Automated CT Perfusion Imaging to Aid in the Selection of Patients With Acute Ischemic Stroke for Mechanical Thrombectomy: A Health Technology Assessment.

Stroke is a sudden interruption in the blood supply to a part of the brain, causing loss of neurological function. It is the third leading cause of death in Canada and affects mainly older people. In the acute setting, neuroimaging is integral to stroke evaluation and decision-making. The neuroimaging results guide patient selection for mechanical thrombectomy. Using automated image processing techniques facilitates efficient review of this information and communication between centres. We conducted a health technology assessment of automated CT perfusion imaging as a tool for selecting stroke patients with anterior circulation occlusion for mechanical thrombectomy. This assessment included an evaluation of clinical effectiveness, cost-effectiveness, and the budget impact of publicly funding automated CT perfusion imaging. We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each study using QUADAS-2 or the Cochrane risk-of-bias tool, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and approximated cost-effectiveness based on previous analyses. We also analyzed the budget impact of publicly funding automated CT perfusion imaging to evaluate people with acute ischemic stroke in Ontario. Automated CT perfusion imaging had a sensitivity of 84% for identifying the infarct core (dead tissue that does not recover despite restoring blood flow with mechanical thrombectomy), compared with diffusion-weighted MRI imaging at 24 hours. One study reported that 7% of patients were misclassified with respect to eligibility for mechanical thrombectomy (either erroneously classified as eligible or erroneously classified non-eligible). Two randomized controlled trials (DEFUSE 3 and DAWN) demonstrated the efficacy of mechanical thrombectomy up to 24 hours after stroke onset, with patient selection guided by automated CT perfusion imaging. These data showed that a significantly higher proportion of patients in the mechanical thrombectomy group achieved functional independence compared with the standard care group (DEFUSE 3: risk ratio: 2.67 [95% confidence interval 1.60-4.48]; DAWN: adjusted rate difference: 33% [95% credible interval 21%-44%]; GRADE: Moderate).A previous health technology assessment in stroke patients presenting at 0 to 6 hours after stroke symptom onset and the results from recent randomized controlled trials for patients presenting at 6 to 24 hours informed the evaluation of cost-effectiveness. Mechanical thrombectomy informed by automated CT perfusion imaging to assess eligibility is likely to be cost-effective for patients presenting at 6 to 24 hours after stroke symptom onset. The annual budget impact of publicly funding automated CT perfusion imaging in Ontario over the next 5 years would be $1.3 million in year 1 and $0.9 million each year thereafter. Some of the costs of automated CT perfusion imaging could be offset by avoiding unnecessary patient transfers between hospitals. Automated CT perfusion imaging has an acceptable sensitivity and specificity for detecting brain areas that have been affected by stroke. In patients selected for mechanical thrombectomy using automated CT perfusion imaging, there was significant improvement in functional independence. Mechanical thrombectomy informed by automated CT perfusion imaging is likely to be cost-effective. We estimate that publicly funding automated CT perfusion imaging in Ontario would result in additional costs of $1.3 million in year 1 and $0.9 million per year thereafter.

Ontario Health (Quality) 《-》

Multi-gene Pharmacogenomic Testing That Includes Decision-Support Tools to Guide Medication Selection for Major Depression: A Health Technology Assessment.

