Smoking in pregnancy is a public health problem. Self-help smoking cessation support can help pregnant women to stop smoking, but the effects of delivering this kind of support via SMS text message are not known. A previous randomised controlled trial (RCT) demonstrated the feasibility and acceptability of providing such support to pregnant smokers using an automated, tailored text message intervention called MiQuit. This larger RCT will estimate key parameters for and will test the feasibility of delivering a major trial run within the United Kingdom National Health Service settings aimed at providing definitive evidence on the utility of MiQuit for helping pregnant smokers to stop.
This will be a multi-centre, parallel group RCT. Participants are being identified in 16 English antenatal care settings and must be >16 years old, pregnant, <25 weeks gestation, smoke >1 daily cigarette, have smoked >5 daily cigarettes before pregnancy, and able to understand texts in English. After consenting and the collection of baseline data, participants are randomised to control or intervention groups in a 1:1 ratio; randomisation is stratified by trial site and gestation and employs computer-generated pseudo-random code using random permuted blocks of randomly varying size, and held on a secure server. All participants receive a National Health Service (NHS) leaflet aimed at helping them to stop smoking. Intervention group women also receive the 12-week MiQuit programme of tailored, supportive, interactive text message, self-help cessation support. Women are followed up by telephone 4 weeks after randomisation and at 36 weeks gestation. The study aims to recruit 400 women, and with this sample we will be able to estimate trial centres’ recruitment rates to within +/−1% (margin of error = half width of 95% confidence interval); individual trial groups’ ascertainment of rates for smoking outcomes between 4 weeks after randomisation until approximately 36 weeks gestation to within +/−4%, and across both groups, the combined cessation rate at 36 weeks +/−3%.
Pilot trial completion will provide data to facilitate planning for a definitive trial investigating whether MiQuit works for smoking cessation in pregnancy.
ClinicalTrials.gov NCT02043509 Registered 14 January 2014.
Smoking cessation; Pregnancy; Self-help; Randomised controlled trial; Protocol
The analysis of randomized controlled trials with incomplete binary outcome data is challenging. We develop a general method for exploring the impact of missing data in such trials, with a focus on abstinence outcomes.
We propose a sensitivity analysis where standard analyses, which could include ‘missing = smoking’ and ‘last observation carried forward’, are embedded in a wider class of models.
We apply our general method to data from two smoking cessation trials.
A total of 489 and 1758 participants from two smoking cessation trials.
The abstinence outcomes were obtained using telephone interviews.
The estimated intervention effects from both trials depend on the sensitivity parameters used. The findings differ considerably in magnitude and statistical significance under quite extreme assumptions about the missing data, but are reasonably consistent under more moderate assumptions.
A new method for undertaking sensitivity analyses when handling missing data in trials with binary outcomes allows a wide range of assumptions about the missing data to be assessed. In two smoking cessation trials the results were insensitive to all but extreme assumptions.
Last observation carried forward; missing data; missing not at random; Russell Standard; sensitivity analysis; smoking cessation trials
Nicotine replacement therapy (NRT) medications have been shown to be effective in increasing smoking cessation rates. There is, however, a lack of good evidence describing how individuals in primary care use these medications and which factors are likely to affect this. The study objectives are to describe adherence and consumption, examine key factors that may determine use, and examine the relationship between consumption of NRT and abstinence from smoking.
Secondary analysis of data from a randomized controlled trial conducted in smoking cessation services in primary care. Adult smokers (n = 633) starting a quit attempt within smoking cessation clinics were followed for 6 months, with NRT use closely monitored for an initial treatment period of 4 weeks. The main outcomes were 4-week adherence to prescribed NRT, mean daily consumption of NRT over the 4-week period, and abstinence from smoking at 4 weeks.
Levels of adherence to prescribed NRT were high: more than 94% in participants who completed the treatment period. After controlling for possible confounders, prescribing higher doses of patch and oral NRT was associated with higher mean daily consumption of NRT. Using an inhalator to deliver oral NRT was associated with both higher adherence and higher consumption. The amount of NRT consumed predicted future abstinence when reverse causation was accounted for.
Most individuals within a clinical trial in primary care who persisted with a quit attempt adhered closely to their prescription. Prescribing higher doses of NRT led to higher consumption and higher consumption to higher abstinence.
Implementation of trial interventions is rarely assessed, despite its effects on findings. We assessed the implementation of a nurse-led intervention to facilitate medication adherence in type 2 diabetes (SAMS) in a trial against standard care in general practice. The intervention increased adherence, but not through the hypothesised psychological mechanism. This study aimed to develop a reliable coding frame for tape-recorded consultations, assessing both a priori hypothesised and potential active ingredients observed during implementation, and to describe the delivery and receipt of intervention and standard care components to understand how the intervention might have worked.
