A cluster randomised controlled trial testing an intervention to lower cardiovascular disease risk for people with severe mental illnesses in primary care Alexandra Burton Programme Manager UCL Division of Psychiatry

Background Chief Investigator: Professor David Osborn (UCL Division of Psychiatry) Funder: National Institute for Health Research Sponsor: Camden and Islington NHS Foundation Trust Delivery: PRIMENT and the NIHR CRN Collaborators: UCL Depts of Primary Care and Pop Health, Statistical Science and Centre of Applied Health Research, McPin Foundation, Rethink Mental Illness, University of Southampton, Kings College London, Imperial College London

Background Increased risk of cardiovascular disease (CVD) and mortality in people with schizophrenia or bipolar: Die up to 20 years earlier than the general population Those under 50 with these conditions are more than 3 times at risk of CVD than their contemporaries The mortality gap is increasing Why? Difficulties managing lifestyle, stress, poverty Illness factors and antipsychotic medications Diagnostic overshadowing and sub optimal management of CVD risk

Why primary care? NICE places the responsibility for physical health of people with SMI in primary care Not all people with SMI are accessing secondary services The Quality Outcomes Framework (QoF) incentivises annual physical health checks for people with SMI Effectiveness of practice nurse management of long term conditions – diabetes, asthma, CVD

Overview of the Primrose Programme Five year National Institute for Health Research (NIHR) Programme Grant with three main work packages: Develop a new tool to better predict cardiovascular disease (CVD) risk in people with severe mental illnesses (SMI): https://www.ucl.ac.uk/primrose-risk-score/ Identify the best available evidence and develop an intervention and training package for GP practice nurses and healthcare assistants to help lower CVD risk in people with SMI. Test the clinical and cost effectiveness of the intervention and training package in a 12-month cluster RCT delivered in GP Practices

Overview of the Primrose Trial Aim: To test the effectiveness and cost effectiveness of a practice nurse/healthcare assistant led service to reduce cholesterol and CVD risk in people with SMI. Method: 12-month pragmatic cluster RCT coordinated in 6 recruitment waves Intervention: Primrose intervention + British Heart Foundation (BHF) leaflets vs treatment as usual (TaU) + BHF leaflets Primary outcome: Total cholesterol at 12 month follow up Secondary outcomes: BMI, HBA1c, waist circumference, blood pressure, CVD risk scores, diet, physical activity, smoking, alcohol use, medication adherence, statin prescriptions, wellbeing, service use and costs Data Collection: Baseline, 6 and 12 month by research nurses in clinical research networks (CRNs)

Overview of the Primrose Trial GP Practice inclusion criteria: SMI register list of >40 patients Resources to deliver the intervention if randomised (practice nurse/HCA) Patient inclusion criteria: SMI (schizophrenia, bipolar, psychosis) 30-75 years old Cholesterol above and including 5 mmol/l and/or total/HDL chol ratio above and including 4 mmol/l and one or more of the following: BMI > 30 kg/m2 Blood pressure above 140mm Hg systolic and/or 90 mm Hg diastolic Current smoker HbA1c 42-47 mmol/ml Diabetes Hypertension

Overview of the Primrose Trial Patient exclusion criteria: Under acute psychiatric care Primary diagnosis of organic mental health problem and/or severe cognitive impairment Life expectancy < 6 months Pre-existing CVD Currently pregnant Personality disorder or depression/anxiety without any psychotic features

What is the Primrose Intervention? 8-12 appointments with a practice nurse or healthcare assistant in the patient’s GP practice over 6 months Support patients to change behaviour by identifying and monitoring goals to improve cardiovascular health e.g. taking medication, stopping smoking, improving diet, increasing physical activity or reducing drinking Refer on to existing support services and/or Brief behavioural support provided directly Follow-up and monitoring including attendance at services and progress with health goals

What is the Primrose Intervention? Two day training programme delivered by a health psychologist and practice nurse with mental health expertise Two week gap between training sessions for nurses/HCAs to practice intervention delivery with a patient Study manual detailing procedures, appointment structures and behaviour change strategies to use within appointments

Recruitment and follow up 327 patients and 76 GP practices recruited to the study across the UK 289/327 (88%) patients followed up at 12 months 155 patients randomised to receive the intervention and 172 patients randomised to receive routine care Average cluster size: 4.3 patients

Primrose Study Sample Variable Primrose TAU n/N or mean % or (SD) Male   n/N or mean % or (SD) Male 67/155 43 87/171 51 Age (10) Ethnicity White 134/154 87 155/171 91 Black 11/154 7 5/171 3 Asian 5/154 Other 4/154 6/171 4 Townsend quintile 1 – least deprived 22/136 16 17/119 14 2 7/136 5 11/119 9 17/136 13 30/136 22 28/119 24 5 – most deprived 60/136 44 52/119 Primary diagnosis Schizophrenia/ schizoaffective 54/155 35 51/171 30 Bipolar 71/155 46 88/171 Other psychoses 30/155 19 32/171

