Ontario Health Technology Assessment Series最新文献

Background: RhD blood group incompatibility during pregnancy can cause serious health problems for the fetus. Noninvasive fetal RhD blood group genotyping is a test for fetal RhD status that may help prevent unnecessary preventive treatment (Rh immunoglobulin [RhIG] injections) and intensive pregnancy monitoring. We conducted a health technology assessment of noninvasive fetal RhD blood group genotyping for RhD-negative (RhD-) pregnancies. Our assessment evaluated the test's diagnostic accuracy, clinical utility, and cost-effectiveness, the budget impact of publicly funding this test, and patients' and providers' preferences and values.

Methods: We performed a systematic literature search of the clinical and economic evidence to conduct an overview of reviews for test accuracy, a systematic review for clinical utility, and a review of the test's cost-effectiveness compared with usual care. We assessed the risk of bias of each included systematic review and study using the ROBIS and RoBANs tools, respectively. We assessed the quality of the body of clinical evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We developed probabilistic Markov microsimulation models to determine the cost-effectiveness and cost-utility of noninvasive fetal RhD genotyping compared with usual care from the Ontario Ministry of Health perspective. We also estimated the 5-year budget impact of publicly funding this test in Ontario. To examine patient and provider preferences related to noninvasive fetal RhD genotyping, we conducted a literature survey of quantitative studies on preference; the Canadian Agency for Drugs and Technologies in Health (CADTH) performed a review of qualitative literature about patient preferences; and we conducted interviews and an online survey with Ontario patients.

Results: We included six systematic reviews in the overview of reviews on diagnostic test accuracy and 11 studies in the clinical utility review. Across systematic reviews, test accuracy was high for noninvasive fetal RhD genotyping. The evidence suggests that implementation of noninvasive fetal RhD genotyping may lead to avoidance of unnecessary RhIG prophylaxis (GRADE: Low), good compliance with targeted RhIG prophylaxis (GRADE: Very low), and high uptake of genotyping (GRADE: Low). Alloimmunization may not increase when using noninvasive fetal RhD genotyping to target prenatal RhIG prophylaxis (GRADE: Very low), and may allow unnecessary monitoring and invasive procedures to be avoided in alloimmunized pregnancies (GRADE: Very low).We included eight published economic studies that reported inconsistent results regarding the cost-effectiveness of noninvasive fetal RhD genotyping. In nonalloimmunized RhD- pregnancies, compared with usual care, the intervention identified more maternal alloimmunization cases (probability: 0.0022 vs. 0.0020) and

Background: Skin conditions are photoresponsive if they respond to ultraviolet (UV) radiation with partial or complete clearing. Ultraviolet phototherapy is performed by exposing the skin to UV radiation on a regular basis under medical supervision. Three types of UV radiation are used to treat photoresponsive skin conditions: broadband ultraviolet B (BB-UVB), psoralen plus ultraviolet A (PUVA), and narrowband ultraviolet B (NB-UVB). Narrowband UVB phototherapy is generally more effective than BB-UVB and safer than PUVA in the management of several photoresponsive skin conditions. While typically performed in an outpatient clinic setting, home NB-UVB phototherapy may be a viable option for people with limited access to outpatient treatment. We conducted a health technology assessment of home NB-UVB phototherapy for people with photoresponsive skin conditions that included an evaluation of the effectiveness, safety, cost-effectiveness, and budget impact of publicly funding home NB-UVB phototherapy, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using version 2 of the Cochrane risk-of-bias tool for randomized studies, and we assessed 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 conducted a cost-utility analysis with a 10-year horizon from a public payer perspective. The cost-utility analysis was conducted for psoriasis based on the available clinical evidence. We also analyzed the budget impact of publicly funding home NB-UVB phototherapy in people with photoresponsive skin conditions in Ontario. To contextualize the potential value of NB-UVB phototherapy, we spoke with people with photoresponsive skin conditions.

