Health Technology Assessment Reports for Non-Oncology Medications in Canada from 2018 to 2022: Methodological Critiques on Manufacturers' Submissions and a Comparison between Manufacturer and Canadian Agency for Drugs and Technologies in Health (CADTH) Analyses.

INTRODUCTION: Identifying key differences between manufacturers' submitted analysis and economic reanalysis by the Canadian Agency for Drugs and Technologies in Health (CADTH) is an important step toward understanding reimbursement recommendations. We compared economic values reported in manufacturers' analysis with the CADTH reanalysis and also assessed methodological critiques. METHODS: Two reviewers extracted data from the clinical and economic reports in publicly available CADTH reports from 2018 to 2022. We used the Wilcoxon rank-sum test to assess the difference between mean economic values, and the Chi-square test to assess the association between the CADTH critique final recommendations. RESULTS: Of the total submissions, 99.4% included effectiveness critiques, 88.8% included model structure critiques, 69.1% included utility score critiques, and 78.7% included cost critiques. The median incremental cost-utility ratio (ICUR) in the manufacturers' analyses was $138,658/quality-adjusted life-year (QALY), 2.5-fold lower than the CADTH's reanalysis at $380,251/QALY (p < 0.001). The median CADTH reanalysis for 3-year budget impact analysis (BIA) was $4,575,102, which was 27% higher than the manufacturers' submitted 3-year BIA (p < 0.001). CADTH requested a price reduction for 95% of all submissions, and the median price reduction request was 63.5%. In 2021 and 2022, the willingness-to-pay threshold identified in CADTH reports remained constant at $50,000 per QALY gained for all medications. CONCLUSION: There was high frequency of CADTH critiques on manufacturers' submissions in all four aspects of economic submissions: effectiveness, cost, utility score and structure. We observed a higher median incremental cost and lower median incremental QALYs in the CADTH reanalysis compared with the manufacturers' submissions. The resulting higher ICUR in the CADTH reanalysis often leads to a recommendation that the manufacturer needs to reduce its price. The 3-year budget impact was higher in the CADTH reanalyses compared with manufacturers' submissions.

A scoping review of costing methodologies used to assess interventions for underserved pregnant people and new parents.

BACKGROUND: Lack of evidence about the long-term economic benefits of interventions targeting underserved perinatal populations can hamper decision making regarding funding. To optimize the quality of future research, we examined what methods and costs have been used to assess the value of interventions targeting pregnant people and/or new parents who have poor access to healthcare. METHODS: We conducted a scoping review using methods described by Arksey and O'Malley. We conducted systematic searches in eight databases and web-searches for grey literature. Two researchers independently screened results to determine eligibility for inclusion. We included economic evaluations and cost analyses of interventions targeting pregnant people and/or new parents from underserved populations in twenty high income countries. We extracted and tabulated data from included publications regarding the study setting, population, intervention, study methods, types of costs included, and data sources for costs. RESULTS: Final searches were completed in May 2024. We identified 103 eligible publications describing a range of interventions, most commonly home visiting programs (n = 19), smoking cessation interventions (n = 19), prenatal care (n = 11), perinatal mental health interventions (n = 11), and substance use treatment (n = 10), serving 36 distinct underserved populations. A quarter of the publications (n = 25) reported cost analyses only, while 77 were economic evaluations. Most publications (n = 82) considered health care costs, 45 considered other societal costs, and 14 considered only program costs. Only a third (n = 36) of the 103 included studies considered long-term costs that occurred more than one year after the birth (for interventions occurring only in pregnancy) or after the end of the intervention. CONCLUSIONS: A broad range of interventions targeting pregnant people and/or new parents from underserved populations have the potential to reduce health inequities in their offspring. Economic evaluations of such interventions are often at risk of underestimating the long-term benefits of these interventions because they do not consider downstream societal costs. Our consolidated list of downstream and long-term costs from existing research can inform future economic analyses of interventions targeting poorly served pregnant people and new parents. Comprehensively quantifying the downstream and long-term benefits of such interventions is needed to inform decision making that will improve health equity.

Improving medication prescribing-related outcomes for vulnerable elderly in transitions on high-risk medications (IMPROVE-IT HRM): a pilot randomized trial protocol.