211 patients were randomised to intervention or comparison groups and 194/211 consultations were tape-recorded. Practice nurses delivered standard care to all patients and motivational and action planning (implementation intention) techniques to intervention patients only. The coding frame was developed and piloted iteratively on selected tape recordings until a priori reliability thresholds were achieved. All tape-recorded consultations were coded and a random subsample double-coded.
Nurse communication, nurse-patient relationship and patient responses were identified as potential active ingredients over and above the a priori hypothesised techniques. The coding frame proved reliable. Intervention and standard care were clearly differentiated. Nurse protocol adherence was good (M (SD) = 3.95 (0.91)) and competence of intervention delivery moderate (M (SD) = 3.15 (1.01)). Nurses frequently reinforced positive beliefs about taking medication (e.g., 65% for advantages) but rarely prompted problem solving of negative beliefs (e.g., 21% for barriers). Patients’ action plans were virtually identical to current routines. Nurses showed significantly less patient-centred communication with the intervention than comparison group.
It is feasible to reliably assess the implementation of behaviour change interventions in clinical practice. The main study results could not be explained by poor delivery of motivational and action planning components, definition of new action plans, improved problem solving or patient-centred communication. Possible mechanisms of increased medication adherence include spending more time discussing it and mental rehearsal of successful performance of current routines, combined with action planning. Delivery of a new behaviour change intervention may lead to less patient-centred communication and possible reduction in overall trial effects.
Fidelity; Implementation; Medication adherence; Behaviour change techniques; Process evaluation
Family history is an important risk factor for many common chronic diseases, but it remains underutilised for diagnostic assessment and disease prevention in routine primary care.
To develop and validate a brief self-completed family history questionnaire (FHQ) for systematic primary care assessment for family history of diabetes, ischaemic heart disease, breast cancer, and colorectal cancer.
Design and setting
Two-stage diagnostic validation study in 10 general practices in eastern England.
Participants aged 18–50 years were identified via random sampling from electronic searches of general practice records. Participants completed a FHQ then had a three-generational ‘gold standard’ pedigree taken, to determine disease risk category. In stage 1, the FHQ comprised 12 items; in stage 2 the shorter 6-item FHQ was validated against the same ‘gold standard’.
There were 1147 participants (stage 1: 618; stage 2: 529). Overall, 32% were at increased risk of one or more marker conditions (diabetes 18.9%, ischaemic heart disease 13.3%, breast cancer 6.2%, colorectal cancer 2.2%). The shorter 6-item FHQ performed very well for all four conditions: pooled data from both stages show diabetes, sensitivity = 98%, specificity = 94%; ischaemic heart disease, sensitivity = 93%, specificity = 81%; breast cancer, sensitivity = 81%, specificity = 83%; colorectal cancer, sensitivity = 96%, specificity = 88%, with an area under the receiver operating characteristic curve of 0.90 for males and 0.89 for females.
This brief self-completed FHQ shows good diagnostic accuracy for identifying people at higher risk of four common chronic diseases. It could be used in routine primary care to identify patients who would be most likely to benefit from a more detailed pedigree and risk assessment, and consequent management strategies.
breast cancer; colorectal cancer; ischaemic heart disease; diabetes mellitus, type 2; family history; primary health care; risk assessment
To report the methods used to assemble a contemporary pregnancy cohort for investigating influences on smoking behaviour before, during and after pregnancy and to report characteristics of women recruited.
Longitudinal cohort survey.
Two maternity hospitals, Nottingham, England.
3265 women who attended antenatal ultrasound scan clinics were offered cohort enrolment; those who were 8–26 weeks pregnant and were currently smoking or had recently stopped smoking were eligible. Cohort enrollment took place between August 2011 and August 2012.
Primary and secondary outcome measures
Prevalence of smoking at cohort entry and at two follow-up time points (34–36 weeks gestation and 3 months postnatally); response rate, participants’ sociodemographic characteristics.
1101 (33.7%, 95% CI 32.1% to 35.4%) women were eligible for inclusion in the cohort, and of these 850 (77.2%, 95% CI 74.6% to 79.6%) were recruited. Within the cohort, 57.4% (N=488, 95% CI 54.1% to 60.7%) reported to be current smokers. Current smokers were significantly younger than ex-smokers (p<0.05), more likely to have no formal qualifications and to not be in current paid employment compared to recent ex-smokers (p<0.001).
This contemporary cohort, which seeks very detailed information on smoking in pregnancy and its determinants, includes women with comparable sociodemographic characteristics to those in other UK cross-sectional studies and cohorts. This suggests that future analyses using this cohort and aimed at understanding smoking behaviour in pregnancy may produce findings that are broadly generalisable.
Public Health; Primary Care; Epidemiology
Interventions to promote physical activity have had limited success. One reason may be that inactive adults are unaware that their level of physical activity is inadequate and do not perceive a need to change their behaviour. We aimed to assess awareness of physical activity, defined as the agreement between self-rated and objective physical activity, and to investigate associations with sociodemographic, biological, behavioural, and psychological factors.
