kickstarting the brain: regulatory approach to measuring safety … · •u.s. post-market...
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Kickstarting the Brain: Regulatory approach to measuring safety and
efficacy for emerging medical devices that treat neuropsychiatric disorders
Bill HeetderksClinical Deputy Director
Division of Neurological and Physical Medicine DevicesOffice of Device Evaluation
Center for Devices and Radiological HealthFood and Drug Administration
September 27, 2016
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It’s About the Patients
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CDRH Vision
• Patients in the U.S. have access to high-quality, safe, and effective medical devices of public health importance first in the world.
• The U.S. is the world’s leader in regulatory science, medical device innovation and manufacturing, and radiation-emitting product safety.
• U.S. post-market surveillance quickly identifies poorly performing devices, accurately characterizes real-world performance, and facilitates device approval or clearance.
• Devices are legally marketed in the U.S. and remain safe, effective, and of high-quality.
• Consumers, patients, their caregivers, and providers have access to understandable science-based information about medical devices and use this information to make health care decisions.
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Center for Devices and Radiological Health (CDRH) OrganizationPathway for Neurological and Physical Medicine Regulatory Submissions
ODEDevice
Evaluation
OIRIn Vitro &
Rad Health
OCCompliance
OCECommunication
& Education
OSELScience &
Engineering
OCDCenter
Director
OSBSurveillance& Biometrics
DSDSurgery
DOEDOphthalmic
ENT
DCDCardio
DODOrtho
Division of Neurological and Physical Medicine Devices
DAGRIDAnesthesiology
General HospitalRespiratory
InfectionDental
DRGUDReproductiveGastro-Renal
Urological
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Who we are
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Division of Neurological and Physical Medicine DevicesNew Branch Organization
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Regulatory face of clinical trials
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Recent activity related to clinical trialsA Few Areas of Engagement
• CDRH’s IDE Clinical Trial Enterprise Strategic Plan 2014-2015-including Neuropsychiatric IDE Studies
• Neuroscience Trials of the Future: Proceedings of a workshop, March 3-4, 2016
• MDIC Chief Medical / Chief Science Officer meeting focused on medical device clinical trials, September 20, 2016
• New Psychiatry Neurostimulation Review BranchOctober, 2016
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Review of clinical trials of significant risk devices (under Investigational Device
Exemption-IDE)
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Basic IDE Submission Elements• Cover Letter• Report of Prior Investigations
– prior clinical, animal, and laboratory testing of the device• Detailed Device Description• Investigational Plan
– Purpose (Proposed Indications for Use and objectives)– Protocol – Risk Analysis (description and analysis of all increased risks
and how these risks will be minimized) – Monitoring Procedures
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Basic IDE Submission Elements• Informed Consent
• Investigator Agreement & List of Investigators
» Certification that all investigators have signed the agreement, that the list of investigators includes all investigators participating in the study, and that new investigators will sign the agreement before being added to the study
• List of IRBs that have or will be asked to review the investigation
• Copies of all labeling for the device
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FDA Decisions on IDEs• Approval
– Approves the trial for a specified number of patients and investigational centers
– Subjects not exposed to unacceptable risks, even if study is not adequately designed to demonstrate the device is safe and effective
• Conditional Approval– Trial may begin if conditions (deficiencies) are addressed
within 45 days. – Generally due to non-clinical testing issues, minor issues
w/ informed consent, other clarifications, corrections, or modifications
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FDA Decisions on IDEs
– Trial may not start until deficiencies are adequately addressed
– Primarily related to subject protection (e.g., critical preclinical testing and study design concerns related to subject safety)
The risks to the subjects are not outweighed by the anticipated benefits to the subjects and the importance of the knowledge to be gained, the investigation is scientifically unsound, or there is reason to believe that the device as used is ineffective
• Disapproval
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FDA Additional Comments on IDEs• Study Design Considerations
– Additional modifications that FDA believes are needed in order for the study design to support a marketing approval or clearance (Pivotal Trial) or a future study (Feasibility Study)
– Recommended (not required) modifications to the investigational plan
• Future ConsiderationsAdditional considerations which FDA considers important for the support of a future submission, e.g., non-clinical testing not required for IDE but at the time of marketing application
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Reducing FDA Review Timelines
442
215
101
30
FY11 FY13* FY14* FY15
Median Days to Full IDE Study Approval
* Values calculated on 10/31/13 and 10/31/14 respectively
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Review of Medical Devices (PMA, IDE, DeNovo)
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An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article that:
• Diagnoses, cures, mitigates, treats or prevents a disease or condition, or
• Affects the function or structure or the body, and
• Does not achieve intended use through chemical action
• Is not dependent upon being metabolized
What is a Medical Device?
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Device ClassClass I
(exempt)
Class I
(not exempt)Class II Class III
Risk Low Low Moderate High
Pre-market requirement
Registration and listing 510(k)
510(k)
(some exempt)PMA
Establishing Safety and Effectiveness
Substantially equivalent to
predicate
Substantially equivalent to
predicate
Clinical evaluation
(IDE)
Regulatory Controls
General Controls General ControlsGeneral and Special
Controls
General Controls and
PMA
FDA decision if successful Cleared Cleared Approved
Risk based approach to regulation since 1976
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FDA Benefit-Risk Considerations
Assessment of Benefits:• Type• Magnitude and duration• Probability of patient
experiencing benefit
Assessment of Risks:• Severity, type, number and
rates of harmful events• Probability of harmful event• Duration of harmful event
Additional Factors:• Type of submission: IDE, 510(k), HDE, PMA• Type of study: EFS/FIH, feasibility, pivotal• Uncertainty• Characterization of Disease• Patient tolerance for risk• Availability of alternative treatments• Risk Mitigation• Novel technology addressing unmet need
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How we review submissions510(K) Review whether the
sponsor has established
substantial equivalence to
a legally marketed
predicate device
New intended use?
Technology – new types of safety and
effectiveness questions?
Do accepted scientific data demonstrate
substantial equivalence?
De Novo
PMA
Review whether the
sponsor has provided
evidence to support
safety and effectiveness
of the new indications for
use/new technology
Data supports:
New Intended Use?
Addresses new types of safety and
effectiveness questions with new
technology?
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Helpful Guidance DocumentsPresubmission Guidance
http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm311176.pdf
IDES for Early Feasibility and First in Human Studies
http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm279103.pdf
Design Considerations for Pivotal Clinical investigations of Medical Devices
http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm373750.htm
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Helpful DRAFT Guidance DocumentsDRAFT - Clinical Considerations for IDEs for Neurological Devices targeting Disease Progression and Clinical Outcomeshttp://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm489111.pdf
DRAFT - Patient Preference Information http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm446680.pdf
DRAFT - Reporting of Computational Modeling Studies in Medical Device Submissionshttp://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm371016.htm
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Helpful Review Division ContactsCarlos Peña, PhD MS Division Director [email protected]
William Heeterks, MD PhD Deputy Division Director (Clinical) [email protected]
Michael Hoffmann Deputy Division Director (Regulatory Policy)
Tim Marjenin Branch Chief, Neurostimulation Devices [email protected]
Vivek Pinto, PhD Branch Chief (Acting), Physical Medicine and Neurotherapeutic Devices
Xiaolin Zheng, PhD Branch Chief, Neurointerventional and Neurosurgical Devices
Devjani Saha, PhD Early Feasibility Study Program [email protected]
Erin Keegan Early Feasibility Study Program [email protected]
