Importance of Publishing Negative Data
The lack of publication of negative data is of ethical concern as well. Negative trials that go unpublished provide no benefits to their patient participants. In addition, patients may experience unnecessary harm or receive an ineffective therapy because oncologists may attempt treatment with a drug or combination that is not beneficial, unaware of data that were never published.4 Furthermore, resources may continue to be wasted in an effort to conduct more research and human studies with a strategy or an approach found to lack benefit or to be intolerable.
In the BEZ235 phase 1 trial, the lack of efficacy and low tolerability, which were also noted in several other solid tumors, indicate that the dual inhibition of PI3K and mTOR is not feasible. Had those data not been published, others may have continued to pursue this strategy with false hope. Resources can now be directed towards other projects, such as isoform-specific PI3K inhibitors with more favorable safety profiles.
Efforts to Improve Publication Rates
Still, an international effort exists to promote publication of negative data. In 2007, the United States mandated the release of all clinical trial data within 12 months of completion, yet 82% of trials were not released. This may be due to non-publicized study extensions, though the completion date should be updated if an extension has been granted. A new federal ruling aims to strengthen the 2007 mandate and will take effect in early 2017, although enforcement will be critical to ensure that it is followed.
Some journals have increased their acceptance of trials reporting negative results. Dr Fojo told Cancer Therapy Advisor that “we are very upfront as to wanting negative trials,” and highlighted that The Lancet Oncology also has “increasingly had the will to publish large negative trials.” But there is still an unwillingness to publish these data by study investigators. “The journey with the Clinical Trial Results Section has been very educational. We have been impressed with how very difficult it is to get investigators to publish negative trials,” he said.
Dr Fojo emphasized that The Oncologist works hard to make the publication of negative data a reality. Yet, “it is surprising how many submissions come in, and the authors are still trying to—in a nuanced sort of way—look for the ‘positive.’ And you have to say, ‘no, this is negative.’ We want investigators to understand that negative is as important as positive.”
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Publication of all data is critical to ensure the forward movement of research that is needed to create clinically meaningful improvement in patient outcomes. “In the end, we must test our hypotheses, obtain results, and move forward. And once we establish this, we must submit it for publication, rapidly and concisely, so that others can learn from it,” Doctors Pongas and Fojo wrote.
Disclosures: the author has no relevant relationships to report.
- Pongas G, Fojo T. BEZ235: when promising science meets clinical reality. The Oncologist. 2016;21:1033-4. doi: 10.1634/theoncologist.2016-0243
- Carlo MI, Molina AM, Lakhman Y, et al. A phase Ib study of BEZ235, a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), in patients with advanced renal cell carcinoma. The Oncologist. 2016;21:787-8. doi: 10.1634/theoncologist.2016-0145.
- Massey PR, Wang R, Prasad V, Bates SE, Fojo T. Assessing the eventual publication of clinical trial abstracts submitted to a large annual oncology meeting. The Oncologist. 2016;21:261-8. doi: 10.1634/theoncologist.2015-0516
- Goodwin PM. Failure to publish trial data puts patients at risk for no gain. Oncol Times. 2016;38:36.
- Clinical Trials Registration and Results Information Submission. Federal Register website. http://www.federalregister.gov/d/2016-22129. Updated Septebmer 2016. Accessed September 2016.