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This study aimed to assess the feasibility of applying two recent phase I meta‐analyses methods to protein kinase inhibitors (PKIs) developed in oncology and to identify situations where these methods could be both feasible and useful. This ancillary study used data from a systematic review conducted to identify dose‐finding studies for PKIs. PKIs selected for meta‐analyses were required to have at least five completed dose‐finding studies involving cancer patients, with available results, and dose escalation guided by toxicity assessment. To account for heterogeneity caused by various administration schedules, some studies were divided into study parts, considered as separate entities in the meta‐analyses. For each PKI, two Bayesian random‐effects meta‐analysis methods were applied to model the toxicity probability distribution of the recommended dose and to estimate the maximum tolerated dose (MTD). Meta‐analyses were performed for 20 PKIs including 96 studies corresponding to 115 study parts. The median posterior probability of toxicity probability was below the toxicity thresholds of 0.20 for 70% of the PKIs, even if the resulting credible intervals were very wide. All approved doses were below the MTD estimated for the minimum toxicity threshold, except for one, for which the approved dose was above the MTD estimated for the maximal threshold. The application of phase I meta‐analysis methods has been feasible for the majority of PKI; nevertheless, their implementation requires multiple conditions. However, meta‐analyses resulted in estimates with large uncertainty, probably due to limited patient numbers and/or between‐study variability. This calls into question the reliability of the recommended doses. [ABSTRACT FROM AUTHOR]

Objective: To explore the implementation of the International Committee of Medical Journal Editors (ICMJE) data-sharing policy which came into force on 1 July 2018 by ICMJE-member journals and by ICMJE-affiliated journals declaring they follow the ICMJE recommendations., Design: A cross-sectional survey of data-sharing policies in 2018 on journal websites and in data-sharing statements in randomised controlled trials (RCTs)., Setting: ICMJE website; PubMed/Medline., Eligibility Criteria: ICMJE-member journals and 489 ICMJE-affiliated journals that published an RCT in 2018, had an accessible online website and were not considered as predatory journals according to Beall's list. One hundred RCTs for member journals and 100 RCTs for affiliated journals with a data-sharing policy, submitted after 1 July 2018., Main Outcome Measures: The primary outcome for the policies was the existence of a data-sharing policy (explicit data-sharing policy, no data-sharing policy, policy merely referring to ICMJE recommendations) as reported on the journal website, especially in the instructions for authors. For RCTs, our primary outcome was the intention to share individual participant data set out in the data-sharing statement., Results: Eight (out of 14; 57%) member journals had an explicit data-sharing policy on their website (three were more stringent than the ICMJE requirements, one was less demanding and four were compliant), five (35%) additional journals stated that they followed the ICMJE requirements, and one (8%) had no policy online. In RCTs published in these journals, there were data-sharing statements in 98 out of 100, with expressed intention to share individual patient data reaching 77 out of 100 (77%; 95% CI 67% to 85%). One hundred and forty-five (out of 489) ICMJE-affiliated journals (30%; 26% to 34%) had an explicit data-sharing policy on their website (11 were more stringent than the ICMJE requirements, 85 were less demanding and 49 were compliant) and 276 (56%; 52% to 61%) merely referred to the ICMJE requirements. In RCTs published in affiliated journals with an explicit data-sharing policy, data-sharing statements were rare (25%), and expressed intentions to share data were found in 22% (15% to 32%)., Conclusion: The implementation of ICMJE data-sharing requirements in online journal policies was suboptimal for ICMJE-member journals and poor for ICMJE-affiliated journals. The implementation of the policy was good in member journals and of concern for affiliated journals. We suggest the conduct of continuous audits of medical journal data-sharing policies in the future., Registration: The protocol was registered before the start of the research on the Open Science Framework (https://osf.io/n6whd/)., Competing Interests: Competing interests: FN, MS and JFG received funding from the French National Research Agency for the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)