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- Germovsek, Eva, et al.
(författare)
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A Time-to-Event Model Relating Integrated Craving to Risk of Smoking Relapse Across Different Nicotine Replacement Therapy Formulations
- 2021
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Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 109:2, s. 416-423
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Tidskriftsartikel (refereegranskat)abstract
- Smoking increases the risk of cancer and other diseases, causing an estimated 7 million deaths per year. Nicotine replacement therapy (NRT) reduces craving for smoking, therefore, increasing an individual's probability to remain abstinent. In this work, we for the first time quantitatively described the relationship between craving and smoking abstinence, using retrospectively collected data from 19 studies, including 3 NRT formulations (inhaler, mouth spray, and patch) and a combination of inhaler and patch. Smokers motivated to quit were included in the NRT or placebo arms. Integrated craving (i.e., craving over a period of time) was assessed with 4-category, 5-category, or 100-mm visual analogue scale. The bounded integer model was used to assess latent craving from all scales. A time-to-event model linked predicted integrated craving to the hazard of smoking relapse. Available data included 9,323 adult subjects, observed for 3 weeks up to 2 years. At the study end, 9% (11% for NRT and 5% for placebo), on average, remained abstinent according to the protocol definition. A Gompertz-Makeham hazard best described the data, with a hazard of smoking relapse decreasing over time. Latent integrated craving was positively related to the hazard of smoking relapse, through a sigmoidal maximum effect function. For the same craving, being on NRT was found to reduce the hazard of relapse by an additional 30% compared with placebo. This work confirmed that low craving is associated with a high probability of remaining smoking abstinent and that NRT, in addition to reducing craving, increases the probability of remaining smoking abstinent.
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| 3. |
- Germovsek, Eva, et al.
(författare)
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Relating Nicotine Plasma Concentration to Momentary Craving Across Four Nicotine Replacement Therapy Formulations
- 2020
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 107:1, s. 238-245
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Tidskriftsartikel (refereegranskat)abstract
- Tobacco use is a major health concern. To assist smoking cessation, nicotine replacement therapy (NRT) is used to reduce nicotine craving. We quantitatively described the relationship between nicotine pharmacokinetics (PKs) from NRTs and momentary craving, linking two different pharmacodynamic (PD) scales for measuring craving. The dataset comprised retrospective data from 17 clinical studies and included 1,077 adult smokers with 39,802 craving observations from four formulations: lozenge, gum, mouth spray, and patch. A PK/PD model was developed that linked individual predicted nicotine concentrations with the categorical and visual analogue PD scales through a joint bounded integer model. A maximum effect model, accounting for acute tolerance development, successfully related nicotine concentrations to momentary craving. Results showed that all formulations were similarly effective in reducing craving, albeit with a fourfold lower potency for the patch. Women were found to have a higher maximal effect of nicotine to reduce craving, compared with men.
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