Draft Task Requirements - FAERS Data Management Program Support Services.pdf

Request for Information FAERS Data Management Program Support Services

Draft Task Requirements

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1.0 Background

The FDA’s Center for Drug Evaluation and Research (CDER) and the FDA’s Center for Biologics Evaluation and Research (CBER) perform a crucial part of FDA's mission, specifically review and analysis of pre-market and post-market safety and efficacy assessments of human drugs and biologics. In this context, CDER and CBER perform safety surveillance, to include the recording of mandatory and voluntary submission of adverse event reports, product problem and medication error reports by the FDA’s Adverse Event Reporting System

(FAERS).

Mandatory adverse reports are submitted electronically by manufactures to the FDA. The mandatory reports are either expedited (i.e., submitted within 15 days after the manufacturer became aware of the adverse event for their product) or non-expedited (i.e., submitted within 90 days after the manufacturer became aware of the adverse event for their product). These reports are XML files that follow the International Council of Harmonization (ICH) E2B (R2) format and are submitted to the FDA’s Electronic Submission Gateway (ESG) also referred in this document as eSubs. Since these reports are electronic in nature, they typically get processed by FAERS without any human intervention. Of the 2.2 million reports submitted by the manufacturer only about 2% of these reports stops for human intervention due to issues with the name of the product or the manufacturer.

Adverse event reports submitted by consumers and healthcare professionals are sent directly to the FDA and are voluntary in nature. Approximately 100,000 reports per year are voluntary adverse event reports and have to be triaged and routed to appropriate Centers within FDA. Of the 100,000 voluntary adverse event reports, 70% are processed via the FAERS system and made available for the reviewers. These voluntary reports come using the MedWatch form and some variation of the MedWatch form. The MedWatch form itself has two variations: i) MedWatch Form 3500 (https://www.fda.gov/media/76299/download) for healthcare professional; and ii) MedWatch Form 3500B (https://www.fda.gov/media/85598/download) for consumers. The form may be sent in by US postal mail, to a special electronic fax line or an electronic version can be filled out using the MedWatch Online website (Https://www.accessdata.fda.gov/scripts/medwatch/index.cfm).

Additionally, there are reports processed into FAERS that are received by CDER’s Office of Pharmaceutical Quality (OPQ) that are related to product quality defects. These reports include MedWatch Product Complaints, Consumer Complaints, Field Alert Reports (FARs) and Biologic Product Deviation Reports (BPDRs) of the post-marketing safety surveillance data for all regulated human medical products including drugs and combination products (drug/biologic, drug/device). The Field Alert Reports (FARs) Form 3331a (https://www.fda.gov/media/85567/download) are mandatory reports submitted by the manufacturer that are used to quickly identify quality defects in distributed drug products that may present a potential safety threat. More than 9,000 FARs per year are submitted to FDA, approximately 95% are submitted in XML format and uploaded directly into the FAERS system similar to post-market eSubs and the remaining 5% come as pdf documents. The Biological Product Deviation Reports (BPDRs) Form 3486 (https://www.fda.gov/media/70604/download) are mandatory reports that are submitted by manufacturers of human cells, tissues and cellular and tissue-based product (HCT/Ps) to report biological product deviations (BPD) to FDA that may affect the safety, purity, or potency of a distributed products.

https://www.fda.gov/media/76299/download https://www.fda.gov/media/85598/download https://www.accessdata.fda.gov/scripts/medwatch/index.cfm https://www.fda.gov/media/85567/download https://www.fda.gov/media/70604/download

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Approximately 300 BPDRs are received per year in both PDF and XML format. The Product Complaint reports are submitted by consumers or healthcare professional using the MedWatch Form 3500 and 3500B and are voluntary reports. As stated above the Product Complaint reports contains complaints about the quality of an FDA regulated product that require review and analysis by FDA Consumer Safety Officers (CSOs).

A Broad Overview of Data Entry

The processing of the adverse event reports is a crucial part of the safety surveillance mission critical program. Below is the high-level view (Figure 1) of the data entry process that enables the reports to pass through multiple activities and finally are made available to the safety reviewers to review and analyze them.

