The study protocol has been published previously [14]. Brief methods for the pilot study are summarised below.
Recruitment and randomisation
Practice recruitment and sample size
As this was a pilot trial, a formal sample size calculation was not required. The initial recruitment target was 100 adults per treatment arm, to ensure that the full range of inflammatory conditions was represented. To achieve this desired final sample size, we estimated that 200 patients would need to be invited per arm, allowing for approximately 50% (n = 100) consenting to participate. Previous work using the Consultation in Primary Care Archive (CiPCA) database of primary care medical records suggested that a “typical” general practice with 10,000 patients will have 25, 20, 3 and 4 patients registered with RA, PMR, AS and PsA respectively per year (GCA numbers were not available) [15]. We estimated therefore that between two and six GP practices per arm (depending on practice size and demographics) would be required. Stratified block randomisation was used; stratification was performed by practice size (splitting by order of highest/lowest practice sizes) and block sizes of 2 and/or 4 used within each stratum to ensure balanced cluster and individual patient numbers across treatment arms.
Patient recruitment
Practice staff identified an initial list of patients aged 18 years and older who had a diagnostic Read code (a UK coded thesaurus of clinical terms which provide a standardised way of recording diagnoses) for one of the 5 IRCs of interest [rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA)] in their primary care records. A general practitioner (GP) in each practice reviewed the list for exclusions (e.g. terminal illness, living in nursing home: a full list of inclusions/exclusions is contained within the protocol paper [14]). Patients were mailed a study baseline pack including a Patient Information Sheet and Baseline Questionnaire with consent form. Reminder postcards were sent after 2 weeks and a reminder invitation pack sent after 4 weeks to non-responders. Patients not responding after 4 weeks were considered non-responders. Participants who consented at baseline but did not report having one of the conditions of interest were deemed ineligible for the study and excluded (this appeared to be a particular problem for Read codes for AS; see the “Lessons learnt” section). Patients who did not complete the consent form fully were sent a second letter to confirm missing details—if this was not received after 1 month, the patients were considered ineligible responders and excluded. The study was approved by the Wales REC 5 Research Ethics Committee (REC reference 17/WA/0427). All participants provided written informed consent.
Study procedures
Responders were sent postal follow-up questionnaires at 3 months and 6 months, with reminder mailings following the same procedure as at baseline. All participants (in both intervention and control arms) received usual GP care for the duration of the study. In consenting participants, medical record review to assess the extent of primary care use was undertaken at 12 months. This was defined as the sum of primary care contacts, which could include face-to-face and telephone consultations, or scanned letters and test results (with several contacts from 1 day counting as a single contact). Furthermore, a rheumatology consultant (lead author SH) reviewed the prescribing records of medications used by participants in this period, a subset of which was subsequently grouped into lipid lowering, antihypertensives, treatments for osteoporosis and antidepressants.
Questionnaire outcome measures
Full details of the questionnaire measures included are detailed in the protocol paper [14]. Key domains included health-related quality of life (EQ-5D-5L) [16, 17], anxiety (using the Generalised Anxiety Disorder Questionnaire (GAD-7)) [18], depression (using the Patient Health Questionnaire PHQ-8) [19, 20], Patient Activation (PAM) [21], Multimorbidity Treatment Burden (MTBQ) [22] and self-efficacy (Self-Efficacy for Managing Chronic Disease) [23]. Items also measured at follow-up included treatment acceptability and credibility [24], patient satisfaction (using the General Practice Assessment Questionnaire (GPAQ)) [25] and healthcare utilisation. Unfortunately, we were unable to obtain aggregated PAM results from Insignia health and therefore are unable to report these results.
Control arm
Control participants received usual GP care for the duration of the study.
Intervention arm
Consenting patients from intervention practices were mailed an INCLUDE intervention appointment letter, giving details of the INCLUDE review appointment at their GP practice (with the option to telephone to rearrange the appointment as required). A reminder telephone call was made approximately 48 h prior to the appointment.
