Ethics and Clinical Research

1
Ethics andClinical Research

• John Butterworth, MD
• Professor Head
• Section on Cardiothoracic Anesthesiology
• Wake Forest University School of Medicine
• Winston-Salem, NC 27157 USA

2
Ethics and Clinical Research Lecture outline

• What is clinical research
• Statistical issues
• Ethical basis of clinical research
• IRB issues
• Recruiting issues
• HIPAA

3
What is clinical research and why is it important?

• Involves humans
• Provides access to advancesin patient care
  (latest drugs,new devices, new processesof
  care)
• Innovative clinical research and innovative care
  provide intellectual stimulation to the
  practicing physician

4
What is a clinical trial?

• Prospective study in humans
• Compares at least 2 interventions
• One is experimental treatment
• One serves as control
• Null hypothesis no treatment difference
• Ideal design
• Randomized subject assignment
• Double-blinded (double-masked)

Friedman, Furberg, DeMets Fundamentals of
Clinical Trials
5
What are the phases of drug development?

• Phase 1 (maximum tolerated dose, pk)
• Phase 2 (biologic effect, rate of AEs)
• Phase 3 (comparative efficacy, safety)
• Phase 4 (post-marketing studies in special
  groups, e.g. children)

Friedman, Furberg, DeMets Fundamentals of
Clinical Trials
6
Ethics and Clinical Research Lecture outline

• What is clinical research
• Statistical issues
• Ethical basis of clinical research
• IRB issues
• Recruiting issues
• HIPAA

7
Ethical studies are well designed!

• Question is worthy (scientifically valid)
• Adequately powered (enough subjects)
• Appropriate randomization procedures\
• Appropriate masking (blinding)
• Appropriate data analysis and publications

8
What is the Hypothesis?

• Each clinical trial has a primary question
  (central hypothesis)
• The one in which investigators have greatest
  interest
• The reason for the study
• Sample size of the study is selected (power) to
  test central hypothesis
• Test of central hypothesis is result on which
  study publication should focus

9
Testing an Hypothesis

• Null hypothesis - typically the negation of what
  you want to show (e.g., treatment A is no better
  than treatment B)
• Alternative hypothesis - typically the statement
  you want to show (e.g., treatment A is better
  than treatment B)
• Assume null hypothesis unless we have convincing
  evidence to the contrary
• Make decision using a statistical test.

10
We can be wrong each time we make a decision!

• We can falsely reject a true null hypothesis
• Type I error
• Probability of this error denoted by ?
• We can fail to reject a false null hypothesis
• Type II error
• Probability of this error denoted by ?
• Complement of type II error (1-?)
• Power
• Probability of correctly rejecting null hypothesis

11
Presenting Evidence inClinical Research

• P-value probability of falsely rejecting null
  hypothesis
• Confidence interval
• Range of likely differences that might exist
  between treatments
• Particularly useful for describing results which
  are not statistically significant

12
Randomization prevents allocation bias

• To assure comparability of groups with respect to
  all factors except for one being studied
• Methods of randomization
• Simple
• Block (Balanced)
• Stratified

13
Blinding

• Mask the treatment from the patient and/or the
  investigator
• Single Blind - Subject blinded - protects against
  response bias
• Double Blind - Subject and investigator blinded -
  also protects against assessment and allocation
  bias

14
Ethics and Clinical Research Lecture outline

• What is clinical research
• Statistical issues
• Ethical basis of clinical research
• IRB issues
• Recruiting issues
• HIPAA

15
Consensus documents, ethics,and clinical research

• Primum Non Nocere First do no harm (Hippocrates
  Epidemics)
• Nuremberg Code
• Declaration of Helsinki (International Conference
  on Harmonisation)
• Belmont Report

• See
• http//www.fda.gov/oc/gcp/regulations.html
• http//ohrp.osophs.dhhs.gov/educmat.htm
• http//ohsr.od.nih.gov