Figure 1: Case processing of Adverse Event Reports

Reports are be received by U.S. Postal Mail, special designated fax lines, dedicated websites or through an FDA electronic gateway which can receive electronic messages in the E2B R2 format from manufacturers.

Postal mail, fax, and MedWatch Online website reports come from consumers and health care providers.

The postal mail reports are picked up by a courier and sent to the Central Triage Unit (CTU) to be scanned and registered into First Look At Reports (FLARe). FLARe is a computer system that support the registration, triaging and disposition of all voluntary reports. Reports received via fax and MedWatch Online are automatically registered into FLARe. Approximately ten fields with basic information are entered into FLARe from the mailed and the fax reports. The reports from MedWatch Online are electronic and no data entry is required. Reports then go to the Triage processing step where each report is reviewed by a pharmacist to make sure it has the four necessary elements of a valid report. Reports that are not valid are logically deleted and no additional data entry is performed. Reports are also reviewed to ensure that the products they describe are regulated by CDER and CBER. FDA products that are regulated by other Centers are routed to them and no further data entry is required. After the reports are triaged and marked as CDER or CBER reports based on the products, they are dispositioned by FLARe as an electronic XML file to the case processing software tool called LifeSphere MultiVigilance (LSMV) which is part of the FAERS system.

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Reports that are sent to FAERS undergo the Data Entry activity step where approximately 50 different fields are entered into the FAERS system. After data entry these reports are sent to undergo Product and Manufacturer Coding. The Product and Manufacturer Coding activity step ensures that the drug product names, and the names of any manufacturer and/or firm are validated using the FAERS Product and Manufacturer dictionary systems. At this point the eSubs sent by the manufacturers may also enter the system if their drug name or manufacturer name is not automatically matching in our dictionaries.

Specialists in these area’s ensure that all reports have validated drug and manufacturers names associated with each report. The reports are then routed to the MedDRA Coding activity step. All reports have a “narrative” (section B5 of the MedWatch Form 3500) free form text box that asks the reporter to “Describe the Event or Problem”. The narrative is read by the MedDRA coder and the appropriate adverse event term, medication error term or defect terms in case of product quality reports is coded into the report in FAERS using the MedDRA dictionary. This “MedDRA coding step” is done by highly trained specialist who normally have backgrounds as doctor, nurse, pharmacist, dentist, or other licensed health care providers. These defined terms are from an international standard called MedDRA. MedDRA stands for Medical Dictionary for Regulatory Activities (https://www.meddra.org) used to code adverse events/medication error/defect terms. After the completion of MedDRA Coding the reports are now ready for evaluation. At this point the report has all data values available entered and each report is coded to FDA dictionaries on drug product name, manufacturer/firm, and a controlled vocabulary for adverse events/medication error/defect terms using MedDRA. Reports that have undergone all data entry activity step can now be efficiently searched by FDA safety reviewers for analysis, identify issues and trends which may result in regulatory actions.

The above process and activity steps are also applicable for processing product quality reports. Activities specific to product quality reports are described in more detail in Section 4.1.6 below.

2.0 Objectives

The primary objectives of this requirement are data management services in support of the CDER Adverse Event Reporting System Data Management Program (CDER-DMP) include:

• Performing case processing of mandatory and voluntary adverse event reports submitted to the FDA via the FLARe and FAERS systems.

• Performing data entry services of drug quality reports submitted to the FDA via the FAERS system.

• Maintain quality assurance programs for data entry process and manage coding services.

• Support changes in the data entry process that will lead to greater program efficiency. For example, this may include updates to processes and software that maintain the accuracy of the data entry process.

3.0 Project Scope:

The Government requires data management support services that include:

• Receiving data in a variety of physical and electronic formats.

• Data entry services, data analysis, tracking services, and stakeholder/user support.

• Sorting and routing this data to the correct work area or correct FDA Center that regulates the product described.

• Scanning physical documents into electronic formats, reviewing electronic submissions and making necessary corrections.

https://www.meddra.org/

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• Entering, registering and processing data into FDA computer system.

• Medical coding of reports using various taxonomies (E. g., MedDRA)

• Performing Quality Assurance and Quality Control on data.