Results: We included one randomized controlled trial in the clinical evidence review. We found that home NB-UVB phototherapy is at least as effective as outpatient clinic NB-UVB phototherapy for the treatment of mild to severe psoriasis (the only photoresponsive skin condition investigated in the included study). In the included study, 82% of participants were treated at home, compared with 79% treated in an outpatient clinic setting (many participants had experience with both treatment settings). They demonstrated an improvement in baseline Psoriasis Area and Severity Index 50 (mean difference 2.8%, 95% confidence interval -8.6% to 14.2%), with the mean difference exceeding the preset noninferiority margin of -15%. Similar results were observed for other psoriasis area and severity indices (GRADE: Moderate). Episodes of mild erythema, burning sensation, severe erythema, and blistering were reported in both treatment groups, but were too few to allow a comparative safety assessment (GRADE: Low).

Background: 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.

Methods: 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.

Results: 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

Background: Chronic pain is costly for patients and for the health care system. It negatively affects people's physical, emotional, social, and mental health. We conducted a health technology assessment of 10-kHz high-frequency spinal cord stimulation (SCS) in adults with chronic noncancer pain that was refractory to medical management, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding 10-kHz high-frequency SCS, and patient preferences and values.

Methods: 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 and ROBINS-I tools 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 analyzed the 5-year budget impact of publicly funding 10-kHz high-frequency SCS in Ontario for adults with chronic noncancer pain who had already tried other available SCS therapies (up to 1.2 kHz). To contextualize the potential value of 10-kHz high-frequency SCS, we spoke with people who had chronic noncancer pain.

Results: We included 5 studies (7 publications) in the clinical evidence review. Overall, 10-kHz high-frequency SCS likely provides reductions in pain intensity and functional disability, and improvements in quality of life in people with chronic noncancer pain (GRADE: Moderate). As well, patients may reduce their opioid consumption with 10-kHz high-frequency SCS (GRADE: Low). The two included economic evaluations found that 10-kHz high-frequency SCS was cost-saving compared with conventional SCS, but neither was applicable to the Ontario context. Owing to limited evidence about the effectiveness of 10-kHz high-frequency SCS in people who have first tried and failed SCS at lower frequencies (up to 1.2 kHz), we did not conduct a cost-effectiveness analysis comparing this pathway of care and 10-kHz high-frequency SCS for Ontario. Publicly funding 10-kHz high-frequency SCS (using the Freedom SCS system) in Ontario over the next 5 years would lead to a total net cost savings of $0.73 million (ranging from about $0.10 million in year 1 to about $0.21 million in year 5). However, if the province outsourced this therapy using the Senza HF10 SCS system, the total 5-year budget impact would be about $8.76 million. The people we spoke with who had chronic noncancer pain reported that their pain had a substantial negative impact on their activities and emotional well-being. Their direct knowledge of different pain therapies allowed them to provide context and comparisons when they discussed the impact of SCS on their chronic pain.

Conclusions: For adults with chronic noncancer pain that was refractory to medical management, 10-kHz high-frequency SCS was effective i

Background: Heart transplantation is the most effective treatment for people experiencing end-stage heart failure whose quality of life and life expectancy are unacceptable. However, there is a chronic shortage of donor hearts to meet the demand, so it is essential to expand the donor pool and increase supply. Heart donation mainly occurs after brain death (neurological determination of death [NDD]), but it may also be feasible after cardiocirculatory death (when the heart has stopped beating and there is no longer blood flow or a pulse), provided specialized preservation techniques are used. An investigational device, a portable normothermic cardiac perfusion system, could make it possible to procure, preserve, and transport hearts donated after cardiocirculatory death (DCD). We conducted a health technology assessment of a portable normothermic cardiac perfusion system for the preservation and transportation of DCD hearts for adult transplantation. This included an evaluation of the effectiveness, safety, value for money, and budget impact of publicly funding this system, as well as an evaluation of patient preferences and values.

