What is CIOMS?

1 Global Guidance on patient involvementJoint PCWP-HCPWP Meeting, EMA, Amsterdam, 4 March 2020 Dr LembitR goSecretary-GeneralCouncil for International Organizations of Medical Sciences (CIOMS)Geneva, is CIOMS? Organization, links with other international organizations Areas of work and Working GroupsCIOMS Working Group XI: Patient Involvement in Drug Development and Safe Use Background and scope WG processes, progress Draft content Examples of selected chapters Plans for futureConclusionsEMA 4 March 2020 What is CIOMS? Acronym & LogoEMA 4 March 20204 Council forInternationalOrganizations ofMedical SciencesFounded in 1949 by WHO and UNESCOIn official relations with WHO and UNESCO associated partnerICH Observer since 2016 Mission Statement CIOMS mission is to advance public health through guidance on health research including ethics , medical product development and safetyCIOMS in shortEMA 4 March 20205 Organization located in Geneva :A. InternationalB. NongovernmentalC. Not-for-ProfitForum for discussion and neutral platform to elaborate new ideas in medical product development, pharmacovigilance and research ethics (bioethics).

2 For WHO, health authorities, academic organizations, pharmaceutical industry and other concerned stakeholdersCIOMS:an umbrella organization of medical science organizationsPrograms, ActivitiesEMA 4 March 202026 Core of activities: Technical Working GroupsRun-time:Mostly 2-4 years, or even more than 10 years (SMQs)Impact:Legally not binding, yet significant influence on healthcare community (including decision makers and other organizations with impact); can also be transformed to be legally binding when embodied in regional/national legislation Since 1967; 1. CIOMS Round Table Conference Biomedical Science and the dilemma of Human Experimentation ) Issuance of significant guidelines; latest revision 2016 Focus on "low and middle income countries ; translated into many languages including Chinese, Spanish, Japanese, RussianBioethics 1986 first PV Working Group, 13 more working group reports until today Several ICH Guidelines are based on results of CIOMS Working GroupsPharmaco-vigilance Trends and Prospects in Drug Research and Development, Proceedings of the 11thCIOMS Round Table Conference, Geneva, Switzerland, 8-9 December 1977.

3 Ed. Z. Bankowski, Dunne, published by Scrip World pharmaceutical News, London, communication Website: 4 March 20207 Members, links with other international organizations9 EMA 4 March 20209 CIOMS membershipRecent new members (2018)EMA 4 March 202010 New international member of CIOMSThe International Federation of Associations of pharmaceutical Physicians and pharmaceutical medicine (IFAPP)New national member of CIOMSB angladesh Medical Research CouncilCIOMS and ICH (2) EMA 4 March 202011 CIOMS is ICH Observer since 2016 MEMBERSF ounding Regulatory Members EC, Europe FDA, US MHLW/PMDA, JapanFounding industry Members EFPIA JPMA PhRMAS tanding Regulatory Members Health Canada, Canada Swissmedic, SwitzerlandRegulatory Members ANVISA, Brazil CFDA, China HSA, Singapore MFDS, Republic of KoreaIndustry Members BIO IGBA WSMIOBSERVERSS tandingObservers IFPMA WHOL egislative or Administrative Authorities CDSCO, India CECMED, Cuba COFEPRIS, Mexico INVIMA, Colombia MCC, South Africa National Center, Kazakhstan Roszdravnadzor, Russia TFDA, Chinese Taipei TGA, AustraliaRegional HarmonisationInitiatives (RHIs) APEC ASEAN EAC GHC PANDRH SADCI nternational pharmaceutical industry Organisation APICI nternational Organisationregulated or affected by ICH Guideline(s) Bill & Melinda Gates Foundation CIOMS EDQM IPEC PIC/S USPCIOMS impact on ICH* GuidelinesEMA 4 March 202012 CIOMS pharmacovigilance guidelines served as a basis for several ICH guidelines.

4 Some examples:*ICH -TheInternational Council for Harmonisationof Technical Requirements for Pharmaceuticals for Human UseWorkingGroupICH GuidelineCIOMS WG I und II Reports (1990, 1992)ICH-E2A (1994): Clinical Safety Data Management Definitions and Standards for Expedited ReportingCIOMS IA Report (1992)ICH E2B: Clinical Safety Data Management Data elements for transmission of individualcase safetyreportsCIOMS WGs II und III Reports (1992, 1995)ICH-E2C (1996): Clinical Safety Data Management Periodic Benefit-Risk Evaluation Reports (PBRER)CIOMS WG V Report (2001)ICH-E2D (2003): Post-Approval Safety Management Definitions and Standards for ExpeditedCIOMS WG VIII Report (2006)ICH-E2F (2010): Development Safety Update ReportsCooperation with ICHEMA 4 March 202013 Extract from MedDRA MC to ICH AssemblyNovember 2019, SingaporeMed= MedicalD= Dictionary forR= RegulatoryA= ActivitiesAreas of Work and Working GroupsPharmacovigilance: Working GroupsOverviewof CIOMS activities, includingWorkingGroup XI15 Working GroupPeriod (someexamples)Report / YearCIOMSI-International Reporting of Adverse Drug Reactions (1990)CIOMS II-International Reporting of Periodic Drug Safety Update Summaries (1992)CIOMS III-Guidelines for Preparing Core Clinical Safety Information on Drugs (1995)CIOMS IV01/1995 07/1997 Benefit-risk balance for marketed drugs (1998)CIOMS V04/1997 08/2000 Current Challenges in Pharmacovigilance: Pragmatic Approaches (1999)CIOMS WG on SMQs05/2002-Development and Rational Use of Standardized MedDRA Queries (SMQs): Retrieving Adverse Drug Reactions with MedDRA (2004)CIOMS VI03/2001 -10/2004 Management of Safety Information from Clinical Trials (2005)CIOMS VII-Development Safety Update Reports (DSUR).

5 Harmonizing the Format and Content for Periodic Safety Report during Clinical Trials (2006)CIOMSVIII-Practical Aspects of Signal Detection in Pharmacovigilance (2010)CIOMS/WHO WG11/2005 10/2010 Definition and Application of Terms for Vaccine Pharmacovigilance (2012)CIOMSIX-Practical Approaches to Risk Minimisationfor Medicinal Products (2014)CIOMS X06/2011 07/2015 Evidence Synthesis and Meta-Analysis for Drug Safety (2016)CIOMS SMQ Implementation WG(05/2002) 2019 Development and Rational Use of StandardisedMedDRA Queries (SMQs): Retrieving Adverse Drug Reactions with MedDRA (2016)CIOMS WG to Vaccine Safety2013 -2016 CIOMS Guide to Active Vaccine Safety Surveillance (2017)CIOMS Guide to VaccineSafety Communication (2018)CIOMS WG on DILI2017 ongoingPharmacovigilance: Recent Safety PublicationsShanghai, December201916 4 March 202017 Geneva, December 2019I17 CIOMS reachesout in manylanguagesE-training course 4 March 202018 Ongoing Working Groups todayEMA 4 March 202019 Five WGs ongoing: CIOMS Working Group on Drug Induced Liver Injury (DILI) (started 2017) CIOMS Working Group on Clinical Research in Resource Limited Settings (November 2017) CIOMS Working Group on Patient Involvement in Development and Safe Use of Medicines (April 2018) WG XI CIOMS Expert Working Group on MedDRAL abelingGroupings (MLGs) (April 2019) Revision of CIOMS IV : Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals (September 2019) WG XIINew WGs2020.

6 CIOMS Working Group on Real World Evidence and Real World Data in Regulatory Decision (March 2020) WG XIII CIOMS Working Group on Severe Cutaneous Adverse Reactions (SCARS) Q3 2020 CIOMS Working Group on Patient Involvement in Development and Safe Use of Medicines (April 2018) WG XIWhenCIOMS WG starteda lot 4 March 202021 Source: Marc M. Boutin , DIA San Diego June2019 EMA 4 March 202022 Working Group objectivesThe CIOMS Working Group XI on Patient Involvement in the Development and Safe Use of Medicines was launched in April 2018 with an ambition to cover the whole product life-cycle from early development until retirement from the market. It includes participants from patient organizations, industry , regulators, academia and the World Medical Association. All F2F meeting minutes are made publicProgress1st meeting held on19-20 April 2018, Geneva, Switzerland (minutes available)2nd meeting held on 23 24 October 2018, Berlin, Germany (minutes available)3rd meeting held on 1-2 May 2019, Geneva, Switzerland (minutes availble) Open meeting held on 30 April 2019, Geneva, Switzerland 4th meeting held on16-17 October 2019, Basel, Switzerland (minutes available)5th meeting to be held on 1-2 April 2020, Utrecht, Netherlands6th meeting to be held in October 2020, Amsterdam, NetherlandsCIOMS Working: Patient Involvement in Development and Safe Use of 4 March23 CIOMS Working Group on Patient Involvement in the Development and Safe Use of Medicines (since April 2018)The CIOMS Working Group on Patient Involvement 4th Meeting in Basel, 4 March 202024 CIOMS Working Group on Patient Involvement in Development and Safe Use of MedicinesDraft content for the future guidance (1).

