1. 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

2. 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

3. 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

4. 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

5. 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):
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

6. 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)

7. 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 mmol/ml
Diabetes
Hypertension

8. 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

10. 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

11. 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

12. 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

14. 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

15. 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

16. 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

17. 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).

18. 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)

19. 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

20. 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?

21. 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.
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