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. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the 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. Through this exercise, we aimed to gain insight into consensus building and deliberation processes and to identify efficiencies in the application of the rating tool. An experienced facilitator led a multidisciplinary committee, consisting of 11 Canadian experts, through consensus building, deliberation, and prioritization. A total of nine RWE proposals were evaluated and prioritized as low (n = 4), medium (n = 3), or high (n = 2) priority. Through an iterative process, efficiencies and recommendations to improve the rating tool and associated procedures were identified. The refined MCDA rating tool can help decision-makers prioritize important and feasible RWE studies for research and can enable the use of RWE for the life-cycle evaluation of cancer drugs.

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. A case was developed using a real-world study on a publicly funded cancer drug. In facilitated group sessions, participants were asked to deliberate upon the evidence presented in the case to issue reassessment recommendations. Several themes were identified through the deliberation discussions. While the generalizability of real-world evidence (RWE) is perceived as a strength, trust in the RWE depends largely on the source of the real-world data. The attendees suggested several improvements to the proposed reassessment process including evidence requirement for reassessment, recommendation categories, and a priori study protocols. This exercise generated important insights on the evidence required for conducting reassessment and considerations for improvements of the proposed reassessment process. Building upon lessons from this exercise, future work would continue to refine the reassessment process as part of the overall CanREValue framework.

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. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.

We assessed the comparative effectiveness and safety of pertuzumab plus trastuzumab and chemotherapy versus trastuzumab and chemotherapy for patients with HER2+ metastatic breast cancer (mBC) in Canada. We conducted a population‐based retrospective study of patients receiving first‐line treatment for mBC across eight Canadian provinces. Patients receiving trastuzumab and chemotherapy were historical comparators, and patients receiving pertuzumab plus trastuzumab and chemotherapy were the treatment group. Patients were followed until death or up to 5 years following the start of treatment (maximum follow‐up to December 31, 2019). The primary outcome was overall survival (OS). One‐year cumulative incidence and RDs were calculated for safety outcomes including hospitalization, emergency department visits, febrile neutropenia, and cardiac‐related events. Propensity score matching (PSM) and inverse‐probability of treatment weighting (IPTW) were applied within provinces. Individual provincial survival estimates were pooled using random effects meta‐analysis. 3063 patients who received first‐line treatment for mBC were identified. Median OS was higher among treatment patients compared to comparator patients in most provinces. Pertuzumab was associated with a statistically significantly lower risk of mortality (pooled HRs, PSM: 0.65, 95%CI: 0.57–0.74; IPTW: 0.65, 95% CI: 0.61–0.70). The treatment group had a lower risk of hospitalization compared to the comparator group (pooled RD: −0.05, 95% CI: [−0.09]–[−0.01]). No difference in 1‐year cumulative incidence of cardiac‐related events was identified between groups. Pertuzumab use in practice was associated with statistically significant improved survival without apparent safety concerns among patients with mBC. Real‐world evaluations allow for assessments of publicly funded treatments to inform funding policies.

Objective The Canadian Real-world Evidence for Value in Cancer (CanREValue) Collaboration was established in response to growing interest in using real-world evidence (RWE) to support health technology assessment (HTA). CanREValue has developed a framework to generate and use RWE to inform cancer drug funding decisions. Design and participants The RWE framework was developed using a multistage, multistakeholder approach. First, an environmental scan and qualitative study were conducted to understand the current state and key stakeholder perspectives on RWE. Next, five formal working groups (WGs) were established consisting of stakeholders with cancer drug funding expertise including clinicians, patients, methodologists, payers, regulatory decision-makers and data analysts. Through stakeholder consultations, including modified Delphi exercises and workshops, each WG developed specific framework components and identified facilitators and barriers that may impact the uptake of RWE. Setting The CanREValue Collaboration consisted of membership and participation from stakeholders and expertise from across Canada. Central research operations were managed from Toronto, Ontario, Canada. Outcomes Development of an RWE framework reflective of the needs and perspectives of stakeholders directly involved and/or impacted by cancer drug funding decisions across Canada. Results Through an iterative process, a comprehensive RWE framework was developed that outlined the end-to-end processes necessary for the generation and use of RWE for HTA reassessment in Canada. The framework consists of four phases that uses various tools, templates and processes, which can be applied as a whole or in part. A diverse range of stakeholders and expertise is involved in the decision-making of each phase of the process: Phase I: identification, selection and prioritisation of RWE questions; phase II: initiating and planning the RWE study; phase III: conducting the RWE study and phase IV: conducting reassessment. Conclusions As the cancer drug funding landscape continues to evolve, the need for RWE to support evidence-based policy reform, pricing and reallocation of funding from low to high value settings is crucial. We have developed a framework that is adaptable and responsive to the changing landscape. The tools, templates and processes within the framework can be applied by various stakeholder groups in whole or in part to support cancer drug funding decision-making in Canada and can be adapted for use in other jurisdictions.