This online survey was designed to capture real-world HRQOL data describing men with CRPC. The study estimated utilities using two alternative methods, and the results show good agreement, suggesting that they are robust. This methodology offers a potentially higher quality alternative to vignette-based methods that are commonly used in oncology submissions.

Purpose To capture UK societal health utility values for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and the disutility associated with treatment-related adverse events (AEs) to inform future cost–utility analyses. Methods A literature review, and patient and clinical expert interviews informed the development of health states characterising mHSPC symptoms and the impact of treatment-related AEs on health-related quality of life (HRQL). Three base health states were developed describing a typical patient with high-risk mHSPC: receiving androgen deprivation therapy (ADT) [Base State 1]; receiving docetaxel plus ADT [Base State 2]; completed docetaxel and still receiving ADT whose disease has not yet progressed [Base State 3]. Six additional health states described treatment-related AEs. The health states were validated with experts and piloted with general public participants. Health state utilities were obtained using the time trade-off (TTO) method with 200 members of the UK general population. A generalised estimating equation (GEE) model was used to estimate disutility weights. Results Mean TTO scores for Base State 1 to 3 were 0.71 (SD = 0.26), 0.64 (SD = 0.27), and 0.68 (SD = 0.26), respectively, indicating that receiving docetaxel plus ADT was most impactful on HRQL. The GEE model indicated when compared to Base State 2 that the nausea and vomiting AE had the most impact on HRQL (− 0.21), while alopecia was least burdensome (− 0.04). Conclusions The study highlights the differences in utility between base health states and the significant impact of treatment-related AEs on the HRQL of patients with mHSPC. These findings underline the importance of accounting for impaired HRQL when assessing treatments for mHSPC. Electronic supplementary material The online version of this article (10.1007/s11136-019-02117-9) contains supplementary material, which is available to authorised users.

BackgroundSilver is a transition metal, toxic when ingested in significant amounts, causing argyria (skin deposition) and argyrosis (eye deposition). It is excreted mainly via the gastrointestinal tract with only small amounts eliminated by the kidneys, and rarely have cases of nephrotoxicity due to silver been reported. Here we present the case of a woman who used colloidal silver as an alternative remedy for a T cell lymphoma, who subsequently developed argyria and a pauci-immune crescentic glomerulonephritis with evidence of extensive glomerular basement membrane silver deposition.Case PresentationA 47 year old woman of Indo-Asian descent with a T-cell lymphoma who refused conventional chemotherapy for 18 months but self-medicated with a remedy containing colloidal silver, was admitted with acute dialysis-dependent kidney injury. A kidney biopsy demonstrated a pauci-immune crescentic glomerulonephritis with deposition of silver particles in the mesangium and along the glomerular basement membranes. The patient was treated with intravenous methylprednisolone and intravenous cyclophosphamide and recovered independent renal function.ConclusionChronological evolution of the the pauci-immune glomerulonephritis suggests that a cellular immune-mediated process was induced, potentially mediated by lymphomatous T cells directed at the glomerular basement membrane, following silver deposition. Immunosuppressive therapy improved the situation and allowed cessation of haemodialysis, supporting the hypothesis of an immune-mediated process.

BackgroundMethotrexate is used in the treatment of Rheumatoid Arthritis, Juvenile Idiopathic Arthritis and other conditions such as Acute Lymphoblastic Leukaemia and psoriasis. It can be administered orally or by injection. With oral administration, methotrexate’s bitter taste may not be masked, particularly when tablets are crushed to facilitate dosing in paediatrics or patients who have difficulty swallowing tablets.1 This can lead to long term treatment adherence issues and inaccurate dosing, putting patients at risk of adverse reactions or inadequate efficacy. A palatable oral liquid presentation of methotrexate would facilitate more accurate dosing and potentially improve treatment adherence; however, methotrexate is difficult to formulate as an oral liquid due to taste, solubility and stability challenges. Despite these difficulties, a palatable, stable oral methotrexate solution has been developed.ObjectivesTo develop a palatable, stable, oral methotrexate solution, which complies with EU requirements for development of paediatric products,2 to aid accurate dosing and treatment adherence.MethodsDuring each of two single-dose (10 mg and 2.5 mg) bioequivalence studies of the test 2 mg/ml methotrexate oral solution with licenced tablets, 24 healthy male subjects were asked to comment on the oral solution’s taste, indicating whether it was: Bitter, Sour, Salty, Sweet, or No Obvious Taste and they could also leave a remark. In parallel to clinical studies, long term ICH stability studies at ambient conditions (25°C/60%RH) and in-use shelf life studies were conducted.ResultsAll subjects in the 10 mg dose study reported the oral solution as sweet tasting. One subject also reported an aftertaste and strange smell. In the 2.5 mg dose study, all subjects except one reported the solution as sweet tasting. The remaining subject reported a ‘soothing’ taste. One subject reported it was also sour and another reported an aftertaste. Two subjects additionally commented that they liked the taste. Both studies demonstrated bioequivalence and a similar safety profile between the oral solution and tablets. The stability studies illustrated that the oral methotrexate solution utilised in these clinical studies was stable at ambient conditions for up to 20 months, including a 3 months in-use period. The oral solution has recently been granted a European Union marketing authorisation and is the first methotrexate oral solution to be authorised for treatment of polyarthritic Juvenile Idiopathic Arthritis in Europe.ConclusionsA 2 mg/ml oral methotrexate solution, developed to improve treatment adherence and dose accuracy, is reported to have a palatable, sweet taste and can be stored long term at ambient conditions with a 3 months in-use period.References[1] 1. Vrignaud S, et al. Int J Pharm 2015;487(1−2):270−3.[2] EMA/CHMP/QWP/805880/2012Rev. 2AcknowledgementsThe clinical studies were conducted at PAREXEL. The development work was conducted at Quay Pharmaceuticals.Disclosure of InterestJ.-A. Penton Employee of: Therakind Ltd, J. Wi...

liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic drug ratio. Compared with 7+3, CPX-351 improves overall survival in older adults with untreated high-risk or secondary AML and differs in its mode of administration. The purpose of this study was to estimate health state utilities associated with AML treatment strategies. Methods: In time trade-off interviews with a 1-year time horizon, participants from the UK general population (London, Edinburgh) valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML in temporary remission. The decrease in utility when adding these treatment regimens represents the disutility of each type of induction/consolidation. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: 200 participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. The addition of any chemotherapy to one year of temporary remission significantly decreased utility (P < 0.0001). Induction had a mean disutility of -0.11 with CPX-351 and -0.15 with 7+3. Mean disutility for consolidation ranged from -0.03 with outpatient CPX-351 to -0.11 with inpatient 5+2. Utilities were also assessed for other AML treatments (e.g., BMT, low-intensity regimens). ConClusions: Induction and consolidation chemotherapy were consistently associated with decreases in health state utility values, but consistently less disutility was seen with CPX-351 versus 7+3 across treatment phases. These utilities may be useful in cost-utility models comparing the value of AML treatments.