EU Clinical Trials Register Proactive publication of clinical study reports – Policy 70 Clinical Trial Regulation and EU Portal and Database 29
Scope of clinical trial Regulation (EU) No. 536/2014 • Interventional clinical trials on medicines conducted in the EU/EEA (i.e. with at least one investigator site in EU/EEA) • Clinical trials authorized under the new Regulation or still ongoing three years after it comes into application 30
Processes for each stakeholders in the system This slide depicts the processes each stakeholder will be able to complete in the new EU Portal and Database: Submission of Union Control Submit submission package (CTA & Submission of CSR Reports dossier) / Address request for information Notification of willingness to be Commission Applicant of Update of Clinical Trial information RMS(Part 1)/Decision on RMS re non substantial modifications a MA Submission of requests for information Submit notifications: Withdrawal • Start of trial • Notification of the final validation First visit first subject • (initial, additional MS or End of recruitment • Substantial Modification) End of trial (in each MS, All MS, • Global) Member Sponsors Temporary halt • Submission final AR Part 1 and 2 States Restart of trial • Early termination • Serious Breaches Final single decision notification • Unexpected events which • affect risk/benefit Submission Inspection Information Search and view CT related information saved in the EU Submission of clinical study result Communication disagreement to database (that is not summary General public part 1 assessment confidential) Runs the system and Submission of Inspection Reports EMA Communication on implementation generates reports on the of third country authorities of corrective measures data in the system 31
EU portal and database – Data standardisation WHO ICTRP standard will be fully met, and data provided to WHO the ICTRP by the EU database Collaboration and discussion on the anticipated changes to the NIH data model (focusing on protocol / results) to ensure convergence and alignment where the same elements are (clinicaltrials.gov) used in both US and EU systems Collaboration on clinical trial registration including study design CDISC data model, and in due course on results model 32
Transparency legal requirements: Clinical Trials Regulation Article 81(4) of Regulation (EU) No. 536/2014 • EU database publically accessible by default, with exceptions justified on any of the following grounds: – Protection of personal data; – Protection of commercially confidential information in particular taking into account the MA status of the medicinal product, unless there is an overriding public interest in disclosure; – Protecting confidential communication between MS in relation to the preparation of the assessment report; – Ensuring effective supervision of the conduct of a clinical trial MSs. 33
• Appendix, on disclosure rules, to the “Functional specifications for the EU portal and EU database to be audited - EMA/42176/2014” • Endorsed on 2 October 2015 by EMA Management Board and published on 6 October 2015 http://www.ema.europa.eu/docs/en_GB/ document_library/Other/2015/10/ WC500195084.pdf 34
Requirements for operation of a feasible system To enable public access to the database, rules for the application of the exceptions, set out in • Article 81(4), are required. Rules, criteria and data to enable the system software to determine, automatically, when a • particular data element or document should be made public. Automatic rules are necessary because there will be 4-5000 clinical trial applications, dozens • of documents and hundreds of data fields per clinical trial and multiple processes per trial taking place in the system every year. Rules designed to produce a consistent and predictable outcome so that those submitting • data and documents and those viewing them know what will be made public and when. A manual override available to enable earlier publication in exceptional circumstances where • an overriding public interest applies, or to remediate a publication error. 35
Summary of rules The same rules apply whether the sponsor is a pharmaceutical company, academic research • group or other type of organisation. The rules depend on the IMPs used in a trial and how they are used. • Trials defined as belonging to one of three categories, at the time of initial assessment of the • clinical trial application: – Category One: Pharmaceutical development trials– essentially Phase I trials in healthy or patient volunteers, bio-equivalence and bio-similarity trials. – Category Two: Therapeutic exploratory and confirmatory trials - essentially Phase II and III trials of novel products or new indications or formulations of existing products – Category Three: Therapeutic use trials – essentially Phase IV and low-intervention trials Depending on the category of trial the sponsor will have the possibility to defer publication of • certain data and documents up to a maximum time limit, if needed, to protect commercially confidential information. The use of deferrals will be monitored and should not exceed what is really needed. • 36
Summary of Rules Public registration of trials at their start including all information needed for patients who may • wish to participate in trials with therapeutic, diagnostic or preventive objectives. Publication of results of all trials (structured summary, layperson summary and in case of • Marketing Authorisation Application in the EU the clinical study report). The structured summary of results and laypersons summary will be made public 12 months • after the end of each trial, regardless of the Marketing Authorisation status of the medicines studied in the trial. Only possibility of justified deferral for summary results in case of category I trials up to a • maximum of 30 months post end of trial (i.e. maximum 18 months deferral). Detailed rules for dossier documents linked to category of trial • 37
Summary - Clinical Trial Transparency – and EMA • Clinical Trials authorised in EU/EEA: – Growing body of clinical trial information and results summaries in EU Clinical Trial Register for trials authorised since 2004. – New clinical trial Regulation - Extensive information on clinical trials from authorisation to the trial summary results of all trials authorised in EU/EEA under the new Regulation. • Clinical Study Reports submitted in Marketing Applications in EU: – All clinical study reports included in marketing applications to EMA from 1 Jan 2015 on – Clinical study reports for all trials authorised in EU/EEA under the new clinical trial Regulation and included in a marketing application in EU. 38
Thank you for your attention Public data and information about medicines, their development and authorisation • Generate trust – information is available; • Build confidence – I understand what is happening; • Empower – knowledge enables decision-making Fergus.Sweeney@ema.europa.eu Further information European Medicines Agency 30 Churchill Place • Canary Wharf • London E14 5EU • United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact Follow us on @EMA_News
Governance Workgroup Rebecca Li, PhD Moderator: Barbara Bierer, MD March 21, 2016
Data Sharing Strategy Phase: Governance • Working Group Main Objec2ves: Develop a high-level charter MRCT Governance Develop principles for organiza4onal Working Group leadership • Governance • Scope and exper2se Informa2on Technology (IT) • Opera2ng guidelines Working Group Strategic policy decisions • PlaUorm Business • Governance Models • Communica2on Working Group 4/5/16 41
Workgroup Deliverables • Key Workgroup Deliverables: – Governance structure – Review Process – PlaUorm par2cipa2ng trials – Data packages – Data Sharing guidance and resource kit 4/5/16 42
Proposed Organiza2onal Structure for Non Profit Vivli Board of Directors President / Exec Director Advisory Technical Finance & Audit External Advisory CommiJee CommiJees CommiJee 4/5/16 43
Proposed Governance Model: Hybrid • Func2onal Hybrid Model – Incorporated as Non-profit Organiza2on – Membership of the Board is combina2on of representa2on of contributors to the organiza2on (ojen financial) and “at-large” posi2ons – Representa2ves can be nominated by a contributor, subject to approval of the board (ojen termina2ng when organiza2on is financially stable and independent) – At-large members, appointed by the nomina2ng commiJee of the Board (ajer ini2al appointment) according to personal investment in the project, e.g: • Academic representa2on • Government • Pa2ent/Pa2ent Advocate, etc. 4/5/16 44
Workgroup Deliverables • Key Workgroup Deliverables: – Governance structure – Review Process – PlaUorm par2cipa2ng trials and data packages – Data Sharing guidance and resource kit 4/5/16 45
Review Process Proposal Vivli will act as a “data library” which respects the needs of requesters and concerns of donors Several review op2ons for shared data were developed: • Tier 1: Data generator would donate data which would not require a review process. • Tier 2: Data generator would cede review to the plaUorm’s selected IRP. • Tier 3 3: Data generator will maintain own review process. PlaUorm will forward requests for review. 4/5/16 46