BACKGROUND: Seniors with recurrent hospitalizations who are taking multiple medications including high-risk medications are at particular risk for serious adverse medication events. We will assess whether an expert Clinical Pharmacology and Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care is feasible and can decrease drug therapy problems amongst this group. METHODS: The design is a pragmatic pilot randomized trial with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis. Participants will be adults 65 years and older admitted to internal medicine services for more than 2 days, who have had at least one other hospitalization in the prior year, taking five or more chronic medications including at least one high-risk medication. The CPT intervention identifies medication targets; completes consult, including priorities for improving prescribing negotiated with the patient; starts the care plan; ensures a detailed discharge medication reconciliation and circle-of-care communication; and sees the patient at least twice after hospital discharge via virtual visits to consolidate the care plan in the community. Control group receives usual care. Primary outcomes are feasibility - recruitment, retention, costs, and clinical - number of drug therapy problems improved, with secondary outcomes examining coordination of transitions in care, quality of life, and healthcare utilization and costs. Follow-up is to 3-month posthospital discharge. DISCUSSION: If results support feasibility of ramp-up and promising clinical outcomes, a follow-up definitive trial will be organized using a developing national platform and medication appropriateness network. Since the intervention allows a very scarce medical specialty expertise to be offered via virtual care, there is potential to improve the safety, outcomes, and cost of care widely. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04077281.

Opioid reduction and enhanced recovery in orthopaedic surgery (OREOS): a protocol for a feasibility randomised controlled trial in patients undergoing total knee arthroplasty.

BACKGROUND: Knee arthritis is a leading cause of limited function and long-term disability in older adults. Despite a technically successful total knee arthroplasty (TKA), around 20% of patients continue to have persisting pain with reduced function, and low quality of life. Many of them continue using opioids for pain control, which puts them at risk for potential long-term adverse effects such as dependence, overdose and risk of falls. Although persisting pain and opioid use after TKA have been recognised to be important issues, individual strategies to decrease their burden have limitations and multi-component interventions, despite their potential, have not been well studied. In this study, we propose a multi-component pathway including personalized pain management, facilitated by a pain management coordinator. The objectives of this pilot trial are to evaluate feasibility (recruitment, retention, and adherence), along with opioid-free pain control at 8 weeks after TKA. METHODS: This is a protocol for a multicentre pilot randomised controlled trial using a 2-arm parallel group design. Adult participants undergoing unilateral total knee arthroplasty will be considered for inclusion and randomised to control and intervention groups. Participants in the intervention group will receive support from a pain management coordinator who will facilitate a multicomponent pain management pathway including (1) preoperative education on pain and opioid use, (2) preoperative risk identification and mitigation, (3) personalized post-discharge analgesic prescriptions and (4) continued support for pain control and recovery up to 8 weeks post-op. Participants in the control group will undergo usual care. The primary outcomes of this pilot trial are to assess the feasibility of participant recruitment, retention, and adherence to the interventions, and key secondary outcomes are persisting pain and opioid use. DISCUSSION: The results of this trial will determine the feasibility of conducting a definitive trial for the implementation of a multicomponent pain pathway to improve pain control and reduce harms using a coordinated approach, while keeping an emphasis on patient centred care and shared decision making. TRIAL REGISTRATION: Prospectively registered in Clinicaltrials.gov (NCT04968132).

Robot-assisted partial knee replacement versus standard total knee replacement (RoboKnees): a protocol for a pilot randomized controlled trial.

BACKGROUND: Total knee arthroplasty is a common surgery for end-stage knee osteoarthritis. Partial knee arthroplasty is also a treatment option for patients with arthritis present in only one or two knee compartments. Partial knee arthroplasty can preserve the natural knee biomechanics, but these replacements may not last as long as total knee replacements. Robotic-assisted orthopedic techniques can help facilitate partial knee replacements, increasing accuracy and precision. This trial will investigate the feasibility and assess clinical outcomes for a larger definitive trial. METHODS: This is a protocol for an ongoing parallel randomized pilot trial of 64 patients with uni- or bicompartmental knee arthritis. Patients are randomized to either receive robot-assisted partial knee arthroplasty or manual total knee arthroplasty. The primary outcome of this pilot is investigating the feasibility of a larger trial. Secondary (clinical) outcomes include joint awareness, return to activities, knee function, patient global impression of change, persistent post-surgical pain, re-operations, resource utilization and cost-effectiveness, health-related quality of life, radiographic alignment, knee kinematics during walking gait, and complications up to 24 months post-surgery. DISCUSSION: The RoboKnees pilot study is the first step in determining the outcome of robot-assisted partial knee replacements. Conclusions from this study will be used to design future large-scale trials. This study will inform surgeons about the potential benefits of robot-assisted partial knee replacements. TRIAL REGISTRATION: This study was prospectively registered on clinicaltrials.gov (identifier: NCT04378049) on 4 May 2020, before the first patient was randomized.