16
Key US Regulations Governing the Conduct of
Clinical Trials
Regulations directed toward protection of human
research subjects 21 CFR Part 50 Informed
Consent 21 CFR Part 56 IRB Regulations These
are nearly identical to the Common Rule
governing protection of human subjects in
federally funded research 45 CFR Part 46
17

• Key US Regulations Governing the Conduct of
  Clinical Trials
• Regulations pertaining to the Food and Drug
  Administration
• 21 CFR Part 312 IND Regulations (drug)
• 21 CFR Part 812 IDE Regulations (device)
• 21 CFR Part 314 NDA Regulations (drug)
• 21 CFR Part 814 PMA Regulations (device)
• 21 CFR Part 11 Electronic Records
• 21 CFR Part 54 Financial Disclosure

18
Declaration of Helsinki Basic Principles I

• Interests of subjects must always prevail over
  interests of science and society
• Research must have importance proportionate to
  inherent risk (risks acceptable given benefits to
  individuals)
• Research must conform to accepted scientific
  principles design appropriate and clear in
  experimental protocol

19
Declaration of HelsinkiBasic Principles II

• Research conducted by qualified persons
• Safeguard subjects integrity privacy
• Abstain unless hazards are predictable
• Inform subjects of their right to withdraw
• Obtain true informed consent from subject or
  legal guardian
• Present results accurately in publications

20
Declaration of HelsinkiUse of placebos

• In any medical study,
• every patient--including
• those of a control group,
• if any--should be
• assured of the best
• proven diagnostic and
• therapeutic method. This does not exclude the
• use of inert placebo in studies where no proven
• diagnostic or therapeutic method exists.

21
Elements of Good Clinical Practice (GCPs) for PIs

• PIs will be held accountable for the ethical
  conduct and integrity of the study
• Qualified PI and staff
• Appropriate delegation of responsibilities
• Adequate staffing, resources, facilities
• Study drug accountability
• Appropriate communication with IRB

22
GCPs for Study Investigators(continued)

• Comply with protocol complete the study
• Enroll appropriate subjects meet enrollment
  targets
• Follow randomization and blinding procedures
• Treatment administration per protocol
• Measurement of study outcomes
• Maintain audit trail (paper/electronic)
• Complete/process/file all study reports
• Appropriate post-study follow-up for participants
• Participate in dissemination of results

23
GCPs for Study Investigators(continued)

• PIs must provide adequate medical care for study
  subjects
• Monitor, treat, report adverse events (AEs)
• Inform participant primary care MD when care is
  needed for intercurrent illness(es)
• PIs may refer subject to primary caregiver when
  appropriate

24
Ethical Safeguards

• Clinical Equipoise Uncertainty
• whether treatment is better
• than control
• Informed consent
• Institutional review board (ethics
• committee) review
• Independent Data and Safety
• Monitoring Board
• Reviews protocol
• Monitors data
• May recommend trial termination

Henry K. Beecher 1904-1976
25
Unethical Study-TuskegeeStudy of Syphilis

• Federally-funded study of natural history of
  syphilis (TSS)
• In 1932, no effective treatment
• 412 infected, indigent blacks enrolled
  (vulnerable population)
• 1951-penicillin standard treatment TSS subjects
  excluded from penicillin
• 1972/74-public disclosure hearings financial
  settlement

26
Unethical Studies HIV Transmission

• Zidovudine reduces HIV transmission from mother
  to child by 2/3 (1994)
• Complex costly treatment regimen
• Simpler regimen suspected effective
• Placebo-controlled trials
• 15 of 16 in developing countries
• 9 of these U.S. funded (1997)
• Stimulated debate re placebo treatment

27
Unethical Treatment of Human Subject-Gene
Transfer Trial

• Jesse Gelsinger, an 18 yr. old with mild
  ornithine transcarbamylase deficiency
• Symptoms controlled with drugs and diet
• Gene-therapy study to determine safety, not
  efficacy consent incomplete
• Injection of virus vector that had killed animals
• Parents inadequately advised about risks
• PI conflict of interest
• 4 days after therapy, patient brain-dead 17 Sep
  99

