AimsFamilial hypercholesterolaemia (FH) is a vastly under-diagnosed genetic disorder, associated with early development of coronary heart disease and premature mortality which can be substantially reduced by effective treatment. Patents have recently expired on high-intensity statins, reducing FH treatment costs. We build a model using UK data to estimate the cost effectiveness of DNA testing of relatives of those with monogenic FH.Methods and ResultsA Markov model was used to estimate the cost effectiveness of cascade testing, using data from UK cascade services. The estimated incremental cost effectiveness ratio (ICER) was £5806 and the net marginal lifetime cost per relative tested was £2781. More than 80% of lifetime costs were diagnosis-related and incurred in the 1st year. In UK services, 23% of 6396 index cases were mutation-positive. For each mutation-positive index case, 1.33 relatives were tested, resulting overall in a rate of 0.31 tested relatives per tested index case. If the number of relatives tested per tested index case rose to 3.2 (projected by National Institute for Health and Care Excellence in 2008) the ICER would reduce to £2280 and lifetime costs to £1092.ConclusionCascade testing of relatives of those with suspected FH is highly cost effective. The current Europe-wide high levels of undiagnosed FH, and associated morbidity and mortality, mean adoption of cascade services should yield substantial quality of life and survival gains.

ObjectiveTo evaluate uptake, risk factor detection and management from the National Health Service (NHS) Health Check (HC).DesignThis is a quasi-randomised controlled trial where participants were allocated to five cohorts based on birth year. Four cohorts were invited for an NHS HC between April 2011 and March 2015.Setting151 general practices in Hampshire, England, UK.Participants366 005 participants born 1 April 1940–31 March 1976 eligible for an NHS HC.InterventionNHS HC invitation.Main outcome measuresHC attendance and absolute percentage changes and ORs of (1) detecting cardiovascular disease (CVD) 10-year risk >10% and >20%, smokers, and total cholesterol (TC) >5.5 mmol/L and >7.5 mmol/L; (2) diagnosing hypertension, type 2 diabetes mellitus, chronic kidney disease (CKD) and atrial fibrillation (AF); and (3) new interventions with statins, antihypertensives, antiglycaemics and nicotine replacement therapy (NRT).ResultsHC attendance rose from 12% to 30% between 2011/2012 and 2014/2015 (p<0.001). HC invitation increased detection of CVD risk >10% (2.0%–3.6, p<0.001) and >20% (0.1%–0.6%, p<0.001–0.392), TC >5.5 mmol/L (4.1%–7.0%, p<0.001) and >7.5 mmol/L (0.3%–0.4% p<0.001), hypertension (0.3%–0.6%, p<0.001–0.003), and interventions with statins (0.2%–0.9%, p<0.001–0.017) and antihypertensives (0.1%–0.6%, p<0.001–0.205). There were no consistent differences in detection of smokers, NRT, or diabetes, AF or CKD. Multivariate analyses showed associations between HC invitation and detecting CVD risk >10% (OR 8.01, 95% CI 7.34 to 8.73) and >20% (5.86, 4.83 to 7.10), TC >5.5 mmol/L (3.72, 3.57 to 3.89) and >7.5 mmol/L (2.89, 2.46 to 3.38), and diagnoses of hypertension (1.33, 1.20 to 1.47) and diabetes (1.34, 1.12 to 1.61). OR of CVD risk >10% plus statin and >20% plus statin, respectively, was 2.90 (2.36 to 3.57) and 2.60 (1.92 to 3.52), and for hypertension plus antihypertensive was 1.33 (1.18 to 1.50). There were no associations with AF, CKD, antiglycaemics or NRT. Detection of several risk factors varied inversely by deprivation.ConclusionsHC invitation increased detection of cardiovascular risk factors, but corresponding increases in evidence-based interventions were modest.

ObjectiveFamilial hypercholesterolaemia (FH) affects 1 in 500 people in the UK population and is associated with premature morbidity and mortality from coronary heart disease. In 2008, National Institute for Health and Care Excellence (NICE) recommended genetic testing of potential FH index cases and cascade testing of their relatives. Commissioners have been slow to respond although there is strong evidence of cost and clinical effectiveness. Our study quantifies the recent reduced cost of providing a FH service using generic atorvastatin and compares NICE costing estimates with three suggested alternative models of care (a specialist-led service, a dual model service where general practitioners (GPs) can access specialist advice, and a GP-led service).MethodsRevision of existing 3 year costing template provided by NICE for FH services, and prediction of costs for running a programme over 10 years. Costs were modelled for the first population-based FH service in England which covers Southampton, Hampshire, Isle of Wight and Portsmouth (SHIP). Population 1.95 million.ResultsWith expiry of the Lipitor (Pfizer atorvastatin) patent the cost of providing a 10-year FH service in SHIP reduces by 42.5% (£4.88 million on patent vs £2.80 million off patent). Further cost reductions are possible as a result of the reduced cost of DNA testing, more management in general practice, and lower referral rates to specialists. For instance a dual-care model with GP management of patients supported by specialist advice when required, costs £1.89 million.ConclusionsThe three alternative models of care are now <50% of the cost of the original estimates undertaken by NICE.

We have carried out an audit of breast screening by mammography under 50 years of age in a cohort of 192 women attending family cancer clinics run by the South Thames genetic services. Of these women, six came from families in which a BRCA mutation had been identified, 61 had > 50%, 35 a 20-50% and 90 had < 20% chance of carrying a high risk mutation. In the 192 women in the screened cohort, 9 breast cancers were diagnosed (4.7%), all in high-risk women. Three were diagnosed at the prevalence screen. Three were detected mammographically at subsequent screening rounds; three were detected by breast self-examination (BSE) between screening episodes. One interval cancer was visible on mammogram at presentation but not at screening five months previously. A second cancer was also visible on mammogram at presentation but the normal screening mammogram had been 17 months earlier, outside the recommended interval. The remaining interval cancer was not visible on the mammogram. A total of 363 two-view screening mammograms were performed in the 280 person-years of follow-up; 109 additional investigations were generated: 23 recall mammograms, 18 symptomatic mammograms, 45 ultrasounds, 12 aspiration cytologies and 11 biopsies. Cytology diagnosed malignancy in 1 of 12 cases; breast biopsy in 9 of 11 cases. Twenty-three additional women had ultrasound screening only. This audit suggests that screening below the age 50 years may be unnecessary in families with a low chance of having a BRCA1 or -2 mutation, but it is important to screen high-risk women at least annually and possibly under 35 years.