Assessing the impact of clinical trial designs on progress against cancer using the PACE Continuous Innovation Indicators™

Background

Clinical trial designs undergo constant evolution driven by changing scientific needs and corresponding regulatory demands. Early clinical research was dominated by case series and anecdotal reports. Randomized controlled trials emerged by the 1940s, and increasingly rigorous standards led to the modern 3-phase system. Recent studies have shifted from larger trials with post-hoc identification of subgroups to smaller trials conducted in selected populations. As trial designs continue to evolve, the field must monitor the success of new approaches to confirm that they lead to faster rates of progress with reproducible results.

Methods

The PACE Continuous Innovation Indicators™ (CII) is a comprehensive historical database of evidence supporting cancer treatments for 12 solid tumors. The CII systematically tracks results from published studies measuring overall survival. An interactive user interface allows users to examine how progress against cancer occurs over time, including the contribution of different types of evidence.

Results

Data from the CII illustrate the accumulation of evidence for improved overall survival over decades of clinical research. Historically, Phase 3 trials contribute only 28% of the evidence, while Phase 2 trials contribute an additional 7%. The remaining evidence arises from observational and retrospective studies, meta-analyses, and systematic reviews. Moreover, approximately 27% of the evidence is from studies combining data from different cohorts to increase statistical power. These larger and heterogeneous designs often provide the first evidence of efficacy at the group or class level and are followed by additional studies to better understand the underlying effect. CII data can be used to track the impact of the current transition toward smaller, targeted studies. Our results highlight the need for timely and data-driven tracking of progress across the spectrum of cancer research and fast learning from real-world evidence to validate outcomes.

Conclusions

We make the CII freely available to all stakeholders and encourage users to perform their own custom analyses. https://pacenetworkusa.com/continuousinnovation

Clinical trial identification

Legal entity responsible for the study

Eli Lilly and Company; Rose Li and Associates, Inc.

Funding

Eli Lilly and Company

Disclosure

S. Paddock, S. Thomas, R. Li: Consultant/advisor for Eli Lilly and Company. Industry employee of Rose Li and Associates, Inc. A. Kanli, J. Zummo: Shareholder of: Eli Lilly and Company. Industry employee of Eli Lilly and Company. D. Grainger: Shareholder of: Eli Lilly and Company. Grant/research support: Steering Committees for Projects Funded by Eli Lilly and Company. Industry employee of Eli Lilly and Company.