28
Unethical Treatment of Human Subject-Gene
Transfer Trial

• Jesse Gelsinger, an 18 yr. old with mild
  ornithine transcarbamylase deficiency
• Symptoms controlled with drugs and diet
• Gene-therapy study to determine safety, not
  efficacy consent incomplete
• Injection of virus vector that had killed animals
• Parents inadequately advised about risks
• PI conflict of interest
• 4 days after therapy, patient brain-dead 17 Sep
  99

29
Hexamethonium challenge study

• Normal volunteers inhaled examethonium as
  pulmonary vasodilator large literature on
  toxicity (in older publications)
• Volunteer 1 with flu not reported to IRB
• Shortly thereafter, volunteer 3, 24 years old
  died of respiratory failure 2 June 2001

Ellen Roche Volunteer 3
30
Investigator Fraud Dr. Robert Fiddes

• Conducted gt200 studies for 47 sponsors at
  Southern California Research Institute
• Used false study subjects, laboratory results,
  urine samples, medical records, radiographs!
• Passed all audits, but turned in by whistle
  blowing former employee
• Sentenced to 15 months in prison, fined 800,000,
  lost medical license (1997)
• FDA debars Dr. Fiddes and 3 nurse coordinators
  from all clinical research activities (2002)

Ref www.thompson.com/libraries/fooddrug/clin/ind
ex.html
31
Investigator Conflicts of Interest

• Professional gain publications/promotion
• Financial gain
• Patient finders fee to collaborators
• Recruitment bonuses
• Affiliation with/funding from sponsor for future
  studies, consultant relationships
• Other incentives (e.g., travel, presentations)
• Per patient payment system presents conflicts of
  interest inherent in capitalist society

32
Potential Consequences of Investigator Conflicts
of Interest

• Attempting to ?study enrollment
• Coercing subjects to enroll and discouraging
  withdrawal, treatment alternatives
• Enrolling fictitious or ineligible patients
• Bias trial toward positive results
• Failure to report AEs
• Failure to comply with protocol regimens
• Alteration of outcome data
• Data fabrication

33
Ethical Safeguards Against Financial Conflicts
of Interest

• Full disclosure (institution, collaborators,
  journal editors, FDA)
• Disclosure not meant to prevent investigators
  from participating in research
• Disclosure statements also apply to study staff,
  spouses, and dependent children
• Restrictions (decisions, presentations)
• Regulatory/legal action for failure to comply

34
Sponsor Conflicts of Interests

• Pressure investigator to withhold negative
  results or to spin positive results
• Unreasonable control of data analyses
• Discrediting investigators research (through
  word-of-mouth, publications, presentations)-
  The Thyroid Storm
• Threat of loss of contractual work
• Threat of legal action

35
Unethical Sponsor BehaviorMIDAS study

• Randomized clinical trial of isradipine vs
  hydrochlorothiazide in 883 hypertensives
• No difference for 1º endpoint (carotid
  intramedial thickness)
• Isradipine caused increase in CV events
• Sponsor not prepared for negative results
• Interfered with publication process

36
Ethics and Clinical Research Lecture outline

• What is clinical research
• Statistical issues
• Ethical basis of clinical research
• IRB issues
• Recruiting issues
• HIPAA

37
Institutional Review Boards (IRBs)

• Primary institutional responsibility for
  protection of human research subjects (PI
  responsible for study conduct)
• Human research may be conducted only after IRB
  review and approval
• Types of IRBs in the USA
• LOCAL (covered by the OHRP Assurance for Human
  Research at academic institutions)
• INDEPENDENT (national) Preferred by most
  pharmaceutical industry sponsors may be used by
  any non-academic independent site