Data Request Model: Phase 1 4/5/16 47
Data Request Models: Aspira2onal 4/5/16 48
Workgroup Deliverables • Key Workgroup Deliverables: – Governance structure – Review Process – PlaForm parHcipaHng trials and data packages – Data Sharing guidance and resource kit 4/5/16 49
Par2cipa2ng Trials and Par2cipants • What defines a parHcipaHng trial on the plaForm? – Registered in ClinicalTrials.gov, WHO ICTRP or other trial register – Metadata (searchable terms) for par2cipa2ng trials are available and curated – IPD is or will be made available • PlaUorm will not be prescrip2ve in the types of trials or datasets that will be included and where appropriate link to exis2ng guidance and regula2ons. • Par2cipa2ng trials - at a minimum we encourage the inclusion of large pivotal trials of marketed products 4/5/16 50
PlaUorm Par2cipa2ng Trials (e.g Sponsors) PlaUorm curates IPD 250 trials metadata for SHARED the 250 trials Sponsor no,fies Review process Searchable pla0orm of # of terms match par,cipa,ng trials available IPD 4/5/16 51
PlaUorm Par2cipa2ng Trials (e.g. Publica2on-based) Submission to PlaUorm • IPD / Data • Publica2on Package and prepared for • Data Package Publica2on held submission Prepared for in Embargo PlaUorm (anonymized) Ar2cle Published Submission to Journal & Data available on plaUorm 4/5/16 52
Data Packages – What to share? • A Data package is the set of data and associated materials about a study that is to be shared via the PlaUorm May include: • Analyzable individual par2cipant-level dataset (IPD) • Final study protocol + amendments • Sta2s2cal analysis plan • Annotated case report forms • Analy2c code suppor2ng the published results • Redacted CSR 4/5/16 53
Data Packages – Recommenda2ons Basic Package (recommended for inclusion) • Analyzable individual parHcipant-level dataset (IPD) • Final study protocol + amendments • StaHsHcal analysis plan May also be included if available to share: • Annotated case report forms • Analy2c code suppor2ng the published results • Redacted CSR A checklist will be available by the pla0orm to provide op,ons 4/5/16 54
Workgroup Deliverables • Key Workgroup Deliverables: – Governance structure – Review Process – PlaUorm par2cipa2ng trials and data packages – Data Sharing guidance and resource kit 4/5/16 55
Data Sharing Resource Kit (See Appendices) • Data Use Agreement • Data Contributor Agreement • ICF 4/5/16 56
Successful Case Studies of Secondary Use of Data Data Recipient Data Generator Impact Reanalysis of the RAVE trial demonstrated a correla2on (1) ITN Network – Inves2gators at the Ins2tute for between pa2ent’s granulocyte subsets at baseline with the Computa2onal Health Sciences, University RAVE Trial – NIAID likelihood of remission at 6 months following either of California, San Francisco (funder) cyclophosphamide or rituximab in pa2ents with ANCA- Associated Vasculi2s. Inves2gators at the University of In a post-hoc analyses of 18 trials of SSRIs u2lizing a single (2) Pfizer, GSK, ra2ng scale versus the Hamilton depression ra2ng scale, SSRIs Lundbeck Gothenberg, Sweden, Swedish Research were shown to be more consistently effec2ve than placebo in Council (funder) the treatment of pa2ents with major depression. Metaanalysis of 4 trials demonstrated that, for pa2ents with (3) Medtronic – YALE Inves2gators at the University of Colorado degenera2ve disc disease following lumbar arthrodesis, the Department of Orthopedics YODA (intermediary) presence of radiographic fusion was correlated with improved clinical outcomes compared to radiographic non-union (Oswestry Disability Index - ODI; Numeric Ra2ng Scales (NRS) for back and leg pain). Inves2gators at University of Bern; Metaanalysis of 18 trials (13,933 pa2ents) demonstrated that (4) J&J, Amgen, administra2on of erythropoiesis-s2mula2ng agents in oncology Hoffman-LaRoche pa2ents increased mortality compared with transfusion German Federal Ministry of Educa2on and and 5 independent therapy alone. The increase in mortality must be balanced Research, Medical Faculty of University of against the poten2al benefits of erythropoiesis -s2mula2ng inves2gators Cologne and Oncosuisse (funder) agents in this pa2ent popula2on. (5) Pfizer, Sanofi Mitoxantrone added to prednisone in the treatment of Inves2gators at University of North pa2ents with post-docetaxel, metasta2c, castrate-resistant Carolina prostate cancer showed no survival benefit over the use of prednisone alone and may be associated with increased 57 toxicity.
