PhUSE Heidelberg, Germany – 12 October 05 The Future of CDISC Rebecca D. Kush, PhD Founder and President, CDISC The Future of CDISC • The Remainder of 2005 (Q4) • The CDISC Technical Roadmap (2006-08) • Strategic Plans for the CDISC Future 2 CDISC Teams and Projects - 2005 CDISC Technical Coordinating Committee Single Source HL7-CDISC Harmonization; Domain Analysis Model eSource Data Interchange Metadata – end-to-end consistency LAB and AE scenarios eCRF HL7 V3 Define.xml Terminology (Codelists) CV Stds TB Stds PRG ODM LAB SDS SEND ADaM OPS: Maintenance, Member Relations, Education and Implementation Groups, Glossary 3 Team; X-team Projects Standard Implementation Version Release Date SDTM, SEND Ready for regulatory submission of CRT 4,000 downloads as of mid-2005 2004* ODM CDISC Transport Standard for acquisition, exchange, submission (define.xml) and archive 2001 LAB Content standard – available for transfer of clinical lab data to sponsors 2002 ADaM General Considerations document and examples of datasets for submission 2004 Protocol Representation Collaborative effort to develop machinereadable standard protocol with data layer In progress Terminology Codelists Developing standard terminology to support all CDISC standards In progress Define.xml Case Report Tabulation Data Definition Specification 2005* Metadata End-to-end (Harmonization activity among standards) – CDISC Roadmap In progress * Specification on FDA Guidance 4 Q4 CDISC Team Goals • SDTM – SDTM IG 3.1.1 final released Sept 05; support implementations of SDTM • SEND – Pilots for reproductive toxicity data in progress; likely to be released as separate IG – Working with SDS on PK domains • ODM – Version 1.3 to be released by December 2005 – Collaborating with NCI on HL7 Message for eData Collection Instrument (e.g. eCRF) • ADaM – Completing analysis dataset examples – Collaborating with SDTM on SDTM-ADaM Pilot • LAB – 1.1.0 update in progress (due Q4) – SDS Lab TESTCD names to be released Q4. 5 Terminology (Vocabulary) A pillar of interoperability CDISC HL7 FDA Identified All SDTM variables Defined Possible attributes of proposed codelists Published 1st Package with 32 draft codelist & value proposals Assigned Most of the missing codelists for SDTM variables DCRI NCI VA 6 NIH Grants • NIH Roadmap contract: BAA-RM-04-23 Re-engineering the Clinical Research Enterprise: Feasibility of Integrating and Expanding Clinical Research Networks • Recognition that therapeutic area standards (Cardiovascular and Tuberculosis) development needs to be done in a public forum, formalized development process and broad participation from experts and stakeholders representing a variety of domains • Focus on contributing to the public domain, not an specific implementation effort. 7 Protocol “Use Case” Priorities 1. To support CDISC Study Data Tabulation Model (SDTM) V3.1 • Trial Design • Planned Interventions • Statistical Analysis Plan -Planned Assessments -Inclusion/Exclusion criteria 2. To support study tracking databases, e.g. EudraCT, clinicaltrials.gov, the protocol/trial tracking aspect of trial registry or results databases, or databases that support project management tools. 3. To support the development of the clinical trial protocol document 8 Protocol Representation Timeline 2005 Draft General Clinical Trial Registry HL7 Message 2006 Ballot General Clinical Trial Registry HL7 Message Draft genCTR BRIDG Implementation Modeling: Guide PR Element Spreadsheet, Develop Clinical Trial Design Trial Eligibility Criteria 2007 2008 2010 Additional Ballot Cycles Draft and Ballot ICH SCTP HL7 Message ANSI Standards Additional Ballot Cycles Finalize genCTR Implementation Guide Draft SCTP Implementation Guide Finalize SCTP Implementation Guide Update CDISC Glossary and Publish Annually in ACT 9 What’s wrong with this picture? Data Sources • Site CRFs •Laboratories •Contract Research Organizations •Development Partners Operational Data Interchange & Archive: ODM, LAB Operational Database •Study Data •Audit Trail •Metadata Submission Data Interchange & Archive: SMM SDS, ADaM Submission Data •CRT/Domain Datasets •Analysis Datasets •Metadata 10 Future of CDISC Models Protocol Data Sources • Site CRFs •Laboratories •Contract Research Organizations •Development Partners Operational Operational Database Future Data Uniform Interchange CDISC Standard •Study Data & Archive: •Audit Trail ODM, LAB •Metadata Submission Data Interchange & Archive: SDTM, SEND, ADaM Submission Data •CRT/Domain Datasets •Analysis Datasets •Metadata ODM = Operational Data Model SDS = Submission Domain Standards LAB = Laboratory Data Model ADaM = Analysis Dataset Models SEND = Std. Exchg. Non-clinical Data Standards Protocol Representation and Terminology 11 The CDISC Roadmap • Purpose: – To provide a concise, common specification of all technical products to be developed by CDISC. • Endpoint: – By 2008, there will be a single CDISC standard for the full lifecycle of a clinical trial or study from protocol representation through the capture of source data to submission and archive, comprising a set of fully integrated and consistent models which will form logically and organically from our current set. • Success Criteria – All submissions to the FDA are being made using the CDISC standard; – The set of CDISC models in use across the full life-cycle of clinical trials; and – The CDISC standard being globally adopted. 