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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.pdf7/29/2019 Drugs vs Devices 1
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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.