Headline results Total cholesterol decreased in both Primrose intervention and treatment as usual groups with no significant difference between groups (5.4 mmol/L [SD 1.1] vs 5.5 mmol/L [1.1]; mean difference estimate 0.03, 95% CI –0.22 to 0.29; p=0.788). No significant differences in secondary outcomes Adjusted intra cluster correlation (ICC) = 0.07 – Effects differed more than we expected between practices

Results by randomised group Baseline 12 months Coefficient 95% CI  Variable Primrose   TAU Primrose  n/N or Mean (% or SD) Total cholesterol (mmol/L) 5.7 (0.9) 5.9 (1.0) 5.4 (1.1) 5.5 (1.1) 0.03 -0.22, 0.29 HDL cholesterol 1.3 (0.4) 1.3 (0.5) -0.01 -0/07, 0.05 Total/HDL cholesterol 4.8 (1.4) 4.9 (2.1) 4.5 (1.4) 4.4 (1.3) 0.13 -0.16, 0.42 HBA1c 41 (11) 39 (8) 40 (9) 0.14 -1.36, 1.65 Systolic 127 (17) 129 (19) 125 (16) 126 (17) -0.97 -4.34, 2.40 Diastolic 82 (11) 80 (10) 80 (0,7) 0.56 -1.69, 2.81 Body mass index 32 (6) 32 (7) -0.44 -1.18, 0.30 Waist circumference 107 (16) 108 (15) 106 (16) 107 (15) -0.55 -2.33, 1.23 AUDIT score 2 (0, 7) 3 (0, 7) 2 (0, 5) -0.51 -1.45, 0.42 Current smoker 80/155(52%) 80/171(47%) 62/134(46%) 68/155(44%) 0.79 0.36, 1.70

Headline results Overall costs were lower in Primrose vs TaU (£1286 [SE 178] vs £2182 [328]; mean difference –£895 (–1631 to –160); p=0·012) Lower psychiatric admission costs in Primrose vs TaU (£157 [135] vs £956 [313]; –£799 (–1480 to –117); p=0·018).

Difference b/w Primrose and TAU (baseline adjusted) Health care service costs by category of health care resource use at baseline and 12 months   Baseline 12 months Difference b/w Primrose and TAU (baseline adjusted) Primrose TAU Mean (SD)  Mean 95% CI  GP £177 (158) £172 (132) £143 (139) £133 (140) £5 (-26 to 35) Primary Care Nurse £34 (47) £31 (£70) £54 (65) £28 (61) £24 (9 to 39) HCA £18 (23) £15 (28) £36 (51) £13 (35) £21 (7 to 34) Community mental health £241 (393) £267 (435) £182 (279) £287 (530) -£98 (-205 to 10) A&E £48 (138) £35 (100) £39 (88) £32 (82) £6 (-13 to 26) Outpatient (physical health) £305 (557) £296 (628) £471 (848) £407 (688) £63 (-126 to 251) Outpatient (mental health) £193 (384) £238 (541) £158 (344) £177 (419) -£9 (-119 to 99) Inpatient (physical health) £117 (611) £186 (1327) £80 (448) £310 (1663) -£182 (-427 to 63) Inpatient (mental health) £972 (5983) £853 (3847) £163 (1485) £950 (4262) -£799 (-1480 to -117) Total Service Cost £2142 (6248) £2126 (4474) £1293 (1997) £2176 (4388) -£895 (-1631 to -160) Statin costs £23 (78) £12 (35) £24 (80) £15 (42) -£2 (-10 to 6) Medication £1209 (3261) £848 (1099) £1215 (2279) £1048 (1508) -£18 (-389 to 353)

Strengths and limitations Pragmatic trial – GP practices across rural and urban practices BUT all participants received CVD screening pre-baseline/ randomisation Inclusion criteria and choice of outcome? Small number of participants per practice Lack of focus on statins

Conclusions The Primrose intervention was not effective over and above routine GP practice care at reducing CVD risk factors in people with SMI ?Good care in the treatment as usual group; short duration of intervention; low prescribing rates of statins, focus on diet and physical activity not statins in goal setting? There was evidence of reduced costs and reduced psychiatric admissions in the Primrose arm. ?Regular contact with a HCP reducing the need for psychiatric service use – but could also be a chance finding?

Trial outputs and social media Osborn D, Burton A, Walters K, Nazareth I, Heinkel S, Atkins L, et al. Evaluating the clinical and cost effectiveness of a behaviour change intervention for lowering cardiovascular disease risk for people with severe mental illnesses in primary care (PRIMROSE study): study protocol for a cluster randomised controlled trial. Trials. 2016;17:80. Epub 2016/02/13 Osborn DP, Burton A, Hunter R, Marston L, Atkins L, Barnes T, et al. Clinical and cost-effectiveness of an intervention for reducing cholesterol and cardiovascular risk for people with severe mental illness in English primary care: a cluster randomised controlled trial. Lancet Psychiatry 2018; 5:145–54. https://doi.org/10.1016/S2215-0366(18)30007-5 Website: www.ucl.ac.uk/Primrose : @UCLPrimrose