Bernadette Sewell

Cost effectiveness of the NHS breast screening programme: life table model

Objective To assess the overall cost effectiveness of the NHS breast screening programme, based on findings of the Independent UK Panel on Breast Cancer Screening and taking into account the uncertainty of associated estimates of benefits, harms, and costs. Design A life table model comparing data from two cohorts. Setting United Kingdom’s health service. Participants and interventions 364 500 women aged 50 years—the population of 50 year old women in England and Wales who would be eligible for screening—were followed up for 35 years without screening, compared with a similar cohort who had regular mammographic screening between ages 50 and 70 years and were then followed for another 15 years. Main outcome measures Between the cohorts, we compared the number of breast cancer diagnoses, number of deaths from breast cancer, number of deaths from other causes, person years of survival adjusted for health quality, and person years of survival with breast cancer. We also calculated the costs of treating primary and end stage breast cancer, and the costs of screening. Probabilistic sensitivity analysis explored the effect of uncertainty in key input parameters on the model outputs. Results Under the base case scenario (using input parameters derived from the Independent Panel Review), there were 1521 fewer deaths from breast cancer and 2722 overdiagnosed breast cancers. Discounting future costs and benefits at a rate of 3.5% resulted in an additional 6907 person years of survival in the screened cohort, at a cost of 40 946 additional years of survival after a diagnosis of breast cancer. Screening was associated with 2040 additional quality adjusted life years (QALYs) at an additional cost of £42.5m (€49.8m;

A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE)

64.7m) in total or £20 800 per QALY gained. The gain in person time survival over 35 years was 9.2 days per person and 2.7 quality adjusted days per person screened. Probabilistic sensitivity analysis showed that this incremental cost effectiveness ratio varied widely across a range of plausible scenarios. Screening was cost effective at a threshold of £20 000 per QALY gained in 2260 (45%) scenarios, but in 588 (12%) scenarios, screening was associated with a reduction in QALYs. Conclusion The NHS breast screening programme is only moderately likely to be cost effective at a standard threshold. However, there is substantial uncertainty in the model parameter estimates, and further primary research will be needed for cost effectiveness studies to provide definitive data to inform policy.

Effectiveness and cost-effectiveness of a universal parenting skills programme in deprived communities: multicentre randomised controlled trial

BACKGROUND Antibiotic-associated diarrhoea (AAD) occurs most commonly in older people admitted to hospital and within 12 weeks of exposure to broad-spectrum antibiotics. Although usually a mild and self-limiting illness, the 15-39% of cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)] may result in severe diarrhoea and death. Previous research has shown that probiotics, live microbial organisms that, when administered in adequate numbers, are beneficial to health, may be effective in preventing AAD and CDD. OBJECTIVES To determine the clinical effectiveness and cost-effectiveness of a high-dose, multistrain probiotic in the prevention of AAD and CDD in older people admitted to hospital. DESIGN A multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial. SETTING Medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK. PARTICIPANTS Eligible patients were aged ≥ 65 years, were exposed to one or more oral or parenteral antibiotics and were without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited. Participants were allocated sequentially according to a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the placebo arm. INTERVENTIONS Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 10(10) organisms per day) were taken daily for 21 days. The placebo was inert maltodextrin powder in identical capsules. MAIN OUTCOME MEASURES The occurrence of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by participant follow-up and checking hospital laboratory records by research nurses who were blind to arm allocation. RESULTS Analysis based on the treatment allocated included 2941 (98.7%) participants. Potential risk factors for AAD at baseline were similar in the two study arms. Frequency of AAD (including CDD) was similar in the probiotic (159/1470, 10.8%) and placebo arms [153/1471, 10.4%; relative risk (RR) 1.04; 95% confidence interval (CI) 0.84 to 1.28; p = 0.71]. CDD was an uncommon cause of AAD and occurred in 12/1470 (0.8%) participants in the probiotic and 17/1471 (1.2%) in the placebo arm (RR 0.71; 95% CI 0.34 to 1.47; p = 0.35). Duration and severity of diarrhoea, common gastrointestinal symptoms, serious adverse events and quality of life measures were also similar in the two arms. Total health-care costs per patient did not differ significantly between the probiotic (£8020; 95% CI £7620 to £8420) and placebo (£8010; 95% CI £7600 to £8420) arms. CONCLUSION We found no evidence that probiotic administration was effective in preventing AAD. Although there was a trend towards reduced CDD in the probiotic arm, on balance, the administration of this probiotic seems unlikely to benefit older patients exposed to antibiotics. A better understanding of the pathogenesis of AAD and CDD and the strain-specific effects of probiotics is needed before further clinical trials of specific microbial preparations are undertaken. Evaluation of the effectiveness of other probiotics will be difficult where other measures, such as antibiotic stewardship, have reduced CDD rates. TRIAL REGISTRATION This trial is registered as ISRCTN70017204. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 57. See the NIHR Journals Library website for further project information.

