BACKGROUND: New discoveries are a critical priority for the pharmaceutical industry, for which the primary aim should be to address unmet medical needs. However, the use of fixed cost-effectiveness (ICER) thresholds for health technology assessment (HTA) may tend to decrease incentives to innovate and affect future treatment options. This presentation highlights, using a case study, the impact of recent generic drug price policies on pharmaceutical innovation in the context of fixed ICER thresholds and proposes a new consideration for the cost-effectiveness analysis (CEA). RATIONALE: There is a direct causal relationship between HTA and the market price of a drug; in jurisdictions where HTA agencies apply fixed ICER thresholds as an important reimbursement listing criterion, the incremental cost of a new drug is expected to be proportional to its incremental benefit over the comparator. However, the comparator price is subject to market forces or sudden policies and may change markedly affecting the cost-effectiveness assessment (e.g. where the comparator patent has expired). Since recent generic price regulations (e.g. 18% or 25% of the innovative price in Canada) increased the price gap between drugs’ generic and patented versions, it is harder to achieve a sufficient level of incremental benefits in order to offset incremental prices of new treatments. This analysis thus demonstrates that with recent changes in generic drug prices in Canada and other jurisdictions, even promising drugs will have challenges to show attractive ICERs. CONCLUSION: Traditional decision-making process should be adapted to reflect these changes and to promote innovation in therapeutic fields with unmet medical needs. A compromise would be to include the comparator’s patented price in the CEA instead of the generic drug in certain areas of unmet needs. By identifying the relevant disease areas, decision-makers and HTA authorities could convey the importance of investing in these therapeutic areas to manufacturers.