The MRCT Center’s Data Sharing Workgroup Members Governance Work Stream Co-Chairs: MRCT Center Wellcome Trust Arnold FoundaHon Team Members: Heather Marino (MRCT Center) Mark Barnes (MRCT Center) Sandra Morris (Johnson & Johnson) Barbara Bierer (MRCT Center) Jennifer O’Callaghan (Wellcome Kris Bolt (MRCT Center) Trust) Stuart Buck (Laura and John Arnold Nicola Perrin (Wellcome Trust) FoundaHon) Paul Seligman (Amgen) Marla Jo Brickman (Pfizer) Ida Sim (UCSF) Nina Hill (Pfizer) Jessica ScoJ (GlaxoSmithKline) Lauren Johnson (MRCT Center) Catrin Tudur Smith (U. of Liverpool) Rebecca Li (MRCT Center) Natalie Zaidman (Pfizer) Nick Lingler (DeloiSe ConsulHng) 4/5/16 58
Ques2ons and Discussion 4/5/16 59
Business Models Workgroup Presenter: Rohin Rajan, DeloiJe Consul2ng LLC Moderator: Frank Rockhold, Duke University 4/5/16 60
MRCT Clinical Trial Data Sharing Business Model Working Group Outputs March 2016
Executive Summary Background and context
Key objectives for the Wellcome Trust / MRCT Business Models workstream 1) To develop sustainable business models for Vivli 2) To align with the governance and IT workgroups on how to best to develop and capacitate the not-for-profit entity , including in regard to its financial viability 63
Framework and Approach Landscape Capabilities Operating Model Timeline Performed an external Defining high-level Define potential Determine near-term scan of existing clinical functionality and operating models that and long-term What we trial data sharing capabilities of the would enable the opportunities to flexibly did technologies and desired platform / capabilities required for evolve Vivli platforms system / entity Vivli Determine existing Define starting point for Determine optimal Develop a viable and market capabilities, the development of execution modes sustainable business Why we gaps and short-term Vivli’s business model based on cost, speed, model to address did it needs; validate scope risk, revenue streams gaps, seek out of Vivli potential partners, and build as needed Context Discussion Proposals discussed in the Business Models workstream need to be aligned to IT and Governance workstreams to finalize operating model and timeline Platform = interconnected or consolidated system for data cataloguing, housing and sharing System = IT infrastructure to support utilization of the platform 64 Entity = future organization to manage the platform and systems
Assumptions and considerations § Should be a “not-for-profit” organization, but can collaborate with for and non-profit companies § Requires sustainable support (resources, funding) from industry, academics and other stakeholders § Over the next 18 – 36 months, the objective is to create valuable offerings to attract users and define opportunities for growth § Cannot reinvent technologies already in place; but in the near-term, potentially: – Connect existing platforms in an extensible and collaborative manner – Improve interoperability by facilitating data warehousing, integration, and curation – Create a marketplace for academic researchers and smaller, non-participating companies § Revenue opportunities will be evaluated continuously as offerings become mature § Long-term, Vivli may be able to unify various data sources into a single multifaceted platform 65
Key findings from the external scan § The scan revealed that numerous initiatives either exist or have been created § No single effort has become the ‘silver bullet’ § Several major biopharmaceutical companies are involved in at least two data sharing initiatives § Smaller players and academics do not have similar modes for sharing clinical trial data 66
Objectives for today’s Business Model presentation § Consider and discuss the various operating models presented; determine if other, distinct models exist § Review and align on near, mid and longer-term options for the evolution of Vivli § Discuss and determine which functional capabilities can be achieved through (post presentations): – Partnerships with existing systems or platforms – Assembly and coordination of current marketplace offerings – Creation / development of unique services and capabilities 67
Executive Summary Overview of potential operating model options
Potential data sharing operating models A number of different routes could be taken to achieve the goal of increasing clinical trial data sharing & creating a data aggregation platform Advocate & Build & Assemble Partner Lobby Develop Engage in advocacy for Find, support, and Identify and partner policy and practical functionalize specific with existing changes to increase solutions to address initiatives (e.g. Build and develop transparency and existing and Project Data Sphere, capabilities as cooperation in clinical emerging gaps in CSDR) to enable needed to facilitate the trial data sharing with clinical trial data immediate access to exchange of clinical existing efforts sharing, to facilitate current capabilities / trial data (platforms / systems / exchange between functionality as a regulators, other platforms foundation for growth stakeholders) Assumptions § Generalized options to be aligned to specific IT and Governance goals and partnership opportunities § Options not mutually exclusive, and could be reconfigured to meet evolving needs § “Advocate and Lobby” model would continue throughout the evolution of Vivli § “Advocate and Lobby” option does not comprise a data sharing entity, and could be an extension of MRCTs 69
