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Treatment Effect Estimation With Potential Outcomes for a Single-Arm Trial Compared With Historical Controls: A Case Study of Locally Recurrent Head and Neck Squamous Cell Carcinoma Patients Treated With Adjuvant Nivolumab. Head Neck 2025 Nov;47(11):2990-2997

Date

06/17/2025

Pubmed ID

40525328

DOI

10.1002/hed.28215

Scopus ID

2-s2.0-105008433952 (requires institutional sign-in at Scopus site)

Abstract

BACKGROUND: Time/resource constraints might preclude a randomized controlled trial. Single-arm oncology trials with historical controls are an alternative. With causal inference, treatment effect estimates can be computed in the absence of randomization.

METHODS: From a single-arm trial of 39 head and neck squamous cell carcinoma patients treated with adjuvant nivolumab, we compare 2-year disease-free survival (DFS) to untreated historical controls. We resort to the potential outcomes framework known as Rubin's causal model (RCM). For time-to-event outcomes, RCM relies upon survival analysis regression with baseline covariates. We contrast the average treatment effect (ATE) estimated by three survival methods: Cox proportional hazards (CPH) versus machine learning alternatives, random survival forests (RSF), and Bayesian Additive Regression Trees (BART).

RESULTS: The ATE in favor of nivolumab: CPH 0.202 (0.098-0.306); RSF 0.159 (0.070-0.248); and BART 0.268 (0.126-0.406).

CONCLUSIONS: The uncertainty is considerable, yet all three methods show nivolumab is superior to control.

Author List

Harun N, Sparapani R, Laud PW, Sivaganesan S, Leddon JL, Haque S, Tang AL, Wise-Draper TM

Authors

Purushottam W. Laud PhD Adjunct Professor in the Data Science Institute department at Medical College of Wisconsin
Rodney Sparapani PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aged
Antineoplastic Agents, Immunological
Bayes Theorem
Case-Control Studies
Chemotherapy, Adjuvant
Disease-Free Survival
Female
Head and Neck Neoplasms
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Proportional Hazards Models
Treatment Outcome