Table 2.

Cost and resource use inputs of the model

Input	Unit Cost	Resource Use	Reference
Diagnosis
Outpatient appointment at local tertiary hospital	£330.14 [19]	1 appointment for each new patient	NHS Reference Costs 2015–2016 [19] NHS UK Genetic Testing Network, 2016 [27]
Genetic testing, WFS1 sequencing	£550.00 [27]		NHS Reference Costs 2015–2016 [19] NHS UK Genetic Testing Network, 2016 [27]
Referral to specialised service (paediatric)
Blood tests (serum osmolality, glucose, HbA1c)	£1.18 [19]		NHS Reference Costs 2015–2016 [19]
Urine osmolality test	£1.18 [19]		NHS Reference Costs 2015–2016 [19]
Genetic counselling	£481.89 [19]		NHS Reference Costs 2015–2016 [19]
MRI scan, brain	£142.99 [19]		NHS Reference Costs 2015–2016 [19]
Orthoptics assessment	£66.05 [19]		NHS Reference Costs 2015–2016 [19]
Retinal photography	£174.16 [19]		NHS Reference Costs 2015–2016 [19]
Ophthalmologist review	£118.59 [19]		NHS Reference Costs 2015–2016 [19]
Psychology assessment	£249.26 [19]	1 appointment for each new patient	NHS Reference Costs 2015–2016 [19]
Audiological examination	£151.69 [19]		NHS Reference Costs 2015–2016 [19]
Auditory brain response (ABR) testing	£29.19 [19]		NHS Reference Costs 2015–2016 [19]
ENT review	£122.78 [19]		NHS Reference Costs 2015–2016 [19]
Consultant review	£330.14 [19]		NHS Reference Costs 2015–2016 [19]
Diabetic specialist review	£391.00 [19]		NHS Reference Costs 2015–2016 [19]
Urological examination	£102.41 [19]		NHS Reference Costs 2015–2016 [19]
Urology review	£124.55 [19]		NHS Reference Costs 2015–2016 [19]
Specialised service (paediatric), annual review
Blood tests (serum osmolality, glucose, HbA1c)	£1.18 [19]	1 specialist paediatric review per patient per year [16]	NHS Reference Costs 2015–2016 [19] NHS Wolfram Syndrome Service (Birmingham Children’s Hospital), 2016 [16]
Urine osmolality test	£1.18 [19]		As above
Genetic counselling	£404.29 [19]		As above
MRI scan, brain	£142.99 [19]		As above
Orthoptics assessment	£65.21 [19]		As above
Retinal photography	£174.16 [19]		As above
Ophthalmologist review	£115.31 [19]		As above
Psychology assessment	£195.59 [19]		As above
Audiological examination	£151.69 [19]		As above
Auditory brain response (ABR) testing	£29.19 [19]		As above
ENT review	£102.65 [19]		As above
Consultant review	£228.68 [19]		As above
Diabetic specialist review	£252.57 [19]		As above
Urological examination	£102.41 [19]		As above
Urology review	£114.81 [19]		As above
Specialised service (paediatric), additional costs
Wellchild family liaison officer, per hour	£59.00 [25]	33 h per clinic	PSSRU, 2016 [25] NHS Wolfram Syndrome Service (Birmingham Children’s Hospital), 2016 [16] Expert opinion (Professor Timothy Barrett), 2016 NHS Reference Costs 2015–2016 [19]
Nurse specialist, per hour	£44.00 [25]	15 h per clinic [16]	As above
Research nurse, per hour	£44.00 [25]		As above
Clinic co-ordinator, per hour	£29.00 [25]	477 h per clinic	As above
MDT meeting, per patient	£107.35 [19]	2 MDT meetings per clinic 6 patients discussed at MDT meetings [16]	As above
Consultant, per hour	£104.00 [25]	6 h per clinic	As above
Number of paediatric specialist clinics, per year	–	4.00 [16]	As above
Transition services
Cost of transition services to adulthood, per year	£979.00 [25]	1 per new patient seen at adult specialist centre	PSSRU, 2016 [25]
Specialised service (adult), new patients
Blood tests (serum osmolality, glucose, HbA1c)	£1.18 [19]	1 per new patient seen at adult specialist centre	NHS Reference Costs 2015–2016 [19]
Urine osmolality test	£1.18 [19]		NHS Reference Costs 2015–2016 [19]
Genetic counselling	£481.89 [19]		NHS Reference Costs 2015–2016 [19]
Psychology assessment	£249.26 [19]		NHS Reference Costs 2015–2016 [19]
Consultant review	£195.87 [19]		NHS Reference Costs 2015–2016 [19]
Neurological review	£216.58 [19]		NHS Reference Costs 2015–2016 [19]
Specialised service (adult), follow-up review
Blood tests (serum osmolality, glucose, HbA1c)	£1.18 [19]	0.75 follow-up appointments per patient per year [17]	NHS Reference Costs 2015–2016 [19] NHS Wolfram Syndrome Service (Queen Elizabeth Hospital), 2016 [17]
