Medical Device Clinical Investigations - Joburmester

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowChapter 4 - GCP Very similar to ICH GCPSubject SafetyData Quality43JoBurmester.comClinical Research KnowhowChapter 5: Ethical Considerations No improper influence or inducementCompensation and healthcareRegistration in a Public Database - NewEthics ReviewVulnerable PopulationsInformed Consent44Informed ConsentJoBurmester.comClinical Research Knowhow Informed Consent is a process not a document.–––––––PI or designate to obtain consentInformation to subjectTime to read, understand and considerSign and date – may now be electronicCopy of informationConsent recorded in source and docs kept in ISFNew information provided as required Provisions for proxy or oral consent and foremergency situations45 JoBurmester.com 202115

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowInformation for Subjects Description and purposePotential benefitsRisks and inconveniencesAlternative proceduresConfidentialityCompensationExpenses to subject46JoBurmester.comClinical Research KnowhowInformation for Subjects (2)Role of sponsor’s representativeContact personsNew informationInform primary care physicianOption to contact someone else or trace the subject forfollow up - New Public Database - New Termination of the investigation 47Consent to include:JoBurmester.comClinical Research Knowhowa)b)c)d)e)voluntary agreementrefusal of participation incurs no penalty for the subject;discontinuation at any time incurs no penalty for the subject;possible consequences of withdrawal;information provided and confirmation that all the subject'squestions were answered;f) consent to the use of the subject's relevant personal data for thepurpose of the clinical investigation;g) agreement to direct access to medical records;h) contact person for follow up if subject cannot be reached - New48 JoBurmester.com 202116

Medical Device Clinical InvestigationsJoBurmester.comChapter 6 – CI planning Sponsor access to medicalexpertise - New Risk evaluationManagement - expanded Justification CIP IB CRFs – completion guidelinesClinical Research Knowhow Monitoring plan –expanded – risk based Site selection expanded Agreements Labelling DMC49JoBurmester.comClinical Research KnowhowChapter 7 - CI Conduct50MonitorJoBurmester.comClinical Research KnowhowRole of the Monitor, to ensure that: CIP is followed Device used according to CIP Staff and facilities are adequate GCP is followed: Data accurate, documentation correct, patientstreated correctly, missing visits/assessments documented. Consent obtained Source Document Verification Procedures for Adverse Event reporting is followed. Documentation of subject withdrawals51 JoBurmester.com 202117

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowMonitoring Case 1 Investigator has obtained informed consentafter the patient entered the trial.52JoBurmester.comClinical Research KnowhowMonitoring Case 2 The site staff are making a lot of errors in theCRF and they say it’s very difficult tounderstand and complete.53JoBurmester.comClinical Research KnowhowMonitoring Case 3 The investigator has entered a patient whodoes not meet the inclusion/exclusioncriteria.54 JoBurmester.com 202118

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowClinical Investigation ConductThe CI conducted according to CIP, and cannot start untilCompetent Authority & REC agreement. Importantaspects are: Investigation site initiation Investigation site monitoring Adverse Events and Device deficiencies Risk Assessment and actions - New CI documents and documentation55JoBurmester.comClinical Research KnowhowClinical Investigation Conduct Additional members of the investigation site team Subject privacy and confidentiality of data Document and Data Control – New guidance onchanges and validation of electronic systems Investigation Device Accountability Accounting for Subjects Auditing56Safety ReportingJoBurmester.comClinical Research KnowhowThe principal investigator shalla) record and assess every adverse event and device deficiencyb) report to the sponsor, without unjustified delay, all seriousadverse eventsc) report to the EC serious adverse events if requiredd) report to regulatory authorities serious adverse events asrequirede) supply the sponsor, upon sponsor's request, with anyadditional information related to the safety reporting of aparticular event.57 JoBurmester.com 202119

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowAdverse Events Sponsor to record:– AEs critical to evaluation of results– All SAEs– Device Deficiency which could have caused anSAE– Any new findings relating to above58JoBurmester.comClinical Research KnowhowReportable EventsCurrent EU Requirements any SAE, any Device Deficiency that might have led to a SAE if:– a) suitable action had not been taken or– b) intervention had not been made or– c) if circumstances had been less fortunate new findings/updates in relation to already reportedevents.59JoBurmester.comClinical Research KnowhowAdverse Events – Reporting TimelinesEU Investigator to Sponsor – within 3 days Sponsor to Competent Authority– 2 days for SAEs which present imminent risk ofdeath, serious injury, or serious illness and thatrequires prompt remedial action– 7 days for other SAEs60 JoBurmester.com 202120

