CPHS: The Cliff Notes

Robert Nobles, MPHAssistant DirectorOffice of Research

Whitney, et al. Article Overview

• Qualitative e-mail survey with 14% response rate• Population: federally funded principal investigators• Comments were analyzed to show underlying

themes• In general, there was consensus that it is important

to protect human subjects from research abuse, but disagreement over how well the IRB system is functioning

Whitney, et al. Article Overview (2)

• Six primary questions in survey:

1. What has been your experience with the human subjects protection system in general? What do you like? What would you change?

2. What has been your experience with the informed consent process with potential subjects? Is there anything you would change?

3. Do you feel your IRB does its job well? If so, what helps you the most? If not, how could it improve?

Whitney, et al. Article Overview (2)

• Six survey questions continued:

4. Do you feel that your IRB usually understands your protocols adequately?

5. Have you ever served on an IRB?

6. What other thoughts do you have on informed consent and the human subjects protection system?

Whitney, et al. Article Overview (3)

• Positive Comments:– IRB functions as a safeguard against overoptimistic

investigators; protects subjects against both nonphysical and physical harms; and promotes “social justice.”

• Negative Comments:• The constraints placed upon investigators and indeed

research subjects by OHRP and so-called ethicists approaches the absurd.

Whitney, et al. Article Overview (4)

• Negative Comments Continued– Getting protocols approved gets worse each year

because you have to document more and more and more USELESS stuff.

– For most of my work I receive coded samples devoid of patient identifiers, yet I have to fill in all sorts of crap and repeat over and over again that I couldn't track down these subjects if I tried.

January 15, 2009 – Presentation Outline

• Research Quiz

• IRB Overview

• HIPAA Documents

• Research Misconduct

• Obtaining Informed Consent

• Questions and Answers

Research Quiz

• Question #1:– What is the purpose of an IRB?

• Question #2:– What is the definition of research and how does

research differ from standard practice?

Research Quiz (2)

• Question #3:– What are quality improvement projects and when

do they qualify as research projects?

• Question #4: – How long does it take for studies to get

approved? Why?

IRB Overview

• Mission: – To protect the rights and welfare of human

research participants.• Definition of Research:

– Systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

Key Features Of Research• Intent: generate new knowledge, principles, or

theories that revises or improves existing knowledge, programs or processes.

• Systematic collection and/or analysis of data.

• Anticipated results that are valid and generalizable

Functions of the IRB• Reviewing research to ensure:

– Risks are minimized– Risks are reasonable vs. benefits– Selection is equitable– Informed Consent is obtained– Data and Safety are protected/monitored– Privacy and confidentiality are upheld– Vulnerable population protections are enhanced

Protect Human Subjects in Research

1Federal Regulations2Investigators (faculty/staff/students)3Committee Members (faculty and community volunteers) 4CPHS Staff5Research Participants6Research Sponsors (funding entities)7Expert Consultants8IRIS (electronic reporting system)9Space Resources1Monitoring Program1Research Intermediary 1Collaborating agencies1UT Legal Affairs

Protocol submission

Protocol review

Modify consent forms

Consultation

Notification

Monitoring/ enforce-ment

Open Communication

Training

Documentation

Research Intermediary

Comply, critique

Approve, disapprove, or alter submission

Simplify, correct

Appropriateness confirmed

Fully informed

Compliance

Trust, efficiency

Competency gained

Record keeping, verification

Verification, reduce coercion

1Science and logistics enhanced2Consent is representative3 Cultural norms enforced4Transparent review process5Protection of subjects through record review6Trained/ethical investigators7QA and QI8Subject consent verified/ rights reiterated9 Quality IRB program implemented

CPHS Logic Model

Materials Submitted for Review

• Application• Protocol• Consent Forms• Letters of

Approval/Cooperation• Recruitment Flyers• HIPAA Forms• Investigator Brochure

• Pediatric Risk Assessment

• Grant Application• Data Collection Forms

(questionnaires)• Translations• *Change Request• *Continuing Review

Protocol Elements

• literature review/current state of knowledge

• justification for the study • potential use of study

findings • study design and

locations• hypothesis 

• Methodology• Description and source

of study population• Inclusion and exclusion

criteria• Number of participants• Sampling and

participant selection

Protocol Elements (2)

• Recruitment/enrollment activities

• Consenting process;• Confidentiality/privacy• Data monitoring• Explanation of study

instruments• Data analysis plan.

Types of Review• Exempt Research

– Case studies and retrospective chart reviews

• Expedited Review– Minimal Risk Protocols and minor changes to approved research– Collection of blood samples – Prospective collection of biological specimens by noninvasive means – Collection of data through noninvasive procedures routinely employed in clinical practice– Research on individual or group characteristics or behavior – Research employing survey, interview, oral history, focus group, program evaluation, human

factors evaluation, or quality assurance methodologies

Types of Review• Full Committee Review

– Protocols that have risks that are unknown or more than minimal

– Clinical trials• Including studies on drugs, devices, and procedures

– Cohort Studies– Case Control Studies– Cross-sectional study techniques in certain settings– Bio-banking and sample repositories

HIPAA Documents and the IRB

• HIPAA Exempt

• HIPAA Waivers subject to approval– Retrospective Chart Review– Screening and Recruitment– Decedent Data

• HIPAA Authorization for PHI

Misconduct Defined• (1) Fabrication, falsification, plagiarism and other forms of

misappropriation of ideas, or additional practices that seriously deviate from those that are commonly accepted in the research community for proposing, conducting, or reporting research.