Urine osmolality test	£1.18 [19]		As above
Genetic counselling	£404.29 [19]		As above
Psychology assessment	£195.59 [19]		As above
Consultant review	£150.38 [19]		As above
Neurological review	£160.76 [19]		As above
DM care
Paediatric outpatient diabetes care, per year	£2925.00 [20]	N/A (costs given are per patient with DM per year)	NHS National Tariff 2016–2017 [20] Cummins et al. 2010 [15] Patient experience (Wolfram Focus Group), 2016 [30] NHS Reference Costs 2015–2016 [19] Expert opinion (Professor Timothy Barrett), 2016 NHS Vale of York CCG, 2015 [21] NHS Southern Derbyshire CCG, 2016, UK [24]
Insulin treatment, multiple daily injections, average annual cost of consumables	£984.10 [15]		As above
Insulin treatment, continuous subcutaneous insulin infusions, average annual cost of consumables	£2863.85 [15]		As above
Endocrinologist outpatient appointment for diabetes management, adult services	£150.38 [19]	2 appointments per year [30]	As above
Diabetic specialist nurse appointment, adult services	£70.59 [19]	2 appointments per year	As above
Diabetic specialist nurse telephone appointment, adult services	£29.90 [19]	2 appointments per year	As above
Diabetic education service appointment	£44.33 [19]	1 appointment per year	As above
Coeliac serology, IgA tTG test	£23.75 [21]	1 per patient with symptoms suggestive of coeliac disease per year	As above
Coeliac serology, EMA test	£11.62 [21]		As above
Duodenal biopsy	£868.79 [19]	1 per patient with coeliac disease per year	As above
Dietician, community health service	£81.32 [19]	3 visits for coeliac disease per year [24]	As above
Ketoacidosis, inpatient care	£600.03 [19]	1 per patient with ketoacidosis per year	As above
Severe hypoglycaemic events, inpatient care	£413.39 [19]	1 per patient with hypoglycaemic event per year	As above
DM complications
Myocardial infarction, year of event	£6234.64 [26]	N/A	Roze et al. 2005 [26]
Myocardial infarction, each subsequent year	£1027.06 [26]		Roze et al. 2005 [26]
Angina, year of onset	£3234.06 [26]		Roze et al. 2005 [26]
Angina, each subsequent year	£1067.37 [26]		Roze et al. 2005 [26]
Congestive heart failure, year of onset	£3606.53 [26]		Roze et al. 2005 [26]
Congestive heart failure, each subsequent year	£1229.97 [26]		Roze et al. 2005 [26]
Stroke, fatal	£4810.09 [26]		Roze et al. 2005 [26]
Stroke, year of event	£3813.61 [26]		Roze et al. 2005 [26]
Stroke, each subsequent year	£7225.56 [26]		Roze et al. 2005 [26]
Peripheral vascular disease, onset	£3321.62 [26]		Roze et al. 2005 [26]
Haemodialysis	£35,352.31 [26]		Roze et al. 2005 [26]
Peritoneal dialysis	£26,543.77 [26]		Roze et al. 2005 [26]
Kidney transplant, first year	£27,795.98 [26]		Roze et al. 2005 [26]
Kidney transplant, subsequent year	£9151.83 [26]		Roze et al. 2005 [26]
Retinal photocoagulation	£958.96 [26]		Roze et al. 2005 [26]
Cataract extraction	£2208.39 [26]		Roze et al. 2005 [26]
Cataract annual follow-up	£148.71 [26]		Roze et al. 2005 [26]
Neuropathy, onset	£1352.27 [26]		Roze et al. 2005 [26]
Uninfected ulcer	£1778.94 [26]		Roze et al. 2005 [26]
Infected ulcer	£1823.42 [26]		Roze et al. 2005 [26]
Major hypoglycaemic event	£307.15 [26]		Roze et al. 2005 [26]
DI and other endocrine disorders care
Blood tests (serum osmolality, glucose, HbA1c)	£1.18 [19]	1 appointment for each new patient	NHS Reference Costs 2015–2016 [19] BNF, March 2016 [14] BNF, May 2016 [14] PSSRU, 2016 [25]
Desmopressin acetate, nasal spray, 10 micrograms/metered spray, 60 metered sprays	£8.76 [14]	2 metered sprays per day [14]	As above
Testosterone enanthate, 250 mg/1 mL solution for injection ampoules, 3 ampoules	£72.50 [14]	1 ampoule per month per male paediatric patient with hypogonadism	As above
Testosterone undecanoate, 250 mg/1 mL solution for injection, 1000 mg/4 mL, 1 vial	£80.00 [14]	1 g per 12 weeks per male adult patient with hypogonadism	As above
GP nurse attendance for testosterone administration, per visit	£9.30 [25]	1 per injection	As above
Estradiol valerate 1 mg, 28 tablets	£3.53 [14]	1 per 3 months per female patient with hypogonadism	As above
