Regulations of Human Subject Research

Assessing Risk and Navigating through IRB Review

Heather Park-May, IRB AdministratorOctober 12, 2016

Agenda:

» Discuss Ethical considerations when doing research, and the Belmont Report

» Getting started with an idea, question, or identified knowledge gap.

» Distinguishing Research from QA/QI

» Elements and requirements of a consent form

» While the focus of this talk is on the IRB piece of the research regulatory pie, keep in mind that there are other things to consider that may apply to your research project such as:

Budget Coverage Analysis Material Transfer Agreement Contracts…

Researchers are Change Agents for the Healthcare Industry

» Research is the path to innovation and can empower all caregivers to discover ways to improve the care we provide in a way that is driven by data.

» Changes made to support our Researchers:1. Research Workshop Education Program

2. New streamlined MSU/Sparrow Reliance Process

3. Research Merit Review Committee

4. Efforts to centralize research at Sparrow to create a gateway for Sparrow and MSU researchers currently underway

Human Subjects ProtectionA Shared Responsibility:

1932-1972 Syphilis Study at Tuskegee1939-1945 Nazi Medical War Crimes1944-1974 Cold War Human Radiation Experiments1946- Nuremberg Doctors’ Trial1947- Nuremberg Code1948- United Nations adopted Universal Declaration 1953- First US Federal Policy for Protection of Human subjects1963- Jewish Chronic Disease Hospital Study1963-1966- Willowbrook Study1974- Federal Protections for Human Subject1979- Publication of the Belmont Report 1980- Publication of FDA Regulations1991- Publication of Common Rule1996- Health Insurance Portability and Accountability Act 1999- Death of Jesse Gelsinger2000- The Office of Human Research Protections Split from NIH.

Human Subjects Historical Timeline

Tuskegee Syphilis Study“ Sometimes, with the best of intentions, scientists and public officials…working for the benefit of us all, forget that people are people. They concentrate so totally on plans and programs, experiments, statistics- on abstractions- that people become objects, symbols on paper, figures in a mathematical formula…”

- Atlanta Constitution, July 27 1972

Belmont Report: 3 Ethical Principles

•Respect For Persons•Beneficence • Justice

Respect For Persons (1785)Idea began with Immanuel Kant:Leading Philosopher of Deontology and the categorical imperative of treating every rational being as a free rational agent, and as ends in themselves.

Principle:•Subjects are respected as Autonomous Beings•Protection of Subjects with Limited Autonomy (Minors, cognitively impaired)

Applications:•Informed Consent • Informed• Competent• Voluntary

•Subjects’ Assent and Third Party Consent

Beneficence (1789)

Beneficence is a concept in research ethics which states that researchers should have the welfare of the research participant as a goal of any clinical trial or other research study. •The antonym of this term, maleficence, describes a practice which opposes the welfare of any research participant.

Jeremy Bentham: Philosopher of Utilitarianism and the Principle of Utility of the Greatest Happiness of the Greatest Number

Principle:•Do No Harm•Maximize Benefits and Minimize Possible Harms

Applications:•Favorable Risk/Benefit Assessment•Systematic Analysis and Minimization of Acceptable Risks of Harm

Justice (350 BCE)Aristotle: Leading philosopher of Aristotelian Philosophy and of the principle of distributive justice, distributing goods, rights, burdens, etc, according to what people deserve.

Principle:•Distribute Burdens and Benefits Equitably•Don’t Exploit Vulnerable Populations

Applications:•Select Individuals and Classes of Subjects Equitably•Link burdens to benefits.

The history of unethical research practices shaped the regulations we follow today.

Refer to the Quality or Research Guidance Form Provided

» Step 1. Set up a good research project» Identify a knowledge gap in your area of interest

» Conduct a literature review. Library!

» Step 2: Determine if your idea/hypothesis will involve research to test.

