CPHS: The Cliff Notes

1. CPHS: The Cliff Notes Robert Nobles, MPH Assistant Director Office of Research

3. 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

4. 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?

5. 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?

6. 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.

7. 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.

8. January 15, 2009 – Presentation Outline • Research Quiz • IRB Overview • HIPAA Documents • Research Misconduct • Obtaining Informed Consent • Questions and Answers

9. 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?

10. 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?

11. 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.

12. 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 resultsthat are valid and generalizable

13. 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

14. Comply, critique Protocol submission • Science and logistics enhanced • Consent is representative • Cultural norms enforced • Transparent review process • Protection of subjects through record review • Trained/ethical investigators • QA and QI • Subject consent verified/ rights reiterated • Quality IRB program implemented Approve, disapprove, or alter submission • Federal Regulations • Investigators (faculty/staff/students) • Committee Members (faculty and community volunteers) • CPHS Staff • Research Participants • Research Sponsors (funding entities) • Expert Consultants • IRIS (electronic reporting system) • Space Resources • Monitoring Program • Research Intermediary • Collaborating agencies • UT Legal Affairs Protocol review Simplify, correct Modify consent forms Appropriateness confirmed Consultation Protect Human Subjects in Research Notification Fully informed Monitoring/ enforce-ment Compliance Trust, efficiency Open Communication Competency gained Training Record keeping, verification Documentation Verification, reduce coercion Research Intermediary CPHS Logic Model

15. 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 Materials Submitted for Review

16. 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

17. Protocol Elements (2) • Recruitment/enrollment activities • Consenting process; • Confidentiality/privacy • Data monitoring • Explanation of study instruments • Data analysis plan.

18. 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

19. 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

20. HIPAA Documents and the IRB • HIPAA Exempt • HIPAA Waivers subject to approval • Retrospective Chart Review • Screening and Recruitment • Decedent Data • HIPAA Authorization for PHI

21. 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.

22. 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.

23. 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.

24. 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.

25. 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”

26. 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

27. 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

28. 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

29. Overview of Informed Consent Process and Forms http://www.uth.tmc.edu/orsc/training/vids/informedconsent.html

30. 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”

31. 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

32. 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

33. Four Tenets • Accurate Information • Understanding • Voluntariness • Decision Making Capacity

34. 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

35. 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

36. 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

37. 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.

38. CPHS Reviewer Checklist

39. Office of Research Support Website

40. IRIS • 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

41. Important Information • 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

42. Discussion/Questions