MaRS EXCITE is an innovation in health technology assessment (HTA) where industry, academia, and the health system collaborate to design and execute a robust evaluation program for innovative medical technologies with high disruptive potential that proactively satisfies regulatory and reimbursement decision-makers requirements. EXCITE compromises five Methodological Centres (MCs) across Ontario, Canada with demonstrated excellence in methodologies for designing and conducting complex, multi-centre trials and HTAs. The MCs develop the protocol collaboratively with industry and experts, and oversee the clinical trials, involving multiple participating sites. In an attempt to promote consistency in Quality Assurance (QA) amongst MCs and participating sites for EXCITE studies, EXCITE has developed SOPs, through the Clinical Trials Methodology Committee, that relate exclusively to the unique collaboration with the MCs. These were developed through an analysis of host institution SOPs and developing overarching SOPs that were either unique to the EXCITE QA program, or where deemed appropriate though lacking from some host institutions. This harmonization of SOPs across the five current EXCITE MCs has allowed EXCITE to address one of the main goals of clinical trial QA that is integrity of data. The second goal of clinical trial QA, patient safety, is achieved through the Safety Advisory committee, which sets safety standards that must be adhered to by the MCs evaluating the technologies. The committee reviews all protocols to ensure that patient safety issues are addressed,makes recommendations for protocol changes as necessary and may also mandate training requirements to ensure competency in utilization of any medical technology undergoing testing in the EXCITE program. Therefore, MaRS EXCITE was able to deploy a collaborative platform to harmonize the QA processes across five independent academic methodological centres in order to conduct efficient and effective clinical trials that are used in evaluating disruptive medical technologies in an effort to optimize patient outcomes.

Screening for type 2 diabetes (DM) has peaked as a controversial issue given the publication of the recent Canadian guidelines and since the clinical trial evidence for the effectiveness of DM screening is lacking. A two-step evidence-based analysis was performed: 1) narrative review of international guidelines 2) systematic review of primary studies. MEDLINE, EMBASE, CINAHL, Wiley Cochrane, and Centre for Reviews and Dissemination (2008-2012) were used to identify primary studies comparing the effectiveness of DM screening to usual care. Randomized controlled trials and observational studies meeting inclusion criteria were meta-analyzed and the quality of evidence was evaluated using GRADE. A cost analysis was developed using Ontario claims data and estimating the downstream health care costs in Canadian dollars of screening in Ontario. Eight guidelines and six studies from 2,780 citations were identified. The recommendations for universal screening or screening for low to moderate risk individuals were heterogeneous, not shown for high or very high risk individuals. The guidelines consistently recommended screening for the latter. Screening was associated with a lower likelihood of retinopathy (RR: 0.54, 95% CI: 0.32-0.92) and lower absolute % HbA1c (MD: -0.32, 95% CI: -0.53, -0.11). Screening was not linked to increased anxiety or false reassurance. One large RCT showed no beneficial effect of screening on long-term mortality outcomes. Two observational studies meta-analyzed showed no beneficial effect of screening for neuropathy and nephropathy. The quality of evidence was moderate to very low. Estimated cost savings is $150.4 million dollars using established parameters, with a range of cost savings as low as $16.7 up to $280.4 million dollars in sensitivity analysis. Despite its widespread acceptance, the evidence for the long-term effectiveness of DM screening is lacking. Further clinical and cost analysis in Canada is needed for short-term outcomes to help clarify the issue.

Many non-drug technologies with regulatory approval fail to be recommended for reimbursement. Reasons include low quality evidence or lack of relevance Excellence in Clinical Innovation and Technology Evaluation (EXCITE) is a collaboration between industry, government and academia to develop a harmonized pre-market evaluation that mitigates risk, improves adoption, and responds to system needs EXCITE works with industry to evaluate evidence of efficacy and safety, cost effectiveness and adoption realities. It builds on Ontario’s field evaluation experience. Structure: 1) Management board representing industry, government, academia and the Ontario Health Technology Advisory Committee (OHTAC); 2) Scientific collaboration of 7 Methodological Centres (MC) and 24 Academic Health Science Centres and a Quality Assurance Committee; and 3) Chief Scientific Officer and secretariat. Process: The management board prioritizes applications based on innovation, relevance, and commercialization. MCs develop a protocol and budget for clinical evaluation, systematic review, and an economic analysis. Human factors and usability analysis, and preference studies are offered. Consideration is underway for conditions of early adoption. Studies are funded by industry through MaRS, which fosters and commercializes innovation. Of 17 applications (year 1), 3 have commenced evaluation, 3 are in protocol development, discussions ongoing in 3 and one declined. Studies are designed to satisfy regulatory and reimbursement requirements and reflect complexities of adoption while maintaining high academic standards. Lessons learnt include a better understanding of the complexities of adoption and the benefit of endorsement in mitigating risk; limited funding for evaluations; tension between needs of industry and independence and objectivity of MCs; and intricacies of contract structures. EXCITE is a potential alternative to post-market HTA in Ontario, and may improve adoption in other jurisdictions. Expansion to a national and international scale will provide global reach for evaluated technologies. This is a potentially innovative and powerful model of early HTA.