Major depression is a substantial public health concern that can affect personal relationships, reduce people's ability to go to school or work, and lead to social isolation. Multi-gene pharmacogenomic testing that includes decision-support tools can help predict which depression medications and dosages are most likely to result in a strong response to treatment or to have the lowest risk of adverse events on the basis of people's genes.We conducted a health technology assessment of multi-gene pharmacogenomic testing that includes decision-support tools for people with major depression. Our assessment evaluated effectiveness, safety, cost-effectiveness, the budget impact of publicly funding multi-gene pharmacogenomic testing, and patient preferences and values. We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias Tool and the Risk of Bias Assessment Tool for Nonrandomized studies (RoBANS) and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria.We performed a systematic literature search of the economic evidence to review published cost-effectiveness studies on multi-gene pharmacogenomic testing that includes a decision-support tool in people with major depression. We developed a state-transition model and conducted a probabilistic analysis to determine the incremental cost of multi-gene pharmacogenomic testing versus treatment as usual per quality-adjusted life-year (QALY) gained for people with major depression who had inadequate response to one or more antidepressant medications. In the reference case (with GeneSight-guided care), we considered a 1-year time horizon with an Ontario Ministry of Health perspective. We also estimated the 5-year budget impact of publicly funding multi-gene pharmacogenomic testing for people with major depression in Ontario.To contextualize the potential value of multi-gene pharmacogenomic testing that includes decision-support tools, we spoke with people who have major depression and their families. We included 14 studies in the clinical evidence review that evaluated six multi-gene pharmacogenomic tests. Although all tests included decision-support tools, they otherwise differed greatly, as did study design, populations included in studies, and outcomes reported. Little or no improvement was observed on change in HAM-D17 depression score compared with treatment as usual for any test evaluated (GRADE: Low-Very Low). GeneSight- and NeuroIDgenetix-guided medication selection led to statistically significant improvements in response (GRADE: Low-Very Low) and remission (GRADE: Low-Very Low), while treatment guided by CNSdose led to significant improvement in remission rates (GRADE: Low), but the study did not report on response. Results were inconsistent and uncertain for the impact of Neuropharmagen, and no significant improvement was observed for Genecept or another unspecified test for either response or remission (GRADE: Low-Very Low). Neuropharmagen may reduce adverse events and CNSDose may reduce intolerability to medication, while no difference was observed in adverse events with GeneSight, Genecept, or another unspecified test (GRADE: Moderate-Very Low). No studies reported data on suicide, treatment adherence, relapse, recovery, or recurrence of depression symptoms.Our review included four model-based economic studies and found that multi-gene pharmacogenomic testing was associated with greater effectiveness and cost savings than treatment as usual, over long-term (i.e., 3-,5-year and lifetime) time horizons. Since none of the included studies was fully applicable to the Ontario health care system, we conducted a primary economic evaluation.Our reference case analysis over the 1-year time horizon found that multi-gene pharmacogenomic testing (with GeneSight) was associated with additional QALYs (0.03, 95% credible interval [CrI]: 0.005; 0.072) and additional costs ($1,906, 95% Crl: $688; $3,360). An incremental cost-effectiveness ratio was $60,564 per QALY gained. The probability of the intervention being cost-effective (vs. treatment as usual) was 36.8% at a willingness-to-pay amount of $50,000 per QALY (i.e., moderately likely not to be cost-effective), rising to 70.7% at a willingness-to-pay amount of $100,000 per QALY (i.e., moderately likely to be cost-effective). Evidence informing economic modeling of the reference case with GeneSight and other multi-gene pharmacogenomic tests was of low to very low quality, implying considerable uncertainty or low confidence in the effectiveness estimates. The price of the test, efficacy of the intervention on remission, time horizon, and analytic perspective were major determinants of the cost-effectiveness results. If the test price were assumed to be $2,162 (compared with $2,500 in the reference case), the intervention would be cost-effective at a willingness-to-pay amount of $50,000 per QALY; moreover, if the price decreased to $595, the intervention would be cost saving (or dominant) compared with treatment as usual.At an increasing uptake of 1% per year and a test price of $2,500, the annual budget impact of publicly funding multi-gene pharmacogenomic testing in Ontario over the next 5 years ranged from an additional $3.5 million in year 1 (at uptake of 1%) to $16.8 million in year 5. The 5-year budget impact was estimated at about $52 million.People with major depression and caregivers generally supported multi-gene pharmacogenomic testing because they believed it could provide guidance that fit their values. They hoped such guidance would speed symptom relief, would reduce side effects and help inform their medication choices. Some patients expressed concerns over maintaining confidentiality of test results and the possibility that physicians would sacrifice patient-centred care to follow pharmacogenomic guidance. Multi-gene pharmacogenomic testing that includes decision-support tools to guide medication selection for depression varies widely. Differences between individual tests must be considered, as clinical utility observed with one test might not apply to other tests. Overall, effectiveness was inconsistent among the six multi-gene pharmacogenomic tests we identified. Multi-gene pharmacogenomic tests may result in little or no difference in improvement in depression scores compared with treatment as usual, but some tests may improve response to treatment or remission from depression. The impact on adverse events is uncertain. The evidence, however, is uncertain, and therefore our confidence that these observed effects reflect the true effects is low to very low.For the management of major depression in people who had inadequate response to at least one medication, some multi-gene pharmacogenomic tests that include decision support tools are associated with additional costs and QALYs over the 1-year time horizon, and maybe be cost-effective at the willingness-to-pay amount of $100,000 per QALY. Publicly funding multi-gene pharmacogenomic testing in Ontario would result in additional annual costs of between $3.5 million and $16.8 million, with a total budget impact of about $52 million over the next 5 years.People with major depression and caregivers generally supported multi-gene pharmacogenomic testing because they believed it could provide guidance that fit their values. They hoped such guidance would speed symptom relief, would reduce side and help inform their medication choices. Some patients expressed concerns over maintaining confidentiality of test results and the possibility that physicians would sacrifice patient-centred care to follow pharmacogenomic guidance.

