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The Children's Oncology Group clinical trial for intermediate risk rhabdomyosarcoma randomized participants to a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) alone or VAC alternating with vincristine plus irinotecan (VAC/VI). Clinical outcomes were similar, but toxicity profiles differed. This study estimates the cost differences between arms from the health care system's perspective.A decision-analytic model was used to estimate the incremental cost-effectiveness ratio (ICER) of VAC versus VAC/VI. Protocol-required or recommended medications and laboratory studies were included. Costs were obtained from national databases or supporting literature and inflated to 2019 US dollars. Demographic and outcome data were obtained from the clinical trial and directed chart reviews. Life-years (LY) were estimated from life-expectancy tables and discounted by 3% annually. Probabilistic sensitivity analyses and alternative clinical scenarios identified factors driving costs.Mean direct medical costs of VAC and VAC/VI were $164,757 and $102,303, respectively. VAC was associated with an additional 0.97 LY and an ICER of $64,386/LY compared with VAC/VI. The ICER was sensitive to survival estimations and to alternative clinical scenarios including outpatient cyclophosphamide delivery (ICER $49,037/LY) or substitution of alternative hematopoietic growth factor schedules (ICER $73,191-$91,579/LY). Applying drug prices from 2012 decreased the total costs of VAC by 20% and VAC/VI by 15% because of changes in dactinomycin and pegfilgrastim prices.Neither arm was clearly more cost-effective. Pharmaceutical pricing and location of treatment drove costs and may inform future treatment decisions. Rising pharmaceutical costs added $30,000 per patient, a finding important for future drug-pricing policy decisions.Two chemotherapy regimens recently tested side-by-side for rhabdomyosarcoma had similar tumor outcomes, but different side effects. The health care costs of each regimen were compared; neither was clearly more cost-effective. However, the costs of each treatment changed dramatically with choices of supportive medicines and location of treatment. Costs of treatment rose by 15% to 20% because of rising US drug costs not associated with the clinical trial.

Biological control agents based on entomopathogenic fungi traditionally contain a single strain that is efficient under certain biotic and abiotic conditions. Since particularly abiotic conditions ...

Biological control with entomopathogenic fungi is a feasible option for regulation of pest insect populations. However, possible effects on beneficial arthropods must be considered. We assessed the non-target effects of the microbial biological control agent Metarhizium brunneum (isolate BIPESCO 5/F 52) applied in soil on four different predatory arthropods: the predatory mite Gaeolaelaps aculeifer (Canestrini), the predatory bug Orius majusculus (Reuter), the rove beetle Dalotia coriaria (Kraatz) and the gall midge Aphidoletes aphidimyza Rondani. All are widespread and naturally occurring in Europe, they represent different classes of arthropods and different insect orders; furthermore, their life cycles involve different levels of contact with the soil. Adult G. aculeifer, O. majusculus, and D. coriaria, and last instar A. aphidimyza larvae were exposed to natural soil (control) or natural soil inoculated with M. brunneum at a concentration of 5 × 106 conidia/g of soil; this represents a worst-case scenario. Mortality, longevity, fecundity and Metarhizium outgrowth on dead individuals were assessed for the first three species; for A. aphidimyza, only mortality (non-emergence rate) and fecundity of emerged females were assessed. The fungal treatment resulted in a significantly higher mortality of O. majusculus and D. coriaria, 96%, and 7.3% respectively, compared with 19%, and 2% for their respective controls. Mortality of G. aculeifer was not significantly affected by exposure to the fungus in the soil. Longevity of O. majusculus and D. coriaria was significantly reduced following exposure to the fungus in the soil (log-rank test: p < 0.0001, Wilcoxon test p < 0.0001 and log-rank test: p = 0.029, Wilcoxon test: p = 0.027, respectively), while G. aculeifer longevity was not affected. Fecundity of O. majusculus and D. coriaria was negatively affected following exposure to the fungus in the soil, which reduced their oviposition by 20% and 4%, respectively, compared with the control, while G. aculeifer fecundity was not affected. Aphidoletes aphidimyza larval mortality was higher following exposure to the fungus in the soil (60% dead) than in the control (40% dead) but its fecundity was not statistically significantly affected by treatment. In conclusion, the predatory arthropods studied demonstrated a range of fitness responses to M. brunneum exposure in the soil, from no response (G. aculeifer), to intermediate (D. coriaria and A. aphidimyza) and high response (O. majusculus). This study demonstrates the relevance of using several fitness parameters and different arthropod species to determine whether a biological control agent should be considered a low-risk substance with respect to non-target effects.