We conducted an exploratory, cross-sectional analysis of awareness of physical activity using baseline data collected from 453 participants of the Feedback, Awareness and Behaviour study (Cambridgeshire, UK). Self-rated physical activity was measured dichotomously by asking participants if they believed they were achieving the recommended level of physical activity. Responses were compared to objective physical activity, measured using a combined accelerometer and heart rate monitor (Actiheart®). Four awareness groups were created: overestimators, realistic inactives, underestimators, and realistic actives. Logistic regression was used to assess associations between awareness group and potential correlates.
The mean (standard deviation) age of participants was 47.0 (6.9) years, 44.4% were male, and 65.1% were overweight (body mass index ≥ 25). Of the 258 (57.0%) who were objectively classified as inactive, 130 (50.4%) misperceived their physical activity by incorrectly stating that they were meeting the guidelines (overestimators). In a multivariable logistic regression model adjusted for age and sex, those with a lower body mass index (Odds Ratio (OR) = 0.95, 95% Confidence Interval (CI) = 0.90 to 1.00), higher physical activity energy expenditure (OR = 1.03, 95% CI = 1.00 to 1.06) and self-reported physical activity (OR = 1.13, 95% CI = 1.07 to 1.19), and lower intention to increase physical activity (OR = 0.69, 95% CI = 0.48 to 0.99) and response efficacy (OR = 0.53, 95% CI = 0.31 to 0.91) were more likely to overestimate their physical activity.
Overestimators have more favourable health characteristics than those who are realistic about their inactivity, and their psychological characteristics suggest that they are less likely to change their behaviour. Personalised feedback about physical activity may be an important first step to behaviour change.
Physical activity; Objective measurement; Awareness; Misperception; Barriers; Correlates; Behaviour change; Personalised feedback
The aim of this study was to assess whether or not a theory-based behaviour change intervention delivered by trained and quality-assured lifestyle facilitators can achieve and maintain improvements in physical activity, dietary change, medication adherence and smoking cessation in people with recently diagnosed type 2 diabetes.
An explanatory randomised controlled trial was conducted in 34 general practices in Eastern England (Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care-Plus [ADDITION-Plus]). In all, 478 patients meeting eligibility criteria (age 40 to 69 years with recently diagnosed screen or clinically detected diabetes) were individually randomised to receive either intensive treatment (n = 239) or intensive treatment plus a theory-based behaviour change intervention led by a facilitator external to the general practice team (n = 239). Randomisation was central and independent using a partial minimisation procedure to balance stratifiers between treatment arms. Facilitators taught patients skills to facilitate change in and maintenance of key health behaviours, including goal setting, self-monitoring and building habits. Primary outcomes included physical activity energy expenditure (individually calibrated heart rate monitoring and movement sensing), change in objectively measured fruit and vegetable intake (plasma vitamin C), medication adherence (plasma drug levels) and smoking status (plasma cotinine levels) at 1 year. Measurements, data entry and laboratory analysis were conducted with staff unaware of participants’ study group allocation.
Of 475 participants still alive, 444 (93%; intervention group 95%, comparison group 92%) attended 1-year follow-up. There were no significant differences between groups in physical activity (difference: +1.50 kJ kg−1 day−1; 95% CI −1.74, 4.74), plasma vitamin C (difference: −3.84 μmol/l; 95% CI −8.07, 0.38), smoking (OR 1.37; 95% CI 0.77, 2.43) and plasma drug levels (difference in metformin levels: −119.5 μmol/l; 95% CI −335.0, 95.9). Cardiovascular risk factors and self-reported behaviour improved in both groups with no significant differences between groups.
For patients with recently diagnosed type 2 diabetes receiving intensive treatment in UK primary care, a facilitator-led individually tailored behaviour change intervention did not improve objectively measured health behaviours or cardiovascular risk factors over 1 year.
The trial is supported by the Medical Research Council, the Wellcome Trust, National Health Service R&D support funding (including the Primary Care Research and Diabetes Research Networks) and National Institute of Health Research under its Programme Grants for Applied Research scheme. The Primary Care Unit is supported by NIHR Research funds. Bio-Rad provided equipment for HbA1c testing during the screening phase.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-014-3236-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
ADDITION-Plus; Diabetes; General practice; Health behaviour; Randomised trial
Electronic monitoring is recommended for accurate measurement of medication adherence but a possible limitation is that it may influence adherence.
To test the reactive effect of electronic monitoring in a randomized controlled trial.
A total of 226 adults with type 2 diabetes and HbA1c ≥58 mmol/mol were randomized to receiving their main oral glucose lowering medication in electronic containers or standard packaging. The primary outcomes were self-reported adherence measured with the MARS (Medication Adherence Report Scale; range 5–25) and HbA1c at 8 weeks.