• Participating in the testing and validation of new software systems used to support new and more efficient data entry systems.

4.0 Specific Task Areas

The Government requires a comprehensive solution to satisfying the stated objectives which provide all required services, qualified personnel, material, equipment, tools and methodologies, not otherwise provided and subject to approval by the FDA, to perform the following tasks:

4.1. Task Area 1: Case Processing Management

The contractor shall provide FAERS data entry support services for reports commonly known as Individual Case Safety Reports (ICSRs) to include tasks such as: scanning, triaging, registering (logging), tracking, data entry, coding of manufacturer and product(s), MedDRA coding, updating of data records, reviewing, editing, filing, quality control, and quality assurance.

Each ICSR shall be legible, and shall contain at least one identifiable suspect product, an identifiable reporter, identifiable patient, and a minimum of one identifiable event converted by the contractor to a MedDRA term to be entered into FAERS.

4.1.1. Report Registration

The contractor shall perform the Registration step, which includes scanning the reports received via mail and sending it to the FLARe system. The FLARe system generates a unique receipt number for each report and automatically attaches the scanned report to the unique receipt number as the source document. The user here enters approximately 10 data fields in the FLARe system from the source document. Once the Registration activity is complete the report is sent to the Triage activity within the Central Triage Unit (CTU).

4.1.2. Central Triage Unit (CTU)

The contractor shall establish and operate a CTU that performs two primary functions: (1) Triage and subsequently routes voluntary reports to the appropriate Center(s) and (2) sends Acknowledgement letters.

The contractor shall perform the following activities:

• Track all voluntary reports received from doctors, consumers, medical personnel, caregivers and attorneys in FLARe. It should be noted that manufacturer reports are not tracked in FLARe.

• Screen reports to distinguish route of receipt (USPS, Internet, Fax)

• Assign a unique CTU identification to each voluntary report received

• Route all triaged reports to the appropriate responsible Center(s), and shall also route misdirected reports to the appropriate recipient

• Generate acknowledgements for all voluntary reports.

• Prepare mail labels and mail the paper acknowledgement letter within one week of receipt of a voluntary report.

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• Generate metrics reports already available in FLARe for workload management.

An FDA on-site Representative will monitor all Report Registration and CTU activities as described above. Once the tasks in the CTU activity are completed, the report along with any source document is dispositioned to the LSMV tool for Case Data Entry which now generates a Case ID in LSMV.

4.1.3. Case Data Entry of Individual Case Safety Reports (ICSRs)

The contractor shall provide Data Entry Specialists who shall process all voluntary reports. It should be noted that reports are also referred to as cases in FAERS. The contractor shall perform the activities as follows:

• Enter the verbatim data for the voluntary case in LSMV tool by looking at the source document.

• Complete Data Entry of reports containing high priority drugs as specified by the FDA within 24 hours after receipt.

• Route the report to the Product/Manufacturer Coding activity after Data Entry is complete.

Note that during case data entry in LSMV data checks are performed via business rules already programmed in the tool.

4.1.4. Product/Manufacturer Coding and Dictionary Maintenance

The contractor shall ensure that the Product/Manufacturer coders resolve discrepancies between the data entered in the FAERS database and information submitted on the actual report form. The coders shall also validate the report data for each primary and secondary suspect drug product.

The contractor shall perform the Product/Manufacturer Coding activity as follows:

• Review the product name(s) and/or National Drug Code (NDC) in the report that does not auto-code to the product dictionary and choose the appropriate name from the product dictionary to code the product name(s).

• Review the manufacturer name and/or Firm Establishment Identifier (FEI) in the report that do not auto-code to the manufacturer dictionary and choose the appropriate name from the manufacturer dictionary to code the manufacturer/firm name.

• Support FDA with updates and corrections to the FAERS product dictionary. This is a specialized task where the contractor works closely with FDA dictionary specialists who maintains the Product/Manufacturer dictionary.

o The contractor shall be responsible for researching and including new drug names into the product dictionary and correcting and updating entries.

o The contractor’s staff assigned to support dictionary maintenance shall report to the FDA’s product dictionary group and help with researching and updating manufacturer dictionary entries

• Route the report to MedDRA Coding once all product name(s) and the manufacturer name is coded.

