A Blueprint For Clinical A Blueprint For Clinical Research: Standard Research: Standard

Operating ProceduresOperating Procedures

Karen Majchrzak, MS, CCRPKaren Majchrzak, MS, CCRP

What are SOPs?What are SOPs?

International Conference on International Conference on Harmonization (ICH) defines a Harmonization (ICH) defines a SOP as “Detailed, written SOP as “Detailed, written instructions to achieve uniformity instructions to achieve uniformity of the performance of a specific of the performance of a specific function.” function.” (ICH GCP 1.55)(ICH GCP 1.55)

What are SOPs?What are SOPs?

In simple terms a SOP is…In simple terms a SOP is…– A written processA written process– A way for the clinical site to perform A way for the clinical site to perform

a task the same way each time it is a task the same way each time it is completed.completed.

SOPs are used to:SOPs are used to:

Identify the responsible person Identify the responsible person for each task.for each task.

Describe actions (what is to be Describe actions (what is to be completed).completed).

Train staff.Train staff. Monitor site performance.Monitor site performance.

Are SOPs Required by Are SOPs Required by Law/Regulations?Law/Regulations?

SOPs are not specifically SOPs are not specifically mentioned in the FDA regulationsmentioned in the FDA regulations

– HOWEVERHOWEVER there is guidance and there is guidance and regulations that infer responsibility and regulations that infer responsibility and SOPs formalize investigator responsibilities. SOPs formalize investigator responsibilities.

– 21 CFR312.53 the investigator will “ensure 21 CFR312.53 the investigator will “ensure that all associates, colleagues, and that all associates, colleagues, and employees assisting in the conduct of the employees assisting in the conduct of the study (ies) are informed of their obligations study (ies) are informed of their obligations in meeting the above commitments.”in meeting the above commitments.”

Are SOPs Required by Are SOPs Required by Law/Regulations?Law/Regulations?

Additionally, SOPs are mentioned Additionally, SOPs are mentioned repeatedly in the ICH GCP repeatedly in the ICH GCP Guidelines.Guidelines.

ICH GCP 2.13 -“ICH GCP 2.13 -“Systems with procedures that assure the quality of every aspect of the trial should be implemented.”

Benefits of a SOP?Benefits of a SOP?

Ensures that all research Ensures that all research conducted within the clinical site conducted within the clinical site follows federal regulations, ICH follows federal regulations, ICH GCP, and institutional policies to GCP, and institutional policies to protect the rights and welfare of protect the rights and welfare of human study participantshuman study participants. .

Benefits of a SOP?Benefits of a SOP?

Provides autonomy within the Provides autonomy within the clinical site. clinical site.

Improves the quality of the data Improves the quality of the data collected, thereby improving the collected, thereby improving the science of the study.science of the study.

Benefits of a SOP?Benefits of a SOP?

Utilized as a reference and Utilized as a reference and guideline as to how research will guideline as to how research will be conducted within the clinical be conducted within the clinical sitesite

Excellent training source for new Excellent training source for new employees and/or fellowsemployees and/or fellows

SOP TopicsSOP Topics

Preparing and Submitting Initial IRB Preparing and Submitting Initial IRB DocumentsDocuments

Preparing and Submitting Continuing Preparing and Submitting Continuing Review IRB DocumentsReview IRB Documents

Preparing and Submitting Amendment Preparing and Submitting Amendment IRB DocumentsIRB Documents

Establishing and Training the Clinical Establishing and Training the Clinical Study Team, and Delegating Study Team, and Delegating ResponsibilitiesResponsibilities

Establishing Study FilesEstablishing Study Files Establishing Source Documents Establishing Source Documents

SOP TopicsSOP Topics

Study Subject Recruitment PlanStudy Subject Recruitment Plan

Contacting and Scheduling Potential Contacting and Scheduling Potential Study Subjects for an Initial VisitStudy Subjects for an Initial Visit

Obtaining Informed Consent from a Obtaining Informed Consent from a Potential Study SubjectPotential Study Subject

Enrolling a SubjectEnrolling a Subject Recording Subject DataRecording Subject Data Making Corrections on Study Documents Making Corrections on Study Documents

SOP TopicsSOP Topics

Monitoring Subject Compliance During a Monitoring Subject Compliance During a StudyStudy

Responding to a Clinical Hold OrderResponding to a Clinical Hold Order Receiving and Storing Investigational DrugsReceiving and Storing Investigational Drugs

Drug and Study Supply Transfer Between Drug and Study Supply Transfer Between SitesSites

Dispensing Study Drugs to Study SubjectsDispensing Study Drugs to Study Subjects

Identifying and Reporting Adverse EventsIdentifying and Reporting Adverse Events Packing, Labeling, and Shipping SamplesPacking, Labeling, and Shipping Samples Identifying and Reporting Protocol DeviationsIdentifying and Reporting Protocol Deviations

SOP TopicsSOP Topics

Additional TopicsAdditional Topics Contact with potential sponsorsContact with potential sponsors Budget review and determinationsBudget review and determinations Pre-study study site visitPre-study study site visit Initiation Site VisitInitiation Site Visit Monitor VisitsMonitor Visits AuditsAudits Data managementData management Study closureStudy closure Long term storageLong term storage

Writing SOPsWriting SOPs

Develop a template for the SOP to be Develop a template for the SOP to be used throughout the document.used throughout the document.

