The STAMPEDE2 Trial: a Site Survey of Current Patterns of Care, Access to Imaging and Treatment of Metastatic Prostate Cancer.

AIMS: The forthcoming STAMPEDE2 trial has three comparisons in metastatic hormone-sensitive prostate cancer. We aim to determine clinical practices among STAMPEDE trial investigators for access to imaging and therapeutic choices and explore their interest in participation in STAMPEDE2. MATERIALS AND METHODS: The survey was developed and distributed online to 120 UK STAMPEDE trial sites. Recipients were invited to complete the survey between 16 and 30 May 2022. The survey consisted of 30 questions in five sections on access to stereotactic ablative body radiotherapy (SABR), 177lutetium-prostate-specific membrane antigen-617 (177Lu-PSMA-617), choice of systemic therapies and use of positron emission tomography/computerised tomography and whole-body magnetic resonance imaging. RESULTS: From 58/120 (48%) sites, 64 respondents completed the survey: 55/64 (86%) respondents were interested to participate in SABR, 44/64 (69%) in 177Lu-PSMA-617 and 56/64 (87.5%) in niraparib with abiraterone comparisons; 45/64 (70%) respondents had access to bone, spine and lymph node metastases SABR delivery and 7/64 (11%) to 177Lu-PSMA-617. In addition to androgen deprivation therapy, 60/64 (94%) respondents used androgen receptor signalling inhibitors and 46/64 (72%) used docetaxel; 29/64 (45%) respondents would consider triplet therapy with androgen deprivation therapy, androgen receptor signalling inhibitors and docetaxel. Positron emission tomography/computerised tomography was available to 62/64 (97%) respondents and requested by 45/64 (70%) respondents for disease uncertainty on conventional imaging and 39/64 (61%) at disease relapse. Whole-body magnetic resonance imaging was available to 24/64 (38%) respondents and requested by 13/64 (20%) respondents in highly selected patients. In low-volume disease, 38/64 (59%) respondents requested scans at baseline and disease relapse. In high-volume disease, 29/64 (45%) respondents requested scans at baseline, best response (at prostate-specific antigen nadir) and disease relapse; 54/64 (84%) respondents requested computerised tomography and bone scan for best response assessment. CONCLUSION: There is noteworthy disparity in clinical practice across current study sites, however most have expressed an interest in participation in the forthcoming STAMPEDE2 trial.

PROMIS--Prostate MR imaging study: A paired validating cohort study evaluating the role of multi-parametric MRI in men with clinical suspicion of prostate cancer.

BACKGROUND: Transrectal ultrasound-guided prostate biopsies are prone to detection errors. Multi-parametric MRI (MP-MRI) may improve the diagnostic pathway. METHODS: PROMIS is a prospective validating paired-cohort study that meets criteria for level 1 evidence in diagnostic test evaluation. PROMIS will investigate whether multi-parametric (MP)-MRI can discriminate between men with and without clinically-significant prostate cancer who are at risk prior to first biopsy. Up to 714 men will have MP-MRI (index), 10-12 core TRUS-biopsy (standard) and 5mm transperineal template mapping (TPM) biopsies (reference). The conduct and reporting of each test will be blinded to the others. RESULTS: PROMIS will measure and compare sensitivity, specificity, and positive and negative predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies. The MP-MRI results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of clinically-significant cancers. For the primary outcome, significant cancer on TPM is defined as Gleason grade >/= 4+3 and/or maximum cancer core length of ≥ 6 mm. PROMIS will also assess inter-observer variability among radiologists among other secondary outcomes. Cost-effectiveness of MP-MRI prior to biopsy will also be evaluated. CONCLUSIONS: PROMIS will determine whether MP-MRI of the prostate prior to first biopsy improves the detection accuracy of clinically-significant cancer.

Long-term cost-effectiveness analysis of endovascular versus open repair for abdominal aortic aneurysm based on four randomized clinical trials.

BACKGROUND: A number of published economic evaluations of elective endovascular aneurysm repair (EVAR) versus open repair for abdominal aortic aneurysm (AAA) have come to differing conclusions about whether EVAR is cost-effective. This paper reviews the current evidence base and presents up-to-date cost-effectiveness analyses in the light of results of four randomized clinical trials: EVAR-1, DREAM, OVER and ACE. METHODS: Markov models were used to estimate lifetime costs from a UK perspective and quality-adjusted life-years (QALYs) based on the results of each of the four trials. The outcomes included in the model were: procedure costs, surveillance costs, reintervention costs, health-related quality of life, aneurysm-related mortality and other-cause mortality. Alternative scenarios about complications, reinterventions and deaths beyond the trial were explored. RESULTS: Models based on the results of the EVAR-1, DREAM or ACE trials did not find EVAR to be cost-effective at thresholds used in the UK (up to £30,000 per QALY). EVAR seemed cost-effective according to models based on the OVER trial. These results seemed robust to alternative model scenarios about events beyond the trial intervals. CONCLUSION: These analyses did not find that EVAR is cost-effective compared with open repair in the long term in trials conducted in European centres. EVAR did appear to be cost-effective based on the OVER trial, conducted in the USA. Caution must be exercised when transferring the results of economic evaluations from one country to another.

Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic aneurysms: implications for surveillance intervals and their cost-effectiveness.

BACKGROUND: Small abdominal aortic aneurysms (AAAs; 3.0-5.4 cm in diameter) are usually asymptomatic and managed by regular ultrasound surveillance until they grow to a diameter threshold (commonly 5.5 cm) at which surgical intervention is considered. The choice of appropriate surveillance intervals is governed by the growth and rupture rates of small AAAs, as well as their relative cost-effectiveness. OBJECTIVES: The aim of this series of studies was to inform the evidence base for small AAA surveillance strategies. This was achieved by literature review, collation and analysis of individual patient data, a focus group and health economic modelling. DATA SOURCES: We undertook systematic literature reviews of growth rates and rupture rates of small AAAs. The databases MEDLINE, EMBASE on OvidSP, Cochrane Central Register of Controlled Trials 2009 Issue 4, ClinicalTrials.gov, and controlled-trials.com were searched from inception up until the end of 2009. We also obtained individual data on 15,475 patients from 18 surveillance studies. REVIEW METHODS: Systematic reviews of publications identified 15 studies providing small AAA growth rates, and 14 studies with small AAA rupture rates, up to December 2009 (later updated to September 2012). We developed statistical methods to analyse individual surveillance data, including the effects of patient characteristics, to inform the choice of surveillance intervals and provide inputs for health economic modelling. We updated an existing health economic model of AAA screening to address the cost-effectiveness of different surveillance intervals. RESULTS: In the literature reviews, the mean growth rate was 2.3 mm/year and the reported rupture rates varied between 0 and 1.6 ruptures per 100 person-years. Growth rates increased markedly with aneurysm diameter, but insufficient detail was available to guide surveillance intervals. Based on individual surveillance data, for each 0.5-cm increase in AAA diameter, growth rates increased by about 0.5 mm/year and rupture rates doubled. To control the risk of exceeding 5.5 cm to below 10% in men, on average a 7-year surveillance interval is sufficient for a 3.0-cm aneurysm, whereas an 8-month interval is necessary for a 5.0-cm aneurysm. To control the risk of rupture to below 1%, the corresponding estimated surveillance intervals are 9 years and 17 months. Average growth rates were higher in smokers (by 0.35 mm/year) and lower in patients with diabetes (by 0.51 mm/year). Rupture rates were almost fourfold higher in women than men, doubled in current smokers and increased with higher blood pressure. Increasing the surveillance interval from 1 to 2 years for the smallest aneurysms (3.0-4.4 cm) decreased costs and led to a positive net benefit. For the larger aneurysms (4.5-5.4 cm), increasing surveillance intervals from 3 to 6 months led to equivalent cost-effectiveness. LIMITATIONS: There were no clear reasons why the growth rates varied substantially between studies. Uniform diagnostic criteria for rupture were not available. The long-term cost-effectiveness results may be susceptible to the modelling assumptions made. CONCLUSIONS: Surveillance intervals of several years are clinically acceptable for men with AAAs in the range 3.0-4.0 cm. Intervals of around 1 year are suitable for 4.0-4.9-cm AAAs, whereas intervals of 6 months would be acceptable for 5.0-5.4-cm AAAs. These intervals are longer than those currently employed in the UK AAA screening programmes. Lengthening surveillance intervals for the smallest aneurysms was also shown to be cost-effective. Future work should focus on optimising surveillance intervals for women, studying whether or not the threshold for surgery should depend on patient characteristics, evaluating the usefulness of surveillance for those with aortic diameters of 2.5-2.9 cm, and developing interventions that may reduce the growth or rupture rates of small AAAs. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The UK EndoVascular Aneurysm Repair (EVAR) trials: randomised trials of EVAR versus standard therapy.

