INTRODUCTION
In the conduct of research, attention to detail is of utmost importance to help ensure the integrity
of the study data and adherence to the regulations and guidelines that govern human subject
research. Throughout their years of conducting audits, the Education and Compliance Office for
Human Subject Research (ECO-HSR) at the University of Pittsburgh has identified practices that
facilitate compliance with research regulations and improve the conduct of research with human
subjects. The attached document provides a reasonable summary of good clinical research
practices. This summary is not meant to be all-inclusive but highlights practices that we hope
will assist you in the conduct of your research study.
Please note that only those investigators who are conducting FDA-regulated human subjects
research are obligated to follow Good Clinical Practices, as discussed at length in “The
International Conference of Harmonization - Good Clinical Practices,” referenced below.
Nevertheless, good clinical research practices, as summarized in our attached document, are a
standard to which all researchers should aspire, and this is the set of standards used by the ECOHSR staff in conducting their audits of research studies. For investigators not conducting FDAregulated research studies, we understand that certain of our recommended procedures may be
modified to reflect the nature of the research study and the likely risks to human subjects.
The summary includes information gathered from:

Observed practices in the research community

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/45cfr46.htm

The FDA Regulations (CFR 21 Parts 50, 56 and 312 )
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm and

The International Conference of Harmonization - Good Clinical Practices
http://www.fda.gov/cder/guidance/959fnl.pdf .
If you have any questions or comments about this material, please contact The Education &
Compliance Office for Human Subject Research at staff member of the Education and
Compliance Office.
HIGHLIGHTS OF GOOD RESEARCH PRACTICE
FOR
PSYCHOSOCIAL/DESCRIPTIVE STUDIES
I.
PROTOCOL ADHERENCE AND OVERSIGHT
A.
Prior to initiation of the study:
1.
Ensure that all study staff have completed the designated Responsible Conduct in
Research computer based training modules and other applicable training (e.g.,
universal precautions, shipping of biological specimens). Training requirements
can be found by going to http://cme.hs.pitt.edu and clicking on the “What is
Required?” link.
2.
Ensure that the study and consent form(s) have received IRB approval and that the
approval is current. The IRB Website is located at: http://www.irb.pitt.edu/
3.
Ensure availability of facilities, equipment, and all supplies to enable the performance of
all procedures per protocol.
4.
Ensure preparation of case report forms/data collection tools to document
eligibility criteria and the performance of all study procedures per the IRB
approved protocol.
5.
Ensure that the IRB protocol includes a comprehensive list of all study
surveys/assessment tools (using the title listed on the tool itself) and that all acronyms are
spelled out in full.
6.
Identify components/members of the DSMP/DSMB and outline responsibilities of each
member; provide a schedule for regular meetings, based on study needs/complexity.
Data and safety monitoring plans are addressed in Appendix L of the Reference Manual
for Use of Human Subjects in Research, (The IRB Reference Manual).
7.
Review study procedures and documentation with study staff:






Provide a copy of the complete current version of the research protocol
and consent form to all members of the research team, i.e., all coinvestigators and other personnel assisting with the conduct of the study
Delegate/assign responsibilities (ensure that assignment of personnel
delegated to obtain signed consent is consistent with IRB requirements
and the IRB approved protocol)
Review case report forms, when and how used, and how to make
corrections
Review randomization plan
Review use of any special equipment
Review methods for subject record identification and protection of
confidentiality


