Hollands Gareth J, Naughton Felix, Farley Amanda, Lindson Nicola, Aveyard Paul
Behaviour and Health Research Unit, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK, CB2 0SR.
Cochrane Database Syst Rev. 2019 Aug 16;8(8):CD009164. doi: 10.1002/14651858.CD009164.pub3.
Pharmacological treatments for tobacco dependence, such as nicotine replacement therapy (NRT), have been shown to be safe and effective interventions for smoking cessation. Higher levels of adherence to these medications increase the likelihood of sustained smoking cessation, but many smokers use them at a lower dose and for less time than is optimal. It is important to determine the effectiveness of interventions designed specifically to increase medication adherence. Such interventions may address motivation to use medication, such as influencing beliefs about the value of taking medications, or provide support to overcome problems with maintaining adherence.
To assess the effectiveness of interventions aiming to increase adherence to medications for smoking cessation on medication adherence and smoking abstinence compared with a control group typically receiving standard care.
We searched the Cochrane Tobacco Addiction Group Specialized Register, and clinical trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) to the 3 September 2018. We also conducted forward and backward citation searches.
Randomised, cluster-randomised or quasi-randomised studies in which adults using active pharmacological treatment for smoking cessation were allocated to an intervention arm where there was a principal focus on increasing adherence to medications for tobacco dependence, or a control arm providing standard care. Dependent on setting, standard care may have comprised minimal support or varying degrees of behavioural support. Included studies used a measure that allowed assessment of the degree of medication adherence.
Two authors independently screened studies for eligibility, extracted data for included studies and assessed risk of bias. For continuous outcome measures, we calculated effect sizes as standardised mean differences (SMDs). For dichotomous outcome measures, we calculated effect sizes as risk ratios (RRs). In meta-analyses for adherence outcomes, we combined dichotomous and continuous data using the generic inverse variance method and reported pooled effect sizes as SMDs; for abstinence outcomes, we reported and pooled dichotomous outcomes. We obtained pooled effect sizes with 95% confidence intervals (CIs) using random-effects models. We conducted subgroup analyses to assess whether the primary focus of the adherence treatment ('practicalities' versus 'perceptions' versus both), the delivery approach (participant versus clinician-centred) or the medication type were associated with effectiveness.
We identified two new studies, giving a total of 10 studies, involving 3655 participants. The medication adherence interventions studied were all provided in addition to standard behavioural support.They typically provided further information on the rationale for, and emphasised the importance of, adherence to medication or supported the development of strategies to overcome problems with maintaining adherence (or both). Seven studies targeted adherence to NRT, two to bupropion and one to varenicline. Most studies were judged to be at high or unclear risk of bias, with four of these studies judged at high risk of attrition or detection bias. Only one study was judged to be at low risk of bias.Meta-analysis of all 10 included studies (12 comparisons) provided moderate-certainty evidence that adherence interventions led to small improvements in adherence (i.e. the mean amount of medication consumed; SMD 0.10, 95% CI 0.03 to 0.18; I² = 6%; n = 3655), limited by risk of bias. Subgroup analyses for the primary outcome identified no significant subgroup effects, with effect sizes for subgroups imprecisely estimated. However, there was a very weak indication that interventions focused on the 'practicalities' of adhering to treatment (i.e. capabilities, resources, levels of support or skills) may be effective (SMD 0.21, 95% CI 0.03 to 0.38; I² = 39%; n = 1752), whereas interventions focused on treatment 'perceptions' (i.e. beliefs, cognitions, concerns and preferences; SMD 0.10, 95% CI -0.03 to 0.24; I² = 0%; n = 839) or on both (SMD 0.04, 95% CI -0.08 to 0.16; I² = 0%; n = 1064), may not be effective. Participant-centred interventions may be effective (SMD 0.12, 95% CI 0.02 to 0.23; I² = 20%; n = 2791), whereas those that are clinician-centred may not (SMD 0.09, 95% CI -0.05 to 0.23; I² = 0%; n = 864).Five studies assessed short-term smoking abstinence (five comparisons), while an overlapping set of five studies (seven comparisons) assessed long-term smoking abstinence of six months or more. Meta-analyses resulted in low-certainty evidence that adherence interventions may slightly increase short-term smoking cessation rates (RR 1.08, 95% CI 0.96 to 1.21; I² = 0%; n = 1795) and long-term smoking cessation rates (RR 1.16, 95% CI 0.96 to 1.40; I² = 48%; n = 3593). In both cases, the evidence was limited by risk of bias and imprecision, with CIs encompassing minimal harm as well as moderate benefit, and a high likelihood that further evidence will change the estimate of the effect. There was no evidence that interventions to increase adherence to medication led to any adverse events. Studies did not report on factors plausibly associated with increases in adherence, such as self-efficacy, understanding of and attitudes toward treatment, and motivation and intentions to quit.
AUTHORS' CONCLUSIONS: In people who are stopping smoking and receiving behavioural support, there is moderate-certainty evidence that enhanced behavioural support focusing on adherence to smoking cessation medications can modestly improve adherence. There is only low-certainty evidence that this may slightly improve the likelihood of cessation in the shorter or longer-term. Interventions to increase adherence can aim to address the practicalities of taking medication, change perceptions about medication, such as reasons to take it or concerns about doing so, or both. However, there is currently insufficient evidence to confirm which approach is more effective. There is no evidence on whether such interventions are effective for people who are stopping smoking without standard behavioural support.
