Use of pre-enrollment randomization and delayed consent to maximize participation in a clinical trial of opt-in versus opt-out tobacco treatment

Abstract

Background: Enrollment in smoking cessation trials remain sub-optimal. The aim of this analysis was to determine the effectiveness of a modified Zelen’s design in engaging hospitalized patients who smoke in a pragmatic OPT-IN versus OPT-OUT tobacco treatment trial. Methods: At bedside, clinical staff screened smokers for eligibility, randomized eligible into study arms, and delivered the appropriate treatment approach. Study staff called randomized patients at one-month post-discharge, debriefed patients on the study design, and collected consent to participate. We used frequencies and percentages for categorical variables and means and standard deviations for quantitative variables to describe the characteristics of those who consented and were enrolled versus those who did not enroll. We also compared the characteristics of participants who consented and those who were reached and explicitly refused consent at one-month follow-up. We used the Cohen’s d measure of effect size to evaluate differences. Results: Of the 1,000 randomized, 741 (74.1%) consented to continue in the study at one-month follow-up. One hundred and twenty-seven (12.7%) refused consent and 132 (13.2%) were unreachable. Cohen’s d effect size differences between those who consented/enrolled (n = 741) and those who were not enrolled (n = 259) were negligible (<0.2) for age, gender, race/ethnicity, and most forms of insurance. The effect size was small for Medicaid (0.36), and other public insurance (0.48). After excluding those unreached at 1 month (12.7%), there were medium Cohen’s d effect size differences between those who consented to participate (n = 741) and those who explicitly refused (n = 127) with respect to age (0.55) and self-pay or no insurance (0.51). There were small to negligible effect size differences with respect to sex, race/ethnicity, and other forms of health insurance. Conclusions: The modified Zelen’s design resulted in successful enrollment of most participants who were initially randomized into the trial, including those not motivated to quit.

Keywords:

• Tobacco use disorder
• smoking cessation
• hospitalized patients
• randomized clinical trial
• motivation
• Zelen’s design

Acknowledgements

We are grateful to the UKanQuit staff: Genevieve Casey, Andrea Elyachar, Alison Hageman, Tresza Hutcheson, Marjorie Paschang, Vivek Patel, Tristan Patterson, Lety Sarmiento, Craig Warlick and to the volunteers who participated in this research.

Author contributions

BF helped conceive the study, and participated in its design and drafted the manuscript; EFE and DC helped conceive the study and provided guidance on study design, measures, and analysis; BG helped in the design of the statistical methods; TS helped develop the measures for the study; LMM finalized all logistics, obtained final human subjects approval and managed the entire project; NN and BJG developed all databases and designed the participant selection and randomization schemes for the study; ES participated in data analysis; KPR conceived the study, and led its design and coordination. All authors contributed to drafts of the manuscript and have read and approved the final manuscript.

Disclosure statement

The authors declare they have no competing interests.

Trial registration

Clinical Trials Registration NCT02721082; Registered March 22, 2016; Date of enrollment of first participant: September 12, 2016

Additional information

Funding

This project is funded by the National Heart, Lung, and Blood Institute [R01HL131512, Richter-PI]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.