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FDA Decisions for 

Investigational 

Device Exemption 

(IDE) Clinical 

Investigations

Owen Faris, Ph.D.

Clinical Trials Director (acting)

Office of Device Evaluation

Center for Devices and Radiological Health

FDA Audio Conference August 14, 2014
Overview

• Streamlining clinical trials as an FDA Strategic Priority

• Define “Guidance” documents

• What is an Investigational Device Exemption (IDE) 

Study?

• History and original goals of this Guidance

• FDASIA Section 601 

• What has changed in this Final Guidance compared to 

the Draft Guidance?

• Decisions for IDEs

• Information Communicated in FDA’s decision letters

3
FDA Strategic Priorities

• CDRH has identified as a strategic priority the goal of 

improving US patient access to new devices by 

strengthening and streamlining the clinical trial enterprise 

so that medical device clinical trials are conducted in the 

US in an efficient, cost-effective manner, while 

maintaining appropriate patient protections.

• This guidance:

– Introduces processes to allow more efficient study enrollment to 

reduce the time and cost associated with the conduct of clinical trials;

– Provides information regarding FDA’s decision-making processes to 

improve predictability of the regulatory process; and

–

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Introduces communications intended to improve the transparency of 

FDA’s decision-making processes to study sponsors and other 

stakeholders.
FDA Guidance documents

• An FDA guidance document:

– Explains FDA’s current thinking on a topic

– Does not establish legally enforceable 

responsibilities

– Should be viewed only as recommendations, unless 

specific regulatory or statutory requirements are 

cited

5
Investigational Device Exemption

• Established in section 520(g) of the FD&C Act and in 

21 CFR Part 812

• FDA approval of an IDE is required for US human 

study of a significant risk device which is not 

approved or cleared for the indication being studied.

• Exempts sponsor from certain provisions of FD&C Act 

(e.g., requirement for a marketing application, 

compliance with full GMPs)

• Requirements for informed consent, labeling, 

monitoring of the study, records/reporting

• Initiation of the study requires approval by 

Institutional Review Board (IRB)

6
History of this Guidance

• Originally published as draft guidance on 

November 10, 2011

• Explained each of the possible FDA decisions

– Approval

– Approval with Conditions

– Disapproval

• Provided examples of reasons that could support 

IDE Disapproval or Approval with Conditions 

• Explained “Staged Approval,” which allows some 

studies to begin while issues are addressed 

concurrently

7
FDASIA Section 601

Amends Section 520(g)(4)(C) of the FD&C Act 

• FDASIA became law on July 9, 2012

• FDA shall not disapprove an IDE because:

– the investigation may not support a substantial equivalence or 

de novo classification determination or approval of a device;

– the investigation may not meet a requirement, including a data 

requirement, relating to the approval or clearance of a device; 

or

– an additional or different investigation may be necessary to 

support clearance or approval of the device.

8
This means that an IDE cannot be 

disapproved on the basis of FDA’s belief that 

the study design is inadequate to support a 

future PMA, 510(k), HDE, or de novo 

classification. 

The standards for market approval (PMA/HDE) 

or clearance (510(k)) have not changed.

9

FDASIA Section 601
• FDA implementation of the law included a 

working group to:

– Develop IDE decision policy

– Modify IDE decision letter templates

– Consider other mechanisms to encourage sponsors to 

work with FDA to develop pivotal trials that are 

appropriately designed to support marketing 

applications 

– Re-issue draft Guidance for public comment. 

(June, 2013)

– Issue final Guidance 

10

FDASIA Section 601
What is (nearly) unchanged 

from the draft Guidance?

• Explanation of the reasons for which FDA may 

disapprove an IDE

• Explanation of mechanisms for approving IDEs

– Approval

– Approval with Conditions

– Staged Approval (some minor modifications for 

clarification)

11
• Changes to how Study Design Considerations 

and Future Considerations will be 

communicated to sponsors 

• Removal of the proposal for a new voluntary, 

comprehensive, interactive review process to 

assist in the development of appropriately 

designed pivotal studies (Pre-Decisional IDE)

• These will be discussed in detail later in the 

talk

12

What has changed from the 

draft Guidance?
• Approval

– Approval of full study cohort

– Staged Approval

• Approval with Conditions

– Approval with Conditions of full study cohort

– Staged Approval with Conditions

• Disapproval

13

Possible FDA decisions for IDEs
Decisions: Approval

– FDA does not have remaining questions that must 

be addressed prior to enrollment of the approved 

number of subjects

– Study is approved for a specified number of 

enrolled subjects and investigational centers

– Study may be initiated upon IRB approval

14
Approval with Conditions

– FDA has determined that, despite some outstanding 

issues, the information provided is sufficient to justify 

human clinical evaluation of the device and the proposed 

study design is acceptable with regard to protection of 

study subjects. 

