Ontario Health Technology Assessment Series最新文献

Background: Pre-eclampsia is when high blood pressure develops after 20 weeks of pregnancy and either proteinuria, maternal end-organ dysfunction, or uteroplacental dysfunction causing fetal growth restriction also develops. The Fetal Medicine Foundation has created an algorithm ("the FMF algorithm") that uses maternal factors in combination with biophysical and biochemical markers to identify people at high risk for pre-eclampsia so that they can been offered acetylsalicylic acid (Aspirin) as a preventive measure. We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of a first-trimester population-wide screening program for pre-eclampsia risk that uses the FMF algorithm ("the FMF-based screening program"). We also evaluated the accuracy of the FMF algorithm, the budget impact of publicly funding the population-wide FMF-based screening program, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each study using the Risk of Bias in Non-randomized Studies-of Interventions tool and the Quality Assessment of Diagnostic Accuracy Studies-Comparative 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 conducted a cost-effectiveness analysis comparing the FMF-based screening program to standard care (screening for risk of pre-eclampsia using maternal factors alone) from a public payer perspective. We also analyzed the budget impact of publicly funding a population-wide FMF-based screening program in Ontario. We spoke with people who have experience with pregnancy and preeclampsia and their family members through direct interviews to gather preferences and values surrounding pre-eclampsia and the potential screening program.

Results: We included nine studies in the clinical evidence review. The FMF-based screening program likely reduces the risk of pre-eclampsia with delivery at less than 37 weeks' gestation compared with standard care, when initiated at 11+⁰ to 13+⁶ weeks' gestation; risk ratios ranged from 0.64 (95% confidence interval [CI] 0.46-0.93) to 0.70 (95% CI 0.58-0.84) (GRADE: Moderate). It may reduce the risks of low birth weight (risk ratio 0.89 [95% CI 0.85-0.94]) and low Apgar score (risk ratio 0.73 [95% CI 0.63-0.85]) (GRADE: Low). Evidence on the effectiveness of the FMF-based screening program in reducing the risk of stillbirth and neonatal death was highly uncertain (GRADE: Very low). In addition, the FMF algorithm can improve the detection rate of pre-eclampsia with delivery at less than 37 weeks' gestation or at less than 34 weeks' gestation compared with conventional algorithms, although there are concerns about bias and applicability ac

Background: Familial hypercholesterolemia (FH) is an inherited disorder characterized by abnormally elevated low-density lipoprotein (LDL) cholesterol serum levels from birth, which increases the risk of premature atherosclerotic cardiovascular disease. Genetic testing is a type of a medical test that looks for changes in genes or chromosome structure to discover genetic differences, anomalies, or mutations that may prove pathological. It is regarded as the gold standard for screening and diagnosing FH. We conducted a health technology assessment on genetic testing for people with FH and their relatives (i.e., cascade screening). The assessment included an evaluation of clinical utility (the ability of a test to improve health outcomes), the diagnostic yield (ability of a test to identify people with FH), cost-effectiveness, the budget impact of publicly funding genetic testing for FH, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. For evaluation of clinical utility, we assessed the risk of bias of each included study using the 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 and conducted a cost-effectiveness and cost-utility analysis with a lifetime horizon from a public payer perspective. We assessed the cost-effectiveness of using genetic testing both for confirming a FH clinical diagnosis and for cascade screening in relatives of genetically confirmed cases. We evaluated the cost effectiveness of cascade screening strategies with genetic testing, sequential testing, and lipid testing approaches. We also analyzed the budget impact of publicly funding genetic testing in Ontario.

