Population, Clinical, and Scientific Impact of National Cancer Institute's National Clinical Trials Network Treatment Studies

Abstract

Purpose: In the United States, the National Cancer Institute National Cancer Clinical Trials Network (NCTN) groups have conducted publicly funded oncology research for 50 years. The combined impact of all adult network group trials has never been systematically examined.

Methods: We identified randomized, phase III trials from the adult NCTN groups, reported from 1980 onward, with statistically significant findings for ≥ 1 clinical, time-dependent outcomes. In the subset of trials in which the experimental arm improved overall survival, gains in population life-years were estimated by deriving trial-specific hazard functions and hazard ratios to estimate the experimental treatment benefit and then mapping this trial-level benefit onto the US cancer population using registry and life-table data. Scientific impact was based on citation data from Google Scholar. Federal investment costs per life-year gained were estimated. The results were derived through December 31, 2020.

Results: One hundred sixty-two trials comprised of 108,334 patients were analyzed, representing 29.8% (162/544) of trials conducted. The most common cancers included breast (34), gynecologic (28), and lung (14). The trials were cited 165,336 times (mean, 62.2 citations/trial/year); 87.7% of trials were cited in cancer care guidelines in favor of the recommended treatment. These studies were estimated to have generated 14.2 million (95% CI, 11.5 to 16.5 million) additional life-years to patients with cancer, with projected gains of 24.1 million (95% CI, 19.7 to 28.2 million) life-years by 2030. The federal investment cost per life-year gained through 2020 was $326 in US dollars.

Conclusion: NCTN randomized trials have been widely cited and are routinely included in clinical guidelines. Moreover, their conduct has predicted substantial improvements in overall survival in the United States for patients with oncologic disease, suggesting they have contributed meaningfully to this nation's health. These findings demonstrate the critical role of government-sponsored research in extending the lives of patients with cancer.

FIG 1.

Cumulative life-years gained through 2020 by study. Each color-coded area represents cumulative life-years for 1 of 133 studies for which life-year gains were estimated.

FIG 2.

Estimated population life-year gains from National Cancer Clinical Trials Network trials for years 2020, 2025, and 2030.

FIG 3.

Life-years gained by treatment duration, effectiveness, and year of adoption. Although the base-case model assumed that the duration of treatment benefit was 5 years, in a sensitivity analysis, we allowed the treatment benefit period to vary from 3 to 7 years by 1-year intervals. Additionally, the base-case model assumed that the overall survival treatment effect translated fully, with 100% effectiveness, to the corresponding cancer treatment population defined by the trial eligibility criteria. However, the benefits of positive trials may not fully generalize to all patient groups, suggesting that the efficiency with which the efficacy estimate translates to effectiveness in the cancer population may be < 100%. Conversely, newly proven treatments are commonly used off-label in populations of patients not represented in the trial. Thus, we allowed this efficiency parameter to vary from 80% to 120% by 10% intervals. Finally, the base case assumed uptake of the new treatment occurred the same year as the primary trial publication. However, uptake of new treatments in the cancer treatment community may precede publication of the article reporting the main trial results, especially if previously presented at a major cancer conference, or uptake may not be immediate (especially for medically disadvantaged patient groups). We allowed the year of adoption to uniformly vary from 2 years before trial publication to 2 years after trial publication by 1-year intervals.

FIG 4.

Clinical impact represented by the number of trials that influenced cancer care guidelines or new FDA drug approvals by cancer type.

FIG 5.

Total number of citations by study through 2020. Each vertical line represents the citation totals for a single study, in increasing order.