Recommendations by countries’ health technology assessment (HTA) agencies are used to decide which new therapies warrant the allocation of limited health-care resources to make them available through publicly funded health systems. This process is of public health importance for balancing the dual aims of optimising patient outcomes while ensuring financial sustainability. We evaluated which factors affect HTA outcomes and the time to positive HTA outcome, focussing on the role of clinical benefit evaluated with the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).

In this retrospective analysis, data were extracted from publicly available HTA reports and related sources from six country settings and their respective HTA agencies (Australia, Canada, England, France, the Canadian province of Quebec, and Scotland). We evaluated new cancer medicines for treating solid tumours in a non-curative setting with published ESMO-MCBS scores and that had been assessed by at least three HTA agencies between Jan 1, 2011, and Dec 31, 2020. Using ESMO-MCBS score as an independent variable, we did descriptive and multivariable regression analyses to evaluate: (1) factors associated with the time between marketing authorisation and positive (unrestricted [List] and restricted [List with Constraints]) HTA outcome; and (2) factors associated with HTA outcomes.

67 medicine–indication pairs used in non-curative settings were identified, totalling 360 HTA submissions (medicine–indication–country triplets) reviewed by the six HTA agencies. Factors significantly associated with a reduced interval between marketing authorisation and a positive (unrestricted or restricted) HTA outcome included a high ESMO-MCBS score (ie, 4 or 5, vs a low or average score of 1–3; hazard ratio [HR] per 1 month increment 1·42 [95% CI 1·11–1·81], p=0·0055), parallel review (vs standard marketing authorisation process; HR 1·69 [1·13–2·54], p=0·011), having a risk-sharing agreement or special funding arrangements (vs no funding agreement, HR 4·62 [95% CI 2·51–8·51], p<0·0001, and HR 4·16 [2·03–8·50], p=0·0001, respectively), and assessment by particular HTA agencies (pan-Canadian Oncology Drug Review vs National Institute for Health and Care Excellence [NICE], HR 2·82 [1·68–4·75], p=0·0001; and Haute Autorité de Santé vs NICE, HR 5·70 [2·87–11·33], p<0·0001). Accelerated marketing authorisation was significantly associated with a longer time to positive HTA outcome (vs standard authorisation process; HR 0·70 [95% CI 0·51–0·95], p=0·024). Positive HTA outcomes (both unrestricted and restricted) were significantly associated with a high ESMO-MCBS score (vs low or average ESMO-MCBS score; relative risk ratio [RRR] 14·10 [95% CI 3·54–56·20], p=0·0002, and RRR 4·52 [1·90–10·75], p=0·0006, respectively) and acknowledgment of unmet medical need (vs unmet need not recorded, RRR 22·73 [5·51–93·73], p<0·0001, and RRR 1·87 [1·18–2·97], p=0·0075, respectively). By contrast, positive HTA outcomes (unrestricted and restricted) were inversely associated with uncertainties regarding inputs to economic models informing HTA submissions (vs uncertainties not recorded, RRR 0·28 [0·10–0·78], p=0·014, and RRR 0·45 [0·25–0·82], p=0·010, respectively). Regarding country-relevant effects, inverse associations with positive HTA outcomes (both unrestricted and restricted) were observed for assessment in Quebec (vs England; RRR 1·15×10⁻⁶ [1·44×10⁻⁷–9·09×10⁻⁶], p<0·0001, and RRR 0·33 (0·24–0·46), p<0·0001, respectively) and for assessment in Australia (vs England; RRR 1·78×10⁻⁶ [1·04×10⁻⁸–3·00×10⁻⁴], p<0·0001, and RRR 0·30 [0·15–0·61], p=0·0008, respectively).

Several factors informed HTA outcomes for new cancer medicines. A high ESMO-MCBS score, defined as indicating substantial clinical benefit, increased the likelihood of a positive HTA outcome and shortened the interval between marketing authorisation and HTA outcome, and this association was not affected by other variables. Additional factors informing HTA outcomes include evidence uncertainties and unmet medical need. Country-relevant differences exist in the time-to-HTA outcome and the propensity of some countries to achieve positive (restricted or unrestricted) outcomes compared with others.

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