Early technology review: towards an expedited pathway.

OBJECTIVES: Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice. METHODS: An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized. RESULTS: Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals. CONCLUSIONS: Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.

The determinants of home and nursing home death: a systematic review and meta-analysis.

BACKGROUND: Most Canadians die in hospital, and yet, many express a preference to die at home. Place of death is the result of the interaction among sociodemographic, illness- and healthcare-related factors. Although home death is sometimes considered a potential indicator of end-of-life/palliative care quality, some determinants of place of death are more modifiable than others. The objective of this systematic review was to evaluate the determinants of home and nursing home death in adult patients diagnosed with an advanced, life-limiting illness. METHODS: A systematic literature search was performed for studies in English published from January 1, 2004 to September 24, 2013 that evaluated the determinants of home or nursing home death compared to hospital death in adult patients with an advanced, life-limiting condition. The adjusted odds ratios, relative risks, and 95% confidence intervals of each determinant were extracted from the studies. Meta-analyses were performed if appropriate. The quality of individual studies was assessed using the Newcastle-Ottawa scale and the body of evidence was assessed according to the GRADE Working Group criteria. RESULTS: Of the 5,900 citations identified, 26 retrospective cohort studies were eligible. The risk of bias in the studies identified was considered low. Factors associated with an increased likelihood of home versus hospital death included multidisciplinary home palliative care, preference for home death, cancer as opposed to other diagnoses, early referral to palliative care, not living alone, having a caregiver, and the caregiver's coping skills. CONCLUSIONS: Knowledge about the determinants of place of death can be used to inform care planning between healthcare providers, patients and family members regarding the feasibility of dying in the preferred location and may help explain the incongruence between preferred and actual place of death. Modifiable factors such as early referral to palliative care, presence of a multidisciplinary home palliative care team were identified, which may be amenable to interventions that improve the likelihood of a patient dying in the preferred location. Place of death may not be a very good indicator of the quality of end-of-life/palliative care since it is determined by multiple factors and is therefore dependent on individual circumstances.

EARLY EVALUATION OF NEW HEALTH TECHNOLOGIES: THE CASE FOR PREMARKET STUDIES THAT HARMONIZE REGULATORY AND COVERAGE PERSPECTIVES.

With an increasing awareness that active engagement between policy decision makers, HTA agencies, regulators and payers with industry in the premarket space is needed, a disruptive comprehensive approach is described which moves the evidentiary process exclusively into this space. Single harmonized studies pre-market to address regulatory and coverage needs and expectations are more likely to be efficient and less costly and position evidence to drive rather than test innovation. An example of such a process through the MaRS EXCITE program in Ontario, Canada, now undergoing proof of concept, is briefly discussed. Other examples of dialogue between decision makers and industry pre-market are provided though these are less robust than a comprehensive evidentiary approach.

Coverage with evidence development: the Ontario experience.

BACKGROUND: For non-drug technologies, there is often residual uncertainty following systematic review, mainly due to inadequate evidence of efficacy. The unwillingness to make decisions in the presence of uncertainty may lead to passive diffusion and intuitive decision making with or without public pressure. This may affect health system sustainability. There is increasing interest in post-market evaluation through processes that include coverage with evidence development (CED) to address residual uncertainty regarding effectiveness and cost-effectiveness. Global experience of CED has been slow to develop despite their potential contribution to decision making. METHODS: Ontario's field evaluation program to better inform decision making represents a collaboration between physicians, policy decision makers and academic centers. We report results of the first ten CEDs from this program to assess whether they achieved their objective of influencing policy by addressing residual uncertainty following systematic review. RESULTS: Since 2003, nineteen field evaluation studies to resolve residual uncertainty following systematic review have been completed, ten of which met the criteria of CED and are the focus of this report. There was more than one patient subgroup or intervention in three of the CEDs. This provided the basis for evaluating thirteen outcomes. In each case, the CED addressed the uncertainty and led to a decision based on the systematic review and CED result. The CEDs led to adoption of the technology in six instances, modified adoption in three instances and withdrawal in four instances. CONCLUSIONS: CED makes an important contribution to translating evidence to decision making. Methodologies are needed to increase the scope and reduce timelines for CEDs, such as the use of linked comprehensive and robust data sets and collaborative studies with other jurisdictions. CED before making long-term funding decisions, especially where there is uncertainty of effectiveness, safety or cost-effectiveness, should be increasingly funded by health systems.

Comparative effectiveness research in Ontario, Canada: producing relevant and timely information for health care decision makers.