– Resolution of those issues is not required prior to 

initiation of enrollment in the study, with the exception 

of certain issues related to the informed consent 

document (which must be corrected prior to enrollment)

– Sponsor may begin study upon receipt of IRB approval on 

the condition that, within 45 days from the date of FDA’s 

decision letter, the sponsor submits information 

addressing the issues identified in FDA’s letter. 

15
– Examples of typical Conditions:

• Requests for additional information, data or changes that 

relate to protecting subjects in the study and can be 

addressed in a timely (45 days) manner but FDA determines 

do not need to be resolved prior to study initiation 

• Late stage follow-up procedures and assessments that 

relate to the care of study subjects but, because they 

occur late in the study, will likely be addressed prior to 

subjects reaching that point in the study

• Minor issues related to the informed consent document 

that must be corrected before study initiation (i.e., 

subject enrollment) but can be reviewed by FDA after 

study initiation

16

Approval with Conditions
Staged Approval

– Approval or Approval with Conditions is granted while 

certain outstanding questions are answered concurrently 

with enrollment of a limited number of subjects

– If the benefit-risk profile is sufficiently favorable to 

justify enrollment of a portion of the study subjects, a 

staged clinical investigation allows initiation of a study 

that might otherwise be disapproved while providing 

additional mitigation of risk by limiting exposure of the 

device to a smaller subject population 

–

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The sponsor will be permitted to expand enrollment once 

an IDE supplement containing the necessary additional 

information is submitted to FDA and found to be 

acceptable. 
– May be appropriate when:

– Additional clinical confirmation of the safety profile or 

the potential for benefit is obtained by reviewing 

initial data from subjects enrolled early in the clinical 

investigation before enrolling the entire subject 

cohort.

– Additional confirmatory non-clinical testing is needed 

to more fully characterize device performance to 

adequately evaluate the potential risks of the device, 

before permitting testing of the entire subject cohort 

and is conducted concurrently with early enrollment in 

the clinical investigation.

18

Staged Approval
– Some additional considerations for pivotal 

studies:

– Successful support of a marketing application under 

staged approval is not expected until the full planned 

cohort of subjects is studied.

– A staged pivotal study should only be considered if the 

additional information that is requested is not 

expected to result in changes to important elements of 

the clinical investigation (e.g., endpoints, sample size, 

stopping rules) or device design. 

19

Staged Approval
Staged Approval

– Some additional considerations for pivotal 

studies:

– FDA may determine that new feasibility data are 

needed prior to approval of the proposed pivotal IDE, 

in order to allow for a comprehensive examination of 

the study outcomes related to the device safety 

profile in a small group of subjects prior to exposing a 

large group of subjects to the risks of the study. 

–

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The data requested by FDA should not inappropriately 

unblind any of the relevant stakeholders, including 

the sponsor, investigators, or study management 

personnel, to critical study data. 
Disapproval

Sponsor may not initiate the clinical 

investigation until the sponsor submits an 

amendment to the IDE to respond to the 

deficiencies identified in FDA’s letter and 

subsequently receives a new letter from FDA 

granting approval or approval with conditions. 

21
IDE disapproval and 

FDASIA Section 601

• Standards for protection of study subjects 

remain unchanged

• Issues regarding the study design that are not 

related to protecting study subjects are not 

the basis for a disapproval or approval with 

conditions decision

22
Consistent with 21 CFR 812.30(b) and section 520(g) of 

the FD&C Act, FDA may disapprove an IDE for any of 

the following reasons:

There has been a failure to comply with any requirement in 21 

CFR Part 812 or section 520(g) of the FD&C Act, any other 

applicable regulation or statute, or any condition of approval 

imposed by an IRB or FDA. (21 CFR 812.30(b)(1))

The application or a report contains an untrue statement of 

material fact, or omits material information required by 21 

CFR Part 812. (21 CFR 812.30(b)(2))

23

The sponsor fails to respond to a request for additional 

information within the time prescribed by FDA. (21 CFR 

812.30(b)(3))

Disapproval
There is reason to believe that risks to the subjects are not outweighed by 

the anticipated benefits to the subjects and the importance of the knowledge 

to be gained (21 CFR 812.30(b)(4)), such as

Subject safety - investigational plan contains elements that would expose subjects 

to unacceptable probable risks, or fails to adequately protect study subjects from 

probable risks 

The informed consent requires changes to adequately inform subjects of the 

study, and must be reviewed by FDA prior to study initiation (21 CFR 

812.30(b)(4))

The investigation, as proposed, is scientifically unsound because it does not 

pose a reasonable scientific question or the investigation does not include the 

collection of data or information related to that scientific question (21 CFR 

812.30(b)(4)) 

24

Note that “scientifically unsound” does not include concerns that the study design 

will not support a marketing application

Disapproval
There is reason to believe that the device as used is ineffective (21 CFR 

812.30(b)(4)), such as

Inadequate potential for benefit – available data suggest the device is ineffective or 

no information has been provided to suggest the device as used may result in patient 

benefit and the generation of knowledge adequate to justify the risks.