Medical Device Clinical InvestigationsJoBurmester.comReportable EventsNew EU RegClinical Research Knowhow any related SAE, any Device Deficiency that might have led to an SAE if:a) suitable action had not been taken orb) intervention had not been made orc) if circumstances had been less fortunate new findings/updates in relation to already reportedevents.61JoBurmester.comClinical Research KnowhowAdverse Events – New ReportingTimelines EU In New Regulation: Investigator to Sponsor – no timeline specified – “ina timely manner” Sponsor to Competent Authority– “Without delay”– Timeline to take into account the severity of the event62JoBurmester.comClinical Research KnowhowAdverse Events adverse event - AEany untoward medical occurrence, unintended diseaseor injury, or untoward clinical signs (including abnormallaboratory findings) in subjects, users or other persons,whether or not related to the investigational medicaldevice adverse device effect - ADEadverse event related to the use of an investigationalmedical device63 JoBurmester.com 202121

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowSerious Adverse Eventserious adverse event – SAEadverse event thata) led to death,b) led to serious deterioration in the health of the subject, that eitherresulted in1) a life-threatening illness or injury, or2) a permanent impairment of a body structure or a body function, or3) in-patient or prolonged hospitalization, or4) medical or surgical intervention to prevent life-threatening illness orinjury or permanent impairment to a body structure or a body function,c) led to foetal distress, foetal death or a congenital abnormality or birthdefect64JoBurmester.comClinical Research KnowhowSerious Adverse Device Effects serious adverse device effect - SADEadverse device effect that has resulted in any of theconsequences characteristic of a serious adverse event unanticipated serious adverse device effect - USADEserious adverse device effect which by its nature,incidence, severity or outcome has not been identified inthe current version of the risk analysis report65JoBurmester.comClinical Research KnowhowAdverse Events Case StudiesPoll66 JoBurmester.com 202122

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowAdverse Events Case Studies1. A patient has a severe headache.67JoBurmester.comClinical Research KnowhowAdverse Events Case Studies2. A patient having blood sample takenexperiences swelling at the site of the needleand subsequently has extensive bruising.68JoBurmester.comClinical Research KnowhowAdverse Events Case Studies3. A patient breaks his leg in a climbing accidentand is admitted to hospital to have the bonereset. The investigator feels it is not related tothe study device69 JoBurmester.com 202123

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowAdverse Events – New Definitions(MDR) AE – added “in the context of a clinical trial” SAE – definition similar but added “chronicdisease” ADE Device Deficiency USADE70JoBurmester.comClinical Research KnowhowData Management Control, traceability and ALCOA Source data Control of electronic data71Data ginalAAccurateJoBurmester.comClinical Research Knowhow72 JoBurmester.com 202124

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowSuspension, Termination,Close OutNeed a process for closing the study or forending early:– Procedure for suspension & termination– Routine Close-out– Clinical Investigation report– Document Retention73JoBurmester.comClinical Research KnowhowClinical Investigation Report Sponsor Responsibility Guidance provided Results to be posted in public database74JoBurmester.comClinical Research KnowhowResponsibilities of the SponsorThe sponsor has many responsibilities, before, duringand after a CI: Clinical quality assurance and quality controlCI planning and conductOutsourcing of duties and functionsCommunication with regulatory authorities75 JoBurmester.com 202125

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowManaging Study and Product SupplyRole of the Sponsor: Selecting Investigators Appointing Monitor Collecting, storing and guarding of all documents: CIP,CRF's, REC opinion, Adverse device effects, Stats, Finalreport. Providing Clinical Investigators brochure.76JoBurmester.comClinical Research KnowhowStudy Management– Agreeing CIP– Supplying devices– Ensuring Training is given– Ensuring Adverse device effects are recordedand reported to the authorities– Termination of Study in discussion withInvestigator.77JoBurmester.comClinical Research KnowhowCIP What information needs to be in the CIP?78 JoBurmester.com 202126

