In Operaon Since 1984—58 Approved Products—Zero 483s Clinical Operaons and Monitoring Trial Rescue Risk Based Monitoring Paent Reported Outcomes (ePRO) Clinical Call Center-Screening, Recruitment and Safety Data Management and EDC IWRS—Fully integrated into EDC Plaorm Trial Masterfile (eTMF) CTMS Management Medical Monitoring / Safety Management Grants , Contracts and Site Payment Quality Assurance Regulatory Compliance Global Strategic Sourcing Medical Wring Biostascs Pharmacovigilance NCGS Inc., 288 Meeng Street, Suite 400, Charleston, SC 29401 (843) 722-8330 www.ncgs.com An internaonal, full-service CRO that specializes in conducng and managing clinical trials.
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In Operation Since 1984—58 Approved Products—Zero 483s
Clinical Operations and Monitoring
Trial Rescue
Risk Based Monitoring
Patient Reported Outcomes (ePRO)
Clinical Call Center-Screening, Recruitment and Safety
Data Management and EDC
IWRS—Fully integrated into EDC Platform
Trial Masterfile (eTMF)
CTMS Management
Medical Monitoring / Safety Management
Grants , Contracts and Site Payment
Quality Assurance
Regulatory Compliance
Global Strategic Sourcing
Medical Writing
Biostatistics
Pharmacovigilance
NCGS Inc., 288 Meeting Street, Suite 400, Charleston, SC 29401
(843) 722-8330 www.ncgs.com
An international, full-service CRO that specializes
in conducting and managing clinical trials.
NCGS, Incorporated is an international full-service CRO, providing clinical development support to Pharmaceutical, Biotechnology, Medical Device and Diagnostic companies. NCGS’ business model is discernibly different than industry standard: Utilizing highly tenured staff, NCGS consistently delivers studies on time, within budget and of the highest quality. NCGS is a WBENC certified Diversity Supplier, has been in operation for over 30 years and supported the approvals or expanded labeling of 58 products with zero 483s.
NCGS understands that the CRO-Sponsor relationship is one of shared vision, complementary expertise and trust. NCGS’ team understands the demands of the life science industries, seeking ways to make each clinical effort more quality based, thorough, timely and cost-effective.
NCGS’ mission is to protect research subjects, capture quality data and maintain the integrity of science with the same passion one would protect their own domain. Each staff member is charged to function under the mantra, “This product could easily be used on your parent, sibling, or yourself.” “It is not only our hope for this product, it is the world’s hope for this product.”
NCGS’ Quality Performance and Discernible Difference:
In operation since 1984
58 approved products
Zero FDA 483s
CRA Average Experience - greater than 10 years
Turnover Rate- 3%
Diversity Supplier- Women Business Enterprise National Certification
Several former clients are currently NCGS staff
Service Offerings
Clinical Operations and Clinical Monitoring
Trial Rescue
Clinical Call Center– Screening, Recruitment and Safety
Data Management, EDC
IWRS—Fully integrated to EDC Platform (eliminating duplicate license fees)
eTMF and CTMS Management
Medical Monitoring and Safety Management
Grants, Contacts, Site and Vendor Payment
Regulatory Compliance and Quality Assurance
Global Strategic Sourcing
Medical Writing
Biostatistics
Phamacovigilance
Ex-US Regulatory Affairs
Global Footprint
US, Canada, and EU (Latin America, Australia, Asia- Pacific including India through col-laborations)
NCGS Overview
ncgs.com
NCGS has a proven quality track record with over 30 years of clinical operational excellence with zero 483s. Sponsor challenges and pain points are addressed with “First in Class” research professionals. Many NCGS field and management professionals were previous NCGS clients. Several staff held site management positions early in their careers, providing them with insight into creative site management for a productive study outcome.
Clinical Operations Staff
Experience– Greater than 10 years tenure on average
Cross-functional expertise
Monitoring and Project Management
Regulatory Due Diligence and GCP/ICH Compliance
Auditing
Strong Clinical Data Management Interface
65% have Director and Global Director Experience
Available under FSP or Full Service
Employ Clinical CAPA (Corrective and Preventative Action) In-Process
Functional Flexibility
Back-Up- Each assigned position has an assigned back-up
Back-up strategy is employed from study onset, not implemented emergently
Absence of attrition and solid clinical development knowledge
Key elements to ensure site performance and relationship success.
