Interventions to increase adherence to medications for tobacco dependence

Gareth J Hollands; Felix Naughton; Amanda Farley; Nicola Lindson; Paul Aveyard

doi:10.1002/14651858.CD009164.pub3

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Figure 1

Study flow diagram for the current review update (eight studies were included in the previous version of the review).

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 3

Forest plot of comparison: 1 Medication adherence intervention plus standard care versus standard care alone, outcome: 1.1 Adherence (combined dichotomous and continuous).

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Figure 4

Funnel plot of comparison: 1 Medication adherence intervention plus standard care versus standard care alone, outcome: 1.1 Adherence (combined dichotomous and continuous).

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Analysis 1.1

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 1 Adherence (combined dichotomous and continuous).

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Analysis 1.2

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 2 Adherence: intervention focus subgroups.

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Analysis 1.3

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 3 Adherence: delivery approach subgroups.

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Analysis 1.4

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 4 Adherence: combined focus and delivery subgroups.

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Analysis 1.5

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 5 Adherence: medication type subgroups.

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Analysis 1.6

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 6 Dichotomous adherence data (for calculation purposes).

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Analysis 1.7

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 7 Continuous adherence data (for calculation purposes).

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Analysis 1.8

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 8 Short‐term smoking abstinence (< 6 months).

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Analysis 1.9

Comparison 1 Medication adherence intervention plus standard care versus standard care alone, Outcome 9 Long‐term smoking abstinence (≥ 6 months).

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Summary of findings for the main comparison. Interventions to increase adherence compared to standard care for improving adherence to medications for tobacco dependence and abstinence from smoking

Interventions to increase adherence compared to standard care for improving adherence to medications for tobacco dependence and abstinence from smoking
Patient or population: adult smokers Settings: typically in‐person clinical settings (China, UK, USA) Intervention: interventions to increase adherence through providing information and facilitating problem‐solving Comparison: behavioural support for smoking cessation
Outcomes	Relative effect (95% CI)	Illustrative comparative risks (95% CI)		No of participants (studies; comparisons)	Certainty of the evidence (GRADE)
		Assumed risk	Corresponding risk
		Standard care	Intervention to increase adherence
Adherence to medications for tobacco dependence	SMD 0.10 (0.03 to 0.18)	Mean proportion of prescribed medication consumed over 28 days was 63.6%	Mean proportion of prescribed medication consumed over 28 days was 3.9% higher (95% CI 1.2% to 7.0% higher)	3655 (10 RCTs; 12 comparisons)	⊕⊕⊕⊝ Moderate^a,b
Short‐term abstinence from smoking (< 6 months)	RR 1.08 (0.96 to 1.21)	357 people per 1000 achieve abstinence)	386 people per 1000 achieve abstinence (95% CI 343 to 432)	1795 (5 RCTs; 5 comparisons)	⊕⊕⊝⊝ Low^a,b,c
Long‐term abstinence from smoking (≥ 6 months)	RR 1.16 (0.96 to 1.40)	203 people per 1000 achieve abstinence	236 per 1000 achieve abstinence (95% CI 195 to 284)	3593 (5 RCTs; 7 comparisons)	⊕⊕⊝⊝ Low^a,b,c
The basis for the illustrative comparative risks is provided in Footnotes^d. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference.
GRADE Working Group grades of evidence High certainty: current evidence provides a very good indication of the likely effect, and the likelihood that the actual effect will be substantially different is low. Moderate certainty: current evidence provides a good indication of the likely effect, and the likelihood that the actual effect of the treatment will not be substantially different is moderate. Low certainty: current evidence provides some indication of the likely effect, but the likelihood that the actual effect will be substantially different is high. Very low certainty: current evidence does not provide a reliable indication of the likely effect, and the likelihood that the actual effect will be substantially different is very high.
^aMost studies were at high or unclear risk of bias which lowers confidence in estimate of effect (risk of bias). ^bWe did not downgrade due to indirectness as we judged the evidence specifically relating to the general population receiving an adherence intervention in addition to behavioural support for smoking cessation, compared to behavioural support alone, is moderate. However, our conclusions cannot be generalised to populations not receiving behavioural support or that are unlikely to adhere, or both. ^cIncluded sufficient sample size for single adequately powered trial but 95% CI overlapped no effect and ranged from minimal harm to moderate benefit (imprecision). ^dConcerning adherence outcomes for the comparison group, as the basis for an illustration of potential effect size on a more familiar metric, we used data from the largest included study that reported adherence as assessed by tablet counts (Marteau 2012). In this study, mean proportion of prescribed nicotine replacement therapy that was consumed at 28 days by the 'standard care' arm was 63.6% (SD 39.0%). Further explanation is provided in Data synthesis. Concerning abstinence outcomes for the comparison group, the percentage of observed events seen in the review's data (which derives from studies with characteristics as specified by the 'Summary of findings' table) was applied to 1000 total events.

