Clinical Evaluation Report Overview And The Literature .

Clinical Evaluation Report Overviewand the Literature Review ProcessHana Vegher, Ph.D., PMPManager, Clinical Evaluation ProgramWorldwide Clinical Affairs, Abbott Vascular

Outline Clinical Evaluation Definition Clinical Data Literature Review Process as a Critical Component of the ClinicalEvaluation Risk Assessment ConclusionSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation The assessment and analysis of clinical data pertaining to a medicaldevice to verify the clinical safety and performance of the device whenused as intended by the manufacturer (MEDDEV 2.7.1. Rev.3) Required by regulatory bodies (OUS) before the manufacturerplaces the device on the market An ongoing and continuous process conducted throughout the lifecycle of the devicesSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Key Applicable Standards andGuidelinesStandard/GuidanceTitleEN ISO 14155:2011Clinical Investigation of Medical Devices for Human SubjectsGood Clinical PracticeNB-MED/2.7/Rec 3 (1999)Notified Bodies’ Recommendations on the Evaluation of Clinical DataMEDDEV 2.7.1 Rev 3(December 2009)European Commissions Guidelines on Medical Devices: Evaluation of Clinical Data, AGuide for Manufacturers and Notified BodiesMEDDEV 2.7.1 Appendix 1(December 2008)Evaluation of Clinical Data: A Guide for Manufacturers and Notified Bodies – ClinicalEvaluation of Coronary StentsMDD 93/42/EECCouncil Directive of the European Communities Concerning Medical DevicesEN ISO 14971: 2012,Medical DevicesBritish Standard: Application of Risk Management to Medical DevicesMEDDEV 2.12-1 Rev 8 (January 2013)Guidelines on a Medical Devices Vigilance SystemIMDRF GHTF SG5/N2R8 (May 2007)Global Harmonization Task Force (Study Group 5) Clinical EvaluationMEDDEV 2.12/2 Rev 2 (January 2012)Guidelines on Medical Devices Post-Market Clinical Follow-Up StudiesSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation ProcessIntegrated into the quality system as an ongoing and continuous process conductedthroughout the life cycle of the deviceRisk ManagementGlobal RegulatoryStrategyBenefit /RiskAnalysisDesign Input/ ProductSpecificationsClinicalEvaluationPost-Market ClinicalExperience/SurveillanceLabeling (IFU)LiteratureReviewPreclinicalStudiesClinical InvestigationSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation Stages (MEDDEV 2.7.1 Rev. 3)The clinical evaluation includes planning, assessment, and analysis of clinical datapertaining to a medical device to verify the clinical safety and performance of thedeviceDETERMINATION OF SCOPEIdentify Essential Requirements thatneed support from clinical dataGenerate additionalclinical dataNOSTAGE 1Identification of clinical data from Literature searching and/or Clinical experience and/or Clinical investigationSTAGE 2Appraisal of individual data sets Suitability Contribution of results todemonstration of safety andperformanceProduce ClinicalEvaluation Report (CER)YESIs clinical evidencesufficient to demonstrateconformity with theEssential Requirements?STAGE 3Analysis of relevant data Strength of overall evidence Conclusions about safety andperformanceSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Planning and PreparationCER Template ExamplePlanning and Preparation Regulatory Standards, Guidelines Internal SOP/DOP for conductingClinical Evaluation and QualitySystem related procedures Templates for Clinical EvaluationPlan (CEP) and Clinical EvaluationReport (CER) CEP (pre-market) Initial CER (pre-market) Update to the CER (post-market) TrainingSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Planning and PreparationScoping the Clinical Evaluation (MEDDEV 2.7.1 Rev. 3) Before a clinical evaluation is undertaken, the manufacturer should define itsscope based on the Essential Requirements that need to be addressed from aclinical perspective Considerations should include:– whether there are any design features of the device or target treatmentpopulations that require specific attention– whether data from equivalent devices can be used to support the safetyand/or performance of the device in question– the data source(s) and type(s) of data to be used in the clinical evaluationSE2941198 Rev A 2015 Abbott. All rights reserved.

Outline Clinical Evaluation Definition Clinical Data Literature Review Process as a Critical Component of the ClinicalEvaluation Risk Assessment ConclusionSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Clinical DataSafety and performance of device is evaluated using weighted clinicaldata from device and/or equivalent predecessor devices Clinical Investigation Data Critically-Evaluated Scientific Literature for device and/or equivalentdevices Post Market Clinical Experience dataSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Defining the Criteria forAppraisal and Analysis of the Identified Clinical DataAppraisal Criteria for SuitabilityMEDDEV 2.7.1 Rev. 3SE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Defining the Criteria forAppraisal and Analysis of the Identified Clinical DataAppraisal Criteria for Data ContributionMEDDEV 2.7.1 Rev. 3SE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Analysis Criteria and ClinicalData WeightingThe clinical data appraised for Suitability and Data Contribution willbe further assessed to evaluate its relative contribution towardssafety and performance A Weighting Level is assigned to data based on the equivalencecriteria to evaluate its relative contribution to the safety andperformance assessmentEXAMPLE: Weight Level 1 will be given to data which reports on the actual device Weight Level 2 will be given to data which reports on an equivalentpredecessor device Weight Level 3 will be given to data which reports on other similar device Overall Weighting: Level 1 Level 2 Level 3SE2941198 Rev A 2015 Abbott. All rights reserved.