Functional and Interactive consistency is achieved employing strategic back-up model - Cross team and site communications highly effective with tenured staff
Continuity breeds quality results and site satisfaction
Consistently delivering studies on time, on budget and with the highest quality
Superior results with an elite development team that functions strategically
24/7/365 call center ensures ready access for clinical, regulatory and safety inquiries
Communication Through Diverse Methods: Avoid “Sea of Sameness”
Relationship strength is communication based beyond weekly CRA Contacts
Medical Monitor monthly rotations and monthly “call” notations
Sponsor Updates: Metrics, early obstacle identification, intervention successes
Site Contingency Plans: Define / Employ / Mitigate Risk
Investigator Teleconferences
Newsletters, FAQs, Email Blasts
Clinical Operations and Monitoring
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Strategic Subject Recruitment—Therapeutic Drivers
Referral(s): Physicians, hospital units, clinics, free clinics, urgent care clinics
Media / Internet: Clinical Trial Website, Therapeutic Website, Site Website
Secure Sponsor/NCGS Web Portal
Create self-referral opportunities– Poster, fliers, ads, support groups
iPad and iPhone free applications
Social Media: future (Twitter Guidance)
Subject Retention
Plan > Outline > Remind > Modify > Caregiver considerations
Electronic and manual recall tools
Direct Subject Alerts—HIPAA Compliant
Electronic reminder via phone or internet
Evaluability
Train and re-train
Compliance management
Query discussion and teaching tool
Avoid repeat errors
Grant payments > fiscal impact deviations > motivation escalates performance
Open Payment Act Compliance
Quality Based Management Standards
Quality Plan / Project Management Plan
Assumptions and Deliverables
Metric Based
Patterns of Errors – Early Detection
Continuous Improvement
Clinical CAPA (Corrective and Preventive Actions) In-Process
Timelines, Milestones, Resource Allocation
Tools, Report Formats
Risk Mitigation Plan
Performance Assessments
Obstacle Identification
Root Cause Analysis
Intervention Success
Communication Plan and Issue Escalation
Senior Management Oversight
Clinical Operations and Monitoring
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Risk Based Monitoring
Trends in Remote Monitoring and/or Risk Based Monitoring
NCGS provides sponsors with quality data management services. EDC, IWRS and CTMS systems are fully integrated. All systems are fully validated, 21 CFR part 11 compliant electronic data capture solutions that are capable of handling small, single site Phase I trials up to multi-national, multi-lingual Phase III and IV trials.
Data Management Plan Development
EDC Solution: Medidata Rave and Merge eClinical OS
Web-based solution with scalability
Accessible through any web-enabled device including mobile platforms
Fully integrated EDC, IWRS and CTMS solution
Adjudication module
Clinical image management
External data uploads and verification
Missing results reports
Edit specifications - CDISC standards
Coding - Adverse Events (MedDRA) and Medications (WHO Drug)
SAE Reconciliation
Source data uploads
Risk based monitoring capable
Compelling pricing structure
User fees based on sites and trial duration, not annual fees
Database Closure/Lock
Rapid subject “cleaning” and datalock– 5 days last monitoring visit
Legacy Experience Other EDC and Data Management Systems
Inform, MediData, Oracle RDC, ClinTrial
IWRS
Randomization
Fully incorporated into EDC user’s flow
One time fee at study initiation
No ongoing duplicate user fees
Automatic database validations to ensure patient eligibility
Auto-population of randomization information onto eCRFs for data review
Drug Supply
Bulk v. unique drug supply
Inventory management
Expiration management
Custom reports
Automatic email notifications
Data Management, EDC and IWRS
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NCGS will establish and maintain your trial master file in audit ready compliance with our robust and expanding TMF/eTMF centralized team of more than 100 experienced regulatory document specialists and regulatory associates. NCGS’ e-TMF preferred solution meets global regulatory compliance requirements (GCP, ICH E6, FDA, 21 CFR Part11 / EU Annex 11 compliant, EMEA, etc.) and follows the hierarchy and indexing standards from DIA’s TMF Reference Model which is an extension of the EDM Reference Model addressing standards for electronic submissions. NCGS has proven talent regarding audit readiness as evidenced during our most recent FDA audit 27FEB-1MAR 2012 for an international infectious disease trial resulting in zero findings.
