Challenges of globalization of cancer drug trials- recruitment in LMICs, approval in HICs

An increasing number of cancer clinical trials are conducted in low-and-middle-income countries (LMICs). 1 Increasing the representation of LMICs in cancer drug trials is encouraging, but we are concerned about research parasitism and parachutism in these practices.2 In this commentary, we explore how LMICs may not have been served by participating in these global cancer drug trials.Despite reduced complexity and lower cost being commonly cited reasons for the industry's motivation in running cancer drug trials in LMICs, 1 there is another incentive that is less frequently discussedthe possibility of running a trial with a substandard control arm that would not be considered appropriate in a high-income country (HIC).For example, a new immune checkpoint inhibitor (ICI) (cemiplimab-rwlc) for patients with advanced Non-Small Cell Lung Cancer Treatment (NSCLC) with tumor PD-L1 expression of 50% or more was run as an international trial (EMPOWER-Lung 1) in several HICs (such as Australia and Spain) and LMICs (including Brazil, Chile, Colombia and Mexico), not including the USA.The trial compared cemiplimab against chemotherapy control between June 2017 and February 2020.3 This was done despite pembrolizumab, another ICI, having been established as the standard of care for this patient population after demonstrating improved survival versus chemotherapy in a randomized controlled trial.4 Nevertheless, the EMPOWER-Lung 1 trial enrolled patients to a trial with chemotherapy as the control arm and proved, unsurprisingly, the superiority of immunotherapy, leading to the drug's approval by the US FDA. 5 This practice of running substandard trials in LMICs to get a drug approved in HICs is unacceptable for several reasons.Firstly, the Helsinki Declaration states that control arms in randomized controlled trials (RCTs) should receive the "best-proven intervention", 6 not the standard of care in the local research setting.Investigators from HICsthe majority of which are sponsored by the pharmaceutical industryfrequently conduct clinical cancer trials in LMICs, where an inferior control arm is used