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2604 Background: The dissociative anaesthetic ketamine is widely used for cancer related pain. A Cochrane review concluded that insufficient evidence was available to support its use in this setting. Methods: This phase III, multisite, double-blind, dose escalation, placebo, randomised controlled study aimed to determine whether ketamine, delivered subcutaneously over three to five days is more effective than placebo, when used in conjunction with adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered to be of net benefit if it provided a reduction in average pain scores by ≥2/10 points from baseline, with limited breakthrough analgesia and acceptable toxicity. Results: For the 185 participants, there was no significant difference between the proportion of positive outcomes (0.04 (-0.10, 0.18) p=0.55) in the placebo and intervention arms (response rates 27% (25/92) and 31% (29/93)). Pain type (nociceptive versus neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (IRR = 1.95 (1.46, 2.61), p

TO THE EDITOR: The evaluation by Hicks and colleagues of the centralised ethics review system in New South Wales codifies important additional time delays facing researchers conducting multicentre trials that include NSW. These delays have direct financial consequences that continue to limit the viability (especially when staff are on time-limited grants) and productivity of multisite research in Australia, without adding value to the ethical conduct of the research. There is also inconsistency between the approaches of the lead ethics committee (LEC) and site-specific ethics committees in the way they deal with protocol amendments and adverse event governance, further compounding the delays in initial review. Five multicentre clinical trials are currently being conducted by the Palliative Care Clinical Studies Collaborative (PaCCSC), a national initiative to improve the evidence for symptom therapeutics at the end of life. Submissions for ethics review occurred between May 2008 and July 2009 across nine sites in five states. As in the study by Hicks et al, ethics review submissions included the NSW LEC, but because these submissions were more recent than those reported by Hicks et al, they were submitted on the National Ethics Application Form (NEAF). Hicks and colleagues state there is benefit in standard documentation, but using the NEAF does not reduce the need for collating complete sets of documentation for each site-specific approval and any subsequent amendments or adverse events.4 For the PaCCSC, LEC and site-specific review in NSW achieved approval in a median of 119 days (range, 76–209), compared with 107 days (range, 6–172) for individual committees in other states. Hicks and colleagues did not quantify the costs generated by these delays. Given that staff are often employed to prepare ethics submissions and then retained for the definitive study, additional delays in approval are costly, especially with finite, competitive grants funding. Costs of multisite ethics review applications have previously been quantified in Australia, but the additional delays in NSW from the requirement for site-specific approval are estimated to have cost the PaCCSC about $4000 per study per site in salaries and on-costs. Across three NSW sites and five studies, $55 000 has been spent without measurable ethical or research governance benefits. Theoretically, LEC review should streamline protocol amendments and adverse events reporting, as they are the responsibility of the LEC. But although protocol amendments are supposed to be reviewed only by the LEC, some site-specific committees continue to insist on approving all amendments. Efforts to consolidate adverse event reporting have made some progress. All adverse events are reported to the LEC for review, and any required response should be shared with site-specific committees. Again, some non-lead sites continue to insist on separately reviewing adverse events rather than using the LEC as intended.

Background Delirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer. The aim of this article is to describe the design of a feasibility study that is being conducted to inform a larger randomized, placebo-controlled, double-blind trial (RCT) to evaluate the role of exogenously administered melatonin in preventing delirium in patients with advanced cancer. Methods/Design Adult patients with a cancer diagnosis who are admitted to the palliative care unit will be randomized into a treatment or placebo group. The pharmacological intervention consists of a single daily dose of immediate-release melatonin (3 mg) at 21:00 ± 1 h, from day 1 to day 28 of admission. The primary objective of this initial study is to assess the feasibility of conducting the proposed RCT by testing recruitment and retention rates, appropriateness of study outcome measures, acceptability of study procedures and effectiveness of the blinding process. The primary outcome measure of the proposed larger RCT is time to first inpatient incident episode of delirium. We also plan to collect data on incident rates of delirium and patient-days of delirium, adjusting for length of admission. Discussion The outcomes of this feasibility study will provide information on recruitment and retention rates, protocol violation frequency, effectiveness of the blinding process, acceptability of the study procedures, and safety of the proposed intervention. This will inform the design of a fully powered randomized controlled trial to evaluate the preventative role of melatonin administration in patients with advanced cancer. Trial registration Registered with ClinicalTrials.gov: NCT02200172 Registered on 21 July 2014. Health Canada protocol number: BRI-MELAT-2013 (Final approved protocol version (Version 3): 18 June 2014) (Notice of Amended Authorization (NOA) received 14 November 2014). Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1525-8) contains supplementary material, which is available to authorized users.

Background: It is estimated that 29% of deaths in Australia are caused by malignant disease each year and can be expected to increase with population ageing. In advanced cancer, the prevalence of fatigue is high at 70-90%, and can be related to the disease and/or the treatment. The negative impact of fatigue on function (physical, mental, social and spiritual) and quality of life is substantial for many palliative patients as well as their families/carers. Method/design. This paper describes the design of single patient trials (n-of-1 s or SPTs) of a psychostimulant, methylphenidate hydrochloride (MPH) (5 mg bd), compared to placebo as a treatment for fatigue, with a population estimate of the benefit by the aggregation of multiple SPTs. Forty patients who have advanced cancer will be enrolled through specialist palliative care services in Australia. Patients will complete up to 3 cycles of treatment. Each cycle is 6 days long and has 3 days treatment and 3 days placebo. The order of treatment and placebo is randomly allocated for each cycle. The primary outcome is a reduction in fatigue severity as measured by the Functional Assessment of Cancer Therapy-fatigue subscale (FACIT-F). Secondary outcomes include adverse events, quality of life, additional fatigue assessments, depression and Australian Karnovsky Performance Scale. Discussion. This study will provide high-level evidence using a novel methodological approach about the effectiveness of psychostimulants for cancer-related fatigue. If effective, the findings will guide clinical practice in reducing this prevalent condition to improve function and quality of life. Trial registration. Australian New Zealand Clinical Trials Registry ACTRN12609000794202. © 2013 Senior et al.; licensee BioMed Central Ltd.

About 9% of Australians aged 65 years and over have a diagnosis of dementia. Clinical practice guidelines aim to enhance research translation by synthesising recent evidence for health and aged care professionals. New clinical practice guidelines and principles of care for people with dementia detail the optimal diagnosis and management in community, residential and hospital settings. The guidelines have been approved by the National Health and Medical Research Council. The guidelines emphasise timely diagnosis; living well with dementia and delaying functional decline; managing symptoms through training staff in how to provide person-centred care and using non-pharmacological approaches in the first instance; and training and supporting families and carers to provide care.