Corrective and Preventive Action Plans: Winship

Stephanie deRijke Clinical Trials Audit and Compliance

Objectives

• Describe the current CAPA environment at Winship

• Outline the steps to take when a problem occurs

• Detail the processes of root cause analysis and corrective and preventive actions

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What is CAPA?

• Corrective and Preventive Actions – Corrective Actions

• The process of reacting to an existing problem and fixing it

– Preventive Actions • The process of detecting potential problems and

eliminating them

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CAPA History at Winship

• 2009-2011: Death by CAPA 2009: NCI Cooperative Group audits, enrollment halt 2010: 6 FDA inspections at Winship, all 6 received 483s

• 2011-2013: Link CAPA to Winship SOPs • Today: Reserve CAPA for significant problems

– Training – Process (streamlining SOPs) – Continuous quality assurance and improvement – Proactive compliance

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CAPA Origins

• IRB reports – Mostly study-specific problems – IRB approves CAPA plans with each event report

• Sponsor monitoring or audits • FDA inspections

– Winship SOPs

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Problems in Research

• Steps to resolve problems – Identify problems – Make immediate corrections – Evaluate risk – Identify root cause of each problem – Identify corrective and preventive action for each

root cause

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Problem Statement

• A problem statement should include – Description of the problem – Where and when it happened – Weight of the problem – Requirements that were not met – Evidence to show that requirements weren’t met

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Corrections

“Immediate corrections” include – Evaluating rights, welfare, and safety of subject – Reporting, if applicable: subject, subject’s family,

sponsor, and/or IRB

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Evaluate Risk

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Risk

• Severity – Rights, welfare, and safety of current and future

subjects

• Frequency – Systematic problem – Protocol design – Departmental, local problem

• If Risk is there, move to RCA and CAPA

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Problem Occurs

Immediate Corrections

Assess Risk

Root Cause Analysis

CAPA Plan

Effectiveness Check

Yes risk

No risk

If CAPA didn’t resolve root cause

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Root Cause

• The root cause is the initiating, most basic cause of a problem that may or may not lead to a chain of causes or other problems (domino effect)

• Eliminating the root cause should prevent recurrence of the problem

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Root Cause Analysis (RCA)

• The RCA is the process of identifying the root cause and the downstream effect on the causal chain

• Since noncompliance is usually from a system failure, not a person failure, RCA should focus on identifying underlying problems that contribute to error rather than focusing on mistakes made by individuals

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RCA Steps

• Questions to ask – Why and how did the problem occur? – What were the steps? – Who was impacted by the problem? – Keep asking “why” and “how” until you reach the

root cause

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Documenting the RCA

• Summarize the problem or event • Note the sequence of events • Note the implicated processes • Summarize the immediate corrections taken • Summarize the root cause investigation

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Corrections vs Corrective Actions

• Corrections – Immediate actions taken to resolve a problem

before the root cause is known – Putting out fires – Could resolve minor deviations/noncompliance

• Corrective Actions – If risk of problem (severity and frequency) is

greater, do RCA and move to CAPA – Process

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FDA Warning Letter Excerpts

• “You failed to secure the investigator’s compliance and allowed subjects to be put at risk for potential adverse effects, such as…Your response is inadequate in that it does not describe your corrective and preventive actions in sufficient detail.”

• “You stated that study subjects will be re-consented with a revised consent form after it is approved by the IRB. Your response is inadequate as it lacks a corrective and preventive action plan to ensure that adequate consent forms are provided to study subjects prior to any study related procedures in the future.”

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CAPA Don’ts!

• We will retrain the study team… • Study team members have been terminated

or will be reassigned… • We will have 5 people check….

– Don’t overpromise with detailed CAPA plans that we can’t maintain

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CAPA Musts!

• Corrective: Assess and correct safety/rights/welfare of subjects. Report to subjects, IRB, sponsor, and/or internal department. Document corrections.

• Preventive: Develop and document a process, train on the process, implement the process, evaluate the process, amend process as necessary.

