Spatial conservation planning under uncertainty: adapting to climate change risks using modern portfolio theory.

Climate change and urban growth impact habitats, species, and ecosystem services. To buffer against global change, an established adaptation strategy is designing protected areas to increase representation and complementarity of biodiversity features. Uncertainty regarding the scale and magnitude of landscape change complicates reserve planning and exposes decision makers to the risk of failing to meet conservation goals. Conservation planning tends to treat risk as an absolute measure, ignoring the context of the management problem and risk preferences of stakeholders. Application of risk management theory to conservation emphasizes the diversification of a portfolio of assets, with the goal of reducing the impact of system volatility on investment return. We use principles of Modern Portfolio Theory (MPT), which quantifies risk as the variance and correlation among assets, to formalize diversification as an explicit strategy for managing risk in climate-driven reserve design. We extend MPT to specify a framework that evaluates multiple conservation objectives, allows decision makers to balance management benefits and risk when preferences are contested or unknown, and includes additional decision options such as parcel divestment when evaluating candidate reserve designs. We apply an efficient search algorithm that optimizes portfolio design for large conservation problems and a game theoretic approach to evaluate portfolio trade-offs that satisfy decision makers with divergent benefit and risk tolerances, or when a single decision maker cannot resolve their own preferences. Evaluating several risk profiles for a case study in South Carolina, our results suggest that a reserve design may be somewhat robust to differences in risk attitude but that budgets will likely be important determinants of conservation planning strategies, particularly when divestment is considered a viable alternative. We identify a possible fiscal threshold where adequate resources allow protecting a sufficiently diverse portfolio of habitats such that the risk of failing to achieve conservation objectives is considerably lower. For a range of sea-level rise projections, conversion of habitat to open water (14-180%) and wetland loss (1-7%) are unable to be compensated under the current protected network. In contrast, optimal reserve design outcomes are predicted to ameliorate expected losses relative to current and future habitat protected under the existing conservation estate.

Comparative Effectiveness of Up To Three Lines of Chemotherapy Treatment Plans for Metastatic Colorectal Cancer.

Modern chemotherapy agents transformed standard care for metastatic colorectal cancer (mCRC) but raised concerns about the financial burden of the disease. We studied comparative effectiveness of treatment plans that involve up to three lines of therapies and impact of treatment sequencing on health and cost outcomes. We employed a Markov model to represent the dynamically changing health status of mCRC patients and used Monte-Carlo simulation to evaluate various treatment plans consistent with existing guidelines. We calibrated our model by a meta-analysis of published data from an extensive list of clinical trials and measured the effectiveness of each plan in terms of cost per quality-adjusted life year. We examined the sensitivity of our model and results with respect to key parameters in two scenarios serving as base case and worst case for patients' overall and progression-free survivals. The derived efficient frontiers included seven and five treatment plans in base case and worst case, respectively. The incremental cost-effectiveness ratio (ICER) ranged between $26,260 and $152,530 when the treatment plans on the efficient frontiers were compared against the least costly efficient plan in the base case, and between $21,256 and $60,040 in the worst case. All efficient plans were expected to lead to fewer than 2.5 adverse effects and on average successive adverse effects were spaced more than 9 weeks apart from each other in the base case. Based on ICER, all efficient treatment plans exhibit at least 87% chance of being efficient. Sensitivity analyses show that the ICERs were most dependent on drug acquisition cost, distributions of progression-free and overall survivals, and health utilities. We conclude that improvements in health outcomes may come at high incremental costs and are highly dependent in the order treatments are administered.