Brief Introduction to Review of Human Subjects Research in the Health Sciences Presentation to Primary Care Faculty Development Program Nichelle Cobb, PhD Director, Health Sciences IRBs November 2010

Definition of Human Subjects Research: A Refresher

Definition of human subjects research Research is defined by the Common Rule as, “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.” A human subject is defined as “a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.”

What is human subjects research? Covers a wide variety of activities, including studies of:  Human testing of drugs, devices, or products developed through research  Data from surveys, interviews, and observation  Employment information or records of earnings  Medical records  Bodily materials, such as cells, blood, urine, tissues, organs, hair, nail clippings, or DNA, when these are linked to specific individuals

QA, QI, & Program Evaluation Difficult to determine sometimes whether a project constitutes research rather than QI/QA or program evaluation May be research if:  There is an intent to publish  Procedures involve randomization  Standard of care is altered

Case Studies/Case Reports Case reports involving three (3) or fewer patients generally do not require review by a UW-Madison IRB because they are not viewed as meeting the definition of research under the Common Rule HIPAA Privacy Rule may apply

What an IRB Assesses Writing Your Application to Address These Issues

What Does the IRB Evaluate? IRBs review research to help ensure: it is as safe as possible for people to take part in the study if there are serious risks, they are as low as possible and the right kind of monitoring is in place to prevent adverse effects or identify adverse outcomes as soon as possible that the subject population is the appropriate population to answer the study question the study design is acceptable so that  the question posed can be answered by the research  the right number of people will be enrolled (not too many or too few) so that as few people are exposed to risk as possible the information given to potential research participants is sufficient to allow them to make an informed choice about whether they want to take part in the research study

Put Another Way (What the Common Rule Says) Risks to subjects are minimized Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result Selection of subjects is equitable Informed consent will be sought from each prospective subject or the subject's legally authorized representative (includes ensuring consent forms contain required elements of consent) – consent can be waived by IRB in some cases Informed consent will be appropriately documented – documentation of informed consent can be waived by IRB in some cases The research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects

Submitting to an IRB

Which IRB? There are four campus IRBs Health Sciences IRB  Primarily reviews clinical trials/research protocols involving medical interventions Minimal Risk IRB  Primarily review medical records research, research database and tissue banking projects, survey and interview research, and exemption applications Social & Behavioral Sciences IRB  Reviews social, behavioral, and non-medical health research Education IRB  Concentrates on K-12 education research

Electronic IRB submission Implementation of ARROW, a system for electronic submission and tracking of IRB protocols, for all researchers as of November 17, 2010 Animal and biosafety committees expected to adopt this system as well Initial roll out began in 2010

Which Application Type? Initial Review Application: Full review Any study that presents more than minimal risk Minimal risk research that is not exempt or not a medical records review Some questionnaires, interviews, and survey studies (e.g., involving children, asking sensitive questions that are linked to identifiers)

Which Application Type? Initial Review Application: Non- Exempt Medical Records Review For studies of medical records or images (e.g., those that retain identifiers) May include some contact with patients for outcome information

Which Application Type? Initial Review Application: Exemption Must be minimal risk Some survey and interview studies Some evaluations of educational activities, curricula Use of existing data (e.g., medical records), specimens that are unidentifiable (e.g., residual tissue)

Exempt Research IRBs, not researchers, make the determination as to whether a research protocol is exempt Common examples of exempt research  Questionnaires, surveys, interviews that are anonymous or not sensitive  Chart review studies and no identifiers are recorded  Evaluations of educational techniques, curricula when the intent is to publish

Not Human Subjects Research IRB Office reviews to determine whether it meets the federal definition of “research” and/or of “human subject”  Once determination made no further interaction with IRB for project needed unless project begins to meet definition of research and/or includes human subjects Examples of not research  Program evaluation, quality assurance activities Examples of not involving human subjects  Use of coded data when researchers do not have access to the key to the code and entity holding code will not release link to researchers  Research on decedents

A Note on Identifiability An identifier includes any information that could be used to link research data with an individual subject.  E.g., initials, address, zip code, phone number, gender, age, birth date, occupation, employer, racial or ethnic group, type of biopsy performed, date sample taken, diagnosis, primary care physician, referring physician, and genealogy. Some of the identifiers listed above become less problematic if the sample size is large enough so that the potential identifiers could describe several individuals and thus cannot be linked to only one person. Data coded by numbers or letters that may be linked to identifiers are not anonymous or unidentifiable.

IRB Review Process

Overview of Submission and Review Process for Full Board Review (I) Electronic copy of application sent to the IRB Office first IRB Office will send to scientific review committee if needed If no scientific review required, the application will be forwarded to an IRB reviewer If scientific review required, IRB review does not proceed until the scientific review committee agrees the study can be forwarded to the IRB for review

Overview of Submission and Review Process for Full Board Review (II) If no scientific review needed or the scientific review committee approves, a staff reviewer will work with the study team to address any missing information, revisions needed to ensure the study complies with campus and federal policies and IRB review conventions 2 cycles of feedback are given by the staff reviewer Once the pre-review is complete, paper copies are then requested and the study is scheduled for review by the full IRB

Pre-Review Concentrates On… Completeness, accuracy of application Compliance with  institutional policy (e.g., PI qualifications, training requirements, COI issues)  State Law  federal regulations Common Rule FDA regulations, if applicable VA regulations, if applicable  other institutional precedents Spotting major issues that will be a challenge at the formal review stage

How to Contact the IRB

There are many ways to get information and help from the IRB…. View the WEBSITE at - contains policies, guidance, forms, news/updateswww.medicine.wisc.edu/irb CALL the HS-IRBs Office at we have nice, smart staff on call daily who can help you us at – general questions answered Make an APPOINTMENT for a consultation Questions about ARROW – or call Join our LIST-SERV – sign up to receive regular updates and newsletters from the IRB

Questions? (General or Project Specific)