Ontario Health (Quality) 《-》

Mechanical Thrombectomy for Acute and Subacute Blocked Arteries and Veins in the Lower Limbs: A Health Technology Assessment.

A blockage to the blood vessels in the lower extremities may cause pain and discomfort. If left unmanaged, it may lead to amputation or chronic disability, such as in the form of post-thrombotic syndrome. We conducted a health technology assessment of mechanical thrombectomy (MT) devices, which are proposed to remove a blood clot, which may form in the arteries or veins of the lower legs. This evaluation considered blockages in the veins and arteries separately, and included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding MT for lower limb blockages, patient preferences and values, and clinical and health system stakeholders' perspectives. We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane tool for randomized controlled trials or the risk of bias among non-randomized studies (RoBANS) tool for nonrandomized studies, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search. We did not conduct a primary economic evaluation since the clinical evidence is highly uncertain. We also analyzed the budget impact of publicly funding MT treatment for inpatients with arterial acute limb ischemia and acute deep vein thrombosis (DVT) in the lower limb in Ontario. To contextualize the potential value of MT, we spoke with people with acute DVT. To understand the barriers and facilitators of accessing MT, we surveyed clinical and health system stakeholders to gain their perspectives. We included 40 studies (3 randomized controlled trials and 37 observational studies) in the clinical evidence review. For patients who experience arterial acute limb ischemia, compared with catheter-directed thrombolysis (CDT) alone, MT has greater technical success and patency and reduced hospital length of stay, but the evidence for these outcomes is uncertain (GRADE: Very low). Mechanical thrombectomy may reduce the volume of thrombolytic medication required and CDT infusion time (a determinant for intensive care unit [ICU] need) in patients experiencing acute DVT, but it is uncertain if this is to a meaningful degree (GRADE: Moderate to Very low). It may also reduce the proportion of people who experience post-thrombotic syndrome and overall hospital length of stay, but it is uncertain (GRADE: Very low).We estimated that publicly funding MT for people with arterial acute limb ischemia in Ontario would lead to an annual cost savings of $0.17 million in year 1 to $0.14 million in year 5, for a total savings of $0.83 million over 5 years. This cost savings was mainly attributed to reduced ICU stays among people who received MT, but the results had considerable uncertainty. For the population with acute DVT, publicly funding MT would lead to an additional cost of $0.77 million in year 1 to $1.44 million in year 5, for a total additional cost of $5.5 million over 5 years.The people with acute DVT with whom we spoke reported that MT was generally seen as a positive option, and those who had undergone the procedure reported positively on its value as a treatment to quickly remove a clot. Accessing treatment for DVT could be a barrier, especially in more remote areas of Ontario.Clinicians using the technology advised that facilitators to accessing the technology included perceived improvements in patient outcomes, resourcing requirements, addressing unmet needs, and avoidance of ICU stay. The main barrier identified was cost. Clinicians who were not using the technology advised that barriers were low case-use volume, along with costs for the equipment and for health human resources. Mechanical thrombectomy may have greater technical success and patency and reduce hospital length of stay for patients experiencing an arterial acute limb ischemia and, for patients with an acute DVT, it may reduce CDT volume and infusion time, the proportion of people who experience post-thrombotic syndrome, and hospital length of stay. Mechanical thrombectomy may reduce the associated ICU costs, but it has higher equipment costs compared with usual care. Publicly funding MT in Ontario for populations with arterial acute limb ischemia may not lead to a substantial budget increase to the province. Publicly funding MT for acute DVT would lead to an additional cost of $5.5 million over 5 years. For people with acute DVT, MT was seen as a potential positive treatment option to remove the clot quickly. Overall, the majority of clinical stakeholders we engaged with (including both those with and without experience with MT) were supportive of the use of the technology.

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Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke.

Higashida RT ，Furlan AJ ，Roberts H ，Tomsick T ，Connors B ，Barr J ，Dillon W ，Warach S ，Broderick J ，Tilley B ，Sacks D ，Technology Assessment Committee of the American Society of Interventional and Therapeutic Neuroradiology ，Technology Assessment Committee of the Society of Interventional Radiology ... -  《-》

Transcatheter Aortic Valve Implantation in Patients With Severe Aortic Valve Stenosis at Low Surgical Risk: A Health Technology Assessment.

