Transdisciplinary Tobacco Use Research Centers Research Articles

The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence From Two Treatment Trials.

Tobacco use disorder is a complex behavior with a strong genetic component. Genome-wide association studies (GWAS) on smoking behaviors allow for the creation of polygenic risk scores (PRSs) to approximate genetic vulnerability. However, the utility of smoking-related PRSs in predicting smoking cessation in clinical trials remains unknown. We evaluated the association between polygenic risk scores and bioverified smoking abstinence in a meta-analysis of two randomized, placebo-controlled smoking cessation trials. PRSs of smoking behaviors were created using the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) consortium summary statistics. We evaluated the utility of using individual PRS of specific smoking behavior versus a combined genetic risk that combines PRS of all four smoking behaviors. Study participants came from the Transdisciplinary Tobacco Use Research Centers (TTURCs) Study (1091 smokers of European descent), and the Genetically Informed Smoking Cessation Trial (GISC) Study (501 smokers of European descent). PRS of later age of smoking initiation (OR [95% CI]: 1.20, [1.04-1.37], p = .0097) was significantly associated with bioverified smoking abstinence at end of treatment. In addition, the combined PRS of smoking behaviors also significantly predicted bioverified smoking abstinence (OR [95% CI] 0.71 [0.51-0.99], p = .045). PRS of later age at smoking initiation may be useful in predicting smoking cessation at the end of treatment. A combined PRS may be a useful predictor for smoking abstinence by capturing the genetic propensity for multiple smoking behaviors. There is a potential for polygenic risk scores to inform future clinical medicine, and a great need for evidence on whether these scores predict clinically meaningful outcomes. Our meta-analysis provides early evidence for potential utility of using polygenic risk scores to predict smoking cessation amongst smokers undergoing quit attempts, informing further work to optimize the use of polygenic risk scores in clinical care.

Very Light Daily Smoking in Young Adults: Relationships Between Nicotine Dependence and Lapse.

Very light daily smoking is increasingly common among young adults. Evidence suggests that levels of nicotine dependence vary significantly among young adults who engage in very light daily smoking. However, the links between dependence and clinically relevant outcomes (eg, lapse) in this population remain unclear. The goal of this study was to address this gap by evaluating how well different nicotine dependence scales predict lapse behavior among very light daily smoking young adults. Very light daily smokers (1-5 cigarettes/day) aged 18-25 participated in an initial laboratory session, during which nicotine dependence was assessed using four commonly used measures: the Fagerstrӧm Test for Cigarette Dependence (FTCD), the Hooked On Nicotine Checklist (HONC), the Transdisciplinary Tobacco Use Research Centers (TTURC) Nicotine Dependence Inventory, and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). After a baseline period, eligible participants (n = 40) completed a 10-day abstinence incentive period in which they attempted to refrain from smoking to earn monetary rewards. Cox proportional hazards models were used to test whether dependence predicted days to first lapse. FTCD scores significantly predicted days to lapse, as did scores on the FTCD item assessing time to first cigarette of the day (TTFC). No other dependence measures predicted time to lapse. Both the FTCD and TTFC continued to independently predict time to lapse after controlling for smoking frequency and duration. The FTCD may be a particularly useful tool for capturing clinically meaningful variability in nicotine dependence among young adults who engage in very light daily smoking. This is the first study to directly link self-reported nicotine dependence with the ability to achieve and maintain abstinence among very light daily smoking young adults. The results may aid clinicians in selecting among variable measures of nicotine dependence when assessing and treating this population.

Confessions of a team science funder

Confessions of a team science funder

Present and Future Horizons for Transdisciplinary Research

In 1998, when one of us (BKR) presented the concept for Transdisciplinary Tobacco Use Research Centers (TTURCs) to the National Cancer Institute's (NCI's) Board of Scientific Advisors (BSA) for approval, they questioned whether transdisciplinary was a word. We provided the Oxford English Dictionary1 definition as proof. Fast-forward to 2008 when one of us (DBA), who was on the BSA and principal investigator for a TTURC, built on the NCI experience to make transdisciplinary systems science the centerpiece of the Office of Behavioral and Social Sciences Research's strategic plan for NIH institutes and centers.

Transdisciplinary Tobacco Use Research Centers: Research achievements and future implications

The University of Wisconsin Transdisciplinary Tobacco Use Research Center (TTURC) has focused on several linked topics: (a) improving our assessment and understanding of nicotine dependence, (b) exploring factors that cause or modulate relapse risk, (c) identifying genetic influences on nicotine dependence and cessation success, and (d) testing smoking cessation interventions and determining their mechanisms of action. This developmental research effort produced a new questionnaire that is now being widely used to assess nicotine dependence: the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68), which has good psychometric properties and is appropriate for use with a broad range of smokers (men and women, ethnic minorities; Piper et al., 2004). This work also produced direct evidence that nicotine dependence is indeed multidimensional, revealing which aspects of dependence are most associated with heightened relapse risk, withdrawal severity, and heavy smoking (Piper et al.).

Bridging basic and clinical science with policy studies: The Partners with Transdisciplinary Tobacco Use Research Centers experience

The Partners with Transdisciplinary Tobacco Use Research Centers (TTURCs) initiative was a transdisciplinary team-building program, funded by the Robert Wood Johnson Foundation, to expand the policy research capacity of the TTURCs. EXPANSION INTO POLICY RESEARCh: Policy research activities at the TTURCs fell into four broad domains: (a) health services research, (b) examination of the business case for cessation treatment and funding, (c) collaborative teams with key stakeholders, and (d) direct assessment of smoking-related policies. Examples of each domain are presented. Goals of the initiative included efforts to foster collaborative, transdisciplinary research, to bring new investigators into the field, to develop programs of policy research, to answer next-step translational questions, and to enhance awareness of policy relevance. Success at meeting each of these goals is discussed. We offer recommendations for incorporating programs of policy research into full-spectrum transdisciplinary research initiatives, including the roles of research teams, senior researchers, infrastructure, stakeholders, and communications activities. The TTURC Partners initiative represented a first-generation effort to fill the gap between scientific discovery and research translation through expansion into policy studies. While all aspects of the effort were not equally successful, the effort demonstrated that it is possible to develop successful collaborations that extend more basic and applied research into studies that examine their policy and practice implications.