Cannabis for medical use versus opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised clinical trials.

OBJECTIVE: The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021. STUDY SELECTION: Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings. RESULTS: Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) -1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI -0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI -4.72 to 5.59). CONCLUSIONS: Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain. PROSPERO REGISTRATION NUMBER: CRD42020185184.

Economic evaluation of non-invasive liver tests for the diagnosis of liver fibrosis in chronic liver diseases: a systematic review protocol.

OBJECTIVE: The objective of this review is to determine the costs and benefits of non-invasive liver tests vs liver biopsy in patients with chronic liver diseases. INTRODUCTION: Hepatic diseases can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. In the past, liver biopsy was the only option for diagnosing fibrosis degree. Liver biopsy is an invasive procedure that depends on the sample size to be able to deliver an accurate diagnosis. In recent years, non-invasive liver tests have been increasingly used to estimate liver fibrosis degree; however, there is a lack of economic assessments of technology implementation outcomes. INCLUSION CRITERIA: This review will include partial (cost studies) and complete economic evaluation studies on hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease that compare non-invasive liver tests with liver biopsies. Studies published in English, French, Spanish, German, Italian, or Portuguese will be included. No date limits will be applied to the search. METHODS: This review will identify published and unpublished studies. Published studies will be identified using MEDLINE (PubMed), Cochrane Library (CENTRAL), Embase, Web of Science, Scopus, and LILACS. Sources of unpublished studies and gray literature will include sources from health technology assessment agencies, clinical practice guidelines, regulatory approvals, advisories and warnings, and clinical trial registries, as well as Google Scholar. Two independent reviewers will screen and assess studies, and extract and critically appraise the data. Data extracted from the included studies will be analyzed and summarized to address the review objective using narrative text, and the JBI dominance ranking matrix. REVIEW REGISTRATION: PROSPERO CRD42023404278.

Inhibitors in hemophilia: association with surgery plans and outcomes in a retrospective cohort study.

Background: The development of antibodies (inhibitors) to clotting factors compromises the management of hemophilia A and B, resulting in resistance to clotting factor replacement and, in many cases, the need for bypassing agents to achieve hemostasis. Objectives: To evaluate the association between the presence of inhibitors and achievement of perioperative hemostasis, development of complications, and presurgical plan deviations. Methods: We conducted a retrospective study using data from the Indiana Hemophilia and Thrombosis Center surgical database (1998-2019). Associations between perioperative outcomes and inhibitor status were assessed while controlling for patient and procedural characteristics. Results: A total of 1492 surgeries were performed in 539 persons with hemophilia, with 72 procedures performed in 20 patients with inhibitors (15 with hemophilia A; 5 with hemophilia B). High-responding inhibitors (>5 BU/mL) were present in 27 procedures, low-responding inhibitors (≤5 BU/mL) were present in in 13 procedures, and 32 procedures were performed in patients with historically persistent inhibitors. Adjusting for age, diagnosis, surgery setting, hemostatic agent, data collection period, and surgery type (major/minor), inhibitors were associated with a higher risk of inadequate perioperative hemostasis (33.4% vs 8.6%; adjusted relative risk [adjRR], 3.78; 95% CI, 1.89-7.56; P < .001). Reported complications include hemorrhage, fever, pain, thrombosis, and infections. Complications were not statistically different based on inhibitor status (31.7% vs 14.6%; adjRR, 1.25; 95% CI, 0.63-2.49; P = .526). Presurgical plan deviations (eg, hemostatic medication dose adjustments, procedure rescheduling, and changes in the length of postoperative hospitalization) occurred more frequently in surgeries involving inhibitors (70.8 vs 39.5%; adjRR, 1.47; 95% CI, 1.12-1.93; P = .005). Conclusion: Inhibitors are associated with higher risks of adverse perioperative outcomes. Strategies to address inhibitor development should be prioritized to avoid undesirable perioperative outcomes.

