Ontario Health Technology Assessment Series最新文献

Background: Allergic rhinitis is the most common type of allergy worldwide. The accuracy of skin testing for allergic rhinitis is still debated. This health technology assessment had two objectives: to determine the diagnostic accuracy of skin-prick and intradermal testing in patients with suspected allergic rhinitis and to estimate the costs to the Ontario health system of skin testing for allergic rhinitis.

Methods: We searched All Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database for studies that evaluated the diagnostic accuracy of skin-prick and intradermal testing for allergic rhinitis using nasal provocation as the reference standard. For the clinical evidence review, data extraction and quality assessment were performed using the QUADAS-2 tool. We used the bivariate random-effects model for meta-analysis. For the economic evidence review, we assessed studies using a modified checklist developed by the (United Kingdom) National Institute for Health and Care Excellence. We estimated the annual cost of skin testing for allergic rhinitis in Ontario for 2015 to 2017 using provincial data on testing volumes and costs.

Results: We meta-analyzed seven studies with a total of 430 patients that assessed the accuracy of skin-prick testing. The pooled pair of sensitivity and specificity for skin-prick testing was 85% and 77%, respectively. We did not perform a meta-analysis for the diagnostic accuracy of intradermal testing due to the small number of studies (n = 4). Of these, two evaluated the accuracy of intradermal testing in confirming negative skin-prick testing results, with sensitivity ranging from 27% to 50% and specificity ranging from 60% to 100%. The other two studies evaluated the accuracy of intradermal testing as a stand-alone tool for diagnosing allergic rhinitis, with sensitivity ranging from 60% to 79% and specificity ranging from 68% to 69%. We estimated the budget impact of continuing to publicly fund skin testing for allergic rhinitis in Ontario to be between $2.5 million and $3.0 million per year.

Conclusions: Skin-prick testing is moderately accurate in identifying subjects with or without allergic rhinitis. The diagnostic accuracy of intradermal testing could not be well established from this review. Our best estimate is that publicly funding skin testing for allergic rhinitis costs the Ontario government approximately $2.5 million to $3.0 million per year.

Background: Untreated vertebral compression fractures can have serious clinical consequences and impose a considerable impact on patients' quality of life and on caregivers. Since non-surgical management of these fractures has limited effectiveness, vertebral augmentation procedures are gaining acceptance in clinical practice for pain control and fracture stabilization. The objective of this analysis was to determine the cost-effectiveness and budgetary impact of kyphoplasty or vertebroplasty compared with non-surgical management for the treatment of vertebral compression fractures in patients with cancer.

Methods: We performed a systematic review of health economic studies to identify relevant studies that compare the cost-effectiveness of kyphoplasty or vertebroplasty with non-surgical management for the treatment of vertebral compression fractures in adults with cancer. We also performed a primary cost-effectiveness analysis to assess the clinical benefits and costs of kyphoplasty or vertebroplasty compared with non-surgical management in the same population. We developed a Markov model to forecast benefits and harms of treatments, and corresponding quality-adjusted life years and costs. Clinical data and utility data were derived from published sources, while costing data were derived using Ontario administrative sources. We performed sensitivity analyses to examine the robustness of the results. In addition, a 1-year budget impact analysis was performed using data from Ontario administrative sources. Two scenarios were explored: (a) an increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario, maintaining the current proportion of kyphoplasty versus vertebroplasty; and (b) no increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario but an increase in the proportion of kyphoplasties versus vertebroplasties.

Results: The base case considered each of kyphoplasty and vertebroplasty versus non-surgical management. Kyphoplasty and vertebroplasty were associated with an incremental cost-effectiveness ratio of $33,471 and $17,870, respectively, per quality-adjusted life-year gained. The budgetary impact of funding vertebral augmentation procedures for the treatment of vertebral compression fractures in adults with cancer in Ontario was estimated at about $2.5 million in fiscal year 2014/15. More widespread use of vertebral augmentation procedures raised total expenditures under a number of scenarios, with costs increasing by $67,302 to $913,386.

Conclusions: Our findings suggest that the use of kyphoplasty or vertebroplasty in the management of vertebral compression fractures in patients with cancer may be a cost-effective strategy at commonly accepted willingness-to-pay thresholds. Nonetheless, more widespread use of kyphoplasty (and vertebroplasty t

Background: Cancers that metastasize to the spine and primary cancers such as multiple myeloma can result in vertebral compression fractures or instability. Conservative strategies, including bed rest, bracing, and analgesic use, can be ineffective, resulting in continued pain and progressive functional disability limiting mobility and self-care. Surgery is not usually an option for cancer patients in advanced disease states because of their poor medical health or functional status and limited life expectancy. The objectives of this review were to evaluate the effectiveness and safety of percutaneous image-guided vertebral augmentation techniques, vertebroplasty and kyphoplasty, for palliation of cancer-related vertebral compression fractures.

