Lead Investigator: Alana Rojewski, Medical University of South Carolina
Title of Proposal Research: Smoking Cessation Pharmacotherapy Efficacy in Comorbid Medical Populations: Secondary Analysis of the EAGLES Randomized Clinical Trial
Vivli Data Request: 6836
Funding Source: Dr. Rojewski (lead researcher) is funded by a career development grant from the National Cancer Institute that supports her efforts, including projects such as the present proposal.
Potential Conflicts of Interest: Dr. Toll has consulted to Pfizer for an advisory board on e-cigarettes and testifies as an expert witness on behalf of plaintiffs who filed litigation against the tobacco industry.
Summary of the Proposed Research:
The objective of this study is to compare medication efficacy in participants who have medical and psychiatric conditions and smoke cigarettes in the EAGLES trial. Nicotine replacement therapy and varenicline may work differently in comorbid populations in terms of ability to quit smoking, particularly as the number of comorbidities increases. We will use statistical analyses to compare these groups. Exploring how well the medications work for medically complex patients has important implications for tobacco treatment.
Statistical Analysis Plan:
Project 1:
All statistical models and missing data assumptions will be performed to remain consistent with the primary study analysis performed by Anthenelli and colleagues (Anthenelli et al, The Lancet, 2016).
Aim 1: Logistic regression will be utilized to determine the efficacy of varenicline, bupropion and NRT on CAR across and within each medical comorbidity group. We will assess linear contrast to estimate odds ratios (OR) and 95% confidence intervals (CI) for specific treatment contrasts; specifically, varenicline vs. NRT, varenicline vs. bupropion, and NRT vs. bupropion on continuous abstinence outcomes (CAR for weeks 9 to 12 [end of treatment] and CAR for weeks 9 to 24 [follow-up]). Regression models will include terms for treatment group, cohort (non-psychiatric cohort and psychiatric cohort), and any interactions with medical comorbidity groups as needed. When interactions are statistically significant, group level estimates and 95% CIs will be presented.
Aim 2: The primary logistic regression models from Aim 1 will include an additional predictor variable, number of comorbidities (0 [reference], 1, 2, 3, 4, or 5+), on end of treatment and follow-up abstinence outcomes. These models will be used to determine if the increasing number of comorbidities is associated with decreasing overall quit rate and increased odds of CAR of varenicline vs. other treatments.
Exploratory: If chronic pain is not able to be used as a comorbid medical condition of interest, the above analyses will be replicated adjusting for pain scores (as available) or with pain score as an outcome.
Pain scores at study entry may modify the efficacy of treatment on CAR. Initial models will include a categorical indication of any vs. no pain (0, >0) as a study moderator through model interaction terms. When significant, continuous pain scores will be included to determine if increasing pain scores (rather than simply the presence of pain), are associated with modification of treatment group efficacy. Additionally, we will assess if treatment affects pain scores at the end of study treatment. In the cohort with pain scores >0 at study entry, linear regression models will be developed with pain scores as the primary outcomes and study group as the primary predictor. Contrasts between treatment groups will be used to determine group level means and 95% CIs.
Requested Studies:
Study Evaluating The Safety And Efficacy Of Varenicline and Bupropion For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders (EAGLES)
Sponsor: Pfizer Inc.
Study ID: NCT01456936
Sponsor ID: NCT01456936
Public Disclosures:
Rojewski AM, Palmer AM, Baker NL, Toll BA. Smoking Cessation Pharmacotherapy Efficacy in Comorbid Medical Populations: Secondary Analysis of the EAGLES Randomized Clinical Trial. Nicotine and Tobacco Research. 2023 Jul 20:ntad126. doi: 10.1093/ntr/ntad126