CDRH Learn

Elias MallisDirectorDivision of Small Manufacturers, International & ConU.S. Food and Drug AdministrationCenter for Devices and Radiological Health
Guidance for Industry and FDA 

Factors to Consider When Making Be

Determinations in Medical Device Premar

and De Novo Classifications 

Date of Publication: March 27, 20

U.S. Food and Drug Administra

Center for Devices and Radiologica

March 2011
Purpose

• To identify and clarify the factor

considers when making benefit-determinations in PMA and de n

classification petitions

• To facilitate transparency, consi

predictability of the premarket reprocess for benefit-risk assessm
Background

• §513(a) of the Federal Food, Drug & Cosm

– FDA determines if PMA applications provide “reason

of safety and effectiveness” by “weighing any probab

health from the use of the device against any probabor illness from such use,” among other relevant facto

– FDA reviews valid scientific evidence to determine if 

claims made by Sponsor

• Clinical data• Non-clinical data• Intended use/Indications for Use

– For de novo classification petitions [513(f)(2)], FDA c

considers a device’s risk profile in order to make a cldetermination for the device under section 513(a)(1) 

Act; these could serve as predicates
Scope of Guidanc

• Submission types impacted:

– PMA applications – de novo classification petitions

• Device types impacted: 

– Therapeutic– Diagnostic
Development Proce

• Contributing Team:

– Benefit-risk working group from CDRH

• Chronology of Key Milestones:

– August 2011: Draft issued for public co– November 15, 2011: Docket closed – Final published on March 27, 2012– Implementation will begin May 1, 2012
Content of Guidan

• Addresses factors FDA considers im

part of the benefit-risk determination

• Provides examples of how FDA uses 

factors in making benefit-risk determ

• Includes worksheet, which reviewers 

in making benefit-risk determinations the premarket process
Factors FDA Consi

When Making Benef

Determinations
Factors FDA Considers 

Making Benefit-Risk (

Determinations

• Factors that characterize benef• Factors associated with risks• Additional factors to be conside
Benefit factors in B-R determ

• Type of benefit

– What primary endpoints or surrogate e

were evaluated?

– What is the public health impact of the 

• Magnitude of the benefit(s)

– Benefit assessed along a scale or acco

specific endpoints or criteria 

– Pre-identified health threshold was ach
Benefit factors in B-R determinations 

• Probability of experiencing one or more 

– Was the study able to predict which patie

experience a benefit?

– What is the probability that a patient will 

the benefit?

– Was there a variation in public health be

different populations?

• Duration of effect

– A treatment whose benefit lasts longer is 

desirable than a treatment that must be r
Risk factors in B-R determi

• Severity, types, number and rates of harmf

– What are the device-related serious advers

– What are the device-related non-serious ad

events?

– What other procedure-related complication

patient be subject to?

• Probability of harmful event

– What percent of the intended patient popul

expect to experience a harmful event?

– Are patients willing to accept the probable 

harmful event, in exchange for potential bedevice?
Risk factors in B-R determination

• Duration of harmful events

– How long does the harmful event last?– What type of intervention is required to 

harmful event? 

• Risk from false-positive or false-n

results for diagnostics

– What are the consequences of a false p– What are the consequences of a false n
Other Factors in B-R Determ

• Uncertainty

– How robust were the data? Are study results rep– What is the probability that a patient in the intend

will receive a benefit or incur a risk?

• Characterization of the disease

– How does the disease affect the patients?– Is the condition treatable?

• Patient tolerance for risk/Their perspective on th

– Would patients tolerate the risks in exchange for 

– How much do patients value this treatment?
Other Factors in B-R Determination

• Availability of alternative treatmen

diagnostics

– What other therapies exist?– How effective are the alternative treatm

• Risk mitigation

– Has the Sponsor identified ways to miti

such as product labeling, education procomplementary testing, etc?
Other Factors in B-R Determination

• Postmarket data

– Are there other devices with similar indications 

market? Are the probabilities for effectiveness harmful events from those devices similar to whfor the device under review?

– Is postmarket data available that changes the b

evaluation from what was available when the pdevices were evaluated? 

– Is there data that otherwise would be provided 

approval that could be deferred to the postmark

• Novelty of technology addressing an unmet me

– How well is the medical need this device addre

met by currently available therapies?

– How desirable is this device to patients?
Impact

• Impact on Industry:

– Industry will understand the factors FDA 

analyzing risk and benefit during the preprocess

• Impact on FDA Review Staff:

– FDA Reviewers will utilize more consist

transparent methods in conducting premof risk and benefit
Conclusions

• Provides greater clarity for FDA revie

Industry regarding the prominent facconsiders when making benefit-risk determinations during the premarket process
Conclusions

• An essential part of FDA’s determina

there are reasonable assurances of effectiveness is considering whether benefits outweigh probable risks

• Improves predictability, consistency, 

transparency of the premarket review 
Questions and Answ

• When will the guidance be implemented?

This guidance will be effective for all PMA applicatiopetition recommendations made beginning May 1, 2

• Will submissions received prior to May 1, 2012 b

using the guidance?They may, depending on how far along in the review 

are. The guidance document and the criteria within implemented beginning May 1, 2012.

• Will Industry be required to fill out the attached 

No. The worksheet and examples provided are pres

what CDRH reviewers consider when making benedeterminations. 
FDA Contacts for Assi

Randall Brockman, M.D.

Chief Medical Officer, Acting

Office of Device Evaluation (O

Randall.Brockman@fda.hhs.

Robert Becker, M.D., Ph.D

Chief Medical Officer, Team Le

Office of In Vitro Diagnostic Device E

and Safety (OIVD)

RobertL.Becker@fda.hhs.go
Links

Factors to Consider When Making Ben

Determinations in Medical Device P

Approval and De Novo Classifica

http://www.fda.gov/downloads/MedicalD

ceRegulationandGuidance/GuidanceD

UCM296379.pdf

CDRH Learn:

www.fda.gov/Training/CDRHLearn/de