Comparative Safety and Effectiveness of Bevacizumab Biosimilars to Originator for the Treatment of Metastatic Colorectal Cancer.

Background: Ontario has publicly funded biosimilar bevacizumab for first-line metastatic colorectal cancer (mCRC) since 2019. Clinical trials demonstrate comparable efficacy and safety of bevacizumab biosimilars to originator bevacizumab. The objective of this study was to assess real-world safety and effectiveness of the implementation of bevacizumab biosimilars compared with originator bevacizumab in patients with mCRC.

Cost-Effectiveness Analysis of Bevacizumab Biosimilars Versus Originator Bevacizumab for Metastatic Colorectal Cancer: A Comparative Study Using Real-World Data.

Objectives: MVASI (Amgen) and Zirabev (Pfizer) are 2 of the earliest bevacizumab biosimilars approved for the first-line treatment of metastatic colorectal cancer (mCRC). We aimed to confirm and quantify the real-world cost savings and cost-effectiveness of MVASI and Zirabev relative to originator bevacizumab for patients with mCRC.

Methods: We conducted a population-based, retrospective cohort study in Ontario, Canada, where originator and biosimilar bevacizumab are universally publicly funded.

Application of Multi-Criteria Decision Analysis (MCDA) to Prioritize Real-World Evidence Studies for Health Technology Management: Outcomes and Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity.

Cost and value of cancer medicines in a single-payer public health system in Ontario, Canada: a cross-sectional study.

Background: The financial impact of cancer medicines on health systems is not well known. We describe temporal trends in expenditure on cancer medicines within the single-payer health system of Ontario, Canada, and the extent of clinical benefit these treatments offer.

Methods: In this cross-sectional study, we identified cancer medicines and expenditures from formularies and costing databases (the New Drug Funding Program, Ontario Drug Benefit Program, and The High-Cost Therapy Funding Program) during 10 consecutive years (April 1, 2012, to March 31, 2022) in Ontario, Canada.

Development of a Multi-Criteria Decision Analysis Rating Tool to Prioritize Real-World Evidence Questions for the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration developed an MCDA rating tool to assess and prioritize potential post-market real-world evidence (RWE) questions/uncertainties emerging from public drug funding decisions in Canada. In collaboration with a group of multidisciplinary stakeholders from across Canada, the rating tool was developed following a three-step process: (1) selection of criteria to assess the importance and feasibility of an RWE question; (2) development of rating scales, application of weights and calculating aggregate scores; and (3) validation testing. An initial MCDA rating tool was developed, composed of seven criteria, divided into two groups.

Cost-effectiveness of second-line ipilimumab for metastatic melanoma: A real-world population-based cohort study of resource utilization.

Background: The efficacy-effectiveness gap between randomized trial and real-world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost-effectiveness, it is critical to assess the real-world cost-effectiveness of second-line ipilimumab versus non-ipilimumab treatments for MM.

Methods: This was a population-based retrospective cohort study of patients who received second-line non-ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario.

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's RWE Data Working Group.

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions.

Comparative Effectiveness and Safety of Pertuzumab and Trastuzumab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy for Treatment of Metastatic Breast Cancer.

Importance: To date, limited studies have examined the comparative outcomes of pertuzumab treatment in the real-world setting. End-of-study analyses of the CLEOPATRA trial found median overall survival (OS) of 57.1 months in patients receiving pertuzumab compared with 40.

Building a National Reassessment Process for Oncology Drugs: Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration through a Simulated Reassessment Exercise.

The CanREValue Collaboration established the Reassessment & Uptake Working Group to develop a preliminary process to reassess funded cancer drugs in Canada. A simulated exercise was conducted to evaluate the proposed reassessment process using a real-world case. We invited 32 attendees including representatives from Health Canada and Health Technology Assessment (HTA) agencies, along with payers, clinicians, academics, and patient representatives.

Considerations for Developing a Reassessment Process: Report from the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's Reassessment and Uptake Working Group.

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions.

Clinician Perspectives of COVID-19-Related Cancer Drug Funding Measures in Ontario.