Results: We included 11 studies in the clinical evidence review. Overall, our review found that genetic testing to diagnose FH improves several health outcomes (GRADE: Moderate) compared with clinical evaluation without a genetic test. We also found that genetic cascade screening leads to a high diagnostic yield of FH.According to our primary economic evaluation, genetic testing is a dominant strategy (more effective and less costly) compared with no genetic testing for individuals with a FH clinical diagnosis. It reduced the number of FH diagnoses, led to fewer cardiovascular events, and improved QALYs. For first-degree relatives of genetically confirmed cases, all cascade screening strategies (genetic testing, sequential testing, and lipid testing) were cost-effective when compared with no cascade screening in a pairwise fashion. The ICERs of cascade screening with genetic, sequential, and lipid testing compared with no cascade screening were $58,390, $50,220, and $45,754 per QALY gained, respectively. When comparing all screening strategies together, cascade screen

Background: Staphylococcus aureus (S. aureus) is the most common cause of surgical site infections, and the nose is the most common site for S. aureus colonization. Pre-surgical (in the days prior to surgery) nasal decolonization of S. aureus may reduce the bacterial load and prevent the organisms from being transferred to the surgical site, thus reducing the risk of surgical site infection. We conducted a health technology assessment of nasal decolonization of S. aureus (including methicillin-susceptible and methicillin-resistant strains) with or without topical antiseptic body wash to prevent surgical site infection in patients undergoing scheduled surgery, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding nasal decolonization of S. aureus, 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 chosen systematic review with a literature search to identify randomized controlled trials published since the systematic review was published in 2019. We used the Risk of Bias in Systematic Reviews (ROBIS) tool to assess the risk of bias of each included systematic review and the Cochrane risk-of-bias tool for randomized controlled trials to assess the risk of bias of each included primary study. 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 both cost-effectiveness and cost-utility analyses using a decision-tree model with a 1-year time horizon from the perspective of Ontario's Ministry of Health. We also analyzed the budget impact of publicly funding nasal decolonization of S. aureus in pre-surgical patients in Ontario. To contextualize the potential value of nasal decolonization, we spoke with people who had recently undergone surgery, some of whom had received nasal decolonization, and one family member of a person who had recently had surgery. We also engaged participants through an online survey.

Results: We included one systematic review and three randomized controlled trials in the clinical evidence review. In universal decolonization, compared with placebo or no intervention, nasal mupirocin alone may result in little to no difference in the incidence of overall and S. aureus-related surgical site infections in pre-surgical patients undergoing orthopaedic, cardiothoracic, general, oncologic, gynaecologic, neurologic, or abdominal digestive surgeries, regardless of S. aureus carrier status (GRADE: Moderate to Very low). Compared with placebo, nasal mupiro

Background: Bioprosthetic valves used to treat mitral or tricuspid valve disease can be expected to deteriorate and eventually fail after 10 to 15 years. For patients who are considered inoperable or high-risk for surgery, medical management (i.e., drug therapy, the current standard of care in Ontario) does not significantly alter the course of valvular heart disease or improve degenerated bioprosthetic valves. An alternative for these patients is transcatheter mitral or tricuspid valve-in-valve implantation (TMViV or TTViV). We conducted a health technology assessment of transcatheter valve-in-valve implantation for adults with degenerated mitral or tricuspid bioprosthetic valves who are considered inoperable or high-risk for surgery, which included an evaluation of effectiveness, safety, the budget impact of publicly funding TMViV or TTViV, and patient preferences and values.

Methods: We leveraged a previously published systematic review, supplementing the work with two new registry studies identified during the development of this report. We assessed the risk of bias of each included study using the Downs and Black checklist and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. As the earlier systematic review did not identify any cost-effectiveness studies, we conducted a hand search of the grey literature using targeted websites to identify relevant cost-effectiveness studies. We analyzed the budget impact of publicly funding transcatheter valve-in-valve implantation for adults with degenerated mitral or tricuspid bioprostheses who are considered inoperable or high-risk for surgery in Ontario. To contextualize the potential value of TMViV and TTViV, we spoke with people who had experience with heart valve replacement or who were awaiting heart valve replacement.