38
How the IRB members see themselves
39
IRB Membership

• gt5 members, both men and women
• Diversity of backgrounds
• Sensitive to community attitudes
• Expertise and experience (ad hoc experts added as
  needed)
• gt1 scientist
• Nonaffiliated member from the local community
• Members must avoid conflict of interest
• gt1 non-scientist must be present for all votes

40
IRB Membership (cont.)

• gt1 member with specific expertise about
  vulnerable subjects
• Children
• Pregnant women
• Prisoners
• Students
• Handicapped
• Mentally disabled
• Chair of the IRB
• Respected individual
• Fair and impartial
• Oblivious to pressure from PIs and administration

41
IRB Jurisdiction

• Research or Therapy?
• Research is a systematic investigation designed
  to contribute to generalizable knowledge
• Human subjects or not?
• Human subjects are living individuals about whom
  an investigator obtains data through intervention
  or interaction or obtains identifiable private
  information

42
Ethical Principles in Human Research What the
IRB Seeks

• Respect for Persons
• Written Informed Consent
• Beneficence
• Risk vs. Benefit Decisions
• Justice
• Subject Selection
• Recruitment
• Inclusion/Exclusion Criteria

Source The Belmont Report, April 18, 1979 see
http//ohsr.od.nih.gov
43
IRB Review

• Well-designed research proposal
• Plan for proper execution of proposal
• Avoids unnecessary risk to subjects
• Protects investigators and institution
• Minimizes risk to subjects (consider risk vs.
  benefit)
• Equitable subject selection
• Informed consent obtained
• Safety monitoring
• Confidentiality of data

44
Categories of Human Research

• Exempt
• Expeditable
• Full Board Review

45
Exempt research

• Educational testing
• Surveys without individuals identification
• Use of existing data, documents, or records with
  no identifiers or links to subjects
• Only the IRB can decide a project is exempt!

46
Expedited Review

• One experienced IRB member
• Reported to full IRB
• Study with minimal risk of harm, and
• 1. Drugs or devices - no IND, IDE
• 2. Blood - healthy adults others
• 3. Hair, nails, teeth, excreta, secretions
• 4. Noninvasive clinical procedures
• 5. Data, documents, records
• 6. Voice, video, image recordings
• 7. Behavior or characteristics

47
WFUSM IRB ProceduresFull Board Review
48
IRB Jurisdiction

• Institutional Officials may disapprove
  IRB-approved research
• Institutional Officials may not approve research
  disapproved by IRB

49
IRB Review and Approval

• Up to one year approval (IRB may shorten
  duration)
• Progress report - renewal one year
• ANY change in protocol or consent form must be
  communicated to IRB
• Minor changes may be expedited

50
Informed Consent

• Provided to subject, or legally authorized
  representative (spouse, next of kin)
• Minors-parental consent (one or both) and assent
  of child, unless child emancipated
• Explanation in lay language
• Questions answered
• Copy of form given to subject
• A process, not a form with a signature!

51
Informed ConsentMandatory Elements

• Research
• Purpose
• Description
• Procedures
• Risks
• Benefits
• Alternatives

• Confidentiality
• Compensation, treatment for injury
• Contact for questions
• Contact for research subjects rights
• Right to refuse or withdraw

52
Minors as Research Subjects

• Assent is the minors affirmative agreement to
  take part in research
• Necessary when IRB judges children are capable of
  assenting (age, maturity
• May be waived if prospect of direct benefit
  available only in research context
• Assent may be oral or written

53
When May IRB WaiveConsent Process?

• Minimal risk
• Rights and welfare not adversely affected
• Not practical without waiver (but must provide
  information after participation)
• Amiodarone for resuscitation
• Procedure does not require written consent
  outside of research

54
Examples of Research Requiring IRB Approval

• Clinic chart review when any identifier recorded
• Clinical trial of investigational new drug
• Venous blood sample from volunteer
• Patient data with identifiers obtained from
  colleagues