Motivational interviewing to promote healthy behaviors for obesity prevention in young adults (MOTIVATE): a pilot randomized controlled trial protocol.

BACKGROUND: Obesity is a chronic disease and is an established risk factor for other chronic diseases and mortality. Young adulthood is a period when people may be highly amenable to healthy behavior change, develop lifelong healthy behaviors, and when primary prevention of obesity may be feasible. Interventions in early adulthood have the potential for primary or primordial prevention (i.e., preventing risk factors before disease onset). The primary objective of this study is to determine the feasibility of a 6-month behavioral and educational intervention to promote healthy behaviors for obesity prevention among young adults. METHODS: This is the study protocol for a pilot randomized controlled trial. Young adults (age 18-29) attending McMaster University, Hamilton, Canada, will be recruited and randomized to either the intervention or control. The intervention will include individual motivational interviewing sessions (online or in-person) with a trained interviewer plus educational materials (based on Canada's food guide and physical activity recommendations). The control group will receive educational materials only. The primary feasibility outcomes that will be evaluated as part of this pilot study include enrollment, retention (≥ 80%), data completion (≥ 80% of weights measured, and surveys completed), and participant satisfaction. Secondary clinical outcomes will include body mass index (BMI) change from baseline to 6 months, physical activity, nutrition risk, health-related quality of life mental health, and economic outcomes. Outcomes will be measured remotely using activity trackers, and online questionnaires at baseline and every 2 months. Risk stratification will be applied at baseline to identify participants at high risk of obesity (e.g., due to family or personal history). Exit questionnaires will collect data on how participants felt about the study and cost analysis will be conducted. DISCUSSION: Our pilot randomized controlled trial will evaluate the feasibility of an obesity prevention intervention in early adulthood and will inform future larger studies for obesity prevention. The results of this study have the potential to directly contribute to the primary prevention of several types of cancer by testing an intervention that could be scalable to public health, post-secondary education, or primary care settings. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05264740 . Registered on March 3, 2022.

Health Technology Reassessment: Addressing Uncertainty in Economic Evaluations of Oncology Drugs at Time of Reimbursement Using Long-Term Clinical Trial Data.

The evidence base to support reimbursement decision making for oncology drugs is often based on short-term follow-up trial data, and attempts to address this uncertainty are not typically undertaken once a reimbursement decision is made. To address this gap, we sought to conduct a reassessment of an oncology drug (pembrolizumab) for patients with advanced melanoma which was approved based on interim data with a median 7.9 months of follow-up and for which long-term data have since been published. We developed a three-health-state partitioned survival model based on the phase 3 KEYNOTE-006 clinical trial data using patient-level data reconstruction techniques based on an interim analysis. We used a standard survival analysis and parametric curve fitting techniques to extrapolate beyond the trial follow-up time, and the model structure and inputs were derived from the literature. Five-year long-term follow-up data from the trial were then used to re-evaluate the cost-effectiveness of pembrolizumab versus ipilimumab for treatment of advanced melanoma. The best fitting parametric curves and corresponding survival extrapolations for reconstructed interim data and long-term data reconstructed from KEYNOTE-006 were different. An analysis of the 5 year long-term follow-up data generated a base case incremental cost-effectiveness ratio (ICER) that was 28% higher than the ICER based on interim trial data. Our findings suggest that there may be a trade-off between certainty and the ICER. Conducting health technology re-assessments of certain oncology products on the basis of longer-term data availability, especially for those health technology adoption decisions made based on immature clinical data, may be of value to decision makers.

Olaparib versus Placebo in Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer: A Cost-Utility Analysis from the Canadian Public Payer's Perspective.