Real-time polymerase chain reaction correlates well with clinical diagnosis of Clostridium difficile infection

Objective To evaluate the effectiveness and cost utility of a universally provided early years parenting programme. Design Multicentre randomised controlled trial with cost-effectiveness analysis. Setting Early years centres in four deprived areas of South Wales. Participants Families with children aged between 2 and 4 years. 286 families were recruited and randomly allocated to the intervention or waiting list control. Intervention The Family Links Nurturing Programme (FLNP), a 10-week course with weekly 2 h facilitated group sessions. Main outcome measures Negative and supportive parenting, child and parental well-being and costs assessed before the intervention, following the course (3 months) and at 9 months using standardised measures. Results There were no significant differences in primary or secondary outcomes between trial arms at 3 or 9 months. With ‘+’ indicating improvement, difference in change in negative parenting score at 9 months was +0.90 (95%CI −1.90 to 3.69); in supportive parenting, +0.17 (95%CI −0.61 to 0.94); and 12 of the 17 secondary outcomes showed a non-significant positive effect in the FLNP arm. Based on changes in parental well-being (SF-12), the cost per quality-adjusted life year (QALY) gained was estimated to be £34 913 (range 21 485–46 578) over 5 years and £18 954 (range 11 664–25 287) over 10 years. Probability of cost per QALY gained below £30 000 was 47% at 5 years and 57% at 10 years. Attendance was low: 34% of intervention families attended no sessions (n=48); only 47% completed the course (n=68). Also, 19% of control families attended a parenting programme before 9-month follow-up. Conclusions Our trial has not found evidence of clinical or cost utility for the FLNP in a universal setting. However, low levels of exposure and contamination mean that uncertainty remains. Trial registration The trial is registered with Current Controlled Trials ISRCTN13919732.

General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial

AIM To determine the clinical utility of a rapid molecular assay for Clostridium difficile infection (CDI) in an acute hospital setting. METHODS From March to September 2011, stool specimens from inpatients in two acute hospitals with suspected CDI were tested prospectively by routine cell culture cytotoxin neutralization assay (CCNA), real-time polymerase chain reaction (PCR) using the GeneXpert (Cepheid Inc., Sunnyvale, CA, USA), and a dual testing algorithm [glutamate dehydrogenase (GDH)/toxin enzyme immuno-assay, Premier, Launch Diagnostics, Longfield, UK]. All patients with positive PCR, CCNA or discrepant results were reviewed by a multi-disciplinary team (treating clinician, gastroenterologist, microbiologist and infection control nurse). RESULTS C. difficile detection rates were 11.7% (PCR), 6% (CCNA) and 13.8% (GDH). Out of 1034 stool specimens included in the study, 974 (94.1%) had concordant CCNA and PCR results. Eighty-nine percent (886/985) had concordant CCNA, PCR and GDH results, and 94.4% (930/985) had concordant GDH and PCR results. Using clinical diagnosis as the reference, PCR had sensitivity of 99.1%, specificity of 98.9%, positive predictive value (PPV) of 91.9% and negative predictive value (NPV) of 99.9%. CCNA on a single sample had sensitivity of 51%, specificity of 99.4%, PPV of 91.9% and NPV of 94.3%. GDH had sensitivity of 83.8%, specificity of 94.5%, PPV of 64.7% and NPV of 97.9%. Almost twice as many patients were positive by PCR compared with CCNA (121 vs 62); 54/59 of those with discrepant results were clinically confirmed as CDI. CONCLUSION Rapid diagnosis of CDI using PCR was timely, accurate and correlated well with clinical diagnosis.