Operating model dimensions Operating models were evaluated using a set of comparison dimensions Advocate & Build / Assemble Partner Lobby Develop Capability • Technological capabilities offered by Vivli to facilitate data sharing across multiple stakeholders Dynamism • Flexibility / elasticity with which Vivli can quickly shift strategic priorities based on the market Investment • Up-front capital and ongoing operational investments to fund Vivli • Data Contributors: risk of providing data to stakeholders who may undermine efficacy and safety of sponsor’s drug leading to regulatory action and / or revenue losses • Data Users: risk of using data that may not be accurately collected, cleansed, integrated and Stakeholder associated implications on users reputation and credibility Risk • Vivli: risk of losing the reputation as a credible, trusted and impartial curator of clinical trial data and inability to sustain profits over the long term; also risk of competition to existing entities / Vivli depending on operating model and capabilities chosen Control • Ability to exercise direct control over the direction of technological capabilities and services Time to build • Speed with which the solution can be implemented / achieved 70
Advocate & Lobby Engage in advocacy, lobbying for policy and practical changes to increase transparency and cooperation in clinical trial data sharing with existing efforts (platforms / systems / regulators and other stakeholders) Advocate & Build / Assemble Partner Lobby Develop Less Favorable More Favorable Ranking Detail Capability • Low capability to directly expand clinical trial data sharing • Opportunity to quickly react to changing trends and dynamics in data Dynamism sharing, and influence the broader environment Investment • Limited investment needs to cover communications / marketing efforts • Low risk level as Vivli will not directly facilitate data sharing, but may not Stakeholder address the needs of stakeholders leaving Vivli with reputational Risk consequences Control • Lowest control given role limited to advocacy / engagement Time to build • Efforts largely underway already as part of MRCT scope and mission 71
Assemble Find, support, and functionalize specific solutions to address existing and emerging gaps in clinical trial data sharing, to facilitate exchange between platforms Advocate & Build / Assemble Partner Lobby Develop Less Favorable More Favorable Ranking Detail • Vivli may not be the central platform for data sharing, but offer capabilities Capability that facilitate sharing by addressing current gaps • Operating model is focused on reacting to changing dynamics and new Dynamism trends in clinical trial data sharing, and to find / fund evolving solutions Neutral Investment • Investment need could vary and would be at Vivli’s volition • Risk due to unpredictability of investing in and / or effectively connecting 3 rd Stakeholder party solutions and driving value Risk • Risk to existing platforms by means of disruption / loss of autonomy • Limited choice over existing solutions / platforms given position as a third Control party, but control achieved through customization and coordination • Accelerated timeframe as efforts would target existing data sharing Time to build technologies, but still may take time to derive and build solution 72
Partner Identify and partner with existing initiatives to enable immediate access to current capabilities / functionality as a foundation for growth Advocate & Build / Assemble Partner Lobby Develop Less Favorable More Favorable Ranking Detail • Partnering would secure existing technical capabilities, with additional build Capability conducted as needed (including to achieve interoperability) • Ability to chose a platform / system as desired, but flexibility (initially) is Neutral Dynamism limited to capabilities offered by the platform / system • Upfront investment to secure partnership, with further investment variable Investment (depending on level of upgrade targeted) • Could leverage non-profit status to enhance investment negotiations • Risk exposure from required upfront investment Stakeholder • Adaptability of current capabilities for further customization & interoperability Risk needs • Ability to select the platform / system with existing capabilities and potential Control for customization • Fastest route to access current capabilities and create a foundation for Time to build enhancements 73
Build / Develop Build and develop capabilities as needed to facilitate the exchange of clinical trial data Advocate & Build / Assemble Partner Lobby Develop Less Favorable More Favorable Ranking Detail • Capabilities can be developed and customized as needed based on current Capability gaps, best practices from existing solutions, and stakeholder needs Dynamism • Limited flexibility and ability to adapt model once build is underway • Significant resource / capital investment required to build model and develop Investment technological solution • High capital outlay Stakeholder • Potential duplication of systems and platforms already in existence Risk • Competition for users / unclear value proposition / differentiation Control • High degree of control afforded to Vivli to customize solution as needed • Significant time required to design, source, and build solution Time to build • Prime target for disruption as other, well-positioned companies able to deploy solutions over a faster timeline 74