Pancreatic cancer has an annual incidence of 2/10,000 in Canada, with a one-year mortality rate greater than 80%. In the absence of a cost-effectiveness analysis in Canada, this study's objective was to assess the cost-effectiveness of olaparib versus a placebo in adult patients with deleterious or suspected deleterious BRCA metastatic pancreatic adenocarcinoma, who did not show any progression for at least 16 weeks with first-line platinum-based chemotherapy. A partitioned survival model with a 5-year time horizon was adopted to estimate the costs and effectiveness. All of the costs were extracted from the public payer's available resources, effectiveness data were obtained from the POLO trial, and Canadian studies were used for utility inputs. Probabilistic sensitivity analyses and scenario analyses were performed. The total costs of olaparib and the placebo over five years were CAD 179,477 and CAD 68,569, with overall quality-adjusted life-years (QALYs) of 1.70 and 1.36, respectively. The incremental cost-effectiveness ratio (ICER) of the olaparib group compared with the placebo was CAD 329,517 per QALY. With a commonly cited willingness to pay (WTP) threshold of CAD 50,000 per QALY, the drug does not achieve acceptable cost-effectiveness mainly due to the high price of the medication and insufficient impact on the overall survival of patients with metastatic pancreatic cancer.

Residual Risk of Breast Cancer After Bariatric Surgery.

Importance: Excess adiposity confers higher risk of breast cancer for women. For women who have lost substantial weight, it is unclear whether previous obesity confers residual increased baseline risk of breast cancer compared with peers without obesity. Objectives: To determine whether there is a residual risk of breast cancer due to prior obesity among patients who undergo bariatric surgery. Design, Setting, and Participants: Retrospective matched cohort study of 69 260 women with index date between January 1, 2010, and December 31, 2016. Patients were followed up for 5 years after bariatric surgery or index date. Population-based clinical and administrative data from multiple databases in Ontario, Canada, were used to match a cohort of women who underwent bariatric surgery for obesity (baseline body mass index [BMI] ≥35 with comorbid conditions or BMI ≥40) to women without a history of bariatric surgery according to age and breast cancer screening history. Nonsurgical controls were divided into 4 BMI categories (<25, 25-29, 30-34, and ≥35). Data were analyzed on October 21, 2021. Exposures: Weight loss via bariatric surgery. Main Outcomes and Measures: Residual hazard of breast cancer after washout periods of 1, 2, and 5 years. Comparisons were made between the surgical and nonsurgical cohorts overall and within each of the BMI subgroups. Results: In total, 69 260 women were included in the analysis, with 13 852 women in each of the 5 study cohorts. The mean (SD) age was 45.1 (10.9) years. In the postsurgical cohort vs the overall nonsurgical cohort (n = 55 408), there was an increased hazard for incident breast cancer in the nonsurgical group after washout periods of 1 year (hazard ratio [HR], 1.40 [95% CI, 1.18-1.67]), 2 years (HR, 1.31 [95% CI, 1.12-1.53]), and 5 years (HR, 1.38 [95% CI, 1.21-1.58]). When the postsurgical cohort was compared with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different regardless of the washout period, whereas there was a reduced hazard for incident breast cancer among postsurgical patients compared with nonsurgical patients in all high BMI categories (BMI ≥25). Conclusions and Relevance: Findings suggest that bariatric surgery was associated with a reduced risk of developing breast cancer for women with prior obesity equivalent to that of a woman with a BMI less than 25 and a lower risk when compared with all groups with BMI greater than or equal to 25.

Return on investment of Canadian tobacco control policies implemented between 2001 and 2016.

OBJECTIVES: To determine the return on investment (ROI) associated with tobacco control policies implemented between 2001 and 2016 in Canada. METHODS: Canadian expenditures on tobacco policies were collected from government sources. The economic benefits considered in our analyses (decrease in healthcare costs, productivity costs and monetised life years lost, as well as tax revenues) were based on the changes in smoking prevalence and attributable deaths derived from the SimSmoke simulation model for the period 2001-2016. The net economic benefit (monetised benefits minus expenditures) and ROI associated with these policies were determined from the government and societal perspectives. Sensitivity analyses were conducted to check the robustness of the result. Costs were expressed in 2019 Canadian dollars. RESULTS: The total of provincial and federal expenditures associated with the implementation of tobacco control policies in Canada from 2001 through 2016 was estimated at $2.4 billion. Total economic benefits from these policies during that time were calculated at $49.2 billion from the government perspective and at $54.2 billion from the societal perspective. The corresponding ROIs were $19.8 and $21.9 for every dollar invested. Sensitivity analyses yielded ROI values ranging from $16.3 to $28.3 for every dollar invested depending on the analyses and perspective. CONCLUSIONS: This analysis has found that the costs to implement the Canadian tobacco policies between 2001 and 2016 were far outweighed by the monetised value associated with the benefits of these policies, making a powerful case for the investment in tobacco control policies.

