Over the last 30 years leading thinkers have taken us beyond mechanistic and reductionist analysis into systems theory and the critical boundary judgements that are fundamental to systems analysis. In defining and discussing boundary conditions, we also redefine values and facts imposed on hydrological and economic analysis that underpins decisions about government policy in water resources. The repeal of legislation for distributed interventions (water-efficient appliances and rainwater harvesting) that was previously enacted to improve the security of a regional water supply system is examined as a case study. The results of the analysis were defined by the costs and benefits that are inside or outside of the boundaries of legitimate and recognized consideration. This paper refers to those differences as boundary conditions and considers how those boundary conditions affect the outcome of analysis. Setting of boundary conditions (what is included, what is excluded and assumptions) in engineering and economic analysis dominates outcomes of decisions about government policy. These insights have general application to development of government water policy. The investigations outlined in this paper were combined to create an enhanced version of a systems analysis of a policy for setting targets for water savings on all new dwellings. It was established, using appropriate boundary conditions, that a 40% target for water savings is feasible for South East Queensland (SEQ) and provides a cost-benefit ratio of 2.1. These results indicate that a policy of mandating targets for sustainable buildings would provide substantial benefits to the state of Queensland, water utilities and citizens.

This article describes how a model-based analysis was used to aid development of a novel formulation technology. Paracetamol (acetaminophen) was used as the motivating example with 4 different formulations (2 developmental and 2 commercial) compared using stochastic (Monte Carlo) pharmacokinetic (PK)-pharmacodynamic (PD) simulations to explore potential differences in pharmacodynamic outcomes. PK models were developed from data collected during an intensively sampled, 4-arm crossover trial in 25 fasted healthy subjects, administered 1 g of paracetamol in 4 different formulations. The PK models were linked to a previously published PD model that quantified pain relief over time following tonsillectomy. The number needed to treat (NNT) was the primary numeric used to compare effectiveness. The developmental formulations were likely to produce faster and greater analgesia with an NNT (compared with placebo) to reduce pain by 50% over a 45-minute interval post dose of 2.75 and 2.88 compared with 4.31 and 3.2 for the commercial products. Over the course of 1 hour, all formulations were comparable. The stochastic simulations provided support that the novel formulation technology was likely to provide a clinically meaningful advantage and should be developed further.