» Definition of Research: Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

Getting Started:

So to be research you must have:

1. Systematic investigation

2. Research development

3. Testing and evaluation

4. Intent of contributing to generalizable knowledge

Your Study Is Research If:» You are testing a hypothesis

» Your activity is outside of the standard of care

» You are doing a group comparison to test your hypothesis

» Your study seeks to test an intervention which is beyond current science and experience

Most resident studies take the form of retrospective or prospective record reviews. If your testing a hypothesis with

the data you are gathering and you intend to develop or contribute to generalizable knowledge your study is research.

QI Study Aim’sIf there is NO intention of using the data for research

purposes and…»improve a process or delivery of care with established or accepted quality standards

»to implement change mandated by sparrow clinical quality improvement program

»to improve performance on a service or program in the hospital and is part of the normal standard of care

MSU Reliance Agreement» MSU affiliated Investigators conducting research at Sparrow Facilities and/or with

Sparrow Patients or Sparrow data will require the use of the Reliance process. This means you go through the MSU IRB as the IRB of record.

» Your requirements for the Sparrow IRB are minimal.

» We ask that you submit your reliance application (Simple 3 page application) along with the completed protocol impact statement to the MSU online submission system. The MSU IRB and the Sparrow IRB communicate through the MSU IRB review process.

Keep in mind Sparrow Patients need to receive a Sparrow template Consent Form, and HIPAA Authorization to Release PHI for Purposes of Research form. Available on IRBNet and on the Website. www.sparrow.org/irb

» You may begin research when you have approval letters from both IRB’s.

When does the Reliance process apply?» You are an MSU individual and your research:

• Involves any intervention for research purposes with Sparrow patients as human subjects of the research by performing invasive or noninvasive procedures.

• Examples of invasive procedures:

• Collecting buccal mucosa cells using a cotton swab

• Administering individual or group counseling or psychotherapy

• Administering drugs or other treatments

• Surgically implanting medical devices

• Utilizing physical sensors

• Utilizing other measurement procedures

When does the Reliance Process Apply Cont.

• Involves the collection of protected health information about the Sparrow patients as subjects of the research.

• Any intervention for research purposes with any Sparrow patients as human subjects by manipulating the environment

Examples: Controlling environmental light, sound, temperature, presenting sensory stimuli, orchestrating environmental events or social interactions.

» And others! See HRPP Manual 4-1 for more information about when MSU review is required

If it is not clear whether your study falls within these descriptions, contact the Sparrow OHRA, or MSU IRB staff. We are here to help!

What the reliance process actually involves:

Prepare Research Protocol

Prepare and submit required documents to the MSU IRB

Obtain Appropriate Sparrow departmental approval

Communicate with MSU and Sparrow IRB through MSU online submission system

Begin Research

Obtain Approval Notification

Protocol Impact Statement

MSU IRB

IRB Submission Requirements

» Complete Initial Application

» Abstract

» Protocol

» Completed Protocol Impact Statement

» Other applicable study documents: Consent form, Investigator’s brochure…

» An Attending Physician to lead the study as PI for resident studies.

» Nursing Research Council approval for nursing studies.

» Curriculum Vitae or Resume of all researchers

All forms and templates are available on the website: sparrow.org/irb, IRBnet (forms and templates) and on New Innovations

Elements of the Consent Form» Study Title

» Researcher’s information department, and contact info

» Introduction

» Why is this study being done?

» How many people will participate?

» What will happen if I participate?

» How long will I be in the study?

» What are the side effects, or risks to my participation?

» What are the benefits of participating?

Elements of the Consent Form» What choices do I have if I chose not to participate?

» What are the costs to me ?

» What happens if I am injured as a result of participating?

» Termination of the Study

» What are my rights if I participate?

» Will my medical information be kept confidential?

» Who can answer my questions about the study?

The research process and medical terminology is confusing for most subjects, which is why we ask that you limit your medical jargon, and spell out all acronyms used, and write the document at an 8th grade reading level.