Methods: We performed a systematic literature search for studies on vertebral augmentation of cancer-related vertebral compression fractures published from January 1, 2000, to October 2014; abstracts were screened by a single reviewer. For those studies meeting the eligibility criteria, full-text articles were obtained. Owing to the heterogeneity of the clinical reports, we performed a narrative synthesis based on an analytical framework constructed for the type of cancer-related vertebral fractures and the diversity of the vertebral augmentation interventions.

Results: The evidence review identified 3,391 citations, of which 111 clinical reports (4,235 patients) evaluated the effectiveness of vertebroplasty (78 reports, 2,545 patients) or kyphoplasty (33 reports, 1,690 patients) for patients with mixed primary spinal metastatic cancers, multiple myeloma, or hemangiomas. Overall the mean pain intensity scores often reported within 48 hours of vertebral augmentation (kyphoplasty or vertebroplasty), were significantly reduced. Analgesic use, although variably reported, usually involved parallel decreases, particularly in opioids, and mean pain-related disability scores were also significantly improved. In a randomized controlled trial comparing kyphoplasty with usual care, improvements in pain scores, pain-related disability, and health-related quality of life were significantly better in the kyphoplasty group than in the usual care group. Bone cement leakage, mostly asymptomatic, was commonly reported after vertebroplasty and kyphoplasty. Major adverse events, however, were uncommon.

Conclusions: Both vertebroplasty and kyphoplasty significantly and rapidly reduced pain intensity in cancer patients with vertebral compression fractures. The procedures also significantly decreased the need for opioid pain medication, and functional disabilities related to back and neck pain. Pain palliative improvements and low complication rates were consistent across the various cancer populations and vertebral fractures that were investigated.

Background: People who are homeless encounter barriers to primary care despite having greater needs for health care, on average, than people who are not homeless. We evaluated the effectiveness of interventions to improve access to primary care for people who are homeless.

Methods: We performed a systematic review to identify studies in English published between January 1, 1995, and July 8, 2015, comparing interventions to improve access to a primary care provider with usual care among people who are homeless. The outcome of interest was access to a primary care provider. The risk of bias in the studies was evaluated, and the quality of the evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria.

Results: From a total of 4,047 citations, we identified five eligible studies (one randomized controlled trial and four observational studies). With the exception of the randomized trial, the risk of bias was considered high in the remaining studies. In the randomized trial, people who were homeless, without serious mental illness, and who received either an outreach intervention plus clinic orientation or clinic orientation alone, had improved access to a primary care provider compared with those receiving usual care. An observational study that compared integration of primary care and other services for people who are homeless with usual care did not observe any difference in access to a primary care provider between the two groups. A small observational study showed improvement among participants with a primary care provider after receiving an intervention consisting of housing and supportive services compared with the period before the intervention. The quality of the evidence was considered moderate for both the outreach plus clinic orientation and clinic orientation alone, and low to very low for the other interventions. Despite limitations, the literature identified reports of interventions developed to overcome barriers in access to primary care in people who are homeless. The interventions studied are complex and include multiple components that are consistent with proposed dimensions of access to care (availability, affordability, and acceptability).

Conclusions: Our systematic review of the literature identified various types of interventions that seek to improve access to primary care by attempting to address barriers to care encountered by people who are homeless. Moderate-quality evidence indicates that orientation to clinic services (either alone or combined with outreach) improves access to a primary care provider in adults who are homeless, without serious mental illness, and living in urban centres.

Background: Leukemia accounts for nearly a third of childhood cancers in Canada, with acute lymphoblastic leukemia (ALL) comprising nearly 80% of cases. Identification of prognostic factors that allow risk stratification and tailored treatment have improved overall survival. However, nearly a quarter of patients considered standard risk on the basis of conventional prognostic factors still relapse, and relapse is associated with increased morbidity and mortality. Relapse is thought to result from extremely low levels of leukemic cells left over once complete remission is reached, termed minimal residual disease (MRD). Poor event-free survival (EFS) as well as overall survival for those who are classified as MRD-positive have been substantiated in seminal studies demonstrating the prognostic value of MRD for EFS in the past few decades. This review sought to further elucidate the relationship between MRD and EFS by looking at relapse, the primary determinant of EFS and the biological mechanism through which MRD is thought to act. This evidence review aimed to ascertain whether MRD is an independent prognostic factor for relapse and to assess the effect of MRD-directed treatment on patient-important outcomes in childhood ALL.