Results: We included 19 studies in the clinical evidence review. No studies compared TMViV or TTViV to medical management (standard care). TMViV was associated with in-hospital, 30-day and 1-year mortality rates of 0% to 5%, 0% to 15%, and 14% to 27%, respectively (GRADE: Very low). TTViV was associated with 30-day and 1-year mortality rates of 0% to 3% and 0% to 14%, respectively (GRADE: Very low). Patients experienced functional improvement related to their heart failure symptoms after TMViV or TTViV. Compared to before the intervention, both TMViV and TTViV were associated with a decrease in the number of patients with New York Heart Association class III or IV symptoms in hospital and at 30-day follow-up (GRADE: Low). We identified no relevant cost-effectiveness studies from our targeted search. The annual budget impact of publicly funding TMViV and TTViV in Ontario over the next 5 years ranges from an additional $0.35 million in year 1 to a cost saving of $0.19 million in year 5, for a total cost saving of $0.33 m

Background: The thyroid is a gland in the lower neck that is responsible for secreting hormones related to growth and metabolism. A cancer growth in the thyroid can spread to other parts of the body, but most thyroid nodules (growths) are benign, and some types of thyroid cancer are nonaggressive and can be managed with active surveillance only. We conducted a health technology assessment of molecular testing in people with thyroid nodules of indeterminate cytology, which included an evaluation of diagnostic accuracy, clinical utility, cost-effectiveness, the budget impact of publicly funding molecular testing, 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 Among Systematic Review (ROBIS) tool for systematic reviews, the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) assessment for primary studies that evaluated diagnostic accuracy, and the Risk of Bias tool for Non-randomized Studies (RoBANS) for primary studies that evaluated clinical utility. We evaluated 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 review and conducted cost-effectiveness and cost-utility analyses with a 5-year time horizon from the Ontario Ministry of Health perspective. We also analyzed the budget impact of publicly funding molecular testing in people with thyroid nodules of indeterminate cytology in Ontario. To contextualize the potential value of molecular testing in people with thyroid nodules of indeterminate cytology, we spoke to people with thyroid nodules.

Results: In the clinical evidence review, we included one systematic review, which contained eight relevant primary studies. Using molecular testing to support the rule-out of cancer in thyroid nodules of indeterminate significance may reduce the number of unnecessary surgeries. For diagnostic accuracy, molecular testing for a diagnosis of malignancy in a nodule of indeterminate significance had a sensitivity of 91% to 94% and a specificity of 68% to 82% (GRADE: Low). As well, lower rates of surgical resections were reported in nodules of indeterminate cytology (GRADE: Very Low). Compared to diagnostic lobectomy, we found that molecular testing would increase the probability of predicting a correct diagnosis, reduce the probability of unnecessary surgery, and lead to a slight improvement in quality-adjusted life-years (QALYs), but it would increase costs. The resulting incremental cost-effectiveness ratio was $220,572 to $298,653 per QALY gained. At the commonly used willingness-to-pay values of $50,000 and $100,000 per QALY gained, molecular testing was unlikely to be cost-effective (probability of molecular testing being cost-effective was les

Background: Bladder cancer begins in the innermost lining of the bladder wall and, on histological examination, is classified as one of two types: non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer. Transurethral resection of bladder tumour (TURBT) is the standard treatment for people with NMIBC, but the high rate of cancer recurrence after first TURBT is a challenge that physicians and patients face. Tumours seen during follow-up may have been missed or incompletely resected during first TURBT. TURBT is conventionally performed using white light to see the tumours. However, small papillary or flat tumours may be missed with the use of white light alone. With the emergence of new technologies to improve visualization during TURBT, better diagnostic and patient outcomes may be expected. We conducted a health technology assessment of two enhanced visualization methods, both as an adjunct to white light to guide first TURBT for people with suspected NMIBC-hexaminolevulinate hydrochloride (HAL), a solution that is instilled into the bladder to make tumours fluoresce under blue-violet light, and narrow band imaging (NBI), a technology that filters light into wavelengths that can be absorbed by hemoglobin in the tumours, making them appear darker. Our assessment included an evaluation of effectiveness, safety, cost-effectiveness, and the budget impact of publicly funding these new technologies to improve patient outcomes following first TURBT. The use of NBI in diagnostic cystoscopy was out of scope for this health technology assessment.