Potential elements of the SOPPotential elements of the SOP– Header – title, original version date, revision Header – title, original version date, revision

date, effective date, approved bydate, effective date, approved by– Purpose – why one has the policyPurpose – why one has the policy– Responsibilities – who the policy pertains toResponsibilities – who the policy pertains to– Instruction/Procedures – how to accomplish Instruction/Procedures – how to accomplish

the items of the policythe items of the policy– References – what the policy is based onReferences – what the policy is based on– Appendix – source documents/case report Appendix – source documents/case report

formsforms

Process Mapping for Writing Process Mapping for Writing SOPsSOPs

Determine which clinical site task Determine which clinical site task needs mapping.needs mapping.

Lay out all the steps currently Lay out all the steps currently used to complete that task.used to complete that task.

““Mapping” involves taking each Mapping” involves taking each step in the task and making it step in the task and making it more efficient and easier to more efficient and easier to follow.follow.

Process Mapping for Making Process Mapping for Making a Cup of Coffeea Cup of Coffee

Primary StepPrimary Step

Ensure the coffee maker is ready

Add the water

Turn on the machine

Serve the coffee

Add the coffee

Woodin, K. (2004) The CRC’s Guide to Coordinating Clinical Research p. 60-65. Centerwatch

Process Mapping for Making Process Mapping for Making a Cup of Coffeea Cup of Coffee

Ensure the coffee maker is ready

Add the coffee

Add the water

Turn on the machine

Serve the coffee

Secondary StepSecondary Step

Ensure the machine is plugged in

Ensure carafe is empty and clean

Place a filter in the basket

Measure the coffee

Use the carafe to measure the water

Place the carafe on the heating element

Wait until the coffee has stopped dripping

Process Mapping for Writing Process Mapping for Writing SOPsSOPs

Once you have finished mapping, Once you have finished mapping, convert your process map to an convert your process map to an outline for easy use.outline for easy use.

Once a task has been mapped, it Once a task has been mapped, it should be tested.should be tested.

SOPs and GuidelinesSOPs and Guidelines

Some SOPs have a two-tiered Some SOPs have a two-tiered system that includes both SOPs system that includes both SOPs and guidelines.and guidelines.

SOPs provide a general view of all SOPs provide a general view of all the main steps whereas the main steps whereas guidelines are significantly more guidelines are significantly more detailed.detailed.

SOPs and GuidelinesSOPs and Guidelines

One advantage of a two-tiered One advantage of a two-tiered system is that SOPs will rarely system is that SOPs will rarely need to be changed, whereas need to be changed, whereas guidelines may need to be guidelines may need to be changed or updated more changed or updated more frequently due to changes in frequently due to changes in organizational structure or organizational structure or equipment.equipment.

Tips for Writing SOPsTips for Writing SOPs

Use clear, concise language.Use clear, concise language.

Use active voice.Use active voice.

Avoid names; use titles instead.Avoid names; use titles instead.

Implementing and Implementing and Monitoring SOPsMonitoring SOPs

SOPs should be introduced SOPs should be introduced gradually. gradually.

Prioritize most relevant SOPs and Prioritize most relevant SOPs and present them first.present them first.

Principle Investigator should Principle Investigator should approve all SOPs and designate approve all SOPs and designate an effective date.an effective date.

Implementing and Implementing and Monitoring SOPsMonitoring SOPs

SOPs should be reviewed on a SOPs should be reviewed on a regular basis (usually annually) to regular basis (usually annually) to ensure policy based regulations ensure policy based regulations are up-to-date.are up-to-date.

Previous versions of SOPs should Previous versions of SOPs should be retained.be retained.

SOP TrainingSOP Training

All staff should have SOP training.All staff should have SOP training.

Training should be documented.Training should be documented.

SOP should be accessible to staff.SOP should be accessible to staff.

What is the difference between What is the difference between a SOP and a Manual of a SOP and a Manual of

Procedures (MOP)?Procedures (MOP)?

These terms have been used These terms have been used interchangeably.interchangeably.

Both provide a standardization of Both provide a standardization of a process.a process.

What is the difference between What is the difference between a SOP and a Manual of a SOP and a Manual of

Procedures (MOP)?Procedures (MOP)?

SOP provides general information SOP provides general information that is to be utilized throughout that is to be utilized throughout anyany research study. research study.– How as a clinical site we will assess How as a clinical site we will assess

delegation of duties.delegation of duties.

MOP is specifically written for a MOP is specifically written for a particular research study which will particular research study which will incorporateincorporate elements of the SOP. elements of the SOP.

MOPMOP

The MOP should be written so The MOP should be written so that anyone in your clinical site that anyone in your clinical site can follow the procedures for that can follow the procedures for that study and find all relevant study and find all relevant materials.materials.

The MOP should be extremely The MOP should be extremely detailed.detailed.

SOP or MOPSOP or MOP

Both documents are important!Both documents are important!

Start with the SOP first. Once you Start with the SOP first. Once you have written general procedures, have written general procedures, the MOP will be easier.the MOP will be easier.

This process will take lots of time This process will take lots of time and patience.and patience.

SOP ResourcesSOP Resources

Examples from National Cancer InstituteExamples from National Cancer Institute

https://cabig.nci.nih.gov/workspaces/CTMS/Meetings/SIGs/Best_Practices/SOPs/SOPs

Standard Operating Procedures for Good Clinical Standard Operating Procedures for Good Clinical Practice at the Investigative / CenterwatchPractice at the Investigative / Centerwatchhttp://www.ccrp.com/sop.shtml Cost $995 for single site licenseCost $995 for single site license

Standard Operating Procedures (SOPs) for Good Standard Operating Procedures (SOPs) for Good Clinical Practice / University of WashingtonClinical Practice / University of Washington

http://www.crc.washington.edu/Resources/GCPSOPInvSites.aspxCost $135Cost $135

Comments and Comments and Questions?Questions?