Demonstrating Clinical Utility
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Transcript of Demonstrating Clinical Utility
Medical Device Development Lifecycle:
Demonstrating Clinical Utility
11 September 2014Mary Lewis
Senior Clinical Research SpecialistWe have studied clinical research
and regulatory compliance issues since 1999.
Plan and Conduct scientifically sound study
Ensure Protection of Human Subjects
Qualified personnel
Provide Adequate Monitoring
Current, complete, and accurate data
Data needed to support Efficacy and Safety determination
Elements of a Quality Clinical Study
Study Planning • Identification of clinical need
– Solutions for patients, clinician customers – Application of novel technology– New indication for an established product
• In concert with a scientific advisory board consisting of medical experts and statisticians– Target patient population– Identify the control– Design the study
Other Planning Considerations
• Time to market• Cost factors• Reimbursement • Pre-clinical and mechanical testing, toxicology,
and carcinogenicity/genotoxicity testing• Risk analysis• Endpoints and Measures
Evidence-Based Medicine
• Critical assessment techniques as reported in literature
• Objective evaluation quality clinical research• Clear eligibility criteria• Generalizability• Sufficient follow-up• Statistical power
Study Design Decisions• Start with pilot /feasibility study (an IDE)
– Multi-center or single center, randomized or non-randomized, controlled or open-label
– Identification of clinician learning curve• RCT (Randomized Controlled Trials)= Level 1
evidence- provide the most compelling evidence that the study treatment causes the expected effect on human health
Statistical Power• How big a difference (effect
size) is expected between groups• numbers of patients increase ability to
reliably detect the effect of the intervention This is described as the "power" of the trial
• The larger the sample size or number of participants in the trial, the greater the statistical power
Economics of Large Studies• in designing a clinical trial, statistical power
must be balanced with cost• more patients = a more expensive trial
The Clinical Study=One Critical PieceSystematic Approach to Quality
• Personnel roles and responsibilities• Training• Policies and Procedures- define controls to reduce/prevent errors• Auditing (QA) and Adequate Monitoring (QC)- identify potential
problems and course correct early• Document management, record retention and reporting • Corrective and Preventative Action (CAPA)
Study Conduct
Planning Stage
Identify, analyze, and strengthen weakness in
compliance areas• Regulations [812 or 312, 11,
50, 54, 56]• Protocol, DMP, SAP• Sponsor requirements/
SOPs/ Risk Analysis• Personal Qualifications and
Training/Site Selection• IRB Requirements• Agreements
Execution Stage
FDA and IRB Review• Overall Organization• Monitoring Activity• Data Collection and
Handling• Electronic Records• Product Accountability• Records Maintenance• Facilities/Equipment• Quality Assurance
Close-Out Stage
Regulatory inspection preparation
• Database lock/ Analysis/ Results Reporting
• Record Retention• Quality Assurance
Planning Stage-Protocol is Written Next?
• Site Selection- # investigators, medical specialty, experience, published in field of interest, geographic location, cost, available staff, worked with site on past studies, FDA restricted?
Planning Stage-Risk Analysis
• Required by law (21 CFR Part 820 Quality System Regulation)• Identifying design problems before distribution eliminates
costs associated with recalls• Offers a measure of protection from product liability damage
awards• Regulatory submissions (PMA and 510k) call for inclusion of
risk analysis• It is the right thing to do
Planning Stage• Monitoring Plan• Data Management Plan
database set-up, data entry methodology, data processing (quarantine), delta checks & queries
• Statistical Analysis Plan• Project Tracking Systems
site payments and performance (accrual, % received, % audited, % queried), AE databases, protocol deviations
Study Conduct
Planning Stage
Identify, analyze, and strengthen weakness in
compliance areas• Regulations [812 or 312, 11,
50, 54, 56]• Protocol, DMP, SAP• Sponsor requirements/
SOPs/ Risk Analysis• Personal Qualifications and
Training/Site Selection• IRB Requirements• Agreements
Execution Stage
FDA and IRB Review• Overall Organization• Monitoring Activity• Data Collection and
Handling• Electronic Records• Product Accountability• Records Maintenance• Facilities/Equipment• Quality Assurance
Close-Out Stage
Regulatory inspection preparation
• Database lock/ Analysis/ Results Reporting
• Record Retention• Quality Assurance
Obtain Approvals
• Regulatory Authority• IRB/EC• Other committees- O.R. product approval
committees, Hospital Research Committees• CMS
Study Initiation
• Select qualified investigators• Build Regulatory Binder (Investigator Brochure)• Ensure proper monitoring- site initiation,
routine monitoring (QC), audit plan (QA) (what variables, at what level and what frequency)
• Shipping Investigational Product and Master Test article accountability
Monitoring Procedures
• Domestic and/or OUS• % SDV- all data or primary endpoint data?• Who, when, and how often?
Human Subject Protection
• Informed Consent= Process• Requirements 21 CFR Part 50
Consent Materials
• “generic” Sponsor-written ICD submitted with IDE• IRB of record is final authority on ICD content• Written at a 8th Grade reading Level or below• 8 required elements, 6 additional elements and
clinical trial registry databank info
Informed Consent Process
• Well informed participants– Understand study requirements– May be less likely to drop-out and more compliant
Qualified Personnel21 CFR 812.43
Investigators• Qualified by training and
experience to investigate the device– Adequate time– Adequate resources– Necessary equipment– Aware of differences between
clinician and clinical investigator
– Knowledge of GCP– Commitment to research
Monitors
• Qualified by training and experience to monitor the investigational study in accordance with the applicable regulations– Specific study protocol
training/therapeutic area– Regulatory knowledge– Human factors concerns– Importance of consent
process
Adequate Monitoring21 CFR 812.46
• Securing compliance [FAIR Shake™]– Federal Regulations– Agreements– Investigational Plan– Requirements of the IRB
Promptly either secure compliance or discontinue shipments of the device to the investigator and terminate their participation in the study
Adequate Monitoring• Set sites up for success• Early and frequently enough to catch
problems and course-correct • Combination of remote and on-site activities• Regular data verification may reduce queries
and avoid late database problems• Provide training/re-training opportunities for
new or current staff
Study Conduct
Planning Stage
Identify, analyze, and strengthen weakness in
compliance areas• Regulations [812 or 312, 11,
50, 54, 56]• Protocol, DMP, SAP• Sponsor requirements/
SOPs/ Risk Analysis• Personal Qualifications and
Training/Site Selection• IRB Requirements• Agreements
Execution Stage
FDA and IRB Review• Overall Organization• Monitoring Activity• Data Collection and
Handling• Electronic Records• Product Accountability• Records Maintenance• Facilities/Equipment• Quality Assurance
Close-Out Stage
Regulatory inspection preparation
• Database lock/ Analysis/ Results Reporting
• Record Retention• Quality Assurance
Auditing versus Monitoring
Auditing Monitoring
Current Complete Accurate Data
Evaluable Data
Efficacy
EligibilitySafety
In Summary
• Clinical trial processes• Issue/Re-Audit CAPA
• Conduct compliant study
•Write Protocol• SOPs
PLAN DO
CHECKACT
Monitoring Function
Auditing Function
SAY WHAT YOU DO DO WHAT YOU SAY
PROVE ITIMPROVE IT
Questions?