Methods: We performed a systematic literature search of the clinical evidence from inception to April 15, 2020. We searched for randomized controlled trials (RCTs) that compared the outcomes of first TURBT with the use of HAL or NBI, both as an adjunct to white light, with the outcomes of first TURBT using white light alone, or studies that made such comparison between HAL and NBI. We conducted pairwise meta-analyses using a fixed effects model where head-to-head comparisons were available. In the absence of any published RCT for comparison between HAL and NBI, we indirectly compared the two technologies through indirect treatment comparison (ITC) analysis. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool. 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 15-year time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding HAL and NBI as an adjunct to white light in people undergoing their first TURBT for suspected non-muscle-invasive bladder cancer in Ontario.

Results: In the clinical evidence review, we identified 8 RCTs that used HAL or NB

Background: Knee instability can arise from various causes and conditions such as neuromuscular disease, central nervous system conditions, and trauma. For people with knee instability, knee orthosis devices are prescribed to help with standing, walking, and performing tasks. We conducted a health technology assessment of stance-control knee-ankle-foot orthoses (SCKAFOs) for people with knee instability, which included an evaluation of the effectiveness, safety, and budget impact of publicly funding SCKAFOs, as well as 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 Nonrandomized Studies (RoBANS) 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 also analyzed the budget impact of publicly funding SCKAFOs in people with knee instabilities in Ontario. We did not conduct a primary economic evaluation as there was limited comparative clinical evidence to inform an economic model. Our reference case budget impact analysis was done from the perspective of the Ontario Ministry of Health; it compared the total costs of a basic mechanical SCKAFO and locked KAFO (LKAFO) for people with knee instability. We also performed scenario analyses varying the following parameters: the price of all classes of SCKAFO (mechanical, electronic, and microprocessor), and the uptake of SCKAFO. To contextualize the potential value of SCKAFO, we spoke with people with knee instability.

Results: We included four studies in the clinical evidence review. We are uncertain if SCKAFOs improve walking ability, energy consumption, or activities of daily living compared with LKAFOs (GRADE: Very low). Our economic evidence review identified one costing analysis that suggested that the costs of orthotic devices such as LKAFOs and SCKAFOs are highly variable according to the cost of materials, professional time, and customization required by the individual patient. The budget impact of publicly funding mechanical SCKAFOs in Ontario over the next 5 years (at a full device cost of $10,784) ranged from an additional $0.50 million in year 1 (at an uptake rate of 30% in the target population [429 eligible people]) to $0.83 million in year 5 (at an uptake rate of 50%), with a total budget impact of $3.34 million over 5 years. We found that the greatest increase in budget impact in the scenario analysis came from the microprocessor SCKAFO device, which had an additional cost of $10.07 million in year 1, increasing to $16.78 million in year 5. When we decreased the cost of a mechanical SCKAFO device (to $7,384), this reduced the 5-year budget impact to $0.89 million (vs. $3.34 million in the reference case). The people with kn

Background: Fluoropyrimidine drugs (such as 5-fluorouracil and capecitabine) are used to treat different types of cancer. However, these drugs may cause severe toxicity in about 10% to 40% of patients. A deficiency in the dihydropyrimidine dehydrogenase (DPD) enzyme, encoded by the DPYD gene, increases the risk of severe toxicity. DPYD genotyping aims to identify variants that lead to DPD deficiency and may help to identify people who are at higher risk of developing severe toxicity, allowing their treatment to be modified before it begins. Recommendations for fluoropyrimidine treatment modification are available for four DPYD variants, which are the focus of this review: DPYD∗2A, DPYD∗13, c.2846A>T, and c.1236G>A. We conducted a health technology assessment of DPYD genotyping for patients who have planned cancer treatment with fluoropyrimidines, which included an evaluation of clinical validity, clinical utility, the effectiveness of treatment with a reduced fluoropyrimidine dose, cost-effectiveness, the budget impact of publicly funding DPYD genotyping, 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 systematic review and primary study using the Risk of Bias in Systematic Reviews (ROBIS) tool and the Newcastle-Ottawa Scale, respectively, 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 review and conducted cost-effectiveness and cost-utility analyses with a half-year time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding pre-treatment DPYD genotyping in patients with planned fluoropyrimidine treatment in Ontario. To contextualize the potential value of DPYD testing, we spoke with people who had planned cancer treatment with fluoropyrimidines.