Methods: We performed a systematic review of the clinical literature published since 1998 that examined the clinical safety and effectiveness of a portable normothermic cardiac perfusion system for DCD heart transplantation. We assessed the risk of bias of each included study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also reviewed the economic evidence published during the same time period for the cost-effectiveness of a portable normothermic cardiac perfusion system for DCD hearts compared with cold storage for NDD hearts. We further estimated the 5-year net budget impact of publicly funding a normothermic cardiac perfusion system for DCD heart transplantation for adults on Ontario's waitlist. To contextualize the potential value of a portable normothermic cardiac perfusion system, we spoke with people waiting for a heart transplant, people who had received a heart transplant, and family members of organ donors.

Results: We screened 2,386 clinical citations. One study and two case reports met the inclusion criteria. The survival of recipients of DCD hearts procured with a portable normothermic cardiac perfusion system did not differ significantly from the survival of recipients of hearts donated after NDD at 30 days or 90 days, nor was there a significant difference in cumulative survival at 1 year post-transplant (GRADE: Very Low). The occurrence of rejection and graft failure also did not significantly differ between the groups (GRADE: Very Low). Cardiac function in the early post-operative period was better in DCD hearts than NDD hearts (GRADE: Very Low). There were no differences in outcomes between DCD procurement techniques.The eco

Background: Neurofibromatosis 2 (NF2) is a rare genetic disorder that causes vestibular schwannomas to develop in both eighth cranial nerves. Almost all people with NF2 eventually become completely deaf as a result of progressive tumour enlargement or following surgical or radiotherapy treatment. Other rare abnormal conditions in the inner ears can also cause complete deafness. For people with either indication who are not candidates for cochlear implantation, auditory brainstem implantation is the only treatment option to restore some functional hearing. We conducted a health technology assessment of auditory brainstem implantation for adults with NF2 and severe inner ear abnormalities, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding auditory brainstem implantation, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) 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. We did not conduct a primary economic evaluation because the outcomes identified in our clinical evidence review were difficult to translate into measures appropriate for health economic modelling. We also analyzed the net budget impact of publicly funding auditory brainstem implantation over the next 5 years in Ontario, including the device, presurgical assessment, surgical procedure, and postsurgical rehabilitation. To contextualize the potential value of auditory brainstem implants, we spoke with six people with lived experience of NF2 and severe inner ear abnormalities.

Results: We included 22 publications (16 in NF2, five in severe inner ear abnormalities, and one in complications of auditory brainstem implantation) in the clinical evidence review. In adults with NF2, auditory brainstem implantation when compared with no intervention allows any degree of improvement in sound recognition (GRADE: High), allows any degree of improvement in speech perception when used in conjunction with lip-reading (GRADE: High), and provides subjective benefits of hearing (GRADE: High). It likely allows any degree of improvement in speech perception when using the implant alone (GRADE: Moderate) and may improve quality of life (GRADE: Low). In adults with severe inner ear abnormalities, auditory brainstem implantation when compared with no intervention likely allows any degree of improvement in sound recognition (GRADE: Moderate) and in any speech perception when using the implant alone (GRADE: Moderate). It may allow any degree of improvement in speech perception when used in conjunction with lip-reading (GRADE: Low),

Background: Single-sided deafness refers to profound sensorineural hearing loss or non-functional hearing in one ear, with normal or near-normal hearing in the other ear. Its hallmark is the inability to localize sound and hear in noisy environments. Conductive hearing loss occurs when there is a mechanical problem with the conduction of sound vibrations. Mixed hearing loss is a combination of sensorineural and conductive hearing loss. Conductive and mixed hearing loss, which frequently affect both ears, create additional challenges in learning, employment, and quality of life. Cochlear implants and bone-conduction implants may offer objective and subjective benefits of hearing for people with these conditions who are deemed inappropriate candidates for standard hearing aids and do not meet the current indication (i.e., bilateral deafness) for publicly funded cochlear implants in Canada.

