The Education and Compliance Office for Human Subject Research ECOHSR

1
The Education and Compliance Office for Human
Subject Research (ECO-HSR)

• Guidelines to Good Research Practices
• http//www.rcco.pitt.edu/educ/

2
Organizational Chart for the Research Conduct
Compliance Office (RCCO)
3
ECO Staff

• Kelly Dornin-Koss, MPPM, RN, CCRC
• Patricia Erb, RN, BSN, CIP

• Cindy Kern, RN, CCRC
• Nancy Nagel, RN, BSN, CCRC

http//graphicfreebies.com/fall2.html
4

• Mission Statement
• To provide education to individuals involved in
  clinical research at the University of Pittsburgh
  and to strive for research excellence and
  integrity throughout the University.

5

• The ECO has performed nearly 300 audits to date
• The ECO has reviewed over 3,600 research records
  for the presence of consent forms

6
(No Transcript)
7
Good Research Practices Taken From

• The Reference Manual for Use of Human Subjects in
  Research (http//www.irb.pitt.edu/)
• The Federal Policy Regulations (CFR 45 Part 46
  http//www.hhs.gov/ohrp/humansubjects/guidance/45c
  fr46.htm )
• The FDA Regulations (CFR 21 Parts 50, 56 and 312
  ) http//www.accessdata.fda.gov/scripts/cdrh/cfdoc
  s/cfcfr/cfrsearch.cfm and
• The International Conference of Harmonization -
  Good Clinical Practices http//www.fda.gov/cder/gu
  idance/959fnl.pdf .
• Observed practices in the research community

8

• Patricia Erb, RN, BSN, CIP

9
PROTOCOL ADHERENCE AND OVERSIGHT

• Get ready
• Get set
• Go
• Done, at last

10
GET READY

• RPF modules and training
• E
• A
• D
• Y

11
GET READY

• RPF modules, training
• Equipment, facilities, supplies
• A
• D
• Y

12
GET READY

• RPF modules, training
• Equipment, facilities, supplies
• Approvals
• D
• Y

13
GET READY

• RPF modules, training
• Equipment, facilities, supplies
• Approvals
• DSMP-who, what, when
• Y

14
GET READY

• RPF modules
• Equipment
• Approvals
• DSMP
• Yes, its in the mail-samples shipped and/or
  stored

15
GET SET

• Standard Operating Procedures (SOPs)
• E
• T

16
GET SET

• SOPs
• Education explain protocol and consent form,
  equipment
• T

17
GET SET

• SOPs
• Education
• Trial records data collection forms (CRFs),
  record storage, confidentiality, randomization
  plan

18
Good Oversight

• Ensure study is conducted per protocol
• Submit mods before implementing changes
• Maintain approvals
• Report AEs and unanticipated problems
• Maintain records, consent forms
• Ensure proper storage of samples
• Staff meetings
• DSMP meetings
• Communications with sponsor

19
DONE

• Documentation
• O
• N
• E

20
DONE

• Documentation
• Out with drugs, devices
• N
• E

21
DONE

• Documentation
• Out with drugs, devices
• Notify IRB, sponsor
• E

22
DONE

• Documentation
• Out with drugs, devices
• Notify IRB, sponsor
• Extended storage

23

• Nancy Nagel, RN, BSN, CCRC

24
INFORMED CONSENT PROCESS

• C Communicate
• O
• N
• S
• E
• N
• T

25
Communicate

• Informed Consent Document
• Vs.
• Informed Consent Process

26
Communicate

• Who introduces the study?
• Who explains details of study?
• Who answers questions?

27
Communicate

• The individuals implementing the informed consent
  process must be authorized to do so as outlined
  in the protocol.
• If someone other than the investigator is
  delegated to conduct the process, it must be
  explained in the protocol and approved by the
  IRB.
• (See IRB Reference Manual, Chapter 8)

28
Communicate (Continued)

• Be Creative..
• Visual aids - pill bottlesdevicesmodels
• Charts
• Diagrams
• Drawings
• Stack of questionnaires
• Anything to draw them in and make them listen
• Create a dialogue.not a monologue

29
Communicate

• Evaluate
• Make some effort to evaluate the subjects
  comprehension. For example
• Ask them to describe the purpose of the study
• Ask them to repeat some of the risks
• Ask them how long their participation will last
• Ask them who they would call with a problem

30
INFORMED CONSENT PROCESS

• C Communicate
• O Obtain consent
• N
• S
• E
• N
• T

31
Obtain Consent

• Be sure you are using the most current version of
  the consent document
• Check the approval date
• Check the renewal date
• Written consent must be provided by the subject
  prior to ANY research activity

32
INFORMED CONSENT PROCESS

• C Communicate
• O Obtain consent
• N Narrative note
• S
• E
• N
• T

33
Narrative Note

• FDA requires documentation of informed consent
  process.
• Recommended for ALL studies as
• Good Clinical Practice and as backup
  documentation if consent is LOST.

