Background: Based on randomized controlled trials, a network meta-analysis was conducted to compare treatment effects across varenicline and related smoking interventions. Methods: English databases were screened for randomized controlled trials reporting the effect of varenicline as treatment for smoking. The risk of bias in included trials was assessed using the Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and the GRADE approach was used to assess the evidence credibility on the tobacco treatment effects of different interventions. Results: Thirty-four studies involving 26,130 smokers were included in the network meta-analysis. Varenicline and 11 other interventions were reported, yielding 66 pairs of comparisons. Network meta-analysis showed that varenicline monotherapy or its combination with other interventions were superior in achieving smoking cessation compared to bupropion, nicotine replacement therapy, counselling, and placebo. Furthermore, compared to the varenicline, evident abstinence superiority was found in varenicline + bupropion (odds ratio = 1.49, 95% confidence interval [1.02, 2.18]). Finally, the surface under the cumulative ranking curve value indicated that varenicline + bupropion has the highest probability to become the best intervention. Conclusions: Varenicline monotherapy increased the odds of smoking cessation further than bupropion monotherapy, nicotine replacement therapy, counselling, and placebo, while varenicline combined with other interventions may even achieve a better abstinence effect. More credible evidence has been reported indicating that the combination of varenicline and bupropion is a superior treatment for smoking.

Objective: A network meta-analysis based on randomized controlled trials was conducted to investigate the effects of pharmacological interventions on smoking cessation. Methods: English databases were searched to obtain randomized controlled trials reporting the effect of pharmacological interventions on smoking cessation. The risk of bias for the included trials was assessed using Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and GRADE approach was used to assess the evidence credibility on the effects of different interventions on smoking cessation. Results: A total of 159 studies involving 60,285 smokers were included in the network meta-analysis. The analysis involved 15 interventions and which yielded 105 pairs of comparisons. Network meta-analysis showed that varenicline was more helpful for smoking cessation than other monotherapies, such as nicotine replacement therapy [Odds Ratio (OR) = 1.42, 95% confidence interval (CI) (1.16, 1.73)] and bupropion [OR = 1.52, 95% CI (1.22, 1.89)]. Furthermore, combined interventions were superior to monotherapy in achieving smoking cessation, such as varenicline plus bupropion over bupropion [OR = 2.00, 95% CI (1.11, 3.61)], varenicline plus nicotine replacement therapy over nicotine replacement therapy [OR = 1.84, 95% CI (1.07, 3.18)], and nicotine replacement therapy plus mecamylamine over naltrexone [OR = 6.29, 95% CI (1.59, 24.90)]. Finally, the surface under the cumulative ranking curve value indicated that nicotine replacement therapy plus mecamylamine had the greatest probability of becoming the best intervention. Conclusion: Most pharmacological interventions demonstrated a benefit in smoking cessation compared with placebo, whether monotherapy or combination therapy. Moreover, confirmed evidence suggested that some combination treatments, such as varenicline plus bupropion and nicotine replacement therapy plus mecamylamine have a higher probability of being the best smoking cessation in

Objective To evaluate the reporting quality of single-patient (N-of-1) trials and protocols based on the CONSORT Extension for N-of-1 trials (CENT) statement and the standard protocol items: recommendations for interventional trials (SPIRIT) extension and elaboration for N-of-1 trials (SPENT) checklist to examine the factors that influenced reporting quality. Methods Four electronic databases were searched to identify N-of-1 trials and protocols from 2015 to 2020. Quality was assessed by two reviewers. We calculated the overall scores based on binary responses in which "Yes" was scored as 1 (if the item was fully reported), and "No" was scored as 0 (if the item was not clearly reported or not definitely stated). Results A total of 78 publications (55 N-of-1 trials and 23 protocols) were identified. The mean reporting score (SD) of the N-of-1 trials and protocols were 29.24 (0.89) and 29.61 (1.83), respectively. For the items related to outcomes, sample size, allocation concealment protocol, and informed consent materials, the reporting quality was low. Our results showed that the year of publication (t = -0.793, p = 0.872 for the trials and t = 1.352, p = 0.623 for the protocols) and the impact factor of the journal (t = 1.416, p = 0.619 for the trials and t = 0.359, p = 0.667 for the protocols) were not factors associated with better reporting quality. Conclusion With the publication of the CENT 2015 statement and the SPENT 2019 checklist, authors should adhere to the relevant reporting guidelines and improve the reporting quality of N-of-1 trials and protocols.