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Safeguarding public healthCLINICAL DATA, EVALUATION andINVESTIGATION:THE FRUSTATIONS OF A CLINICIAN( a personal view)DR SUSANNE LUDGATEClinical Director Medicines and Healthcare products RegulatoryName MHRADate 2010Agency, UK©

COSTS TO NHS 90,000 devices £11.2 billion annually £300 million maintenance drug bill: £ 11.6 billionSafeguarding Public HealthMHRASlide 22010©

NHS NEGLIGANCE2009/10£827,367,000Safeguarding Public HealthMHRASlide 32010©

TOP TEN CLAIMS (devices)Safeguarding Public HealthMHRASlide 42010©

NUMBERS/CLAIM VALUESafeguarding Public HealthMHRASlide 52010©

COSTS: ADVERSE EVENTS £2 billion annually hospital stay 20% device related 50% preventable 60,00050,00040,00030,00020,00010,00001999 2000 2001 2002 2003 2004 2005 2006 2007 2008Safeguarding Public HealthMHRAIndemnity Costs £'000Defence Costs £'000Slide 62010©

EU REGULATORY SYSTEMarticle 20investigationaction, includingrecall, safeguardcompliance ERssafety, performanceprovide ifuNotified Body• quality systems• design dossier• clinical data• ifu• pmcf plan• pms planaccreditauditclinicalinvestigationCompetentAuthorityEuropean marketSafeguarding Public HealthMHRApmcfpost market surveillancevigilanceSlide 72010©

WHY IMPORTANT“…...must not make the assumption that awell designed and constructed device willfunction properly and safely in a diseasedstate and be of benefit to the patient…….”Safeguarding Public HealthMHRASlide 82010©

CLINICAL DATA“……..as a general rule, confirmation ofconformity…must be based on clinicaldata in particular in the case of implantabledevices and devices in class III……….”MDD: Annex XSafeguarding Public HealthMHRASlide 92010©

CLINICAL DATA“…..safety and/or the performance informationgenerated from the use of the device sourcedfrom:- clinical investigations- other studies in the scientific literature forwhich equivalence can be demonstrated- published and/or unpublished reports onother clinical experience of device orequivalent…….”MDD: article 1Safeguarding Public HealthMHRASlide 102010©

ESSENTIALREQUIREMENTS“…..demonstration of conformity with the essentialrequirements must include a clinical evaluation inaccordance with Annex X…….”MDD: annex I:6aSafeguarding Public HealthMHRASlide 112010©

POST MARKET ADDRESSED“…clinical evaluation.…must be actively updatedwith data obtained from post market surveillance.Where post-market clinical follow up……....is notdeemed necessary, this must be duly justified…”MDD: annex X: 1.1cSafeguarding Public HealthMHRASlide 122010©

GHTF DOCUMENTS clinical evidence: definitions clinical evaluation• when• general principles• sources of data• appraisal/analysis• evaluation report clinical investigation• general principles need/ design• specific details• ethical considerations pmcf• when needed/study type• objectives/plansreplacesMEDDEVsSafeguarding Public HealthMHRASlide 132010©

GENERAL PRINCIPLES scope• data sources, types of data• data from comparable devices• special design features how performed/methodology• objective• identification• appraisal• analysis who performsSafeguarding Public HealthMHRASlide 142010©

SOURCES OF DATA literature searching• protocol• rationale• sources, extent searches• selection criteria• inclusions, exclusions clinical experience• pms reports, adverse events, FCAs clinical investigation• plan (objectives, numbers, duration, end points)• compliance• regulatory authority/REC letters• modifications• final reportSafeguarding Public HealthMHRASlide 152010©

EQUIVALENCE clinical- same condition, purpose/body site/critical performance- similar population technical- similar conditions of use/ specifications/design/ deployment/ principles operation biological- same materials- same tissue contactSafeguarding Public HealthMHRASlide 162010©

APPRAISAL suitability of data type of publication (case reports, random experience etc) relative weighting demonstration equivalence completeness of data contribution results to demonstration performance, safetySafeguarding Public HealthMHRASlide 172010©

ANALYSIS aim: to determine if data demonstrates performance andsafety in relation to intended use basis of demonstration• performs as intended• poses no undue threat to patient, user• risk/benefit acceptable factors to be considered:• numbers• type, adequacy patient monitoring• number, severity adverse events• severity, natural history condition• alternative technologySafeguarding Public HealthMHRASlide 182010©

STAGES EVALUATIONidentify clinical data from- literature- clinical experience- investigationgenerate new oradditional datanois clinical evidence sufficientto demonstrate conformitywith relevant ERsappraisal of data sets- suitability- contribution safety, performanceanalysis relevant data- strength of evidence- conclusions about performance, safetySafeguarding Public HealthMHRAyesproduce clinicalevaluation reportSlide 192010©

ISSUES clinical evaluations often not done/poor literature search incomplete (all +ve) regulatory letters/ethics documents not read lack challenge, need c/i equivalence!!Safeguarding Public HealthMHRASlide 202010©

? EQUIVALENCE atrial appendage plug importance claims identical defect plugs differences consequences no pmcfSafeguarding Public HealthMHRASlide 212010©

? EQUIVALENCE cerebral stent claimed equivalence forces different consequences severe no pmcf plan/pmsSafeguarding Public HealthMHRASlide 222010©

CLINICAL INVESTIGATION when undertaken/ general principles general principles of need general principles design specific details design ethical considerationsSafeguarding Public HealthMHRASlide 232010©

GENERAL PRINCIPLESDESIGN based on results clinical evaluation process follow a risk management procedure compliant with all relevant legal, regulatory requirements appropriately designed• factors influencing extent data requirements• objectives, endpoints• justification parameters including numbers• minimisation of bias• design configuration follow appropriate ethical principlesSafeguarding Public HealthMHRASlide 242010©

ISSUES pre-market testing inadequate to justify safety parameters not applicable/inadequate (time, numbers) stopped too early CE marked outwith data demonstrated by trial no pmcf plan/justification for absenceSafeguarding Public HealthMHRASlide 252010©

ENDPOINTS ease of deployment improved symptoms improved blood flow need surgerybut no incidence cerebral thrombiSafeguarding Public HealthMHRASlide 262010©

ENDPOINTS clinical investigation replacement single disc incomplete trial CE-marked multiple levels forces serious consequencesSafeguarding Public HealthMHRASlide 272010©

PMFU STUDY a late unexpected result a good news story?Safeguarding Public HealthMHRASlide 282010©

PMCFpost-market clinical follow-up studies what is it when needed type of study plan, objectivesSafeguarding Public HealthMHRASlide 292010©

POST MARKETSURVEILLANCE none, other than customer complaints inappropriate/inadequate strategies clinical frustration! patient safetySafeguarding Public HealthMHRA IVC filter increased claims retrievability complete change clinical practice increased morbiditySlide 302010©

SUMMARY the requirements Directives are fine the guidance documents are comprehensive…..we just all need to read,interpret and implement better…..Safeguarding Public HealthMHRASlide 312010©

SUMMARYSafeguarding Public HealthMHRASlide 322010©