psychological testing of homeless subjects with identifiers maintained. e.None of the above. 14 Which of the following studies may qualify for an exemption determination?

 IRB review (& determination) is required  A consent process must be in place, when applicable, that discloses:  That the activities involve “research”  The research procedures  That participation is “voluntary”  The PI’s name & contact information  Submit Exemption Request Form (consultation required to access form)  Any Harvard LMA agent can serve as PI, including students  Human Subjects Training, e.g., CITI, may be required 15 How to obtain an Exemption determination

 Eligible for Expedited review if minimal risk and fits into one/more expedited review categoriesreview categories  Research with drugs/devices not used for investigational purposes  Blood collection  Collection of biological specimens by noninvasive means, e.g., hair, nail, teeth, saliva, etc.  Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, e.g., weighing or testing sensory acuity; sensors; strength testing, MRI, etc.  Collection of materials that have already been collected (data, documents, records, or specimens)  Survey, interview procedure 16 Non-exempt Human Research

 Convened IRB review  Greater than minimal risk  Doesn’t fit into one/more expedited review categories  Identification would reasonably place participants at risk of criminal or civil liability or be damaging to their financial standing, employability, insurability, reputation, or be stigmatizing,  unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality  Institutional policy, e.g., study procedures/target population 17 Non-exempt Human Research (cont.)

 Submit a Research Protocol & applicable study- specific materials  E.g., consent forms; survey tools; local IRB approval  PI must be a Harvard LMA faculty member (students may not serve as PI)  Human Subjects Training, e.g., CITI  Required for PI, and any member of study staff who has direct contact with participants and/or access to identifiable data 18 How to obtain Approval for Non-Exempt Human Research

Dr. Kim plans to analyze SAT scores from 2006 to 2015 from 10 Boston-area schools. The schools will provide Dr. Kim with a de-identified data set and neither Dr. Kim nor the schools will be able to link the scores back to the students. She will collect basic demographics about the school from their websites. 19 Case Study #5

Dr. Smith has a freezer of blood samples that were originally collected for a research study which ended several years ago. Patient codes (which can be linked to patient medical records) remain on the samples. The consent form originally signed by the subjects indicated whether or not their stored blood could be used for future research. A student advisee of Dr. Smith has requested access to the samples to conduct his own secondary data analyses. Dr. Smith agrees. 20 Case Study #6

Type of Determination or Review Average review turnaround times Not Human Subjects Research Determination 1 week Exemption Determination1 week Expedited2-3 weeks Full Board1 month 21 When will I Hear back?

 Be Realistic  Enrollment size  Amount of time  Analysis  Use of vulnerable populations  Use lay language  IRB composition is required to have non-scientists and community members  If the protocol is written in too technical of a manner (i.e., it’s not clear what you are doing), it may unnecessarily go to the Full Board  Be clear as to what is standard of care and what is research 22 Advice

 Submit modifications  Personnel to an existing study?  Make Changes to the IRB protocol. Don’t do anything before it’s approved  Report if things happen (they do sometimes)  Get External Institutions’ IRB/ERC Approvals  Explore Cede-reviews with collaborating institutions (Domestic)  Local IRB Review (International)  No Research can be conducted until all approvals are obtained-plan ahead  Is a Community Advisory Board Necessary? 23 More Advice

 Contact the HLMA Quality Improvement Program (QIP)  QIP Service Request Form QIP Service Request Form  Study Consultation  scheduled or impromptu  In-person or on phone  Submission Assistance  Walk through the submission forms/system with a staff member  the protocol or other documents for detailed comments and edits prior to submitting to the IRB  Online Resources   Investigator Manual Investigator Manual  Investigator Portal Investigator Portal  ESTR Submission tools ESTR Submission tools 24 What help is available?