# Presentation: 680593

## Clinical Trials of Medical Devices

**Pediatric Workshop**
**January 20, 2006**
**Sheila Brown, RN, CCRC**
**Investigational Device Exemptions (IDE) and  **
**Humanitarian Device Exemption (HDE) Programs**
**Office of Device Evaluation**
**Center for Devices and Radiological Health**
**Food and Drug Administration**

## Objectives

- Review the regulatory process for conducting clinical studies of medical devices
- How to collaborate with CDRH on development of clinical trials (Pre-IDE process)

- DARPA FDA Training 10/05

## IDEs

_**Purpose**_**:**
- 	To _***encourage discovery and development  of useful medical devices***_ for human use, to the extent consistent with the _*protection of the public health and safety and with ethical standards*_, while maintaining optimum freedom for scientific investigators in their pursuit of that purpose

- DARPA FDA Training 10/05

## Sponsoring an IDE 

- Sponsor could be:
- Government Agency
- Company
- Individual investigator
- Clinical Research Organization (CRO)
- Other (as long as US entity)
- _Sponsor assumes all legal responsibilities for IDE_

- DARPA FDA Training 10/05

## Studies Subject to             Device Regulation

- If used to support a marketing application:                  PMA, HDE or 510(k), OR
- Collection of safety and effectiveness information (e.g., for a new intended use of a legally marketed device), OR
- Sponsor-investigator studies of unapproved devices or new intended use of approved device (_even if no marketing application planned_)

- DARPA FDA Training 10/05

## Provisions of the IDE Regulation

- All clinical investigations subject to FDA oversight must be _approved_ _before_ they can begin
- _Assigns responsibilities_ to all participants in clinical investigation
- All subjects in the investigation must give written _informed consent_

- DARPA FDA Training 10/05

## Regulatory Requirements for       Clinical Studies of Medical Devices

- Informed Consent and Human Subject Protections
- Institutional Review Board **oversight**
- Financial Disclosure
- Investigational Device Exemption (IDE) application. Required elements web link:
- 	http://www.fda.gov/cdrh/devadvice/ide/application.shtml#required_element

- DARPA FDA Training 10/05

## Required Elements of an IDE

- U.S. Sponsor (manufacturer or investigator)
- Prior Investigations
- Preclinical animal and bench testing
- Investigational Plan (detailed protocol, informed consent, case report forms)
- Manufacturing Information
- Investigator (CV, agreement) and IRB Information
- Sales Information (can recover cost of study but not more)
- Labeling (INVESTIGATIONAL)

- DARPA FDA Training 10/05

## IDE Review Process:

- Sponsor submits application to FDA
_**FDA approves, conditionally approves or disapproves IDE within 30 calender days**_
- Sponsor obtains IRB approval
_**After both**_ FDA and IRB approve the investigation, study can begin

- DARPA FDA Training 10/05

## Financial Disclosure by Investigators 

- Financial compensation not prohibited, nor is divestiture required
- Not required to be submitted in an IDE, but if will eventually support a marketing application, needs to be _**gathered**_ at this phase
- Required to be submitted in any marketing application relying on investigators’ data
- Details:
- 	http://www.fda.gov/oc/guidance/financialdis.html

- DARPA FDA Training 10/05

## Early Collaboration with CDRH:    “Pre-IDE” process

- A valuable informal mechanism to exchange feedback about proposed bench/animal/clinical testing of a device _**BEFORE**_** **an IDE is submitted
- Collaboration is by:  	Meetings/teleconferences/email
- We do hundreds every year; they work!

- DARPA FDA Training 10/05

## Pre-IDE meetings may be held at several points in premarket phase:

**Prior to conducting “proof of concept” animal studies**
**During preclinical testing (prior to feasibility study)**
**Prior to expanding clinical trial from feasibility to pivotal phase**

- DARPA FDA Training 10/05

## Pre-IDE benefits

- Earlier consensus on design testing and development plans that will expedite review and approval
- Save money and time
- More collaborative approach
- Minimize surprises

- DARPA FDA Training 10/05

## Summary

- All clinical studies have same basic applicable regulations regardless of marketing application type
- Center for Devices will work collaboratively with sponsors in developing a study plan
- FDA “Device Advice” website:
- http://www.fda.gov/cdrh/devadvice/ide/index.shtml

- DARPA FDA Training 10/05

## Thank you

- Contact information:
- Sheila Brown
- (301) 594-1190 x 107
- sheila.brown@fda.hhs.gov

- DARPA FDA Training 10/05

## Backup slides

- DARPA FDA Training 10/05

**All Device Investigations**

**Studies Exempt from the IDE Regulation**

**Studies Subject to the IDE Regulation**

**SR Investigations**

**Full Requirements**

**NSR Studies**

**Abbreviated**** ****Requirements**

- DARPA FDA Training 10/05

## Studies Exempt from             Device Regulation (no IDE needed)

- Pre-1976 devices
- 510(k)-cleared and HDE- or PMA-approved devices,    _***if used in accordance with approved label***_
***In vitro*** diagnostic devices (most)
- Consumer preference testing of marketed device
- Combinations of legally marketed devices
- Custom devices (_**NARROWLY**_ defined)
- Foreign Studies; **Declaration of Helsinki**

- DARPA FDA Training 10/05

## If NOT Exempt from                   Device Regulation, Then...

- Need to assess whether proposed study of device is considered _**SIGNIFICANT RISK (SR), or NONSIGNIFICANT RISK (NSR)**_
- IRBs can and do make this assessment most of the time
- FDA can assist IRBs and/or investigators by making risk determinations; this determination is final
- See IRB Information Sheet on SR/NSR: http://www.fda.gov/oc/ohrt/irbs/devices.html#risk

- DARPA FDA Training 10/05

**All Device Investigations**

**Studies Exempt from the IDE Regulation**

**Studies Subject to the IDE Regulation**

**SR Investigations**

**Full Requirements**

**NSR Studies**

**Abbreviated**** ****Requirements**

- DARPA FDA Training 10/05

## Non-significant Risk IDEs 

- Sponsor presents protocol to IRB and a statement why investigation does not pose significant risk
- If IRB approves the investigation as NSR, it can begin
- Abbreviated IDE requirements (labeling, IRB, consent, monitoring, reporting, prohibition on promotion)
_**No**_ IDE submission to FDA needed

- DARPA FDA Training 10/05

## Non-significant Risk Study Examples 

- Most functional MRI studies
- Study of non-invasive blood pressure measuring device
- Electroencephalography studies
- Studies of wound dressings
- Contact lens studies
- Studies of conventional laparoscopes

- DARPA FDA Training 10/05

**All Device Investigations**

**Studies Exempt from the IDE Regulation**

**Studies Subject to the IDE Regulation**

**SR Investigations**

**Full Requirements**

**NSR Studies**

**Abbreviated**** ****Requirements**

- DARPA FDA Training 10/05

## Significant Risk (SR) Study

-    Presents a _**potential serious risk**_ to the health, safety, and welfare of a subject and is:
- an implant; or
- used in supporting or sustaining human life; or
- of substantial importance in diagnosing, curing, mitigating, or treating disease or preventing impairment of human health

- DARPA FDA Training 10/05

## Significant Risk (SR)           Study Examples

**Evaluation of a marketed biliary stent for use in the peripheral vasculature**
**Evaluation of unapproved radiofrequency ablation device for treatment of primary hepatic neoplasia **

- DARPA FDA Training 10/05