Aim of the study: Different drug modification rules or growth factor support guidance may affect the results in oncology randomised controlled trials. We aimed to estimate the prevalence of unequal rules for dose modification rules or the use of myeloid growth factors in head-to-head registration Food and Drug Administration trials.
Methods: This cross-sectional analysis included all head-to-head registration randomised controlled trials leading to a US Food and Drug Administration approval between 2009 and 2021. Trials examined anti-cancer drugs in the advanced or metastatic setting where a comparison could be made between arms regarding either dose modification rules or myeloid growth factors recommendations. Sixty-two registration trials met inclusion criteria. Information abstracted for each trial included tumour type, setting, phase, and type of sponsor. We assessed, according to pre-specified rules, imbalance in drug modification rules, myeloid growth factors recommendations or both.
Results: We find 40 of 62 (65%) selected trials have unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use or both. Six trials (10%) had rules favouring the control arm, while 55% of selected trials (34/62) favoured the experimental arm. Among these, 50% (17/34) had unequal drug modification rules, 41% (14/34) had unequal G-CSF rules and 9% contained both (3/34).
Conclusion: We find that 55% of trials testing anti-cancer drugs against each other used protocol rules that favoured the experimental arm. This leaves open the question of whether new molecules are truly superior to older molecules or if instead different outcomes are due to more aggressive dosing or growth factor support. Trials should utilise equal rules for dose medication and G-CSF support.
Keywords: Comparative effectiveness trials; Drug dosing; Head-to-head trials; Myeloid growth factor; Oncology; Pharmacology; Posology; Randomised controlled trials.
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