CONTEXT: Comparative effectiveness research is increasingly being recognized as a method to link research with the information needs of decision makers. As the United States begins to invest in comparative effectiveness, it would be wise to look at other functioning research networks to understand the infrastructure and funding required to support them. METHODS: This case study looks at the comparative effectiveness research network in Ontario, Canada, for which a neutral coordinating committee is responsible for prioritizing topics, assessing evidence, providing recommendations on coverage decisions, and determining pertinent research questions for further evaluation. This committee is supported by the Medical Advisory Secretariat and several large research institutions. This article analyzes the infrastructure and cost needed to support this network and offers recommendations for developing policies and methodologies to support comparative effectiveness research in the United States. FINDINGS: The research network in place in Ontario explicitly links decision making with evidence generation, in a transparent, timely, and efficient way. Funding is provided by the Ontario government through a reliable and stable funding mechanism that helps ensure that the studies it supports are relevant to decision makers. CONCLUSIONS: With the recent allocation of funds to support comparative effectiveness research from the American Recovery and Reinvestment Act, the United States should begin to construct an infrastructure that applies these features to make sure that evidence generated from this effort positively affects the quality of health care delivered to patients.

Building bridges between academic research and policy formulation: the PRUFE framework - an integral part of Ontario's evidence-based HTPA process.

Healthcare expenditure in Ontario has been escalating at increasing rates and a growing proportion of this has come from medical devices and other technologies. A comprehensive evidence-based process for the assessment of new health technologies in Ontario was recently established (the Health Technology Policy Analysis [HTPA] process). Requests for funding for new technologies are directed through a department of the Ministry called the Medical Advisory Secretariat (MAS) who, using a systematic and evidence-based approach, provides information on the safety, effectiveness, and cost effectiveness of the technology to the Ontario Health Technology Advisory Committee (OHTAC). If the OHTAC determines that the evidentiary base for making recommendations is too uncertain, a request is made to reduce this uncertainty through the conduct of a 'real world' Ontario-based study. The Program for Assessment of Technology in Health (PATH) reduction of Uncertainty through Field Evaluation (PRUFE) framework is an iterative process for collecting new information, updating prior knowledge and providing new 'real world' evidence back to the Ministry regarding the cost effectiveness of new health technologies. MAS/OHTAC has undertaken evidence-based analyses for >50 new technologies. The PRUFE framework has been successful for reducing uncertainty and controlling healthcare expenditures while providing access and improving patient outcomes.

Photoselective vaporization for the treatment of benign prostatic hyperplasia.

BACKGROUND: As an alternative to transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP) provides a bloodless, relatively painless relief of lower urinary tract symptoms for men with benign prostatic hyperplasia. Following a review of the evidence in 2006, the Ontario Health Technology Advisory Committee recommended that a study be conducted to evaluate PVP in Ontario. OBJECTIVES: To compare the clinical effectiveness, safety, cost-effectiveness, and budget impact of PVP compared to conventional TURP for the treatment of benign prostatic hyperplasia in Ontario. METHODS: A prospective, nonrandomized trial was conducted in 3 Ontario centres. Consenting subjects were assessed at baseline and 1, 3, and 6 months following surgery. Outcome measures included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), post-void residual (PVR) volume, prostate-specific antigen (PSA), health-related quality of life (HRQOL) using the EuroQol 5 Domain questionnaire, and the Sexual Health Inventory for Men (SHIM) score. Adverse events, resource utilization, and productivity losses were also assessed. Cost-effectiveness and budget impact analyses were completed using data from the study. RESULTS: Between February 2008 and August 2010, 164 subjects were enrolled in the study (n = 140 for PVP and n = 24 for TURP). Treatment outcomes were similar between the 2 groups at 6 months, with the IPSS decreasing similarly over time (P = 0.718). For other treatment outcomes (Qmax, PSA, HRQOL, SHIM) both treatments provided similar benefit over time; only changes in PVR volume favoured PVP (P = 0.018). The majority of PVP patients were managed on an outpatient basis, with only 7.1% requiring admission (all TURP subjects were inpatients). At 6 months, PVP was less costly than TURP ($3,891 versus $4,863; P = 0.001), with similar quality-adjusted life-years (0.448 versus 0.441; P = 0.658). PVP remained the most cost-effective treatment across all decision-making thresholds, with the technology costing less and providing similar clinical outcomes. Extrapolating the results to a provincial level indicated (based on an estimated case volume of 12,335 TURPs) that there is an opportunity to reallocate just over $14 million (Cdn), primarily related to the reduced need for hospital admission. LIMITATIONS: This study was nonrandomized, and the results should be interpreted with some caution, despite generally similar baseline characteristics between the 2 groups. Recruiting individuals to the TURP arm was a challenge, resulting in a size imbalance between treatment arms. CONCLUSIONS: Based on this analysis, PVP appears to be a cost-effective alternative to TURP, providing similar clinical benefit at a lower cost to the health system.

A prospective trial of GreenLight PVP (HPS120) versus transurethral resection of the prostate in the treatment of lower urinary tract symptoms in Ontario, Canada.

