The impact of sequential analysis on drug decision-making in Canada

Aim: In Canada (excluding Québec), public drug coverage generally relies on health technology assessment and reimbursement recommendations produced by Canada’s Drug Agency – L'Agence des medicaments du Canada (CDA-AMC). At CDA-AMC, when multiple comparators are included in the pharmacoeconomic analysis, the corresponding results are reported using a sequential analysis. The aim of this review was to understand how the sequential analysis approach impacts the price reductions recommended in CDA-AMC drug reimbursement reviews. Materials & methods: A search was conducted of CDA-AMC reimbursement review reports published from January 2022 to December 2023 that included a cost–utility analysis with sequential analysis performed by the Sponsor and the economic re-analysis by CDA-AMC. An analysis of included reimbursement reviews was conducted to determine if the comparators chosen through the sequential analysis and selected for the price reduction in the final reimbursement recommendation were also the comparators most commonly used in current clinical practice. Additional analyses further examining reported market shares and list prices were conducted among reimbursement recommendations where the selected comparator was not the most commonly used comparator. An assessment examining the impact of comparator selection based on the sequential analysis on cost-effectiveness conclusions in CDA-AMC reimbursement reviews was also conducted. Results are presented by type of drug review (i.e., oncology vs nononcology products). Results: A total of 150 CDA-AMC reimbursement reviews published from January 2022 to December 2023 were identified and screened for eligibility. Of these, 37 reimbursement reviews – comprising a total of 60 recommendations (13 oncology and 47 nononcology products) based on sequential analyses – were included in the analysis. Among the included reimbursement recommendations, CDA-AMC chose a comparator that was not the most commonly used in clinical practice in 25 (42%) recommendations when determining the price reduction of the new medication (in accordance with CDA-AMC guidelines that permit selection of any comparator regardless of clinical utilization). Among these 25 reimbursement recommendations, the selected comparator represented <10% of the market share in 60% of the recommendations and was the least expensive comparator in 56%. Similar findings were observed within reimbursement recommendations for oncology and nononcology products. Furthermore, in 21 (84%) of these 25 recommendations, it was found that comparing new drugs to the most commonly used comparators, rather than the CDA-AMC selected comparators, led to more favorable reimbursement assessments for new drugs, with lower or no required price reductions to meet the $50,000/quality-adjusted life year threshold commonly applied during the respective review period. Conclusion: Comparator selection is a vital aspect of health technology assessment. At CDA-AMC, comparator selection is driven by the sequential analysis approach, playing an important role in their economic assessment and reimbursement recommendation. Despite the relatively small number of sequential analyses examined, this review found that CDA-AMC recommendations based on a sequential analysis frequently refer to a comparator that is not widely used in real-world clinical practice, which can impede subsequent health technology assessment decisions that need to consider clinically prevalent comparators. This is notable as pairwise analyses conducted for this review demonstrated that selecting the treatments most often used in clinical practice as the comparator, rather than the CDA-AMC comparator, likely yields lower price reductions for new treatments that are more costly and more effective. These findings reinforce the importance of transparent and clinically informed comparator selection and points to the need for CDA-AMC to commit to providing economic assessments of all clinically relevant comparators to ensure payers have a complete and balanced picture of the evidence.