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“SMART” CAPAs

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Effectiveness Check

• Build in an effectiveness check as the final step of CAPA

• Effectiveness checks verify that the CAPAs resolved the root cause

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Documenting the CAPA

• Action type (corrective or preventive) • Action description • Owner • Due date • Plan for effectiveness check • Effectiveness check outcome

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In Summary

• Problem occurs • Immediate corrections taken • Determine impact of problem and risk of

recurrence (risk = severity + frequency) • Root cause analysis • CAPA plan • Effectiveness check

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CTAC Website

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Contacts

• Stephanie deRijke – Emory University Clinical Trials Audit and

Compliance – www.ctac.emory.edu – smickle@emory.edu – (404) 712-5159

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Standard Operating Procedures

Pre-Test

The Delegation of Authority Log will be reviewed and updated by the Principal Investigator over the course of the study and reviewed for completeness to ensure it is updated and maintained:

A. At the time of the continuing review B. Monthly C. Quarterly D. Never

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The Regulatory Specialist is responsible for maintaining a list of appropriately qualified individuals whom the investigator has delegated significant study related duties.

A. True B. False

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A Winship Signature Sheet will be completed by each study team member and will include the following information: A. Printed name of study team member B. Job Title (not study specific task) C. Signature(s), initials and date of completion D. A and C only E. All of the above

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Essential regulatory documents will be maintained in a paper format housed in OnCore.

A. True B. False

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When will external study sponsors/monitors be informed that the essential regulatory documents are kept and maintained electronically? A. Site-Selection Visit B. Close-out Visit C. Site Initiation Visit D. A and C only E. All of the above

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Standard Operating Procedures 8.0 & 8.3

Kim Nguyen, BS Assistant Director, Regulatory Affairs

Purpose: To establish standards for creating and maintaining electronic regulatory documents Scope: Winship Regulatory specialists and any others who create or maintain records for Winship clinical trials.

SOP 8.0 Electronic Maintenance of the Winship Regulatory Documents

Electronic File storage location: • Essential regulatory documents for the conduct of human subject research will be

maintained in an electronic format housed in OnCore. OnCore is a password protected software system especially designed for cancer studies.

• Scanned copies of paper documents with appropriate documentation will be considered certified copies. Certified copy means a copy of original information that has been verified, as indicated by dated signature, as an exact copy having all of the same attributes and information as the original.

• The Set up in OnCore outlined in “Guide for Oncore eREG/secure drive documents” (attached) will mimic the set up utilized in a paper regulatory binder. Documents will be scanned, verified, and uploaded into OnCore as certified documents following the drop down menu in the IRB Review tab – Detail tab. The appropriate drop down menu is selected for a given document. Study personnel documents such as CV, medical licenses, signature page, and general required training are kept under the staff tab in Oncore.

• Non-study specific documents as outlined in the “Guide for Oncore eREG/secure drive” will be kept on the password protected secure network drive. These documents are labeled as non-study specific documents such as laboratory CLIA/CAP certificates, laboratory norm values.

Procedure: • The Winship Regulatory specialist will review original study records and complete

and sign the Certified Copy Cover Sheet (attached) noting the number of pages. The Regulatory Specialist will scan the Certified Copy Cover Sheet and original study records into Adobe® portable document file (PDF) electronic format.

• The regulatory specialist will ensure that the scanned PDF version appears as the original paper version; verification must include the following: legibility of the scanned document, intact head and footer, and all pages appear “in total”.

• Following review of the scanned documents, the regulatory specialist will upload the PDF, which includes Certified Copy Cover Sheet and original documents, into OnCore. If the scanned documents do not meet the requirements of a certified copy (an exact copy having all of the same attributes and information as the original), the regulatory Specialist will scan again prior to uploading into OnCore.

• Scanned and certified documents will be named in such manner that they clearly reference the document content. Examples of this could be; “Protocol version 1.02 dated 12/4/2014”.

• Each scanned file will only contain one document. • Electronic documents provided by sponsor or from secure electronic systems will

be renamed and placed in OnCore/secure drive directly without any conversion. The regulatory specialist will name these documents so that they reference their original content.