TMF/eTMF Sponsor Drivers - Establishing or Merging TMFs/eTMF:
Launch of a new compound
Acquisition of a company or compound and need to merge critical TMF documents
Joint development effort
Acquisition of a new eTMF system requiring resources for consolidation efforts
TMF centralization efforts requiring a preferred TMF or eTMF vendor
Access, Security and Achieving Compliance:
Web-based secure centralized access to CRO and stakeholders
Decreases regulatory start-up time and review processes
Eliminates duplication of resources and multiple back-up paper repositories
Improves ongoing document reconciliation
Provides document capacity to meet global trial management needs
Regulatory compliance
CFR Part 11 compliance (limited access, password protected, audit trails, date and time stamps)
Accuracy, completeness and legibility
Certified - employing a validated QC process
Records are enduring and available when required
Provides standard reports - missing and incomplete documents with visual indicators
Provides a competitive advantage to stakeholders in providing evidence of GCP and of the trial’s overall scientific credibility
Risk Mitigation Noncompliance
Demonstrate compliance of the investigator, sponsor and monitor with the standards of good clinical practice (GCP) with all applicable global regulatory requirements
Standardizes processes for ensuring document compliance
Predefines list of expected documents for every trial based on specific study characteristics
Decreases complexity of maintaining required FDA regulatory documents by streamlining the creation, collection, management and storage of critical clinical research documentation
Image and indexing quality checks
Reports against client-defined milestones; expected versus actual
Clarifies picture of incomplete or overdue documents
eTMF and CTMS Management
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Benefits: Rapid start-up Wizards - Simplify design processes (quick and repeatable) No additional capital equipment outlay or investment by sponsor Native MS Office and Adobe PDF support Rapid QA process Unique trial-based or compound-based user licensing model Email-like interface Metrics
Planned versus actual milestones Decreases audit preparation time Customizable reports, views and document sub-type Reduces expensive redundant storage requirements Eliminates paper handling, paper storage and fire and security expense Managers no longer need to produce off-line tracking spreadsheets
Configurable detailed reports by site, study, compound Case Study: NCGS merged worldwide documents for 200 ongoing trials for one of the largest Pharma companies in the industry. Merging historical documents into one central system in the presence of ongoing trials from fifteen (15) different repositories and alternate system types is a complex operation. NCGS’ Discernible Difference and Competitive Advantage: Robust regulatory compliance staff with years of previous experience in essential
document processing during trial launch Staff is fully versed in document quality control standards, document conversion, critical
adherence to specified naming conventions and electronic transfer from multiple formats or environments
NCGS can manage your eTMF in our eTMF electronic preferred platform or your preferred platform
NCGS can provide this level of expertise at costs substantially less than our global competitors
NCGS’ eTMF preferred solution provide stakeholders evidence of GCP compliance and a clinical trial’s overall scientific credibility
eTMF and CTMS Management
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NCGS medical monitors have medical practice and clinical research experience which leads to an understanding of site challenges and resolution recommendations. Therapeutic expertise is provided by board certified in-house physicians in key therapeutic areas. Medical monitors are familiar with key opinion leaders (KOL) and high-enrolling sites. They drive physician to physician communication with 24/7/365 coverage.
Medical Monitoring and Compound Development Services
Compound development plan
Statistical analysis plan review
Clinical data capture plan review
Investigator site selection input
Protocol training / PI meeting
Call center site support 24/7/365 and language translation services
Interaction with regulatory agency
Protocol development
Safety Management Services
Eligibility and safety assessments
Safety management plan
Data safety monitoring board
Safety data capture plan
Data Safety Charter
Protocol safety section
Reconcile safety and clinical databases
Distribution of expedited reports to PI/IRBs
Safety Reporting Services
Clinical study reports
Abstracts and manuscripts
SAE report review
Safety narratives
Safety legacy database integration
Coding – MedDRA (or sponsor)
Data safety listings and reports
Annual reports
Medical Monitoring / Safety Management
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Rapid Study Start-Up
Rapid contract execution from site qualification visit
NCGS contract processes employ efficiency in language and budget negotiation
Standard acceptable changes identified at study initiation and updated as language negotiations are accomplished
Discovery of any obstacles to contract full execution at individual sites
Discovery of any site contract language mandates that may assist sponsor legal prior to receipt of contract comments (i.e., indemnification agreements, third party agreements, investigator fraud clauses, etc.)