Methods: Large prospective cohort studies with a priori multivariable analysis that includes potential confounders are required to draw confirmatory conclusions about the independence of a prognostic factor. Data on the prognostic value of MRD for relapse measured by molecular methods (polymerase chain reaction [PCR] of immunoglobulin or T-cell receptor rearrangements) or flow cytometry for leukemia-associated immunophenotypes or difference-from-normal approach were abstracted from included studies. Relevant data on relapse, EFS, and overall survival were abstracted from randomized controlled trials (RCTs) evaluating the effect of MRD-directed treatment.

Results: A total of 2,832 citations were reviewed, of which 12 studies were included in this review. All cohort studies evaluating MRD as a prognostic factor for relapse found significant independent value when added to various existing prognostic factors. Seven studies showed prognostic value of MRD measured at the end of induction therapy and two at the end of consolidation therapy in de novo ALL, one study in relapsed ALL after re-induction therapy, and three studies before hematopoietic stem cell transplant. One large RCT in standard-risk patients found no compromise to outcomes when reducing treatment in MRD-negative patients, and also showed a 45% reduction in relapse risk and nearly 40% benefit in EFS when escalating treatment in MRD-positive patients.

Conclusions: Minimal residual disease is an independent prognostic factor for relapse in childhood ALL. Relapse is a key determinant of EFS and patients' quality of life. Treatment selected on the basis of MRD status appears to improv

Background: Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario.

Methods: A systematic literature search (1998-2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years.

Results: In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In the budget-impact analysis, the 1-year cost expenditure for MRD testing by flow cytometry in newly diagnosed patients with precursor B-cell ALL was estimated at $340,760. We forecasted that the province would have to pay approximately $1.3 million over 3 years and $2.4 million over 5 years for MRD testing by flow cytometry in this population.

Conclusions: Compared with no testing, MRD testing by flow cytometry in newly diagnosed patients with precursor B-cell ALL represents good value for money at commonly used willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY.

Background: To date, several randomized controlled trials (RCTs) have shown the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression.

Objective: This analysis examined the antidepressant efficacy of rTMS in patients with treatment-resistant unipolar depression.

Methods: A literature search was performed for RCTs published from January 1, 1994, to November 20, 2014. The search was updated on March 1, 2015. Two independent reviewers evaluated the abstracts for inclusion, reviewed full texts of eligible studies, and abstracted data. Meta-analyses were conducted to obtain summary estimates. The primary outcome was changes in depression scores measured by the Hamilton Rating Scale for Depression (HRSD), and we considered, a priori, the mean difference of 3.5 points to be a clinically important treatment effect. Remission and response to the treatment were secondary outcomes, and we calculated number needed to treat on the basis of these outcomes. We examined the possibility of publication bias by constructing funnel plots and by Begg's and Egger's tests. A meta-regression was undertaken to examine the effect of specific rTMS technical parameters on the treatment effects.

Results: Twenty-three RCTs compared rTMS with sham, and six RCTs compared rTMS with electroconvulsive therapy (ECT). Trials of rTMS versus sham showed a statistically significant improvement in depression scores with rTMS (weighted mean difference [WMD] 2.31, 95% CI 1.19-3.43; P < .001). This improvement was smaller than the pre-specified clinically important treatment effect. There was a 10% absolute difference between rTMS and sham in the rates of remission or response. This translates to a number needed to treat of 10. Risk ratios for remission and response were 2.20 (95% CI 1.44-3.38, P = .001 and 1.72 [95% CI], 1.13-2.62, P = .01), respectively, favouring rTMS. No publication bias was detected. Trials of rTMS versus ECT showed a statistically and clinically significant difference between rTMS and ECT in favour of ECT (WMD 5.97, 95% CI 0.94-11.0, P = .02). Risk ratios for remission and response were 1.44 (95% CI 0.64-3.23, P = .38) and 1.72 (95% CI 0.95-3.11, P = .07), respectively, favouring ECT.

Conclusions: Overall, the body of evidence favoured ECT for treatment of patients who are treatment-resistant. Repetitive transcranial magnetic stimulation had a small short-term effect for improving depression in comparison with sham, but follow-up studies did not show that the small effect will continue for longer periods.

