J.10 - Example Regulatory Compliance QM Plan Template.pdf

Attachment J.10 - Solicitation # 75D301-20-R-67869 TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan

Regulatory compliance and quality management includes ALL processes aimed at adherence to clinical research regulations and prevention of errors as well as those associated with identifying and correcting of errors. Proactive prevention of errors results in less time and resources being required to resolve issues downstream. The Regulatory

Compliance and Quality Management (RCQM) plan review and verification processes promotes: 1) data accuracy and completeness of data capture, 2) enhances protection of human subject’s rights and welfare, and 3) ensures that Good

Clinical Practice (GCP) standards and regulatory requirements are met.

Clinical research sites need a RCQM strategy that includes written procedures; ongoing verification of documentation;

and review of compliance with the investigational plan, procedures, guidelines and regulations. The overall objective is participant safety, data quality and data integrity.

The RCQM plan is a tool that describes the quality control (QC), quality assurance (QA) and quality improvement (QI) processes to be implemented in the conduct of CDC/TBTC/TBESC-funded human subjects research. Definitions and examples are listed below.

• Quality Control – ensures that a protocol and accepted procedures are being followed o Real time, “day-to-day” activities o Operational techniques o Observations and documentation of the site’s work

• Quality Assurance - ensures that activities are conducted effectively and efficiently o Written standard operating procedures (SOPs) o Audit reports o Computer system validations o Training records

• Quality Improvement – evaluates and improves performance and efficiency o Systematic, data-guided activities o Strategies and methods to close the gap between the current and the expected levels of quality.

Every TBTC and TBESC site will have a written plan for local RCQM activities including quality control, assurance and improvement strategies. All sites will participate in the TBTC/TBESC Quality Assurance Program, which includes, but is not limited to data inquiries and scheduled QA reviews by the Data Coordinating Center (DCC).

The following sections are the required components of the RCQM Plan (RCQMP).

If a site has internal SOPs that address components of the RCQMP, those SOPs can be submitted in lieu of addressing specific questions. If SOPs will be submitted, indicate in the RCQMP that an SOP is submitted and the SOP name.

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Prior to creating your plan

Determine a realistic approach to the sample size/percentage of documents and records that will be reviewed during the QC and QA process and the frequency of QA reviews. Ensure that your site has the capacity to support the level of

QC and QA effort indicated in the plan. For each component of the RCQMP, ask yourself “How does our site do things?”

General instructions when submitting your plan to the Study 37/Part D Team

1) Include a list of persons who will be involved in implementing the RCQMP (name, degree, title or position) and a brief description of his/her responsibilities relative to implementing the RCQMP.

2) If your site has current, approved SOPs detailing tasks and activities related to components of this plan, it is allowable to submit the SOPs with the RCQMP. If SOPs are submitted, you must describe the SOP within the RCQMP and specify the text in the SOP that address the specific RCQMP section. You cannot simply submit SOPs in lieu of completing this plan.

3) If your plan references any external documents such as your Delegation of Authority Log, SOPs, review tools, and worksheets, submit them along with your plan.

4) Indicate if your site will use QA review tools and attach these as applicable.

5) Include a description of the initial dissemination of the RCQMP, and evaluation and revision (if applicable) of the

RCQMP:

• How site research personnel will be informed of and receive initial training regarding their site-specific

RCQMP.

• When quality management activities and protocol changes will be reviewed and assessed to determine if revisions and additions are needed in the RCQMP.

• How site research personnel will be informed of and receive training regarding changes made in their site-specific RCQMP.

6) Italicized text are instructions or prompts to help complete the plan.

7) The EXAMPLE of the RCQMP is provided as a guide for drafting your site specific RCQMP. It is an EXAMPLE only.

It should be edited and personalized relative to your site’s practices and policies. Each site should determine a reasonable quality management process that can and will be implemented as described. Hint: For each component of the RCQMP, ask yourself “How does our site do things?”

