For more information about EXCITE and how to apply, please visit: e xcite.marsdd

1. For more information about EXCITE and how to apply, please visit: excite.marsdd.com

2. Ontario’s Evidence Revolution Commitment to Evidence in Healthcare Ontario Excellent Care for All Act (2010) The people of Ontario and their Government: • Will ensure that healthcare providers are supported to plan for and improve the quality of care they deliver based on the best available scientific evidence.(HQO formed to promulgate quality-based evidence) Drummond Report (2012) • (Healthcare) Policies should be based on evidence that provides guidance on what services, procedures, devices and drugs are effective, efficient and eligible for public funding Ontario Government Budget (2012) • Evidence will drive decisions on funding new and existing procedures. The government is committed to funding only those services that are supported by medical evidence. • The government will accelerate the evidence-based approach to care by building on the mandate of Health Quality Ontario (HQO)

3. Dealing with Uncertainty – Field Evaluation Studies • Post-market assessment of technology performance in the real world through primary data gathering • Improves decision making prior to long-term commitment through appropriate adoption • Designed to inform policy and funded by government • Alternative is passive diffusion and intuitive decision making • Completed 19 and 19 ongoing. Ten CEDs significantly impacted policy decision making and published in peer reviewed journals

4. Barriers to Adoption Poor pre-market quality clinical trial produces uncertainty Accuracy versus clinical utility for diagnostic tests No prospective economic analysis Research failed to address health system perspectives Me-too technologies Lack of generalisability Inadequate trial design e.g. randomization,concealment, ITT – leading to low quality evidence Policy including non-affordability, competing pressures Evidence used to police adoption in Isolation from innovators

5. Health Technology Lifecycle in Ontario POST-MARKET PRE-MARKET Device Development Device Manufacture and Testing Device Licensing Patients have access to the device • Pre-clinical • Design • Prototyping • Effectiveness and safety testing in models • Clinical • Effectiveness and safety testing in patients or using patient samples • Government licensing • Application to Health Canada for Licenses approving sale/use Marketing, sales, distribution, education, training

6. Life-Cycle Diffusion Curve (Pre-Market Evidence Based Analysis) Pre-Market Post-Market U 1 Systematic review Systematic review Obsolescence Effectiveness Effectiveness Cost-Effectiveness (CE) Cost-Effectiveness (CE) • Efficacy Safety • Value (CE) Affordability • Ethical & societal • Post market conditions HORIZON DEVELOP TEST Diffusion Unconditional Yes Unconditional No Uncertainty R&D Investment Regulation TIME

7. Milestone accomplishments • Since December 2011, 20 companies have applied to EXCITE over 3 rounds. • 10 technologies from innovative companies have been selected from a tournament process and are proceeding: • The first round/pilotprojects have gone through the full intake process, consultation & proposal/budget generation, and contract execution. Currently recruiting the first patients into the clinical studies. • The second round has completed review, consultation, and proposal generation. They are now in contract negotiations. • Thethirdround are in consultation and proposal generation. • The fourth round applications are due October 7, 2013. • On May 30th, Minister Matthews announced EXCITE’s pilot participants: • ApneaDx – Home Sleep Apnea diagnosis • Medtronic of Canada Ltd. – Symplicity Renal Denervation for hypertension • Rna Diagnostics – Rna Disruption Assay (RDA) for early prediction of complete response to chemotherapy in breast cancer • EXCITE works with home-grown innovators from across Ontario while also attracting multinationals to conduct critical R&D in Ontario

8. EXCITE is a world-first process

9. The EXCITE process

10. The application process

11. EXCITE selection criteria • Applicants must submit an executive summary and all relevant reports, articles and materials related to the technology • Health technologies are prioritized for participation in EXCITE based on the following criteria: • Relevance to the needs of the health system • Disruptive potential (i.e., the promise of substantially better clinical outcomes, including safety, and/or substantially lower system costs than existing approaches) • Opportunities to identify obsolescence for existing alternative technologies • Estimated magnitude of effect for the target population • The stage of readiness of the technology and how effectively it can be evaluated • Potential benefit to Ontario, Canada (if relevant)

12. The EXCITE process

13. Consultation/protocol development • Acceptance of the invitation is made by way of a $10,000 fee to EXCITE, which is transferred in full to the Methodological Center (MC) to cover costs of developing the evaluation protocols • For SMEs, the amount is $5000 from SMEs, which is then matched by EXCITE for transfer of $10,000 to the MC. • The company is matched with a suitable MC, who is tasked with developing a proposal/protocol to meet the evaluation needs of the technology. • Iterative process in consultation with the company • Typically takes 8-10 weeks • The proposal contains a detailed overview of the proposed evaluation + robust budget for consideration

14. METHODS CENTRE METHODOLOGICAL CENTRES Specialized Methodological Centres & 24 Research Hospitals across the province.

15. EXCITE offers comprehensive analysis packages Core Evidentiary Bundle: Optional Additional Analyses: • Safety + Effectiveness • Systematic Review • Economic Analysis • Assess usability/human factors • Develop education system for training end users • Investigate patient preferences • Analyze factors influencing of uptake • Develop a registry for tracking post-adoption effectiveness + long-terms safety • Knowledge transfer Pg 15

16. The EXCITE process

17. The Evaluation • Acceptance of the proposal is made by way of signed agreements • The duration and cost of evaluations varies based on the complexity of the technology and the investigational testing protocol, including the sample size required • Evaluations typically require 12-30 months to complete and cost $1-3 million • EXCITE and the methodological centre report back regularly regarding progress and any recommendations for technology improvement

18. MaRS EXCITE A B EXCITE contract framework C Methodological Centre Company (Technology Innovator) D-X Participating Centres A: Participation Agreement: MaRS and MC B: Participation Agreement: MaRS and Company C: Statement of Work: MC and Company D-X: Subcontracts: MC and participating centre/sub-contracting MCs.

19. The EXCITE process

20. EXCITE’s unique advantages to innovators • EXCITE evaluations increase likelihood of adoption and market uptake of disruptive health technology innovations • EXCITE provides access to a vast, coordinated network of world-class medical expertise with experience in real-time evaluation of health technologies • EXCITE’s earlier feedback loop provides insight during formative stage • EXCITE’s single, harmonized pre-market evidence development process helps companies navigate the evidence requirements and accelerate market access

21. For more information about EXCITE and how to apply, please visit: excite.marsdd.com