Trastuzumab beyond progression: a cost-utility analysis

Background: The continuation of trastuzumab beyond progression in combination with capecitabine as secondary chemotherapy for HER2-positive metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase in toxicity. Patients and methods: A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Information on response rates and major adverse effects was derived, and transition probabilities were estimated, based on the results of the Breast International Group 03-05 clinical trial. Direct costs were assessed from the perspective of the Swiss health care system. Results: The addition of trastuzumab to capecitabine is estimated to cost on average an additional of €33 980 and to yield a gain of 0.35 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of €98 329/QALYs gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of €60 000/QALY was reached in 12% of cases. Conclusion: The addition of trastuzumab to capecitabine in MBC patients is more expensive than what is typically regarded as cost-effective but falls within the value ranges found for established regimens in the treatment of MB

The prisoners dilemma on a stochastic non-growth network evolution model

We investigate the evolution of cooperation on a non - growth network model with death/birth dynamics. Nodes reproduce under selection for higher payoffs in a prisoners dilemma game played between network neighbours. The mean field characteristics of the model are explored and an attempt is made to understand the size dependent behaviour of the model in terms of fluctuations in the strategy densities. We also briefly comment on the role of strategy mutation in regulating the strategy densties.Comment: 8 pages, 8 figure

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < −2.5 standard deviation). Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherap

Disordered Environments in Spatial Games

The Prisoner's dilemma is the main game theoretical framework in which the onset and maintainance of cooperation in biological populations is studied. In the spatial version of the model, we study the robustness of cooperation in heterogeneous ecosystems in spatial evolutionary games by considering site diluted lattices. The main result is that due to disorder, the fraction of cooperators in the population is enhanced. Moreover, the system presents a dynamical transition at $\rho^*$, separating a region with spatial chaos from one with localized, stable groups of cooperators.Comment: 6 pages, 5 figure

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

In this trial, stopping bevacizumab after completion of induction chemotherapy was associated with a shorter time to progression, but no statistically significant difference in overall survival compared with the bevacizumab continuation strategy. Non-inferiority could not be demonstrated. Treatment costs are substantially higher for continuous bevacizumab treatmen

Different reactions to adverse neighborhoods in games of cooperation

In social dilemmas, cooperation among randomly interacting individuals is often difficult to achieve. The situation changes if interactions take place in a network where the network structure jointly evolves with the behavioral strategies of the interacting individuals. In particular, cooperation can be stabilized if individuals tend to cut interaction links when facing adverse neighborhoods. Here we consider two different types of reaction to adverse neighborhoods, and all possible mixtures between these reactions. When faced with a gloomy outlook, players can either choose to cut and rewire some of their links to other individuals, or they can migrate to another location and establish new links in the new local neighborhood. We find that in general local rewiring is more favorable for the evolution of cooperation than emigration from adverse neighborhoods. Rewiring helps to maintain the diversity in the degree distribution of players and favors the spontaneous emergence of cooperative clusters. Both properties are known to favor the evolution of cooperation on networks. Interestingly, a mixture of migration and rewiring is even more favorable for the evolution of cooperation than rewiring on its own. While most models only consider a single type of reaction to adverse neighborhoods, the coexistence of several such reactions may actually be an optimal setting for the evolution of cooperation.Comment: 12 pages, 5 figures; accepted for publication in PLoS ON

An economic analysis of email-based telemedicine: A cost minimisation study of two service models

<p>Abstract</p> <p>Background</p> <p>Email-based telemedicine has been reported to be an efficient method of delivering online health services to patients at a distance and is often described as a low-cost form of telemedicine. The service may be low-cost if the healthcare organisation utilise their existing email infrastructure to provide their telemedicine service. Many healthcare organisations use commercial-off-the-shelf (COTS) email applications. COTS email applications are designed for peer-to-peer communication; hence, in situations where multiple clinicians need to be involved, COTS applications may be deficient in delivering telemedicine. Larger services often rely on different staff disciplines to run their service and telemedicine tools for supervisors, clinicians and administrative staff are not available in COTS applications. Hence, some organisations may choose to develop a purpose-written email application to support telemedicine. We have conducted a cost-minimisation analysis of two different service models for establishing and operating an email service. The first service model used a COTS email application and the second used a purpose-written telemedicine application.</p> <p>Methods</p> <p>The actual costs used in the analysis were from two organisations that originally ran their counselling service with a COTS email application and later implemented a purpose-written application. The purpose-written application automated a number of the tasks associated with running an email-based service. We calculated a threshold at which the higher initial costs for software development were offset by efficiency gains from automation. We also performed a sensitivity analysis to determine the effect of individual costs on the threshold.</p> <p>Results</p> <p>The cost of providing an email service at 1000 consultations per annum was $19,930 using a COTS email application and$31,925 using a purpose-written application. At 10,000 consultations per annum the cost of providing the service using COTS email software was $293,341 compared to$272,749 for the purpose-written application. The threshold was calculated at a workload of 5216 consultations per annum. When more than 5216 email consultations per annum are undertaken, the purpose-written application was cheaper than the COTS service model. The sensitivity analysis showed the threshold was most sensitive to changes in administrative staff salaries.</p> <p>Conclusion</p> <p>In the context of telemedicine, we have compared two different service models for email-based communication – purpose-written and COTS applications. Under the circumstances described in the paper, when workload exceeded 5216 email consultations per annum, there were savings made when a purpose-written email application was used. This analysis provides a useful economic model for organisations contemplating the use of an email-based telemedicine system.</p

Critical dynamics in the evolution of stochastic strategies for the iterated Prisoner's Dilemma

The observed cooperation on the level of genes, cells, tissues, and individuals has been the object of intense study by evolutionary biologists, mainly because cooperation often flourishes in biological systems in apparent contradiction to the selfish goal of survival inherent in Darwinian evolution. In order to resolve this paradox, evolutionary game theory has focused on the Prisoner's Dilemma (PD), which incorporates the essence of this conflict. Here, we encode strategies for the iterated Prisoner's Dilemma (IPD) in terms of conditional probabilities that represent the response of decision pathways given previous plays. We find that if these stochastic strategies are encoded as genes that undergo Darwinian evolution, the environmental conditions that the strategies are adapting to determine the fixed point of the evolutionary trajectory, which could be either cooperation or defection. A transition between cooperative and defective attractors occurs as a function of different parameters such a mutation rate, replacement rate, and memory, all of which affect a player's ability to predict an opponent's behavior.Comment: 27 pages, including supplementary information. 5 figures, 4 suppl. figures. Version accepted for publication in PLoS Comp. Bio