• If you need guidance and/or answers to questions contact:

1st - Your ‘buddy site’ (if applicable) 2nd – Email the Study 37 mailbox: tbtcstudy37@cdc.gov mailto:tbtcstudy37@cdc.gov

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Site ##

Location

TBTC Study 37/TBESC Part D

Regulatory Compliance & Quality Management Plan (RCQMP)

Version X.X

Version Date

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Table of Contents DESCRIPTION OF Insert site number

ROLES and RESPONSIBILITIES

Regulatory Compliance

Informed Consent

Quality Control

Quality Assurance, Improvement and Monitoring

Glossary

Upon completion of your plan, update this table to include the proper page numbers.

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

DESCRIPTION OF Insert site number

Insert brief description of site where study will be implemented

ROLES and RESPONSIBILITIES

Describe the specific responsibilities relative to implementing the RCQMP.

At a minimum, the PI and Quality Program Coordinator must be included here. If other staff have RCQMP responsibilities, also include them. If no other staff have responsibilities, delete the last row in the table below.

The Quality Program Coordinator is likely the study or project coordinator at each site. This person may not have the official title of “Quality Program Coordinator” yet has the responsibility of ensuring compliance with the site’s quality management program.

Role Name Email Responsibility

Principal Investigator (PI)

Quality Program Coordinator

Additional staff

Additional staff

Regulatory Compliance

In this section, you will describe storage location, and frequency of review and updating of regulatory documents.

Also, describe any site-specific tools or checklists used to ensure regulatory compliance. Site-specific tools and checklists should be submitted as attachments to this plan.

For each document in the tables below, insert the storage location and frequency of review/updating in the appropriate columns.

Regarding storage location – The response to storage location should be either a physical place (e.g. specific binder) or electronic storage location. It is not required to have both printed and electronic copies of documents. If storage will be electronic only, TBTC/TBESC DCC strongly suggests creation of a “map” of electronic storage locations, and that the storage locations are accessible by at least the site PI, study or project coordinator, and staff responsible for regulatory compliance. Submission of a “map” of electronic storage locations is not required as part of the RCQMP.

Regarding frequency of review – Describe the frequency of review and updating, if applicable, after study initiation. It is expected that all documents will be reviewed at least annually.

a. Describe any site-specific tools or checklists used to ensure regulatory compliance.

Attach any site-specific tools, checklists, etc.

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

b. Regulatory Documents

Site Specific IEC/IRB Documents

Document Storage Location Frequency of review and updating

IEC/IRB assurance letter

IEC/IRB membership or roster (as applicable)

Protocol approval

Amendment(s) approval(s)

Informed consent approval(s) including translations

Assent approval(s) including translations

Investigator’s brochure acknowledgment

Continuing review/progress report approval(s)

Information given to participants approval(s)

Safety report(s) acknowledgement

Site Specific Documents

FDA 1572

Staff curriculum vitae

Financial disclosure statement(s)

Conflict of interest statement(s)

Delegation of authority/signature log

Approvals for research in pregnant females

Approvals for research in children

Human subjects protection training certificate(s)

Good Clinical Practice

Shipping dangerous goods

Study specific in-service training log(s)

CDC Site Specific Approvals and Communications

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Initial site registration

Amendment site registration

Pharmacy plan approval

Regulatory compliance and quality management plan approval

Laboratory approval

CDC-IRB annual continuation approval(s)

Study memo(s)

Data Safety Monitoring Board memo(s)

Monitoring Site Visits, Audits and Inspections

Monitoring site visit confirmation letter(s)

Monitoring site visit log

Monitoring site visit report(s)

Monitoring site visit follow-up log

CDC technical assistance visit report(s)

Compliance audit confirmation letter(s)

Compliance audit report(s)

Federal agency inspection announcement/correspond ence

Federal agency inspection(s) report(s)

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Informed Consent

Proper informed consent procedures are required for clinical research to ensure that participant rights are respected. In this section, you will describe quality control and assurance activities for informed consent procedures.

In the table below, describe how the following components of the informed consent procedure will be accomplished, documented, monitored, and errors corrected, when applicable, by your site team.

Attach site-specific tools or checklists that will be used to ensure proper informed consent procedures were performed.

How will this be accomplished? How will this be documented? How will this be monitored?

What is the corrective action/error resolution plan?