55
Examples of Research not Requiring IRB Approval

• Use of autopsy material
• Case report
• Chart review - no identifiers recorded (IRB
  declares exempt)
• Monitoring of clinic operations for quality
  control

56
Ethics and Clinical Research Lecture outline

• What is clinical research
• Statistical issues
• Ethical basis of clinical research
• IRB issues
• Recruiting issues
• HIPAA

57
Recruiting StrategiesRecruitment always takes
longerthan initially anticipated

• Physician/nurse referrals
• Chart reviews
• Direct patient contact (within practice)
• Media (radio, TV, cable, newspapers)
• Mass mailing
• Mass screening (shopping mall, sporting events)
• Internet
• IRB MUST APPROVE ALL ADVERTISEMENTS

58
Factors reducing volunteer willingness to
participate in clinical trials (n941)

• Insufficient compensation 21
• Hospitalization needed 29
• Possibility of receiving placebo 46
• Inconvenient location 62
• Risk of side effects 63

CenterWatch, March 2003, p 4
59
Reasons that pre-qualified volunteers drop out
before randomization

• No follow up contact from site 23
• No interest after contacted by site 14
• No convenient site available 13

CenterWatch, March 2003, p 1
60
Ethics and Clinical Research Lecture outline

• What is clinical research
• Statistical issues
• Ethical basis of clinical research
• IRB issues
• Recruiting issues
• HIPAA

61
The Health Insurance Portability and
Accountability Act of 1996AKA Public Law
104-191AKA HIPAA
Congressional attempt at incremental health care
reform through portability administrative
simplification
62
HIPPA Components
63
What is Covered in the Privacy Rule? Protected
Health Information (PHI)

• Health information Identifier PHI
• Transmitted or maintained in any form (paper,
  electronic, web-based, etc.)
• Decedents information included
• Does not include de-identified health information

64
What Health Information is envisioned by the
Privacy Rule?

• Any information, oral or recorded that
• Is created or received by a health care provider,
  health plan, public health authority, employer,
  life insurer, school or university, or health
  care clearinghouse, and
• Relates to the past, present, or future physical
  or mental health or condition of an individual
  the provision of health care to an individual or
  the past, present or future payment for the
  provision of health care to an individual, and
• That identifies the individual, or
• Where there is a reasonable basis to believe that
  the information can be used to identify the
  individual

65
The Privacy Rule defines 18 identifiers

• Name
• Geographic information (including city, state and
  zip)
• Elements of dates (including admission/discharge
  dates service dates birth date, date of death)
• Telephone numbers
• FAX numbers
• E-mail addresses
• Social Security number
• Medical Record number, prescription number, etc.
• Health plan beneficiary number

• Account Numbers
• Certification numbers
• VIN and Serial numbers, license plate numbers
• Device identifiers and serial numbers
• Web URLs
• IP address numbers
• Biometric identifiers (finger prints, voice
  prints, retinal scans, etc.)
• Full face or comparable photo images
• Unique identifying numbers

66
How does the Privacy Ruleprotect PHI?

• Establishes conditions for use of PHI
• Establishes conditions for disclosure of PHI
• Has additional protections for uses and
  disclosures made without the persons permission
  (minimum necessary standard)
• Gives individuals rights to information about
  themselves and how it has been used and disclosed

67
Key Terms in HIPAA

• Use
• Sharing of PHI within or among the Medical Center
  departments
• Disclosure
• Sharing of PHI to external entities
• Incidental Disclosures
• Patient logs
• Waiting/Patient rooms
• Non-Specific Telephone conversations

68
Key Terms in HIPAA

• Research
• Systematic investigation, including research
  development, testing and evaluation, designed to
  develop or contribute to generalizable knowledge
• Authorization
• Customized document gives permission to use PHI
  for specific purposes
• Patient Authorization is NOT synonymous with
  patient consent for either research or clinical
  care