OBJECTIVE: To assess the efficacy of endovascular aneurysm repair (EVAR) against standard alternative management in patients with large abdominal aortic aneurysm (AAA). DESIGN: Two national, multicentre randomised trials - EVAR trials 1 and 2. SETTING: Patients were recruited from 38 out of 41 eligible UK hospitals. PARTICIPANTS: Men and women aged at least 60 years, with an AAA measuring at least 5.5 cm on a computerised tomography scan that was regarded as anatomically suitable for EVAR, were assessed for fitness for open repair. Patients considered fit were randomised to EVAR or open repair in EVAR trial 1 and patients considered unfit were randomised to EVAR or no intervention in EVAR trial 2. INTERVENTIONS: EVAR, open repair or no intervention. MAIN OUTCOME MEASURES: The primary outcome was mortality (operative, all-cause and AAA related). Patients were flagged at the UK Office for National Statistics with centrally coded death certificates assessed by an Endpoints Committee. Power calculations based upon mortality indicated that 900 and 280 patients were required for EVAR trials 1 and 2, respectively. Secondary outcomes were graft-related complications and reinterventions, adverse events, renal function, health-related quality of life and costs. Cost-effectiveness analyses were performed for both trials. RESULTS: Recruitment occurred between 1 September 1999 and 31 August 2004, with targets exceeded in both trials: 1252 randomised into EVAR trial 1 (626 to EVAR) and 404 randomised into EVAR trial 2 (197 to EVAR). Follow-up closed in December 2009 with very little loss to follow-up (1%). In EVAR trial 1, 30-day operative mortalities were 1.8% and 4.3% in the EVAR and open-repair groups, respectively: adjusted odds ratio 0.39 [95% confidence interval (CI) 0.18 to 0.87], p = 0.02. During a total of 6904 person-years of follow-up, 524 deaths occurred (76 AAA related). Overall, there was no significant difference between the groups in terms of all-cause mortality: adjusted hazard ratio (HR) 1.03 (95% CI 0.86 to 1.23), p = 0.72. The EVAR group did demonstrate an early advantage in terms of AAA-related mortality, which was sustained for the first few years, but lost by the end of the study, primarily due to fatal endograft ruptures: adjusted HR 0.92 (95% CI 0.57 to 1.49), p = 0.73. The EVAR procedure was more expensive than open repair (mean difference £1177) and not found to be cost-effective, but the model was sensitive to alternative assumptions. In EVAR trial 2, during a total of 1413 person-years of follow-up, a total of 305 deaths occurred (78 AAA related). The 30-day operative mortality was 7.3% in the EVAR group. However, this group later demonstrated a significant advantage in terms of AAA-related mortality, but this became apparent only after 4 years: overall adjusted HR 0.53 (95% CI 0.32 to 0.89), p = 0.02. Sadly, this advantage did not result in any benefit in terms of all-cause mortality: adjusted HR 0.99 (95% CI 0.78 to 1.27), p = 0.97. Overall, EVAR was more expensive than no intervention (mean difference £10,222) and not found to be cost-effective. CONCLUSIONS: EVAR offers a clear operative mortality benefit over open repair in patients fit for both procedures, but this early benefit is not translated into a long-term survival advantage. Among patients unfit for open repair, EVAR is associated with a significant long-term reduction in AAA-related mortality but this does not appear to influence all-cause mortality. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 55703451. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 9. See the HTA programme website for further project information.

Modelling the long-term cost-effectiveness of endovascular or open repair for abdominal aortic aneurysm.

BACKGROUND: Recent randomized trials have shown that endovascular abdominal aortic aneurysm repair (EVAR) has a 3 per cent aneurysm-related survival benefit in patients fit for open surgery, but it also has uncertain long-term outcomes and higher costs. This study assessed the cost-effectiveness of EVAR. METHODS: A decision model was constructed to estimate the lifetime costs and quality-adjusted life years (QALYs) with EVAR and open repair in men aged 74 years. The model includes the risks of death from aneurysm, other cardiovascular and non-cardiovascular causes, secondary reinterventions and non-fatal cardiovascular events. Data were taken largely from the EVAR trial 1 and supplemented from other sources. RESULTS: Under the base-case (primary) assumptions, EVAR cost 3800 pounds sterling (95 per cent confidence interval (c.i.) 2400 pounds sterling to 5200 pounds sterling) more per patient than open repair but produced fewer lifetime QALYs (mean -0.020 (95 per cent c.i. -0.189 to 0.165)). These results were sensitive to alternative model assumptions. CONCLUSION: EVAR is unlikely to be cost-effective on the basis of existing devices, costs and evidence, but there remains considerable uncertainty.

Final 12-year follow-up of surgery versus surveillance in the UK Small Aneurysm Trial.

