Commentary: NCI-sponsored Clinical Trials are Clinically Meaningful and Cost-Effective

SWOG, ECOG, Alliance, NRG, COG, and NCTN. What does this alphabet soup mean for advancing care for patients? Some view the cooperative groups as a mechanism by which studies, that the pharmaceutical industry will undertake, get done. A few even go as far as describe them as the place to conduct a negative study implying that every effort will lead to a null result. When I hear this, it makes me think of Mike Polk Jr’s characterization of First Energy Stadium as a “Factory of Sadness” resulting in perpetual negativity for diehard Browns fans. But is that really true? Are the US cooperative groups really a factory of clinical trial sadness?

The cooperative groups that make up the National Cancer Institute’s (NCI) National Clinical Trials Network (NCTN) do have a mandate to “routinely achieve change in clinical practice” through conducting thoughtful, well-conducted clinical trials. This is in contrast to the pharmaceutical industry which is ultimately beholden to shareholders and profits as opposed to the public good. This may lead to the skewing of the number of positive versus negative industry-sponsored studies relative to those conducted through the NCTN. However, negative studies can influence practice just as much as positive ones, even more so when they identify costly therapies that are not effective or are able to reduce the toxicity of treatment.

In order to better assess the impact of NCTN trials on practice, Unger and collaborators evaluated 182 phase III trials conducted by SWOG Cancer Research Network including 148,028 patients over 37.5 years starting January 1, 1980. They found that 82 (45%) trials had practice-influencing results with 39% serving as the basis for recommendations in National Comprehensive Cancer Network (NCCN) guidelines, 3.3% serving as the basis for regulatory approval, and 3.3% doing both.

As mentioned above, cooperative groups are sometimes jokingly called “a place to conduct negative studies.” However, negative studies can be instrumental in shaping care, and nearly 30% of the 117 negative studies evaluated by Unger et al. were found to be practice influencing. Moreover, 35 (43%) of the 82 practice-influencing studies had negative findings, with almost half of these studies confirming standard of care treatment.

The NCTN also provides good bang-for-the-buck. In this analysis of practice-influencing SWOG studies, the total federal investment was estimated to be $1.36 billion in 2017 dollars for the 182 trials. This breaks down to $7.5 million per completed phase 3 trial, $16.6 million per practice-influencing trial, and $123.6 million per new drug approval. By way of comparison, it is estimated to cost over $1.1 billion in 2017 dollars for a pharmaceutical company to get a new drug through development process and all the way to regulatory approval (DiMasi JA et al. J Health Econ. 2003). This is by no means a fair comparison, considering that the pharmaceutical industry research process not only supports late-phase trials, but initial drug discovery and early trials, for which the regulatory oversight is much more costly. Nevertheless, it’s a good return on investment for the public.

So, unlike the Browns' season that has been mired in disappointment (perhaps there is still time for a turnaround), the NCI-funded cooperative groups deliver as a factory of clinically meaningful results, and do so at a good value. Case Comprehensive Cancer Center members are highly involved in the NCTN and their activities are supported by one of only thirty-two LAPS (Lead Academic Participating Site) grants awarded by the NIH. These funds allow us to continue to develop, implement, and lead these practice-influencing clinical trials throughout the National Clinical Trials Network cooperative groups.

Aaron T. Gerds, MD, MS
Co-PI, Case Comprehensive Cancer Center LAPS grant
Hematologist/Medical Oncologist, Cleveland Clinic