Efficiency and productivity gains of robotic surgery: The case of the English National Health Service.

This paper examines the effect of new medical technology (robotic surgery) on efficiency gains and productivity changes for surgical treatment in patients with prostate cancer from the perspective of a public health sector organization. In particular, we consider three interrelated surgical technologies within the English National Health System: robotic, laparoscopic and open radical prostatectomy. Robotic and laparoscopic techniques are minimally invasive procedures with similar clinical benefits. While the clinical benefits in adopting robotic surgery over laparoscopic intervention are unproven, it requires a high initial investment cost and carries high on-going maintenance costs. Using data from Hospital Episode Statistics for the period 2000-2018, we observe growing volumes of prostatectomies over time, mostly driven by an increase in robotic-assisted surgeries, and further analyze whether hospital providers that adopted a robot see improved measures of throughput. We then quantify changes in total factor and labor productivity arising from the use of this technology. We examine the impact of robotic adoption on efficiency gains employing a staggered difference-in-difference estimator and find evidence of a 50% reduction in length of stay (LoS), 49% decrease in post-LoS and 44% and 46% decrease in postoperative visits after 1 year and 2 years, respectively. Productivity analysis shows the growth in radical prostatectomy volume is sustained with a relatively stable number of urology surgeons. The robotic technique increases total production at the hospital level between 21% and 26%, coupled with a 29% improvement in labor productivity. These benefits lend some, but not overwhelming support for the large-scale hospital investments in such costly technology.

The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2.

BACKGROUND: Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). METHODS: Our study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. RESULTS: Our study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY. CONCLUSION: OC surveillance for women deferring RRSO in a 'real-world' setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.

Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial.

BACKGROUND: In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy. METHODS: UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50-74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov, NCT00058032. FINDINGS: 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04-13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4-13·0; p=0·042) at 18 years (21% [95% CI 15·6-26·2] vs 14% [95% CI 10·5-17·4]). INTERPRETATION: To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer. FUNDING: National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal.

Ovarian cancer symptoms in pre-clinical invasive epithelial ovarian cancer - An exploratory analysis nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

OBJECTIVE: UKCTOCS provides an opportunity to explore symptoms in preclinical invasive epithelial ovarian cancer (iEOC). We report on symptoms in women with pre-clinical (screen-detected) cancers (PC) compared to clinically diagnosed (CD) cancers. METHODS: In UKCTOCS, 202638 postmenopausal women, aged 50-74 were randomly allocated (April 17, 2001-September 29, 2005) 2:1:1 to no screening or annual screening till Dec 31,2011, using a multimodal or ultrasound strategy. Follow-up was through national registries. An outcomes committee adjudicated on OC diagnosis, histotype, stage. Eligible women were those diagnosed with iEOC at primary censorship (Dec 31, 2014). Symptom details were extracted from trial clinical-assessment forms and medical records. Descriptive statistics were used to compare symptoms in PC versus CD women with early (I/II) and advanced (III/IV/unable to stage) stage high-grade-serous (HGSC) cancer. ISRCTN-22488978; ClinicalTrials.gov-NCT00058032. RESULTS: 1133 (286PC; 847CD) women developed iEOC. Median age (years) at diagnosis was earlier in PC compared to CD (66.8PC, 68.7CD, p = 0.0001) group. In the PC group, 48% (112/234; 90%, 660/730CD) reported symptoms when questioned. Half PC (50%, 13/26PC; 36%, 29/80CD; p = 0.213) women with symptomatic HGSC had >1symptom, with abdominal symptoms most common, both in early (62%, 16/26, PC; 53% 42/80, CD; p = 0.421) and advanced (57%, 49/86, PC; 74%, 431/580, CD; p = 0.001) stages. In symptomatic early-stage HGSC, compared to CD, PC women reported more gastrointestinal (change in bowel habits and dyspepsia) (35%, 9/26PC; 9%, 7/80CD; p = 0.001) and systemic (mostly lethargy/tiredness) (27%, 7/26PC; 9%, 7/80CD; p = 0.017) symptoms. CONCLUSIONS: Our findings, add to the growing evidence, that we should reconsider what constitutes alert symptoms for early tubo-ovarian cancer. We need a more nuanced complex of key symptoms which is then evaluated and refined in a prospective trial.