Non-significantly higher adherence and lower HbA1c were observed in the electronic container group (differences in means, adjusting for baseline value: MARS, 0.4 [95 % CI −0.1 to 0.8, p = 0.11]; HbA1c (mmol/mol), −1.02 [−2.73 to 0.71, p = 0.25]).
Electronic containers may lead to a small increase in adherence but this potential limitation is outweighed by their advantages. Our findings support electronic monitoring as the method of choice in research on medication adherence. (Trial registration Current Controlled Trials ISRCT N30522359)
Measurement reactivity; Medication adherence; Electronic monitoring; Diabetes
Smokers attend preferentially to cigarettes and other smoking-related cues in the environment, in what is known as an attentional bias. There is evidence that attentional bias may contribute to craving and failure to stop smoking. Attentional retraining procedures have been used in laboratory studies to train smokers to reduce attentional bias, although these procedures have not been applied in smoking cessation programmes. This trial will examine the efficacy of multiple sessions of attentional retraining on attentional bias, craving, and abstinence in smokers attempting cessation.
This is a double-blind randomised controlled trial. Adult smokers attending a 7-session weekly stop smoking clinic will be randomised to either a modified visual probe task with attentional retraining or placebo training. Training will start 1 week prior to quit day and be given weekly for 5 sessions. Both groups will receive 21 mg transdermal nicotine patches for 8–12 weeks and withdrawal-orientated behavioural support for 7 sessions. Primary outcome measures are the change in attentional bias reaction time and urge to smoke on the Mood and Physical Symptoms Scale at 4 weeks post-quit. Secondary outcome measures include differences in withdrawal, time to first lapse and prolonged abstinence at 4 weeks post-quit, which will be biochemically validated at each clinic visit. Follow-up will take place at 8 weeks, 3 months and 6 months post-quit.
This is the first randomised controlled trial of attentional retraining in smokers attempting cessation. This trial could provide proof of principle for a treatment aimed at a fundamental cause of addiction.
Current Controlled Trials: ISRCTN54375405.
There is limited evidence about predictors of health behaviour change in people with type 2 diabetes. The aim of this study was to assess change in health behaviours over one year and to identify predictors of behaviour change among adults with screen-detected and recently clinically diagnosed diabetes.
ADDITION-Plus was a randomised controlled trial of a behaviour change intervention among 478 patients (40–69 years). Physical activity and diet were measured objectively (physical activity at 1 year) and by self-report at baseline and one year. Associations between baseline predictors and behaviour change were quantified using multivariable linear regression.
Participants increased their plasma vitamin C and fruit intake, reduced energy and fat intake from baseline to follow-up. Younger age, male sex, a smaller waist circumference, and a lower systolic blood pressure at baseline were associated with higher levels of objectively measured physical activity at one year. Greater increases in plasma vitamin C were observed in women (beta-coefficient [95% CI]: beta = −5.52 [−9.81, -1.22]) and in those with screen-detected diabetes (beta = 6.09 [1.74, 10.43]). Younger age predicted a greater reduction in fat (beta = −0.43 [−0.72, -0.13]) and energy intake (beta = −6.62 [−13.2, -0.05]). Patients with screen-detected diabetes (beta = 74.2 [27.92, 120.41]) reported a greater increase in fruit intake. There were no significant predictors of change in self-reported physical activity. Beliefs about behaviour change and diabetes did not predict behaviour change.
Older patients, men and those with a longer duration of diabetes may need more intensive support for dietary change. We recommend that future studies use objective measurement of health behaviours and that researchers add predictors beyond the individual level. Our results support a focus on establishing healthy lifestyle changes early in the diabetes disease trajectory.
Health behaviour; Behaviour change; Predictors; Type 2 diabetes; Newly diagnosed
Low levels of physical activity are a major public health concern, and interventions to promote physical activity have had limited success. Whether or not personalised feedback about physical activity following objective measurement motivates behaviour change has yet to be rigorously examined.
And Findings: In a parallel group, open randomised controlled trial, 466 healthy adults aged 32 to 54 years were recruited from the ongoing population-based Fenland Study (Cambridgeshire, UK). Participants were randomised to receive either no feedback until the end of the trial (control group, n=120) or one of three different types of feedback: simple, visual, or contextualised (intervention groups, n=346). The primary outcome was physical activity (physical activity energy expenditure (PAEE) in kJ/kg/day and average body acceleration (ACC) in m/s2) measured objectively using a combined heart rate monitor and accelerometer (Actiheart®). The main secondary outcomes included self-reported physical activity, intention to increase physical activity, and awareness of physical activity (the agreement between self-rated and objectively measured physical activity). At 8 weeks, 391 (83.9%) participants had complete physical activity data. The intervention had no effect on objectively measured physical activity (PAEE: β=-0.92, 95% CI=-3.50 to 1.66, p=0.48 and ACC: β=0.01, 95% CI=-0.00 to 0.02, p=0.21), self-reported physical activity (β=-0.39, 95% CI=-1.59 to 0.81), or intention to increase physical activity (β=-0.05, 95% CI=-0.22 to 0.11). However, it was associated with an increase in awareness of physical activity (OR=1.74, 95% CI=1.05 to 2.89). Results did not differ according to the type of feedback.
