High impact of positive and negative clinical trial results

From the Unger Group, Division of Public Health Sciences

Results from clinical trials provide the foundation for the development and refinement of clinical care guidelines. Within the field of cancer research, the National Cancer Institute (NCI) Clinical Trial Network (NCTN) supports the conduct of primary clinical trials that are designed to serve the community of cancer patients by improving treatments for cancer. Despite decades of NCI-sponsored research, there have not been any systematic or comprehensive assessments of the influence of NCTN trials on real-world clinical practice in the United States. Thus, researchers from Dr. Joseph Unger’s research group in the Division of Public Health Sciences and colleagues set out to determine the proportion of NCI-sponsored phase 3 clinical trials associated with clinical care guidelines or new drug indications. The results were recently published in the journal JAMA Network Open.

The NCTN is comprised of five groups in the United States and one in Canada. The authors examined 182 clinical trials that were conducted or contributed to by the SWOG (formerly Southwest Oncology Group) Cancer Research Network with a primary end point published between January 1980 and June 2017. The authors first considered a trial to have been “practice influential” (PI) if it provided evidence that it informed recommended clinical guideline care or new drug approvals by the US Food and Drug Administration (FDA). Trials with negative findings could be classified as PI if the results were consistent with the standard of care recommendation for a given type of cancer or if they supported other standard of care.

Graphical representation of influence of National Cancer Institute Clinical Trial Network trials on guideline care in National Comprehensive Cancer Network (NCCN) or new drug indications approved by the US Food and Drug Administration (FDA).
Influence of National Cancer Institute Clinical Trial Network trials on guideline care in National Comprehensive Cancer Network (NCCN) or new drug indications approved by the US Food and Drug Administration (FDA). Image from Dr. Joseph Unger

Of the 182 trials, 45% were classified as PI (see Figure). Among these 82 PI trials, 70 were influential only on clinical practice guidelines, 6 were influential on FDA indications (drug approvals), and 6 were influential on both. The PI trials were nearly split between those with positive findings (57%) and those with negative findings (43%). With the exception of only one trial, all of the negative PI trials were influential on NCCN guidelines only. Approximately half of these negative trials provided evidence in favor of the existing standard of care, illustrating the importance of negative trials in showing which new treatments do not work. This finding of the impact of negative trials results on clinical care is especially notable as the scientific community and beyond may not fully appreciate the importance and impact of negative study results.

Another goal of the study was to estimate the costs associated with conducting NCI-sponsored trials. Using the National Institutes of Health online reporting tool, the combined cost of the 182 trials was estimated to be $1.36 billion when inflated to 2017 dollars. When this total cost was considered for the 82 PI trials, the breakdown was $123.6 million for each new FDA drug approval and $16.6 million per PI trial. “We found that the NCI’s clinical trials program contributes clinically meaningful, cost-effective evidence to guide care of cancer patients,” said Dr. Unger.

Dr. Unger summarized the overall results, “The take-home message is that NCI-sponsored studies provide clinically meaningful evidence for patients that influences their care routinely and does so at a relatively cost-effective level”. This research also highlights the impact of primary clinical trials and the downstream effects of both positive and negative trial results. “It’s important that people appreciate just how valuable these federally sponsored trials are in terms of benefit to patients with cancer,” emphasized Dr. Unger.    

This work was supported by the National Cancer Institute and the Hope Foundation for Cancer Research.

Fred Hutch/UW Cancer Consortium members Drs. Joseph Unger and Michael LeBlanc contributed to this research.

Unger JM, Nghiem VT, Hershman DL, Vaidya R, LeBlanc M, Blanke CD. 2019. Association of National Cancer Institute-sponsored clinical trial network group studies with guideline care and new drug indications. JAMA Network Open. doi: 10.1001/jamanetworkopen.2019.10593.