12 CDISC Roadmap - Guiding Principles • • Complete original mission, but focus on harmonization of CDISC models A single CDISC standard: – ODM XML defines format • • – – Maintain Clinical Research scope while mapping to HL7 Remain platform-independent and platform-neutral Define.xml describes common metadata SDTM, LAB and AdaM define content • • • Standard ItemGroups and Items Standard business rules and code lists Metadata and information needed to support analysis 13 CDISC Roadmap – Guiding Principles • Alignment with the BRIDG model – HL7 as portal to healthcare • Leverage cross-functional teams – Fund projects not just teams, but assign teams as stewards and maintainers – Strive to achieve stability and maturity for current standards • Prioritize processes over separate, individual models • Support sites, sponsors and FDA as stakeholders. • Expand Goals to include: Improving patient safety, process optimization, facilitating scientific and regulatory review. 14 CDISC Roadmap Timeline 15 CDISC Models: The View Forward • Keep models stable so industry can catch up – ODM, SDTM, LAB • Support terminology team efforts to improve semantic interoperability • More cross-team interactions focused on harmonization – More cross-team projects like Define.XML, Trial Design • Complete End-2-End Traceability and SDTM/ADaM Projects • Support the needs of existing users – Standard maintenance, support, implementation and evolution – Harmonmize, but maintain stable, backwards compatibility • Support additional data uses based on CDISC standards – Integrated summary data, ECGs, Narratives, devices, etc . . . . • Execute the roadmap – All submissions to the FDA use the CDISC standard; – CDISC models in use across the full life-cycle of clinical trials – The CDISC standard is globally adopted. 17 Data Flow Using THE CDISC Standard = ODM (transport) = SDTM and Analysis Data (content) = Protocol information (content) = Source data (other than SDTM/CRF data) Protocol Representation Patient Info Trial Design (SDTM) Analysis Plan Clinical (CRF or eCRF) Trial Data (defined by SDTM) Clinical Trial Protocol ODM XML (e)Source Document ODM XML Integrated Reports Administrative, Tracking, Lab Acquisition Info CRF, Analysis Data Operational & Analysis Databases ODM XML Define.xml SDTM Data, Analysis Data, Metadata Regulatory Submissions 18 Interchange Standards: Long-term Desired Outcomes • A holistic approach to standards, facilitating data interchange from sites through regulatory submission, utilizing XML • Standards for data acquisition supporting the population of a cross-trial warehouse within FDA • HL7-CDISC models harmonized to yield value for both clinical research and healthcare – sharing of information between EMR and clinical trials • Global adoption of CDISC data standards CDISC Meeting with FDA Commissioner, April 2003 19 “Neither a wise man nor a brave man lies down on the tracks of history to wait for the train of the future to run over him.” Dwight D. Eisenhower 20 The mission of CDISC is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare. 21 Future of CDISC Models Protocol Data Sources Operational Operational Future Uniform Database Data •Laboratories CDISC Standard Interchange •Contract •Study Data & Archive: Research Harmonized with HL7 •Audit Trail ODM, LAB Organizations •Metadata •Development Partners • Site CRFs Submission Data Interchange & Archive: SDTM, SEND, ADaM Submission Data •CRT/Domain Datasets •Analysis Datasets •Metadata ODM = Operational Data Model SDS = Submission Domain Standards LAB = Laboratory Data Model ADaM = Analysis Dataset Models SEND = Std. Exchg. Non-clinical Data Standards Protocol Representation and Terminology 22 CDISC Teams and Projects - 2005 CDISC Technical Coordinating Committee Single Source HL7-CDISC Harmonization; Domain Analysis Model eSource Data Interchange Metadata – end-to-end consistency LAB and AE scenarios eCRF HL7 V3 Define.xml Terminology (Codelists) CV Stds TB Stds PRG ODM LAB SDS SEND ADaM OPS: Maintenance, Member Relations, Education and Implementation Groups, Glossary 23 CDISC Projects - 2005 Initiatives towards the Mission Initiative/Project Deliverable(s) Status HL7 Harmoniz CDISC standards harmonized with the HL7 RIM In progress eCRF HL7 V3 (eDCI) V3 RIM Message representing data collection instrument for clinical research (eDCI) In progress Single Source Proof-of-concept project to demonstrate feasibility of collecting data once (eSource) for multiple purposes (healthcare and clinical research) Proof-of-concept done; pilots in progress eSource Data Interchange Document to describe the value and benefits of CDISC standards (particularly ODM) to facilitate the use of technology for eSource data collection Document posted for open review and comment CV and TB Standards Standards to facilitate interactions among sites and sponsors for specific therapeutic areas (NIH Roadmap grants) In progress 24 Interchange vs Interoperability Syntax Structure • Main Entry: in·ter·op·er·a·bil·i·ty Semantics Meaning : ability of a system ... to use the parts or equipment of another system