Appraisals by Health Technology Assessment Agencies of Economic Evaluations Submitted as Part of Reimbursement Dossiers for Oncology Treatments: Evidence from Canada, the UK, and Australia.

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019-2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran's Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ.

Opioid reduction and enhanced recovery in orthopaedic surgery (OREOS): A feasibility randomized controlled trial in knee replacement patients.

Background: Total knee arthroplasties are the second most common surgery in Canada. Most patients recover well, but 20% or more still suffer from persistent pain and opioid use. Though opioids are an important part of perioperative pain management, their potential for long-term adverse effects is well recognized. Limiting opioids may be insufficient to overcome the issue of opioid overuse. Pain and opioid use are highly linked, so an effective alternative needs to address both issues. Objectives: The principal objective of this pilot trial is to assess the feasibility. The clinical objectives are to determine the effects of a multicomponent care pathway on opioid-free pain control, persisting pain and opioid use, functional knee outcomes, quality of life, and return to function. Methods: We will include adult patients scheduled for primary elective total knee arthroplasty. Patients in the intervention group will undergo a multicomponent intervention pathway that will be facilitated by an intervention coordinator linking each patient and their surgical/ perioperative team. The interventional pathway will include (1) preoperative education on pain and opioid use, (2) preoperative risk identification and mitigation using cognitive behavioral skills, (3) personalized postdischarge analgesic prescriptions, and (4) continued support for pain control and recovery up to 8 weeks. Patients in the control group will receive the usual care at their institution. Discussion: The overarching goal is to implement and evaluate a coordinated approach to clinical care to improve pain control and reduce harms, with an emphasis on patient-centered care and shared decision making.Trial Registration Number: NCT04968132 (informed consent/ research ethics board statement).

Contexte: L'arthroplastie totale du genou est la deuxième chirurgie la plus courante au Canada. La plupart des patients se rétablissent bien, mais au moins 20 pour cent d'entre eux souffrent encore de douleur persistante et de consommation d'opioïdes. Bien que les opioïdes soient un élément important de la prise en charge périopératoire de la douleur, leur potentiel d'effets indésirables à long terme est bien reconnu. La limitation des opioïdes peut être insuffisante pour surmonter le problème de la surconsommation d'opioïdes. La douleur et la consommation d'opioïdes sont étroitement liées, de sorte qu'une option de rechange efficace doit s'attaquer à ces deux problèmes.Objectifs: L'objectif principal de cet essai pilote est d'évaluer la faisabilité. Les objectifs cliniques sont de déterminer les effets d'une voie de soins à composantes multiples sur la maitrise de la douleur sans opioïdes, la douleur persistante et la consommation d'opioïdes, les résultats fonctionnels du genou, la qualité de vie et le retour à la fonction.Méthodes: Nous inclurons les patients adultes devant subir une arthroplastie primaire totale élective du genou. Les patients du groupe d'intervention seront soumis à une voie d'intervention à composantes multiples qui sera facilitée par un coordonnateur d'intervention reliant chaque patient et son équipe chirurgicale/périopératoire. La voie d'intervention comprendra (1) une éducation préopératoire sur la douleur et la consommation d'opioïdes, (2) la détermination et l'atténuation des risques préopératoires à l'aide de compétences comportementales cognitives, (3) des prescriptions analgésiques personnalisées après la sortie, et (4) un soutien continu pour la maîtrise de la douleur et la récupération pendant une période allant jusqu'à huit semaines. Les patients du groupe témoin recevront les soins habituels à leur établissement.Discussion: L'objectif global est de mettre en œuvre et d'évaluer une approche coordonnée des soins cliniques afin d'améliorer la maitrise de la douleur et réduire les méfaits, en mettant l'accent sur les soins centrés sur le patient et la prise de décision partagée. Numéro d'enregistrement de l'essai : NCT04968132 (consentement éclairé/déclaration du comité d'éthique de la recherche).

Challenges of Conducting Value Assessment for Comprehensive Genomic Profiling.

