The model had a time cycle of one-month, believed sufficiently short that half cycle correction was not performed and both costs and health were discounted at a.
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Doherty M, Jenkins W, Richardson H, et al. Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial. Lancet 2018; 392: 1403–12.
Appendix Contents 1 Key elements to be included within patient information on gout 2. Technical Appendix – cost-effectiveness 3. Participants who remained versus participants who dropped out: comparison by group 4. Mean change in BMI and renal function: Complete case analysis 5. Allopurinol use during the trial: per protocol analysis 6. Number of nurse contacts 7. Risk ratios (RRs) and 95% confidence intervals (CIs) of dichotomous efficacy outcomes: per protocol analysis 8. Mean (SD) of serum urate, tophi size and quality of life scores at baseline, year 1 and year 2: per protocol analysis 9. Participating General Practices
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Appendix 1. Key elements to be included within patient information on gout (1)
A clear verbal explanation of gout backed up by written information (e.g. Arthritis Research UK patient booklet). The explanation should include the following key messages: • • • • • • • • •
(2)
we know its cause - it is due to deposition of urate crystals in and around peripheral joints crystals form when serum urate (SU) levels rise above the critical “saturation point” for crystal formation in people with persistently raised SU, crystals slowly accumulate without causing any symptoms when sufficient crystals have formed in cartilage some occasionally “spill out” into the joint cavity, triggering severe inflammation of the joint lining and presenting as a gout flare over many years gout flares may increase in frequency and spread to involve other joints in addition to gout flares, continuing deposition may eventually result in hard, slowly expanding lumps of crystals (“tophi”) that can damage joint cartilage and bone and even appear as palpable lumps under the skin in some people the joint damage (i.e. osteoarthritis) caused by tophi can result in regular daily pain when using the joints also there is increasing concern that persistently high urate levels increase the risk of atherosclerosis, heart disease, chronic kidney disease and dying younger reduction and maintenance of SU levels below the saturation point (1) stops production of new crystals and (2) encourages existing crystals to dissolve – so eventually there are no crystals and therefore no gout. An individualised explanation of relevant risk factors that elevate urate above the saturation point (insufficient elimination or too much production of urate) including:
• • • • •
hereditary factors that result in inefficient renal excretion of urate a high body mass – most urate in the body is made by the body’s cells by breaking down “purines” and this production increases with overweight and obesity a diet containing plenty of foods that are high in purines drugs (such as diuretics) that reduce the kidney’s ability to excrete urate chronic renal impairment from any cause often greatly reduces urate excretion
(3)
Individualised advice on management of a gout flare (selecting from ice packs, oral colchicine, oral NSAID plus PPI, oral corticosteroid)
(4)
Individualised advice on ways to reduce urate levels by lifestyle modification, if this is appropriate (e.g. reducing weight if overweight or obese, reduction in excessive intake of beer or high-purine foods)
(5)
Advice on ULT (in line with current recommended guidelines), including a slow upward titration regimen when initiating ULT (with approximately one month between each incremental increase in ULT), consideration of prophylaxis (to reduce risk of provoking flares through crystal shedding), and allopurinol as the first-line drug to consider (febuxostat and available uricosurics also considered, as appropriate).
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Appendix 2. Technical Appendix – Cost Effectiveness Methods. Model structure The model has two stages. The first stage is for a period of two years and is a replication of the data observed in the RCT, the second part used a Markov model to extrapolate results beyond the duration of the study to a maximum of 20 years. In the RCT stage data from the trial were used, alongside published estimates which informed the costs, patient utility, and incidence of gout flares, in the Markov stage the model was populated by data within the literature or data collected within the RCT and with the assumption of no further nurse-led management, although this assumption was relaxed in a sensitivity analysis whereby the addition of an extra hour of nurse time for two 6 monthly reviews or one yearly review, as undertaken for many other chronic conditions, was conducted. Patients were classified into one of four serum urate (SU) levels, measured in µmol/L: SU