Source: Merriam-Webster web site • interoperability : ability of two or more systems or components to exchange information and to predictably use the information that has been exchanged. • Source: IEEE Standard Computer Dictionary: A Compilation of IEEE Standard Computer Glossaries, IEEE, 1990] Syntactic interoperability (interchange) Semantic interoperability Source: Charles Mead, MD, HL7 25 HL7 Reference Information Model (RIM) HEALTH LEVEL 7 REFERENCE INFORMATION MODEL RIM_0088 released January, 1999 reflects agreements made through harmonization in November, 1998 Healthc Healthc are_finances are_finances Mas ter_tables Healthc are_finances HealtHealthc hcare_stak are_finances eholders Patient_encount Healthc are_finances ers has_as_participant Financi al_transaction alternat e_desc is_c ategorized_by 0. .* desc extended_amt is_associated_with 0. .* fee_schedule_cd insurance_amt post ing_dt qty transact ion_batch_id is_entered_by t ransaction_cd 0. .* transact ion_dt transact ion_id t ransaction_t ype_cd is_associated_with unit_amt 0. .* unit_cos t_amt is_the_purc haser_of 1 Authentication aut henticat ion_dt t ype_cd 0. .* is_related_to 1 Cli nical _document_header aut henticat ion_dt availability_stat us_cd change_reason_cd complet ion_stat us_cd confident iality_stat us_cd content _present ation_cd doc ument_header_c reat ion_dt file_nm id has_been_originat ed_by 0. .* last_edit _dt originat ion_dt reporting_priority_cd results _report _dtt m storage_stat us_cd has_been_received_by 0. .* 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requests Master_service allowable_proc essing_priority_cd is _produced_by 0. .1 allowable_reporting_priority_cd billing_reference_t xt challenge_information_t xt is_request ed_by 1 confidentiality_cd effect ive_dt fact ors_t hat _may _affect _observation_desc fee_amt fixed_canned_mes sage_cd is_target 1 imaging_measurement_modality_cd incompatible_change_dtt m has_target 0. .* instrument_identifier_coding_syst em_nm Master_servi ce_rel ati onship instrument_identifier_nm relationship_t ype_cd int erpret ation_considerat ions_desc reflex_test ing_trigger_rules_desc kind_of_quantity_observed_cd constraint_t xt last_update_dtt m quant ityt iming_qt 1. .* is_covered_by met hod_cd method_desc nature_of_service_cd has_source 0. .* is_source 1 observation_id_suffix_t xt orderable_s ervice_ind patient _preparation_desc point_versus_interval_cd is_delivered_during 1 port able_device_ind preferred_ordering_met hod_t xt preferred_scheduling_met hod_t xt 1 is_inst ant iat ed_as procedure_medic ation_cd report _display_order_t xt required_credentials_desc servic e_alternate_id service_alt ernate_identifier_coding_syst em_nm service_alternate_identifier_nm service_alternate_name_use_cd servic e_alternate_nm Master_speci men_requirement additive_cd service_c ontraindic ation_cd c ontainer_desc service_desc container_preparation_desc service_performance_schedule_cd container_volume_amt service_primary _nm derived_spec imen_cd service_requirement _desc minimum_collec tion_volume_amt service_t ype_cd normal_collec tion_volume_amt s tandard_t ime_t o_perform_dtt m special_handling_desc t arget_anatomic _site_cd spec imen_priorities_cd t arget_of_service_cd specimen_retention_t ime_amt universal_service_id spec imen_t ype_cd univers al_s ervice_identifier_coding_syst em_nm univers al_s ervice_identifier_nm quant ityt iming_qt is_s pecified_for 0. .* join_cd has_as_basis Em ployee Insurance_certification appeal_reason_cd cert ific ation_day _qty effect ive_dt id insurance_verificat ion_dtt m 0. .* affirms_insurance_c overage_for modificat ion_dtt m non_concur_cd 0. .* provides _validation_for non_conc ur_effective_dtt m penalty_amt terminat ion_dt report_of_eligibilit y_dt report _of_eligibility_ind 0. .* contains is_request ed_by 0. .1 involves has_as_employee 0. .* 1 issues 1 offers 0. .* may _act_in_ t he_role_of has_as_ employer Insurer effect ive_dt terminat ion_dt 1 Durable_m edical _equipment id slot_size_inc rement _qty belongs_to 1. .* t ype_cd is_a_s ubdivision_of 1 0. .1 0. .* may_request 0. .* requests produces 0. .* 0. .1 has _as_a_subdivis ion 0. .* is_a_c ontac t_for has_as_a _cont act 0. .* may_request is_request ed_by Resource_slot offset _qty quant ity_amt resource_t ype_cd slot _state_cd start _dtt m 0. .*is_reserved_by 0. .*is _managed_by is_a_role_of 0. .1 Accident_inform ati on_source 0. .1 cat egorizes Organization organization_name_t ype_cd 1 takes_on_role_of organizat ion_nm 1 assigns standard_industry_class_cd 1 takes_on_role_of 0. .* requests I ndivi dual_healthcare_practi ti oner_group id 0. .* is_for Employer effect ive_dt 0. .1 is_a_role_of has_as_a_cont act terminat ion_dt 1 is_employer_of 0. .1 Pati ent_service_location_request t ype_cd 0. .* requests 0. .* may_request is_request ed_by 0. .1 is_the_recipient _of P ati ent_information_recipient Heal th_chart health_chart _id 0. .* belongs_to health_chart_t ype_cd contains 0. .1 stat us_cd 0. .* is_housed_at Pati ent_appoi ntm ent_request Durabl e_m edical _equipm ent_request quant ity_amt t ype_cd Indi vidual _healthcare_practi ti oner_request practit ioner_t ype_cd contains is_used_by 0. .