Alerts for revisions driven by enrollment feasibility questionnaire information that may provide insight into site processes and mandates
Timeline, order and impact of contract verses IRB approvals researched to determine if site can meet study initiation target dates
Payments tied to Evaluability Metrics
Quality driven payment structure
Feedback to the site is provided for each subject payment and incremental decrease of full payment is employed for evaluations the site fails to perform
Feedback and payment reductions lead to site realization (cause and fiscal effect) of sub-quality performance impact
NCGS payment method eliminates improper incentives for non-performance which is a growing agency concern
Fiscal accountability shifted to the site for study related procedures drives study compliance metrics and evaluability
Evaluability Shifts
In previous trials where NCGS has rescued the study - grant savings of $250,000 have been realized due to improved evaluability
Quality performance of NCGS initiated trials avoids needless lost grant fees due to focused subject management and close fiscal review of payments
NCGS’ payment process offers sites efficient and expeditious payment turnaround
CRF in-house and reviewed clinically and for payment within 24 hours
Eliminates duplication of effort between clinical and contract payment group
Reasonable fund retains are held until query resolution accomplished
Open Payment Compliance
Site Satisfaction
Payment efficiencies lead to investigator and site satisfaction
Grants, Contacts and Site Payments
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NCGS recognizes the importance of quality initiatives in all aspects of research. The Quality Management Plan is the cornerstone of all development efforts ensuring regulatory compliance and quality deliverables.
Quality Management Plan / CAPA (Corrective and Preventative Actions)
Development of standards of operations to achieve a quality-based system
Applicable regulations addressed
Identify quality and efficiency objectives
Clear delegation of responsibilities
Root cause analysis
Implementation of quality-based standards of operations
Resource allocation and training
Define metrics to measure efficiency
Define preventive measures to avoid common areas of non-compliance
Communication algorithm and issue escalation
Plan for assessing effectiveness of any interventions or preventative methods
Maintenance of quality-based standards of operations
Assess defined and collected metrics for quality performance
Employ intervention when required and test efficiency of intervention
Root cause analysis (RCA) and proper “Action Plan”
Documentation and evaluation of quality-based standard of operations
Define the level of documentation required to assess quality performance
Define the frequency of documentation to assess quality performance
Assess effectiveness of any intervention or preventative measures
Process approach to meet objectives
Anticipated outcomes defined
Mitigating risks and consequences
Focus on prioritized improvement opportunities
Factual approach to decision making
Effective decisions are based on analysis of data and information
Continuous improvement
Conduct audits - contracted and internal
Cost effective system to meet objectives
Host sponsor audits and regulatory authority inspections
All of these activities provide:
Input into improving NCGS’ quality processes
Assurance of regulatory compliance
Fiscal responsibility
Quality Assurance & Regulatory Compliance
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NCGS global strategic sourcing solution is a hybrid model offering a customized balance of our Strategic Sourcing staffing capabilities with or without engaging our full service CRO. Strategic Sourcing provides individuals or functional teams or multi-disciplinary teams tailored around our client’s specific requirement(s).
Customized Solutions to Resourcing Needs
Individual contract placement or permanent placement
Interim/Short-term solutions for peak periods and special projects
Teams developed - Functional areas, partial or full teams
Dedicated staff for duration of client need / sourcing allocation
Seamlessly expand limited resourcing to full service sourcing or any hybrid solution required
Benefits of Strategic Sourcing
Significant cost reduction compared to a fully outsourced study
Reducing employment risks
Increasing ability to meet project deadlines and peak periods of activity
Maintaining smooth operations when staffing needs to fluctuate
Flexible Billing Models
Hours worked including travel if partial or fluctuating FTEs are required
Per FTE for the specific duration of the assignment
Billing frequency and format is negotiated in MSA
All reasonable pass-through expenses will be agreed upon in the MSA
Operational Gaps
NCGS provides clinical research professionals across a broad range of job functions with significant industry experience, in a wide variety of therapeutic areas. Our personnel can be located at your office, NCGS office or regional field based positions. Service areas include:
Choosing NCGS Strategic Sourcing
Staff turnover (<3%) due to high employee satisfaction
NCGS tailors team processes to match client standard of operation
NCGS provides highly tenured staff
Sponsor has first right of access to re-assign staff members to another project benefiting from corporate intelligence
Therapeutic Concentrations in Complex Arenas - Oncology, Hematology, CNS, Infectious Disease, Cardiology, Pulmonary, etc.