Personalised feedback about physical activity following objective measurement increased awareness but did not result in changes in physical activity in the short term. Measurement and feedback may have a role in promoting behaviour change but are ineffective on their own.
Current Controlled Trials ISRCTN92551397 http://www.controlled-trials.com/ISRCTN92551397
Physical activity (PA) levels in type 2 diabetes mellitus (T2DM) patients are generally low. Poor PA perception may impede healthy behaviour change in this high risk group. We describe (i) objective PA levels, (ii) the difference between objective and self-reported PA (‘PA disparity’) and the correlates of (iii) PA disparity and (iv) overestimation in recently diagnosed T2DM patients.
Cross-sectional analysis of 425 recently diagnosed T2DM patients aged 42 to 71, participating in the ADDITION-Plus study in Eastern England, UK. We define ‘PA disparity’ as the non-negative value of the difference (in mathematical terms the absolute difference) between objective and self-reported physical activity energy expenditure (PAEE in kJ · kg-1 · day-1). ‘Overestimators’ comprised those whose self-reported- exceeded objective-PAEE by 4.91 kJ · kg-1 · day-1(the equivalent of 30 minutes moderate activity per day). Multivariable linear regression examined the association between PA disparity (continuous) and socio-demographic, clinical, health behaviour, quality of life and psychological characteristics. Logistic regression examined the association between PA overestimation and individual characteristics.
Mean objective and self-reported PAEE levels ± SD were 34.4 ± 17.0 and 22.6 ± 19.4 kJ · kg-1 · day-1, respectively (difference in means =11.8; 95% CI = 9.7 to 13.9 kJ · kg-1 · day-1). Higher PA disparity was associated with male sex, younger age, lower socio-economic status and lower BMI. PA overestimators comprised 19% (n = 80), with those in routine/manual occupations more likely to be overestimators than those in managerial/professional occupations.
T2DM patients with poor physical activity perception are more likely to be male, younger, from a lower socio-economic class and to have a lower BMI. PA overestimators were more likely to be in lower socio-economic categories. Self-monitoring and targeted feedback, particularly to those in lower socio-economic categories, may improve PA perceptions and optimise interventions in T2DM patients. Our findings suggest that strategies for enabling realistic assessment of physical activity levels, through self-monitoring or feedback, warrant further investigation and may help refine and improve physical activity interventions.
Type 2 diabetes mellitus; Physical activity; Overestimation; Awareness; Perception; Health behaviour; Lifestyle behaviour; Social correlates of health; Health promotion intervention
Primary care is an important setting for smoking cessation interventions. There is evidence for the effectiveness of tailored interventions for smoking cessation, and text messaging interventions for smoking cessation show promise. The intervention to be evaluated in this trial consists of two components: (1) a web-based program designed to be used by a practice nurse or other smoking cessation advisor (SCA); the program generates a cessation advice report that is highly tailored to relevant characteristics of the smoker; and (2) a three-month programme of automated tailored text messages sent to the smoker’s mobile phone. The objectives of the trial are to assess the acceptability and feasibility of the intervention and to estimate the short-term effectiveness of the intervention in increasing the quit rate compared with usual care alone.
The design is a two parallel group randomised controlled trial (RCT). 600 smokers who want to quit will be recruited in up to 30 general practices in the East of England. During a consultation with an SCA, they will be individually randomised by computer program to usual care (Control) or to usual care plus the iQuit system (Intervention). At the four-week follow-up appointment, the SCA will record smoking status and measure carbon monoxide level. There will be two further follow-ups, at eight weeks and six months from randomisation date, by postal questionnaire sent from and returned to the study centre or by telephone interview conducted by a research interviewer. The primary outcome will be self-reported abstinence for at least two weeks at eight weeks. A sample size of 300 per group would give 80% power to detect an increase in quit rate from 20% to 30% (alpha = 0.05, 2-sided test). The main analyses of quit rates will be conducted on an intention-to-treat basis, making the usual assumption that participants lost to follow up are smoking.
This trial will focus on acceptability, feasibility and short-term effectiveness. The findings will be used to refine the intervention and to inform the decision to proceed to a pragmatic trial to estimate longer-term effectiveness and cost-effectiveness.