* Person_alternate_name effect ive_dt cd nm reason_cd terminat ion_dt t ype_cd S takeholder_affiliate family_relationship_cd is_a_role_of takes_on_ role_of Resource_request allowable_substitutions_cd durat ion_qty start _dtt m is_request ed_by 0. .* start_offset _qty stat us_cd Appoi ntm ent_request appointment_rqst _reason_cd 1 requests appointment _rqs t_t ype_cd equip_select ion_criteria_pv id location_select ion_criteria_pv occurence_id 1 requests priority_cd repeating_interval_durat ion_qty requested_ri requests is_request ed_by rqst_event _reason_cd 1. .* 0. .* rqsted_durat ion_qty st art _dt Servi ce_schedul ing_request allowable_substitutions_cd t ime_select ion_criteria_pv durat ion_qty start _dtt m start_offset _qty stat us_cd Transcriptioni st 1 takes_on_role_of Stakeholder addr 1 takes_on_role_of is_assigned 1 credit_rating_cd email_address_t xt 1 may_act _as_a is_a_role_of 0. .1 1 takes_on_role_of takes_on_role_of 1 phon t ype_cd 1 takes_on_role_of participates_as_primary _in 1 0. .* has_as_primary_participant 0. .1 participates _in takes_on_role_of 1 0. .* refers_t o_person_by takes_on_role_of 1 1 collects takes_on_role_of 1 takes_on_role_of 1 0. .* has_as_secondary_participant participates _as_secondary _in is_related_to 0. .* may_be_contained_in transcribes 0. .1 issues 1 Identifier_issuing_authori ty effect ive_dt terminat ion_dt Producer_of_m aster_service service_producing_depart ment_t ype_cd 0. .* 0. .* pert ains_to Heal thcare_document_authenticator has_as_a_cont act 0. .1 0. .* is_associated_with 1. .* Consent Advance_di rective competence_ind directive_cd disclosure_level_cd life_qualit y_desc mortuary_preference_nm not arizat ion_dt assessment _dtt m employment_related_ind Encounter_practitioner participation_t ype_cd Care_event Procedure anesthesia_cd anes thesia_minutes _qty delay_reason_t xt inc ision_closed_dtt m incision_open_dtt m priority_amt procedure_cd proc edure_dtt m procedure_functional_t ype_cd procedure_minute_qty modifier_cd Treatm ent_servi ce_event prescript ion_id refills_remaining_qty notes_t xt PTrout PTc omp indic ation_cd expirat ion_dtt m subst ance_lot_number_t xt subst ance_manufact urer_cd collects 0. .1 0. .* is_part ic ipant_for 0. .1 is_request ed_by Treatment_service_dispense dispense_package_met hod_cd dispense_pack age_size_amt needs_human_review_ind rejec tion_reason_t xt s ubstit ution_cd suppliers_special_dispens ing_instruction_cd total_daily_dose_amt Treatm ent_servi ce_give administ ration_desc give_per_time_unit_cd give_quant ityt iming_qt give_rate_amt max_give_amt min_give_amt needs_human_review_ind subst itut ion_stat us_cd supplier_special_administrat ion_instruction_cd Treatm ent_servi ce_admi nistration administered_rate_t xt complet ion_stat us_cd substance_refusal_reason_cd s ubstit ution_cd s ystem_entry _dtt m Treatment_intent_or_order_revi sion dispense_package_met hod_cd is_part _of 1. .* dispense_pack age_size_amt give_indic ation_cd give_per_time_unit_cd give_rate_amt las t_refilled_dtt m max_give_amt min_give_amt needs_human_review_ind order_revision_PTc omp order_revision_PTrout order_revision_quant ityt iming_qt ordered_administration_met hod_cd prescript ion_id providers _administrat ion_instruction_cd refills_allowed_qty refills_dos es_dispensed_qty refills_remaining_qty subst itut ion_stat us_cd suppliers_dispens ing_instruction_cd total_daily_dose_amt total_daily_dose_cd 1 has_parts Assessment Clinical _observation abnormal_result_ind las t_observed_normal_values _dtt m nat ure_of_abnormal_testing_cd clinically_relevant_begin_dtt m clinically_relevant_end_dtt m observation_met hod_cd observat ion_stat us_cd observation_st atus _dtt m obs ervation_sub_id observat ion_value_t xt probability_amt references_range_t xt universal_servic e_identifier_suffix_t xt user_defined_access_check_t xt value_t ype_cd value_units_cd Goal action_cd act ion_dtt m c lass ific ation_cd current _review_stat us_cd current_review_st atus _dtt m episode_of_care_id est ablished_dtt m evaluation_cd evaluation_comment_t xt expected_achievement _dtt m goal_list _priority_amt life_c ycle_dtt m life_cy cle_stat us_cd management _discipline_cd next _review_dtt m previous_review_dtt m review_interval_cd t arget_t xt t arget_t ype_cd goal_cd Heal th_issue diagnosis_cd onset _dtt m billing_priority_amt severity_cd c lass ific ation_cd confirmat ion_stat us_cd persist ence_cd probability_amt probability_t xt prognosis_desc prognosis_awareness_desc cd Allergy allergen_id allergy_cd allergy_reaction_cd allergy _reac tion_desc ription_t xt allergy_severity_cd allergy_t ype_cd assessment _dtt m employment_related_ind Condition_node act ual_resolut ion_dtt m estimated_resolut ion_dtt m life_cycle_st atus _dtt m lifecy cle_stat us_cd management _discipline_cd ons et_t ime_t xt onset _dtt m ranking_amt employment_related_ind 0. .