All current approved versions, English and translations, used with valid date stamp

Informed consent obtained before study procedures initiated

Participant given sufficient time to consider participation in the study

Understanding of study assessed

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

All cosigners (participants, parents/LARs, witnesses, persons obtaining consent) personally sign and date the consent document

Policy regarding obtaining consent from an adult who cannot read adhered to and documented

Policy regarding obtaining consent from an adult who cannot sign their name is adhered to and documented

Applicable regulation(s) and IEC/IRB policy pertaining to person(s) legally authorized to consent on behalf of a minor is adhered to and documented

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Applicable regulation(s) and IEC/IRB policy pertaining to requirement for one or both biologic/adoptive parents consenting on behalf of a minor is adhered to and documented

Minor provides assent (affirmative agreement) for study participation and personally sign and date the assent document

Person obtaining consent is an approved signatory per local regulatory authority

Documenting the informed consent process (initial consent and re-consent) in each participant’s study record and/or medical record

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Applicable regulation(s) and/or IEC/IRB policy pertaining to requirement for re-consent is adhered to and documented

Copy of signed and dated consent/assent document provided to participant

Copy of signed and dated consent/assent document filed in participant study record

Local requirements for scanned/photocopies of the signed and dated consent/assent document filed in participant medical record is adhered to and documented

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Original signed and dated consent/assent document is filed in the study regulatory binder or another appropriate binder

Quality Control

In this section, you will describe the data flow process from participant encounters to validation of data reported to the TBTC2 online study management system.

A simple data flow schematic is below. Using the screening and enrollment encounter as an example, describe your site’s data flow from participant encounter to eCRF data entry, including data verification and validation steps and the data correction process. Include the expected amount of time each step takes.

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

PARTICIPANT ENCOUNTER

Screening

Data Verification and/or Validation Process

Data Correction Process Expected length of time to complete step

Enrollment/Non-Enrollment

Data Verification and/or Validation Process

Data Correction Process Expected length of time to complete step

Participant encounter

Creation and organization of source documents

CRF transcription eCRF data entry

Data Verification (green arrows) is the comparison of abstracted/reported data to the previous data in the site’s data flow

Data Validation (red arrow) is the comparison of reported data to source documents

Errors identified through data verification or validation must be corrected

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

CREATION AND ORGANIZATION OF SOURCE DOCUMENTS

Consent/Assent

Data Verification and/or Validation Process

Data Correction Process

Screening/Enrollment

Process

Data Correction Process

CRF TRANSCRIPTION (OPTIONAL)

Process

Data Correction Process

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018 eCRF DATA ENTRY

Process

Data Correction Process

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

a. Source Documentation and Data Validation

All data reported to TBTC/TBESC via the TBTC2 study management system must be available in source documents. Case Report Forms cannot be used as source documents for TBTC Study 37 / TBESC Part D.

In the table below, list the source documents that will be used to document data on each case report form.

Include the percent of CRFs to be validated and how often validation tasks will be completed. Please note that the percent validated and frequency of validation must be reasonable and achievable for your site given staff capacity.

Regarding Worksheets – TBTC/TBESC DCC does not create worksheets. Experienced TBTC site coordinators often create worksheets for use at their sites, and share with all coordinators. Use of worksheets is not required, but has proven to be extremely useful for many sites over the history of TBTC studies.

Regarding CRFs – there is no requirement to complete paper CRFs from source documents. For this study, all CRFs are electronic, thus the eCRFs are the study data of record. Site teams often find that data entry is more efficient when using the paper CRFs, and may choose to transcribe data from source documents to paper case report forms prior to online data entry.

Source Document(s) Case Report Form (CRF) Percent of

CRFs Validated

Frequency of Validation

Non-enrollment

Enrollment

History

Concomitant Medication

LTBI Dose Record

Clinical Evaluation

Laboratory Evaluation

Mycobacteriology Evaluation

Signs and Symptoms

Study Treatment Evaluation

Study Treatment Completion

Follow-up Evaluation

Follow-up Completion

Adverse Event

Adverse Event Follow-up

Possible Poor Treatment Outcome

Notification of Death

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Quality Assurance, Improvement and Monitoring

a. DCC-provided quality assurance

Describe activities related to reviewing and responding to DCC-provided quality assurance reports and communications. A description of each type of DCC-provided quality assurance tool is below.

Site-specific tools or checklists that will be used in implementing site quality management activities should be submitted with this plan.

