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: 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 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 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 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 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

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-to-date. 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 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 Examples from National Cancer Institute https://cabig.nci.nih.gov/workspaces/CTMS/Meetings/SIGs/Best_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.aspx Cost $135

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