Comparison of response surface methodology and the Nelder and Mead simplex method for optimization in microsimulation models

Microsimulation models are increasingly used in the evaluation of cancer screening. Latent parameters of such models can be estimated by optimization of the goodness-of-fit. We compared the efficiency and accuracy of the Response Surface Methodology and the Nelder and Mead Simplex Method for optimization of microsimulation models. To this end, we tested several automated versions of both methods on a small microsimulation model, as well as on a standard set of test functions. With respect to accuracy, Response Surface Methodology performed better in case of optimization of the microsimulation model, whereas the results for the test functions were rather variable. The Nelder and Mead Simplex Method performed more efficiently than Response Surface Methodology, both for the microsimulation model and the test functions.health;simulation;optimization

A decision-analytic approach to define poor prognosis patients: A case study for non-seminomatous germ cell cancer patients

Background. Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to define the treatment threshold for more aggressive treatment. This approach is illustrated by a case study in advanced testicular cancer, where patients with a high risk of mortality under standard treatment may be eligible for high-dose chemotherapy with stem cell support, which is currently defined by the IGCC classification. Methods. We use

The management of cervical intra-epithelial neoplasia (CIN): Extensiveness and costs in The Netherlands

In order to provide greater insight into both the extensiveness and the medical costs of the diagnosis and treatment of screen-detected cervical intra-epithelial neoplasia (CIN) in general medical practice in The Netherlands, data from national registries and gynaecology departments were retrieved, and experts were interviewed. Of the 5060 women diagnosed with CIN in 1988, more than 50% were treated in hospital with conisation or hysterectomy, which on average took 5.5 days stay per admission. The assessed average duration of the total pre- and post-treatment period is 4.6 years. The average total medical costs in women with detected CIN III are Dfl 3700 per woman. The diagnosis of CIN I and II involves more medical procedures and time than CIN III, but fewer women have conisation or hysterectomy, resulting in lower total medical costs (Dfl 2572). The overall extent and costs of the management of CIN should be accounted for when balancing the benefits, unfavourable effects and costs of cervical cancer screening

Blood transfusions for severe malaria-related anemia in Africa: a decision analysis

Severe childhood malarial anemia is commonly treated using blood transfusion. Although transfusion may decrease short-term mortality, the risk of human immunodeficiency virus (HIV) transmission is considerable in Africa. We constructed a decision tree to weigh the short-term mortality benefit of transfusion against HIV infection risk. Probability estimates were derived from published studies. The base-case was a two-year-old child with a 13.5% mortality risk to be transfused with screened or unscreened blood (1% or 13% HIV contamination risk, respectively), with reduction of mortality to 5.5% by transfusion (odds ratio=2.7), and a 2.4% risk of fatal transfusion complications. A sensitivity analysis was performed to assess the influence of variation in these estimates. If a child developed acquired immunodeficiency syndrome, survival was weighed as one-tenth of normal survival. For the base-case, we found that transfusion with screened blood provided a survival benefit of 5%. In contrast, transfusion with unscreened blood decreased survival by 2%. Patients with a mortality risk < 5% derived no benefit from a transfusion with screened blood. Other important factors for the benefit of transfusion were the effectiv

The reproductive lifespan of Onchocerca volvulus in West African savanna

Abstract The epidemiological model ONCHOSIM — a model and computer simulation program for the transmission and control of onchocerciasis — has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on different lifespan quantifications were compared with the results of longitudinal skin-snip surveys undertaken in 4 reference villages during 13 to 14 years of successful vector control in the Onchocerciasis Control Programme in West Africa. Good fits between predicted and observed trends in skin microfilarial loads could be obtained for all villages. It is concluded that the reproductive lifespan of the savanna strain of O. volvulus lies between 9 and 11 years, and that 95% of the parasites reach the end of reproduction before the age of 13 to 14 years

LYMFASIM, a simulation model for predicting the impact of lymphatic filariasis control: quantification for African villages.

LYMFASIM is a simulation model for lymphatic filariasis transmission and control. We quantified its parameters to simulate Wuchereria bancrofti transmission by Anopheles mosquitoes in African villages, using a wide variety of reported data. The developed model captures the general epidemiological patterns, but also the differences between communities. It was calibrated to represent the relationship between mosquito biting rate and the prevalence of microfilariae (mf) in the human population, the age-pattern in mf prevalence, and the relation between mf prevalence and geometric mean mf intensity. Explorative simulations suggest that the impact of mass treatment depends strongly on the mosquito biting rate and on the assumed coverage, compliance and efficacy. Our sensitivity analysis showed that some biological parameters strongly influence the predicted equilibrium pre-treatment mf prevalence (e.g. the lifespan of adult worms and mf). Other parameters primarily affect the post-treatment trends (e.g. severity of density dependence in the mosquito uptake of infection from the human blood, between-person variability in exposure to mosquito bites). The longitudinal data, which are being collected for evaluation of ongoing elimination programmes, can help to further validate the model. The model can help to assess when ongoing elimination activities in African populations can be stopped and to design surveillance schemes. It can be a valuable tool for decision making in the Global Programme to Eliminate Lymphatic Filariasis

Adaptive extensions of the Nelder and Mead Simplex Method for optimization of stochastic simulation models

We consider the Nelder and Mead Simplex Method for the optimization of stochastic simulation models. Existing and new adaptive extensions of the Nelder and Mead simplex method designed to improve the accuracy and consistency of the observed best point are studied. We comparethe performance of the extensions on a small microsimulation model, as well as on five test functions. We found that gradually decreasing the noise during an optimization run is the most preferred approach for stochastic objective functions. The amount of computation effort needed for successful optimization is very sensitive to the timing of noise reduction and to the rate of decrease of the noise. Restarting the algorithm during the optimization run, in the sense that the algorithm applies a fresh simplex at certain iterations during an optimization run, has adverse effects in our tests for the microsimulation model and for most test functions.simulation;health care;programming;Nelder and Mead Simplex Method