Analysis of the control arms of oncology randomized clinical trials in Brazil

Introduction: In the past decades, there has been an increase in the participation of low-middle-income countries (LMICs), including Brazil, in international multicentric oncology trials. This phenomenon led to significant advancements in LMICs, including access to better treatments. However, there has been substantial criticism of the international community regarding trials offering substandard control arms compared to the standard of care in high-income countries. Herein, we investigate the control arms of trials recruiting in Brazil.

Objective: To describe the control arm of randomized oncology trials recruiting in Brazil and to rank its appropriateness according to guidelines.

Methods: This is a cross-sectional study including randomized clinical trials recruiting in Brazil on December 4, 2023, according to data from https://clinicaltrials.gov. Data from the studies were abstracted, including the intended number of patients, sponsor, tumor site, phase of study, and control arm. The control arm was ranked as “superior”, “equal”, or “inferior” by NCCN guidelines, supplementary healthcare (supplementary) standards in Brazil, and SUS standards by 2 independent investigators. Brazilian Health Ministry diretrizes diagnósticas e terapêuticas and the ICESP handbook were used to determine SUS standards. Data was summarized in means, medians, and proportions. Fisher’s exact test was used to compare categories. A p<0.05 was considered statistically significant.

Results: Ninety-eight studies were included. The median number of intended patients was 555 (54-6000). Most trials were phase 3 (84.7%) and sponsored by pharma (97%). The most frequent tumor types were lung (29.6%) and breast (24.4%). Regarding the line of treatment, 23 (23.5%), 48 (49%), and 27 (27.5%) were (neo)adjuvant, 1st line, or 2nd or higher, respectively. In terms of the control arms, 0 studies had its control arms superior to both NCCN or supplementary standards, while 37 (37.8%) were superior to SUS. 79 (80.6%), 81 (82.7%), 56 (57.1%), were equal and 19 (19.4%), 17 (17.3%) and 5 (5.1%), were inferior to NCCN, supplementary and SUS, respectively. Of the 19 control arms considered inferior to NCCN, 3 were ranked as superior, and 16 as equal to SUS.

Conclusion: A significant number of studies have a control arm inferior to NCCN guidelines. However, the same controls were considered superior or equal to the standards offered in SUS. Such discrepancies may compromise the interpretation of the studies’ findings.

Corresponding author: Ana Elisa Boracini Sanches (e-mail: anaelisaboracini@gmail.com).