Association of Industry and Academic Sponsorship With Negative Phase 3 Oncology Trials and Reported Outcomes on Participant Survival

Addeo, Alfredo; Weiss, Glen J.; Gyawali, Bishal

doi:10.1001/jamanetworkopen.2019.3684

Cited by 7 publications

(3 citation statements)

References 72 publications

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“…The average cost of an oncological phase III trial has been estimated to be up to $200 million. 44 , 45 Phase II data should be critically assessed about whether the phase III studies likely to be positive, potentially with some absolute thresholds based on data such as provide in our study. Ideally, drugs with clinically meaningful and statistically significant benefits are developed.…”

Section: Discussionmentioning

confidence: 99%

Inefficiencies in phase II to phase III transition impeding successful drug development in glioblastoma

Balasubramanian

Gunjur

Hafeez

et al. 2020

Neuro-Oncology Advances

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Background Improving outcomes of patients with glioblastoma (GBM) represents a significant challenge in neuro-oncology. We undertook a systematic review of key parameters of phase II and III trials in GBM to identify and quantify the impact of trial design on this phenomenon. Methods Studies between 2005 and 2019 inclusive were identified though MEDLINE search and manual bibliography searches. Phase II studies (P2T) were restricted to those referenced by the corresponding phase III trials (P3T). Clinical and statistical characteristics were extracted. For each P3T, corresponding P2T data was “optimally matched,” where same drug was used in similar schedule and similar population; “suboptimally matched” if dis-similar schedule and/or treatment setting; or “lacking.” Phase II/III transition data were compared by Pearson Correlation, Fisher’s exact or chi-square testing. Results Of 20 P3Ts identified, 6 (30%) lacked phase II data. Of the remaining 14 P3T, 9 had 1 prior P2T, 4 had 2 P2T, and 1 had 3 P2T, for a total of 20 P3T-P2T pairs (called dyads). The 13 “optimally matched” dyads showed strong concordance for mPFS (r2 = 0.95, P < .01) and mOS (r2 = 0.84, P < .01), while 7 “suboptimally matched” dyads did not (P > .05). Overall, 7 P3Ts underwent an ideal transition from P2T to P3T. “Newly diagnosed” P2Ts with mPFS < 14 months and/or mOS< 22 months had subsequent negative P3Ts. “Recurrent” P2Ts with mPFS < 6 months and mOS< 12 months also had negative P3Ts. Conclusion Our findings highlight the critical role of optimally designed phase II trials in informing drug development for GBM.

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Section: Discussionmentioning

confidence: 99%

Inefficiencies in phase II to phase III transition impeding successful drug development in glioblastoma

Balasubramanian

Gunjur

Hafeez

et al. 2020

Neuro-Oncology Advances

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“…For example, preclinical animal models serve as the foundation for clinical trials, but have exhibited suboptimal methods,38 which may explain why animal study results fail to successfully translate to clinical benefit. In fact, it was recently shown that many phase 3 trials in Oncology are conducted despite no significant phase 2 results 39. One possible explanation for why phase 3 trials proceed despite non-significant phase 2 results is the strong bioplausibility demonstrated in preclinical studies.…”

Section: Discussionmentioning

confidence: 99%

Do oncology researchers adhere to reproducible and transparent principles? A cross-sectional survey of published oncology literature

et al. 2019

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ObjectivesAs much as 50%–90% of research is estimated to be irreproducible, costing upwards of $28 billion in USA alone. Reproducible research practices are essential to improving the reproducibility and transparency of biomedical research, such as including preregistering studies, publishing a protocol, making research data and metadata publicly available, and publishing in open access journals. Here we report an investigation of key reproducible or transparent research practices in the published oncology literature.DesignWe performed a cross-sectional analysis of a random sample of 300 oncology publications published from 2014 to 2018. We extracted key reproducibility and transparency characteristics in a duplicative fashion by blinded investigators using a pilot tested Google Form.Primary outcome measuresThe primary outcome of this investigation is the frequency of key reproducible or transparent research practices followed in published biomedical and clinical oncology literature.ResultsOf the 300 publications randomly sampled, 296 were analysed for reproducibility characteristics. Of these 296 publications, 194 contained empirical data that could be analysed for reproducible and transparent research practices. Raw data were available for nine studies (4.6%). Five publications (2.6%) provided a protocol. Despite our sample including 15 clinical trials and 7 systematic reviews/meta-analyses, only 7 included a preregistration statement. Less than 25% (65/194) of publications provided an author conflict of interest statement.ConclusionWe found that key reproducibility and transparency characteristics were absent from a random sample of published oncology publications. We recommend required preregistration for all eligible trials and systematic reviews, published protocols for all manuscripts, and deposition of raw data and metadata in public repositories.

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“…For example, preclinical animal models serve as the foundation for clinical trials, but have exhibited suboptimal methods 36 , which may explain why animal study results fail to successfully translate to clinical benefit. In fact, it was recently shown that many phase 3 trials in Oncology are conducted despite no significant phase 2 results 37 . One possible explanation for why phase 3 trials proceed despite nonsignificant phase 2 results is the strong bioplausibility demonstrated in preclinical studies.…”

Section: Discussionmentioning

confidence: 99%

Reproducibility and transparency characteristics of oncology research evidence

Walters¹,

Harter²,

Wayant³

et al. 2019

Preprint

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Introduction: As much as 50%-90% of research is estimated to be irreproducible, costing upwards of $28 billion in the United States alone. Reproducible research practices are essential to improving the reproducibility and transparency of biomedical research, such as including pre-registering studies, publishing a protocol, making research data and metadata publicly available, and publishing in open access journals. Here we report an investigation of key reproducible or transparent research practices in the published oncology literature. Methods: We performed a cross-sectional analysis of a random sample of 300 oncology studies published from 2014-2018. We extracted key reproducibility and transparency characteristics in a duplicative fashion by blinded investigators using a pilot tested Google Form. Results: Of the 300 studies randomly sampled, 296 studies were analyzed for study reproducibility characteristics. Of these 296 studies, 194 were contained empirical data that could be analyzed for reproducible and transparent research practices. Raw data was available for 9 studies (4.6%). Approximately 5 studies (2.6%) provided a protocol. Despite our sample including 15 clinical trials and 7 systematic reviews/meta-analyses, only 7 included a pre-registration statement. Less than 25% (65/194) of studies provided an author conflict of interest statement. Discussion: We found that key reproducibility and transparency characteristics were absent from a random sample of published oncology studies. We recommend required pre-registration for all eligible trials and systematic reviews, published protocols for all manuscripts, and deposition of raw data and metadata in public repositories.

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Association of Industry and Academic Sponsorship With Negative Phase 3 Oncology Trials and Reported Outcomes on Participant Survival

Cited by 7 publications

References 72 publications

Inefficiencies in phase II to phase III transition impeding successful drug development in glioblastoma

Inefficiencies in phase II to phase III transition impeding successful drug development in glioblastoma

Do oncology researchers adhere to reproducible and transparent principles? A cross-sectional survey of published oncology literature

Reproducibility and transparency characteristics of oncology research evidence

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