BACKGROUND: The aim was to determine whether early open surgical repair would benefit patients with small abdominal aortic aneurysm compared with surveillance on long-term follow-up. METHODS: The 1090 patients who were enrolled into the UK Small Aneurysm Trial between 1991 and 1995 were followed up for aneurysm repair and mortality until November 2005. RESULTS: By November 2005, 714 patients (65.5 per cent) had died, 929 (85.2 per cent) had undergone aneurysm repair, 150 (13.8 per cent) had died without aneurysm repair and 11 (1.0 per cent) remained alive without aneurysm repair. After 12 years, mortality in the surgery and surveillance groups was 63.9 and 67.3 per cent respectively, unadjusted hazard ratio 0.90 (P = 0.139). Three-quarters of the surveillance group eventually had aneurysm repair, with a 30-day elective mortality of 6.3 per cent (versus 5.0 per cent in the early surgery group, P = 0.366). Estimates suggested that the cost of treatment was 17 per cent higher in the early surgery group, with a mean difference of 1326 pounds. The death rate in these patients was about twice that in the population matched for age and sex. CONCLUSION: There was no long-term survival benefit of early elective open repair of small abdominal aortic aneurysms. Even after successful aneurysm repair, the mortality among these patients was higher than in the general population.

The UK Endovascular Aneurysm Repair (EVAR) trials: design, methodology and progress.

OBJECTIVES: The endovascular aneurysm repair (EVAR) trials aim to assess the efficacy of EVAR in the treatment of AAA in terms of mortality, quality of life, durability and cost-effectiveness. DESIGN: Male and female patients aged at least 60 years with an AAA diameter measuring at least 5.5 cm on a computed tomography (CT) scan are assessed for anatomical suitability for EVAR. Suitable patients are offered entry either into EVAR Trial 1 if they are considered fit for conventional open repair or EVAR Trial 2 if they are considered unfit. EVAR 1 randomly allocates patients to EVAR or open repair and EVAR 2 randomly allocates patients to EVAR with best medical treatment or best medical treatment alone. Target recruitment for EVAR Trials 1 and 2 is 900 and 280 patients, respectively. PROGRESS: Recruitment began in September 1999 and there are currently 40 UK centres participating in the trials. Monthly targets are being exceeded in EVAR Trial 1 with 1037 patients randomised by October 2003. EVAR Trial 2 is also meeting monthly targets with a total of 319 patients randomised. When recruitment closes in December 2003 patients will need to be followed for at least 1 year from their operation. Publication of full results for both trials is expected in mid 2005.

As outcomes measurement and management become widespread, providers should beware of legal pitfalls.

Until new statutes and court decisions clarify the law applicable to outcomes research, providers will continue to face new questions. In the meantime, paying careful attention to satisfying the requirements of existing laws protecting peer review information will put providers in the best position to minimize their exposure. Providers should review their current outcomes measurement and management systems to ensure that (1) they are structured to take full advantage of the confidentiality protections available under state law, and (2) appropriate access to outcomes data for those who need it is clearly provided for in the relevant documentation.

The Delta Dental case: "Fair procedure" comes to managed care. Delta Dental Plan of California v. Banasky.

All providers contemplating managed care contracts, both individual and institutional, should carefully review the health plans' internal administrative review and dispute resolution procedures before making their decisions, especially if the contracts will represent significant income for the provider. While there may be judicial recourse in California and in other states that adopt the holding in Delta Dental, in other states providers may well be held to the health plans' internal administrative decisions as a matter of contractual agreement. Health plans should also review their own policies and procedures for adequacy under applicable state law. The health care community will not know the full extent of Delta Dental's implications until later cases area decided, but for now it seems certain that another wave of change in this area is just beginning.

Special report on patient care. The new federal patient-dumping regulations: some commonly asked questions and answers.

Until both providers and government surveyors become more familiar with the new EMTALA regulations, there will be an uncomfortable period of adjustment, and perhaps some turmoil as well, particularly regarding the new requirement that facilities who receive suspicious transfers report those transfers to HCFA. Providers should carefully examine their internal policies on discharge and transfer of emergency patients to assure that those policies are consistent with the new regulations. Particular attention should be given to inservice training for medical and support personnel in the emergency department, because they must precisely comply with the law and their errors can subject the hospital to costly investigations and potential fines of $50,000 for each violation.

Special report on patient care. HCFA finally issues patient-dumping regulations.

EMTALA has always been an especially worrisome law for providers because its requirements are both sweeping and vague, with potentially drastic penalties for violations. The new regulations remove only some of the law's vagueness. As with previous EMTALA amendments, all United States hospitals, as well as emergency department physicians and other doctors who see patients in the emergency department, should carefully review their internal policies regarding patient ++ transfers in light of the new regulations. For example, hospitals must have an internal policy for following up on suspicious transfers, as failure to detect an inappropriate transfer can now potentially result in a Medicare decertification action. Also, hospitals with specialized services (e.g., burn units or shock-trauma units) should review their policies on receiving transfer patients in light of the greater specificity of the new regulations. Finally, because of the confusing new requirements regarding ambulance services, all hospitals should review their relationships with and policies regarding, ambulance services and ambulance diversion.