* specified_in 26 The BRIDG Model (a.k.a. PSM, DSAM, DAM) • Vision: Create a domain analysis model for the clinical research domain to harmonize clinical research standards among each other and to harmonize standards between clinical research and healthcare • A Key Goal: Define a structured computable protocol representation that supports the entire life-cycle of clinical trials protocol to achieve syntactic and semantic interoperability • Milestones: – January 2004 - Initiated by CDISC Board, with HL7 RIM expertise and leadership from Dr. Charlie Mead; followed HL7 Development Framework (HDF) – Contributions of resources from NCI, HL7 RCRIM, FDA, CDISC, NIH and others collaborated to create the Biomedical Research Integrated Domain Group (BRIDG) model – January 2005 – Adopted by HL7 RCRIM as Clinical Research Domain Analysis Model and posted on open source website – February 2005 – CDISC ODM mapped to HL7 RIM (collaborative effort among CDISC, NCI, HL7) 27 Mapping ODM to the RIM Sally Cassells, ODM Team Leader 28 CDISC and HL7: Why BRIDG? Level of Abstraction Domain Anaysis Model or Problem Space Model (a la HDF) RIM ODM 29 CDISC Standards Harmonization Protocol Data Sources Operational Submission Operational Data Database Data •Laboratories Harmonizing to THE CDISCInterchange Standard Interchange •Contract BRIDG: & Archive: •Study Data & Archive: Research SDS, ADaM •Audit Trail ODM, LAB Organizations SEND •Metadata •Development Partners • Site CRFs Submission Data •CRT/Domain Datasets •Analysis Datasets •Metadata ODM = Operational Data Model/Std SDS = Submission Domain Standards LAB = Laboratory Data Model/Std ADaM = Analysis Data Models SEND = Standards for the Exchange of Non-Clinical Data 30 CDISC Roadmap Timeline 31 Early BRIDG Implementations and Use Cases • NCI-CDISC: eData Collection Instrument (eDCI) Message Development • CDISC-HL7 Protocol Representation Group: Trial Tracking and Registries • NCI-CDISC: Clinical Trials Object Model (CTOM), a reference implementation of BRIDG to support collaborative research • FDA-NCI: CRIX Clinical Data Repository based on Janus, populated with SDTM data, with data accessible via BRIDG • caMATCH: Matching subjects to protocols – in implementation 32 cd Comprehensiv e Logical Model Design Concepts::Masking Clinical Trial Design + + + + level: objectOfMasking (set): procedureToBreak: unmaskTriggerEvent (set): Protocol Concepts:: Control HasSubElements AbstractActivity «Period» Design Concepts::Element Protocol Concepts::DesignCharacteristic Name: Author: Version: Created: Updated: Comprehensive Logical Model Fridsma 1.0 7/22/2005 2:53:51 PM 7/29/2005 2:33:32 PM + + + + + + Protocol Concepts:: Scope Protocol Authoring and Documentation - Protocol Concepts:: Configuration synopsis: type: test value domain = a,d,f,g summaryDescription: summaryCode: detailedMethodDescription: detailedMethodCode: Children: Set epochType: EpochTypes AbstractActivity displayName: char[] whoPerforms: int sequence: int procDefID: PSMCodedConcept sourceText: char[] SubjectEvent Protocol Concepts::StudyBackground(w hy) + + + + + + + + + + + hasElements hasScheduledEvents Design Concepts::PlannedTask - Protocol Concepts::Bias Design Concepts::Arm Design Concepts::ProtocolEv ent description: PSMDescription summaryOfPreviousFindings: PSMDescription summaryOfRisksAndBenefits: PSMDescription justificationOfObjectives: PSMDescription justificationOfApproach: PSMDescription populationDescription: PSMDescription rationaleForEndpoints: PSMDescription rationaleForDesign: PSMDescription rationaleForMasking: PSMDescription rationaleForControl: PSMDescription rationaleForAnalysisApproach: PSMDescription hasElements Protocol Concepts::StudyObligation + + + + 1 type: ENUMERATED description: PSMDescription commissioningParty: responsibleParty: Design Concepts:: Randomization + + Protocol Concepts:: Concurrency - - parent: AbstractActivity eventType: ScheduledEventType studyOffset: PSMInterval studyDayOrTime: char nameOfArm: char[] plannedEnrollmentPerArm: char[] randomizationWeightForArn: int associatedSchedules: Set tasksPerformedThisSchedule taskAtEvent hasOngoingEvents minimumBlockSize: maximumBlockSize: 1..* AbstractActivity +correlativeStudy 0..* Design Concepts::Ev entTask BusinessObj ects::Study BusinessObj ects:: ClinicalDev elopmentPlan -_DevelopmentPlan + + + + + + BusinessObj ects: :Amendment * - +primaryStudy 1 startDate: Date endDate: Date type: PSMCodedConcept phase: PSMCodedConcept randomizedIndicator: Text SubjectType: PSMCodedConcept localFacilityType: LocalFacilityType centralFacilitityType: CentralFacilitiyType eventID: OID taskID: OID purposes: Set - Protocol Concepts::StudyObj ectiv e(w hat) + + + + 1 + description: PSMDescription intentCode: SET ENUMERATED objectiveType: ENUM{Primary,Secondary,Ancillary} id: PSMID + + + + + + + + + + + + 1 1..* - BusinessObj ects:: ClinicalStudyReport description: BRIDGDescription ranking: OutcomeRank associatedObjective: Set analyticMethods: Set asMeasuredBy: Set outcomeVariable: threshold: - Design Concepts::Ev entTaskPurpose BasicTypes::StudyDatum isBaseline: boolean purposeType: PurposeType associatedOutcome: - type: +target 0..