The INCLUDE review
The content of the INCLUDE review was developed with patients (at two patient advisory groups) and practitioners, and was designed to be a holistic consultation to include case-finding and identification and initial management of CVD (using QRISK2) [26], obesity (assessing body mass index (BMI)), fracture risk (using FRAX) [27], anxiety and depression (using GAD2 and PHQ-2 with full measures (GAD-7 and PHQ-9) used when appropriate) [18,19,20]. The consultation was recorded by the specialist nurse delivering the INCLUDE review using a study-specific EMIS computer template (the INCLUDE template), which was then saved as part of the patient’s clinical care record within EMIS at the GP study general practice, and then de-identified and securely transferred for analysis. As part of the study template, an individualised management plan was agreed with the patient who was provided with a summary sheet at the end of the review for information. A sample of INCLUDE reviews were digitally recorded, following consent obtained by a study researcher prior to the review consultation.
Nurse training
The nurses delivering the review (N = 2) (who had backgrounds in rheumatology and research) participated in an evidence-based training package delivered over two and a half days, which was designed by clinicians with input from the patient advisory group, to equip them to deliver the review. The training was delivered by members of the research team (CCG and AM). This involved the use of written materials, a slide-set, role play using simulated patients and training to use the GP software system EMIS and the INCLUDE template.
Process evaluation
A random sample of consultations were digitally recorded (n = 24). These were listened to by members of the research team and scored against a pre-specified fidelity checklist, developed by the research team (AM, CCG, EE) (for full checklist, see supplementary table), ensuring that key components of the intervention (around purpose of consultation, physical health measures, cardiovascular risk, fracture risk, mood and signposting for follow-up) had been covered within the consultation. In addition, as part of a mixed methods process evaluation to examine the acceptability of the integrated care review from the perspectives of practitioners and patients participating in the review, a nested qualitative interview study was conducted and is reported separately [28].
Pilot trial success criteria
We pre-specified a series of criteria to define the success of the pilot trial using criteria adapted from Avery et al. [29], following discussion with the TSC. To fully assess the impact of the INCLUDE intervention, we pre-specified a high retention rate as being key to inform the feasibility and economics of any future large-scale trial. Given that patients were identified in an efficient manner using GP records, it was decided a priori that an uptake rate of 50% would be acceptable. These were based on a Red Amber Green (RAG) rating system and pertained to the following:
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1.
Response rates: participant response
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Red—Uptake < 25% of eligible patients
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Amber—Uptake 25–50% of eligible patients
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Green—Uptake > 50% of eligible patients
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2.
Retention rates (at 3 and 6 months)
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3.
Intervention uptake rates (i.e. uptake from invitation to nurse- led review)
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Red—< 30% patients
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Amber—30–50% patients
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Green—> 50% patients
Statistical analysis
As a pilot study, analysis was exploratory, focused upon process outcomes. Descriptive statistics were used to summarise patient eligibility, recruitment, intervention uptake and retention in the follow-up, overall and stratified by study arm. Self-reported baseline patient data are also summarised by study arm; continuous data were summarised via means and standard deviations or median and interquartile range, depending on data skewness. We estimated means and medians, as appropriate, and associated 95% confidence intervals and interquartile range (IQR) for change between 3 months and 6 months and baseline for each outcome measure, by study arm to determine which outcomes were most sensitive to change over time. Variance component random effects models were used to estimate a range of practice-level intra-cluster correlation coefficients (ICCs), measuring proportion of the individual variance attributable to cluster membership, in order to help inform the sample size calculation for a definitive trial.
Medical records of consenting participants were reviewed for the period between baseline and 12 months follow-up, to assess extent of primary care use. Prescriptions within the first 90 days were considered as baseline (to account for being prescribed medication up to 3 monthly) and compared with those seen at 12 months.
As this study was a feasibility study and not powered to detect differences between arms, p values are not presented. All participants were analysed on a randomised complete case basis. Analyses were conducted in Stata 14 (StataCorp LP).