Examining the correlation between treatment effects in clinical trials and economic modeling

ABSTRACT

Introduction

Many diseases have a sequential treatment pathway. Compared with patients without previous treatment, patients who fail initial treatment may have lower success rates with a second treatment. This phenomenon can be explained by a correlation between treatment effects.

Methods

We developed a statistical model of covariance for the underlying unobserved correlation between treatments and established a mathematical expression for the magnitude of the latent correlation term. We conducted a simulation study of clinical trials to investigate the correlation between two treatments and explored clinical examples based on published literature to illustrate the identification and evaluation of these correlations.

Results

Our simulation study confirmed that a treatment correlation reduces the probability of success for the second treatment, compared with no correlation. We found that treatment correlations may be observable in clinical trials, such as for depression and lung cancer, and the magnitude of correlation may be estimated. We illustrated that treatment correlations can be incorporated into an economic model, with possible impacts on cost-effectiveness results. Additional applications of correlation concepts are also discussed.

Conclusions

We evaluated the correlation between treatment effects and our approach can be applied to clinical trial design and economic modeling of sequential clinical treatment pathways.

KEYWORDS:

• Clinical trial
• correlation between treatment effects
• depression
• economic modeling
• independence

Acknowledgments

The research of A. Volodin was supported by the Natural Science and Engineering Research Council of Canada. We would like to thank Dr. Nandini Dendukuri (Director of the Technology Assessment Unit of the McGill University Health Centre, Canada) and anonymous reviewers for their constructive comments and suggestions. We would like to thank Dr. Jun Li (Department of Gastroenterology, Peking University Third Hospital, Beijing, China) and Mr. Wanqing Li (Regulatory Affairs Department, Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd., Hangzhou, China) for their suggestions on clinical examples.

Declaration of interest

D Blumberger receives research support from CIHR, NIH, Brain Canada, and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for one sponsor-initiated study for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. He participated in a Scientific Advisory Board for Janssen and Welcony Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

X Xie conceived the study idea. X Xie, M Wang and A Volodin designed the study and drafted the manuscript. O Gajic-Veljanoski, C Ye, and D Blumberger provided important intellectual content and revised the draft manuscript. All authors agree for the final version of the manuscript to be published.

Disclaimer

The opinions expressed in this publication do not necessarily represent the opinions of Ontario Health and Genentech. No endorsement is intended or should be inferred.

Code availability

The SAS code for generating and analyzing the data is available upon request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737167.2022.2079497

Additional information

Funding

This paper was not funded.