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Possible Causes of Failing to Meet Primary Endpoints: A Systematic Review of Randomized Controlled Phase 3 Clinical Trials in Patients With Non–Small Cell Lung Cancer

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Abstract

Background

Non—small cell lung cancer (NSCLC) is the most common cause of cancer-related mortality worldwide and represents a huge unmet medical need. Despite the favorable results of phase 2 clinical trials, many phase 3 clinical trials fail to meet primary endpoints. Therefore, we investigated the causes of failure to meet primary endpoints in phase 3 clinical trials

Methods

We performed a systematic review of phase 3 clinical trials in patients with NSCLC. The results of phase 3 clinical trials collected from the survey were categorized as “negative” (failed to meet the primary endpoint) or “positive” (met the primary endpoint)

Results

Of a total of 106 trials collected from this survey, 40 positive trials (38%) and 66 negative trials (62%) were identified. The majority of the primary endpoints were overall survival (OS) or progression-free survival (PFS) (94%). More trials using OS as the primary endpoint were negative (42 of 56 trials), and more trials using PFS as the primary endpoint were positive (24 of 44 trials). The median OS in the control arm in negative trials was significantly longer than the pretrial estimate (P <.001), whereas the median PFS in the control arm in positive trials was relatively consistent with the pretrial estimate

Conclusions

Our findings suggest that the selection of the primary endpoint and the pretrial estimate can potentially impact the results of phase 3 clinical trials in patients with NSCLC and are critical success factors when planning phase 3 clinical trials

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Authors and Affiliations

  1. Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan

    Mitsugu Ikeda MSc, Tatsuya Ochibe & Masahiro Tohkin PhD

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  1. Mitsugu Ikeda MSc
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  2. Tatsuya Ochibe
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  3. Masahiro Tohkin PhD
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Correspondence to Masahiro Tohkin PhD.

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Ikeda, M., Ochibe, T. & Tohkin, M. Possible Causes of Failing to Meet Primary Endpoints: A Systematic Review of Randomized Controlled Phase 3 Clinical Trials in Patients With Non–Small Cell Lung Cancer. Ther Innov Regul Sci 53, 324–331 (2019). https://doi.org/10.1177/2168479018791135

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