Outline Clinical Evaluation Definition Clinical Data Literature Review Process as a Critical Component ofthe Clinical Evaluation Risk Assessment ConclusionSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Literature Review Process as aCritical Component of the Clinical EvaluationObjective and Strategy of the Literature ReviewSearch Search criteria Databases Selection &exclusion criteriaAppraisalandAnalysis Exclude Select Critique Appraise Analyze Abstracts Full textScreenReportSE2941198 Rev A 2015 Abbott. All rights reserved. Risk/Benefit Conclusion Write the report

Clinical Evaluation: Literature Search ProtocolExample of Literature Search Protocol– Search 1 Device Name Equivalent Predecessor Device Name Period Covered by Search Name of the Person Undertaking the Search Literature sources used to identify data: list databases (details can be included in anappendix) Boolean Search Terminology: list specific terms Selection Criteria Unedited Search AlgorithmSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Literature Dataset Appraisal andAnalysisThe clinical data appraised for Suitability and Data Contribution is further assessedwithin each level to evaluate its relative contribution towards safety and performanceExample of Appraisal and AnalysisArticleAuthor &Appraisal Criteria for SuitabilityArticle No.Date[Actual 1R3[Equivalent Predecessor Device]2D2A1P1R13D2A1P1R27D2A2P2R3[Other Similar allWeightingAppraisal Criteria for Data S3C1C1C2C1C1Level 1T2T2T2O1O1O1F1F1F1S2S2S3C1C1C1Level 1F1F1S2S2S1S3S3S3S1S1S3C1C1C1C1C1C1C1C1C1SE2941198 Rev A 2015 Abbott. All rights reserved.Level 3

Clinical Evaluation: Literature Review Conclusion Conclusion of the Literature Review– Provide conclusions for clinical evidence categorized into weight levelsbased on their relevance towards addressing the safety and performance ofthe device Level 1 Evidence: Actual Device Level 2 Evidence: Equivalent Predecessor Device Level 3 Evidence: Other Similar Device– Provide conclusions about any new risks and evaluate their impact on theproduct literature, risk assessment, product design, etc.SE2941198 Rev A 2015 Abbott. All rights reserved.

Example of Literature Review ProcessClinical Lead, ClinicalScientist and Librariandiscuss the preliminaryliterature searchstrategyLibrarian adjusts thesearch criteria inconsultation withScientistLibrarian conductspreliminary literaturesearch(s)Clinical Lead/Scientistevaluates the outputSE2941198 Rev A 2015 Abbott. All rights reserved.

Example of Literature Review Process Cont’dLibrarian conductsadditional literaturesearch(s)Medical Writer requestsfull articles from theLibrarian and conducts2nd round of screeningClinical Lead/Scientistreviews output andsubmits the searchresults to the medicalwriterMedical Writer screensabstracts/conducts 1stround of screeningSE2941198 Rev A 2015 Abbott. All rights reserved.

Example of Literature Review Process Cont’dMedical Writerdocuments all articleswith reasons forselection and exclusionScientist conductsreview and providesfeedback(Multi-step reviewprocess follows)Scientist reviews &approves thedocumented articleselection and exclusionMedical Writerproceeds withcritiquing and appraisal& analysis of theselected literatureSE2941198 Rev A 2015 Abbott. All rights reserved.

Outline Clinical Evaluation Definition Clinical Data Literature Review Process as a Critical Component of the ClinicalEvaluation Risk Assessment ConclusionSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Risk Assessment The current Risk Assessment Report Evaluation of Clinical Data (e.g. literature review) for any new risks notdiscussed/considered in the Risk Assessment Report and IFU– Consider whether Risk Assessment Report or IFU needs to be updated Clinical Risk to Benefit Assessment– Summarize the benefits– Summarize the risks– Summarize the mitigation of the risks Conclude whether the over-all benefits outweigh the risksSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation: Conclusion Outline clearly the conclusions reached about the safety andperformance of the device from the evaluation, with respect to theintended use of the device State whether:– clinical evidence demonstrates conformity with relevant EssentialRequirements– performance and safety of the device as claimed have been established– risks associated with the use of the device are acceptable when weighedagainst the benefits to the patientSE2941198 Rev A 2015 Abbott. All rights reserved.

Clinical Evaluation ProcessIntegrated into the quality system as an ongoing and continuous process conductedthroughout the life cycle of the deviceRisk ManagementProduct Specifications(Design Control)Labeling (IFU)Benefit ancePreclinicalStudiesClinical InvestigationSE2941198 Rev A 2015 Abbott. All rights reserved.

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Clinical Investigation of Medical Devices for Human Subjects Good Clinical Practice NB-MED/2.7/Rec 3 (1999) Notified Bodies’ Recommendations on the Evaluation of Clinical Data MEDDEV 2.7.1 Rev 3 (December 2009) European Commissions Guidelines on Medical Devices: Evaluation of Clinical