69
Key Terms in HIPAA

• Notice of Privacy Practices (NPP)
• Document that explains how patients information
  is used disclosed in the Medical Center.
• Explains patients rights.
• Will be available to each patient who enters the
  Medical Center.
• RESEARCHERS MUST MAKE SURE THIS IS AVAILABLE TO
  RESEARCH SUBJECTS
• Is NOT an Authorization for the use and
  disclosure of PHI
• Patients Rights include
• Inspect Copy PHI
• An Accounting of Disclosures
• Request Restrictions
• Request Confidential Contacts
• Paper Copy of the Notice of Patient Privacy
• Opt out of Hospital Directory

70
Privacy Rule and ResearchGeneral Concepts

• HIPAA establishes conditions for use and
  disclosure of PHI in research
• Applies to all research regardless of funding
• HIPAA exceeds other privacy protections in the
  Common Rule and FDA regulations
• Written Authorization is required for the use or
  disclosure of PHI unless Authorization is waived
  or excepted
• Authorization waivers can be granted by IRBs or
  Privacy Boards under limited circumstances
• Decedents information is protected but
  Authorization is not required
• Accounting and reporting of disclosures are
  required

71
Research under HIPAA

• Situation in which PHI may be used for research
  purposes
• With individual Authorization
• With waiver of Authorization by IRB or Privacy
  Board
• By De-Identification of PHI
• As a Limited Data Set with Data Use Agreement
• As an activity preparatory to research
• For research on decedents information

72
Research Use and Disclosure of PHI With
Authorizations for Research

• Must be for a specific research study blanket
  Authorization NOT permitted
• Review/approval by IRB or Privacy Board not HIPAA
  required but likely to be IRB required
• Authorization may be combined with the research
  study informed consent
• Must contain core elements and required
  statements in the Rule
• Research authorizations need not expire
• Authorization needed to create a repository (data
  or biological material) for future research

73
Research Use and Disclosure of PHI Without
Authorization

• IRB or Privacy Board waiver of Authorization
  requirement
• De-identify PHI
• Limited Data Set with Data Use Agreement
• Activity preparatory to research
• Research is on decedents information
• Disclosure to a public health authority or as
  required by law
• Research that qualifies for the Transition
  Provisions

74
Research Use and Disclosure of PHI Without
Authorization Waiver of Authorization

• Documentation that IRB or Privacy Board
  determined that all waiver criteria were
  satisfied
• Use or disclosure involves no more than minimal
  risk because of an adequate plan/assurance
• To protect PHI from improper use or disclosure
• To destroy identifiers at earliest opportunity
• That PHI will not be inappropriately reused or
  disclosed
• Research not practical without waiver
• Research not feasible without use of PHI

75
Research Use and Disclosure of PHI Without
Authorization De-identified Health Information

• Completely de-identified information (18 elements
  removed) and no knowledge that remaining
  information can identify the individual
• Statistically de-identified information
  statistician certifies that only very small
  risk that information could be identify
  individual
• Consider risk of identification by inference
• The combination of several data fields makes the
  data identifiable
• If subsets of ten or fewer, individuals are at
  risk for identification by inference

76
De-identified Data
Excludes the following identifiers

• Health plan beneficiary number
• Account Numbers
• Certification numbers
• VIN and Serial numbers, license plate numbers
• Device identifiers and serial numbers
• Web URLs
• IP address numbers
• Biometric identifiers (finger prints, voice
  prints, retinal scans, etc.)
• Full face or comparable photo images
• Unique identifying numbers

• Name
• Geographic information (other than state or the
  initial three digits of the zip code)
• Elements of dates except for year (including
  admission/discharge dates service dates birth
  date, date of death) and age over 89
• Telephone numbers
• FAX numbers
• E-mail addresses
• Social Security number
• Medical Record number, prescription number, etc.