Authors' objectives The objective of this study was to evaluate the cost-effectiveness and budget impact of the following interventions in moderate to very severe COPD, investigated in the Medical Advisory Secretariat Chronic Obstructive Pulmonary Disease Mega-Analysis Series: smoking cessation programs in moderate COPD in an outpatient setting: – intensive counselling (IC) versus usual care (UC) – nicotine replacement therapy (NRT) versus UC – IC + NRT versus placebo – bupropion versus placebo multidisciplinary care (MDC) teams versus UC in moderate to severe COPD in an outpatient setting pulmonary rehabilitation (PR) versus UC following acute exacerbations in moderate to severe COPD long-term oxygen therapy (LTOT) versus UC in severe hypoxemia in COPD in an outpatient setting ventilation: – noninvasive positive pressure ventilation (NPPV) + usual medical care versus usual medical care in acute respiratory failure due to an acute exacerbation in severe COPD in an inpatient setting – weaning with NPPV versus weaning with invasive mechanical ventilation in acute respiratory failure due to an acute exacerbation in very severe COPD in an inpatient setting

BACKGROUNDMetal-on-metal (MOM) hip resurfacing arthroplasty (HRA) is in clinical use as an appropriate alternative to total hip arthroplasty in young patients. In this technique, a metal cap is placed on the femoral head to cover the damaged surface of the bone and a metal cup is placed in the acetabulum.OBJECTIVESThe primary objective of this analysis was to compare the revision rates of MOM HRA using different implants with the benchmark set by the National Institute of Clinical Excellence (NICE). The secondary objective of this analysis was to review the literature regarding adverse biological effects associated with implant material.REVIEW METHODSA literature search was performed on February 13, 2012, to identify studies published from January 1, 2009, to February 13, 2012.RESULTSThe revision rates for MOM HRA using 6 different implants were reviewed. The revision rates for MOM HRA with 3 implants met the NICE criteria, i.e., a revision rate of 10% or less at 10 years. Two implants had short-term follow-ups and MOM HRA with one of the implants failed to meet the NICE criteria. Adverse tissue reactions resulting in failure of the implants have been reported by several studies. With a better understanding of the factors that influence the wear rate of the implants, adverse tissue reactions and subsequent implant failure can be minimized. Many authors have suggested that patient selection and surgical technique affect the wear rate and the risk of tissue reactions. The biological effects of high metal ion levels in the blood and urine of patients with MOM HRA implants are not known. Studies have shown an increase in chromosomal aberrations in patients with MOM articulations, but the clinical implications and long-term consequences of this increase are still unknown. Epidemiological studies have shown that patients with MOM HRA implants did not have an overall increase in mortality or risk of cancer. There is insufficient clinical data to confirm the teratogenicity of MOM implants in humans.CONCLUSIONSMetal-on-metal HRA can be beneficial for appropriately selected patients, provided the surgeon has the surgical skills required for performing this procedure.

To assess the cost-effectiveness of epidermal growth factor receptor (EGFR) gene mutation testing for guiding the application of gefitinib as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) living in Ontario. A decision analytic model was developed to compare EGFR gene mutation testing strategy versus no testing strategy in patients with advanced NSCLC. Under the testing strategy, patients tested positive for mutation would receive gefitinib as first-line therapy. Under no testing strategy, patients would receive conventional chemotherapy as first-line therapy. Probability variables were estimated through literature review. Utility variables were estimated from a multivariate linear regression analysis taking into account of the clinical responses and side-effects associated with treatment for NSCLC. Cost variables were based on two Ontario cost studies for NSCLC. Both benefits and costs were discounted at 5% per annum. Compared to no testing strategy, the incremental cost-effectiveness ratio for EGFR gene mutation testing was $46,021 per life year or $81,071 per quality adjusted life year (QALY). The cost-effectiveness of EGFR gene mutation testing was sensitive to the cost and efficacy of gefitinib. The budget impact analysis projected that EGFR gene mutation testing would cost Ontario health care system $4.6M, $7.0M, $7.9M, $8.1M, and $8.1M more a year in the next five years. EGFR gene mutation testing would not be cost-effective in patients with advanced NSCLC in Ontario until willingness-to-pay was above $81,000 per QALY. The efficacy and cost of gefitinib significantly affected the cost-effectiveness of EGFR gene mutation testing.