• Paper documents that have been scanned, certified, and placed into OnCore/secure drive can be returned to sponsor, if requested or destructed by shredding the document.

Institutional/external review and audits: • External study sponsors/ monitors will be informed during the study start up (site-

selection or the site initiation visit) that the essential regulatory documents are kept and maintained electronically, with records not originally electronic transferred into PDFs as certified copies.

• Electronic certified copies of documents in OnCore will be made available for review either by assigning a monitor study specific “log in” to OnCore and/or via a flash drive. Study specific log in for monitors will be requested by the regulatory specialist.

Retention of study records in OnCore once study is closed: • Electronic documents stored in OnCore and on secure network drive will be maintained

for the period specified in the study protocol, study contract, institutional policies, cooperative study group policies, and/or research regulation for whichever period is longer.

Attachments: Guide for OnCore/secure drive documents Certified Copy Cover

SOP 8.3 Delegation of Authority

Purpose: To document the delegation of authority by the Principal Investigator. Scope: All Winship investigators and staff involved in the management of subjects who participate in cancer-related clinical research involving drugs, biologics, devices or invasive procedures. Responsibilities: The Principal Investigator (referred to as the "qualified investigator" in the federal regulations) is responsible for maintaining a list of appropriately qualified individuals to whom the investigator has delegated significant study related duties.

• The Principal Investigator will ensure that all persons assisting with the trial are adequately informed about the protocol, the investigational product(s) and their trial related duties and functions. Protocol specific training will be documented for each individual with delegated responsibilities.

• The Principal Investigator is responsible for personally supervising the conduct

of the investigation and for providing oversight of members of the research team with delegated responsibilities.

• The Principal Investigator should assess study requirements and assign

responsibility to specific qualified team members. Minimum qualifications include meeting the following requirements: – Curriculum Vitae/evidence of qualifications in the study file – Copy of professional license, if applicable in the study file – Current CITI certification – HIPAA training – Completion of investigator or CRN/CRC mandatory training requirements – Completion of study specific training – Included in the IRB submission for studies reviewed by the Emory IRB

• A Delegation of Authority (DOA) Log will be used to document the tasks and functions delegated to research team members by the Principal Investigator. The log may be provided by the sponsor or created by the study team (see Attachment). The DOA Log must be completed at the time the study is initially open to accrual. The DOA Log will be reviewed and updated by the Principal Investigator over the course of the study and reviewed for completeness at the time of the continuing review to ensure it is updated and maintained. Review of the DOA Log will be documented with the signature and date of review by the Principal Investigator.

• A Winship Signature Sheet will be completed by each study team member and will include the study team member’s name in print, job title (not study specific task), signature(s), initials and date for completion.

• The Delegation of Authority log and Winship Signature Sheet will be maintained

by the regulatory specialist or designee and filed with the study regulatory documents.

Attachments: • Delegation of Authority Log • Winship Signature Sheet

Winship CTO SOPs and Forms can be found on Winship Intranet: https://apps.winship.emory.edu/intranet/clinicaltrials

Questions?

Standard Operating Procedure

Post Test

The Delegation of Authority Log will be reviewed and updated by the Principal Investigator over the course of the study and reviewed for completeness to ensure it is updated and maintained:

A. At the time of the continuing review B. Monthly C. Quarterly D. Never

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The Regulatory Specialist is responsible for maintaining a list of appropriately qualified individuals whom the investigator has delegated significant study related duties.

A. True B. False

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A Winship Signature Sheet will be completed by each study team member and will include the following information: A. Printed name of study team member B. Job Title (not study specific task) C. Signature(s), initials and date of completion D. A and C only E. All of the above

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Essential regulatory documents will be maintained in a paper format housed in OnCore.

A. True B. False

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When will external study sponsors/monitors be informed that the essential regulatory documents are kept and maintained electronically? A. Site-Selection Visit B. Close-out Visit C. Site Initiation Visit D. A and C only E. All of the above

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