OBJECTIVES: Clinical practice is shifting toward an era of precision medicine. The use of comprehensive genomic profiling (CGP) in oncology has broad potential as a universal companion diagnostic for targeted therapies which may significantly improve health outcomes while using healthcare resources more efficiently. Given the nature of this technology, assessing the value of CGP presents unique challenges. METHODS: This paper draws on evidence from the academic and policy literature in oncology, as well as stakeholder interviews (health economists, payers, clinicians, and public policy officials) in countries using incremental cost-effectiveness ratios (ICER) as part of health technology assessment (HTA). RESULTS: The degree to which CGP is subject to a value assessment varies significantly across healthcare systems. Current HTA processes focus on evaluating diagnostic testing through co-dependent assessment of diagnostic testing and associated therapeutic interventions. Diagnostic tests with multiple associated therapeutic interventions are rapidly evolving and poorly unsuited to current HTA approaches. Moreover, HTA approaches are limited in their ability to consider broader systemic benefits of the expanded diagnostic capabilities and enhanced opportunities for clinical trial participation offered by CGP. CONCLUSIONS: The assessment of the overall value of CGP is limited by the current models of HTA. This paper suggests policy proposals for value assessment and funding reforms to help broaden patient access to CGP. These include investing in genomic testing infrastructure; decoupling the assessment of the value of CGP testing to identifying predetermined therapeutic interventions; tailoring evaluation methodology; and developing approaches to collecting evidence of clinical, healthcare system and societal benefit.

Reverse Total Shoulder Arthroplasty Is the Most Cost-effective Treatment Strategy for Proximal Humerus Fractures in Older Adults: A Cost-utility Analysis.

BACKGROUND: Proximal humerus fractures are the second-most common fragility fracture in older adults. Although reverse total shoulder arthroplasty (RTSA) is a promising treatment strategy for proximal humerus fractures with favorable clinical and quality of life outcomes, it is associated with much higher, and possibly prohibitive, upfront costs relative to nonoperative treatment and other surgical alternatives. QUESTIONS/PURPOSES: (1) What is the cost-effectiveness of open reduction internal fixation (ORIF), hemiarthroplasty, and RTSA compared with the nonoperative treatment of complex proximal humerus fractures in adults older than 65 years from the perspective of a single-payer Canadian healthcare system? (2) Which factors, if any, affect the cost-effectiveness of ORIF, hemiarthroplasty, and RTSA compared with nonoperative treatment of proximal humerus fractures including quality of life outcomes, cost, and complication rates after each treatment? METHODS: This cost-utility analysis compared RTSA, hemiarthroplasty, and ORIF with the nonoperative management of complex proximal humerus fractures in adults older than 65 years over a lifetime time horizon from the perspective of a single-payer healthcare system. Short-term and intermediate-term complications in the 2-year postoperative period were modeled using a decision tree, with long-term outcomes estimated through a Markov model. The model was initiated with a cohort of 75-year-old patients who had a diagnosis of a comminuted (three- or four-part) proximal humerus fractures; 90% of the patients were women. The mean age and gender composition of the model's cohort was based on a systematic review conducted as part of this analysis. Patients were managed nonoperatively or surgically with either ORIF, hemiarthroplasty, or RTSA. The three initial surgical treatment options of ORIF, hemiarthroplasty, and RTSA resulted in uncomplicated healing or the development of a complication that would result in a subsequent surgical intervention. The model reflects the complications that result in repeat surgery and that are assumed to have the greatest impact on clinical outcomes and costs. Transition probabilities and health utilities were derived from published sources, with costs (2020 CAD) sourced from regional costing databases. The primary outcome was the incremental cost-utility ratio, which was calculated using expected quality-adjusted life years (QALYs) gained and costs. Sensitivity analyses were conducted to explore the impact of changing key model parameters. RESULTS: Based on both pairwise and sequential analysis, RTSA was found to be the most cost-effective strategy for managing complex proximal humerus fractures in adults older than 65 years. Compared with nonoperative management, the pairwise incremental cost-utility ratios of hemiarthroplasty and RTSA were CAD 25,759/QALY and CAD 7476/QALY, respectively. ORIF was dominated by nonoperative management, meaning that it was both more costly and less effective. Sequential analysis, wherein interventions are compared from least to most expensive in a pairwise manner, demonstrated ORIF to be dominated by hemiarthroplasty, and hemiarthroplasty to be extendedly dominated by RTSA. Further, at a willingness-to-pay threshold of CAD 50,000/QALY, RTSA had 66% probability of being the most cost-effective treatment option. The results were sensitive to changes in the parameters for the probability of revision RTSA after RTSA, the treatment cost of RTSA, and the health utilities associated with the well state for all treatment options except ORIF, although none of these changes were found to be clinically realistic based on the existing evidence. CONCLUSION: Based on this economic analysis, RTSA is the preferred treatment strategy for complex proximal humerus fractures in adults older than 65 years, despite high upfront costs. Based on the evidence to date, it is unlikely that the parameters this model was sensitive to would change to the degree necessary to alter the model's outcome. A major strength of this model is that it reflects the most recent randomized controlled trials evaluating the management of this condition. Therefore, clinicians should feel confident recommending RTSA for the management of proximal humerus fractures in adults older than 65 years, and they are encouraged to advocate for this intervention as being a cost-effective practice, especially in publicly funded healthcare systems wherein resource stewardship is a core principle. Future high-quality trials should continue to collect both clinical and quality of life outcomes using validated tools such as the EuroQOL-5D to reduce parameter uncertainty and support decision makers in understanding relevant interventions' value for money. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Infectious diseases, comorbidities and outcomes in hospitalized people who inject drugs (PWID) infections in persons who inject drugs.