Summary of findings for the main comparison. Interventions to increase adherence compared to standard care for improving adherence to medications for tobacco dependence and abstinence from smoking

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Table 1. Brief descriptions of adherence interventions

Study	Brief description of specific intervention components intended to increase adherence^a	Additional contact time relative to standard care?	Medication for which adherence was targeted	Intervention focused on perceptions, practicalities or both	Participant‐ or clinician‐centred intervention
Chan 2010	Added counselling contact time to standard behavioural support, focusing specifically on medication adherence	Yes	NRT	Practicalities	Participant
Chan 2011	Added counselling contact time to standard behavioural support, focusing specifically on medication adherence	Yes	NRT	Practicalities	Participant
Marteau 2012	Tailored and communicated about NRT dosage using a more potent rationale (genotype vs phenotype)	No	NRT	Perceptions	Clinician
Mooney 2005	Personalised feedback of questionnaire responses regarding medication	No	NRT	Perceptions	Participant
Mooney 2007	Personalised feedback of externally validated medication adherence	Yes	Bupropion	Practicalities	Participant
Nollen 2011	Added counselling contact time to standard behavioural support, focusing specifically on medication adherence	Yes	Varenicline	Both	Clinician
Schlam 2018	Added contact time to standard behavioural support with: 1. medication adherence counselling; 2. automated reminder calls; 3. electronic monitoring counselling	Yes	NRT	1. Perceptions 2. Both 3. Practicalities	1. Participant 2. Clinician 3. Participant
Schmitz 2005	Personalised feedback of externally validated medication adherence	Yes	Bupropion	Practicalities	Participant
Smith 2013	Added counselling contact time to standard behavioural support, focusing specifically on medication adherence	Yes	NRT	Both	Participant
Tucker 2017	Added contact time to standard behavioural support with module focused on improving adherence to nicotine patch	Yes	NRT	Both	Participant
^aFor further details see Characteristics of included studies table. NRT: nicotine replacement therapy.

Table 1. Brief descriptions of adherence interventions

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Comparison 1. Medication adherence intervention plus standard care versus standard care alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Adherence (combined dichotomous and continuous) Show forest plot	10	3655	Std. Mean Difference (Random, 95% CI)	0.10 [0.03, 0.18]

2 Adherence: intervention focus subgroups Show forest plot	10	3655	Std. Mean Difference (Random, 95% CI)	0.10 [0.03, 0.18]

2.1 Perceptions	3	839	Std. Mean Difference (Random, 95% CI)	0.10 [‐0.03, 0.24]
2.2 Practicalities	5	1752	Std. Mean Difference (Random, 95% CI)	0.21 [0.03, 0.38]
2.3 Both perceptions and practicalities	4	1064	Std. Mean Difference (Random, 95% CI)	0.04 [‐0.08, 0.16]
3 Adherence: delivery approach subgroups Show forest plot	10	3655	Std. Mean Difference (Random, 95% CI)	0.10 [0.03, 0.18]

3.1 Participant‐centred	8	2791	Std. Mean Difference (Random, 95% CI)	0.12 [0.02, 0.23]
3.2 Clinician‐centred	3	864	Std. Mean Difference (Random, 95% CI)	0.09 [‐0.05, 0.23]
4 Adherence: combined focus and delivery subgroups Show forest plot	10	3655	Std. Mean Difference (Random, 95% CI)	0.10 [0.03, 0.18]

4.1 Perceptions + participant	2	206	Std. Mean Difference (Random, 95% CI)	0.03 [‐0.25, 0.30]
4.2 Perceptions + clinician	1	633	Std. Mean Difference (Random, 95% CI)	0.13 [‐0.03, 0.29]
4.3 Practicalities + participant	5	1752	Std. Mean Difference (Random, 95% CI)	0.21 [0.03, 0.38]
4.4 Both + participant	2	833	Std. Mean Difference (Random, 95% CI)	0.08 [‐0.16, 0.32]
4.5 Both + clinician	2	231	Std. Mean Difference (Random, 95% CI)	‐0.01 [‐0.27, 0.24]
5 Adherence: medication type subgroups Show forest plot	10	3655	Std. Mean Difference (Random, 95% CI)	0.10 [0.03, 0.18]

5.1 Nicotine replacement therapy	7	3442	Std. Mean Difference (Random, 95% CI)	0.09 [0.02, 0.17]
5.2 Bupropion	2	152	Std. Mean Difference (Random, 95% CI)	0.58 [0.14, 1.01]
5.3 Varenicline	1	61	Std. Mean Difference (Random, 95% CI)	‐0.22 [‐0.73, 0.29]
6 Dichotomous adherence data (for calculation purposes) Show forest plot	6	1664	Odds Ratio (M‐H, Random, 95% CI)	1.53 [1.05, 2.21]

7 Continuous adherence data (for calculation purposes) Show forest plot	5	4604	Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.03, 0.19]

8 Short‐term smoking abstinence (< 6 months) Show forest plot	5	1795	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.96, 1.21]

9 Long‐term smoking abstinence (≥ 6 months) Show forest plot	5	3593	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.96, 1.40]

Comparison 1. Medication adherence intervention plus standard care versus standard care alone

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