Although government-funded specialist smoking cessation services in England offer advice and support to smokers motivated to quit, only a small proportion of smokers make use of this service. Evidence suggests that if smokers are proactively and personally invited to use services, use will be higher than with a standard referral made by health professionals. Computer-based systems generating personalised tailored communications also have the potential to engage with a larger proportion of the smoking population. In this study smokers are proactively invited to use the NHS Stop Smoking Service (SSS), with a personal computer-tailored letter and the offer of a no-commitment introductory session designed to give more information about the service. The primary objective is to assess the relative effectiveness on attendance at the NHS SSS, of proactive recruitment by a brief personal letter, tailored to individual characteristics, and invitation to a taster session, over a standard generic letter advertising the service.
This randomised controlled trial will recruit smokers from general practice who are motivated to quit and have not recently attended the NHS SSS. Smokers aged 16 years and over, identified from medical records in participating practices, are sent a brief screening questionnaire and cover letter from their GP. Smokers giving consent are randomised to the Control group to receive a standard generic letter advertising the local service, or to the Intervention group to receive a brief personal, tailored letter with risk information and an invitation to attend a ‘Come and Try it’ taster session. The primary outcome, assessed 6 months after the date of randomisation, is the proportion of people attending the NHS SSS for at least one session. Planned recruitment is to secure 4,500 participants, from 18 regions in England served by an NHS SSS.
Personal risk information generated by computer, with the addition of taster sessions, could be widely replicated and delivered cost effectively to a large proportion of the smoking population. The results of this trial will inform the potential of this method to increase referrals to specialised smoking cessation services and prompt more quit attempts.
Current Controlled Trials ISRCTN76561916
Smoking cessation; Stop smoking clinics; Computer-tailoring; Personalisation; Risk information
Missing outcome data are very common in smoking cessation trials. It is often assumed that all such missing data are from participants who have been unsuccessful in giving up smoking (“missing=smoking”). Here we use data from a recent Internet based smoking cessation trial in order to investigate which of a set of a priori chosen baseline variables are predictive of missingness, and the evidence for and against the “missing=smoking” assumption.
We use a selection model, which models the probability that the outcome is observed given the outcome and other variables. The selection model includes a parameter for which zero indicates that the data are Missing at Random (MAR) and large values indicate “missing=smoking”. We examine the evidence for the predictive power of baseline variables in the context of a sensitivity analysis. We use data on the number and type of attempts made to obtain outcome data in order to estimate the association between smoking status and the missing data indicator.
We apply our methods to the iQuit smoking cessation trial data. From the sensitivity analysis, we obtain strong evidence that older participants are more likely to provide outcome data. The model for the number and type of attempts to obtain outcome data confirms that age is a good predictor of missing data. There is weak evidence from this model that participants who have successfully given up smoking are more likely to provide outcome data but this evidence does not support the “missing=smoking” assumption. The probability that participants with missing outcome data are not smoking at the end of the trial is estimated to be between 0.14 and 0.19.
Those conducting smoking cessation trials, and wishing to perform an analysis that assumes the data are MAR, should collect and incorporate baseline variables into their models that are thought to be good predictors of missing data in order to make this assumption more plausible. However they should also consider the possibility of Missing Not at Random (MNAR) models that make or allow for less extreme assumptions than “missing=smoking”.
Type 2 diabetes (T2D) is associated with increased risk of morbidity and premature mortality. Among those at high risk, incidence can be halved through healthy changes in behaviour. Information about genetic and phenotypic risk of T2D is now widely available. Whether such information motivates behaviour change is unknown. We aim to assess the effects of communicating genetic and phenotypic risk of T2D on risk-reducing health behaviours, anxiety, and other cognitive and emotional theory-based antecedents of behaviour change.
In a parallel group, open randomised controlled trial, approximately 580 adults born between 1950 and 1975 will be recruited from the on-going population-based, observational Fenland Study (Cambridgeshire, UK). Eligible participants will have undergone clinical, anthropometric, and psychosocial measurements, been genotyped for 23 single-nucleotide polymorphisms associated with T2D, and worn a combined heart rate monitor and accelerometer (Actiheart®) continuously for six days and nights to assess physical activity. Participants are randomised to receive either standard lifestyle advice alone (control group), or in combination with a genetic or a phenotypic risk estimate for T2D (intervention groups). The primary outcome is objectively measured physical activity. Secondary outcomes include self-reported diet, self-reported weight, intention to be physically active and to engage in a healthy diet, anxiety, diabetes-related worry, self-rated health, and other cognitive and emotional outcomes. Follow-up occurs eight weeks post-intervention. Values at follow-up, adjusted for baseline, will be compared between randomised groups.
This study will provide much needed evidence on the effects of providing information about the genetic and phenotypic risk of T2D. Importantly, it will be among the first to examine the impact of genetic risk information using a randomised controlled trial design, a population-based sample, and an objectively measured behavioural outcome. Results of this trial, along with recent evidence syntheses of similar studies, should inform policy concerning the availability and use of genetic risk information.
Current Controlled Trials ISRCTN09650496
Genetic; Phenotypic; Risk; Communication; Type 2 diabetes; Physical activity; Behaviour; Randomised controlled trial; Protocol
Supereruptions violently transfer huge amounts (100 s–1000 s km3) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted ∼760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500–3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies.
