Health Technology Assessment (HTA) Case Studies : Factors Influencing Divergent HTA Reimbursement Recommendations in Australia, Canada, England, and Scotland

This document is the accepted manuscript version of the following article: Nicola Allen, Stuart R. Walker, Lawrence Liberti, and Sam Salek, ‘Health Technology Assessment (HTA) Case Studies: Factors Influencing Divergent HTA Reimbursement Recommendations in Australia, Canada, England, and Scotland’, Vol. 20 (3): 320-328, 2017, is made available under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The final, definitive version is available online at doi:https://doi.org/10.1016/j.jval.2016.10.014.OBJECTIVES: To evaluate the national regulatory, health technology assessment (HTA), and reimbursement pathways for public health care in Australia, Canada, England, and Scotland, to compare initial Canadian national HTA recommendations with the initial decisions of the other HTA agencies, and to identify factors for differing national HTA recommendations between the four HTA agencies. METHODS: Information from the public domain was used to develop a regulatory process map for each jurisdiction and to compare the HTA agencies' reimbursement recommendations. Medicines that were reviewed by all four agencies and received a negative recommendation from only one agency were selected as case studies. RESULTS: All four countries have a national HTA agency. Their reimbursement recommendations are guided by both clinical efficacy and cost-effectiveness, and the necessity for patient input. Their activities, however, vary because of different mandates and their unique political, social, and population needs. All have an implicit or explicit quality-adjusted life-year threshold. The seven divergent case studies demonstrate examples in which new medicine-indication pairs have been rejected because of uncertainties surrounding a range of factors including cost-effectiveness, comparator choice, clinical benefit, safety, trial design, and submission timing. CONCLUSIONS: The four HTA agencies selected for inclusion in this study share common factors, including a focus on clinical efficacy and cost-effectiveness in their decision-making processes. The differences in recommendations could be considered to be due to an individual agency's approach to risk perception, and the comparator choice used in clinical and cost-effectiveness studies.Peer reviewedFinal Accepted Versio

Numerical modeling of three-dimensional stratified tidal flow over Camarinal Sill, Strait of Gibraltar

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): C12026, doi:10.1029/2011JC007093.The baroclinic response to barotropic tidal forcing in the Camarinal Sill area, within the Strait of Gibraltar, is investigated with a three-dimensional, fully nonlinear, nonhydrostatic numerical model. The aim of numerical efforts was the assessment of three-dimensional effects, which are potentially significant in the area because of rather irregular bottom topography, variable background stratification, and complex structure of barotropic tides. Model results reveal a complex baroclinic response under relatively moderate flood tidal currents, which includes the formation of internal hydraulic jumps upstream of the sill, internal cross waves close to the channel walls, and a plunging pycnocline at the lee side of the sill crest. These structures exhibit significant cross-channel spatial dependence and may appear to be aligned together across the channel. This fact makes their identification difficult from the surface pattern captured by remote sensing images. Under strong barotropic forcing (spring tides) the upstream hydraulic jumps are shifted to the lee side of Camarinal Sill, where a single internal hydraulic jump is formed. Significant first- and second-mode hydraulic jumps are also generated near smaller secondary sills in Tangier basin, thus extending the occurrence of intense water mixing and energy dissipation to other zones of the strait.This work is a contribution to the Spanishfunded National Project INGRES-2 (CTM2006-02326). Partial financial support from Acción Complementaria CTM2009-05810/E (Spanish Ministry of Science and Innovation) and project P08-RNM-3738 from Plan Andaluz de Investigación (Andalucia regional government) is acknowledged.2012-06-1

Regulatory reliance pathways during health emergencies: enabling timely authorizations for COVID-19 vaccines in Latin America

Objectives: To map the timing and nature of regulatory reliance pathways used to authorize COVID-19 vaccines in Latin America. Methods: An observational study was conducted assessing the characteristics of all COVID-19 vaccine authorizations in Latin America. For every authorization it was determined whether reliance was used in the authorization process. Subgroups of reference national regulatory authorities (NRAs) and non-reference NRAs were compared. Results: 56 authorizations of 10 different COVID-19 vaccines were identified in 18 countries, of which 25 (44.6%) used reliance and 12 (21.4%) did not. For the remaining 19 (33.0%) it was not possible to determine whether reliance was used. Reference agencies used reliance less often (40% of authorizations with a known pathway) compared to non-reference agencies (100%). The median review time was just 15 days and does not meaningfully differ between reliance and non-reliance authorizations. Conclusions: This study demonstrated that for these vaccines, despite reliance pathways being associated with numerous rapid authorizations, independent authorization review times were not considerably longer than reliance reviews; reliance pathways were not a prerequisite for rapid authorization. Nevertheless, reliance pathways provided rapid authorizations in response to the COVID-19 emergency