The COVID-19 pandemic has a significant impact on cancer patients and the delivery of cancer care. To allow clinicians to adapt treatment plans for patients, Ontario Health (Cancer Care Ontario) issued a series of interim funding measures for the province's New Drug Funding Program (NDFP), which covers the cost of most hospital-delivered cancer drugs. To assess the utility of the measures and the need for their continuation, we conducted an online survey of Ontario oncology clinicians.

Use of real-world evidence in cancer drug funding decisions in Canada: a qualitative study of stakeholders' perspectives.

Background: Real-world evidence (RWE) can provide postmarket data to inform whether funded cancer drugs yield expected outcomes and value for money, but it is unclear how to incorporate RWE into Canadian cancer drug funding decisions. As part of the Canadian Real-World Evidence Value for Cancer Drugs (CanREValue) Collaboration, this study aimed to explore stakeholder perspectives on the current state of RWE in Canada to inform a Canadian framework for use of RWE in cancer drug funding decisions.

Methods: This was a qualitative descriptive study.

Real-world, population-based cohort study of toxicity and resource utilization of second-line ipilimumab for metastatic melanoma in Ontario, Canada.

Second-line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real-world toxicity of second-line ipilimumab compared to standard second-line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included.

Are We Making a Difference? A Qualitative Study of Patient Engagement at the pan-Canadian Oncology Drug Review: Perspectives of Patient Groups.

Objectives: Despite wide support for patient involvement in health technology assessments (HTA), determining meaningful engagement is complex. This article explores experiences and perceptions among patient groups participating in the Canadian Agency for Drugs and Technologies in Health (CADTH)'s pan-Canadian Oncology Drug Review (pCODR) process.

Methods: We created a qualitative interview study comprising 22 semi-structured telephone interviews with individuals representing 21 different patient groups registered with the pCODR process.

Impact of rarity on Canadian oncology health technology assessment and funding.

Objectives: The pan-Canadian Oncology Drug Review (pCODR) evaluates new cancer drugs for public funding recommendations. While pCODR's deliberative framework evaluates overall clinical benefit and includes considerations for exceptional circumstances, rarity of indication is not explicitly addressed. Given the high unmet need that typically accompanies these indications, we explored the impact of rarity on oncology HTA recommendations and funding decisions.

Developing a framework to incorporate real-world evidence in cancer drug funding decisions: the Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration.

Background: Oncology therapy is becoming increasingly more expensive and challenging the affordability and sustainability of drug programmes around the world. When new drugs are evaluated, health technology assessment organisations rely on clinical trials to inform funding decisions. However, clinical trials are not able to assess overall survival and generalises evidence in a real-world setting.

Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice.

Prader-Willi Syndrome is the most common syndromic form of human obesity and is caused by the loss of function of several genes, including MAGEL2. Mice lacking Magel2 display increased weight gain with excess adiposity and other defects suggestive of hypothalamic deficiency. We demonstrate Magel2-null mice are insensitive to the anorexic effect of peripherally administered leptin.

The role of NPY in hypothalamic mediated food intake.

Neuropeptide Y (NPY) is a highly conserved neuropeptide with orexigenic actions in discrete hypothalamic nuclei that plays a role in regulating energy homeostasis. NPY signals via a family of high affinity receptors that mediate the widespread actions of NPY in all hypothalamic nuclei. These actions are also subject to tight, intricate regulation by numerous peripheral and central energy balance signals.

Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2.

Magel2 belongs to the MAGE/necdin family of proteins, which have roles in cell cycle, differentiation, and apoptosis. The Magel2 gene is expressed in various brain regions, most notably the hypothalamus. Mice with a targeted deletion of Magel2 display hypoactivity, blunted circadian rhythm, decreased fertility, and increased adiposity.

Loss of magel2, a candidate gene for features of Prader-Willi syndrome, impairs reproductive function in mice.

Background: MAGEL2 is one of several genes typically inactivated in the developmental obesity disorder Prader-Willi syndrome (PWS). The physiological consequences of loss of MAGEL2, but without the concurrent loss of other PWS genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts circadian rhythm and metabolism causing reduced total activity, reduced weight gain before weaning, and increased adiposity after weaning.