Clinical Management Medical Monitoring Biostatisticians
Site Monitoring Drug Safety Data Management
Site Recruitment / Start-Up Medical Writers CTMS Management
Site Study Coordinators Quality Assurance Staff Training
Grant and Contracts * eTMF Management Regulatory Affairs
Global Strategic Sourcing
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NCGS provides sponsors with the highest possible quality of standards-compliant, scientific documentation and medical writing services to the medical research community. Documentation is clear, concise and scientifically accurate with format and content in strict accordance with regulations and guidance.
➢ Clinical Operations Staff
➢ Protocols
➢ Investigator Brochures
➢ Clinical Sections of Regulatory Filing Documents including:
Clinical study reports (Full ICH or FDA-Abbreviated)
Integrated summaries of efficacy and safety
Module 2 of the common technical document
➢ Full Template Support to Ensure FDA, ICH, and Sponsor Compatibility
➢ Abstracts
➢ FDA Briefing Materials
➢ NDAs in CTD format
➢ Journal Publications and Scientific Presentations
➢ Risk Evaluation and Mitigation Strategy (REMs)
Medical Writing
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NCGS provides sponsors with the highest possible quality of statistical support services to the medical research community.
Clinical Development Services
Design and Related Statistical Consulting for:
Pre-clinical and clinical (Phases I-IV) trials
Toxicity, pharmacokinetic/dynamic, and generic equivalence
Analysis of results for IDE, NDA, ANDA, PMA and 510(k) submissions
Assistance with Strategic Preparation for FDA Meetings
Established contacts with FDA personnel
Representation at FDA/Sponsor Meetings
Knowledgeable of eCTD Structure and Components:
Required versus optional elements and structure granularity
Experienced in building eCTDs and producing eCTD components
Documents: Modules 2,5, ISE, ISS
SAS XPT files: 1999 Guidance (Raw[Listing] and Analysis)
CDISC (Clinical Data Interchange Standards Committee)
• SDTM (Study Data Tabulation Model)
• ADaM (Analysis Data Model)
Documentation: define.pdf and define.xml
SAS programs
Biostatistical Services
Protocol Development, Statistical Design and Statistical Modeling
Sample Size Determination
Generation of Randomization Codes
Statistical Programming and Analyses:
Tables, figures, listings
Patient profiles
Integrated efficacy and safety databases
Independent Statistical Team for Interim Analyses & DSMB
Data Transfer
Biostatistics
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Patient safety is of paramount importance in every clinical trial. Individualized safety management and reconciliation plans are developed for each study. NCGS provides sponsors with the highest possible quality of global Pharmacovigilance services to the medical research community.
➢ Global Safety Database
Hosted client specific global solution (ARISg)
Remote entry of cases in sponsor global safety database
➢ Comprehensive Safety Management Plans (SMPs)
Including MedWatch and CIOMS reporting
➢ Clinical Trials and Post Marketed Products
➢ Expedited Electronic Reporting to EudraVigilance System
➢ Paper Based Reporting
Investigators, Ethic Committees and National Authorities
➢ Annual and 6 Monthly Aggregate Trial Safety Reporting
➢ Preparation/Submission of Aggregate Safety Reports (PSUR/PADER)
➢ Signal Detection
➢ Global Literature Searches (Retrospective/Prospective)
➢ Legacy Data Upload Projects
➢ Medical Coding
➢ 24/7 Safety Call Center with Language Translation Services
➢ Global Drug Safety Database:
Fully validated database with a client specific schema
3-4 weeks for set-up and testing before going live
PSURs and aggregated reports are produced appropriately
Remote access
Runs directly with annual reports, periodic safety reports
CIOMs and MedWatch reports
➢ Ad-Hoc Listing
➢ Reconciliation of Safety Database and Clinical Database