* complete: bool value: Value timestamp: timestamp itemOID: Defined By + + + + - «ODM:ItemData» Design Concepts:: SubjectDatum - «ODM ItemData» Design Concepts:: DiagnosticImage BasicTypes::RIMActiv ityRelationship BasicTypes::StudyVariable - «ODM:ItemData» Design Concepts:: TreatmentConfirmed 1 geographicAddress: electronicCommAddr: standardIndustryClassCode: 1 BusinessObj ects:: StatisticalAnalysisPlan + + + + - birthTime: sex: deceasedInd: boolean deceasedTime: multipleBirthInd: boolean multipleBirthOrderNumber: int organDonorInd: boolean + hasHypotheses relationshipCode: PSMCodedConcept sequenceNumber: NUMBER negationIndicator: BOOLEAN time: TimingSpecification contactMediumCode: PSMCodedConcept targetRoleAwarenessCode: PSMCodedConcept signatureCode: PSMCodedConcept signature: PSMDescription slotReservationIndicator: BOOLEAN substitionConditionCode: PSMCodedConcept id: PSMID status: PSMCodedConcept + + + + + + # jobCode: PSMCodedConcept -source activity + confidentialityCode: Entities and Roles:: Access Entities and Roles::Person significanceLevel: double lowerRejectionRegion: int upperRejectionRegion: int testStatistic: comparisonType: AnalyticComparisonTypes associatedSummaryVariables: BasicTypes::ActActRelation hasAnalysisSets hasAnalyses geographicAddress: maritalStatusCode: educationLevelCode: raceCode: disabilityCode: livingArrangementCdoe: electronicCommAddr: religiousAffiliationCode: ethnicGroupCode: kindOfActRelation kindOfAnalysis * Statistical Concepts:: StatisticalAssumption + - * Protocol Concepts::StudyObj ectiv eRelationship + type: PSMCodedConcept statement: PSMDescription associatedObjective: clinicallySignificantDiff: char AbstractActivity -_Hypothesis * hasAnalyses + description: PSMDescription analysisType: Set{AnalysisTypes} analysisRole: rationaleForAnalysisApproach: PSMDescription associatedStrategy: associatedHypotheses: * manufacturerModelName: softwareName: localRemoteControlStateCode: alertLevelCode: lastCalibrationTime: +contains 1 hasModel OStudy Design and Data Collection:: OBRIDGDeriv ationExpression BasicTypes::BRIDGInterv al + startTime: timestamp endTime: timestamp + + + + description: PSMDescription outputStatistic: StudyVariable computations: Set assumptions: Set + + + source: Text version: Text value: Text + + OProtocolStructure:: ResponsibilityAssignment code: TEXT codeSystem: codeSystemName: TEXT codeSystemVersion: NUMBER displayName: TEXT originalText: TEXT translation: SET{PSMCodedConcept} + + + BusinessObj ects:: EnrollmentRecord randomizationCode: subjectID: assignmentDateTime: alphaSpendingFunction: timingFunction: analysis: trialAdjustmentRule: effectiveEndDate: effectiveStartDate: statusValue: implements + + + + + + + name: TEXT value: controlledName: PSMCodedConcept businessProcessMode: PSMBusinessProcessMode type: PSMCodedConcept effectiveTime: BRIDGInterval usage: PSMCodedConcept «implementationClass» BusinessObj ects:: BusinessRule «implementationClass» Design Concepts:: ClinicalDecision description: PSMDescription algorithm: char input: AbstractStatisticalParameter output: AbstractStatisticalParameter hasSchedules BusinessObj ects:: SiteSubj ectManagementProj ectPlan 1..* 1 BusinessObj ects:: SiteStudyManagementProj ectPlan BusinessObj ects:: SponsorStudyManagementProj ectPlan 1 1..* BusinessObj ects::Inv estigatorRecruitmentPlan BusinessObj ects:: DataMonitoringCommitteePlan BusinessObj ects::BiospecimenPlan BusinessObj ects:: FinalRandomizationAssignment BusinessObj ects:: Waiv er BasicTypes::BRIDGContactAddr «abstraction» «implementationClass» Design Concepts:: TemporalRule AbstractActivity Statistical Concepts::Computation - OProtocolStructure:: Activ ityDeriv edData BusinessObj ects::Guide OStudy Design and Data Collection:: OEncounterDefinitionList--??? + + + Implements BusinessObj ects:: ClinicalTrialMaterialPlans BusinessObj ects:: RandomizationAssignment criterion: RULE eventName: TEXT Protocol Concepts::Constraint BasicTypes::BRIDGStatus run() : bool +passedTo +generates 0..* BasicTypes::BRIDGAnalysisVariable BasicTypes::BRIDGCodedConcept - implements Statistical Concepts:: SequentialAnalysisStrategy + + + + 1..* +targetActivity +sourceActivity 1 Protocol activities and Safety monitoring (AE) BusinessObj ects: : RegulatoryRecord type: ENUM{transformation, selection} rule: TEXT id: PSMID name: TEXT OStudy Design and Data Collection::OBRIDGTransition BasicTypes::BRIDGID isExclusive: bool + Statistical Concepts::StatisticalModel + # - Plans::Protocol/Plan modeValue: ENUM {Plan, Execute} - hasAssumptions hasComputations 1 BasicTypes::BRIDGBusinessProcessMode BasicTypes:: AbstractRule description: PSMDescription Statistical Concepts::Analysis + + + + # # Entities and Roles::Dev ice +IsContainedIn + «property» relationQualifier() : PSMCodedConcept «property» sourceAct() : AbstractActivity «property» destAct() : AbstractActivity kindOfAnalysis -_StatisticalAnalysisSet hasStrategy - + + + clinicalJustification: TEXT Statistical Concepts::Hypothesis hasChildAnalyses strain: genderStatusCode: description: BRIDGDescription relationQualifier: BRIDGCodedConcept mode: PSMBusinessProcessMode effectiveTime: BRIDGInterval priorityNumber: NUMBER negationRule: AbstractRule detail: char sourceAct: AbstractActivity destAct: AbstractActivity sequence: int AbstractActivity businessProcessMode: PSMBusinessProcessMode code: PSMCodedConcept derivationExpression: TEXT status: PSMCodedConcept +TerminatingActivity 1..* availabilityTime: TimingSpecification priorityCode: PSMCodedConcept confidentialityCode: PSMCodedConcept repeatNumber: rangeOfIntegers +EndEvent 1 interruptibleIndicator: BOOLEAN uncertaintyCode: CodedConcept +StartEvent 1 reasonCode: PSMCodedConcept Entities and Roles:: NonPersonLiv ingEntity + - + - Statistical Concepts:: SampleSizeCalculation +FirstActivity 1..