This survey assessed SOP usage at a medical center to provide baseline information and identify training needs. It found that SOPs were not used by all respondents, including some PIs and staff. Fewer PIs felt SOPs were important for compliance compared to CRCs and managers. While most CRCs and managers used SOP monitoring, fewer PIs did. Most CRCs were interested in SOP training versus PIs. The study limitations included a small sample size and potential non-response bias. Future work should present results, provide training, conduct additional surveys, and test an SOP support program to improve usage.

1. Clinical Research Standard
Operating Procedure (SOP) Usage
Survey Report
Ying Lu, MB, PhD; Denise Owensby, BS, CCRP;
Debary Bell, BS; Michael Wong, MD; Richard Perez, MD
UC Davis Medical Center
July 2011
1

2. Elements of Clinical Trial Quality
2

3. Standard Operating Procedures (SOPs)
 It is a set of written instructions that document a routine or
repetitive activity followed by an organization
 The term “SOP” may not always be appropriate
 Terms such as protocols, instructions, worksheets, and laboratory
operating procedures may also be used
 It is used in healthcare, clinical research, manufacturing, business, and
etc
International Conference on Harmonisation (ICH) defines
SOPs as:
"Detailed, written instructions to achieve uniformity of the performance
of a specific function.” (ICH-GCP1.55)
3

4. Good Clinical Practice (GCP)
GCP is an international ethical and scientific quality
standard for designing, conducting, recording, and reporting
trials that involve the participation of human subjects.
GCP provides public assurance for
 the rights, safety and well-being of human subjects
involved in research are protected
 the rights, safety, and wellbeing
of trial subjects are protected, consistent with the
principles that have their origin in the Declaration of
Helsinki,
 the clinical trial data are credible
4

5. Clinical Trial Quality Management
QA & QC -- Quality Assurance & Quality Control
"Systems with written SOPs to ensure that trials are conducted and data
are generated, documented (recorded), and reported in compliance with
the protocol, GCP, and the applicable regulatory requirement(s)." (ICH-
GCP 5.1.1)
5

6. GCP Requirements
 "The sponsor is responsible for implementing and maintaining quality
assurance and quality control systems with written SOPs." (ICH-
GCP 5.1.1)
FDA Warning Letters Relates to SOPs
 Missing SOPs
 Failure to follow established procedures
 No evidence that SOPs were followed
6

7. "… you have not submitted the revised SOPs …."
e.g., FDA Warning Letters
7

8. UC Davis Clinical Research Studies List
at clinicaltrial.gov
Key words search:
"University of California, Davis" (Aug. 2011)
 248 total clinical trials
 57.3% are sponsored by industry, NIH, NCI & other
Federal Agencies
 42.7% are sponsored by UC Davis investigators
(investigator-sponsor)
8

9. UC Davis Clinical Research Studies List
at clinicaltrial.gov
UC Davis sponsor (106) & Other sponsors (142)
There are 197 trials are conducted at CA
9

10. UC Davis Sponsored Clinical Studies
at clinicaltrial.gov
38 28 Observational
Drug (I-IV)
40 Other intervention
UC Davis Sponsor = 106
10

11. Study Objectives
The purpose of this pilot survey study was to assess
clinical research SOP usage status, provide baseline
information, and identify need for developing an
effective SOP implementation support program.
11

12. Study Methods
Subjects: All clinical research personnel who signed up for receiving
email updates on clinical trial information and training announcement
at UC Davis Clinical Translational Science Center (CTSC).
. Procedures: This study is exempted by the UC Davis IRB for
anonymous online survey via SurevyMonkey.com. Ten questions, with
sub-questions, multiple choice and open-ended answers, was
developed to collect feedback from clinical research personnel,
regarding SOPs being used across the full spectrum of clinical trial
settings for drugs, devices, biologics, diagnostics and observations.
Statistics: descriptive, Fisher's exact test, or student t-test
12

13. Data Collection
13

14. Survey Questionnaires
1. Do you use SOP in your clinical study(s)?
2. Please indicate SOP resource(s) for your study.
3. Do you use UC Davis IRB SOP?
4. Where did you obtain copy(s) of IRB & CTSC SOP?
5. Do you have an internal or external monitoring program regarding SOP
adherence?
6. Do you use different procedure(s) other than SOP?
7. Rate the importance of SOP in supporting compliance with GCP
8. Your professional responsibility
9. Would you like to receive a summary of this survey?
10. Are you interested in receiving future SOP training information?
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15. Demographics of SOP Survey Participants
• Program Managers
Co-PI CRC • Research Managers
7.6% 34.8%
• Nurse Managers
• Research Nurse
Other
17.4% • Head of Biostatistics
PI
33.7% • Analyst
• Quality Assurance
• Co-PI & CRC
Staff
6.5% • Graduate Student
n = 92
Return rate = 10.2%
15