What is the right level of spending needed for health and care in the UK?

The health and care sector plays a valuable role in improving population health and societal wellbeing, protecting people from the financial consequences of illness, reducing health and income inequalities, and supporting economic growth. However, there is much debate regarding the appropriate level of funding for health and care in the UK. In this Health Policy paper, we look at the economic impact of the COVID-19 pandemic and historical spending in the UK and comparable countries, assess the role of private spending, and review spending projections to estimate future needs. Public spending on health has increased by 3·7% a year on average since the National Health Service (NHS) was founded in 1948 and, since then, has continued to assume a larger share of both the economy and government expenditure. In the decade before the ongoing pandemic started, the rate of growth of government spending for the health and care sector slowed. We argue that without average growth in public spending on health of at least 4% per year in real terms, there is a real risk of degradation of the NHS, reductions in coverage of benefits, increased inequalities, and increased reliance on private financing. A similar, if not higher, level of growth in public spending on social care is needed to provide high standards of care and decent terms and conditions for social care staff, alongside an immediate uplift in public spending to implement long-overdue reforms recommended by the Dilnot Commission to improve financial protection. COVID-19 has highlighted major issues in the capacity and resilience of the health and care system. We recommend an independent review to examine the precise amount of additional funds that are required to better equip the UK to withstand further acute shocks and major threats to health.

The changing health needs of the UK population.

The demographics of the UK population are changing and so is the need for health care. In this Health Policy, we explore the current health of the population, the changing health needs, and future threats to health. Relative to other high-income countries, the UK is lagging on many health outcomes, such as life expectancy and infant mortality, and there is a growing burden of mental illness. Successes exist, such as the striking improvements in oral health, but inequalities in health persist as well. The growth of the ageing population relative to the working-age population, the rise of multimorbidity, and persistent health inequalities, particularly for preventable illness, are all issues that the National Health Service (NHS) will face in the years to come. Meeting the challenges of the future will require an increased focus on health promotion and disease prevention, involving a more concerted effort to understand and tackle the multiple social, environmental, and economic factors that lie at the heart of health inequalities. The immediate priority of the NHS will be to mitigate the wider and long-term health consequences of the COVID-19 pandemic, but it must also strengthen its resilience to reduce the impact of other threats to health, such as the UK leaving the EU, climate change, and antimicrobial resistance.

Securing a sustainable and fit-for-purpose UK health and care workforce.

Approximately 13% of the total UK workforce is employed in the health and care sector. Despite substantial workforce planning efforts, the effectiveness of this planning has been criticised. Education, training, and workforce plans have typically considered each health-care profession in isolation and have not adequately responded to changing health and care needs. The results are persistent vacancies, poor morale, and low retention. Areas of particular concern highlighted in this Health Policy paper include primary care, mental health, nursing, clinical and non-clinical support, and social care. Responses to workforce shortfalls have included a high reliance on foreign and temporary staff, small-scale changes in skill mix, and enhanced recruitment drives. Impending challenges for the UK health and care workforce include growing multimorbidity, an increasing shortfall in the supply of unpaid carers, and the relative decline of the attractiveness of the National Health Service (NHS) as an employer internationally. We argue that to secure a sustainable and fit-for-purpose health and care workforce, integrated workforce approaches need to be developed alongside reforms to education and training that reflect changes in roles and skill mix, as well as the trend towards multidisciplinary working. Enhancing career development opportunities, promoting staff wellbeing, and tackling discrimination in the NHS are all needed to improve recruitment, retention, and morale of staff. An urgent priority is to offer sufficient aftercare and support to staff who have been exposed to high-risk situations and traumatic experiences during the COVID-19 pandemic. In response to growing calls to recognise and reward health and care staff, growth in pay must at least keep pace with projected rises in average earnings, which in turn will require linking future NHS funding allocations to rises in pay. Through illustrative projections, we show that, to sustain annual growth in the workforce at approximately 2·4%, increases in NHS expenditure of 4% annually in real terms will be required. Above all, a radical long-term strategic vision is needed to ensure that the future NHS workforce is fit for purpose.

Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS. METHODS: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032. FINDINGS: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group. INTERPRETATION: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended. FUNDING: National Institute for Health Research, Cancer Research UK, and The Eve Appeal.

Evaluation of progress toward universal health coverage in Myanmar: A national and subnational analysis.

BACKGROUND: Universal health coverage (UHC) encompasses 2 main components: access to essential healthcare services and protection from financial hardship when using healthcare. This study examines Myanmar's efforts to achieve UHC on a national and subnational level. It is a primer of studying the concept of UHC on a subnational level, and it also establishes a baseline for assessing future progress toward reaching UHC in Myanmar. METHODS AND FINDINGS: The study uses the Demographic and Health Survey (2015) and the Myanmar Living Conditions Survey (MLCS; 2017) and adapts a previously developed UHC index to provide insights into the main barriers preventing the country's progress toward UHC. We find a negative correlation between the UHC index and the state/region poverty levels. The equity of access analysis reveals significant pro-rich inequity in access to all essential healthcare services. Socioeconomic status and limited availability of healthcare infrastructure are the main driving forces behind the unequal access to interventions that are crucial to achieving UHC by 2030. Finally, financial risk protection analysis shows that the poor are less likely to use healthcare services, and, once they do, they are at a greater risk of suffering financial catastrophe. Limitations of this study revolve around its correlational, rather than causal, nature. CONCLUSIONS: We suggest a 2-pronged approach to help Myanmar achieve UHC: Government and state authorities should reduce the financial burden of seeking healthcare, and, coupled with this, significant investment in and expansion of health infrastructure and the health workforce should be made, particularly in the poorer and more remote states.

Predicting Hospital Resource Use During COVID-19 Surges: A Simple but Flexible Discretely Integrated Condition Event Simulation of Individual Patient-Hospital Trajectories.

OBJECTIVES: To assist with planning hospital resources, including critical care (CC) beds, for managing patients with COVID-19. METHODS: An individual simulation was implemented in Microsoft Excel using a discretely integrated condition event simulation. Expected daily cases presented to the emergency department were modeled in terms of transitions to and from ward and CC and to discharge or death. The duration of stay in each location was selected from trajectory-specific distributions. Daily ward and CC bed occupancy and the number of discharges according to care needs were forecast for the period of interest. Face validity was ascertained by local experts and, for the case study, by comparing forecasts with actual data. RESULTS: To illustrate the use of the model, a case study was developed for Guy's and St Thomas' Trust. They provided inputs for January 2020 to early April 2020, and local observed case numbers were fit to provide estimates of emergency department arrivals. A peak demand of 467 ward and 135 CC beds was forecast, with diminishing numbers through July. The model tended to predict higher occupancy in Level 1 than what was eventually observed, but the timing of peaks was quite close, especially for CC, where the model predicted at least 120 beds would be occupied from April 9, 2020, to April 17, 2020, compared with April 7, 2020, to April 19, 2020, in reality. The care needs on discharge varied greatly from day to day. CONCLUSIONS: The DICE simulation of hospital trajectories of patients with COVID-19 provides forecasts of resources needed with only a few local inputs. This should help planners understand their expected resource needs.

Ovarian cancer symptoms, routes to diagnosis and survival - Population cohort study in the 'no screen' arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

OBJECTIVE: There are widespread efforts to increase symptom awareness of 'pelvic/abdominal pain, increased abdominal size/bloating, difficulty eating/feeling full and urinary frequency/urgency' in an attempt to diagnose ovarian cancer earlier. Long-term survival of women with these symptoms adjusted for known prognostic factors is yet to be determined. This study explored the association of symptoms, routes and interval to diagnosis and long-term survival in a population-based cohort of postmenopausal women diagnosed with invasive epithelial tubo-ovarian cancer (iEOC) in the 'no screen' (control) UKCTOCS arm. METHODS: Of 101,299 women in the control arm, 574 were confirmed on outcome review to have iEOC between randomisation (2001-2005) and 31 December 2014. Data was extracted from medical notes and electronic records. A multivariable model was fitted for individual symptoms, time interval from symptom onset to diagnosis, route to diagnosis, speciality, morphological Type, age at diagnosis, year of diagnosis (period effect), stage, primary treatment, and residual disease. RESULTS: Women presenting with symptoms listed in the NICE guidelines (HR1.48, 95%CI1.16-1.89, p = 0.001) or the modified Goff Index (HR1·68, 95%CI1·32-2.13, p < 0.0001) had significantly worse survival than those who did not. Each additional presenting symptom decreased survival (HR1·20, 95%CI1·12-1·28, p < 0.0001). In multivariable analysis, in addition to advanced stage, increasing residual disease and inadequate primary treatment, abdominal pain and loss of appetite/feeling full were significantly associated with increased mortality. CONCLUSIONS: The ovarian cancer symptom indices identify postmenopausal women with a poorer prognosis. This study however cannot exclude the possibility of better outcomes in those who are aware and act on their symptoms.

