Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial

Background Androgen-deprivation therapy is offered to men with prostate cancer who have a rising prostate-specific antigen after curative therapy (PSA relapse) or who are considered not suitable for curative treatment; however, the optimal timing for its introduction is uncertain. We aimed to assess whether immediate androgen-deprivation therapy improves overall survival compared with delayed therapy. Methods In this randomised, multicentre, phase 3, non-blinded trial, we recruited men through 29 oncology centres in Australia, New Zealand, and Canada. Men with prostate cancer were eligible if they had a PSA relapse after previous attempted curative therapy (radiotherapy or surgery, with or without postoperative radiotherapy) or if they were not considered suitable for curative treatment (because of age, comorbidity, or locally advanced disease). We used a database-embedded, dynamically balanced, randomisation algorithm, coordinated by the Cancer Council Victoria, to randomly assign participants (1:1) to immediate androgen-deprivation therapy (immediate therapy arm) or to delayed androgen-deprivation therapy (delayed therapy arm) with a recommended interval of at least 2 years unless clinically contraindicated. Randomisation for participants with PSA relapse was stratified by type of previous therapy, relapse-free interval, and PSA doubling time; randomisation for those with non-curative disease was stratified by metastatic status; and randomisation in both groups was stratified by planned treatment schedule (continuous or intermittent) and treatment centre. Clinicians could prescribe any form and schedule of androgen-deprivation therapy and group assignment was not masked. The primary outcome was overall survival in the intention-to-treat population. The trial closed to accrual in 2012 after review by the independent data monitoring committee, but data collection continued for 18 months until Feb 26, 2014. It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000301561) and ClinicalTrials.gov (NCT00110162). Findings Between Sept 3, 2004, and July 13, 2012, we recruited 293 men (261 with PSA relapse and 32 with non-curable disease). We randomly assigned 142 men to the immediate therapy arm and 151 to the delayed therapy arm. Median follow-up was 5 years (IQR 3·3–6·2) from the date of randomisation. 16 (11%) men died in the immediate therapy arm and 30 (20%) died in the delayed therapy arm. 5-year overall survival was 86·4% (95% CI 78·5–91·5) in the delayed therapy arm versus 91·2% (84·2–95·2) in the immediate therapy arm (log-rank p=0·047). After Cox regression, the unadjusted HR for overall survival for immediate versus delayed arm assignment was 0·55 (95% CI 0·30–1·00; p=0·050). 23 patients had grade 3 treatment-related adverse events. 105 (36%) men had adverse events requiring hospital admission; none of these events were attributable to treatment or differed between treatment-timing groups. The most common serious adverse events were cardiovascular, which occurred in nine (6%) patients in the delayed therapy arm and 13 (9%) in the immediate therapy arm. Interpretation Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention in men with PSA-relapsed or non-curable prostate cancer. The results provide benchmark evidence of survival rates and morbidity to discuss with men when considering their treatment options. Funding Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia.

Development of an evidence-based scoring system (HF-IS) to assess the quality of heart failure programmes for patients postdischarge from hospital

Aim.  The aim of this study was to develop a potential scoring algorithm for interventions in a chronic heart failure management programme – the Heart Failure Intervention Score – to facilitate quality improvement and programme auditing.

Background.  The overall efficacy of chronic heart failure management programmes has been demonstrated in several meta-analyses. However, meta-analyses did not determine individual interventions in a programme that resulted in beneficial patient outcomes.

Design.  A prospective cross-sectional survey design.

Method.  All chronic heart failure management programmes in Australia (n = 62), identified by a national register, were surveyed to determine programme characteristics and interventions.

Results.  Of the 62 national chronic heart failure management programmes, 48 (77%) completed the survey and 27 individual interventions were identified. Variability in the use of the key interventions was common among the programmes. Each intervention was given an arbitrary weighted score according to the level of supportive evidence available and a total score calculated. Programmes were then categorised into low or high complexity based on several interventions implemented and their weighted score. A total score of ≥190 (median = 178, interquartile range 176–195) was used to divide programmes into two groups. Nine programmes were categorised into high Heart Failure Intervention Score group and majority of these were based in the acute hospital setting (78%). In the low Heart Failure Intervention Score group, there were 39 programmes of which there were a higher proportion of community-based programmes (38%) and programmes in small community hospitals (10%).

Conclusion.  The Heart Failure Intervention Score provides a potential evidence-based quality improvement tool through which a set of minimum standards can be developed. Implementation of the Heart Failure Intervention Score provides guidance to programme coordinators to enable monitoring of standards of heart failure programmes, which may potentially result in better patient outcomes.

Using technology to improve peer review and collaborative conversations to benchmark academic standards

In 2010 the Australian government commissioned the Australian Learning and Teaching Council (ALTC) to undertake a national project to facilitate disciplinary development of threshold learning standards. The aim was to lay the foundation for all higher education providers to demonstrate to the new national higher education regulator, the Tertiary Education Quality and Standards Agency (TEQSA), that graduates achieved or exceeded minimum academic standards. Through a yearlong consultative process, representatives of employers, professional bodies, academics and students, developed learning standards applying to any Australian higher education provider. Willey and Gardner reported using a software tool, SPARKPLUS, in calibrating academic standards amongst teaching staff in large classes. In this paper, we investigate the effectiveness of this technology to promote calibrated understandings with the national accounting learning standards. We found that integrating the software with a purposely designed activity provided significant efficiencies in calibrating understandings about learning standards, developed expertise and a better understanding of what is required to meet these standards and how best to demonstrate them. The software and supporting calibration and assessment process can be adopted by other disciplines, including engineering, seeking to provide direct evidence about performance against learning standards. © 2012 IEEE.