kickstarting the brain: regulatory approach to measuring safety … · •u.s. post-market...

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 Carols.Pena@fda.hhs.gov

William Heeterks, MD PhD Deputy Division Director (Clinical) William.Heetderks@fda.hhs.gov

Michael Hoffmann Deputy Division Director (Regulatory Policy)

Michael.Hoffmann@fda.hhs.gov

Tim Marjenin Branch Chief, Neurostimulation Devices Timothy.Marjenin@fda.hhs.gov

Vivek Pinto, PhD Branch Chief (Acting), Physical Medicine and Neurotherapeutic Devices

Vivek.Pinto@fda.hhs.gov

Xiaolin Zheng, PhD Branch Chief, Neurointerventional and Neurosurgical Devices

Xiaolin.Zheng@fda.hhs.gov

Devjani Saha, PhD Early Feasibility Study Program Devjani.Saha@fda.hhs.gov

Erin Keegan Early Feasibility Study Program Erin.Keegan@fda.hhs.gov

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Thank You

William Heetderkswilliam.heetderks@fda.hhs.gov