It is otherwise unreasonable to begin or to continue the investigation 

owing to the way in which the device is used or the inadequacy of (i) 

the report of prior investigations or the investigational plan; (ii) the 

methods, facilities, and controls used for the manufacturing, 

processing, packaging, storage, and where appropriate, installation of 

the device; or (iii) monitoring and review of the investigation (21 CFR 

812.30(b)(5), such as

Device safety – the data and information provided are insufficient to adequately 

characterize the safety profile of the device such that human clinical investigation is 

not considered reasonable

Additional detail and examples are provided in the Guidance 25

Disapproval
Study Design 

Considerations (SDCs)

• FDA recommendations to a sponsor regarding changes 

that FDA believes should be made in order for the 

study to support its primary goals

• Examples include issues related to:

– Primary and major secondary endpoints

– Randomization, control, and blinding

– Follow-up duration and assessments

– Statistical analysis plan

– Enrollment criteria (if not related to subject protection)

26
Future Considerations (FCs)

• Intended to provide helpful advice to sponsors 

regarding important elements of the future 

application that the IDE may not specifically address.

• Examples

– Known limitations of the IDE clinical investigation with regard 

to supporting certain claims or indications. 

– Specific non-clinical testing that, while not necessary to 

support approval of the IDE, will be needed to support the 

marketing application. 

27
Communication of SDCs 

• The draft guidance proposed that SDCs be included in 

a section of the IDE decision letter.

• FDA received comments from several stakeholders 

that proposed that FDA provide SDCs and FDA’s 

assessment of the study design as a separate 

communication and not in the decision letter. 

• Other stakeholders expressed support for inclusion of 

SDCs in the letter. 

• Still others focused on ensuring that the decision 

letter clearly conveys whether or not FDA believes 

the study design is adequate to support its goals.

28
Communication of SDCs 

• Based on the comments received, FDA believes that, 

when SDCs are included in the body of the decision 

letter, there is the potential for SDCs to be 

misinterpreted by sponsors and other stakeholders as 

issues that are required to be addressed. 

• Therefore, FDA intends to convey SDCs in a separate 

attachment included with the decision letter, rather 

than in the body of the letter. 

•

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The decision letter itself will state whether FDA 

believes that the study design is adequate to support 

the study goals or whether FDA recommends study 

design considerations in order for the study to do so. 
Communication of SDCs 

• If FDA recommends study design considerations, 

FDA’s letter will note the following: “These 

recommendations do not relate to the safety, rights 

or welfare of study subjects and they do not need to 

be addressed in order for you to conduct your 

study.” 

• FDA will continue to engage with stakeholders on this 

issue and may make modifications to this approach in 

the future.

30
Communication of FCs 

• FDA received comments proposing that the Agency 

provide future considerations as a separate 

communication and not in the decision letter. 

• Based on the comments received, FDA intends to 

convey future considerations in a separate 

attachment included with the decision letter rather 

than in the body of the letter.

31
Removal of Pre-Decisional IDE 

• The draft guidance proposed a new mechanism for 

review and interaction for pivotal IDEs called the PreDecisional IDE. 

• The process included a comprehensive FDA review of a 

draft IDE prior to formal IDE submission, followed by 

written feedback from FDA and an interactive 

discussion between FDA and the sponsor. 

• The goal of the Pre-Decisional IDE was to facilitate the 

development of an improved IDE submission that would 

be more likely to be approved, and include a study 

design that would be adequate to support a future 

32marketing application.
• FDA received comments expressing concern that the 

Pre-Decisional IDE process itself might be too time 

consuming or require extensive FDA resources that 

could be better allocated elsewhere. 

• FDA believes the Pre-submission process and other 

interaction mechanisms can address many of the same 

goals

• Based on the comments received and FDA’s 

consideration of the points raised, FDA will not pursue 

the Pre-Decisional IDE at the present time. 

33

Removal of Pre-Decisional IDE 
How to find the guidance

• To read the guidance, go to:

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulatio

nandGuidance/GuidanceDocuments/UCM279107.pdf

34
Questions?

Owen Faris

owen.faris@fda.hhs.gov

Division of Industry and Consumer Education: 

DICE@fda.hhs.gov

CDRHQuestions@fda.hhs.gov