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Studies of new Higgs boson interactions through nonresonant HH production in the b¯bγγ fnal state in pp collisions at √s = 13 TeV with the ATLAS detector

A search for nonresonant Higgs boson pair production in the b ¯bγγ fnal state is performed using 140 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. This analysis supersedes and expands upon the previous nonresonant ATLAS results in this fnal state based on the same data sample. The analysis strategy is optimised to probe anomalous values not only of the Higgs (H) boson self-coupling modifer κλ but also of the quartic HHV V (V = W, Z) coupling modifer κ2V . No signifcant excess above the expected background from Standard Model processes is observed. An observed upper limit µHH < 4.0 is set at 95% confdence level on the Higgs boson pair production cross-section normalised to its Standard Model prediction. The 95% confdence intervals for the coupling modifers are −1.4 < κλ < 6.9 and −0.5 < κ2V < 2.7, assuming all other Higgs boson couplings except the one under study are fxed to the Standard Model predictions. The results are interpreted in the Standard Model efective feld theory and Higgs efective feld theory frameworks in terms of constraints on the couplings of anomalous Higgs boson (self-)interactions

Comparison of inclusive and photon-tagged jet suppression in 5.02 TeV Pb+Pb collisions with ATLAS

Parton energy loss in the quark–gluon plasma (QGP) is studied with a measurement of photon-tagged jet production in 1.7 nb−1 of Pb+Pb data and 260 pb−1 of pp data, both at sNN=5.02 TeV, with the ATLAS detector. The process pp →γ+jet+X and its analogue in Pb+Pb collisions is measured in events containing an isolated photon with transverse momentum (pT) above 50 GeV and reported as a function of jet pT. This selection results in a sample of jets with a steeply falling pT distribution that are mostly initiated by the showering of quarks. The pp and Pb+Pb measurements are used to report the nuclear modification factor, RAA, and the fractional energy loss, Sloss, for photon-tagged jets. In addition, the results are compared with the analogous ones for inclusive jets, which have a significantly smaller quark-initiated fraction. The RAA and Sloss values are found to be significantly different between those for photon-tagged jets and inclusive jets, demonstrating that energy loss in the QGP is sensitive to the colour-charge of the initiating parton. The results are also compared with a variety of theoretical models of colour-charge-dependent energy loss

Model-independent search for the presence of new physics in events including H → γγ with s \sqrt{s} = 13 TeV pp data recorded by the ATLAS detector at the LHC

Abstract A model-independent search for new physics leading to final states containing a Higgs boson, with a mass of 125.09 GeV, decaying to a pair of photons is performed with 139 fb−1 of s $$\sqrt{s}$$ = 13 TeV pp collision data recorded by the ATLAS detector at the Large Hadron Collider at CERN. This search examines 22 final states categorized by the objects that are produced in association with the Higgs boson. These objects include isolated electrons or muons, hadronically decaying τ-leptons, additional photons, missing transverse momentum, and hadronic jets, as well as jets that are tagged as containing a b-hadron. No significant excesses above Standard Model expectations are observed and limits on the production cross section at 95% confidence level are set. Detector efficiencies are reported for all 22 signal regions, which can be used to convert detector-level cross-section limits reported in this paper to particle-level cross-section constraints

Search for neutral long-lived particles in pp collisions at √s = 13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

A search for decays of pair-produced neutral long-lived particles (LLPs) is presented using 139 fb−1 of proton-proton collision data collected by the ATLAS detector at the LHC in 2015–2018 at a centre-of-mass energy of 13 TeV. Dedicated techniques were developed for the reconstruction of displaced jets produced by LLPs decaying hadronically in the ATLAS hadronic calorimeter. Two search regions are defined for different LLP kinematic regimes. The observed numbers of events are consistent with the expected background, and limits for several benchmark signals are determined. For a SM Higgs boson with a mass of 125 GeV, branching ratios above 10% are excluded at 95% confidence level for values of c times LLP mean proper lifetime in the range between 20 mm and 10 m depending on the model. Upper limits are also set on the cross-section times branching ratio for scalars with a mass of 60 GeV and for masses between 200 GeV and 1 TeV. [Figure not available: see fulltext.