Att 1 SOW.pdf

Audit Support for NIDDK Office of Clinical Research Support (OCRS) Statement of Work

Audit Support for NIDDK OCRS

As of: 8/23/2021

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. SCOPE

The Contractor shall provide specialized support for the NIDDK Office of Clinical Research Support (OCRS) to assist in all aspects of activities related to the sponsor’s assessment of compliance with study protocol and procedures, Food and Drug Administration (FDA) regulations, Good Clinical Practice (GCP) guidelines, and other applicable laws or regulations at awardee institutions or subaward/subcontract locations of an extramurally funded multi-center consortium. Develop a strategy that clearly defines the scope of the independent assessment, a plan and timeline to conduct on-site and remote audits, document and formally report findings to NIDDK, and provide a final report that summarizes findings within and across participating institutions and includes suggestions for improvements, recommendations for follow-through, or corrective actions. On-site and remote audits must evaluate compliance with FDA regulations and GCP guidelines in general and specific to 21 CRF 312, with focus on 21 CRF 312.61 Control of Investigational Drug, and other applicable regulations or laws. It will be necessary to collect and review relevant background information, study documents, and other information as necessary to gain sufficient familiarity with the study protocol, implementation, monitoring and oversight structure to then develop a strategy to evaluate compliance across designated awardee institutions. Additionally, expert consulting services or activities related to the review and evaluation of any subaward/subcontract institutions or facilities (e.g. drug distribution center) may be included. This may involve reviewing practices and procedures related to study drug distribution to clinical centers and study participants, record keeping, delegation of responsibilities, clinical center monitoring, independent oversight of protocol conduct and participant safety, and data integrity. The strategy should allow for a phased, stepwise, or tiered approach that will allow ongoing assessment activities to be informed by earlier findings, providing a flexible and adaptive plan. For example, the strategy may propose on-site audits at a select subset of the clinical centers and then a decision process supported by early findings to determine whether additional on-site or remote audits should be performed, further auditing delegated to individual institutions (e.g. IRB), or a strategy that includes a combination of remote and on-site auditing procedures to target different aspects of compliance.

The independent assessment must address the following, at a minimum:

1) Determine whether current and relevant past versions of study protocols and procedures are/were aligned with GCP, regulations, and laws for a study operating under an FDA Investigational New Drug (IND).

2) Determine whether clinical center practices are/were in compliance with the study protocol/procedures, GCP, regulations, and laws for a study operating under an FDA IND including but not limited to:

a. Clinical center investigator engagement in the study; investigator responsibilities performed or delegated with appropriate oversight

b. Clinical center IRB review, monitoring, and oversight of protocol and procedures

c. Manner in which study-provided drug was distributed to clinical centers, stored locally, dispensed to/returned from study participants, and final disposition

d. Retention of essential documents per GCP International Council for Harmonisation (ICH) E6, Section 8: Essential Documents

3) Determine whether there were any potential or actual participant safety concerns related to managing study drug, from central drug distribution processes through to dispensation to participants and return/final disposition of study drug

4) Evaluate impact of findings from items 1-3 on scientific integrity of study.

2. BACKGROUND

The consortium initially conducted a multi-center randomized clinical trial with a Coordinating Center and 20-some clinical centers and then transitioned to a long-term follow-up protocol. During the follow-up period, drug treatments were unmasked, the placebo was discontinued, and study-provided drug was continued in those initially randomized to it. All participants have been followed for long-term health outcomes and have two visits each year. Study-provided drug was distributed to participants in that treatment arm at these visits. The initial clinical trial operated under an FDA IND. The IND was withdrawn during the follow-up period, and then a new IND put in place later during that period when the study drug supplier was changed to a supplier that had not been inspected by the FDA. Study leadership with concurrence from the Data and Safety Monitoring Board (DSMB) subsequently discontinued study-provided drug therapy.

In mid-2020, the NIDDK learned that an IRB at one of the clinical centers had identified a potential issue of noncompliance and later in 2020 that IRB made a final determination that the issue was considered to be non-compliant with Federal regulations and GCP guidelines. Following this determination, NIDDK leadership and OCRS personnel consulted with relevant NIH offices and then decided that an independent ‘for cause’ assessment to address both funder and sponsor responsibilities should be conducted.

3. TECHNICAL REQUIREMENTS

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below. Specifically, the Contractor shall:

Base POP: 6 months (To be proposed on a time and material basis based on offerors best estimates)

1) Identify, gather, and review necessary background information, study documents, and information on finding of noncompliance. NIDDK OCRS personnel will assist with this activity and it may be an iterative process.

2) Coordinate routine meetings/calls with NIDDK OCRS personnel (or others as requested by NIDDK OCRS) to discuss activities, review status and progress, and adapt strategy, plan, timeline, etc. as necessary to complete independent assessment or as specified by NIDDK OCRS personnel.

3) Develop a strategy to assist with or perform all aspects of activities related to sponsor’s assessment of compliance with study protocol and procedures, FDA regulations, GCP guidelines, and other applicable laws or regulations as specified under Scope. Strategy to be reviewed and approved by NIDDK OCRS personnel prior to finalizing.

