Selection criteria limit generalizability of smoking pharmacotherapy studies differentially across clinical trials and laboratory studies: A systematic review on varenicline

Motschman, Courtney A.; Gass, Julie C.; Wray, Jennifer M.; Germeroth, Lisa J.; Schlienz, Nicolas J.; Munoz, Diana A.; Moore, Faith E.; Rhodes, Jessica D.; Hawk, Larry W.; Tiffany, Stephen T.

doi:10.1016/j.drugalcdep.2016.10.018

Cited by 20 publications

(17 citation statements)

References 33 publications

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“…The consistency of the null effect size between our matched and unmatched analysis suggests that this lack of effectiveness does not appear to come from differential use patterns of pharmaceutical aids between subpopulations. One alternative explanation is that exclusion criteria in efficacy trials would remove half of the real-world smokers, thus seriously limiting generalizability ( 32 ). Another alternative is that the explanation comes from the way that pharmaceutical aids are made available in the general population.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers

Leas

Pierce

Benmarhnia

et al. 2017

JNCI: Journal of the National Cancer Institute

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BackgroundDespite strong efficacy in randomized trials, the population effectiveness of pharmaceutical aids in long-term smoking cessation is lacking, possibly because of confounding (factors that are associated with both pharmaceutical aid use and difficulty quitting). Matching techniques in longitudinal studies can remove this confounding bias.MethodsUsing the nationally representative Tobacco Use Supplement to the Current Population Survey (TUS-CPS), we assessed the effectiveness of medications to aid quitting among baseline adult smokers who attempted to quit prior to one year of follow-up in two longitudinal studies: 2002–2003 and 2010–2011. Pharmaceutical aid users and nonusers with complete data (n = 2129) were matched using propensity score models with 12 potential confounders (age, sex, race-ethnicity, education, smoking intensity, nicotine dependence, previous quit history, self-efficacy to quit, smoke-free homes, survey year, and cessation aid use). Using matched data sets, logistic regression models were fit to assess whether use of any individual pharmaceutical aid increased the proportion of patients who were abstinent for 30 days or more at follow-up.ResultsPropensity score matching markedly improved balance on the potential confounders between the pharmaceutical aid use groups. Using matched samples to provide a balanced comparison, there was no evidence that use of varenicline (adjusted risk difference [aRD] = 0.01, 95% confidence interval [CI] = –0.07 to 0.11), bupropion (aRD = 0.02, 95% CI = –0.04 to 0.09), or nicotine replacement (aRD = 0.01, 95% CI = –0.03 to 0.06) increased the probability of 30 days or more smoking abstinence at one-year follow-up.ConclusionsThe lack of effectiveness of pharmaceutical aids in increasing long-term cessation in population samples is not an artifact caused by confounded analyses. A possible explanation is that counseling and support interventions provided in efficacy trials are rarely delivered in the general population.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers

Leas

Pierce

Benmarhnia

et al. 2017

JNCI: Journal of the National Cancer Institute

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“…Exclusion criteria employed by most clinical trials impacts the generalizability and representativeness of the sample, which has been demonstrated among those with cannabis dependence in a community sample (Okuda et al, 2010), for other substances of abuse (Blanco et al, 2008; Le Strat et al, 2011; Motschman et al, 2016), and among other medical disorders (Humphreys et al, 2013). Studies should consider more inclusive criteria to improve sample representativeness, when appropriate based on the phase of the study and other potential factors (e.g., risks of study intervention).…”

Section: Discussionmentioning

confidence: 99%

Comparing adult cannabis treatment-seekers enrolled in a clinical trial with national samples of cannabis users in the United States

McClure

King

Wahle

et al. 2017

Drug and Alcohol Dependence

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Background Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Methods Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings.

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“…Despite the high levels of alcohol (EtOH) and nicotine (NIC) comorbidity in humans, preclinical research often focuses on investigating the effects of individual drugs of abuse (Srisurapanont and Jarusuraisin 2005;Jorenby et al 2006;Motschman et al 2016). In order to develop successful therapeutics for AUD as a polydrug disorder, a better understanding of the mechanisms behind these associations is needed.…”

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confidence: 99%

Co‐administration of ethanol and nicotine heightens sensitivity to ethanol reward within the nucleus accumbens (NAc) shell and increasing NAc shell BDNF is sufficient to enhance ethanol reward in naïve Wistar rats

Waeiss

Knight

Engleman

et al. 2019

Journal of Neurochemistry

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Alcohol use disorder most commonly presents as a polydrug disorder where greater than 85% are estimated to smoke. EtOH and nicotine (NIC) co‐abuse or exposure results in unique neuroadaptations that are linked to behaviors that promote drug use. The current experiments aimed to identify neuroadaptations within the mesolimbic pathway produced by concurrent EtOH and NIC exposure. The experiments used four overall groups of male Wistar rats consisting of vehicle, EtOH or NIC alone, and EtOH+NIC. Drug exposure through direct infusion into the posterior ventral tegmental area (pVTA) stimulated release of glutamate and dopamine in the nucleus accumbens (NAc) shell, which was quantified through high‐performance liquid chromatography. Additionally, brain‐derived neurotrophic factor (BDNF) protein levels were measured via enzyme‐linked immunosorbent assay (ELISA). A second experiment investigated the effects of drug pretreatment within the pVTA on the reinforcing properties of EtOH within the NAc shell through intracranial self‐administration (ICSA). The concluding experiment evaluated the effect of NAc shell pretreatment with BDNF on EtOH reward utilizing ICSA within that region. The data indicated that only EtOH+NIC administration into the pVTA simultaneously increased glutamate, dopamine, and BDNF in the NAc shell. Moreover, only pVTA pretreatment with EtOH+NIC enhanced the reinforcing properties of EtOH in the NAc shell. BDNF pretreatment in the NAc shell was also sufficient to enhance the reinforcing properties of EtOH in the NAc shell. The collected data suggest that concurrent EtOH+NIC exposure results in a distinct neurochemical response and neuroadaptations within the mesolimbic pathway that alter EtOH reward.

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Selection criteria limit generalizability of smoking pharmacotherapy studies differentially across clinical trials and laboratory studies: A systematic review on varenicline

Cited by 20 publications

References 33 publications

Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers

Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers

Comparing adult cannabis treatment-seekers enrolled in a clinical trial with national samples of cannabis users in the United States

Co‐administration of ethanol and nicotine heightens sensitivity to ethanol reward within the nucleus accumbens (NAc) shell and increasing NAc shell BDNF is sufficient to enhance ethanol reward in naïve Wistar rats

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