Desogestrel 75 microgram, 84 tablets	£5.21 [14]	1 per 3 months per female patient with hypogonadism	As above
Visual impairment care
Optometry assessment	£95.84 [19]	2 per year per patient both before and after symptom onset [30]	NHS Reference Costs 2015–2016 [19] Patient experience (Wolfram Focus Group), 2016 [30] Federation of (Ophthalmic and Dispensing) Opticians, 2016 [18] Warren 1995 [28]
Retinal photography	£174.16 [19]		As above
Ophthalmologist review at local centre	£115.31 [19]		As above
Glasses, single vision lenses, ≤6 dioptres SPH	£39.10 [18]	1 averaged cost per patient per year	As above
Glasses, single vision lenses, > 6–≤10 dioptres SPH	£59.30 [18]		As above
Glasses, single vision lenses, > 10–≤14 dioptres SPH	£86.90 [18]		As above
Glasses, single vision lenses, > 14 dioptres SPH	£196.00 [18]		As above
Cataract surgery	£875.11 [19]	1 per patient requiring cataract surgery	As above
Low vision services assessment	£78.31 [19]	1 per patient requiring visual impairment care	As above
Occupational therapist visit	£131.02 [19]	6 visits per year per patient requiring visual impairment care [28]	As above
Hearing impairment care
Audiological examination	£151.69 [19]	1 per year per patient both before and after symptom onset [30]	NHS Reference Costs 2015–2016 [19] Patient experience (Wolfram Focus Group), 2016 [30]
Auditory brain response (ABR) testing	£29.19 [19]		As above
ENT annual review	£102.65 [19]		As above
Audiology hearing aid fitting	£89.58 [19]	1 per patient requiring hearing aid	As above
Audiology hearing aid follow-up	£96.90 [19]		As above
Audiology annual review	£358.31 [19]	1 per patient with SNHL per year	As above
Cochlear implants, bilateral	£31,481.77 [19]	1 per patient requiring cochlear implant	As above
ENT follow-up post-implant for external cochlear implant fitting	£89.14 [19]		As above
Audiology follow-up post-implant, maintenance and programming	£291.73 [19]		As above
ENT annual review for severe hearing loss	£89.14 [19]		As above
Renal/neurogenic bladder care
Urodynamic studies, paediatrics	£102.41 [19]	1 review per patient per year prior to symptom onset [30] 2 reviews per patient per year after symptom onset [29]	NHS Reference Costs 2015–2016 [19] Patient experience (Wolfram Focus Group), 2016 [30] Wolfram Syndrome Guideline Development Group, 2014, Europe [29] NCGC Infection prevention and control, 2012 [12] NCGC Urinary incontinence in neurological disease, 2012 [12] NHS Drug Tariff, May 2016 [22]
Urodynamic studies, adult services	£134.75 [19]		As above
Urology review, paediatrics	£114.81 [19]		As above
Urology review, adult services	£99.79 [19]		As above
Urine dipstick	£1.18 [19]		As above
Intermittent self-catheterisation, mean annual cost	£2771.58 [12]	Annual cost for patients managed by clean intermittent self-catheterisation [12]	As above
Indwelling catheter	£5.22 [12]	7 indwelling catheter changes per patient per year with indwelling catheter [22]	As above
Catheter leg bag	£2.39 [22]	60 drainage bag changes per patient per year with neurogenic bladder [22]	As above
Catheter drainage bag	£1.10 [22]		As above
Annual cost of symptomatic UTI	£40.06 [12]	Annual cost for patients with different forms of UTI and urethral complication	As above
Annual cost of first-line antibiotic resistant UTI	£60.42 [12]		As above
Annual cost of multidrug resistant UTI	£2232.50 [12]		As above
Annual cost of bacteraemia secondary to UTI	£3535.95 [12]		As above
Annual cost of urethral complication	£1402.07 [12]		As above
Mental health care initial assessment	£257.59 [19]	1 appointment per patient after symptom onset [30]	As above
Community mental health care, adult	£120.61 [19]	1 appointment per patient per year after symptom onset [30]	As above
Inpatient treatment of psychiatric disorders, per bed day	£390.20 [19]	15 days review period per patient [30]	As above
Rehabilitation of psychiatric disorders	£377.77 [19]	1 appointment per patient per year after symptom onset [30]	As above
Neurological care
