The Impact of Clinical Evidence on the Inclusion of Non-Small Cell Lung Cancer Drugs in Brazil's Supplementary Healthcare System
Author(s)
Luiza Osuna Falavigna, BSc, Larissa Faia, BSc, Franciele Iachecen, MASc, Iara Muller Bernz, PharmD, Cristhiane Gennaro Simões, MBA.
IQVIA Brazil, São Paulo, Brazil.
IQVIA Brazil, São Paulo, Brazil.
OBJECTIVES: To evaluate the impact of clinical trial evidence on the regulatory outcomes of non-small cell lung cancer (NSCLC) drugs submitted for inclusion in the Brazilian National Supplementary Health Agency (ANS) listing since October 2021.
METHODS: A review was conducted on June 25, 2025, identifying all NSCLC drug submissions to the ANS list since October 2021. Submissions were categorized based on the presence of Phase 2 and Phase 3 trials. Two 2x2 contingency tables were built to compare the type of clinical evidence with the recommendation outcome. Fisher’s exact test with Monte Carlo simulation (10,000 replicates) was used to assess associations, accounting for small sample size and zero-count cells. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) were calculated using the Haldane-Anscombe correction. Analyses were conducted in R (version 4.5.1).
RESULTS: Six NSCLC drug submissions were identified. Favorable recommendations were issued for brigatinib, lorlatinib as first-line treatment, and osimertinib, all supported by Phase 3 trials, with network meta-analyses for brigatinib and lorlatinib. Unfavorable decisions were observed for lorlatinib as a second-line treatment, tepotinib, and selpercatinib, which relied primarily on Phase 2 data, although selpercatinib also included some Phase 3 evidence. Fisher’s exact test with Monte Carlo simulation indicated a significant association between Phase 3 evidence and favorable recommendation (p = 0.0101). Adjusted ORs showed a directional trend: Phase 3 trials were more likely associated with favorable outcomes (OR = 11.67; 95% CI: 0.322-422.166), while Phase 2 trials were linked to a higher likelihood of rejection (OR = 0.02; 95% CI: 0-1.348).
CONCLUSIONS: Regulatory decisions by ANS are influenced by the robustness of clinical trial evidence. These findings suggest that submissions relying solely on early-phase studies may face greater barriers to approval. This analysis provides valuable insights for optimizing future drug submission strategies within Brazil’s supplementary healthcare system.
METHODS: A review was conducted on June 25, 2025, identifying all NSCLC drug submissions to the ANS list since October 2021. Submissions were categorized based on the presence of Phase 2 and Phase 3 trials. Two 2x2 contingency tables were built to compare the type of clinical evidence with the recommendation outcome. Fisher’s exact test with Monte Carlo simulation (10,000 replicates) was used to assess associations, accounting for small sample size and zero-count cells. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) were calculated using the Haldane-Anscombe correction. Analyses were conducted in R (version 4.5.1).
RESULTS: Six NSCLC drug submissions were identified. Favorable recommendations were issued for brigatinib, lorlatinib as first-line treatment, and osimertinib, all supported by Phase 3 trials, with network meta-analyses for brigatinib and lorlatinib. Unfavorable decisions were observed for lorlatinib as a second-line treatment, tepotinib, and selpercatinib, which relied primarily on Phase 2 data, although selpercatinib also included some Phase 3 evidence. Fisher’s exact test with Monte Carlo simulation indicated a significant association between Phase 3 evidence and favorable recommendation (p = 0.0101). Adjusted ORs showed a directional trend: Phase 3 trials were more likely associated with favorable outcomes (OR = 11.67; 95% CI: 0.322-422.166), while Phase 2 trials were linked to a higher likelihood of rejection (OR = 0.02; 95% CI: 0-1.348).
CONCLUSIONS: Regulatory decisions by ANS are influenced by the robustness of clinical trial evidence. These findings suggest that submissions relying solely on early-phase studies may face greater barriers to approval. This analysis provides valuable insights for optimizing future drug submission strategies within Brazil’s supplementary healthcare system.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA319
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology