Exploring Structural Uncertainty and Impact of Health State Utility Values on Lifetime Outcomes in Diabetes Economic Simulation Models: Findings from the Ninth Mount Hood Diabetes Quality-of-Life Challenge

Background Structural uncertainty can affect model-based economic simulation estimates and study conclusions. Unfortunately, unlike parameter uncertainty, relatively little is known about its magnitude of impact on life-years (LYs) and quality-adjusted life-years (QALYs) in modeling of diabetes. We leveraged the Mount Hood Diabetes Challenge Network, a biennial conference attended by international diabetes modeling groups, to assess structural uncertainty in simulating QALYs in type 2 diabetes simulation models. Methods Eleven type 2 diabetes simulation modeling groups participated in the 9th Mount Hood Diabetes Challenge. Modeling groups simulated 5 diabetes-related intervention profiles using predefined baseline characteristics and a standard utility value set for diabetes-related complications. LYs and QALYs were reported. Simulations were repeated using lower and upper limits of the 95% confidence intervals of utility inputs. Changes in LYs and QALYs from tested interventions were compared across models. Additional analyses were conducted postchallenge to investigate drivers of cross-model differences. Results Substantial cross-model variability in incremental LYs and QALYs was observed, particularly for HbA1c and body mass index (BMI) intervention profiles. For a 0.5%-point permanent HbA1c reduction, LY gains ranged from 0.050 to 0.750. For a 1-unit permanent BMI reduction, incremental QALYs varied from a small decrease in QALYs (−0.024) to an increase of 0.203. Changes in utility values of health states had a much smaller impact (to the hundredth of a decimal place) on incremental QALYs. Microsimulation models were found to generate a mean of 3.41 more LYs than cohort simulation models ( P = 0.049). Conclusions Variations in utility values contribute to a lesser extent than uncertainty captured as structural uncertainty. These findings reinforce the importance of assessing structural uncertainty thoroughly because the choice of model (or models) can influence study results, which can serve as evidence for resource allocation decisions. Highlights The findings indicate substantial cross-model variability in QALY predictions for a standardized set of simulation scenarios and is considerably larger than within model variability to alternative health state utility values (e.g., lower and upper limits of the 95% confidence intervals of utility inputs). There is a need to understand and assess structural uncertainty, as the choice of model to inform resource allocation decisions can matter more than the choice of health state utility values.

The Mount Hood fault zone, active faulting at the crest of the dynamic Cascade Range, north-central Oregon, USA

ABSTRACT The Mount Hood fault zone is a N-trending, ~55-km-long zone of active faulting along the western margin of the Hood River graben in north-central Oregon. The Mount Hood fault zone occurs along the crest of the Cascade Range and consists of multiple active fault segments. It is presently unclear how much Hood River graben extension is actively accommodated on the fault zone, and how Cascade intra-arc extension accommodates regional patterns of clockwise rotation and northwest translation of crustal blocks in the Pacific Northwest region of the United States. Evidence for Holocene activity on the Mount Hood fault zone was discovered in 2009 after acquisition of high-resolution lidar topography of the area. This trip will visit sites displaying evidence of Holocene surface rupture on fault strands within the Mount Hood fault zone. Day 1 starts with a two-hour drive from Portland to Mount Hood, a 3429-m-high glaciated active volcano, where we will visit sites south of the summit along the Twin Lakes fault segment, including several fault scarps and two sites where dating of offset buried soils constrains the timing of the most recent surface-rupturing event to the Holocene. Day 1 includes two hikes of ~1 km and will be partly cross-country. The trip will overnight at the historic Timberline Lodge, an architectural masterpiece from the Civilian Conservation Corps (1933–1942) era, located at tree line on the southern flank of Mount Hood. Day 2 will visit sites north of the summit, stopping along the Blue Ridge fault segment to view the site of 2011 paleoseismic trenches and an offset glacial moraine. We will visit an unusual uphill-facing scarp in coarse talus along the Gate Creek fault segment near the north end of the Mount Hood fault zone. We will conclude Day 2 with a short hike into the Mark O. Hatfield Wilderness along the Gate Creek fault segment to view evidence of a surface-rupturing earthquake that occurred only a few centuries ago, illuminated by a nearby paleoseismic trench hand-dug in 2020. Our neotectonic and paleoseismic data are among the first efforts to document and characterize seismic sources within the Mount Hood fault zone. However, even with our new age data, fault slip rates and earthquake recurrence remain poorly constrained. With our limited earthquake timing data, it is not clear whether all segments of the Mount Hood fault zone rupture together as a ≥ M 7 earthquake, or alternatively, if the fault segments rupture independently in a sequence of smaller ~M 6–sized events.