Most people who stop smoking successfully for a few weeks will return to smoking again in the medium term. There are few effective interventions to prevent this relapse and none used routinely in clinical practice. A previous exploratory meta-analysis suggested that self-help booklets may be effective but requires confirmation. This trial aims to evaluate the effectiveness and cost-effectiveness of a set of self-help educational materials to prevent smoking relapse in the National Health Service (NHS) Stop Smoking Service.
This is an open, randomized controlled trial. The target population is carbon monoxide (CO) verified quitters at four weeks in the NHS stop smoking clinic (total sample size N = 1,400). The experimental intervention tested is a set of eight revised Forever Free booklets, including an introduction booklet and more extensive information on all important issues for relapse prevention. The control intervention is a leaflet that has no evidence to suggest it is effective but is currently given to some patients using NHS stop smoking services.
Two follow-up telephone interviews will be conducted at three and 12 months after the quit date. The primary outcome will be prolonged abstinence from months four to 12 with no more than five lapses, confirmed by a CO test at the 12-month assessment. The secondary outcomes will be seven-day self-report point prevalence abstinence at three months and seven-day biochemically confirmed point prevalence abstinence at 12 months. To assess cost-effectiveness, costs will be estimated from a health service perspective and the EQ-5D will be used to estimate the QALY (Quality Adjusted Life Year) gain associated with each intervention.
The comparison of smoking abstinence rates (and any other binary outcomes) between the two trial arms will be carried out using odds ratio as the outcome statistic and other related statistical tests. Exploratory subgroup analyses, including logistic regression analyses with interaction terms, will be conducted to investigate possible effect-modifying variables.
The possible effect of self-help educational materials for the prevention of smoking relapse has important public health implications.
Current Controlled Trials ISRCTN36980856
Smoking relapse; Self-help booklets; Effectiveness; Intervention
The behavioural impact of pharmacogenomics is untested. We tested two hypotheses concerning the behavioural impact of informing smokers their oral dose of NRT is tailored to analysis of DNA.
Methods and Findings
We conducted an RCT with smokers in smoking cessation clinics (N = 633). In combination with NRT patch, participants were informed that their doses of oral NRT were based either on their mu-opioid receptor (OPRM1) genotype, or their nicotine dependence questionnaire score (phenotype). The proportion of prescribed NRT consumed in the first 28 days following quitting was not significantly different between groups: (68.5% of prescribed NRT consumed in genotype vs 63.6%, phenotype group, difference = 5.0%, 95% CI −0.9,10.8, p = 0.098). Motivation to make another quit attempt among those (n = 331) not abstinent at six months was not significantly different between groups (p = 0.23). Abstinence at 28 days was not different between groups (p = 0.67); at six months was greater in genotype than phenotype group (13.7% vs 7.9%, difference = 5.8%, 95% CI 1.0,10.7, p = 0.018).
Informing smokers their oral dose of NRT was tailored to genotype not phenotype had a small, statistically non-significant effect on 28-day adherence to NRT. Among those still smoking at six months, there was no evidence that saying NRT was tailored to genotype adversely affected motivation to make another quit attempt. Higher abstinence rate at six months in the genotype arm requires investigation.
Failure to take medication reduces the effectiveness of treatment leading to increased morbidity and mortality. We evaluated the efficacy of a consultation-based intervention to support objectively-assessed adherence to oral glucose lowering medication (OGLM) compared to usual care among people with type 2 diabetes.
This was a parallel group randomised trial in adult patients with type 2 diabetes and HbA1c≥7.5% (58 mmol/mol), prescribed at least one OGLM. Participants were allocated to a clinic nurse delivered, innovative consultation-based intervention to strengthen patient motivation to take OGLM regularly and support medicine taking through action-plans, or to usual care. The primary outcome was the percentage of days on which the prescribed dose of medication was taken, measured objectively over 12 weeks with an electronic medication-monitoring device (TrackCap, Aardex, Switzerland). The primary analysis was intention-to-treat.
211 patients were randomised between July 1, 2006 and November 30, 2008 in 13 British general practices (primary care clinics). Primary outcome data were available for 194 participants (91.9%). Mean (sd) percentage of adherent days was 77.4% (26.3) in the intervention group and 69.0% (30.8) in standard care (mean difference between groups 8.4%, 95% confidence interval 0.2% to 16.7%, p = 0.044). There was no significant adverse impact on functional status or treatment satisfaction.
This well-specified, theory based intervention delivered in a single session of 30 min in primary care increased objectively measured medication adherence, with no adverse effect on treatment satisfaction. These findings justify a definitive trial of this approach to improving medication adherence over a longer period of time, with clinical and cost-effectiveness outcomes to inform clinical practice.