The Evaluation of Large Research Initiatives

Over the past few decades there has been a rise in the number of federally funded large scientific research initiatives, with increased calls to evaluate their processes and outcomes. This article describes efforts to evaluate such initiatives in one agency within the U.S. federal government. The authors introduce the Evaluation of Large Initiatives (ELI) project, a preliminary effort to explore how to accomplish such evaluation. They describe a pilot effort of this project to evaluate the Transdisciplinary Tobacco Use Research Center (TTURC) initiative of the National Cancer Institute. They present a summary of this pilot evaluation including the methods used (concept mapping, logic modeling, a detailed researcher survey, content analysis and systematic peer-evaluation of progress reports, bibliometric analysis and peer evaluation of publications and citations, and financial expenditures analysis) and a brief overview of results. Finally, they discuss several important lessons and recommendations that emerged from this work.

Communications strategies to broaden the reach of tobacco use research: Examples from the Transdisciplinary Tobacco Use Research Centers

One of the initial goals of the Transdisciplinary Tobacco Use Research Center (TTURC) initiative was to broaden the traditional model of how research results are communicated, going beyond scholarly journals, as a way to accelerate the discovery-to-dissemination process. A strategy in meeting this goal was the establishment of a communications program at the seven initially funded TTURCs. This paper reports the results of the communications efforts from the TTURC initiative. Specific communications activities are described, highlighting efforts to reach broad audiences and increase the impact of the research. We present lessons learned from this effort to enhance knowledge translation through the development of communications infrastructure and dissemination activities, focusing especially on the guidance they offer for the development of future research-communications partnerships.

Translating basic science to improve pharmacotherapy for nicotine dependence

Nicotine dependence has a complex multifactorial etiology, underscoring the value of applying a transdisciplinary research model. The important goal of treating nicotine dependence can be realized by transdisciplinary research that translates discoveries in basic neuroscience, pharmacology, genetics, and behavioral science to develop new treatment models that can be translated readily into the clinic and community. As part of this special issue highlighting work at the Transdisciplinary Tobacco Use Research Centers (TTURCs), we describe transdisciplinary research at the University of Pennsylvania TTURC aimed at elucidating the neurobiological and genetic basis of nicotine dependence, the development of novel medications, and the translation of this research to practice.

Facilitating transdisciplinary research: the experience of the transdisciplinary tobacco use research centers.

Cigarette smoking is the largest preventable cause of death and morbidity in the United States. Heightened recognition of this public health concern has led researchers from multiple and varied disciplines to address this complex and multidimensional behavior. The need for an alternative research paradigm, focusing on a transdisciplinary approach that integrates work across disciplines in order to advance the field most quickly, has been identified. This recognized need led to the development of the Transdisciplinary Tobacco Use Research Centers (TTURC) initiative, funded jointly by the National Cancer Institute, the National Institute on Drug Abuse, and The Robert Wood Johnson Foundation. This paper discusses the formation and early implementation stages of the initiative, including meetings that led to the development of the TTURCs, funders' and research centers' perspectives on implementation, and early observations about the products of the initiative.

Evaluating transdisciplinary science.

The past two decades have seen a growing interest and investment in transdisciplinary research teams and centers. The Transdisciplinary Tobacco Use Research Centers (TTURCs) exemplify large-scale scientific collaborations undertaken for the explicit purpose of promoting novel conceptual and methodological integrations bridging two or more fields. Until recently, few efforts have been made to evaluate the collaborative processes, and the scientific and public policy outcomes, of such centers. This manuscript offers a conceptual framework for understanding and evaluating transdisciplinary science and describes two ongoing evaluation studies covering the initial phase of the TTURC initiative. The methods and measures used by these studies are described, and early evaluative findings from the first 4 years of the initiative are presented. These data reveal progress toward intellectual integration within and between several of the TTURCs, and cumulative changes in the collaborative behaviors and values of participants over the course of the initiative. The data also suggest that different centers may follow alternative pathways toward transdisciplinary integration and highlight certain environmental, organizational, and institutional factors that influence each center's readiness for collaboration. Methodological challenges posed by the complexities of evaluating large-scale scientific collaborations (including those that specifically aspire toward transdisciplinary integrations spanning multiple fields) are discussed. Finally, new directions for future evaluative studies of transdisciplinary scientific collaboration, both within and beyond the field of tobacco science, are described.

Genetic Variation May Increase Nicotine Craving and Smoking Relapse

help with a variety of treatments, including counseling, nicotine replacement therapy (patches, gum, lozenges, or inhalers), and medications. Some smokers use these treatments and succeed; for many, however, the discomfort of withdrawal and craving for nicotine lead to relapse. Recent NIDAfunded research suggests that our genes may partly explain this variable success. The research evaluated the effect of an enzyme, designated CYP2B6, on craving and relapse. This enzyme breaks down nicotine in the brain. Some people’s genes produce a more active form of the enzyme, while others have a less active form. Dr. Caryn Lerman at the NIDAand NCIsupported Transdisciplinary Tobacco Use Research Center (TTURC) at the University of Pennsylvania found that