HIPAA Authorization Documentation

HIPAA Authorization Documentation and Covered Entities

Individuals engaged in human subject research are responsible for complying with all requirements regarding use or disclosure of PHI, including those set forth in HIPAA and implemented by the covered entity(ies).

What HIPAA form template should I use?

» MSU: If the PHI will be obtained from a clinic that is part of the MSU covered entity, use of the template “MSU Health Team Research Authorization Form” is required.

» If your research requires subjects to sign a consent form and you will be using Sparrow PHI, you will use the Sparrow HIPAA Authorization Form Template

» If your research only involves a retrospective record review of Sparrow PHI, and/or it is not practicable to obtain authorization from the patient to use their PHI for research, you will complete the Sparrow Request for Waiver of Authorization form.

» If you will need to obtain Sparrow PHI before you are able to meet with your subject and discuss the study for enrollment purposes, you will complete the Partial Waiver of Authorization

HIPAA Documentation By Study Type

» Research designed in a way where it is not practicable to obtain signed HIPAA Authorization:

HIPAA Waiver of Authorization » Research designed in a way where it IS possible to

obtain signed HIPAA Authorization:HIPAA Authorization to Disclose PHI for Research

» Access to limited PHI such as name and address for recruitment purposes:

HIPAA Partial Waiver of Authorization

* CITI TrainingWhat is it?»An internet based system that provides and tracks human subjects research (HST) training required by OHRP to conduct research

Who does it apply to?»All individuals engaged in research activities. This includes anyone delegated to collect or analyze data.

How long does it take?»Everyone works at a different pace, however it can take anywhere from 4-8 hours. It can be completed in more than one sitting. The program saves your progress. So be sure to calculate this time into your research project plan

Does it expire?»Yes. The CITI program training is good for 3 years, so it is important to be aware of when it expires.

How Do I Complete My CITI Training» Go to www.citiprogram.com

» Register as a new user (or sign in)

» When prompted, select “Sparrow Health System” under “Participating Institutions” then continue to Step 2.

» Complete the required fields in steps 2 thru 6

» For Step 7, question 1, select the learner group that best represents you. In most cases it will be the Biomedical Researcher learner group.

Learner Modules» Biomedical Researcher» Chose this group if your research does not fall within any of the other

categories below» Sparrow Clinical Research Institute Researchers» Chose this group if you are involved in research through the Sparrow Clinical research institute

» Cancer Center Researchers

» Chose this group if you are involved in research through the Sparrow Cancer Center

» Humanitarian Use Device (HUD) Investigators

» Chose this group if you are involved in HUD Studies

» Nursing Research Council Members

» Chose this group if you are a member of the Nursing Research Council

» IRB Members

» IRB Community/Non-Scientific Member

Optional Modules» For researchers working with a sponsor, you may find

that the Sponsor has specific requirements for HST training modules. In order to comply with additional sponsor requirements, we have several optional modules.

» There are modules on hot topics such as stem cell research and Social Behavioral Methodologies in Biomedical Research.

» Our newest module is on Clinical Trial Billing Compliance.

Using IRBNet

To begin the registration process, go to www.irbnet.org and click on the New User Registration link.

Users that are not registered on IRBNet may click here to self-register

If you have forgotten your password, click here.

New Project Submission

As a Researcher, Research Manager, or Research Coordinator you should know how to:

Log In to IRBNet• Access My Projects• Build Your First Electronic Project Package• Share with Your Research Team• Communicate with Your Team• Sign Your Project Package• Submit Your Project Package for Review• Revise Incomplete Submissions• Access Review Decisions and Board Documentation

Continuing Review; AmendmentsContinuing Review:Pay close attention to the expiration date of the study on the approval letter.

Be sure to submit your continuing review application to renew your study well in advance of the expiration date to avoid a lapse in IRB approval.

60 day IRBNet e-mail reminder Exempt studies are not required to be renewed yearly, however it is

Sparrow’s procedure to touch base with researchers of exempt status studies to see if the study is still ongoing, or if it has been closed.