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4.1.5. MedDRA Coding

The contractor shall perform the MedDRA Coding activity as follows:

• Code MedDRA lowest level terms (LLTs) and MedDRA version discrepancies, which includes:

o Reading the narrative section of the report to identify the reported adverse event o Searching MedDRA for an appropriate term that corresponds to the identified reported term in the report or key in the identified reported term directly into the appropriate data field o Verify that all adverse events/medication errors/product defects are coded to a term in the MedDRA dictionary according to the coding guidelines before transferring the report to the FDA Safety Evaluators o Seeking assistance from the FDA MedDRA Dictionary team when unable to identify and/or code a reported verbatim term

• Utilize MedDRA in the FAERS database to capture and code reported adverse events, indications, medication errors and product defects.

• Route the MedDRA coded report to the final status “Evaluation Ready”. This allows the report to be available to the Safety Reviewer.

4.1.6. Processing of Drug Quality Reports

The Drug Quality Reports include FARs, BPDRs, and Product Complaint reports received by FDA are processed into FAERS following a similar process flow from Registration to Data Entry to Product/Manufacturer Coding to MedDRA Coding as described above. These reports also require a few additional process activities as follows:

• Send Information Requests (IRs) to MedWatch Consumer Complaint reporters to collect specific product details that are sometimes missing on the report (e.g., NDC number, Lot number, etc.)

• Route the MedDRA coded report to the CSO Review activity to be reviewed by the Consumer Safety Officer (CSO) instead of the final status “Evaluation Ready” as done for adverse event and/or medication error reports.

4.1.7. Systems & Management Support

During the life of the contract, FAERS and other software currently used may be enhances or replaced and the contractor will be expected to be an active partner during these transitions. The contractor shall support the implementation of new software by development of business rules, perform User Acceptance Testing (UAT), train their staff on existing, new, and updated software, create new SOPs, and update current SOPs. In selected cases they may help FDA with business analysis and testing in areas like Optical Character Recognition (OCR) or data analysis.

4.1.8. Develop and Update Standard Operating Procedures (SOPs)

The contractor shall develop and update existing FAERS SOPs in coordination with the FDA by performing the following:

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• Update, review, and post SOPs as needed according to FDA enterprise records management policies

• Maintain a change history of all SOPs related to this contract and assure that only current SOPs are posted on the FDA provided intranet

• Ensure that appropriate FDA personnel review and approve all SOPs prior to issuance

• Perform SOP revisions within 21 days from notification by COR

• Ensure that up-to-date SOPs are available electronically to all contractor personnel and

FDA/CDER internal users

• Ensure that all hyperlinks used within SOPs are maintained

• Review SOPs on an annual basis and provide COR with a summary of changes needed.

The FDA COR and FDA on-site Representatives shall review and approve all new and updated SOPs.

4.1.9. Document Delivery (Local Courier Services)

The contractor shall provide local courier services to deliver US Postal Mail, CDER reports that were sent in error to other centers, non-CDER reports that were sent in error, and physical media from companies as follows:

• The contractor shall provide a local courier service with up to two (2) routings per day, as needed, and oversight of these services.

• Provide courier service to multiple FDA facilities each weekday, as tasked. The Contractor shall have the capability to provide expedited delivery services of FDA materials within the specified timeframes.

• Possess the capability to deliver records materials after hours. After hours are after normal business hours Monday through Friday, weekends, and holidays. The contractor is responsible for providing back- up couriers/drivers services.

• Be responsible for providing courier services and distributing mail and stored files between off-site and on-site locations.

• The contractor shall have the capability to provide local courier services in accordance with the government’s local courier route.

4.2. Task Area 2: Program and Project Management

4.2.1. Program and Project Management

The contractor shall provide program and project management services. The contractor shall manage cost, schedule, and quality. The project manager shall be available (on-site or cell phone) 24 hours/7 days/week to address FDA operational shutdowns or emergency situations. The contractor shall provide all management services required to plan, staff, coordinate, schedule, manage, communicate, report, and steward all tasks, activities, and deliverables for the contract throughout the period of performance.

