Ontario Health Technology Assessment Series最新文献

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

Background: Wounds may be caused in a variety of ways. Some wounds are difficult to heal, such as diabetic foot ulcers and venous leg ulcers. We conducted a health technology assessment of skin substitutes for adults with neuropathic diabetic foot ulcers and venous leg ulcers, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding skin substitutes, 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 for randomized studies (version 2), 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-utility analysis with a 26-week time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding skin substitutes in adults with diabetic foot ulcers and venous leg ulcers in Ontario. We explored the underlying values, needs, and priorities of those who have lived experience with diabetic leg ulcers and venous leg ulcers, as well as their preferences for and perceptions of skin substitutes.

Results: We included 40 studies in the clinical evidence review. Adults with difficult-to-heal neuropathic diabetic foot ulcers who used dermal (GRADE: High) or multi-layered (GRADE: Moderate) skin substitutes as an adjunct to standard care were more likely to experience complete wound healing than those whose who used standard care alone. Adults with difficult-to-heal venous leg ulcers who used dermal (GRADE: Moderate) or multi-layered (GRADE: High) skin substitutes as an adjunct to standard care were more likely to experience complete wound healing than those who used standard care alone. The evidence for the effectiveness of epidermal skin substitutes was inconclusive for venous leg ulcers because of the small size of the individual studies (GRADE: Very low). We found no studies on epidermal skin substitutes for diabetic foot ulcers. We could not evaluate the safety of skin substitutes versus standard care, because the number of adverse events was either very low or zero (because sample sizes were too small).In our economic analysis, the use of skin substitutes as an adjunct to standard care was more costly and more effective than standard care alone for the treatment of difficult-to-heal diabetic foot ulcers and venous leg ulcers. For diabetic foot ulcers, the incremental cost-effectiveness ratio (ICER) of skin substitutes plus standard care compared with standard care alone was $48,242 per quality-adjusted life-year (QALY), and the cost per ulcer-free week was $158. For venous leg ulcers, the ICER was $1,868,850 per QALY, and the cost per ulcer-free week was $3,235. At the commonly used willin

Background: Varicose veins are part of the spectrum of chronic venous disease and are a sign of underlying chronic venous insufficiency. Treatments to address varicose veins include surgical vein removal under general anesthesia, or endovenous laser (EVLA) or radiofrequency ablation (RFA) under tumescent anesthesia. Two newer nonthermal endovenous procedures can close veins without any tumescent anesthesia, using either mechanochemical ablation (MOCA, a combination of mechanical and chemical techniques) or cyanoacrylate adhesive closure (CAC). We conducted a health technology assessment of these nonthermal endovenous procedures for people with symptomatic varicose veins, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding MOCA and CAC, 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 or RoBANS tool, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Meta-analysis was conducted using Review Manager 5.2, where appropriate.We performed a systematic economic literature search and conducted a cost-utility analysis with a 5-year time horizon from the perspective of Ontario Ministry of Health. In our primary economic evaluation, we assessed the cost-effectiveness of nonthermal endovenous procedures (CAC and MOCA) compared with surgical vein stripping and thermal endovenous therapies (EVLA and RFA). We also analyzed the budget impact of publicly funding nonthermal and thermal endovenous therapies for adults with symptomatic varicose veins in Ontario over the next 5 years. Costs are expressed in 2020 Canadian dollars.To contextualize the potential value of nonthermal endovenous treatments, we spoke with 13 people with varicose veins who had sought various treatment options. We conducted phone interviews and qualitatively analyzed their responses regarding their care journey and the impact of different treatment options; the only nonthermal treatment that participants had experience with was CAC.