Amendments: Any changes to protocol, IRB approved forms, documentation, data

collection procedures or researchers involved need to be submitted to the IRB through an amendment application.

PI Responsibilities

The term Principal Investigator (PI) defined as the individual under whose immediate direction the research activities (i.e., focus group, survey, and drug or device trial) occur.

The protection of human research subjects is a shared responsibility between the PI, the institutional review boards and the sponsor (as applicable). The PI must acknowledge that regulations governing human subjects’ research are an additional area of expertise and that the Sparrow OHRA staff are available to provide guidance as needed.

The PI is ultimately responsible for:» Submitting proposed research for approval by the IRB

» All actions that take place during a clinical study to ensure patient safety at all times by abiding by and promoting Good Clinical Practices guidelines. The PI may delegate some tasks and responsibilities but retains ultimate responsibility for the ethical conduct of the research.

» Training and communicating with research team members.

» Requesting continuing review of the research and ensuring the IRB that the research is proceeding according to all applicable regulations

» Notifying the IRB of any upcoming audits (Sponsor, FDA, OHRP, etc) and then providing the IRB with a copy of the audit report. (Notification of routine monitoring visits not required.)

» Reporting to the IRB any findings and allegations of non-compliance

» Notifying the IRB in writing prior to leaving the institution. (Sparrow, or MSU) with a plan to either terminate ongoing studies, or designate a new PI.

In order to fulfil these responsibilities the PI should:» Be aware of the resources available :

» Department of Health and Human Services, Office for Human Research Protections, and the Food and Drug Administration

» Have realistic expectations of research team members and understanding their positions and time commitments

» Have access to the internet

» Understand and follow institutional policies, SOP’s and guidance concerning human subject research.

» Understand and follow FDA, DHHS and OHRP rules and regulations for human subject research

» Have access to and read/respond to email

» Obtain informed consent and continuing consent from subjects if applicable.

» Carefully review lab reports and subjects history/physical findings noting any abnormalities while reviewing in the context of known effects of drug/device under study.

» Delegate Duties of research team in writing

» Complete required HST training (CITI or MSU’s HST training modules)

» Ask questions when needed and encourage other research team members to do the same

New Project SubmissionAs a Researcher, Research Manager, or Research Coordinator you should know how to:

Log In to IRBNet• Access My Projects• Build Your First Electronic Project Package• Share with Your Research Team• Communicate with Your Team• Sign Your Project Package• Submit Your Project Package for Review• Revise Incomplete Submissions• Access Review Decisions and Board Documentation

Additional Technical Guidance»www.sparrow.org/researchers

Tips for a Smooth Review• Assess the feasibility of your protocol

• Literature Review!: Check out the Sparrow Library!

• Is there enough data available

• Do you have a well defined research plan

• Does your study address a valid need

• Do you have appropriate resources and funding

• Obtain appropriate Sparrow departmental approval prior to IRB submission.

• Discuss ALL resources that will be required to follow the protocol

• Be as detailed as possible when responding to questions in the IRB application

• Submit all required documents:

• Read all instructional material provided

MSU Researchers:

• Check the comments in the MSU online review system frequently

• Contact the MSU IRB if you have any questions.

More information available on websites

» Sparrow: www.sparrow.org/researchers

»http://www.sparrow.org/?id=2365&sid=1

»http://www.sparrow.org/sparrowlibrary

» MSU: http://hrpp.msu.edu/

»http://hrpp.msu.edu/forms

The Sparrow Way» In order to address the challenges of increasing prevalence of chronic disease

and an aging population, to improve the quality of care and the Patient experience while also ensuring greater affordability, Sparrow needs to implement profound changes in how care is provided.

The work of the brilliant minds in this room is how we get there!

» This change starts with the system-wide adoption of the Sparrow Way. In partnership with our Caregivers and Physicians, the Sparrow Way is a commitment to ensuring that the Patient care delivered at Sparrow adheres to Patient-centered, evidence-based best practices.

http://www.sparrow.org/?id=1540&sid=1

Thank You!