ReviewThe oncologist2022
Optimism Bias in the Design of Phase III Randomized Control Trials Evaluating PD-1/PD-L1 Targeting Monoclonal Antibodies.
Review in The oncologist, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed, 2 citations in OpenAlex.
No citing paper in PubMed yet.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany randomized control trials (RCTs) evaluating programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) targeting monoclonal antibodies (mAbs) have been completed or are in progress. We examined hypothesized hazard ratios (HHRs) and observed hazard ratios (OHRs) from published RCTs evaluating these mAbs.
methodsPublications of RCTs evaluating at least one PD-1/PD-L1 targeting mAbs approved by the US Food and Drug Administration were identified through PubMed searches. The primary reports of RCTs were retrieved. Two investigators extracted HHR, OHR for the primary endpoint among other data elements independently. The differences (∆HR) in HHR and OHR were analyzed statistically. A separate search was conducted for secondary reports after longer follow-ups, the updated OHR was extracted.
resultsForty-nine RCTs enrolling 36 867 patients were included. The mean HHR and OHR were 0.672 and 0.738 respectively. The mean ∆HR was 0.067 (range: -0.300 to 0.895; 95% confidence interval (CI), 0.003-0.130). HHR was met or exceeded in 22 (45%) RCTs. OHR was ≥ 1.0 in 6 RCTs (12%). PD-L1 expression was not associated with the magnitude of effect. Of 18 RCTs with follow-up reports, the magnitude of benefit decreased in 8 RCTs with extended follow-ups.
conclusionThe majority of published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve their hypothesized magnitude of benefit. The optimism bias requires attention from the cancer clinical research community given the number of these agents in development and the intense interest in evaluating these agents in a variety of disease settings.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.