Comparison across dimensions Advocate & Build / Assemble Partner Lobby Develop Less Favorable More Favorable Dimension Rankings Capability (N) Dynamism (N) Investment Stakeholder Risk Control Time to build Cumulative 75
Learnings from the operating model comparison § The “Build” option offers greatest control – “Partner” & “Assemble” models could achieve similar capabilities more flexibly, faster and at lower cost – “Partner” offers established capabilities and contain the largest data-sets – Certain unique capabilities may require build as they are currently unavailable not suitable in current form (e.g. due to cost, capabilities, content etc.) - to be discussed post IT presentation § The “Advocate and Lobby” option is the lowest investment and could be an extension of MRCT – Offers no technological capabilities in the near-term, but serves to align other initiatives and grow users – As a lobbying entity, can influence the key technology, service and regulatory priorities 76
Executive Summary Potential near / medium term operating model evolution & revenue considerations
Proposed timeline for the evolution of Vivli Near-term (0 – 6 mos) Mid-term (6 – 18 mos) Long-term (18 - 36+ mos) Advocate & Lobby Determine viability of next step Partner Assemble Build / Develop (as needed) § Clearly define mission, scope, and § Agreements / partnerships § Substantial and growing user base timeline for Vivli achieved with other data sharing § Technological capabilities organizations § Widespread awareness and buy in established to facilitate data to Vivli’s mission amongst the § Clearly defined scope / roles and sharing broader industry stakeholders responsibilities between Vivli and § Sufficient revenue flow to sustain (academics, regulators/ editors complementary organizations ongoing operations of Vivli etc.) § If possible Vivli will endeavor to not achieved § Service offerings and revenue be in “addition to” existing targets identified platforms but will assume their role/ services to reduce burden § Participation / sign on by biotechs & academic organizations 78
Timeline Details: Near-term – 0 to 6 months 0 – 6 Months 6 – 18 Months 18 – 36+ Months Advocate & Lobby Key Considerations / Requirements Investment Required (annualized) § Screen potential targets for partnership / assembly; conduct § Capital: 0 capability gap analysis § Operational: 2-2.5 FTEs ~ $400 – 500K – Leadership: 1 FTE § Achieve partnership with a major data sharing platform – Project manager: 1 FTE § Identify required investment level, revenue sources, and – SME: 1 FTE (mix of partial or full-invested time) operating model of Vivli § Determine scope of Vivli – Type of companies / willingness to participate – Type of capabilities targeted (technology, services) Potential Revenue Streams – Scope / type of data to be shared § Align with ongoing industry data sharing platform / effort § Grants and donations § Establish a clear value proposition for Vivli § Create a detailed project plan for Vivli § Seek immediate implementation to support gaps (e.g. for academic ICMJE compliance) if needed 79
Timeline Details: Medium term – 6 to 18 months 0 – 6 Months 6 – 18 Months 18 – 36+ Months Partner & Assemble + Advocate & Lobby Key Considerations / Requirements Investment Required (annualized) § Facilitate transition / partnering of existing platform to Vivli § Capital: $5M - $10M § Operational: 19 – 25 FTEs ~ $2M – $4M* § Launch cross-platform services by facilitating connectivity – Leadership / management: 5 FTEs (3 from prior stage and uniformity of approach (IRP, DSA etc) plus two additional) § Achieve user base growth / positive indications for user base – Technology: 5-7 FTEs growth for cross-platform/academic data) – Service: 3-5 FTEs § Create and release RFP to conduct technology build – Operations: 6-8 FTEs § Enact detailed project plan (earlier in phase) § Begin to defining services and capabilities for which Vivli may Potential Revenue Streams be able to generate revenue (e.g. data warehousing for academics) § Grants and donations § Proposal Review & Refinement § Data repository services for academics and § Pay Per Use / Request others § Data retrieval § Data Anonymization / § Value add services De-identification § Rare disease populations § Data submission support § Advertising services 80 * For off-the-shelf purchases, vendor FTEs could be included, reducing total number of projected FTEs § Annual Subscription
Timeline Details: Longer term – 18 to 36+ months 0 – 6 Months 6 – 18 Months 18 – 36+ Months Build / Develop + Partner & Assemble Advocate & Lobby Key Considerations / Requirements Investment Required (annualized) § Expand technological capabilities to improve efficiency and § Capital: TBD capability of platform § Operational: TBD – Leadership / management: 5+ FTEs (TBD) § Achieve sustainable revenue generation – Technology: 7+ FTEs (TBD) § Increase industry / academic organization participation – Service: 5+ FTEs (TBD) § Expand service offerings – Operations: +8 FTEs (TBD) § Proceed with detailed project plan § Interface / engage with regulators this should be in lobby/ advocate and should be earlier Potential Revenue Streams § All revenue streams from prior phase § Access to Tools § Customized report generation services 81