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4.2.2. FDA Mandated Contractor Training

The contractor shall complete all required contractor employee training, to include FDA-mandated contractor training courses, for example: FDA Records Management Training, Computer Security Awareness Training, IT Security Recertification, and Emergency Preparedness Training and other newly mandated training as required by FDA.

4.2.3. Data Entry Quality Assurance Program

The contractor shall provide a Data Entry Quality Assurance Program for data entry contractor personnel as follows:

• Gather data entry errors by running FAERS reports, and front-end queries designed for this purpose

• Collect feedback from the FDA on data quality issues and correct them

• Collect feedback from the FDA Quarterly Data Extract quality control group that publishes FAERS data to the public

• Document in a Data Entry Quality Report:

o The data entry errors collected o Any correlation among the errors o Any trends among the errors o Corrective and preventive action taken to address the data entry or coding errors

• Deliver the Data Entry Quality Report to the COR at the monthly meetings

• Host short weekly meetings with the staff to go over trends in data entry errors to assist with improving the accuracy of data entry

• Ensure that all new data entry personnel are initially trained and certified by the contractor on a pre-production system before starting to process reports on the production system

4.2.4. MedDRA Coding Quality Assurance Program

The contractor shall work with COR/PM and the FDA MedDRA Dictionary team to identify updates and changes in the MedDRA coding standard. The FDA MedDRA Dictionary team may inform the Contractor periodically on updates to the MedDRA coding standard that shall be acknowledged, train their staff and update the SOPs .

All new MedDRA coders shall be first trained and certified by the Contractor on a pre-production system before working on a production system.

The COR and/or the FDA MedDRA Dictionary team will report to the contractor, in writing, any issues noted with MedDRA coding. The contractor shall develop and implement a plan, to address any issues.

4.2.5. Contractor Meeting Requirements

The contractor shall participate in meetings in a variety of roles, such as government-led discussions, participation in discussions, contributing questions and answers, raising issues, risks and concerns, developing and giving presentations, and other active oral and written communications.

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4.2.6. Meeting Agenda

The contractor shall prepare meeting agendas which include any meeting notes, issues, risks and action items prior to the meeting and submit them to the COR/PM.

4.2.7. Meeting Notes

The contractor shall take formal meeting notes at all meetings below. After the meeting, the contractor shall publish meeting notes, detailing the discussion, and listing any risks, actions, and/or issues identified during the meeting. Each risk, action, and issue shall have an owner and a target date for decision, resolution or mitigation strategy. The meeting notes shall also identify any decisions that need to be made as a result of the meeting and who has to make the decision.

4.2.8. Ad-Hoc Meetings

The contractor may be required to participate in Ad-hoc meetings, as needed, to discuss and resolve business technical issues.

4.2.9. Weekly Summary Report of Case Processing Activities

The contractor shall run a Weekly Summary Report of Case Processing Activities as defined by the COR/PM. The reports are run in the FLARe and LSMV systems and contain a collection of detailed metrics and counts outlining the reports received, those that are in-process, and those that were completed per week. The report shows the different report types and includes the days it took to process each type.

These metrics are used by the contractor and FDA for monitoring staff productivity, planning, resource allocation, continuous process/quality improvement, and contractor performance against contract objectives. These metrics contain historical counts in order to help predict monthly and yearly reporting trends.

4.2.10. Monthly Status and Review Meetings

The contractor shall participate in monthly status and review meetings to go over the invoice, budget and quality metrics.

4.2.11. Program Review Meetings

The contractor shall host a formal program review meeting every six months at the FDA White Oak facility in Silver Spring, MD, to brief key stakeholders and FDA leadership of accomplishments and trends.

Contractors who would need to travel can attend virtually.

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4.3. Task Area 3: Training

The contractor shall conduct ongoing comprehensive training for all newly hired and existing contractor employees to ensure all employees are qualified to perform their assigned duties.

4.3.1. Training Program

The contractor shall develop employee proficiency standards as part of a comprehensive training program. The training program for data entry, quality control and MedDRA coder personnel is subject to approval by the COR or COR Representative.

