A Blueprint For Clinical
Research: Standard
Operating Procedures
Karen Majchrzak, MS, CCRP
What are SOPs?

International Conference on
Harmonization (ICH) defines a SOP as
“Detailed, written instructions to
achieve uniformity of the performance
of a specific function.” (ICH GCP 1.55)
What are SOPs?

In simple terms a SOP is…
– A written process
– A way for the clinical site to perform a
task the same way each time it is
completed.
SOPs are used to:


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Identify the responsible person for
each task.
Describe actions (what is to be
completed).
Train staff.
Monitor site performance.
Are SOPs Required by
Law/Regulations?

SOPs are not specifically mentioned
in the FDA regulations
–
HOWEVER there is guidance and regulations
that infer responsibility and SOPs formalize
investigator responsibilities.
–
21 CFR312.53 the investigator will “ensure
that all associates, colleagues, and employees
assisting in the conduct of the study (ies) are
informed of their obligations in meeting the
above commitments.”
Are SOPs Required by
Law/Regulations?


Additionally, SOPs are mentioned
repeatedly in the ICH GCP Guidelines.
ICH GCP 2.13 -“Systems with
procedures that assure the quality of
every aspect of the trial should be
implemented.”
Benefits of a SOP?

Ensures that all research conducted
within the clinical site follows federal
regulations, ICH GCP, and institutional
policies to protect the rights and
welfare of human study participants.
Benefits of a SOP?


Provides autonomy within the clinical
site.
Improves the quality of the data
collected, thereby improving the
science of the study.
Benefits of a SOP?


Utilized as a reference and guideline
as to how research will be conducted
within the clinical site
Excellent training source for new
employees and/or fellows
SOP Topics




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Preparing and Submitting Initial IRB
Documents
Preparing and Submitting Continuing Review
IRB Documents
Preparing and Submitting Amendment IRB
Documents
Establishing and Training the Clinical Study
Team, and Delegating Responsibilities
Establishing Study Files
Establishing Source Documents
SOP Topics





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Study Subject Recruitment Plan
Contacting and Scheduling Potential Study
Subjects for an Initial Visit
Obtaining Informed Consent from a
Potential Study Subject
Enrolling a Subject
Recording Subject Data
Making Corrections on Study Documents
SOP Topics





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
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Monitoring Subject Compliance During a
Study
Responding to a Clinical Hold Order
Receiving and Storing Investigational Drugs
Drug and Study Supply Transfer Between
Sites
Dispensing Study Drugs to Study Subjects
Identifying and Reporting Adverse Events
Packing, Labeling, and Shipping Samples
Identifying and Reporting Protocol
Deviations
SOP Topics
Additional Topics
 Contact with potential sponsors
 Budget review and determinations
 Pre-study study site visit
 Initiation Site Visit
 Monitor Visits
 Audits
 Data management
 Study closure
 Long term storage
Writing SOPs


Develop a template for the SOP to be used
throughout the document.
Potential elements of the SOP
– Header – title, original version date, revision
date, effective date, approved by
– Purpose – why one has the policy
– Responsibilities – who the policy pertains to
– Instruction/Procedures – how to accomplish the
items of the policy
– References – what the policy is based on
– Appendix – source documents/case report forms
Process Mapping for Writing
SOPs



Determine which clinical site task
needs mapping.
Lay out all the steps currently used to
complete that task.
“Mapping” involves taking each step in
the task and making it more efficient
and easier to follow.
Process Mapping for Making a
Cup of Coffee
Woodin, K. (2004) The CRC’s Guide to Coordinating Clinical Research p. 60-65. Centerwatch
Primary Step
Ensure
the coffee
maker is
ready
Add the
coffee
Add the
water
Turn on
the
machine
Serve the
coffee
Process Mapping for Making a
Cup of Coffee
Secondary Step
Ensure
the coffee
maker is
ready
Add the
coffee
Add the
water
Ensure the
machine is
plugged in
Place a
filter in
the basket
Use the
carafe to
measure
the water
Ensure
carafe is
empty and
clean
Measure
the coffee
Place the
carafe on
the
heating
element
Turn on
the
machine
Serve the
coffee
Wait until
the coffee
has
stopped
dripping
Process Mapping for Writing
SOPs


Once you have finished mapping,
convert your process map to an
outline for easy use.
Once a task has been mapped, it
should be tested.
SOPs and Guidelines


Some SOPs have a two-tiered system
that includes both SOPs and
guidelines.
SOPs provide a general view of all the
main steps whereas guidelines are
significantly more detailed.
SOPs and Guidelines

One advantage of a two-tiered system
is that SOPs will rarely need to be
changed, whereas guidelines may
need to be changed or updated more
frequently due to changes in
organizational structure or equipment.
Tips for Writing SOPs

Use clear, concise language.

Use active voice.

Avoid names; use titles instead.
Implementing and Monitoring
SOPs



SOPs should be introduced gradually.
Prioritize most relevant SOPs and
present them first.
Principle Investigator should approve
all SOPs and designate an effective
date.
Implementing and Monitoring
SOPs


SOPs should be reviewed on a regular
basis (usually annually) to ensure
policy based regulations are up-todate.
Previous versions of SOPs should be
retained.
SOP Training

All staff should have SOP training.

Training should be documented.

SOP should be accessible to staff.
What is the difference between a
SOP and a Manual of Procedures
(MOP)?


These terms have been used
interchangeably.
Both provide a standardization of a
process.
What is the difference between a
SOP and a Manual of Procedures
(MOP)?

SOP provides general information that
is to be utilized throughout any
research study.
– How as a clinical site we will assess delegation
of duties.

MOP is specifically written for a
particular research study which will
incorporate elements of the SOP.
MOP


The MOP should be written so that
anyone in your clinical site can follow
the procedures for that study and find
all relevant materials.
The MOP should be extremely
detailed.
SOP or MOP


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Both documents are important!
Start with the SOP first. Once you
have written general procedures, the
MOP will be easier.
This process will take lots of time and
patience.
SOP Resources

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Examples from National Cancer Institute
https://cabig.nci.nih.gov/workspaces/CTMS/Meetings/SIGs/Be
st_Practices/SOPs/SOPs
Standard Operating Procedures for Good Clinical Practice at
the Investigative / Centerwatch
http://www.ccrp.com/sop.shtml
Cost $995 for single site license
Standard Operating Procedures (SOPs) for Good Clinical
Practice / University of Washington
http://www.crc.washington.edu/Resources/GCPSOPInvSites.as
px
Cost $135
Comments and
Questions?