Current Controlled Trials ISRCTN30522359
Adherence; Brief intervention; Diabetes
The increasing prevalence of type 2 diabetes poses both clinical and public health challenges. Cost-effective approaches to prevent progression of the disease in primary care are needed. Evidence suggests that intensive multifactorial interventions including medication and behaviour change can significantly reduce cardiovascular morbidity and mortality among patients with established type 2 diabetes, and that patient education in self-management can improve short-term outcomes. However, existing studies cannot isolate the effects of behavioural interventions promoting self-care from other aspects of intensive primary care management. The ADDITION-Plus trial was designed to address these issues among recently diagnosed patients in primary care over one year.
ADDITION-Plus is an explanatory randomised controlled trial of a facilitator-led, theory-based behaviour change intervention tailored to individuals with recently diagnosed type 2 diabetes. 34 practices in the East Anglia region participated. 478 patients with diabetes were individually randomised to receive (i) intensive treatment alone (n = 239), or (ii) intensive treatment plus the facilitator-led individual behaviour change intervention (n = 239). Facilitators taught patients key skills to facilitate change and maintenance of key behaviours (physical activity, dietary change, medication adherence and smoking), including goal setting, action planning, self-monitoring and building habits. The intervention was delivered over one year at the participant's surgery and included a one-hour introductory meeting followed by six 30-minute meetings and four brief telephone calls. Primary endpoints are physical activity energy expenditure (assessed by individually calibrated heart rate monitoring and movement sensing), change in objectively measured dietary intake (plasma vitamin C), medication adherence (plasma drug levels), and smoking status (plasma cotinine levels) at one year. We will undertake an intention-to-treat analysis of the effect of the intervention on these measures, an assessment of cost-effectiveness, and analyse predictors of behaviour change in the cohort.
The ADDITION-Plus trial will establish the medium-term effectiveness and cost-effectiveness of adding an externally facilitated intervention tailored to support change in multiple behaviours among intensively-treated individuals with recently diagnosed type 2 diabetes in primary care. Results will inform policy recommendations concerning the management of patients early in the course of diabetes. Findings will also improve understanding of the factors influencing change in multiple behaviours, and their association with health outcomes.
Estimates of the risk of developing Crohn's disease (CD) can be made using DNA testing for mutations in the NOD2 (CARD15) gene, family history, and smoking status. Smoking doubles the risk of CD, a risk that is reduced by stopping. CD therefore serves as a timely and novel paradigm within which to assess the utility of predictive genetic testing to motivate behaviour change to reduce the risk of disease. The aim of the study is to describe the impact upon stopping smoking of communicating a risk of developing CD that incorporates DNA analysis. We will test the following main hypothesis:
Smokers who are first degree relatives (FDRs) of CD probands are more likely to make smoking cessation attempts following communication of risk estimates of developing CD that incorporate DNA analysis, compared with an equivalent communication that does not incorporate DNA analysis.
A parallel groups randomised controlled trial in which smokers who are FDRs of probands with CD are randomly allocated in families to undergo one of two types of assessment of risk for developing CD based on either:
i. DNA analysis, family history of CD and smoking status, or
ii. Family history of CD and smoking status
The primary outcome is stopping smoking for 24 hours or longer in the six months following provision of risk information. The secondary outcomes are seven-day smoking abstinence at one week and six month follow-ups. Randomisation of 470 smoking FDRs of CD probands, with 400 followed up (85%), provides 80% power to detect a difference in the primary outcome of 14% between randomised arms, at the 5% significance level.
This trial provides one of the strongest tests to date of the impact of communicating DNA-based risk assessment on risk-reducing behaviour change. Specific issues regarding the choice of trial design are discussed.
Despite concerns that facilitating informed choice would decrease diabetes screening uptake, 'informed choice' invitations that increased knowledge did not affect attendance (the DICISION trial). We explored possible reasons using data from an experimental analogue study undertaken to develop the invitations. We tested a model of the impact on knowledge, attitude and intentions of a diabetes screening invitation designed to facilitate informed choices.
417 men and women aged 40-69 recruited from town centres in the UK were randomised to receive either an invitation for diabetes screening designed to facilitate informed choice or a standard type of invitation. Knowledge of the invitation, attitude towards diabetes screening, and intention to attend for diabetes screening were assessed two weeks later.
Attitude was a strong predictor of screening intentions (β = .64, p = .001). Knowledge added to the model but was a weak predictor of intentions (β = .13, p = .005). However, invitation type did not predict attitudes towards screening but did predict knowledge (β = -.45, p = .001), which mediated a small effect of invitation type on intention (indirect β = -.06, p = .017).
These findings may explain why information about the benefits and harms of screening did not reduce diabetes screening attendance in the DICISION trial.
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.
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).
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.
Funder: Medical Research Council (MRC)
Grant number: G0500274
Date trial stated: June 2007
Expected end date: December 2009
Expected reporting date: December 2010