* + + + + description: char subgroupVariable: StudyDatum sequence: int + BasicTypes::RIMActivity + + + + + + + + + + + OProtocolStructure:: ElectronicSystem lotNumberText: string expirationTime: stabilityTime: description: PSMDescription scopeType: AnalysisScopeTypes hasCriteria -source activity +target activity 1 Entities and Roles:: ManufacturedMaterial + - Statistical Concepts::HypothesisTest Entities and Roles::Patient - Statistical Concepts:: StatisticalAnalysisSet hasAnalysisSets evaluableSubjectDefinition: char intentToTreatPopulation: char clinicallyMeaningfulDifference: char proceduresForMissingData: char statSoftware: char methodForMinimizingBias: char subjectReplacementStrategy: char randAndStratificationProcedures: char Statistical Concepts::AnalysisSetCriterion Entities and Roles::Employee formCode: - - 1..* Entities and Roles::Material «ODM:ItemDef» Design Concepts:: PlannedObserv ation restates Objective * Entities and Roles::Activ ityRoleRelationship + + + + + * + + + + + + + OID: long Name: char unitOfMeasureID: OID minValid: maxValid: controlledName: ENUM relationshipCode: PSMCodedConcept sequenceNumber: NUMBER pauseCriterion: checkpointCode: splitCode: joinCode: negationIndicator: BOOLEAN conjunctionCode: 1 id: code: PSMCodedConcept name: status: effectiveStartDate: effectiveEndDate: geographicAddress: electronicCommAddr: certificate/licenseText: kindOfActivityRelation subjectID: int Statistical Concepts::StatisticalConceptArea * + + + + + + + + + roleInAnalysis: RoleInAnalysisTypes transactionType: - type: description: PSMDescription version: ID: SET PSMID * Entities and Roles::Role «ODM:ItemDef» Design Concepts:: PlannedInterv ention kindOf «abstract» Design Concepts:: StudyActivityDef BusinessObj ects:: SupplementalMaterial 1..* instantiationType: ENUM {Placeholder, Actual} id: SET <PSMID> 1 name: string code: PSMCodedConcept quantity: int description: PSMDescription statusCode: BRIDGStatus 1 existenceTime: BRIDGInterval riskCode: PSMCodedConcept handlingCode: PSMCodedConcept contactInformation: SET <PSMContactAddr> AbstractActivity isKindOf BasicTypes::AnalysisVariableInst associatedVariable «ODM ItemData» Design Concepts::Observ ation Entities and Roles:: Study Entities and Roles::Liv ingEntity Design Concepts:: StudyActiv ityRef Defined By as Measured By Entities and Roles::Entity Entities and Roles::Organization activityID: OID 1..* Protocol Concepts::Outcome BusinessObj ects:: ProtocolDocument effectiveEndDate: DATETIME version: author: SET effectiveStartDate: DATETIME ID: SET PSMID documentID: type: ENUMERATED = formal plus non... description: PSMDescription title: status: PSMStatus confidentialityCode: PSMCodedConcept businessProcessMode: PSMBusinessProcessMode + + + + + + + + + + + - «execution mode» Scheduled Sub Activities -source objective Protocol Concepts::StudyDocument + + + + + + + + + + + + eventType: UnscheduledEventType 0..* +source 1 gpsText: mobileInd: boolean addr: directionsText: positionText: SubjectEvent Design Concepts::UnscheduledEv ent - hasPurposes * Entities and Roles:: ResearchProgram + - hasUnscheduledEvents description: PSMDescription BusinessObj ects:: CommunicationRecord Entities and Roles::Place Periods: Set Tasks: Set TaskVisits: Set associatedArms: Set BusinessObj ects:: Activ itySchedule (the "how ", "w here", "w hen", "w ho") BusinessObj ects:: IntegratedDev elopmentPlan Clinical Trial Registration hasArms Design Concepts::StudySchedule + Protocol Concepts:: EligibilityCriterion listOfDataCollectionInstruments: Protocol Concepts:: Variance Protocol Concepts:: ExclusionCriterion BusinessObj ects: :ProtocolRev iew + + date: result: Protocol Concepts:: Milestone Eligibility Determination Structured Statistical Analysis BusinessObj ects:: DataManagementPlan BusinessObj ects::AssayProcedures BusinessObj ects:: Adv erseEv entPlan BusinessObj ects:: ContingencyPlan BusinessObj ects:: Subj ectRecruitmentPlan BusinessObj ects::SafetyMonitoringPlan 33 Patient Care World Clinical Research World An industry initiative that has successfully demonstrated clinical information interoperability between physician clinical systems and pharmaceutical clinical trials systems based on open standards. Data are collected once and subsequently rendered into multiple formats/systems using CDISC and HL7 standards – streamlines workflow. Single Source creates one “source record” for medical data collection regardless of purpose (patient care or research). Single Source opens the door for semantic interoperability 34 Patient Safety Institute/CDISC Proposed Single Source for Safety Monitoring in Clinical Care/Clinical Research EMR Provider A Provider B PSI Data Cache PSI Hub Provider C Clinical Trial Sponsor CONNECTIONS LEGEND: PSI provided connections (HIPAA compliant) Provider site connections (HIPAA compliant) Single Source overlay (21 CFR -11 compliant) Source: L. Bain 35 “The same EHR systems critical for improving patient care can also help accelerate clinical research and its impact on practice and improve pharmaceutical safety (pharmacovigilance) and biosurveillance for public health...dual use of EHR systems that could reduce total system costs.” Slide Courtesy Meredith Nahm 36 data conception Healthcare Delivery (e)Source Documents EHR eSource (e)CRFs Clinical Research auto reconciliation and archive Can we not make it easier for the investigative sites and ourselves to do clinical trials? 