Surgical aortic valve replacement (SAVR) is the conventional treatment for patients with severe aortic valve stenosis at low surgical risk. Transcatheter aortic valve implantation (TAVI) is a less invasive procedure. We conducted a health technology assessment (HTA) of TAVI for patients with severe aortic valve stenosis at low surgical risk, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding TAVI, and patient preferences and values. We used the 2016 Health Quality Ontario HTA on TAVI2 as a source of eligible studies and performed a systematic literature search for studies published since the 2016 review. Eligible primary studies identified both through the 2016 HTA and through our complementary literature search were used in a de novo analysis. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria.An applicable, previously conducted cost-effectiveness analysis was available, so we did not conduct a primary economic evaluation. We analyzed the budget impact of publicly funding TAVI in people at low surgical risk in Ontario. We also performed a literature survey of the quantitative evidence of preferences and values of patients for TAVI. The Canadian Agency for Drugs and Technologies in Health (CADTH) conducted a review to evaluate the qualitative literature on patient and provider preferences and values for TAVI. To contextualize the potential value of TAVI, we spoke with people with severe aortic valve stenosis. We identified two randomized controlled trials that compared TAVI (transfemoral route) and SAVR in patients with severe aortic valve stenosis at low surgical risk. Both studies have an ongoing follow-up of 10 years, but 1-year and limited 2-year follow-up results are currently available. At 30 days, compared with SAVR, TAVI had a slightly lower risk of mortality (risk difference -0.8%, 95% confidence interval [CI] -1.5% to -0.1%, GRADE: Moderate) and disabling stroke (risk difference -0.8%, 95% CI -1.8% to -0.2%, GRADE: Moderate), and resulted in more patients with symptom improvement (risk difference 11.8%, 95% CI 8.2% to 15.5%, GRADE: High) and in a greater improvement in quality of life (GRADE: High). At 1 year, TAVI and SAVR were similar with regard to mortality (GRADE: Low), although TAVI may result in a slightly lower risk of disabling stroke (GRADE: Moderate). Both TAVI and SAVR resulted in a similar improvement in symptoms and quality of life at 1 year (GRADE: Moderate). Compared with SAVR, TAVI had a higher risk of some complications and a lower risk of others.Device-related costs for TAVI (about $25,000) are higher than for SAVR (about $6,000). A published cost-effectiveness analysis conducted from an Ontario Ministry of Health perspective showed TAVI to be more expensive and, on average, slightly more effective (i.e., it was associated with more quality-adjusted life-years [QALYs]) than SAVR. Compared with SAVR, the incremental cost-effectiveness ratios (ICERs) were $27,196 per QALY and $59,641 per QALY for balloon-expandable and self-expanding TAVI, respectively. Balloon-expandable TAVI was less costly (by $2,330 on average) and slightly more effective (by 0.02 QALY on average) than self-expanding TAVI. Among the three interventions, balloon-expandable TAVI had the highest probability of being cost-effective. It was the preferred option in 53% and 59% of model iterations, at willingness-to-pay values of $50,000 and $100,000 per QALY, respectively. Self-expanding TAVI was preferred in less than 10% of iterations. The budget impact of publicly funding TAVI in Ontario is estimated to be an additional $5 to $8 million each year for the next 5 years. The budget impact could be significantly reduced with reductions in the device price.We did not find any quantitative or qualitative evidence on patient preferences and values specific to the low-risk surgical group. Among a mixed or generally high-risk and population, people typically preferred the less invasive nature and the faster recovery time of TAVI compared with SAVR, and people were satisfied with the TAVI procedure. Patients with severe aortic valve stenosis at low surgical risk and their caregivers perceived that TAVI minimized pain and recovery time. Most patients who had TAVI returned to their usual activities more quickly than they would have if they had had SAVR. Our direct patient and caregiver consultations indicated a preference for TAVI over SAVR. Both TAVI (transfemoral route) and SAVR resulted in improved patient symptoms and quality of life during the 1 year of follow-up. The TAVI procedure is less invasive and resulted in greater symptom improvement and quality of life than SAVR 30 days after surgery. The TAVI procedure also resulted in a small improvement in mortality and disabling stroke at 30 days. At 1 year, TAVI and SAVR were similar with regard to mortality, although TAVI may result in a slightly lower risk of disabling stroke. According to the study authors, longer follow-up is needed to better understand how long TAVI valves last and to draw definitive conclusions on the long-term outcomes of TAVI compared with SAVR beyond 1 year.The TAVI procedure might be cost-effective for patients at low surgical risk; however, there is some uncertainty in this result. We estimated that the additional cost to provide public funding for TAVI in people with severe aortic valve stenosis at low surgical risk would range from about $5 million to $8 million over the next 5 years.Among a mixed or generally high-risk population, people typically preferred the less invasive nature and the faster recovery time of TAVI compared with SAVR.

Ontario Health (Quality) 《-》