Prevost A Toby

Publications of Prevost A Toby

• Trial Protocol: Communicating DNA-based risk assessments for Crohn's disease: a randomised controlled trial assessing impact upon stopping smoking

  Authors: Sophia Whitwell, Christopher Mathew, Cathryn Lewis, Alastair Forbes, Sally Watts, Jeremy Sanderson, Gareth Hollands, Prevost A Toby, David Armstrong, Ann Kinmonth, Stephen Sutton, Theresa Marteau

  BMC Public Health. 01/2011;

  Abstract Background 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. SmokingAbstract Background 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. Methods/design 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. Discussion 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. Trial Registration ISRCTN: ISRCTN21633644

• Protocol for the MoleMate™ UK Trial: a randomised controlled trial of the MoleMate system in the management of pigmented skin lesions in primary care [ISRCTN 79932379]

  Authors: Fiona Walter, Helen Morris, Elka Humphrys, Per Hall, Ann Kinmonth, Prevost A Toby, Edward Wilson, Nigel Burrows, Paul Norris, Margaret Johnson, Jon Emery

  BMC Family Practice. 01/2010;

  Abstract Background Suspicious pigmented lesions are a common presenting problem in general practice consultations; while the majority are benign a small minority are melanomas. DifferentiatingAbstract Background Suspicious pigmented lesions are a common presenting problem in general practice consultations; while the majority are benign a small minority are melanomas. Differentiating melanomas from other pigmented lesions in primary care is challenging: currently, 95% of all lesions referred to a UK specialist are benign. The MoleMate system is a new diagnostic aid, incorporating a hand-held SIAscopy scanner with a primary care diagnostic algorithm. This trial tests the hypothesis that adding the MoleMate system to current best primary care practice will increase the proportion of appropriate referrals of suspicious pigmented lesions to secondary care compared with current best practice alone. Methods/design The MoleMate UK Trial is a primary care based multi-centre randomised controlled trial, with randomisation at patient level using a validated block randomisation method for two age groups (45 years and under; 46 years and over). We aim to recruit adult patients seen in general practice with a pigmented skin lesion that cannot immediately be diagnosed as benign and the patient reassured. The trial has a 'two parallel groups' design, comparing 'best practice' with 'best practice' plus the MoleMate system in the intervention group. The primary outcome is the positive predictive value (PPV) of referral defined as the proportion of referred lesions seen by secondary care experts that are considered 'clinically significant' (i.e. biopsied or monitored). Secondary outcomes include: the sensitivity, specificity and negative predictive value (NPV) of the decision not to refer; clinical outcomes (melanoma thickness, 5 year melanoma incidence and mortality); clinician outcomes (Index of Suspicion, confidence, learning effects); patient outcomes (satisfaction, general and cancer-specific worry), and cost-utility. Discussion The MoleMate UK Trial tests a new technology designed to improve the management of suspicious pigmented lesions in primary care. If effective, the MoleMate system could reduce the burden on skin cancer clinics of patients with benign pigmented skin lesions, and improve patient care in general practice.

• Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence

  Authors: Theresa Marteau, Marcus Munafò, Paul Aveyard, Chloe Hill, Sophia Whitwell, Thomas Willis, Rachel Crockett, Gareth Hollands, Elaine Johnstone, Alison Wright, Prevost A Toby, David Armstrong, Stephen Sutton, Ann Kinmonth

  BMC Public Health. 01/2010;

  Abstract Background The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to thisAbstract 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. Trial details Funder: Medical Research Council (MRC) Grant number: G0500274 ISRCTN: 14352545 Date trial stated: June 2007 Expected end date: December 2009 Expected reporting date: December 2010

• Impact of an informed choice invitation on uptake of screening for diabetes in primary care (DICISION): trial protocol

  Authors: Eleanor Mann, Prevost A Toby, Simon Griffin, Ian Kellar, Stephen Sutton, Michael Parker, Simon Sanderson, Ann Kinmonth, Theresa Marteau

  BMC Public Health. 01/2009;

  Abstract Background Screening invitations have traditionally been brief, providing information only about population benefits. Presenting information about the limited individual benefits andAbstract Background Screening invitations have traditionally been brief, providing information only about population benefits. Presenting information about the limited individual benefits and potential harms of screening to inform choice may reduce attendance, particularly in the more socially deprived. At the same time, amongst those who attend, it might increase motivation to change behavior to reduce risks. This trial assesses the impact on attendance and motivation to change behavior of an invitation that facilitates informed choices about participating in diabetes screening in general practice. Three hypotheses are tested: 1. Attendance at screening for diabetes is lower following an informed choice compared with a standard invitation. 2. There is an interaction between the type of invitation and social deprivation: attendance following an informed choice compared with a standard invitation is lower in those who are more rather than less socially deprived. 3. Amongst those who attend for screening, intentions to change behavior to reduce risks of complications in those subsequently diagnosed with diabetes are stronger following an informed choice invitation compared with a standard invitation. Method/Design 1500 people aged 40–69 years without known diabetes but at high risk are identified from four general practice registers in the east of England. 1200 participants are randomized by households to receive one of two invitations to attend for diabetes screening at their general practices. The intervention invitation is designed to facilitate informed choices, and comprises detailed information and a decision aid. A comparison invitation is based on those currently in use. Screening involves a finger-prick blood glucose test. The primary outcome is attendance for diabetes screening. The secondary outcome is intention to change health related behaviors in those attenders diagnosed with diabetes. A sample size of 1200 ensures 90% power to detect a 10% difference in attendance between arms, and in an estimated 780 attenders, 80% power to detect a 0.2 sd difference in intention between arms. Discussion The DICISION trial is a rigorous pragmatic denominator based clinical trial of an informed choice invitation to diabetes screening, which addresses some key limitations of previous trials. Trial registration Current Controlled Trials ISRCTN73125647

