Evidence map›Paper›PMID 26142345›Full record

Trial reportDrug and alcohol dependence2015

Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.

Li-Shiun Chen, Timothy B Baker, Douglas Jorenby, Megan Piper, Nancy Saccone, Eric Johnson, Naomi Breslau, Dorothy Hatsukami, Robert M Carney, Laura J Bierut

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Drug and alcohol dependence, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 4 pooled it
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 4 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Nicotine receptor partial agonists for smoking cessation.The Cochrane database of systematic reviews · 2023
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. CHRNA5-A3-B4 and DRD2 Genes and Smoking Cessation Throughout Adulthood: A Longitudinal Study of Women.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2023
    Article
  9. Article
  10. Compartmentalized Devices as Tools for Investigation of Human Brain Network Dynamics.Developmental dynamics : an official publication of the American Association of Anatomists · 2019
    Review
  11. Neurobiological Considerations for Tobacco Use Disorder.Current behavioral neuroscience reports · 2018
    Article
  12. Article
  13. Review
  14. Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision Medicine: Why and How.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2018
    Review
  15. The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2018
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 1 country.

Li-Shiun ChenDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, United States; The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 63110, United States. Electronic address: chenli@psychiatry.wustl.edu.
Timothy B BakerCenter for Tobacco Research and Intervention, University of Wisconsin, School of Medicine and Public Health, Madison, WI, 53711, United States.
Douglas JorenbyCenter for Tobacco Research and Intervention, University of Wisconsin, School of Medicine and Public Health, Madison, WI, 53711, United States.
Megan PiperCenter for Tobacco Research and Intervention, University of Wisconsin, School of Medicine and Public Health, Madison, WI, 53711, United States.
Nancy SacconeDepartment of Genetics, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Eric JohnsonDivision of Health, Social and Economic Research, Research Triangle Institute International, Research Triangle Park, NC, 27709, United States.
Naomi BreslauDepartment of Epidemiology, Michigan State University, East Lansing, MI, 48824, United States.
Dorothy HatsukamiDepartment of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, United States.
Robert M CarneyDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, United States.
Laura J BierutDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, United States; The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 63110, United States.
University of Wisconsin–Madison · USWashington University in St. Louis · USAlvin J. Siteman Cancer CenterMichigan State University · USRTI International · USUniversity of Minnesota · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
Testing Relapse Recovery Intervention ComponentsP01CA180945 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI COOK, JESSICA MEGAN · 2014 to 2023
$23.0M
Enhancing the Effectiveness of Varenicline Based Smoking Cessation TreatmentR01HL109031 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI BAKER, TIMOTHY B, STEIN, JAMES H · 2011 to 2020
$17.5M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI GOATE, ALISON M · 2001 to 2012
$17.3M
RELAPSE: LINKING SCIENCE AND PRACTICEP50CA084724 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI FIORE, MICHAEL C · 1999 to 2003
$8.9M
Washington University Institute of Clinical and Translational SciencesKL2TR000450 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$8.8M
Tobacco Dependence: Treatment and OutcomesP50DA019706 · NIDA · UNIVERSITY OF WISCONSIN-MADISON · PI FIORE, MICHAEL C · 2004 to 2008
$8.6M
Washington University Institute of Clinical and Translational Sciences (KL2)KL2RR024994 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$8.6M
Genome Wide Association Coordinating CenterU01HG004446 · NHGRI · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2007 to 2011
$6.6M
Genetics Study of Nicotine Dependence in African AmericansR01DA025888 · NIDA · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J., JOHNSON, ERIC OTTO · 2009 to 2014
$4.7M
Genetically Informed Smoking Cessation TrialR01DA038076 · NIDA · WASHINGTON UNIVERSITY · PI CHEN, LI-SHIUN · 2014 to 2018
$3.3M
NCATS NIH HHS KL2 TR000450NCI NIH HHS K05 CA139871NCI NIH HHS P01 CA089392NCI NIH HHS P01 CA180945NCI NIH HHS P30 CA036583NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA084724NCI NIH HHS P50 CA84724NCRR NIH HHS KL2 RR024994NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004422NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004446NHLBI NIH HHS R01 HL109031NIDA NIH HHS K02 DA021237NIDA NIH HHS K08 DA030398NIDA NIH HHS K08DA030398NIDA NIH HHS P50 DA019706NIDA NIH HHS P50 DA19706NIDA NIH HHS R01 DA025888NIDA NIH HHS R01 DA036583NIDA NIH HHS R01 DA038076Wellcome Trust
6 · The paper itself

Abstract

objectiveRecent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes.

methodIn two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment.

resultsFor abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X(2)=8.15, df=2, omnibus-p=0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald=3.94, df=1, p=0.047), this non-replication can alter the interpretation of pharmacogenetic findings.

conclusionsResults from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking.

Indexed as

Tobacco Use Cessation DevicesAdultFemaleGenetic VariationGenotypeHumansMaleMiddle AgedNerve Tissue ProteinsReceptors, NicotinicSmokingSmoking CessationTreatment OutcomeVareniclineYoung AdultCHRNA5 protein, humanNerve Tissue ProteinsReceptors, NicotinicVareniclineCHRNA5Nicotine replacement therapypharmacogeneticSmoking cessationVarenicline

Identifiers

PMID26142345
PMCPMC4537319
OpenAlexW2108280401

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.