Are too many Phase III cancer clinical trials set up to fail?

Date:
September 23, 2021
Source:
National Comprehensive Cancer Network
Summary:
New research finds four out of five cancer therapies tested in
Phase III trials do not achieve clinically-meaningful benefit in
prolonging survival, and is the first study to quantify the number
of false- positive, false-negative, and true-negative trial results.



FULL STORY ==========================================================================
New research in the September 2021 issue of JNCCN -- Journal of
the National Comprehensive Cancer Networkfinds that more than 80% of
therapies tested in Phase III oncology trials did not achieve meaningful clinical benefit in prolonging survival. The researchers analyzed 362 industry-sponsored Phase III randomized trials in oncology from 2008 to
2017, and found that 87% were either false-positive or true-negative
for meeting overall survival goals. More than half of the initially
reported positive trials were found to be false-positive (58.4%) for
overall survival, while the overwhelming majority of negative results
were determined to be true-negative (with only 0.9% false-negative).


==========================================================================
Dr. Shen continued: "Our study shows that reducing false positive errors
by imposing more stringent statistical threshold in Phase III trials is
not likely to be practically feasible. A better strategy is to rethink the process that leads to the decision of moving a new therapy to Phase III
testing to begin with. More research is needed in this regard.""Our study highlights the need to more efficiently identify which new therapies
merit Phase III testing," said lead researcher Changyu Shen, PhD,
Associate Professor at Harvard Medical School at the time this study
was conducted. "In order to sustain the rate of innovation in cancer therapeutics and ensure that our patients have access to effective yet affordable therapies, the clinical trial pipeline in oncology must be
efficient and accurate. Our work shows that in the past ten years, this
has not been the case." Most of the trials in this novel study focused on lung, breast, gastrointestinal, and hematologic cancers; trials with fewer
than 100 participants were excluded, meaning rare cancer types were less
likely to be included. The Phase III trials were predominately two-arm
studies of an interventional regimen compared with a control treatment.

"This paper shows that a lot of drugs with 'positive' Phase III trials
may have a smaller ultimate benefit than was expected, and that changing
the threshold for statistical significance is not a quick fix," said
Elizabeth A. Handorf, PhD, Associate Research Professor, Fox Chase Cancer Center, who was not involved in this research. "I think it highlights
the need for more efficient study designs, like adaptive trials,
and clear definitions of what makes an effect clinically meaningful." ========================================================================== Story Source: Materials provided by
National_Comprehensive_Cancer_Network. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Changyu Shen, Enrico G. Ferro, Huiping Xu, Daniel B. Kramer, Rushad
Patell, Dhruv S. Kazi. Underperformance of Contemporary Phase III
Oncology Trials and Strategies for Improvement. Journal of the
National Comprehensive Cancer Network, 2021; 19 (9): 1072 DOI:
10.6004/ jnccn.2020.7690 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210923102034.htm

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