Revenue considerations & proposed approach § Over the next 36 months “revenue” should refocused towards grants and charitable donations – If near-term includes support for ICMJE requirements, earlier revenue options may available § The rationale is as follows: – Services will take time to launch, and should be refined and enhanced before charging users – Services and capabilities should be extensible for interoperability with Vivli / other platforms – The barrier to entry for investigators should be kept low – Time will allow positive interactions with partners, reviews and press coverage of effort to build – Prices should be in-line with what industry and stakeholders are willing to pay – “Non-profit” title will facilitate collaboration and should de-incentivize competition § Once a substantial user base / repository size is established revenue generation can be expanded 82
Executive Summary Summary & next steps
Summary § Building a technology will require significant effort and investment and may not allow flexibility to change directions if the marketplace changes dynamically § Assemble and Partner offer significant flexibility for marketplace demands / disruptions and may be cheaper, faster options in the near-term § In the immediate-term (~6 months), the lowest risk option is Advocate and Lobby with an emphasis on working towards an Assemble and Partner model § Despite feasibility of launching revenue streams in the medium term (6-18 months), focus on securing grants, donations, and other philanthropic sources of support 84
Key questions for discussion Potential operating model options: Are there other operating models that could be perceived as distinct from the ones presented? § Does the group agree on the choices and tradeoffs therein? § Near term operating model evolution: Does the near term evolution of Vivli seem sensible? § Are there assembly / partnership activities we can take on in the near term? What other near § term considerations should we keep in mind? What capabilities do we want to focus on to achieve: § – Partner? – Assemble? – Build? Can the build stage begin during an earlier phase than currently targeted? 85
Data Sharing Workgroup Members Co-Chairs: Wellcome Trust and MRCT Center Team Members : § Mark Barnes (MRCT) § Barbara Bierer (MRCT) § Patrick Cullinan (Takeda) § Rob Frost (GSK) § Rebecca Li (MRCT) § Peter Lyons (Deloitte Consulting) § Nicola Perrin (Wellcome Trust) § Rohin Rajan (Deloitte Consulting) 86
Executive Summary Appendix
Potential evolution of Vivli’s operating model 0 – 6 Months 6 – 18 Months 18 – 36+ Months Advocate & Lobby Partner Assemble Build / Develop § Engage in advocacy § Begin developing functionality to § Build additional add-on functionality enable Vivl’s vision and mission (as desired) and improve and expand § Align with other industry efforts service offerings § Create partnerships with other § Engage with other clinical trial data platforms / data sharing organizations § Refine and operationalize the sharing platforms platform § Launch data sharing and value-add § Screen other platforms for assembly / services § Increase user base and frequency of partnership potential use of platform § Define additional desired add-on § Define platform and specifications for functionality requiring further build § Streamline process and reduce Vivli Vivli’s efforts to expand / host clinical burden for all through technology Imperatives trial data sharing § Engage with biotechs / academics (donators and requestors) & Goals and garner buy-in / participation § Begin scoping potential IT “build § Launch efforts to monetize and/or needs” and identifying services Vivli § Begin facilitating exchange of data generate revenue to sustain Vivli will provide with and between non-participating biotechs / academics § Test viability of existing revenue § Identify preliminary targeted revenue streams and determine new streams for Vivli § Facilitate alignment with other data opportunities sharing efforts § Socialize data sharing ecosystem with non-participating pharma / biotechs / academics § Define mission, scope, and timeline § Agreements / partnerships achieved § Substantial and growing user base to establish Vivli with other data sharing organizations § Technological capabilities established § Widespread awareness and buy in to § Clearly defined scope / roles and to facilitate data sharing Vivli's mission amongst the broader responsibilities between Vivli and § Sufficient revenue flow to sustain industry/stakeholders (academics, complementary organizations Critical ongoing operations of Vivli achieved regulators/editors etc) Success § If possible Vivli will endeavor to not Factors § Service offerings and revenue targets be in “addition to” existing platforms 88 identified but will assume their role/services to reduce burden
EMA Policy 70 Implementa2on Presenter: Frances NuJall, European Medicines Agency 4/5/16 89
European Medicines Agency Policy on publication of Clinical Data for medicinal products for human use (policy 0070) MRCT CENTRE – Wellcome Trust meeting The Future of Clinical Trial Data Sharing Frances Nuttall, Senior Policy Adviser, EMA, 21 March 2016 An agency of the European Union