34
Narrative Note

• The consent form doesnt provide specifics of
  the consent discussion or interaction.
• Develop your own system.
• Example Form Included
• (Original concept developed by I. Macio of Magee
  Womens Hospital. Generic form developed by N.
  Nagel)

35
IRB ____________ PI ________Subject ID
__________
Signature and Date of Investigator/Co-Investigator
(or IRB approved delegate) who administered the
consent process and completed this
form.Signature ______________ Date
______________ Time____________
36
Narrative Note

• Include
• Who was present for the discussion
• All risks were presented
• All questions were answered
• Subject appears to understand
• Agrees to participate by signing
• Sign date time (especially if research
  procedures will be performed on the same day

37
INFORMED CONSENT PROCESS

• C Communicate
• O Obtain consent
• N Narrative note
• S Signatures
• E
• N
• T

38
Signatures

• Subject
• (or Legally authorized representative)
• Person obtaining consent
• If the study involves a drug, device or
  surgical
• procedure..
• must be a listed investigator
• listed on first page of consent
• MUST be an M.D.
• (Exceptions See Reference Manual,
  Chapter 8)

39
Signatures

• If the study does NOT involve a drug, device
  or surgical procedure, and is considered to be
  MINIMAL RISK, members of the research team may be
  delegated the task of educating the subject and
  obtaining consent.
• INCLUDE A DESCRIPTION IN PROTOCOL

40
Signatures

• Retention of consent document..
• Principal investigator must retain ORIGINAL
• Copy in medical records if hospitalized
• Copy to subject

41
INFORMED CONSENT PROCESS

• C Communicate
• O Obtain consent
• N Narrative note
• S Signatures
• E Emergency Contact
• N
• T

42
Emergency Contact

• If a research study involves risk of physical
  harm (or emotional distress leading to physical
  harm, i.e., suicide), subjects must know what to
  do and whom to contact. 24 hrs./7 days/wk.
• Include contact information on first page of
  consent
• Subject should reach someone on the research team
  within two phone calls

43
INFORMED CONSENT PROCESS

• C Communicate
• O Obtain consent
• N Narrative note
• S Signatures
• E Emergency Contact
• N Notify IRB
• T

44
Notify IRB

• If you discover any problems..
• No consent
• Lost or missing consent
• Incorrect consent
• DOCUMENT ALL FINDINGS AND CIRCUMSTANCES
• Call the IRB for guidance

45
INFORMED CONSENT PROCESS

• C Communicate
• O Obtain consent
• N Narrative note
• S Signatures
• E Emergency Contact
• N Notify IRB
• T Trust

46
Trust

• Develop a relationship with your subjects so that
  they trust you
• You can trust them to be compliant with study
  conduct
• The IRB trusts that you will implement the
  consent process and conduct the study as outlined
  in your protocol and consent document

47

• Cindy Kern, RN, CCRC

48

• Study Documentation

49
(No Transcript)
50
STUDY DOCUMENTATION

• Source Documents
• T
• U
• D
• Y

51
Source Documents

• The International Conference on Harmonization
  (ICH), the Code of Federal Regulations and Good
  Clinical Practice require the following
• Written, informed consent by all subjects prior
  to the implementation of any study-related
  procedures and
• Accurate, complete and appropriate clinical
  research documentation

52
Source Documents

• Data collection tools should be developed and
  completed to address all study activities.

53
Source Documents

• The data collection tools should include
• Eligibility criteria presence of inclusion
  criteria and absence of exclusion criteria
• Screening
• Study procedures
• Drug/device dispensing
• Follow-up procedures
• Any and all contacts with the study participant

54
Source Documents

• Supportive documentation should also be included
  in the research subjects file, e.g.
• Psychological assessment tools
• Bloodwork results
• X-ray, CT, MRI reports
• Electrocardiograms
• SCID (Structured Clinical Interview for DSM-IV)
  testing

55

• Source documents
• Tell the entire story
• U
• D
• Y

56
Tell the entire story

• Narrative notes should also be generated to
  document
• How the subject tolerated the study procedures
• Any telephone calls or contacts with the subjects
• Missed visits or protocol deviations
• Adverse events or unanticipated problems

57

• Study documents
• Tell the entire story
• Understand
• D
• Y

58
Understand

• All subject-specific source documents should be
  labeled with subject ID and date and should be
  signed by the person completing the document
• Separate research records should be maintained
• Never use white-out on study documents

59

• Source documents
• Tell the entire story
• Understand
• Document
• Y

60
Document

• DOCUMENT
• DOCUMENT
• DOCUMENT

61

• Study documents
• Tell the entire story
• Understand
• Document
• Yield

62
Yield

• Yield the best possible study results by
  maintaining accurate and complete study
  documentation.

