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DRUGS VS. DEVICES

Jeng Mah & Gosford A Sawyerr

Sept 16, 2005

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OUTLINE

Design Challenges

Analysis Issues: Device Database Challenges

Challenges with Diagnostics

Post-marketing surveillance

Working with Clinical Investigators

Regulatory Landscape

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DESIGN ISSUES

Double-blind device trials not common with device trials

Single blind possible within device type

Difficulty in going head to head with competitor devicesPre-market trials tend to be simpler to demonstratesafety with regard to intended use

Compliance is easier to measure in device trials than indrug trials

In medical devices, single arm trials with ObjectivePerformance Criteria are used to determine safety ofleads

Single arm pharma trials may appear in early Phase IIwhere the objective may be to rule out drugs with littlepossibility of clinical benefit (e.g., two-stage designs; ref:Simon)

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DESIGN ISSUES (2)

Dose of drug may be an issue; size of devicemay be an issue

Implanting carries greater risk than prescribing adrug

Device trials offer more opportunity to beBayesian lots of prior information re:pacemakers and defibrillators

Device implant studies drive revenue muchmore than prescription drug trials

Post-market device trials are important inproviding clinical evidence for physicians,payors and patients

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DESIGN ISSUES (3)

More precise endpoint determination due toelectronic information storage on device

Drug trial endpoints subjective at timesConsideration of recurrent episodes mayprovide increased statistical power and hencefewer patients

Some endpoint definitions in device trials mayvary from device to device (e.g., AF burdencalculation)

Memory capacity may lead to missing episodes

Device date stamp resets may lead to

inaccurate information re: endpoints

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ANALYSIS ISSUES

Analysis cohort may differ from full randomizedset: e.g., analysis of proportion of VT/VFepisodes appropriately treated may include onlypatients with episodesDevice storage limitations may miss episodes

Heterogeneity in occurrence of episodesbetween patients needs to be considered in

choice of statistical method so that few patientsdo not drive the results

Sensitivity and specificity defined only relative towhat the device records and hence are biasedestimates

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CHALLENGES WITH

DIAGNOSTICSThresholds (cutpoints) which determinediagnostic action need to be established a priori(in drug trials retrospective analysis may bepossible to determine sensitivity to variousdefinitions)

Co-development of drug with diagnostic difficult(studying two drugs simultaneously notnecessarily at same level of difficulty) see FDA Concept Paper:

http://www.fda.gov/cder/genomics/pharmacoconceptfn.pdf

Sensitivity and specificity issues critical

Clinical utility of test drug only trials do not

have this challenge

http://www.fda.gov/cder/genomics/pharmacoconceptfn.pdfhttp://www.fda.gov/cder/genomics/pharmacoconceptfn.pdf

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POST-MARKETING

SURVEILLANCEIn both device and drug trials,registry/observational studies can play a key

role in better understanding of endpointsPossible to trace all patients with device:problematic in drugs

Data from return products, MDRs andregistry studies can assist in betterassessment of system longevity and adversedevice effects Extent of exposure difficult to measure for allpatients who may have taken a drug

MDR analysis may help trend analysis

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WORKING WITH CLINICAL

INVESTIGATORS

Strong partnership between device companypersonnel and implanting physicians (EP,

Cardiologist, etc.) Development of study design highly collaborativewith PI

Delivery of device at implant and device

programming requires participation by companypersonnel

Steering committee actively involved inassessment of study and publication

Events adjudication by clinicians on periodic basis

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REGULATORY PROCESS

Drugs: INDs, NDAs, sNDAs etc.

Devices/Diagnostics IDEs, 510(k)s, PMAs, PMA-Ss etc.