Brief Introduction to Review ofHuman Subjects Research in the

Health SciencesPresentation 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 randomizationStandard 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 reviewAny study that presents more than

minimal riskMinimal risk research that is not

exempt or not a medical records reviewSome 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: ExemptionMust be minimal riskSome survey and interview studiesSome evaluations of educational

activities, curriculaUse 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 researchQuestionnaires, surveys, interviews that are

anonymous or not sensitiveChart 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

Health Sciences IRBs Submission Process May 28, 2009

To the IRB for triage

OR

APPROVAL

APPROVAL

IRB ReviewAPPROVAL

Pre-Review by IRB Staff

Communication with Research

Team

No institutional scientific review needed

Modifications requested

Communication with Research

Team

Submission of New Protocol by Research Team

Institute of Clinical &

Translational Research (ICTR) Scientific Review

Communication with Research

Team

Cancer Center Scientific Review

Communication with Research

Team

OR

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 applicationCompliance with

institutional policy (e.g., PI qualifications, training requirements, COI issues)

State Lawfederal regulations

Common RuleFDA regulations, if applicableVA regulations, if applicable

other institutional precedentsSpotting 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 www.medicine.wisc.edu/irb - contains policies, guidance, forms, news/updates

CALL the HS-IRBs Office at 263-2362 - we have nice, smart staff on call daily who can help you

EMAIL us at AsktheIRB@medicine.wisc.edu – general questions answered promptly

Make an APPOINTMENT for a consultationQuestions about ARROW – email

askarrowirb@medicine.wisc.edu or call 262-0041 Join our LIST-SERV – sign up to receive regular

updates and newsletters from the IRB

Questions?(General or Project Specific)