Policy purpose + objective To date : • Access to Documents – individual request, route continues New policy: • 2 October 2014, Clinical Data Publication (human medicinal products) What is it : • Public presentation of clinical data, clinical reports • Transparency, continued EMA commitment, regulatory decision basis of medicinal products • Proactive publication enables public scrutiny: establishes trust, confidence • Better public information: Public access enables application of new Benefits: knowledge in future research, increases efficiency of medicine development, learning from experience • Avoids clinical trials duplication: limits unnecessary patient exposure • Enhanced scientific knowledge/value of secondary analysis: sharing scientific knowledge, contribution to public health, confirmation of regulatory decisions/need to review regulatory decisions taken. 91 Clinical Data Publication policy
Clinical data publication policy & Clinical Trial Regulation Clinical data publication Clinical Trial policy Regulation Clinical data publication policy: Clinical Trial Regulation: EU all the clinical reports (trials clinical trials located in EU or non EU) in the regulatory submission to EMA 92 Clinical Data Publication Policy
Clinical Data Publication Policy scope 1 January 2015: Marketing 1 July 2015: authorisation extension of applications Policy effective: 2015 indication and • Withdrawn line extensions applications pre opinion included - Innovation To add later: post authorisation regulatory categories Not in scope: Legacy data, pre 2015 93 Clinical Data Publication policy
Policy implementation Two phase implementation • Clinical reports = clinical overview, clinical summary, clinical study reports, protocol & amendments, sample case report form, Phase I documentation of statistical methods • EMA is working on Phase I implementation • Individual patient data (IPD) • To approach later Phase II 94 Clinical Data Publication policy
Clinical Data Publication Guidance Introduction, scope, definitions External guidance on the procedural aspects related to the submission of clinical reports for the purpose of publication in accordance with EMA policy 0070 Guidance on the identification and redaction of commercially confidential information (CCI) in clinical reports submitted to the EMA Guidance to pharmaceutical industry on the anonymisation of clinical reports for the purpose of publication in accordance with EMA policy 0070 Published on EMA website: 3 March 2016 95 Clinical Data Publication Policy
Clinical reports public presentation Commercially confidential information (CCI) EMA position: majority of clinical report content is not CCI Redaction principles set out in the policy The company justifies each redaction, EMA reviews redactions & decides if accepted or not Anonymisation Data utility: important for researchers, EMA encourages utmost data utility, balance to protect personal data, EMA guidance recommends methodology to avoid (re)identification of clinical trial participants, various techniques, evolving area. Anonymisation report: requirement, reviewed by EMA + published, shows the company’s approach for the specific case. 96 Clinical Data Publication policy
Access to clinical data published General information purpose: Academic/non-commercial research View on screen only (no save, download, purpose: § print, copy). Save, download, copy etc. • Digital rights management applied. § Text searchable. • Text searchable. § More personal data on registration. • Minimum user registration requirement. § Specific Terms of Use • Specific Terms of Use § Watermark: The EMA applies a watermark to the clinical reports before their publication to emphasise the prohibition of their use for commercial purposes The watermark text is: “www.ema.europa.eu This document cannot be used to support any marketing authorisation application and any extensions or variations thereof” 97 Clinical Data Publication Policy
Watermark Samples These examples follow how the watermark will be presented on the published information 98 Clinical Data Publication Policy
Preparation to Go-Live Operational start up beginning Learning curve for all parties EMA will contact the first company with a product coming under the policy granted a CHMP opinion (September 2015). EMA will work forward chronologically from this point. It will take time to recover the ‘waiting list’ . Other companies are being informed to wait, for now, until EMA contacts them . 99 Clinical Data Publication Policy
Implementation status + issues Go live current • End September 2016 forecast: • Download + View only permanent public access linked to the relevant Public website: regulatory decision • Industry co-operation • Data utility: Anonymisation vs redaction only, improve CCI understanding • Secondary analysis: • Regulatory effect, public scrutiny of published material • Any negative public health impact, publications with misleading conclusions Consequences • Advance info to EMA, not obligatory, reciprocal transparency • Public/stakeholder response • EMA Annual report on experience of the policy’s implementation, to include a list of the non-compliant companies • Non-compliance: In the event of non-compliance by companies at the various stages of the process, EMA will take remedial action including, where appropriate, publication of a non-compliance notice 100 Clinical Data Publication policy
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