Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence
Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence
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DOI：
10.1186/1471-2458-10-680
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发表时间：
2010-11-09
影响因子：
4.5
通讯作者：
Kinmonth, Ann Louise
中科院分区：
文献类型：
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作者：
Marteau, Theresa M.;Munafo, Marcus R.;Kinmonth, Ann Louise
背景：药物基因组学对行为的影响未经测试；告知吸烟者对戒烟药物的反应的基因测试结果可能会增加对该药物的依从性。这项试验的目的是评估告知吸烟者他们的口服NRT剂量已根据DNA分析量身定做对坚持尼古丁替代疗法(NRT)的影响。将被测试的假设如下：i吸烟者对NRT的依从性更强，被告知他们的口服NRT剂量是根据DNA分析(基因)量身定做的，而不是根据尼古丁依赖问卷评分(表型)量身定做的。在6个月后仍未戒烟的吸烟者中，当被告知他们的NRT口服剂量是根据基因而不是表型定制的时，再次戒烟的动机就会降低。方法/设计：一项开放标签的平行分组随机试验，其中630名使用国家卫生服务(NHS)初级保健戒烟服务的成年吸烟者被随机分配到两组中：i.通过DNA分析(OPRM1基因)(基因)定制的NRT口服剂量(基因)，或ii.NRT口服剂量根据尼古丁依赖问卷评分(表型)主要结果是在首次戒烟尝试后的头28天内服用的NRT的比例，次要结果是在6个月后未戒烟的吸烟者中再次尝试戒烟的动机。其他结果包括在前七天坚持NRT，以及在六个月内经过生化验证的戒烟。初步结果将在630名吸烟者身上收集，允许足够的力量通过两组之间5%的显着性水平的双尾测试来检测NRT平均消耗比例的7.5%的差异。将使用独立样本t检验和通过估计观察到的平均NRT消耗量(假设I)的95%可信区间来比较ARM之间的所有NRT消耗在戒烟前四周内的比例。六个月后仍未戒烟的人的戒烟动机将被比较(假设II)。讨论：这是第一个使用遗传信息而不是表型信息来评估开药依从性对行为的影响的临床试验。讨论了关于这类干预试验设计选择的具体问题。
Background: The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication. The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy (NRT) of informing smokers that their oral dose of NRT has been tailored to a DNA analysis. Hypotheses to be tested are as follows: I Adherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA (genotype), compared to one tailored to nicotine dependence questionnaire score (phenotype). II Amongst smokers who fail to quit at six months, motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype.Methods/Design: An open label, parallel groups randomised trial in which 630 adult smokers (smoking 10 or more cigarettes daily) using National Health Service (NHS) stop smoking services in primary care are randomly allocated to one of two groups: i. NRT oral dose tailored by DNA analysis (OPRM1 gene) (genotype), or ii. NRT oral dose tailored by nicotine dependence questionnaire score (phenotype) The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt, with the secondary outcome being motivation to make another quit attempt, amongst smokers not abstinent at six months. Other outcomes include adherence to NRT in the first seven days and biochemically validated smoking abstinence at six months. The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5% difference in mean proportion of NRT consumed using a two-tailed test at the 5% level of significance between groups. The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent samples t-test and by estimating the 95% confidence interval for observed between-arm difference in mean NRT consumption (Hypothesis I). Motivation to make another quit attempt will be compared between arms in those failing to quit by six months (Hypothesis II).Discussion: This is the first clinical trial evaluating the behavioural impact on adherence of prescribing medication using genetic rather than phenotypic information. Specific issues regarding the choice of design for trials of interventions of this kind are discussed.