Globalization of clinical trials for breast cancer with innovative and highly priced drugs: ethical implications in resource-limited settings

Introduction: Breast cancer (BC), the most frequent cancer in women, is one “big killer” in oncology. Innovative, highly-priced drugs dramatically changed prognosis in affluent countries, where as most patients in low-income settings still lack access to innovative drugs. The geography of BC clinical trials with innovative drugs has not been investigated yet. Aim: We aimed at describing the geographic distribution of industry-sponsored BC clinical trials evaluating innovative“targeted small molecules” and monoclonal antibodies. Methods: Industry-sponsored trials registered as of June 30,2017 were extracted from clinicaltrials.gov. Search criteria were:(i) study type: Interventional studies; (ii) condition/disease: breastcancer; (iii) phases: all phases (1 to 4); (iv) funder type: industry.Countries were classified by income according to the World Bank. Results: 1323 trials were analysed.Among all phase 3,interventional, industry-sponsored clinical trials against BC, 141/276 (51.08%) involved middle income countries (MICs),including both lower-MICs 55/276 (20.99%) and upper-MICs 144/276 (52.17%). Phase 1 and 2 trials were run in MICs in smaller proportions (41/315, 13.02% and 146/676, 21.60%,respectively). Phase 4 trials involved MICs in 13/56 (23.21%) instances. No trials were run in low-income countries. Countries most frequently involved in trials were India (n=61), Ukraine(n=50), Philippines (n=21), Guatemala (n=17), Egypt(n=15) among lower-MICs, and Russian Federation (n=117),Brazil (n=108), Argentina and China (n=90 each), Mexico(n=78) among upper MICs. Conclusion: Trials with innovative drugs against BC are increasingly delocalized to countries that are unlikely to be able to bear the cost of such drugs. This scenario is reminiscent of that previously reported by us for the rarer haematological cancers, but the magnitude observed for BC is far greater. Most research ethics guidelines state that research can be conducted in a given population only if there is a reasonable likelihood that this population will benefit from the research; otherwise, it will be deemed exploitative. Regulatory or legal measures are needed to ensure that innovative BC drugs are rapidly registered and made available at fair prices in all the countries that participated in clinical development. Also, Ethics Committees reviewing the trials’ protocols should systematically ask if adequate measures are planned to do so