4.3.2. Conduct of Training

The contractor shall use the SOPs and more in-depth User Training Guides to assist new employees in understanding individual field level job activities. The contractor shall conduct training in a pre-production environment.

4.3.3. Evaluation of Competency

The contractor shall develop methods to monitor and evaluate competency of data-entry, scanning, quality control, and MedDRA coder personnel. The contractor shall examine pre-production records to assess personnel proficiency levels. Personnel shall demonstrate appropriate proficiency as a pre-requisite to work on production data.

4.3.4. Evaluation of Competency for Subject Matter Expert (Medical) II, III and IV (MedDRA Coders)

The contractor shall develop a qualification for new or existing contractor employees to document the progress of MedDRA coding and provide the qualification results to the COR/PM. The contractor shall double check all MedDRA coding performed during the training period. A MedDRA coder shall be considered qualified only if, in addition to the training requirements for all employees, the employee:

• Passes a written test developed by the contractor and approved by the FDA COR/PM based on the training performed.

• Performs accurately on a simulation test of actual coding

4.3.5. Training Progress Reporting

The contractor shall provide overall contractor employee test results to the COR/PM.

4.3.6. Post Training Data Entry

Only contractor employees who have completed the required training for data entry shall be allowed to enter data in the production system.

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4.3.7. On-going Maintenance of Competency

The contractor shall perform on-going assessments of competency for data entry, quality control, and MedDRA Coding personnel. The contractor shall conduct proficiency maintenance training based on:

• Data entry errors derived from FAERS reports and front-end queries

• Feedback from the FDA FAERS data quality workgroup

• Feedback from the FDA Quarterly Data Extract quality control group

The contractor’s monitoring of scanning personnel shall include:

• Accuracy of received reports as viewed in the database

• Completeness of received reports as viewed in the database

• Accessibility of received reports in the database

4.4. Task Area 4: Support of Updated Software for Greater Program Efficiencies

The contractor shall be involved in requirements gathering, and User Acceptance Testing (UAT). In the event there are changes to any software and processes , the SOPs shall be updated.

The contractor shall support the FDA’s new Enterprise CDER-wide Optical Character Recognition (OCR) systems. Support in this area shall include creating and analyzing test data sets. This shall include assisting with the development of business rules for the new OCR software and new tasks with system maintenance when this system goes into production.

5.0 Deliverable Schedule

The contractor shall submit the following deliverables to the COR as follows:

Item Deliverable Frequency/Delivery Due Date 1 Meeting Agenda

(Pre-Production, Ad hoc, Weekly, Monthly, and

Within Two (2) Business Days After Written Notice of the Meeting by the COR/PM

2 Meeting Minutes (Pre-Production, Ad hoc, Weekly, Monthly, and P R i )

Within Two (2) Business Days After the Meeting

3 FAERS Reports for Six Month Program Review.

Every Six Months

4 Certification of MedDRA Coding Competency Before any new MedDRA coder can do production work. Note: Used for each new MedDRA Coder

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5 Weekly Summary Report of Case Processing Activities (These are metrics and counts outlining the reports processed per week by different report types, including the days it took to process them)

Weekly

6.0 Place of Performance

The contractor shall perform all services at these locations as follows:

• Scanning and Courier Route Services (Onsite) - The contractor shall perform all scanning and courier services on-site at the FDA White Oak Facility in Silver Spring, MD. The on-site rates are subject to the applicable labor category positions under the U. S. Department of Labor Wage Determination in Montgomery County, MD and Frederick County, MD.

• All Other Services (Remotely) - The contractor shall allow for all other services to be performed remotely by the contractor employees. The contractor shall maintain a remote work agreement for all contractor employees.

This contract does not permit for off-site rates at the contractor’s primary place of business location.

Travel expenses are not authorized under this contract.

7.0 DMP Labor Categories

Below is a historical table of labor categories typically used for such a program:

Labor Category Est. No. of Contractor Personnel

Project Manager III 1

Data Processing Specialist III 9

Data Processing Specialist II 4

Analyst Coder II 10

Analyst Coder I 2

Subject Matter Expert IV 9

Subject Matter Expert III 3

Subject Matter Expert II 1

Technology Consultant 1

Pharmacist 3