8.
B.
Review storage of study records/computer data to maintain confidentiality
Address who has access to the records.
If blood/tissue samples will be stored, ensure availability of proper storage site
and adequate oversight of the facility. If samples will be shipped to an outside
site, ensure proper shipping containers/procedures are available. Also ensure that
staff responsible for shipping have received appropriate training and/or
certification. If samples are to be shipped to another site, a material transfer
agreement may need to be executed. Details about material transfer agreements
can be found on the Office of Research website at:
http://www.pitt.edu/~offres/mta.html.
Throughout the course of the study:
1.
Maintain current IRB approval of the protocol and informed consent document(s).
2.
Ensure that any modifications to the protocol/consent form are submitted to the
IRB for review and approval prior to their implementation.
3.
Ensure that informed consent is obtained from all subjects and the original signed
consent document is retained in the study records.
4.
Ensure that all study procedures are conducted per the IRB approved protocol.
5.
Report unanticipated problems and adverse events per IRB requirements.
Unanticipated problem and adverse event reporting is addressed in Chapter 3 of
the Reference Manual for Use of Human Subjects in Research. Reporting forms
are located online at: http://www.irb.pitt.edu/irbforms/irbforms.htm.
6.
Ensure that adequate, current and accurate records of research data, outcomes, and
adverse events are maintained to permit an ongoing assessment of the risks and
benefits of study participation.
7.
Review subject files for notes to file explaining any protocol variations or
deviations. Notify the sponsor and the IRB of deviations and corrective actions to
prevent recurrence.
8.
If blood/tissue samples are being collected and stored, ensure proper storage (e.g.,
temperature of refrigerator, secure location).
9.
Maintain ongoing communication with study staff to address problems/concerns
in a timely manner. Maintain minutes of staff meetings.
10.
Ensure conduct of DSMP/DSMB meetings as indicated in the IRB approved
protocol. Maintain minutes of meetings.
C.
11.
Perform interim analysis, as required per protocol.
12.
When the research is sponsored by an external agency (e.g., NIH; NSF), maintain records
of communications with the sponsor (i.e., e-mails, letters, monitor visits, and a log of
telephone conversations).
Upon completion of study:
1.
Ensure that all documentation is complete (or provide notes to file explaining
omissions).
2.
Prepare and submit final report to sponsor, if applicable. Notify IRB that the study
is terminated and submit the necessary summary report.
3.
Retain and store subject records per requirements of IRB (UP IRB is five years
after termination of the study) and/or sponsor. Note: Retain records for the longer
time period, if differing dates.
II.
CONSENT PROCESS
A.
Conducting the Informed Consent Process
1.
Ensure that the IRB has granted approval and that the consent document is the
most current version. Information on each page of the consent should list:
 University of Pittsburgh IRB #
 Current Approval Date
 Most Recent Modification Approval Date (if applicable)
 Renewal Date
2.
For studies with risk of emotional distress that may lead to physical harm (i.e.,
suicide), assure that emergency contact information is provided on the first page
of the consent document. The subject must be able to reach a "member of the
research team" within two phone calls at all times.
3.
Ensure that the individual conducting the consent process is authorized to do so as
outlined in the protocol. If someone other than an investigator is delegated to
conduct the process, it must be explained in the protocol and approved by the
IRB.
4.
The subject or legally authorized representative must provide written consent
prior to ANY research activities unless certain activities have received a waiver
of the requirement to obtain signed informed consent from the IRB (e.g., phone
screening). Informed consent is addressed in Chapter 8 of the IRB Reference
Manual.
B.
Documenting the Process
1.
Ensure that the consent document is properly signed and dated.
 All signatures must be obtained at the time the subject provides consent.
 The subject or legally authorized representative must sign and date the
consent document.
 The investigator or authorized delegate must sign and date the consent
document.
 All signatories must date their own signature.
 If there are any discrepancies (i.e., dates), a narrative note must be
included in the research record explaining the circumstances.
2.
It is recommended but not required that in addition to the signed consent
document, a narrative note of the informed consent "process" should also be
included in the research records. This is most likely to be the case when studies
include an intervention or where risks to participants are more than minimal. The
note should include reference to:
 who was present during the discussion,
 that all risks were presented,
 that all questions were answered, and
 that the subject appears to understand and provides consent to participate
by signing the consent document prior to any research procedures.
This narrative note should be signed, dated and the time recorded by the
individual writing the narrative note.
Recording the time the consent was signed is most important when research
procedures are to be performed on the same day that consent is obtained.
3.
The principal investigator must retain the original signed consent document.
A copy must be given to the subject.
A copy should be placed in the clinic/hospital record.
4.
If any problems are identified, i.e., lost or missing consent forms and/or use of an
incorrect/outdated consent form, document the findings and contact the IRB for
guidance and instructions.
III.
STUDY DOCUMENTATION
A.
Source Documents
Source documents are the original documents containing the first recording of
information used as research data. If these documents are generated in the course of
routine care, copies of the documents should be maintained in the subjects research file.
1.
Data collection tools should be developed and completed to address all study
activities. This includes:
 Eligibility criteria
 Screening
 Study procedures
 Follow-up procedures
2.
Supportive documentation should also be included in the research subject’s file,
e.g.,
 Psychological assessment tools
 Bloodwork results
 Results of other tests/procedures
3.
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, and
 adverse events.
4.
All subject-specific source documents should be labeled with subject ID and the
date and should be signed and dated by the person completing the document.
5.
Separate research records should be maintained. Investigators should not rely on
clinical records to maintain research documentation.
6.
If corrections need to be made to source documents or case report forms:
 draw a single line through the error
 note the correct information beside the error
 initial and date the correction
 place a note to file explaining the reason for the correction and if
applicable describe the corrective actions that will be taken to avoid a
future reoccurrence of the error.
Note that white-out should never be used to correct research documentation.
B.
Regulatory Binder/Files
All investigators must maintain regulatory binders/files that contain all vital study documentation.
The files should be organized in such a manner that they can be easily retrieved and documents
located. The regulatory file should contain the following items.