Injection drug use poses a public health challenge. Clinical experience indicates that people who inject drugs (PWID) are hospitalized frequently for infectious diseases, but little is known about outcomes when admitted. Charts were identified from local hospitals between 2013-2018 using consultation lists and hospital record searches. Included individuals injected drugs in the past six months and presented with infection. Charts were accessed using the hospital information system, undergoing primary and secondary reviews using Research Electronic Data Capture (REDCap). The Wilcoxon rank-sum test was used for comparisons between outcome categories. Categorical data were summarized as count and frequency, and compared using Fisher's exact test. Of 240 individuals, 33% were admitted to the intensive care unit, 36% underwent surgery, 12% left against medical advice (AMA), and 9% died. Infectious diagnoses included bacteremia (31%), abscess (29%), endocarditis (29%), cellulitis (20%), sepsis (10%), osteomyelitis (9%), septic arthritis (8%), pneumonia (7%), discitis (2%), meningitis/encephalitis (2%), or other (7%). Sixty-six percent had stable housing and 60% had a family physician. Fifty-four percent of patient-initiated discharges were seen in the emergency department within 30 days and 29% were readmitted. PWID are at risk for infections. Understanding their healthcare trajectory is essential to improve their care.

Bariatric Surgery and Breast Cancer Incidence: a Population-Based, Matched Cohort Study.

PURPOSE: Obesity is associated with increased breast cancer risk in women. Bariatric surgery induces substantial weight loss. However, the effects of such weight loss on subsequent breast cancer risk in women with obesity are poorly understood. To examine breast cancer incidence and related outcomes in women with obesity undergoing bariatric surgery. MATERIALS AND METHODS: This was a population-based matched cohort study of breast surgery outcomes utilizing linked clinical databases in Ontario, Canada. Women with obesity who underwent bariatric surgery were 1:1 matched using a propensity score to non-surgical controls for age and breast cancer screening history. The main outcomes were incidence of breast cancer after lag periods of 1, 2, and 5 years. Additional outcomes included tumor hormone receptor status, cancer stage, and treatments undertaken. Time-varying Cox proportional hazard models accounting for screening during follow-up were used to model cancer incidence. RESULTS: A total of 12,724 women per group were included, average age 45.09. After a 1-year lag, breast cancer incidence occurred in 1.09% and 0.79% of the control and surgery groups, respectively (adjusted hazard ratio, 0.81 [95%CI 0.69-0.95]; p = 0.01). This association was maintained after lag periods of 2 and 5 years. Women in the surgical cohort diagnosed with breast cancer were more likely to have low-grade tumors and less likely to have high-grade tumors (overall p < 0.01). No association was found for tumor hormone receptor status, although the surgical group was more likely to have her2neu-negative tumors (p = 0.01). CONCLUSION: Bariatric surgery was associated with a lower incidence of breast cancer and lower tumor grade in women with obesity. Further evaluation of outcomes, including mortality, is required.