Therapeutic Options in Docetaxel-Refractory Metastatic Castration-Resistant Prostate Cancer: A Cost-Effectiveness Analysis.

Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis.

PLoS One. 2013; 8(5): e64275
Zhong L, Pon V, Srinivas S, Nguyen N, Frear M, Kwon S, Gong C, Malmstrom R, Wilson L

Docetaxel is an established first-line therapy to treat metastatic castration-resistant prostate cancer (mCRPC). Recently, abiraterone and cabazitaxel were approved for use after docetaxel failure, with improved survival. National Institute for Health and Clinical Excellence (NICE) preliminary recommendations were negative for both abiraterone (now positive in final recommendation) and cabazitaxel (negative in final recommendation).To evaluate the cost-effectiveness of abiraterone, cabazitaxel, mitoxantrone and prednisone for mCRPC treatment in US.A decision-tree model was constructed to compare the two mCRPC treatments versus two placebos over 18 months from a societal perspective. Chance nodes include baseline pain as a severity indicator, grade III/IV side-effects, and survival at 18 months. Probabilities, survival and health utilities were from published studies. Model cost inputs included drug treatment, side-effect management and prevention, radiation for pain, and death associated costs in 2010 US dollars.Abiraterone is a cost-effective choice at $ 94K/QALY (quality adjusted life years) compared to placebo in our base-case analysis. Cabazitaxel and abiraterone are the most effective, yet also most expensive agents. The incremental cost-effectiveness ratios (ICER) at base-case are $ 101K/QALY (extended dominated) for mitoxantrone vs. placebo, $ 91K/QALY for abiraterone vs. mitoxantrone, $ 956K/QALY for cabazitaxel vs. abiraterone. Abiraterone becomes less cost-effective as its AWP increases, or if the cost of mitoxantrone side-effect management decreases. Increases in the percentage of patients with baseline pain leads to an increased ICER for both mitoxantrone and abiraterone, but mitoxantrone does relatively better. Cabazitaxel remains not cost-effective.Our base case model suggests that abiraterone is a cost-effective option in docetaxel-refractory mCRPC patients. Newer treatments will also need a CEA assessment compared to abiraterone. HubMed – drug


Proteomic Analysis of Oesophagostomum dentatum (Nematoda) during Larval Transition, and the Effects of Hydrolase Inhibitors on Development.

PLoS One. 2013; 8(5): e63955
Ondrovics M, Silbermayr K, Mitreva M, Young ND, Razzazi-Fazeli E, Gasser RB, Joachim A

In this study, in vitro drug testing was combined with proteomic and bioinformatic analyses to identify and characterize proteins involved in larval development of Oesophagostomum dentatum, an economically important parasitic nematode. Four hydrolase inhibitors ?-phenanthroline, sodium fluoride, iodoacetamide and 1,2-epoxy-3-(pnitrophenoxy)-propane (EPNP) significantly inhibited (?90%) larval development. Comparison of the proteomic profiles of the development-inhibited larvae with those of uninhibited control larvae using two-dimensional gel electrophoresis, and subsequent MALDI-TOF mass spectrometric analysis identified a down-regulation of 12 proteins inferred to be involved in various larval developmental processes, including post-embryonic development and growth. Furthermore, three proteins (i.e. intermediate filament protein B, tropomyosin and peptidyl-prolyl cis-trans isomerase) inferred to be involved in the moulting process were down-regulated in moulting- and development-inhibited O. dentatum larvae. This first proteomic map of O. dentatum larvae provides insights in the protein profile of larval development in this parasitic nematode, and significantly improves our understanding of the fundamental biology of its development. The results and the approach used might assist in developing new interventions against parasitic nematodes by blocking or disrupting their key biological pathways. HubMed – drug


Rates of Switching Antiretroviral Drugs in a Primary Care Service in South Africa before and after Introduction of Tenofovir.

PLoS One. 2013; 8(5): e63596
Njuguna C, Orrell C, Kaplan R, Bekker LG, Wood R, Lawn SD

Antiretroviral changes (single drug substitutions and regimen switches) limit treatment options and introduce challenges such as increased cost, monitoring and adherence difficulties. Patterns of drug substitutions and regimen switches from stavudine (d4T) and zidovudine (AZT) regimens have been well described but data on tenofovir (TDF) are more limited. This study describes the patterns and risk factors for drug changes of these antiretroviral drugs in adults.This retrospective cohort study included HIV positive, antiretroviral treatment (ART) naïve adults aged ?18 years who started ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor. Follow-up was censored at first drug change and analysis focused on NRTI changes only.Between September 2002 and April 2011, 5095 adults initiated ART in Gugulethu. This comprised 948 subjects on TDF, 3438 on d4T and 709 subjects on AZT. Virological suppression rates at 1 year, regimen switching due to virological failure and overall losses to the programme were similar across the three groups. TDF had the lowest incidence rate of drug substitutions (2.6 per 100 P/Ys) compared to 17.9 for d4T and 8.5 per 100 P/Ys for AZT. Adverse drug reactions (ADRs) accounted for the majority of drug substitutions of d4T. Multivariate analysis showed that increasing age, female sex and d4T exposure were associated with increased hazard of drug substitution due to ADRs. Conversely, TDF exposure was associated with a substantially lower risk of substitution (adjusted hazards ratio 0.38; 95% CI 0.20-0.72).Regimen switches and virological suppression were similar for patients exposed to TDF, d4T and AZT, suggesting all regimens were equally effective. However, TDF was better tolerated with a substantially lower rate of drug substitutions due to ADRs. HubMed – drug


Access to essential medicines in pakistan: policy and health systems research concerns.

PLoS One. 2013; 8(5): e63515
Zaidi S, Bigdeli M, Aleem N, Rashidian A

Inadequate access to essential medicines is a common issue within developing countries. Policy response is constrained, amongst other factors, by a dearth of in-depth country level evidence. We share here i) gaps related to access to essential medicine in Pakistan; and ii) prioritization of emerging policy and research concerns.An exploratory research was carried out using a health systems perspective and applying the WHO Framework for Equitable Access to Essential Medicine. Methods involved key informant interviews with policy makers, providers, industry, NGOs, experts and development partners, review of published and grey literature, and consultative prioritization in stakeholder’s Roundtable.A synthesis of evidence found major gaps in essential medicine access in Pakistan driven by weaknesses in the health care system as well as weak pharmaceutical regulation. 7 major policy concerns and 11 emerging research concerns were identified through consultative Roundtable. These related to weaknesses in medicine registration and quality assurance systems, unclear and counterproductive pricing policies, irrational prescribing and sub-optimal drug availability. Available research, both locally and globally, fails to target most of the identified policy concerns, tending to concentrate on irrational prescriptions. It overlooks trans-disciplinary areas of policy effectiveness surveillance, consumer behavior, operational pilots and pricing interventions review.Experience from Pakistan shows that policy concerns related to essential medicine access need integrated responses across various components of the health systems, are poorly addressed by existing evidence, and require an expanded health systems research agenda. HubMed – drug