16. SOP Usage by Survey Respondents
36% % of respondents
34%
SOP user
Non-SOP user
12
29
16%
19 8% 13
7%
2
2
5 4 4
2
PI/Co-PI (n=38,Co-PI
PI 41.3%) CRC CRC/Other (n=54, 58.7%)
Other Staff
16

17. SOP Resources & User Group Profiles
5%
4% Other Trial Sponsor
10%
19%
SOP Usage by PI/Co-PI
CRO 10%
3% 20%
NIH 14% Department
2%
CTSC
NCI
1% 11%
8%
2% 6% % of SOP Provided
Private CCRC
0%
0% 10% 20% 30%
SOP Usage by CRC/Other
*CCRC – CTSC Clinical Research Center.
**CRO – Contract Research Organization. 17

18. IRB SOP Resources & User Group Profiles
New study 5% 15%
Renewal 5% 14%
Modification 4% 14%
AE/SAE 3% 15%
Deviation 3% 14%
Non-compliance 1% 9%
PI/Co-PI CRC/Other
18

19. SOP Monitoring
yes
no
Monitoring Used
36
27
18
11
PI/co-PI CRC/Other
19

20. Other Working Instructions
MOP
Work Instruction
No 25
Number of User
18
14
12 12
9
PI/Co-PI CRC/Other
20

21. Importance of SOP & Interest in SOP Training
Respondents PI/Co-PI CRC/Other
P-value
(n=92) (n=38) (n=54)
SOP is very
11% (4/38) 61% (33/54)
important
<0.0001
SOP is not
37% (14/38) 15% (8/54)
applicable
Interested in
41% (15/37) 68% (36/53) 0.0169
SOP training
21

22. Summary
Survey Respondents PI/Co-PI CRC/Other
(n=92) (n=38, 41%) (n=54, 59%)
SOP user 37% (14/38) 82% (44/54)
SOP very important 11% (4/38) 61% (33/54)
SOP not applicable 37% (14/38) 15% (8/54)
SOP monitoring 29% (11/38) 67% (36/54)
SOP training 41% (15/37) 68% (36/53)
IRB SOP usage 21% 79%
22

23. Conclusion
This is an initial effort to assess SOP usage at our institute. This results
might be biased because subjects who do not know GCP or SOP might
chose not to respond.
1. It provided a current usage of SOPs at our institute
2. SOPs were not used by all study respondents including PI, Co-PI, CRC
and other research support staff
3. Considerably fewer PIs and Co-PIs used and were correlated SOPs with
GCP compliance
4. Further studies are necessary to determine whether there is a need to
develop a training program at our institute for supporting investigator–
sponsors and other clinical research professionals in developing and
implementing SOPs in all types of clinical research studies involving
human subjects.
23

24. Limitations
The overall survey response rate was only 10.2%, and
sample size is small for both groups. Target audiences who
do not know GCP or SOP might chose not to respond.
CRCs and study managers more likely have had GCP
training experiences through different resources, such as
UC Davis CTSC annual clinical research training program
and brown bag seminars. Therefore, differences between
these study groups might be biased.
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25. Future Directions
To further assess SOP usage
Plan To identify need for training
To present survey results
Do To deliver an SOP introductory seminar
To conduct an SOP survey & analyze results
To identify a small group for testing an SOP
Study implementation supporting program
To test an SOP support program & monitor
Act changes
25

26. Future Direction & Study Timeline
The upcoming cycle
This study
cycle
10/11 01/12 07/12 12/12
Plan Do Study Act
26

27. Reference
• Hector VizosoPC. A Primer on Good Clinical Practice and Continuous
Quality Improvement in Clinical Research Monitor. 2009(Oct):23-8.
• Theobald K, Capan M, Herbold M, Schinzel S, Hundt F. Quality assurance
in non-interventional studies. Ger Med Sci. 2009;7:Doc29.
• Krockenberger K, Luntz SP, Knaup P. Usage and usability of standard
operating procedures (SOPs) among the coordination centers for
clinical trials (KKS). Methods Inf Med. 2008;47(6):505-10.
• Heeringa S, West BT, Berglund PA. Applied survey data analysis. Boca
Raton, FL: Chapman & Hall/CRC; 2010.
• Nelson EC, Batalden PB, Godfrey MM. Quality by design : a clinical
microsystems approach. 1st ed. [Lebanon, NH] San Francisco: Center
for the Evaluative Clinical Sciences at Dartmouth ; Jossey-Bass/Wiley;
2007.
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28. Special Thanks to Our
Survey Study Participants
This study is supported by
Department of Surgery,
UC Davis Medical Center
Lu et. Al., 2011
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