Leveraging DICE (Discretely-Integrated Condition Event) Simulation to Simplify the Design and Implementation of Hybrid Models.

OBJECTIVES: Using an example of an existing model constructed by the National Institute for Health and Care Excellence (NICE) to inform a real health technology assessment, this study seeks to demonstrate how a discretely integrated condition event (DICE) simulation can improve the implementation of Markov models. METHODS: Using the technical report and spreadsheet, the original model was translated to a standard DICE simulation without making any changes to the design. All original analyses were repeated and the results were compared. Aspects that could have improved the original design were then considered. RESULTS: The original model consisted of 32 copies (8 risk strata × 4 treatments) of the Markov structure, containing more than 6000 Microsoft Excel® formulas (18 MB files). Three aspects (nonadherence, scheduled treatment stop, and end of fracture risk) were handled by incorporating weighted averages into the cycle-specific calculations. The DICE implementation used 3 conditions to represent the states and a single transition event to apply the probabilities; 3 additional events processed the special aspects, and profiles handled the 8 strata (0.12 MB file). One replication took 16 seconds. The original results were reproduced but extensive additional sensitivity analyses, including structural analyses, were enabled. CONCLUSION: Implementing a real Markov model using DICE simulation both preserves the advantages of the approach and expands the available tools, improving transparency and ease of use and review.

Improving quality care for diabetes in the community: What do Cypriot patients want?

OBJECTIVE: To measure patient preferences for their diabetic care in community setting. DESIGN: Discrete-choice survey. SETTING: Community setting (primary physician and hospital sites) in Cyprus. PARTICIPANTS: Diabetic patients attending community sites. MAIN OUTCOME MEASURE(S): Patient preferences, to estimate which components of quality healthcare service people value, their relative importance but also the potential shift to shared decision-making (SDM). RESULTS: Older respondents with experience of the private sector already received SDM (managing their care and choosing their treatments; detailed and accurate information, continuity of care; compassion for their personal situation) from their primary care physician with waiting time shorter than 1 h. They valued their 'current' option and they did not want to change it with other services. Younger people from the public sector valued a change in policy and wanted to move from their 'current' to alternative diabetic care services where the waiting times were shorter, they could not only manage their care but also choose their treatments (together with receiving information, continuity of care and compassionate care). Individuals agreed with receiving multidisciplinary care from a team of healthcare providers but they mostly preferred being supported by their primary care physician. The pooled sample valued their 'current' option but they also supported policy changes that would implement SDM service for everybody. CONCLUSIONS: Diabetic patients value SDM and are willing to support a shift of practice to receive it not only in the private but also in the public sector. The forthcoming National Health Insurance Service would aim to address such developments as anticipated both in the European Troika's recommendations and the relevant laws.

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: To assess the within-trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy. METHODS: Within-trial economic evaluation of no screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second-line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model. RESULTS: Using a CA125-ROCA cost of £20, the within-trial results show USS to be strictly dominated by MMS, with the MMS vs C comparison returning an incremental cost-effectiveness ratio (ICER) of £91 452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15, the ICER becomes £77 818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30 033 per LYG, while Markov modelling produces an ICER of £46 922 per QALY. CONCLUSION: Analysis suggests that, after accounting for the lead time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared with the within-trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations.