• (2) Material failure to comply with federal and University requirements for the protection of researchers, human subjects, or the general public or for ensuring the welfare of laboratory animals.

Misconduct Defined (2)• (3) Failure to adhere to other material legal requirements

governing the field of research.• (4) Failure to comply with established standards regarding

author names on publications.• (5) Retaliation of any kind against a person who reported or

provided information about suspected or alleged misconduct and who has not acted in bad faith.

Additional Definitions• Plagiarism – appropriation of another person’s ideas,

processes, results, or words without giving appropriate credit• Fabrication – making up data or results and recording or

reporting them.• Falsification – manipulating research materials, equipment,

or processes, or changing or omitting data or results such that the research is not accurately represented in the research record.

Additional Definitions (2)• Noncompliance: Noncompliance is a failure by an investigator to

abide by research related requirements, good clinical practice requirements, CPHS requirements and applicable regulatory requirements. :– Failure to obtain approval for research prior to initiating the research

activities,– Continuing research activities beyond the expiration date without obtaining

continuing review approval, – Failure to obtain informed consent when required,– Failure to file an adverse event report,– Implementing changes to the protocol without prior approval.

Examples of Violated Research Ethics• 1945-1946 - Nuremburg Trials

– Included studies on hypothermia, infectious disease, altitude, pharmacologics, sterilization, surgery and traumatic injuries

• 1950’s – Willowbrook Hepatitis Study (New York)– Intentionally infected healthy “retarded” children by feeding

them feces from children with active hepatitis (with food) • 1955 – The Wichita Jury Study (Kansas)

– Audiotaped jurors to analyze decision-making without consent

• 1962 – The Thalidomide Experience (nationwide)– Investigational treatment given to pregnant women to

alleviate “unpleasant symptoms”

Examples of Violated Research Ethics Cont….• 1966 – “Ethics of Clinical Research” published by Dr. Beecher

(Harvard Medical School), NE Journal of Medicine– Cited ethical violations in 22 published articles

• 1960’s – Jewish Chronic Disease Hospital Studies (New York)– Injected live cancer cells in demented patients with weakened

immune systems• 1960’s – Milgram Studies of Obedience to Authority (Yale

University)– Participants deceived into thinking the study was evaluating the

role of negative reinforcement on learning• 1970’s – San Antonio Contraception Study

– Clinic randomized patients to active birth control or placebo

Examples of Violated Research Ethics Cont….• 1970’s – Tearoom Trade Study

– PhD Dissertation of Laud Humphrey’s from Washington University

– Observed men participating in sexual activities, served as a “watch queen”, copied license plates, and followed up with men one year later in disguise to gather additional information (i.e. marital status, employment, etc.)

• 1932 – 1972 – Tuskegee Syphilis Study (Alabama)– Evaluated the natural history of untreated syphilis– Led to the creation of NIH Office for the Protection – from Research Risks (now OHRP) and IRB’s

Oversight Of Human Subject Research

• 1949 – Nuremberg Code• 1964 – WMA Declaration of Helsinki• 1966 – PHS policy leading to IRBs• 1974 – National Research Act of 1974

established 45 CFR 46 • 1978 – The Belmont Report• 1991 – Common rule

Overview of Informed Consent Process and Forms

http://www.uth.tmc.edu/orsc/training/vids/informedconsent.html

Informed Consent Overview

• All modern codes of ethics concerning research with human subjects affirm the moral importance of a principle of informed consent.

• “The voluntary consent of the human subject is absolutely essential”

Overview (2)

• Obtaining consent is an ongoing process of communication and mutual understanding

• The process is misrepresented as:• A piece of paper• A moment in time• A legal contract

Overview (3)• Must be obtained for each research subject• Must be obtained prior to initiation of screening

procedures• Must be tailored to the level of understanding• If a medical term is essential, a lay definition is

needed• Sufficient opportunity must be given for consideration,

no coercion

Four Tenets

1. Accurate Information

2. Understanding

3. Voluntariness

4. Decision Making Capacity

Practical Benefits

• Increases subject adherence to the protocol and the quality of the research.

• Provides the benefit of an additional layer of risk review tailored to the interests of the individual subject.

• Fosters public trust

Four Reasons to Waive Informed Consent• 1) Investigations that do not constitute

research involving human subjects

• 2) Human subjects research that is exempt from compliance with federal regulations

Four Reasons to Waive Informed Consent (2)• 3) Non-exempt human subjects research in

which it is not possible to obtain participants’ written informed consent – For reasons of age, cognitive impairment, or the

like, some individuals are incapable of providing informed consent

– Research in emergency medicine

Four Reasons to Waive Informed Consent (2)• 4) Non-exempt human subjects research in

which it is not desirable to obtain participants’ written informed consent. – a signed informed consent document may pose a

risk to subjects, and – obtaining informed consent may diminish the

scientific merit of the research.

CPHS Reviewer Checklist

Office of Research Support Website

• https://iris.uth.tmc.edu/Login.jsp • Electronic submission of protocols to the IRB

– Initial submission– Change requests and amendments– Continuing reviews– Adverse Events, etc.

• Electronic routing and review by CPHS• Notifications are electronic and available via e-mail and within

iRIS

IRIS

• iRIS Web Site: http://iris.uth.tmc.edu • CPHS Web Site:

http://www.uth.tmc.edu/orsc/index.html • iRIS assistance: 713-500-7960• Office of Research Support Committees: 713-

500-7943• Robert Nobles: 713-500-7937

Important Information

Discussion/Questions