Padraig Dixon

Telehealth for patients at high risk of cardiovascular disease: pragmatic randomised controlled trial

Objective To assess whether non-clinical staff can effectively manage people at high risk of cardiovascular disease using digital health technologies. Design Pragmatic, multicentre, randomised controlled trial. Setting 42 general practices in three areas of England. Participants Between 3 December 2012 and 23 July 2013 we recruited 641 adults aged 40 to 74 years with a 10 year cardiovascular disease risk of 20% or more, no previous cardiovascular event, at least one modifiable risk factor (systolic blood pressure ≥140 mm Hg, body mass index ≥30, current smoker), and access to a telephone, the internet, and email. Participants were individually allocated to intervention (n=325) or control (n=316) groups using automated randomisation stratified by site, minimised by practice and baseline risk score. Interventions Intervention was the Healthlines service (alongside usual care), comprising regular telephone calls from trained lay health advisors following scripts generated by interactive software. Advisors facilitated self management by supporting participants to use online resources to reduce risk factors, and sought to optimise drug use, improve treatment adherence, and encourage healthier lifestyles. The control group comprised usual care alone. Main outcome measures The primary outcome was the proportion of participants responding to treatment, defined as maintaining or reducing their cardiovascular risk after 12 months. Outcomes were collected six and 12 months after randomisation and analysed masked. Participants were not masked. Results 50% (148/295) of participants in the intervention group responded to treatment compared with 43% (124/291) in the control group (adjusted odds ratio 1.3, 95% confidence interval 1.0 to 1.9; number needed to treat=13); a difference possibly due to chance (P=0.08). The intervention was associated with reductions in blood pressure (difference in mean systolic −2.7 mm Hg (95% confidence interval −4.7 to −0.6 mm Hg), mean diastolic −2.8 (−4.0 to −1.6 mm Hg); weight −1.0 kg (−1.8 to −0.3 kg), and body mass index −0.4 ( −0.6 to −0.1) but not cholesterol −0.1 (−0.2 to 0.0), smoking status (adjusted odds ratio 0.4, 0.2 to 1.0), or overall cardiovascular risk as a continuous measure (−0.4, −1.2 to 0.3)). The intervention was associated with improvements in diet, physical activity, drug adherence, and satisfaction with access to care, treatment received, and care coordination. One serious related adverse event occurred, when a participant was admitted to hospital with low blood pressure. Conclusions This evidence based telehealth approach was associated with small clinical benefits for a minority of people with high cardiovascular risk, and there was no overall improvement in average risk. The Healthlines service was, however, associated with improvements in some risk behaviours, and in perceptions of support and access to care. Trial registration Current Controlled Trials ISRCTN 27508731.

Cost-effectiveness of telehealth for patients with raised cardiovascular disease risk: evidence from the Healthlines randomised controlled trial

Objectives To investigate the cost-effectiveness of a telehealth intervention for primary care patients with raised cardiovascular disease (CVD) risk. Design A prospective within-trial patient-level economic evaluation conducted alongside a randomised controlled trial. Setting Patients recruited through primary care, and intervention delivered via telehealth service. Participants Adults with a 10-year CVD risk ≥20%, as measured by the QRISK2 algorithm, with at least 1 modifiable risk factor. Intervention A series of up to 13 scripted, theory-led telehealth encounters with healthcare advisors, who supported participants to make behaviour change, use online resources, optimise medication and improve adherence. Participants in the control arm received usual care. Primary and secondary outcome measures Cost-effectiveness measured by net monetary benefit at the end of 12 months of follow-up, calculated from incremental cost and incremental quality-adjusted life years (QALYs). Productivity impacts, participant out-of-pocket expenditure and the clinical outcome were presented in a cost-consequences framework. Results 641 participants were randomised—325 to receive the telehealth intervention in addition to usual care and 316 to receive only usual care. 18% of participants had missing data on either costs, utilities or both. Multiple imputation was used for the base case results. The intervention was associated with incremental mean per-patient National Health Service (NHS) costs of £138 (95% CI 66 to 211) and an incremental QALY gain of 0.012 (95% CI −0.001 to 0.026). The incremental cost-effectiveness ratio was £10 859. Net monetary benefit at a cost-effectiveness threshold of £20 000 per QALY was £116 (95% CI −58 to 291), and the probability that the intervention was cost-effective at this threshold value was 0.77. Similar results were obtained from a complete case analysis. Conclusions There is evidence to suggest that the Healthlines telehealth intervention was likely to be cost-effective at a threshold of £20 000 per QALY. Trial registration number ISRCTN27508731; Results. Prospectively registered 05 July 2012.