Methods: We conducted a health technology assessment, which included an evaluation of clinical benefits and harms, cost-effectiveness, budget impact, and patient preferences and values related to implantable devices for single-sided deafness and conductive or mixed hearing loss. We performed a systematic literature search for systematic reviews and cost-effectiveness studies of cochlear implants and bone-conduction implants, compared to no interventions, for these conditions in adults and children. We conducted cost-utility analyses and budget impact analyses from the perspective of the Ontario Ministry of Health to examine the impact of publicly funding both types of hearing implants for the defined populations. We also interviewed 22 patients and parents of children about their experience with hearing loss and hearing implants.

Results: We included 20 publications in the clinical evidence review. For adults and children with single-sided deafness, cochlear implantation when compared with no treatment improves speech perception in noise (% correct responses: 43% vs. 15%, P < .01; GRADE: Moderate), sound localization (localization error: 14° vs. 41°, P < .01; GRADE: Moderate), tinnitus (Visual Analog Scale, loudness: 3.5 vs. 8.5, P < .01; GRADE: Moderate), and hearing-specific quality of life (Speech Spatial and Qualities of Hearing Scale, speech: 5.8 vs. 2.6, P = .01; spatial: 5.7 vs. 2.3, P < .01; GRADE: Moderate); for children, speech and language development also improve (GRADE: Moderate). For those with single-sided deafness in whom cochlear implantation is contraindicated, bone-conduction implants when compared with no intervention provide clinically important functional gains in hearing thresholds (36-41 dB improvement in pure tone audiometry and 38-56 dB improvement in speech reception threshold, P < .05; GRADE: Moderate) and improve speech perception in noise (signal-to-noise ratio -2.0 vs. 0.6, P < .05 for active percutaneous devices; signa

Background: High-grade gliomas are a type of malignant brain tumour. Optimal management often includes maximal surgical resection. 5-aminolevulinic acid hydrochloride (5-ALA) is an imaging agent that makes a high-grade glioma fluoresce under blue light, which can help guide the surgeon when removing the tumour. We conducted a health technology assessment of 5-ALA-guided surgical resection of high-grade gliomas, which included an evaluation of effectiveness, safety, the budget impact of publicly funding 5-ALA, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence to retrieve systematic reviews, and selected and reported results from one review that was recent, of high quality, and relevant to our research question. We complemented the identified systematic review with a literature search to identify randomized controlled trials published after the review. We reported the risk of bias of each included study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also performed a systematic economic literature search to identify economic studies that compared 5-ALA-guided surgical resection of high-grade gliomas with standard surgical care or other intraoperative imaging modalities. We did not conduct a primary economic evaluation due to lack of high-quality published clinical evidence evaluating 5-ALA-guided surgical resection. From the perspective of the Ontario Ministry of Health, we analyzed the 5-year budget impact of publicly funding 5-ALA-guided surgical resection for adults with newly diagnosed, primary, high-grade gliomas for which resection is considered feasible. To contextualize the potential value of 5-ALA, we spoke with someone who had experience with high-grade glioma, 5-ALA-guided resection, and standard surgical treatment.

Results: We included one systematic review reporting on a single randomized controlled trial in the clinical evidence review. 5-ALA increased the proportion of patients achieving complete tumour resection compared with standard care (relative risk of incomplete resection 0.55, 95% confidence interval 0.42-0.71; GRADE: Low). Evidence was uncertain for an effect on overall survival with 5-ALA (hazard ratio for death 0.82, 95% confidence interval 0.62-1.07; GRADE: Low), but there may be an improvement in 6-month progression-free survival (GRADE: Very low). Adverse events between groups was insufficiently reported, but appeared similar between groups for overall and neurological adverse events, with an observed increase in neurological deficits 48 hours after surgery with 5-ALA (GRADE: Very low). The economic literature search identified five studies that met our inclusion criteria because they evaluated the cost-effectiveness of 5-ALA-guided surgical resection as compared with surgery with a