PWE-008 Placide: Probiotics in the Prevention of Antibiotic Associated Diarrhoea (AAD) and Clostridium Difficile Associated Diarrhoea (CDD) in Elderly Patients Admitted to Hospital – Results of a Large Multi-Centre RCT in the UK

BackgroundMost patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status.Methods/designThis is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out.DiscussionIf shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD.Trial registrationISRCTN registry, ID: ISRCTN24346473. Registered on 20 August 2014.

VP132 Cost Effectiveness Of A Predictive Risk Model In Primary Care

Introduction Antibiotic associated diarrhoea (AAD) and Clostridium difficile associated diarrhoea (CDD) occur in 5–39% of pts exposed to antibiotics. Despite previous papers proposing a beneficial role of probiotics, there has been no large randomised controlled trial evaluating their preventative effect. Methods This large RCT funded by the HTA was aimed at finding the efficacy and cost-effectiveness of a high dose, multi-strain probiotic for prevention of AAD and CDD in older people admitted to hospital. Pts aged > 65yrs, exposed to one or more oral/parenteral antibiotics without pre-existing diarrhoea, recent CDD or risk of probiotic adverse effects were eligible. Of 17,420 patients screened, 2,981(17.1%)were recruited and allocated sequentially by a computer-generated random allocation sequence stratified by centre. 1,493(50.1%)were allocated to probiotic and 1,488(49.9%)to placebo arm. Two strains of lactobacilli and two strains of bifidobacteria with a total of 6x1010 organisms/day were taken as a daily single capsule for 21 days. The placebo was inert maltodextrin powder. Occurrence of AAD or CDD within 12 weeks of recruitment was assessed by research nurses, blinded to arm allocation. Results ITT analysis included 2,941(98.7%)participants. Potential risk factors for antibiotic-associated diarrhoea at baseline were similar in both arms. The frequency of AAD was similar in the probiotic (159/1470, 10.8%)and placebo arms (153/1471, 10.4%), RR: 1.04; 95%CI0.84–1.28; P = 0.72.CDD was an uncommon cause of AAD and occurred in 12/1470(0.8%)participants in the probiotic and 17/1471(1.2%)in the placebo arm (RR 0.71; 95%CI0.34–1.47; P = 0.35).Adverse events and other outcomes were similar in both arms. Total health care costs per patient did not differ significantly between probiotics (£8020.11; 95%CI£7622.31-£8417.90) and placebo (£8011.37; 95%CI£7600.53-£8422.22).The incremental cost-effectiveness ratio of £45,636/QALY was robust to changes in key parameters. Conclusion This study found no evidence that probiotic administration was effective in the elderly in preventing AAD, although there was a trend towards reduced CDD in the probiotic arm. Disclosure of Interest S. Allen: None Declared, K. Wareham: None Declared, D. Wang: None Declared, C. Bradley: None Declared, B. Sewell: None Declared, H. Hutchings: None Declared, W. Harris: None Declared, A. Dhar Grant/Research Support from: NIHR Grant Holder, Speaker bureau with: Shire Pharmaceuticals, Warner Chilcott UK, H. Brown: None Declared, A. Foden: None Declared, M. Gravenor: None Declared, S. Plummer Employee of: Research Director of Obsidian Research Limited and Director of Cultech Limited, D. Mack: None Declared, C. Phillips: None Declared

VP172 Clinical Effectiveness Of A Predictive Risk Model In Primary Care

The deterministic ICER was GBP7,654/QALY (quality adjusted life year) for combination therapy versus monotherapy. The mean difference in ICER uncertainty for the evidence-based vs. ±15 percent variation method was GBP3,251/QALY (p = .0096). Six inputs had a mean difference in ICER uncertainty of >10 percent of GBP7,654/QALY (that is, mean difference in ICER uncertainty > GBP765) for the evidence-based variation method, compared to only two inputs for the constant percentage variation method.

Predictive risk stratification model: a progressive cluster-randomised trial in chronic conditions management (PRISMATIC) research protocol

New approaches are needed to safely reduce emergency admissions to hospital by targeting interventions effectively in primary care. A predictive risk stratification tool (PRISM) identifies each registered patient’s risk of an emergency admission in the following year, allowing practitioners to identify and manage those at higher risk. We evaluated the introduction of PRISM in primary care in one area of the United Kingdom, assessing its impact on emergency admissions and other service use.