Feasibility cluster randomised controlled trial of a within-consultation intervention to reduce antibiotic prescribing for children presenting to primary care with acute respiratory tract infection and cough

Objective To investigate recruitment and retention, data collection methods and the acceptability of a ‘within-consultation’ complex intervention designed to reduce antibiotic prescribing. Design Primary care feasibility cluster randomised controlled trial. Setting 32 general practices in South West England recruiting children from October 2014 to April 2015. Participants Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI). Intervention A web-based clinician-focussed clinical rule to predict risk of future hospitalisation and a printed leaflet with individualised child health information for carers, safety-netting advice and a treatment decision record. Controls Usual practice, with clinicians recording data on symptoms, signs and treatment decisions. Results Of 542 children invited, 501 (92.4%) consented to participate, a month ahead of schedule. Antibiotic prescribing data were collected for all children, follow-up data for 495 (98.8%) and the National Health Service resource use data for 494 (98.6%). The overall antibiotic prescribing rates for children’s RTIs were 25% and 15.8% (p=0.018) in intervention and control groups, respectively. We found evidence of postrandomisation differential recruitment: the number of children recruited to the intervention arm was higher (292 vs 209); over half were recruited by prescribing nurses compared with less than a third in the control arm; children in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03) and appeared to be more unwell than those in the control arm with higher respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews with clinicians confirmed preferential recruitment of less unwell children to the trial, more so in the control arm. Conclusion Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records. Trial registration number ISRCTN 23547970 UKCRN study ID 16891

Cost-effectiveness modelling of telehealth for patients with raised cardiovascular disease risk: evidence from a cohort simulation conducted alongside the Healthlines randomised controlled trial

Objectives To investigate the long-term cost-effectiveness (measured as the ratio of incremental NHS cost to incremental quality-adjusted life years) of a telehealth intervention for patients with raised cardiovascular disease (CVD) risk. Design A cohort simulation model developed as part of the economic evaluation conducted alongside the Healthlines randomised controlled trial. Setting Patients recruited through primary care, and intervention delivered via telehealth service. Participants Participants with a 10-year CVD risk ≥20%, as measured by the QRISK2 algorithm, and with at least 1 modifiable risk factor, individually randomised from 42 general practices in England. Intervention A telehealth service delivered over a 12-month period. The intervention involved a series of responsive, theory-led encounters between patients and trained health information advisors who provided access to information resources and supported medication adherence and coordination of care. Primary and secondary outcome measures Cost-effectiveness measured by net monetary benefit over the simulated lifetime of trial participants from a UK National Health Service perspective. Results The probability that the intervention was cost-effective depended on the duration of the effect of the intervention. The intervention was cost-effective with high probability if effects persisted over the lifetime of intervention recipients. The probability of cost-effectiveness was lower for shorter durations of effect. Conclusions The intervention was likely to be cost-effective under a lifetime perspective. Trial registration number ISRCTN27508731; Results.

Estimating marginal healthcare costs using genetic variants as instrumental variables: Mendelian Randomization in economic evaluation

Accurate measurement of the marginal healthcare costs associated with different diseases and health conditions is important, especially for increasingly prevalent conditions such as obesity. However, existing observational study designs cannot identify the causal impact of disease on healthcare costs. This paper explores the possibilities for causal inference offered by Mendelian randomization, a form of instrumental variable analysis that uses genetic variation as a proxy for modifiable risk exposures, to estimate the effect of health conditions on cost. Well-conducted genome-wide association studies provide robust evidence of the associations of genetic variants with health conditions or disease risk factors. The subsequent causal effects of these health conditions on cost can be estimated using genetic variants as instruments for the health conditions. This is because the approximately random allocation of genotypes at conception means that many genetic variants are orthogonal to observable and unobservable confounders. Datasets with linked genotypic and resource use information obtained from electronic medical records or from routinely collected administrative data are now becoming available and will facilitate this form of analysis. We describe some of the methodological issues that arise in this type of analysis, which we illustrate by considering how Mendelian randomization could be used to estimate the causal impact of obesity, a complex trait, on healthcare costs. We describe some of the data sources that could be used for this type of analysis. We conclude by considering the challenges and opportunities offered by Mendelian randomization for economic evaluation.

