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.

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.

Background: Ontario publicly funds reference trastuzumab (Herceptin) and four biosimilar trastuzumab products for adjuvant treatment of HER2+ breast cancer. We assessed the real-world safety and effectiveness of biosimilar trastuzumab compared to Herceptin for adjuvant treatment of patients with HER2+ breast cancer. Methods: This was a population-based, retrospective study comparing the safety and effectiveness of biosimilar trastuzumab and Herceptin for neoadjuvant/adjuvant treatment of HER2+ breast cancer from 2016 to 2021. Treatment patients started biosimilar trastuzumab from November 2019 to June 2021; historical comparator patients started Herceptin from June 2016 to October 2019. Safety outcomes death within 30 days of last dose of trastuzumab, direct hospitalization, emergency department visit leading to hospitalization, early treatment discontinuation, and in-patient admission for congestive heart failure were measured using logistic/negative binomial regression. Overall survival (OS) was measured using Kaplan–Meier methods and Cox proportional hazards regression. Propensity score matching was applied. Results: From June 2016 to 2021, 5071 patients with breast cancer were treated with neoadjuvant/adjuvant trastuzumab. The rate of direct hospitalization (RR: 0.85, 95% CI: 0.74–0.98, p-value: 0.032) was significantly lower in biosimilar compared to Herceptin patients. OS (log-rank test p = 0.98) and risk of mortality (HR: 1.29, 95% CI: 0.72–2.30, p-value = 0.39) did not significantly differ between treatment groups. Conclusions: Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars and demonstrate the value of real-world evidence generation for supporting biosimilar implementations and reassessments.

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. Group A criteria assess the importance of an RWE question by examining the (1) drug’s perceived clinical benefit, (2) magnitude of uncertainty identified, and (3) relevance of the uncertainty to decision-makers. Group B criteria assess the feasibility of conducting an RWE analysis including the (1) feasibility of identifying a comparator, (2) ability to identify cases, (3) availability of comprehensive data, and (4) availability of necessary expertise and methodology. Future directions include partnering with the Canadian Agency for Drugs and Technology in Health’s Provincial Advisory Group for further tool refinement and to gain insight into incorporating the tool into drug funding deliberations.

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration established the Engagement Working Group (WG) to ensure that all key stakeholders had an opportunity to provide input into the development and implementation of the CanREValue Real-World Evidence (RWE) Framework. Two consultations were held in 2021 to solicit patient perspectives on key policy and data access issues identified in the interim policy and data WG reports. Over 30 individuals, representing patients, caregivers, advocacy leaders, and individuals engaged in patient research were invited to participate. The consultations provided important feedback and valuable lessons in patient engagement. Patient leaders actively shaped the process and content of the consultation. Breakout groups facilitated by patient advocacy leaders gave the opportunity for open and thoughtful contributions from all participants. Important recommendations were made: the RWE framework should not impede access to new drugs; it should be used to support conditional approvals; patient relevant endpoints should be captured in provincial datasets; access to data to conduct RWE should be improved; and privacy issues must be considered. The manuscript documents the CanREValue experience of engaging patients in a consultative process and the useful contributions that can be achieved when the processes to engage are guided by patients themselves.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, Ontario Health had implemented an interim measure to extend the dosing interval for durvalumab treatment of locally advanced, stage III non-small cell lung cancer (NSCLC) from every 2 weeks at 10 mg/kg (standard dosing) to every 4 weeks at 20 mg/kg (extended dosing). This was meant to optimize patient access while minimizing patients’ exposure to healthcare facilities. Prior studies have shown comparable efficacy and safety between extended and standard dosing in clinical trials albeit with small sample sizes and treatment groups with varying dose schedule criteria. Population-based studies comparing extended to standard dosing in real-world patients are needed to support more generalizable evidence. The objective of this study was to assess the real-world effectiveness and safety of durvalumab extended versus standard dosing for patients with stage III NSCLC in the adjuvant setting post-chemoradiation during the COVID-19 pandemic. Methods: This was a retrospective, population-based observational cohort study using administrative health data for Ontario patients with locally advanced, stage III NSCLC starting durvalumab between December 2018 and December 2021. A propensity score matching (PSM) cohort was created to reduce imbalances in baseline characteristics between groups. Overall survival, the primary outcome, was measured using Kaplan-Meier methods and Cox proportional hazards regression. Safety outcomes, unscheduled emergency department (ED) visits and hospital admissions until 30 days after the last dose of durvalumab, were measured using negative binomial regression. Results: The crude cohort included 642 Ontario patients with locally advanced, stage III NSCLC starting durvalumab between December 2018 and December 2021; 248 (38.6%) received extended dosing (EXT) of durvalumab and 394 (61.4%) received standard dosing (STD). The mean age of EXT patients was 67.4 years and of STD patients was 67.8 years (P=0.55). Male sex was reported for 54.8% of EXT and 56.1% of STD patients (P=0.76). Rurality was reported for 16.9% of EXT and 19.8% of STD patients (P=0.005). In the crude cohort no significant differences were observed for EXT versus STD on the risk of mortality [hazard ratio (HR): 0.94, 95% confidence interval (CI): 0.70–1.28; P=0.71], ED visits [rate ratio (RR): 1.79, 95% CI: 0.85–3.76; P=0.12], or hospital admissions (RR: 0.60, 95% CI: 0.19–1.87; P=0.38). The PSM cohort included 448 patients (224 in each treatment group). No significant differences were observed for EXT versus STD on the risk of mortality (HR: 0.94, 95% CI: 0.66–1.35; P=0.74), ED visits (RR: 2.07, 95% CI: 0.84–5.05; P=0.11), or hospital admissions (RR: 0.38, 95% CI: 0.09–1.65; P=0.20). Conclusions: Our study found no significant differences in the effectiveness or safety of extended versus standard dosing of durvalumab among patients with NSCLC. The findings confirm that the interim measure of extending the dosing interval of durvalumab minimized patients’ treatment visits to healthcare facilities during the COVID-19 pandemic without compromising the effectiveness and safety of their treatment.