Protocol
Informed consent
Investigators’ CV’s
Copies of professional licenses









Training certificates
IRB approval/correspondence
Sponsor/granting agency correspondence
Signature list of research staff
Monitoring log/reports
Adverse event reports
Minutes from staff meetings
DSMP/DSMB meeting minutes
Final study report
Note: 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 binder noting where these documents are
located. For example, the central file may contain:


Investigator/staff CVs / licenses / certificates
Staff training records
HIGHLIGHTS OF GOOD RESEARCH PRACTICE
FOR
MEDICAL/INTERVENTIONAL STUDIES
I.
PROTOCOL ADHERENCE AND OVERSIGHT
A.
Prior to initiation of the study:
1. Ensure that all study staff have completed the designated Responsible Conduct in
Research computer based training modules (and applicable training (e.g., universal
precautions, shipping of biological specimens). Training requirements can be found by
going to http://cme.hs.pitt.edu and clicking on the “What is Required?” link.
2. Ensure that the study and consent form(s) have received IRB approval and that the approval is
current. The IRB Website is located at: http://www.irb.pitt.edu/ .
3. Ensure availability of facilities, equipment, drugs, and all supplies to enable the performance of
all procedures per protocol.
4. Ensure preparation of case report forms/data collection tools to document eligibility
criteria and the performance of all study procedures per the IRB approved protocol.
5. Ensure that the IRB protocol includes a comprehensive list of all study surveys/assessment tools
(using the title listed on the tool itself) and that all acronyms are spelled out in full.
6. Identify components/members of the DSMP/DSMB and outline responsibilities of each member;
provide a schedule for regular meetings, based on study needs/complexity. Data and safety
monitoring plans are addressed in Appendix L of the Reference Manual for Use of Human
Subjects in Research, (The IRB Reference Manual).
7. Review study procedures and documentation with study staff:







Provide a copy of the complete current version of the research protocol and consent
form to all members of the research team, i.e., all co-investigators and other personnel
assisting with the conduct of the study
Delegate/assign responsibilities (ensure that assignment of personnel delegated to
obtain signed consent is consistent with IRB requirements and the IRB approved
protocol)
Review case report forms, when and how used, and how to make corrections
Review randomization plan; drug/device accountability and storage
Review use of any special equipment
Review methods for subject record identification and protection of confidentiality
Review storage of study records/computer data to maintain confidentiality. Address
who has access to the records.
8. If blood/tissue samples will be stored, ensure availability of proper storage site and
adequate oversight of the facility. If samples will be shipped to an outside site, ensure
proper shipping containers/procedures are available. Also ensure that staff responsible
for shipping have received appropriate training and/or certification. If samples are to be
shipped to another site, a material transfer agreement may need to be executed. Details
about material transfer agreements can be found on the Office of Research website at:
http://www.pitt.edu/~offres/mta.html.
B.
Throughout the course of the study:
1. Maintain current IRB approval of the protocol and informed consent document(s).
2. Ensure that any modifications to the protocol/consent form are submitted to the
IRB for review and approval prior to their implementation.
3. Ensure that informed consent is obtained from all subjects and the original signed
consent document is retained in the study records.
4. Ensure that all study procedures are conducted per the IRB approved protocol.
5. Report unanticipated changes and adverse events per IRB, sponsor, and hospital
requirements. Unanticipated changes and adverse event reporting is addressed in
Chapter 3 of the Reference Manual for Use of Human Subjects in Research.
Reporting forms are located online at:
http://www.irb.pitt.edu/irbforms/irbforms.htm.
6. Ensure that adequate, current and accurate records of research data, outcomes, and
adverse events are maintained to permit an ongoing assessment of the risks and
benefits of study participation.
7. Review subject files for notes to file explaining any protocol variations or
deviations. Notify sponsor and IRB of deviations and corrective actions to prevent
recurrence.
8. Review investigational product accountability on a regular basis.
9. If blood/tissue samples are being collected and stored, ensure proper storage (e.g.,
temperature of refrigerator, secure location).
10. Maintain ongoing communication with study staff to address problems/concerns in
a timely manner. Maintain minutes of staff meetings.
11. Ensure conduct of DSMP/DSMB meetings as indicated in the IRB approved
protocol. Maintain minutes of meetings.
12. Perform interim analysis, as required per protocol.
13. Maintain record of communications with the sponsor (i.e., e-mails, letters, monitor visits,
and a log of telephone conversations).
C.
Upon completion of the study:
1.
Ensure that all documentation is complete (or provide notes to file explaining
omissions).
2.
Return or destroy investigational product per sponsor’s requirements.
3.
Prepare and submit final report to sponsor. Notify IRB that the study is terminated
and submit the necessary summary report.
4.
Retain and store subject records per requirements of IRB (UP IRB is five years
after termination of the study) and/or sponsor. Note: Retain records for the longer
time period, if differing dates.
II.
CONSENT PROCESS
A.
Conducting the Informed Consent Process
1.
Ensure that IRB has granted approval and that the consent document is the most
current version. Information on each page of the consent should include:
 University of Pittsburgh IRB #
 Current Approval Date
 Most Recent Modification Approval Date (if applicable)
 Renewal Date
2.
For studies with risk of physical harm, assure that emergency contact information
is provided on the first page of the consent document. The subject must be able to
reach a "member of the research team" within two phone calls at all times.
3.
Ensure that the individual conducting the consent process is authorized to do so as
outlined in the protocol. If someone other than an investigator is delegated to
conduct the process, it must be explained in the protocol and approved by the
IRB.
4.
The subject or legally authorized representative must provide written consent
prior to ANY research activities unless certain activities have received a waiver of
the requirement to obtain signed informed consent from the IRB (e.g., phone
screening). Informed consent is addressed in Chapter 8 of the IRB Reference
Manual.
B.
Documenting the Process
1.
Ensure that the consent document is properly signed and dated.
 All signatures must be obtained at the time the subject provides consent.
 The subject or legally authorized representative must sign and date the
consent form.
 The investigator or authorized delegate must sign and date the consent
form.
 All signatories must date their own signature.
 If there are any discrepancies (i.e., dates), a narrative note must be
included in the research record explaining the circumstances.
2.
If the study involves a drug, device or surgical procedure, an investigator who is
listed on the first page of the consent form and who is an MD, must participate in
the informed consent process. This investigator MUST sign and date the
informed consent document.
3.
In addition to the signed consent document, a narrative note of the informed
consent "process" should also be included in the research records. The note
should include reference to:
 who was present during the discussion,
 that all risks were presented,
 that all questions were answered, and
 that the subject appears to understand and provides consent to participate
by signing the consent document prior to any research procedures.
This narrative note should be signed, dated and the time recorded by the
individual writing the narrative note.
Recording the time the consent was signed is most important when research
procedures are to be performed on the same day that consent is obtained.
4.
The principal investigator must retain the original signed consent document.
A copy must be given to the subject.
A copy should be placed in the clinic/hospital record.
5.
If any problems are identified, i.e., lost or missing consent forms and/or use of an
incorrect/outdated consent form, document the findings and contact the IRB for
guidance and instructions.
III.
STUDY DOCUMENTATION
A.
Source Documents
Source documents are the original documents containing the first recording of
information used as research data. If these documents are generated in the course of
routine medical care, copies of the documents should be maintained in the subjects
research file.
1.
Data collection tools should be developed and completed to address all study
activities. This includes:
 Eligibility criteria
 Screening
 Study procedures
 Drug dispensing
 Follow-up procedures
2.
Supportive documentation should also be included in the research subject’s file,
e.g.,
 Psychological assessment tools
 Bloodwork results
 X-ray reports
 Electrocardiograms
3.
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, and
 adverse events.
4.
All subject-specific source documents should be labeled with subject ID and the
date and should be signed and dated by the person completing the document.
5.
Separate research records should be maintained. Investigators should not rely on
medical records to maintain research documentation.
6.
If corrections need to be made to source documents or case report forms:
 draw a single line through the error,
 note the correct information beside the error, and
 initial and date the correction, and
 place a note to file explaining the reason for the correction and if
applicable describe the corrective actions that will be taken to avoid a
future reoccurrence of the error.
Note that white-out should never be used to correct research documentation.
B.
Regulatory Binder/Files
1.
All investigators must maintain regulatory binders/files that contain all vital study
documentation. The files should be organized in such a manner that they can be easily
retrieved and documents located. The regulatory file should contain the following items.













