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

Elements of Clinical Trial Quality

2

3

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)

Standard Operating Procedures (SOPs)

Good Clinical Practice (GCP)

4

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

Clinical Trial Quality Management

5

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)

6 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

7

"… you have not submitted the revised SOPs …."

e.g., FDA Warning Letters

UC Davis Clinical Research Studies List

at clinicaltrial.gov

8

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)

UC Davis Clinical Research Studies List

at clinicaltrial.gov

9

UC Davis sponsor (106) & Other sponsors (142)

There are 197 trials are conducted at CA

UC Davis Sponsored Clinical Studies

at clinicaltrial.gov

10

UC Davis Sponsor = 106

28

40

38 Observational

Drug (I-IV)

Other intervention

Study Objectives

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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.

.

Study Methods

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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

Data Collection

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Survey Questionnaires

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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?

• Program Managers

• Research Managers

• Nurse Managers

• Research Nurse

• Head of Biostatistics

• Analyst

• Quality Assurance

• Co-PI & CRC

• Graduate Student

n = 92

Return rate = 10.2%

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PI

33.7%

Co-PI

7.6%

CRC

34.8%

Other

17.4%

Staff

6.5%

Demographics of SOP Survey Participants

SOP Usage by Survey Respondents

16

34%

8%

36%

16%

7% 19

5 4 2

4

12

2

29

13

2

PI Co-PI CRC Other Staff

% of respondents

SOP user

Non-SOP user

PI/Co-PI (n=38, 41.3%) CRC/Other (n=54, 58.7%)

SOP Resources & User Group Profiles

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19% 10%

14%

8% 2%

20%

11%

6%

10%

0%

1%

2%

3%

4%

5%

0% 10% 20% 30%

SO

P U

sage b

y P

I/C

o-P

I

SOP Usage by CRC/Other

% of SOP Provided

NIH

Trial Sponsor Other

CRO

CTSC NCI

CCRC Private

Department

*CCRC – CTSC Clinical Research Center.

**CRO – Contract Research Organization.

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5%

5%

4%

3%

3%

1%

15%

14%

14%

15%

14%

9%

New study

Renewal

Modification

AE/SAE

Deviation

Non-compliance

PI/Co-PI CRC/Other

IRB SOP Resources & User Group Profiles

19

11

36

27

18

PI/co-PI CRC/Other

Mo

nit

ori

ng U

sed

yes

no

SOP Monitoring

Other Working Instructions

20

12 12

9

18 14

25

PI/Co-PI CRC/Other

Nu

mb

er

of

Use

r MOP

Work Instruction

No

21

Respondents

(n=92)

PI/Co-PI

(n=38)

CRC/Other

(n=54) P-value

SOP is very

important 11% (4/38) 61% (33/54)

<0.0001

SOP is not

applicable 37% (14/38) 15% (8/54)

Interested in

SOP training 41% (15/37) 68% (36/53) 0.0169

Importance of SOP & Interest in SOP Training

Summary

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Survey Respondents

(n=92)

PI/Co-PI

(n=38, 41%)

CRC/Other

(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%

Conclusion

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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.

Limitations

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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.

Future Directions

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Plan To further assess SOP usage

To identify need for training

Do To present survey results

To deliver an SOP introductory seminar

Study

To conduct an SOP survey & analyze results

To identify a small group for testing an SOP implementation supporting program

Act To test an SOP support program & monitor changes

Future Direction & Study Timeline

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Plan Do Study Act

10/11 01/12 07/12 12/12

This study cycle

The upcoming cycle

Reference

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•Hector Vizoso PC. 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.

This study is supported by

Department of Surgery,

UC Davis Medical Center

Lu et. Al., 2011

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Special Thanks to Our

Survey Study Participants