药物治疗烟草依赖，如尼古丁替代疗法（NRT），已被证明是戒烟的安全有效干预措施。更高水平地坚持使用这些药物会增加持续戒烟的可能性，但许多吸烟者使用这些药物的剂量低于最佳剂量，且使用时间也短于最佳时长。确定专门为提高药物依从性而设计的干预措施的有效性非常重要。此类干预措施可解决使用药物的动机问题，如影响对服药价值的信念，或提供支持以克服维持依从性方面的问题。
与通常接受标准护理的对照组相比，评估旨在提高戒烟药物依从性的干预措施对药物依从性和戒烟的有效性。
我们检索了Cochrane烟草成瘾小组专业注册库以及截至2018年9月3日的临床试验注册库（ClinicalTrials.gov和世界卫生组织国际临床试验注册平台）。我们还进行了向前和向后的引文检索。
随机、整群随机或半随机研究，其中使用积极药物治疗戒烟的成年人被分配到一个主要侧重于提高烟草依赖药物依从性的干预组，或一个提供标准护理的对照组。根据具体情况，标准护理可能包括最少的支持或不同程度的行为支持。纳入的研究使用了一种能够评估药物依从程度的测量方法。
两位作者独立筛选研究的合格性，提取纳入研究的数据并评估偏倚风险。对于连续结局指标，我们计算效应量为标准化均数差（SMD）。对于二分结局指标我们计算效应量为风险比（RR）。在依从性结局的荟萃分析中，我们使用通用逆方差法合并二分和连续数据，并将合并效应量报告为SMD；对于戒烟结局，我们报告并合并二分结局。我们使用随机效应模型获得合并效应量及95%置信区间（CI）。我们进行亚组分析以评估依从性治疗的主要重点（“实际情况”与“认知”与两者兼顾）、实施方式（以参与者为中心与以临床医生为中心）或药物类型是否与有效性相关。
我们确定了两项新研究，共10项研究，涉及3655名参与者。所研究的药物依从性干预措施均在标准行为支持之外提供。它们通常会提供关于服药基本原理的更多信息，强调坚持服药的重要性，或支持制定克服维持依从性问题的策略（或两者兼顾）。七项研究针对NRT的依从性，两项针对安非他酮，一项针对伐尼克兰。大多数研究被判定为高偏倚风险或偏倚风险不明确，其中四项研究被判定为高失访或检测偏倚风险。只有一项研究被判定为低偏倚风险。对所有10项纳入研究（12项比较）的荟萃分析提供了中等确定性证据，表明依从性干预措施导致依从性有小幅改善（即平均服药量；SMD 0.10，95%CI 0.；I² = 6%；n = 3655），受偏倚风险限制。主要结局的亚组分析未发现显著的亚组效应，亚组效应量估计不精确。然而，有非常微弱的迹象表明，侧重于坚持治疗“实际情况”（即能力、资源、支持水平或技能）的干预措施可能有效（SMD 0.21，95%CI 0.03至0.38；I² = 39%；n = 1752），而侧重于治疗“认知”（即信念、认知、担忧和偏好；SMD 0.10，95%CI -0.03至0.24；I² = 0%；n = 839）或两者兼顾（SMD 0.04，95%CI -0.08至0.16；I² = 0%；n = 1064）的干预措施可能无效。以参与者为中心的干预措施可能有效（SMD 0.12，95%CI 0.02至0.23；I² = 20%；n = 2791），而以临床医生为中心的干预措施可能无效（SMD 0.09，95%CI -0.05至0.23；I² = 0%；n = 864）。五项研究评估了短期戒烟情况（五项比较），而一组重叠的五项研究（七项比较）评估了六个月或更长时间的长期戒烟情况。荟萃分析得出低确定性证据，表明依从性干预措施可能会略微提高短期戒烟率（RR 1.08，95%CI 0.96至1.21；I² = 0%；n = 1795）和长期戒烟率（RR 1.16，95%CI 0.96至1.40；I² = 48%；n = 3593）。在这两种情况下，证据都受到偏倚风险和不精确性的限制，置信区间既包含最小危害也包含中等益处，但很有可能进一步的证据会改变效应估计。没有证据表明提高药物依从性的干预措施会导致任何不良事件。研究未报告与依从性增加可能相关的因素，如自我效能、对治疗的理解和态度以及戒烟的动机和意图。
在正在戒烟并接受行为支持的人群中，有中等确定性证据表明，侧重于坚持戒烟药物的强化行为支持可适度提高依从性。只有低确定性证据表明这可能会在短期或长期内略微提高戒烟的可能性。提高依从性的干预措施可以旨在解决服药的实际情况、改变对药物的认知，如服药的原因或对服药的担忧，或两者兼顾。然而，目前没有足够的证据来确认哪种方法更有效。没有证据表明此类干预措施对未接受标准行为支持的戒烟者是否有效。