2.
Protocol
Informed consent
Investigators’ CV’s
Copies of professional licenses
Training certificates
IRB approval/correspondence
Sponsor/granting agency correspondence
Signature list of research staff
Monitoring log/reports
Adverse event reports
Minutes from staff meetings
DSMP/DSMB meeting minutes
Final study report
If applicable to the study design, the following may also apply:




Investigator’s brochure
Form FDA 1572 (or Investigator’s Agreement)
Drug accountability documentation
Laboratory certifications and range of normal laboratory values
Note: 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 binder noting where these
documents are located. For example, the central file may contain:



Investigator/staff CVs / licenses / certificates
UPMC laboratory certifications and range of normal laboratory values
Staff training records
C.
Test Article Accountability
1.
Note that the Investigational Drug Service, UPMC Department of Pharmacy must
be notified of all research protocols wherein the research involves the
administration of an investigational new drug or an approved drug. The
Investigational Drug Service can be reached at: (412) 647-5350.
2.
When conducting a study that involves an investigational agent, the principal
investigator should maintain an inventory log for the test article. This log should
include information such as the:















Protocol number or title
Name of the principal investigator
Drug/device name
Drug dosage form, strength and schedule
Shipping records including the date and quantity of receipt
Initial and ongoing inventory balance
Lot number
Expiration date
Identification of the study participant
Quantity and date dispensed
Initials of the individual preparing and dispensing the product
Amount transferred or wasted
Date(s) and quantity returned by the study participant
Date(s) and quantity returned to the sponsor
Name, address, and telephone number of the sponsor
3.
There should be a signed physician’s order for every test article dispensed.
4.
In addition, the investigator should ensure that periodic inventories of the test
article are performed. These inventories should ensure that each test article can
be accounted for and any discrepancies reconciled.