Results: We included 19 primary studies reported in 25 publications comparing either MOCA or CAC with at least one other invasive treatment for symptomatic varicose veins. No studies compared MOCA with CAC. Based on evidence of low to moderate quality, MOCA resulted in slightly poorer technical outcomes (vein closure and recanalization) than thermal endovenous ablation procedures. However, clinical outcomes, quality of life improvement, and patient satisfaction were similar compared with RFA (GRADE: Very low to Moderate) and EVLA (GRADE: High). Cyanoacrylate adhesive closure resulted in little to no difference in technical outcomes, clinical outcomes, and quality of life improvement compar

Background: Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate that commonly affects older people with prostates and may lead to obstructive urinary symptoms. Symptoms may initially be mild but tend to worsen over time. Prostatic artery embolization (PAE) is an endovascular procedure to treat BPH, wherein an interventional radiologist inserts a catheter into the patient to inject tiny particles intended to reduce blood flow to the enlarged prostate, causing it to shrink in size. We conducted a health technology assessment on PAE for people with BPH, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding PAE, 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 for randomized controlled trials (RCTs) and the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) tool for observational studies. 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 review of the economic literature. We then assessed the cost-effectiveness of PAE compared with alternative treatments (i.e., transurethral resection of the prostate [TURP] or open simple prostatectomy [OSP]) using a Markov microsimulation model. The analysis was conducted from the Ontario Ministry of Health perspective over a time horizon of 6.5 years. We also analyzed the budget impact of publicly funding PAE in people with moderate to severe BPH in Ontario.

Results: We included six studies in our systematic review. Four RCTs and one observational study compared PAE with TURP, and one observational study compared PAE with OSP. All studies had considerable risk-of-bias concerns. PAE may improve BPH symptoms and urodynamic measures, but we are uncertain whether PAE achieves better results than TURP (GRADE: Very low to Low). Compared with TURP, PAE may result in higher patient satisfaction and fewer adverse events (GRADE: Not assessed). Compared with OSP, PAE may result in smaller improvements in BPH symptoms and urodynamic measures and may lead to fewer adverse events, but the evidence is very uncertain (GRADE: Very low).We did not find any published cost-effectiveness studies in the economic literature review. Our primary economic evaluation showed that, compared with TURP, PAE has an incremental cost of $328 (95% CrI: -$686 to $1,423) and a very small incremental quality-adjusted life-year (QALY) of 0.007 (95% CrI: -0.004 to 0.018). The resulting incremental cost-effectiveness ratio (ICER) of PAE versus TURP is $44,930 per QALY gained. At the commonly used willingness-to-pay values of $50,000 and $100,000 per QALY, the cost-effectiveness of PAE is uncertain (5

Background: Early detection of melanoma is key, as survival rates are substantially better when the cancer is detected in its early stages. Currently, the standard of care is to biopsy any lesion suspected of melanoma for diagnostic confirmation by histopathology. As a result, most people who undergo biopsy receive negative melanoma results. If effective, a non-invasive alternative, such as pigmented lesion assay, could minimize the number of unnecessary biopsies performed. We conducted a health technology assessment of pigmented lesion assay for people with suspected melanoma lesions, which included an evaluation of diagnostic accuracy, clinical utility, the budget impact of publicly funding pigmented lesion assay, and the preferences and values of people who have undergone biopsy for suspected melanoma.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and the Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS). 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 literature search of the economic evidence. We also analyzed the budget impact of publicly funding pigmented lesion assay in adults with suspected melanoma in Ontario. To contextualize the potential value of pigmented lesion assay, we spoke with people who had undergone skin biopsy for melanoma. We also used the qualitative research synthesis from a report by the Canadian Agency for Drugs and Technologies in Health to provide context for the preferences and values of those with suspected melanoma.

Results: We included seven studies in the clinical evidence review. Pigmented lesion assay has a sensitivity of 79% (95% confidence interval [CI] 58%-93%) and a specificity of 80% (95% CI 73%-85%; GRADE: Low). We found one published cost-effectiveness study with potentially serious limitations. Therefore, the cost-effectiveness of pigmented lesion assay compared with the standard care pathway is currently uncertain. Assuming a very low uptake, we estimated that the budget impact of publicly funding pigmented lesion assay in Ontario over the next 5 years is about $3.44 million if the test is used exclusively by primary care providers, or about $2.56 million if it is used exclusively by specialists. The people with whom we spoke who had experienced biopsy for suspected melanoma responded positively to the potential benefits of pigmented lesion assay, emphasizing its ease-of-use, potential increase in early detection of melanoma, and reduction in physical and emotional burden of unnecessary biopsies. Participants also felt that the accuracy of this tool was essential to ensure minimal false negatives.

Conclusions: