1. A Blueprint For Clinical Research: Standard Operating Procedures
Karen Majchrzak, MS, CCRP

2. 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)

3. 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.

4. SOPs are used to: Identify the responsible person for each task.
Describe actions (what is to be completed).
Train staff.
Monitor site performance.

5. 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 CFR 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.”

6. Are SOPs Required by Law/Regulations?
Additionally, SOPs are mentioned repeatedly in the ICH GCP Guidelines.
ICH GCP “Systems with procedures that assure the quality of every aspect of the trial should be implemented.”

7. 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.

8. Benefits of a SOP? Provides autonomy within the clinical site.
Improves the quality of the data collected, thereby improving the science of the study.

9. 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

10. SOP Topics 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

11. SOP Topics 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

12. SOP Topics 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

13. 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

14. 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

20. 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.

21. Process Mapping for Making a Cup of Coffee
Woodin, K. (2004) The CRC’s Guide to Coordinating Clinical Research p Centerwatch
Primary Step
Ensure the coffee maker is ready
Add the coffee
Add the water
Turn on the machine
Serve the coffee

22. Process Mapping for Making a Cup of Coffee
Secondary Step
Ensure the coffee maker is ready
Add the coffee
Add the water
Turn on the machine
Serve the coffee
Ensure the machine is plugged in
Place a filter in the basket
Use the carafe to measure the water
Wait until the coffee has stopped dripping
Ensure carafe is empty and clean
Measure the coffee
Place the carafe on the heating element

23. 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.

25. 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.

26. 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.

29. Tips for Writing SOPs Use clear, concise language. Use active voice.
Avoid names; use titles instead.

30. 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.

31. Implementing and Monitoring SOPs
SOPs should be reviewed on a regular basis (usually annually) to ensure policy based regulations are up-to-date.
Previous versions of SOPs should be retained.

32. SOP Training All staff should have SOP training.
Training should be documented.
SOP should be accessible to staff.

33. 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.

34. 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.

38. 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.

39. SOP or MOP 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.

40. SOP Resources Examples from National Cancer Institute
Standard Operating Procedures for Good Clinical Practice at the Investigative / Centerwatch
Cost $995 for single site license
Standard Operating Procedures (SOPs) for Good Clinical Practice / University of Washington
Cost $135

41. Comments and Questions?