63
(No Transcript)
64
Regulatory Binder/Files

• Reference
• E
• G
• U
• L
• A
• T
• O
• R
• Y

65
Reference

• You should be able to easily reference all
  vital study information.

66
Reference

• Reference
• Explain
• G
• U
• L
• A
• T
• O
• R
• Y

67
Explain

• It is acceptable to establish a central
  departmental file for documentation that
  pertains to all studies conducted within that
  department. A cross-reference note should be
  placed in the specific study regulatory file
  noting the location of these documents.

68
Explain

• For example, the central file may contain
• Investigator-staff
• CVs
• Licenses
• Certificates
• Staff training records

69

• Reference
• Explain
• Groundwork
• U
• L
• A
• T
• O
• R
• Y

70
Groundwork

• Before the study starts, organize all of the
  study documentation in a binder or file.

71
SITE PERSONNEL SIGNATURES DELEGATED
RESPONSIBILITIES Investigator ___________________
_______ Project _________________________ Study
Site __________________________ Sponsor
________________________
72

• Reference
• Explain
• Groundwork
• Unimportant
• L
• A
• T
• O
• R
• Y

73
Unimportant

• No matter how unimportant a study document seems
  to you, dont discard it.
• E.g., shipping or mailing labels

74

• Reference
• Explain
• Groundwork
• Unimportant
• Laboratory
• A
• T
• O
• R
• Y

75
Laboratory

• If applicable, laboratory certifications and
  ranges of normal laboratory values should be
  maintained in the regulatory files.

76

• Reference
• Explain
• Groundwork
• Unimportant
• Laboratory
• Adverse Event Reports
• T
• O
• R
• Y

77
(No Transcript)
78
Adverse Event Reports

• All adverse event reports should be sent to
  the appropriate agencies and copies should be
  maintained in the regulatory files.

79

• Reference
• Explain
• Groundwork
• Unimportant
• Laboratory
• Adverse Event Reports
• Telephone conversations, emails
• O
• R
• Y

80
(No Transcript)
81
Telephone conversations, emails

• Document all telephone conversations with the
  sponsor or regulatory agency. These should be
  maintained in the regulatory files and should
  include
• Date and time
• Who initiated the call
• Topic of discussion
• Resolution

82
TELEPHONE COMMUNICATIONS LOG Investigator
__________________________ Project
___________________________ Study Site
_________________________ Sponsor
___________________________

• Record chronologically all contacts with sponsor
• Sign and date each entry

83
Telephone conversations, emails

• Also, print and file all relevant e-mail
  correspondence regarding the study in the
  regulatory files.

84

• Reference
• Explain
• Groundwork
• Unimportant
• Laboratory
• Adverse Event
• Telephone conversations, emails
• Organization
• R
• Y

85
Organization

• It is best to organize the regulatory files in
  chronological order. This will make it easier
  for you to locate information when you need it.

86

• Reference
• Explain
• Groundwork
• Unimportant
• Laboratory
• Adverse Event Reports
• Telephone conversations, emails
• Organization
• Reproach
• Y

87
(No Transcript)
88
Reproach

• If you keep your regulatory files organized you
  will be above reproach.

89

• Reference
• Explain
• Groundwork
• Unimportant
• Laboratory
• Adverse Event Reports
• Telephone conversations, emails
• Organization
• Reproach
• Your work

90
Your work

• Your study files reflect your work. Let them
  speak highly of you.

91
(No Transcript)
92
Test Article Accountability

• Tell
• E
• S
• T

93
Tell

• The Investigational Drug Service must be
  notified of all research protocols wherein the
  research involves the administration of an
  investigational new drug or an approved drug.

94

• Send the following items to the Investigational
  Drug Service
• The research protocol
• The informed consent document
• The Investigators Brochure
• Fiscal review
• UPMC IDS Questions - 647- 4958
• Magee Pharmacy Questions 641-6626
• Shirley Podnar

95

• Tell
• Elaborate
• S
• T

96
Elaborate

• The principal investigator/coordinator should
  maintain an inventory log for the test article.
  This responsibility may be performed by IDS.

97
(No Transcript)
98

• Tell
• Elaborate
• Sign
• T

99
Sign

• There should be a signed physicians order for
  every test article dispensed.

100

• Tell
• Elaborate
• Sign
• Thorough

101
Thorough

• The investigator should ensure that periodic
  inventories of the test article are performed.
  Each test article must be accounted for and any
  discrepancies reconciled.

102
(No Transcript)
103
(No Transcript)
104
References

• MB Ott, GL Yingling. Guide to Good Clinical
  Practice.  Thomas Publishing Group, Washington,
  DC, 2000.
• International Conference on Harmonisation
  Guidelines http//www.ifpma.org/ich5.html
• FDA regulations 21 CFR 312.62, 600.12, 812.14
• Deborrah Norris. Clinical Research Coordinator
  Handbook. Plexus Publishing
• Photos from Webshots.com, Allposters.com,
  Picsearch.com