7 Of patient involvement in the development and safe use of medicines; principles and considerations for patient engagement; involvement in advancing treatments for their disease; involvement in patient product labelling; for patient involvement in additional risk minimization measures; participation in the generation and utilization of safety and effectiveness data; input in developing safety issue communications regarding medicinal products; and opportunities in patient involvement in resource-limited settings; principles for patient participation in therapeutic 4 March 202025 CIOMS Working Group on Patient Involvement in Development and Safe Use of MedicinesDraft content for the future guidance (2a)Chapter 6 Opportunities for Patient Involvement in Additional Risk MinimisationDescription of Risk MinimisationPurpose: Optimisea product s benefit-risk profile Enhance safe use Preserve patient accessTypes:Regulatory Aspects of Additional Risk MinimisationCurrent regulatory landscape for EU, USA, and JapanCase examples of patient involvement with regulators for additional risk minimisationplanningDetermining the Need for Additional Risk MinimisationDescription of pharma adaptation of Failure Mode and Effects Analysis (FMEA) and opportunities for including patient perspectiveRoutineAdditionalAdequate for most productsReserved for specific products / risks Product Label Packaging Prescription Status Communication / Educational Measures Controlled Product Distribution and UseEMA 4 March 202026 CIOMS Working Group on Patient Involvement in Development and Safe Use of MedicinesDraft content for the future guidance (2b)Chapter 6.

8 Opportunities for Patient Involvement in Additional Risk MinimisationPatient Involvement in the Design, Implementation and Effectiveness of Additional Risk MinimisationMeasures (aRMMs) Additional Risk MinimisationProcess StepsPatient input can inform design of aRMMsto promote behaviors /actions to minimize ideas or feedback can optimisetool prototypes and enhance health literacy of input can help customiseimplementation on country level and lessen burden on healthcare can provide input on design and conduct of aRMMseffectiveness evaluations and participate in evaluation 4 March 202027 CIOMS Working Group on Patient Involvement in Development and Safe Use of MedicinesDraft content for the future guidance (3a)Chapter 7. Patient participation in the generation and utilization of safety and effectiveness dataOverview Sources of data, entities with which patients interact, and the existing rules of engagement are reviewed. Followed by critical appraisal of gaps, needs, and opportunities.

9 Specific challenges and promising future directions are highlighted, followed by a set of recommendations. Current environmentSources of data Adverse Event Spontaneous reporting Real-World Evidence: Post-authorisationsafety studies (PASS), Health Economics and Outcomes Research (HEOR) Studies, Patient Surveys, Risk Management Registries Expanded access programs and compassionate use programs Qualitative Studies (Structured Interviews and Focus Groups) industry Medical Information Systems Internet Posts/Social media Personal sensors and wearable devices (new forms of data)EMA 4 March 202028 CIOMS Working Group on Patient Involvement in Development and Safe Use of MedicinesDraft content for the future guidance (3b)Chapter 7. Patient participation in the generation and utilization of safety and effectiveness ..Data linkageSharing of data and rules of engagement Patients regulatory authorities, industry , healthcare professionals, patient organizations, patient s perspectiveGaps, needs, and untapped opportunitiesMobilizing patients, caregivers, and patient families as advocates for open access to patient benefit-risk data.

10 Increasing patient engagement in regards to providing their data. ChallengesLegal requirements, Global Environment on Data Privacy, large volume data, societal attitudes towards industry and regulators/government partnering with patientsEMA 4 March 202029 CIOMS Working Group on Patient Involvement in Development and Safe Use of MedicinesDraft content for the future guidance (4)Chapter 8. Patient input in developing safety issue communications regarding medicinal productsScope -Definition of An Urgent CommunicationPatient involvement ContentType of issuesCrisis Communication in Clinical TrialsCrisis Communications for Marketed Products Crisis Communications for GenericsType of distributionType of communicationClarificationAdditional communicationEducational Contact for informationLinks for communicationPatient organisationsto assist in communicationVulnerable patientsEMA 4 March 202030 CIOMS Working Group on Patient Involvement in Development and Safe Use of MedicinesDraft content for the future guidance (5)Gaps / additional topics identified Resource-Limited Settingschallenges and opportunities CHAIN Uganda workshop Resource-Limited Settings subgroup.