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowMedical Advisor Responsibilities Safety and efficacy review and decisions during theCI. Reviewing reported safety events and providingapplicable recommendations to the sponsor. This facilitates early detection of safety signals.79JoBurmester.comClinical Research KnowhowResponsibilities of thePrincipal Investigator Day-to-day conduct of CI,ensure data integrity &patient safety Qualifications of PI Qualifications ofInvestigational Site80JoBurmester.comResponsibilities of thePrincipal InvestigatorClinical Research Knowhow Communication with the REC Informed Consent Process Compliance with CIP Medical care of subjects Safety reporting81 JoBurmester.com 202127

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowMedical Devices in the EUSummary of changes coming General tightening of CE marking process General tightening of GCP requirements for MDCIs Centralised review process for approval Central Database - EUDRAMED Tightening of reporting requirements82JoBurmester.comClinical Research KnowhowRecapPoll8383JoBurmester.comClinical Research KnowhowDesign of Medical DeviceClinical InvestigationsDESIGN – Study Population Study population should be a relevant subset of thetarget population Study population defines before investigation toestablish inclusion & exclusion criteria Assessment of prognostic factors such as age and sex84 JoBurmester.com 202128

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowDESIGN – Controls Most clinical investigations with medicaldevices do not need comparative group Would need a control group if:– End points are subjective / qualitative– Assessment in comparison with alternative or notreatment85JoBurmester.comClinical Research KnowhowDESIGN - Blinding In most Clinical Investigations it is impossible to blind theinvestigator and patient to the product. Especially incomparator trials. In this case it is necessary, if possible to have a separateevaluator who is unaware of the treatment received. In many cases there is no way of blinding the trial.86JoBurmester.comClinical Research KnowhowDESIGN - Randomisation Randomisation must still be performed in CI’s where acomparator product is used. Dependent on the type of product the study design can becrossover or parallel groups. However crossover design is used mainly in studies ofClass II devices as Class III are often implantable thusexcluding the possibility of using a crossover design.87 JoBurmester.com 202129

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowDESIGN - Device Accountability The Investigator must ensure all devices used in a trial areaccounted for. Devices as required should be provided by the Sponsor. Must be correctly labelled in accordance with MDD. Monitor must check devices are used according to the CIP andinstructions for use and check the supply of devices isadequate Sponsor should have systems to ensure the devices trackedand accounted for: i.e. Lot No / Batch No.88JoBurmester.comClinical Research KnowhowDESIGN - Device Accountability Accountability of Devices presents many problems. Usually all you are left with is the packaging and that isthe only way to account for used devices. However, all efforts should be made to performaccountability of devices in accordance with GCPwherever possible.89JoBurmester.comClinical Research KnowhowDESIGN - SterilizationFor devices intended for clinical investigations,the documentation must contain methods ofmanufacture envisaged, in particular asregards sterilization90 JoBurmester.com 202130

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowDESIGN - LabellingThe label must bear the following particulars:a) Name / trade name and address of the manufacturerb) Details necessary for the user to identify the device and thecontents of the packaging;c) Where appropriate, the word 'STERILE';d) Where appropriate, the batch code / serial number;e) Where appropriate use by date (year and month)91JoBurmester.comClinical Research KnowhowDESIGN – Labelling cont.(f) where appropriate, an indication that the device is for single use;(g) if the device is custom-made, the words 'custom-made device';(h) if the device is intended for clinical investigations, the words'exclusively for clinical investigations';(i) any special storage and/or handling conditions;(j) any special operating instructions;(k) any warnings and/or precautions to take;92JoBurmester.comClinical Research KnowhowSummary Regulatory EnvironmentMedical Device Clinical Investigations (Trials)ISO14155 Ethical Considerations PlanningConduct ResponsiblitiesDesign considerations93 JoBurmester.com 202131

Medical Device Clinical InvestigationsJoBurmester.comClinical Research KnowhowThank you for coming! Certificates Post Course Resources Feedback forms94 JoBurmester.com 202132

Medical Devices & Clinical Investigations with Medical Devices An opportunity to test your knowledge during a series of exercises 2 JoBurmester.com Clinical Research Knowhow Agenda Introduction Regulatory Environment Medical Device Clinical Investigations (Trials) ISO14155 Ethical Considerations Planning Conduct