Background: Stroke is a serious health issue in which an interruption in blood flow to any part of the brain damages brain cells. About 83% of people survive with substantial morbidity after their first stroke. We conducted a health technology assessment of continual long-term physiotherapy for people with a diagnosis of stroke, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding continual long-term physiotherapy for people with a diagnosis of stroke, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We also performed a systematic literature search of the economic evidence. We did not conduct a primary economic evaluation because there was insufficient clinical evidence. We also analyzed the budget impact of publicly funding continual long-term physiotherapy after stroke in Ontario. To contextualize the potential value of continual long-term physiotherapy after stroke, we spoke with people who had been diagnosed with stroke, as well as their caregivers.

Results: We did not find any published studies that met the specific clinical inclusion criteria. We did not identify any studies that compared the cost-effectiveness of continual long-term versus short-term physiotherapy after stroke. The budget impact of publicly funding continual long-term physiotherapy after stroke in Ontario over the next 5 years ranges from $445,000 in year 1 at an uptake rate of 8% to $888,000 in year 5 at an uptake rate of 16%. The people who had been diagnosed with stroke with whom we spoke reported that they had benefitted from continual long-term physiotherapy.

Conclusions: We did not identify studies that addressed the specific research question. Based on the clinical evidence review, we are unable to determine the benefits of continual long-term compared with short-term physiotherapy after stroke. The cost-effectiveness of continual long-term physiotherapy after stroke in Ontario is unknown. We estimate that publicly funding continual long-term physiotherapy after stroke in Ontario would result in additional costs of between $445,000 and $888,000 annually over the next 5 years. Patients and caregivers who we spoke with felt that patients who have experienced a stroke should be able to continue with physiotherapy.

Background: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy used to stabilize patients with hemodynamic compromise such as refractory cardiogenic shock or cardiac arrest. When used for cardiac arrest, ECMO is also known as extracorporeal cardiopulmonary resuscitation (ECPR). We conducted a health technology assessment of venoarterial ECMO for adults (aged ≥ 18 years) with cardiac arrest refractory to conventional cardiopulmonary resuscitation (CPR) or with cardiogenic shock refractory to conventional medical management (i.e., drugs, mechanical support such as intra-aortic balloon pump and temporary ventricular assist devices). Our assessment included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding ECMO for these indications, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias in Systematic Reviews (ROBIS) tool for systematic reviews and the Risk of Bias Among Nonrandomized Trials (ROBINS-I) tool for observational 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 and conducted a cost-effectiveness analysis with a lifetime horizon from a public payer perspective. We also analyzed the budget impact of publicly funding ECMO in Ontario for patients with refractory cardiogenic shock or cardiac arrest. To contextualize the potential value of ECMO for cardiac indications, we spoke with patients and caregivers with direct experience with the procedure.

Results: We included one systematic review (with 13 observational studies) and two additional observational studies in the clinical review. Compared with traditional CPR for patients with refractory cardiac arrest, ECPR was associated with significantly improved 30-day survival (pooled risk ratio [RR] 1.54; 95% CI 1.03 to 2.30) (GRADE: Very Low) and significantly improved long-term survival (pooled RR 2.17; 95% CI 1.37 to 3.44) (GRADE: Low). Overall, ECPR was associated with significantly improved 30-day favourable neurological outcome in patients with refractory cardiac arrest compared with traditional CPR; pooled RR 2.02 (95% CI 1.29 to 3.16) (GRADE: Very Low). For patients with cardiogenic shock, ECMO was associated with a significant improvement in 30-day survival compared with intra-aortic balloon pump (pooled RR 2.11; 95% CI 1.23 to 3.61) (GRADE: Very Low). Compared with temporary percutaneous ventricular assist devices, ECMO was not associated with improved survival (pooled risk ratio 0.94; 95% CI 0.67 to 1.30) (GRADE: Very Low).We estimated the incremental cost-effectiveness ratio of ECPR compared with conventional CPR is $18,722 and $28,792 per life-year gained (LYG) fo