• Screening for type 2 diabetes is feasible, acceptable, but associated with increased short-term anxiety: A randomised controlled trial in British general practice

  Authors: Paul Park, Rebecca Simmons, Prevost A Toby, Simon Griffin

  BMC Public Health. 01/2008;

  Abstract Background To assess the feasibility and uptake of a diabetes screening programme; to examine the effects of invitation to diabetes screening on anxiety, self-rated health and illnessAbstract Background To assess the feasibility and uptake of a diabetes screening programme; to examine the effects of invitation to diabetes screening on anxiety, self-rated health and illness perceptions. Methods Randomised controlled trial in two general practices in Cambridgeshire. Individuals aged 40–69 without known diabetes were identified as being at high risk of having undiagnosed type 2 diabetes using patient records and a validated risk score (n = 1,280). 355 individuals were randomised in a 2 to 1 ratio into non-invited (n = 238) and invited (n = 116) groups. A stepwise screening programme confirmed the presence or absence of diabetes. Six weeks after the last contact (either test or invitation), a questionnaire was sent to all participants, including non-attenders and those who were not originally invited. Outcome measures included attendance, anxiety (short-form Spielberger State Anxiety Inventory-STAI), self-rated health and diabetes illness perceptions. Results 95 people (82% of those invited) attended for the initial capillary blood test. Six individuals were diagnosed with diabetes. Invited participants were more anxious than those not invited (37.6 vs. 34.1 STAI, p-value = 0.015), and those diagnosed with diabetes were considerably more anxious than those classified free of diabetes (46.7 vs. 37.0 STAI, p-value = 0.031). Non-attenders had a higher mean treatment control sub-scale (3.87 vs. 3.56, p-value = 0.016) and a lower mean emotional representation sub-scale (1.81 vs. 2.68, p-value = 0.001) than attenders. No differences in the other five illness perception sub-scales or self-rated health were found. Conclusion Screening for type 2 diabetes in primary care is feasible but may be associated with higher levels of short-term anxiety among invited compared with non-invited participants. Trial registration ISRCTN99175498

• Protocol for SAMS (Support and Advice for Medication Study): A randomised controlled trial of an intervention to support patients with type 2 diabetes with adherence to medication

  Authors: Andrew Farmer, Prevost A Toby, Wendy Hardeman, Anthea Craven, Stephen Sutton, Simon Griffin, Ann Louise Kinmonth

  BMC Family Practice. 01/2008;

  Abstract Background Although some interventions have been shown to improve adherence to medication for diabetes, results are not consistent. We have developed a theory-based intervention which weAbstract Background Although some interventions have been shown to improve adherence to medication for diabetes, results are not consistent. We have developed a theory-based intervention which we will evaluate in a well characterised population to test efficacy and guide future intervention development and trial design. Methods and Design The SAMS (Supported Adherence to Medication Study) trial is a primary care based multi-centre randomised controlled trial among 200 patients with type 2 diabetes and an HbA1c of 7.5% or above. It is designed to evaluate the efficacy of a two-component motivational intervention based on the Theory of Planned Behaviour and volitional action planning to support medication adherence compared with standard care. The intervention is delivered by practice nurses. Nurses were trained using a workshop approach with role play and supervised using assessment of tape-recorded consultations. The trial has a two parallel groups design with an unbalanced three-to-two individual randomisation eight weeks after recruitment with twelve week follow-up. The primary outcome is medication adherence measured using an electronic medication monitor over 12 weeks and expressed as the difference between intervention and control in mean percentage of days on which the correct number of medication doses is taken. Subgroup analyses will explore impact of number of medications taken, age, HbA1c, and self-reported adherence at baseline on outcomes. The study also measures the effect of dispensing medication to trial participants packaged in the electronic medication-monitoring device compared with conventional medication packaging. This will be achieved through one-to-one randomisation at recruitment to these conditions with assessment of the difference between groups in self-report of medication adherence and change in mean HbA1c from baseline to eight weeks. Anonymised demographic data are collected on non-respondents. Central randomisation is carried out independently of trial co-ordination and practices using minimisation to adjust for selected confounders. Discussion The SAMS intervention and trial design address weaknesses of previous research by recruitment from a well-characterised population, definition of a feasible theory based intervention to support medication taking and careful measurement to estimate and interpret efficacy. The results will inform practice and the design of a cost-effectiveness trial [ISRCTN30522359].