A randomised controlled trial assessing the severity and duration of depressive symptoms associated with a clinically significant response to sertraline versus placebo, in people presenting to primary care with depression (PANDA trial): study protocol for a randomised controlled trial

BackgroundDepressive symptoms are usually managed within primary care and antidepressant medication constitutes the first-line treatment. It remains unclear at present which people are more likely to benefit from antidepressant medication. This paper describes the protocol for a randomised controlled trial (PANDA) to investigate the severity and duration of depressive symptoms that are associated with a clinically significant response to sertraline compared to placebo, in people presenting to primary care with depression.Methods/designPANDA is a randomised, double blind, placebo controlled trial in which participants are individually randomised to sertraline or placebo. Eligible participants are those who are between the ages of 18 to 74; have presented to primary care with depression or low mood during the past 2 years; have not received antidepressant or anti-anxiety medication in the 8 weeks prior to enrolment in the trial and there is clinical equipoise about the benefits of selective serotonin reuptake inhibitor (SSRI) medication. Participants who consent to participate in the trial are randomised to receive either sertraline or matching placebo, starting at 50 mg daily for 1 week, increasing to 100 mg daily for up to 11 weeks (with the option of increasing to 150 mg if required). Participants, general practitioners (GPs) and the research team will be blind to treatment allocation. The primary outcome will be depressive symptoms measured by the Patient Health Questionnaire-9 (PHQ-9) at 6 weeks post randomisation, measured as a continuous outcome. Secondary outcomes include depressive symptoms measured with the PHQ-9 at 2 and 12 weeks as a continuous outcome and at 2, 6 and 12 weeks as a binary outcome; follow-up scores on depressive symptoms measured with the Beck Depression Inventory-II, anxiety symptoms measured by the Generalized Anxiety Disorder-7 and quality of life measured with the Euroqol-5D-5L and Short Form-12; emotional processing task scores measured at baseline, 2 and 6 weeks; and costs associated with healthcare use, time off work and personal costs.DiscussionThe PANDA trial uses a simple self-administered measure to establish the severity and duration of depressive symptoms associated with a clinically significant response to sertraline. The evidence from the trial will inform primary care prescribing practice by identifying which patients are more likely to benefit from antidepressants.Trial registrationControlled Trials ISRCTN Registry, ISRCTN84544741. Registered on 20 March 2014. EudraCT Number: 2013-003440-22; Protocol Number: 13/0413 (version 6.1).

The association between adiposity and inpatient hospital costs in the UK Biobank cohort

Background High adiposity is associated with higher risks for a variety of adverse health outcomes, including higher rates of age-adjusted mortality and increased morbidity. This has important implications for the management of healthcare systems, since the endocrinal, cardiometabolic and other changes associated with increased adiposity may be associated with substantial healthcare costs. Methods We studied the association between various measures of adiposity and inpatient hospital costs through record linkage between UK Biobank and records of inpatient care in England and Wales. UK Biobank is a large prospective cohort study that aimed to recruit men and women aged between 40 and 69 from 2006 to 2010. We applied generalised linear models to cost per person year to estimate the marginal effect and averaged adjusted predicted cost of adiposity on inpatient costs. Results Valid cost and body mass index (BMI) data from 457,689 participants were available for inferential analysis. Some 54.4% of individuals included in the analysis sample had positive inpatient healthcare costs over the period of follow-up. Median hospital costs per person year of follow-up were £89, compared to mean costs of £481. Mean BMI overall was 27.4 kg/m2 (standard deviation 4.8). The marginal effect of a unit increase in BMI was £13.61 (99% confidence interval: £12.60 to £14.63) per person year of follow up. The marginal effect of a standard deviation increase in BMI was £69.20 (99% confidence interval: £64.98 to £73.42). The marginal effect of becoming obese was £136.35 (99% confidence interval: £124.62 to £148.08). Average adjusted predicted inpatient hospital costs increased almost linearly when modelled using continuous measure of adiposity. Sensitivity analysis of different scenarios did not substantially change these conclusions, although there was some evidence of attenuation of the effects of adiposity when controlling for waist-hip ratios, and when individuals who self-reported any pre-existing conditions were excluded from analysis. Conclusions Higher adiposity is associated with higher inpatient hospital costs. Further scrutiny using causal inferential methods is warranted to establish if further public health investments are required to manage the large healthcare costs observationally associated with overweight and obesity. Ethics statement: Not applicable