A Systematic Review of Methods to Incorporate External Evidence into Trial-Based Survival Extrapolations for Health Technology Assessment

Background: External evidence is commonly used to inform survival modeling for health technology assessment (HTA). While there are a range of methodological approaches that have been proposed, it is unclear which methods could be used and how they compare. Purpose: This review aims to identify, describe, and categorize established methods to incorporate external evidence into survival extrapolation for HTA. Data Sources: Embase, MEDLINE, EconLit, and Web of Science databases were searched to identify published methodological studies, supplemented by hand searching and citation tracking. Study Selection: Eligible studies were required to present a novel extrapolation approach incorporating external evidence (i.e., data or information) within survival model estimation. Data Extraction: Studies were classified according to how the external evidence was integrated as a part of model fitting. Information was extracted concerning the model-fitting process, key requirements, assumptions, software, application contexts, and presentation of comparisons with, or validation against, other methods. Data Synthesis: Across 18 methods identified from 22 studies, themes included use of informative prior(s) (n = 5), piecewise (n = 7), and general population adjustment (n = 9), plus a variety of “other” (n = 8) approaches. Most methods were applied in cancer populations (n = 13). No studies compared or validated their method against another method that also incorporated external evidence. Limitations: As only studies with a specific methodological objective were included, methods proposed as part of another study type (e.g., an economic evaluation) were excluded from this review. Conclusions: Several methods were identified in this review, with common themes based on typical data sources and analytical approaches. Of note, no evidence was found comparing the identified methods to one another, and so an assessment of different methods would be a useful area for further research. This review aims to identify methods that have been used to incorporate external evidence into survival extrapolations, focusing on those that may be used to inform health technology assessment. We found a range of different approaches, including piecewise methods, Bayesian methods using informative priors, and general population adjustment methods, as well as a variety of “other” approaches. No studies attempted to compare the performance of alternative methods for incorporating external evidence with respect to the accuracy of survival predictions. Further research investigating this would be valuable

Stabilization of the coupled oxygen and phosphorus cycles by the evolution of bioturbation

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record Animal burrowing and sediment-mixing (bioturbation) began during the run up to the Ediacaran/Cambrian boundary, initiating a transition between the stratified Precambrian and more well-mixed Phanerozoic sedimentary records, against the backdrop of a variable global oxygen reservoir probably smaller in size than present. Phosphorus is the long-term limiting nutrient for oxygen production via burial of organic carbon, and its retention (relative to carbon) within organic matter in marine sediments is enhanced by bioturbation. Here we explore the biogeochemical implications of a bioturbation-induced organic phosphorus sink in a simple model. We show that increased bioturbation robustly triggers a net decrease in the size of the global oxygen reservoir - the magnitude of which is contingent upon the prescribed difference in carbon to phosphorus ratios between bioturbated and laminated sediments. Bioturbation also reduces steady-state marine phosphate levels, but this effect is offset by the decline in iron-adsorbed phosphate burial that results from a decrease in oxygen concentrations. The introduction of oxygen-sensitive bioturbation to dynamical model runs is sufficient to trigger a negative feedback loop: the intensity of bioturbation is limited by the oxygen decrease it initially causes. The onset of this feedback is consistent with redox variations observed during the early Cambrian rise of bioturbation, leading us to suggest that bioturbation helped to regulate early oxygen and phosphorus cycles. © 2014 Macmillan Publishers Limited. All rights reserved.Natural Environment Research Council (NERC)Inge Lehmann ScholarshipVILLUM FoundationNational Basic Research Program of ChinaNational Natural Science Foundation of ChinaDeutsche Forschungsgemeinschaft (DFG

Likelihood of Germline Mutation with Solitary Unilateral Retinoblastoma Based on Patient Age at Presentation. A Real-World Analysis of 482 Consecutive Patients.

Introduction: Retinoblastoma due to germline mutation has a greater risk of bilateral presentation, and multifocal or extraocular involvement. In solitary unilateral retinoblastoma, the inheritance pattern is less understood and assumed to be somatic. We assessed the likelihood of germline inheritance in children with unilateral retinoblastoma and whether it varies based on age at presentation. Methods: This was a retrospective case study assessing 482 consecutive patients with solitary unilateral retinoblastoma at Wills Eye Hospital between 1972 and 2020 for the likelihood of germline inheritance based on age at presentation (≤1 year vs. \u3e1 year). Germline inheritance was deemed likely if there was a family history of retinoblastoma, positive genetic testing, and/or progression to bilateral retinoblastoma. Only patients with \u3e1-month follow-up were included. Chi-square test and Odds Ratio analyses were performed. Results: 465 of the 482 patients had sufficient follow-up data. 16% (n=72) of all patients, and 29% (n=37) of patients ≤1 year of age with unilateral retinoblastoma were likely to have germline disease (p=0.001). When compared to patients \u3e1 year of age (n=339), patients ≤1 year (n=126) demonstrated a greater likelihood of germline inheritance with a 2.96 odds ratio ([1.55 – 5.65]). Discussion: The inheritance of unilateral retinoblastoma is poorly understood. We found that 16% of children with unilateral retinoblastoma likely have germline inheritance, with a greater likelihood in children ≤1 year of age. Therefore, early assessment of inheritance and genetic testing of unilateral retinoblastoma may uncover germline disease and potential bilateral progression, for which a more conservative management approach to preserve vision should be considered

Outcomes Following Open Reduction and Internal Fixation for Distal Humerus Fracture: Does Handedness Matter?

Introduction: No studies have assessed the relationship between extremity dominance and distal humerus fractures. This study sought to compare post-operative outcomes between patients with distal humerus fractures treated by open reduction and internal fixation (ORIF) of their non-dominant vs dominant arm. Methods: A retrospective review of patients who sustained a distal humerus fracture treated with ORIF at one hospital between 2011-2015 was performed. Data collection included demographics, hand dominance, injury information, and surgical management. Post-operative outcomes included complications, time to fracture union, painful hardware, removal of hardware, Mayo Elbow Performance Index (MEPI), and range of motion. Results: Of the 69 patients, 40 (58.0%) underwent ORIF of a distal humerus fracture on their non-dominant arm and 29 (42.0%) on their dominant arm. Groups did not differ with respect to demographics, injury information, or surgical management. Mean overall follow up was 14.1 ± 10.5 months with no difference in follow up or time to fracture union between groups. The non-dominant cohort experienced a higher proportion of post-operative complications (P = 0.048), painful hardware (P = 0.018), and removal of hardware (P = 0.002). At latest follow up, the non-dominant cohort had lower MEPI scores (86.4 vs 94.7, P = 0.037) but no difference in arc of motion (104.3° vs 112.5°, P = 0.314). Discussion: Patients who sustain a distal humerus fracture of their non-dominant arm treated surgically experience more post-operative complications and have worse functional recovery. Physicians should emphasize the importance of therapy and maintaining arm movement, especially with the non-dominant arm