77
Research Use and Disclosure of PHI Without
AuthorizationLimited Data Set with Data Use
Agreement

• The Privacy Rule permits limited types of
  identifiers to be released with health
  information (referred to as a Limited Data Set).
• Excludes direct or facial identifiers
• Includes full elements of dates (e.g.
  admission/discharge dates, service dates, birth
  date, date of death) all ages town/city state
  full zip code
• Limited Data Sets can only be used and released
  in accordance with a Data Use Agreement between
  the covered entity and the recipient.

78
Limited Use Data Set
Excludes the following direct identifiers

• Name
• Geographic information (other than city, state
  and zip)
• Telephone numbers
• FAX numbers
• E-mail addresses
• Social Security number
• Medical Record number, prescription number, etc.
• Health plan beneficiary number
• Account Numbers

• Certification numbers
• VIN and Serial numbers, license plate numbers
• Device identifiers and serial numbers
• Web URLs
• IP address numbers
• Biometric identifiers (finger prints, voice
  prints, retinal scans, etc.)
• Full face or comparable photo images
• Unique identifying numbers

79
Research Use and Disclosure of PHI Without
Authorization Preparatory to Research

• Requires notification of the entity holding the
  PHI
• Researcher must provide representation that
• PHI is to be used solely to prepare a protocol or
  a similar purpose
• PHI will not be removed from the covered entity
• PHI is necessary for research
• May be used to develop hypothesis, protocol or
  characteristics of research cohort
• May not be summarized, used or presented as a
  research study without prior IRB approval
• May allow access to PHI to identify subjects for
  recruitment

80
Privacy Rule and ResearchIRBs/Privacy Board
Reviewunder the Privacy Rule

• Because the Privacy Rule assumes Authorization
  will be obtained, IRBs/Privacy Boards will see
  Requests to WAIVE Authorization requirement
• IRBs will see Authorizations combined with
  informed consent documents
• IRBs will likely request to see Authorizations
  that are separate from informed consent documents

81
Privacy Rule and ResearchAccess to Research
Records

• Individuals have right to view and copy their
  health records maintained by covered entities
• Patients may access research records if
• Records involve treatment (e.g., some clinical
  trials) or are used to make decisions about
  individuals AND
• Researcher is a covered entity
• EXCEPT While a trial is ongoing, covered
  researchers may deny access if the individual
  agrees in advance (e.g., in an Authorization)

82
Privacy Rule and ResearchRevoking an
Authorization

• Individuals may revoke Authorization
• EXCEPT, covered entities may continue to use or
  disclose PHI that was obtained before a
  revocation if necessary to maintain the
  integrity of the research study (Reliance
  exception)
• For example, researcher can continue using PHI to
  account for subjects withdrawal from study

83
Privacy Rule and ResearchSubject Recruitment

• A patients physician may discuss possible
  research participation with a patient
• A patients physician may NOT discuss PHI with
  research colleagues for potential enrollment
  purposes without the patients Authorization or
  Waiver of Authorization by IRB or Privacy Board
• Researcher may search through medical records to
  identify potential research subjects only if
• The researcher is the subjects physician
• Individual Authorization has been provided
• A Waiver of Authorization has been granted by the
  IRB or Privacy Board
• As Preparatory to Research
• All subject recruitment strategies and material
  MUST be approved by the IRB (Common Rule
  requirement)

84
Privacy Rule and ResearchSecurity of PHI

• Principal investigator responsible for security
  of research related PHI
• Research team members access
• Security of transmitted data
• Security of on site data
• Destruction of data
• Compliance with HIPAA regulations
• Compliance with Medical Center specific Security
  and Privacy Policies, including

85
Ethics and Clinical Research Conclusions
Suggestions

• Learn more about clinical trials
• Take a training course
• Review Belmont Report, Declaration of Helsinki,
  other consensus documents
• When planning a clinical study consult early with
  a statistician
• Get to know your IRB or ethics committee
• Review HIPAA-related protocols for your center
  and IRB