37 eSource Data Interchange (eSDI) • Purpose of eSDI Initiative – to facilitate the use of electronic technology in the context of existing regulations for the collection of source data in clinical trials for regulatory submission by leveraging the power of the CDISC standards, in particular the Operational Data Model (ODM). – Note: eSource pertains to eDiaries, ePRO, eDCI, Electronic Health Records… • Document Posted for Open Public Review and Comment by 17 October 38 Standard CRF Generation, Viewing Metadata and Data Review and Archive ODM XML XSLT Transformation ACRO: SDTM can provide standard content/format for standard CRFs ODM XML XSLT Transformation Source: Dave Iberson-Hurst, Assero 39 Data Flow Using CDISC Standard Linking Clinical Research and Healthcare = ODM (transport) Electronic Health Record = SDTM and Analysis Data (content) = Protocol information (content) Patient Info HL7 or ODM XML HL7 or ODM XML = Source data (other than SDTM/CRF data) Clinical Trial Data Protocol Representation Trial Design (SDTM) Analysis Plan Clinical Trial Protocol Patient Info ODM XML Clinical (CRF or eCRF) Trial Data (defined by SDTM) (e)Source Document Integrated Reports Administrative, Tracking, Lab Acquisition Info ODM XML CRF, Analysis Data Operational & Analysis Databases ODM XML Define.xml SDTM Data, Analysis Data, Metadata Regulatory Submissions 40 CDISC in the “World of Standards” 2003 International Conference on Harmonization (ICH) EFPIA JPMA EMEA MHLW KIKO U.S. Dept. of Health and Human Services (HHS) PhRMA U.S. FDA Protocol Std CDISC ADaM SDS ODM LAB MedDRA = Dictionary, Codelist NIH/NCI NLM DICOM TC: RCRIM Health Level 7 (HL7) Reference Information Model RIM = Standard ISO LOINC SNOMED Clinical Document Architecture eCTD = Organization CDC = Model = Document Standard, or Architecture 41 CDISC in the “World of Standards” 2005 International Conference on Harmonization (ICH) EFPIA JPMA EMEA MHLW U.S. Dept. of Health and Human Services (HHS) PhRMA U.S. FDA TC: RCRIM CDISC ADaM SDS ODM LAB MedDRA Protocol Representation NIH/NCI CDC NLM Health Level 7 (HL7) Reference Information Model RIM SNOMED LOINC CDA eCTD = Organization = Dictionary, Codelist = Standard = Model = Document Standard, or Architecture 42 CDISC in the “World of Standards” 2005 International Conference on Harmonization (ICH) EFPIA JPMA EMEA MHLW PhRMA U.S. Dept. of Health and Human Services (HHS) U.S. FDA NIH/NCI CDC NLM RCRIM Technical Committee CDISC ADaM SDS ODM Health Level 7 (HL7) LAB MedDRA Protocol Representation Reference Information Model RIM SNOMED LOINC CDA eCTD = Organization = Dictionary, Codelist = Standard = Model = Document Standard, or Architecture 43 CDISC in the “World of Standards” 2005 International Conference on Harmonization (ICH) EFPIA JPMA EMEA MHLW PhRMA U.S. Dept. of Health and Human Services (HHS) U.S. FDA NIH/NCI CDC NLM RCRIM Technical Committee CDISC ADaM SDS ODM Health Level 7 (HL7) LAB MedDRA Protocol Representation eCTD = Organization Reference Information Model RIM SNOMED LOINC CDA BRIDG Model = Dictionary, Codelist = Standard = Model = Document Standard, or Architecture 44 CDISC in the “World of Standards” 2005 World Health Organization (WHO) International Conference on Harmonization (ICH) EFPIA JPMA EMEA MHLW PhRMA U.S. Dept. of Health and Human Services (HHS) U.S. FDA NIH/NCI CDC NLM RCRIM Technical Committee CDISC ADaM SDS ODM Health Level 7 (HL7) LAB MedDRA Protocol Representation eCTD = Organization Reference Information Model RIM SNOMED LOINC CDA BRIDG Model = Dictionary, Codelist = Standard = Model = Document Standard, or Architecture 45 “ Politics are almost as exciting as war, and quite as dangerous. In war you can only be killed once, but in politics many times.” > Winston Churchill 46 CDISC Board/IAB/TCC Strategic Planning: Today’s Clinical Research Environment • More intense focus on patient safety and pharmacovigilance • Need for transparency of clinical information through publicly accessible registries and databases • Direct data capture tools are now available • Importance of interoperability • Increasing focus on electronic healthcare records 47 CDISC Board/IAB/TCC Strategic Planning • Board Committee, with input from Industry Advisory Board (3 Board Members, 2 IAB Cochairs, 2 Operations), is working on CDISC Strategic Plan 2006 – 08 • CDISC Technical Roadmap and Input from IAB, TCC (environment and needs) will be incorporated • To be completed by December 2005, with operational plan and budget • David Hardison, PhD will be Board Chair 2006 • Ed Helton, PhD will be Board Chair-elect 2006 48 Knowing is not enough; we must apply. Willing is not enough; we must do. - Goethe- To the gracious supporters who ‘apply’ and ‘do’…. THANK YOU! Rebecca Kush rkush@cdisc.org 49 Information and Contacts • For standards and information, see www.cdisc.org • eNewsletters available via e-mail; contact Shirley Williams swilliams@cdisc.org or sign up on the CDISC website. • Technical questions: Julie Evans jevans@cdisc.org or Public Discussion Forum • Education and Membership: Frank Newby fnewby@cdisc.org • Rebecca Kush: rkush@cdisc.org 50