Real time data checks – these query reports will be posted on the TBTC2 web portal and updated daily. The site will be responsible for logging into the system and reviewing the report and either correcting the issue listed or contacting the DCC if no error is found.

Missing forms reports – these reports will be posted on the TBTC2 web portal and updated daily. The reports will list forms that are late and need to be submitted in the system. If the form has been submitted and is still listed on the report the following day, DCC should be contacted.

QA Performance Metrics – these reports will be posted on the TBTC2 web portal and updated daily. The reports will list areas where the site is deficient in the measure that is listed (e.g. Data quality (late forms), Ineligible enrollments, Blood specimens (labs not performed), Missed visits). Reports should be reviewed regularly (as determined by the site) to assess site study management and data quality. If errors are noticed in reports, sites should contact

DCC. Formal QA reviews will occur, typically twice per year, where sites will be required to review the posted QA Performance measure reports and respond to deficiencies.

Emailed queries – DCC will email queries to sites related to inconsistencies in the data, protocol deviations, and other data checks. These queries will typically be emailed to the study coordinator and data manager, as listed in the TBTC2 Member Module

DCC-

Provided Quality

Assurance

How often will the reports available on

TBTC2

reviewed?

What is your site’s goal (in days) for resolution of quality assurance issues after receipt of query or review of report?

How will errors be documented?

Real time data checks

Missing forms reports

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

DCC-

Provided Quality

Assurance

How often will the reports available on

TBTC2

reviewed?

What is your site’s goal (in days) for resolution of quality assurance issues after receipt of query or review of report?

How will errors be documented?

QA

performance metrics

Emailed queries

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

b. Important protocol deviations

Important protocol deviations are any protocol deviation that may significantly impact the completeness, accuracy, and/or reliability of the study data, that may significantly affect a subject's rights, safety, or well-being and that requires reporting to your local IRB or CDC IRB. Examples include, but are not limited to: enrollment of ineligible persons; failure to assess all required inclusion and exclusion criteria; failure to obtain informed consent before after the initiation of study procedures; participant given the wrong treatment or incorrect dose;

participant met withdrawal criteria during the study but was not withdrawn; and execution of unnecessary, invasive study procedures.

In the table below, describe the process for identifying and reporting important protocol deviations.

Consult with your local IRB to determine the specific type of reportable events.

If your site relies on CDC IRB, and do not have a local IRB, please request the list of reportable events from

TBTCStudy37@cdc.gov.

Type of events reportable to your local IRB

Identification activities

Reporting activities Goal (in days) for reporting

c. Internal monitoring

Describe activities related to monitoring of the topics included in the table below

QA Topic What data or information will be used for monitoring?

How often will monitoring be done?

If problems are found, what corrective actions will be taken?

Timeliness of data submission

Timeliness of query resolution

Timeliness of adverse event reports

Completeness of adverse event reports

Important protocol deviations

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Approved

Site Principal Investigator: _______________________________________________________

Signature: ___________________________________________________ Date: ____________

Quality Program Coordinator: _____________________________________________________

Signature: ___________________________________________________ Date: ___________

Acknowledged

Enter site staff role: _______________________________________________________

Signature: ___________________________________________________ Date: ____________

Enter site staff role: _____________________________________________________

Enter site staff role: _____________________________________________________

TBTC Study 37/TBESC Part D Regulatory Compliance & Quality Management Plan – Version October 31, 2018

Glossary

Site Evaluation Report Form (SERF) = the quality assurance review form used to document participation in and compliance with TBTC/TBESC formal quality assurance reviews

Verification = the process by which site staff ensure that data at one step in the site’s data flow exactly match the data from the previous step (e.g. to verify paper CRFs completed from source documents, site staff would compare the paper CRFs to the source). Best practice is for different staff members to abstract/report and verify data, however, at small sites with limited staff, one person can be responsible for data abstraction/reporting and data verification.

Valid data = data reported to TBTC/TBESC via the TBTC2 study management system that match data on source documents exactly

Validation = the process by which site staff ensure that the data reported in TBTC2 are correct and match data on source documents, regardless of whether the site completes paper CRFs from source documents. Best practice is for different staff members to report and validate data, however, at small sites with limited staff, one person can be responsible for both data reporting and validation.