Results: We included 29 observational studies in the clinical evidence review, 25 of which compared the risk of severe toxicity in carriers of a DPYD variant treated with a standard fluoropyrimidine dose with the risk in wild-type patients (i.e., non-carriers of the variants under assessment). Heterozygous carriers of a DPYD variant treated with a standard fluoropyrimidine dose may have a higher risk of severe toxicity, dose reduction, treatment discontinuation, and hospitalization compared to wild-type patients (GRADE: Low). Six studies evaluated the risk of severe toxicity in DPYD carriers treated with a genotype-guided reduced fluoropyrimidine dose versus the risk in wild-type patients; one study also included a second comparator group of DPYD carriers treated with a standard dose. The evidence was uncertain, because the results of

Background: 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.

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 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.

Results: 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.

Background: Glaucoma is a condition that causes progressive damage to the optic nerve, which can lead to visual impairment and potentially to irreversible blindness. The iStent and iStent inject are devices implanted in the eye during a type of minimally invasive glaucoma surgery (MIGS) to reduce intraocular pressure by increasing trabecular outflow by bypassing the trabecular meshwork. We summarized two health technology assessments and additional recent publications that evaluated iStent for people with glaucoma, including effectiveness, safety, cost-effectiveness, the budget impact of publicly funding iStent, and patient preferences and values.

Methods: We summarized two health technology assessments recently completed in Canada. In addition, we summarized new evidence we identified through expert consultation and scoping of the literature. We reported the quality of the body of clinical evidence as reported by the included health technology assessments, according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria.

Results: Comparing iStent with pharmacotherapy, there may be no difference in comparative clinical effectiveness (GRADE: Very low to Low). There was uncertainty around the comparative clinical effectiveness of iStent compared with filtration surgery and of iStent plus cataract surgery compared with a different MIGS procedure plus cataract surgery (GRADE: Very low). iStent with cataract surgery may improve comparative clinical effectiveness (reduced intraocular pressure and number of medications) compared with cataract surgery alone (GRADE: Low).iStent may be cost-effective compared with pharmacotherapy (incremental cost-effectiveness ratios [ICER]: $14,120-$25,596/quality-adjusted life-year [QALY]; 60%-76% and 65%-100% of iterations cost-effective at willingness-to-pay values of $50,000/QALY and $100,000/QALY, respectively). iStent with cataract surgery may not be cost-effective compared with cataract surgery alone (ICERs: $108,934-$112,380/QALY; 17%-46% and 46%-68% of iterations cost-effective at willingness-to-pay values of $50,000/QALY and $100,000/QALY, respectively). iStent may not be cost-effective compared with filtration surgery (iStent was less effective and more expensive than filtration surgery). These estimates are influenced by the long-term effectiveness of iStent.The iStent device costs approximately $1,250 (for two iStent or iStent inject devices). Based on a recent analysis by Quebec's Institut national d'excellence en santé et en services sociaux (INESSS) and our previous analysis on MIGS, publicly funding iStent may reduce some spending on glaucoma medication but, overall, iStent is likely to lead to additional costs for the public health care system. In Ontario, publicly funding MIGS over 5 years is estimated to cost a total of $40 million if uptake is slow (25,000 people) and $199 million, if u