BACKGROUND: Photoselective vaporization of the prostate (PVP) is a bloodless, relatively painless alternative to transurethral resection of the prostate (TURP) for relief of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). OBJECTIVE: We compare the effectiveness, safety and cost-effectiveness of Greenlight Laser PVP (HPS-120) and TURP. METHODS: We conducted a prospective, non-randomized trial in 3 Ontario centres from March 2008 to February 2011. Assessments were completed at baseline, 1 and 6 months following surgery at the physicians' offices and at 12 and 24 months by phone. The primary outcome was the change in International Prostate Symptoms Score (IPSS) score at 6 months versus baseline. Secondary outcomes were changes in flow rate, postvoid residual (PVR), prostate-specific antigen (PSA) and sexual health inventory for men (SHIM) scores. Adverse events, health-related quality of life (HRQoL), resource utilization and productivity losses were collected. RESULTS: Although the IPSS decreased in both arms (n = 140 for PVP and n = 24 for TURP) between baseline and 6 months, the difference in change over time between the groups was not statistically significant (p = 0.718). Other outcomes improved equally from baseline and 6 months (Qmax, SHIM, PSA and HRQoL), with only changes in PVR favouring PVP (p = 0.018). There were no statistical differences in serious adverse events. In total, 130 of 140 PVP patients were outpatients, all TURP subjects were inpatients. PVP was less costly than TURP ($3891 vs. $4863; p < 0.001) with similar quality-adjusted life years (0.448 vs. 0.441; p = 0.658). CONCLUSION: Greenlight Laser PVP (HPS-120) is a safe and cost-effective alternative to TURP for outpatient treatment of LUTS and can be completed as an outpatient with minimal blood loss.

Ontario multidetector computed tomographic coronary angiography study: field evaluation of diagnostic accuracy.

BACKGROUND: Computed tomographic coronary angiography (CTCA) has gained clinical acceptance for the detection of obstructive coronary artery disease. Although single-center studies have demonstrated excellent accuracy, multicenter studies have yielded variable results. The true diagnostic accuracy of CTCA in the "real world" remains uncertain. We conducted a field evaluation comparing multidetector CTCA with invasive CA (ICA) to understand CTCA's diagnostic accuracy in a real-world setting. METHODS: A multicenter cohort study of patients awaiting ICA was conducted between September 2006 and June 2009. All patients had either a low or an intermediate pretest probability for coronary artery disease and underwent CTCA and ICA within 10 days. The results of CTCA and ICA were interpreted visually by local expert observers who were blinded to all clinical data and imaging results. RESULTS: Using a patient-based analysis (diameter stenosis ≥50%) of 169 patients, the sensitivity, specificity, positive predictive value, and negative predictive value were 81.3% (95% confidence interval [CI], 71.0%-89.1%), 93.3% (95% CI, 85.9%-97.5%), 91.6% (95% CI, 82.5%-96.8%), and 84.7% (95% CI, 76.0%-91.2%), respectively; the area under receiver operating characteristic curve was 0.873. The diagnostic accuracy varied across centers (P < .001), with a sensitivity, specificity, positive predictive value, and negative predictive value ranging from 50.0% to 93.2%, 92.0% to 100%, 84.6% to 100%, and 42.9% to 94.7%, respectively. CONCLUSIONS: Compared with ICA, CTCA appears to have good accuracy; however, there was variability in diagnostic accuracy across centers. Factors affecting institutional variability need to be better understood before CTCA is universally adopted. Additional real-world evaluations are needed to fully understand the impact of CTCA on clinical care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00371891.

Establishing a comprehensive continuum from an evidentiary base to policy development for health technologies: the Ontario experience.

OBJECTIVES: The aim of this study was to describe a comprehensive continuum that has developed in Ontario between government and key stakeholder groups, including hospitals, physicians, academic institutions, clinical epidemiologists, health economists, industry, and bioethicists to achieve evidence-based recommendations for policy development. METHODS: The various components of the comprehensive model that has evolved to develop an evidentiary platform for policy development are summarized, and the flow between these components is described. RESULTS: The development of the Ontario Health Technology Advisory Committee (OHTAC) and associated programs demonstrate the need to go beyond the traditional steps taken within most health technology assessment paradigms. These components include pragmatic postmarketing studies, human factors, and safety analyses, and formalized interactions with a broad spectrum of potential end-users of each technology, experts, and industry. Thesecomponents, taken together with an expanded systematic review to include a range of economic analyses, and societal impacts augment the traditional systematic review processes. This approach has been found to be important in assisting decision making and has resulted in an 81 percent conversion from evidence to policy consideration for eighty-three technologies that had been assessed at the time this article was submitted. CONCLUSIONS: The comprehensive model, centered around OHTAC, has added important new dimensions to health policy by improving its relevance to decision makers and providing an accountable and transparent basis for government to invest appropriately in health technologies. This study could also form a basis for further research into appropriate methodologies and outcome measurements as they relate to each component of this approach.