Neurological review, paediatric	£343.79 [19]	1 review per patients per year prior to symptom onset [29] 2 reviews per patient per year after symptom onset [4]	NHS Reference Costs 2015–2016 [19] Wolfram Syndrome Guideline Development Group, 2014, Europe [29] Urano et al. 2016 [4] Expert opinion (Professor Timothy Barrett), 2016 NHS Bolton Foundation Trust, 2015 [23]
Neurological review, adult services	£160.76 [19]		As above
Specialist nurse, paediatric, community health services	£137.36 [19]	2 appointments per patient per year after symptom onset	As above
Specialist nurse, telephone appointment, paediatric, community health services	£43.23 [19]	2 appointments per patient per year after symptom onset	As above
Specialist nurse, adult services, community health services	£77.24 [19]	1 appointment per patient per year after symptom onset	As above
Specialist nurse, adult services, telephone appointment, community health services	£33.08 [19]		As above
Physiotherapy, first appointment	£56.60 [19]		As above
Physiotherapy, follow-up	£45.86 [19]		As above
Speech and language therapist, first appointment	£87.04 [19]		As above
Speech and language therapist, follow-up	£99.32 [19]		As above
Occupational therapist, first appointment	£142.11 [19]		As above
Occupational therapist, follow-up	£58.25 [19]		As above
Clinical physiology, first appointment	£76.39 [19]		As above
Clinical physiology, follow-up	£51.58 [19]		As above
Gastroenterologist, first appointment	£164.54 [19]		As above
Gastroenterologist, follow-up	£132.50 [19]		As above
Podiatry, community health services	£39.88 [19]	1 appointment per patient per year after symptom onset and during late-stage symptoms	As above
Rehabilitation services	£94.26 [19]	1 appointment per patient per year after symptom onset	As above
MRI scan, brain and spine	£133.64 [19]	1 appointment per patient per year after symptom onset	As above
Nerve conduction studies, paediatric	£281.58 [19]		As above
Nerve conduction studies, adult services	£206.71 [19]		As above
Sleep studies	£501.71 [19]		As above
Bronchoscopy, paediatric	£1589.23 [19]		As above
Bronchoscopy, adult services	£632.10 [19]		As above
Tracheostomy insertion	£3489.92 [19]		As above
Orthopaedics, paediatrics, first appointment	£135.97 [19]	1 appointment per patient per year after symptom onset	As above
Orthopaedics, adult services, first appointment	£135.74 [19]	1 appointment per patient per year after symptom onset	As above
Orthopaedics, adult services, follow-up	£109.51 [19]		As above
Walking aids	£7.60 [23]	1 per patient requiring wheelchair or walking aids	As above
Wheelchair, assessment, paediatric	£309.04 [19]		As above
Wheelchair, equipment, paediatric	£485.57 [19]		As above
Wheelchair, maintenance, paediatric	£66.47 [19]		As above
Wheelchair, review, paediatric	£249.11 [19]		As above
Wheelchair, assessment	£247.21 [19]		As above
Wheelchair, equipment	£167.64 [19]		As above
Wheelchair, maintenance	£60.03 [19]		As above
Wheelchair, review	£151.66 [19]		As above
Psychological/psychiatric care
Community mental health care, paediatric	£242.38 [19]	12 appointments per patient with symptoms per year [30]	NHS Reference Costs 2015–2016 [19] Patient experience (Wolfram Focus Group), 2016 [30]
Mental health care initial assessment	£257.59 [19]	1 appointment per patient after symptom onset [30]	As above
Community mental health care, adult	£120.61 [19]	1 appointment per patient per year after symptom onset [30]	As above
Inpatient treatment of psychiatric disorders, per bed day	£390.20 [19]	15 days review period per patient [30]	As above
Rehabilitation of psychiatric disorders	£377.77 [19]	1 appointment per patient per year after symptom onset [30]	As above

ABR auditory brain response, BNF British National Formulary, CCG Clinical Commissioning Group, DI diabetes insipidus, DM diabetes mellitus, EMA endomysial antibody, ENT ear, nose and throat, GP general practitioner, HbA1c haemoglobin A1c, IgA immunoglobulin A, MDT multi-disciplinary team, MRI magnetic resonance imaging, NCGC National Clinical Guideline Centre, NHS National Health Service, PSSRU Personal Social Services Research Unit, SALT Speech and Language Therapist, SPH sphere, tTG tissue transglutaminase, UTI urinary tract infection, WFS1 Wolfram syndrome type 1 (gene)