4) In collaboration with the NIDDK OCRS, the Contractor will develop audit criteria to assess clinical center, Coordinating Center, or other participating institutions compliance with GCP, FDA regulations, and other laws and regulations as appropriate

a. Audits will be conducted according to the Contractor’s Standard Operating Procedures (SOPs) following NIDDK OCRS review and approval unless the NIDDK OCRS decide to use an alternate Standard Operating Procedure.

b. Provide written assessment of clinical center compliance per audit criteria. The written report will include any findings as well as suggestions for corrections, improvements, or further reporting to oversight entities.

c. If NIDDK OCRS deems it necessary, the Contractor will be asked to repeat a clinical center audit or perform a follow-up audit. The Contractor will confirm if any non-compliance issues have been resolved and/or appropriate measures outlined in a Corrective Action and Preventive Action (CAPA) plan have been taken to correct issues identified during initial or any subsequent audits.

d. Contractor will be required to generate an audit report for every audit performed

5) Provide procedural and reporting documents that will be utilized including, but not limited to, SOPs, remote and on-site audit templates, preliminary and final report templates, subject to approval from NIDDK OCRS personnel.

6) Provide an audit plan and report template for NIDDK OCRS review before each specific clinical center or other institution audit. Based on NIDDK OCRS feedback, the Contractor will generate a final pre-audit plan and audit template.

7) Perform on-site and/or remote audits at clinical centers or other awardee or sub-award/sub-contract locations, subject to approval from NIDDK OCRS personnel.

Optional task 1: 6 months (To be proposed on and evaluated after initial award and prior to the completion of task 7)

1) Additional audits or assessments, develop materials to be used by NIDDK projects (e.g. SOPs, guidance documents, training tools, audit/report templates, etc.).

Qualifications and Other Requirements:

Contractor must provide consultants/workers who have documented experience in reviewing policy, procedures, and practices along with documents and records to determine compliance with federal regulations, GCP, laws and regulations applicable to the conduct of NIH extramurally funded clinical research studies that utilize pharmaceutical products under an FDA IND (e.g. FDA regulations, GCP guidelines in general and specific to 21 CRF 312, with focus on 21 CRF 312.61 Control of Investigational Drug; GCP ICH E6, Section 8: Essential Documents). Contractor must also be familiar with NIH funder and sponsor responsibilities related to conduct of same.

Non-Disclosure Agreements:

The NIH will be responsible for contacting awardee institutions or sub-awardee/subcontract institutions to discuss the audit and coordinate any non-disclosure agreements between the government and the

CMO/CRO.

Travel and Training Requirements (in addition to NIH specific training for all contract employees):

Travel expenses for CMO/CRO on-site visits.

Deliverables and Reporting Requirements:

Deliverable Due Date (calendar days unless specified otherwise)

Draft of proposed strategy for independent assessment, to include:

- planning period to become familiar with study protocol, procedures, and obtain relevant history and background information

- on-site and remote audit plan

- report findings, individual audits and cumulative final report

- suggestions for improvements or recommendations for corrective actions, follow-through activities, to include reporting findings (e.g.

protocol deviations, noncompliance) to other entities (i.e. IRB, DSMB, OHRP, FDA)

4 weeks from authorization to proceed (contract award date)

Final strategy for independent assessment 1 week following NIDDK approval of draft strategy

Draft SOPs, audit templates, report templates, etc. related to activities to be performed

1 week following NIDDK approval of final strategy

Final SOPs, audit templates, report templates, etc. related to activities to be performed

1 week following NIDDK approval of draft documents

Pre-audit agenda and audit report template (prior to first on-site audit) 3 weeks prior to audit visit

Summary of audit (on-site or remote) findings via email Within 48 hours of audit

Audit report (on-site or remote), draft Within 7 days of audit

Audit report (on-site or remote), final Within 3 days of NIDDK approval of draft report

Routine or ad hoc reports as requested by NIDDK OCRS As specified in SOW or to be discussed with the NIDDK as needed

Draft of final summary report, including summary of assessment findings within and across institutions, with suggestions for improvements, recommendations, corrective actions, follow-through activities (e.g.

Within 7 days of completion of last audit, Deliverable Due Date (calendar days unless specified otherwise) reporting findings to IRB, DSMB, OHRP, etc.), and guidance to NIDDK OCRS and leadership as determined by NIDDK

Final summary report (same specifics as draft summary report) Within 3 days of NIDDK approval of draft report

Monthly progress report Within the first 10 days of each month

Final progress report

A draft of the Final Report shall be submitted 15 days prior to the completion of the contract. The Final Report shall be submitted 5 days prior to the completion of the contract.

Agendas and minutes for in-person or virtual meetings with NIDDK OCRS or others

Agenda to be provided at least 24 hours prior to meeting; draft minutes to be provided to NIDDK two business days after meeting and distributed within 1 business day after approval by NIDDK

Roster of employees requiring suitability investigation 14 days of the effective date of contract award date

Reporting of new and departing employees Within 5 days of staffing change

Contractor employee non-disclosure agreement(s) 5 days following contract award date

Loss and/or disclosure of Personally Identifiable Information (PII);

notification of data breach Notification shall be made via email to IRT@nih.gov

Within one hour of discovering the incident. Contractor shall follow up with IRT within 3 days of incident discovery

Additional audits or assessments, develop materials to be used by NIDDK projects (e.g. SOPs, guidance documents, training tools, audit/report templates, etc.), only if option period is exercised

As specified in SOW or to be discussed with the NIDDK as needed

* NIDDK = NIDDK OCRS for Deliverables and Reporting mailto:IRT@nih.gov

Audit Support for NIDDK Office of Clinical Research Support (OCRS) Statement of Work