BACKGROUND: Newer approaches to genetic counselling are required for population-based testing. We compare traditional face-to-face genetic counselling with a DVD-assisted approach for population-based BRCA1/2 testing. METHODS: A cluster-randomised non-inferiority trial in the London Ashkenazi Jewish population. INCLUSION CRITERIA: Ashkenazi Jewish men/women >18 years; exclusion criteria: (a) known BRCA1/2 mutation, (b) previous BRCA1/2 testing and (c) first-degree relative of BRCA1/2 carrier. Ashkenazi Jewish men/women underwent pre-test genetic counselling prior to BRCA1/2 testing in the Genetic Cancer Prediction through Population Screening trial (ISRCTN73338115). Genetic counselling clinics (clusters) were randomised to traditional counselling (TC) and DVD-based counselling (DVD-C) approaches. DVD-C involved a DVD presentation followed by shorter face-to-face genetic counselling. Outcome measures included genetic testing uptake, cancer risk perception, increase in knowledge, counselling time and satisfaction (Genetic Counselling Satisfaction Scale). Random-effects models adjusted for covariates compared outcomes between TC and DVD-C groups. One-sided 97.5% CI was used to determine non-inferiority. SECONDARY OUTCOMES: relevance, satisfaction, adequacy, emotional impact and improved understanding with the DVD; cost-minimisation analysis for TC and DVD-C approaches. RESULTS: 936 individuals (clusters=256, mean-size=3.6) were randomised to TC (n=527, clusters=134) and DVD-C (n=409, clusters=122) approaches. Groups were similar at baseline, mean age=53.9 (SD=15) years, women=66.8%, men=33.2%. DVD-C was non-inferior to TC for increase in knowledge (d=-0.07; lower 97.5% CI=-0.41), counselling satisfaction (d=-0.38, 97.5% CI=1.2) and risk perception (d=0.08; upper 97.5% CI=3.1). Group differences and CIs did not cross non-inferiority margins. DVD-C was equivalent to TC for uptake of genetic testing (d=-3%; lower/upper 97.5% CI -7.9%/1.7%) and superior for counselling time (20.4 (CI 18.7 to 22.2) min reduction (p<0.005)). 98% people found the DVD length and information satisfactory. 85-89% felt it improved their understanding of risks/benefits/implications/purpose of genetic testing. 95% would recommend it to others. The cost of genetic counselling for DVD-C=£7787 and TC=£17 307. DVD-C resulted in cost savings=£9520 (£14/volunteer). CONCLUSIONS: DVD-C is an effective, acceptable, non-inferior, time-saving and cost-efficient alternative to TC. TRIAL REGISTRATION NUMBER: ISRCTN 73338115.

Avoidable costs of stenting for aortic coarctation in the United Kingdom: an economic model.

BACKGROUND: Undesirable outcomes in health care are associated with patient harm and substantial excess costs. Coarctation of the aorta (CoA), one of the most common congenital heart diseases, can be repaired with stenting but requires monitoring and subsequent interventions to detect and treat disease recurrence and aortic wall injuries. Avoidable costs associated with stenting in patients with CoA are unknown. METHODS: We developed an economic model to calculate potentially avoidable costs in stenting treatment of CoA in the United Kingdom over 5 years. We calculated baseline costs for the intervention and potentially avoidable complications and follow-up interventions and compared these to the costs in hypothetical scenarios with improved treatment effectiveness and complication rates. RESULTS: Baseline costs were £16 688 ($25 182) per patient. Avoidable costs ranged from £137 ($207) per patient in a scenario assuming a 10% reduction in aortic wall injuries and reinterventions at follow-up, to £1627 ($2455) in a Best-case scenario with 100% treatment success and no complications. Overall costs in the Best-case scenario were 90.2% of overall costs at Baseline. Reintervention rate at follow-up was identified as most influential lever for overall costs. Probabilistic sensitivity analysis showed a considerable degree of uncertainty for avoidable costs with widely overlapping 95% confidence intervals. CONCLUSIONS: Significant improvements in the treatment effectiveness and reductions in complication rates are required to realize discernible cost savings. Up to 10% of total baseline costs could be avoided in the best-case scenario. This highlights the need to pursue patient-specific treatment approaches which promise optimal outcomes.