Background: Major depressive disorder (MDD, 10% over a person's lifetime) is common and costly to the health system. Unfortunately, many MDD cases are resistant to treatment with antidepressant drugs and require other treatment to reduce or eliminate depression. Electroconvulsive therapy (ECT) has long been used to treat persons with treatment-resistant depression (TRD). Despite its effectiveness, ECT has side effects that make patients intolerant to the treatment, or they refuse to use it. Repetitive transcranial magnetic stimulation (rTMS), which has fewer side effects than ECT and might be an alternative for TRD patients who are ineligible for or unwilling to undergo ECT, has been developed to treat TRD.

Objectives: This analysis evaluates the cost-effectiveness of rTMS for patients with TRD compared with ECT or sham rTMS and estimates the potential budgetary impact of various levels of implementation of rTMS in Ontario.

Review methods: A cost-utility analysis compared the costs and health outcomes of two treatments for persons with TRD in Ontario: rTMS alone compared with ECT alone and rTMS alone compared with sham rTMS. We calculated the six-month incremental costs and quality-adjusted life-years (QALYs) for these treatments. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model's results. A 1-year budget impact analysis estimated the costs of providing funding for rTMS. The base-case analysis examined the additional costs for funding six centres, where rTMS infrastructure is in place. Sensitivity and scenario analyses explored the impact of increasing diffusion of rTMS to centres with existing ECT infrastructure. All analyses were conducted from the Ontario health care payer perspective.

Results: ECT was cost effective compared to rTMS when the willingness to pay is greater than $37,640.66 per QALY. In the base-case analysis, which had a six-month time horizon, the cost and effectiveness for rTMS was $5,272 and 0.31 quality-adjusted life-years (QALYs). The cost and effectiveness for ECT were $5,960 and 0.32 QALYs. This translates in an incremental cost-effectiveness ratio of $37,640.66 per QALY gained for ECT compared to rTMS. When rTMS is compared with sham rTMS, an additional $2,154.33 would be spent to gain 0.02 QALY. This translates to an ICER of $98,242.37 per QALY gained. Probabilistic sensitivity analysis showed that the probability of rTMS being cost-effective compared to sham rTMS was 2% and 45% at the thresholds of $50,000 and $100,000 per QALY gained, respectively.

Conclusions: Repetitive transcranial magnetic stimulation may be cost-effective compared to sham treatment in patients with treatment-resistant depression, depending on the willingness-to-pay threshold.

Background: In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke.

Methods: We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates.

Results: There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88-3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60-1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66-1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for mechanical thrombectomy were $126,939 and 1.484 quality-adjusted life-years (QALYs) (2.969 life-years). The costs and effectiveness for IVT alone were $124,419 and 1.273 QALYs (2.861 life-years), respectively. Mechanical thrombectomy was associated with an incremental cost-effectiveness ratio of $11,990 per QALY gained. Probabilistic sensitivity analysis showed that the probability of mechanical thrombectomy being cost-effective was 57.5%, 89.7%, and 99.6%, at thresholds of $20,000, $50,000, and $100,000 per QALY gained, respectively. We estimated that adopting mechanical thrombectomy would lead to a cost increase of approximately $1 to 2 million.

Conclusions: High quality evidence showed that mechanical thrombectomy significantly improved functional independence and appeared to be cost-effective compared to IVT alone for patients with acute ischemic stroke.

Background: Intrathecal drug delivery systems can be used to manage refractory or persistent cancer pain. We investigated the benefits, harms, cost-effectiveness, and budget impact of these systems compared with current standards of care for adult patients with chronic pain due owing to cancer.

Methods: We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library databases, National Health Service's Economic Evaluation Database, and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014 for evidence of effectiveness, harms, and cost-effectiveness. We used existing systematic reviews that had employed reliable search and screen methods and searched for studies published after the search date reported in the latest systematic review to identify studies. Two reviewers screened records and assessed study validity. The cost burden of publicly funding intrathecal drug delivery systems for cancer pain was estimated for a 5-year timeframe using a combination of published literature, information from the device manufacturer, administrative data, and expert opinion for the inputs.

Results: We included one randomized trial that examined effectiveness and harms, and one case series that reported an eligible economic evaluation. We found very low quality evidence that intrathecal drug delivery systems added to comprehensive pain management reduce overall drug toxicity; no significant reduction in pain scores was observed. Weak conclusions from economic evidence suggested that intrathecal drug delivery systems had the potential to be more cost-effective than high-cost oral therapy if administered for 7 months or longer. The cost burden of publicly funding this therapy is estimated to be $100,000 in the first year, increasing to $500,000 by the fifth year.

Conclusions: Current evidence could not establish the benefit, harm, or cost-effectiveness of intrathecal drug delivery systems compared with current standards of care for managing refractory cancer pain in adults. Publicly funding intrathecal drug delivery systems for cancer pain would result in a budget impact of several hundred thousand dollars per year.