Bureaucracy stifles medical research in Britain: a tale of three trials

<p>Abstract</p> <p>Background</p> <p>Recent developments aiming to standardise and streamline processes of gaining the necessary approvals to carry out research in the National Health Service (NHS) in the United Kingdom (UK), have resulted in lengthy and costly delays. The national UK governmental Department of Health’s Research Governance Framework (RGF) for Health and Social Care requires that appropriate checks be conducted before research involving human participants, their organs, tissues or data can commence in the NHS. As a result, medical research has been subjected to increased regulation and governance, with the requirement for approvals from numerous regulatory and monitoring bodies. In addition, the processes and outcomes of the attribution of costs in NHS research have caused additional difficulties for researchers. The purpose of this paper is to illustrate, through three trial case studies, the difficulties encountered during the set-up and recruitment phases of these trials, related to gaining the necessary ethical and governance approvals and applying for NHS costs to undertake and deliver the research.</p> <p>Methods</p> <p>Empirical evidence about delays and difficulties related to regulation and governance of medical research was gathered during the period 2009–2010 from three UK randomised controlled trials with sites in England, Wales and Scotland (1. SAFER 2- an emergency care based trial of a protocol for paramedics to refer patients directly to community based falls services; 2. COnStRUCT- a trial of two drugs for acute ulcerative colitis; and 3. Family Links - a trial of a public health intervention, a 10 week community based parenting programme). Findings and recommendations were reported in response to a call for evidence from The Academy of Medical Sciences regarding difficulties encountered in conducting medical research arising from R&D governance and regulation, to inform national policy.</p> <p>Results</p> <p>Difficulties and delays in navigating and gaining the appropriate approvals and NHS costs required to undertake the research were encountered in all three trials, at various points in the bureaucratic processes of ethical and research and information governance approvals. Conduct of each of the three trials was delayed by at least 12 months, with costs increasing by 30 – 40%.</p> <p>Conclusions</p> <p>Whilst the three trials encountered a variety of challenges, there were common issues. The processes for gaining approvals were overly complex and differed between sites and UK countries; guidance about processes was unclear; and information regarding how to define and claim NHS costs for undertaking the research was inconsistent. The competitive advantage of a publicly funded, open access health system for undertaking health services research and clinical trials within the UK has been outweighed in recent years by stifling bureaucratic structures and processes for governance of research. The recommendations of the Academy of Medical Sciences are welcomed, and the effects of their implementation are awaited with interest.</p> <p>Trial Registration numbers</p> <p>SAFER 2: ISRCTN 60481756; COnStRUCT: ISRCTN22663589; Family Links: ISRCTN 13929732</p

Abrupt Ice Age Shifts in Southern Westerlies and Antarctic Climate Forced from the North

The Southern Hemisphere (SH) mid-latitude westerly winds play a central role in the global climate system via Southern Ocean upwelling, carbon exchange with the deep ocean, Agulhas Leakage, and Antarctic ice sheet stability. Meridional shifts in the SH westerlies have been hypothesized in response to abrupt North Atlantic Dansgaard-Oeschger (DO) climatic events of the last ice age, in parallel with the well-documented shifts of the intertropical convergence zone. Shifting moisture pathways to West Antarctica are consistent with this view, but may represent a Pacific teleconnection pattern. The full SH atmospheric-circulation response to the DO cycle, as well as its impact on Antarctic temperature, have so far remained unclear. Here we use five volcanically-synchronized ice cores to show that the Antarctic temperature response to the DO cycle can be understood as the superposition of two modes: a spatially homogeneous oceanic “bipolar seesaw” mode that lags Northern Hemisphere (NH) climate by about 200 years, and a spatially heterogeneous atmospheric mode that is synchronous with NH abrupt events. Temperature anomalies of the atmospheric mode are similar to those associated with present-day Southern Annular Mode (SAM) variability, rather than the Pacific South America (PSA) pattern. Moreover, deuterium excess records suggest a zonally coherent migration of the SH westerlies over all ocean basins in phase with NH climate. Our work provides a simple conceptual framework for understanding the circum-Antarctic temperature response to abrupt NH climate change. We provide observational evidence for abrupt shifts in the SH westerlies, with ramifications for global ocean circulation and atmospheric CO₂. These coupled changes highlight the necessity of a global, rather than a purely North Atlantic, perspective on the DO cycle

Amplified melt and flow of the Greenland ice sheet driven by late-summer cyclonic rainfall

Intense rainfall events significantly affect Alpine and Alaskan glaciers through enhanced melting, ice-flow acceleration and subglacial sediment erosion, yet their impact on the Greenland ice sheet has not been assessed. Here we present measurements of ice velocity, subglacial water pressure and meteorological variables from the western margin of the Greenland ice sheet during a week of warm, wet cyclonic weather in late August and early September 2011. We find that extreme surface runoff from melt and rainfall led to a widespread acceleration in ice flow that extended 140 km into the ice-sheet interior. We suggest that the late-season timing was critical in promoting rapid runoff across an extensive bare ice surface that overwhelmed a subglacial hydrological system in transition to a less-efficient winter mode. Reanalysis data reveal that similar cyclonic weather conditions prevailed across southern and western Greenland during this time, and we observe a corresponding ice-flow response at all land- and marine-terminating glaciers in these regions for which data are available. Given that the advection of warm, moist air masses and rainfall over Greenland is expected to become more frequent in the coming decades, our findings portend a previously unforeseen vulnerability of the Greenland ice sheet to climate change

Synchronous volcanic eruptions and abrupt climate change ∼17.7 ka plausibly linked by stratospheric ozone depletion.

Glacial-state greenhouse gas concentrations and Southern Hemisphere climate conditions persisted until ∼17.7 ka, when a nearly synchronous acceleration in deglaciation was recorded in paleoclimate proxies in large parts of the Southern Hemisphere, with many changes ascribed to a sudden poleward shift in the Southern Hemisphere westerlies and subsequent climate impacts. We used high-resolution chemical measurements in the West Antarctic Ice Sheet Divide, Byrd, and other ice cores to document a unique, ∼192-y series of halogen-rich volcanic eruptions exactly at the start of accelerated deglaciation, with tephra identifying the nearby Mount Takahe volcano as the source. Extensive fallout from these massive eruptions has been found >2,800 km from Mount Takahe. Sulfur isotope anomalies and marked decreases in ice core bromine consistent with increased surface UV radiation indicate that the eruptions led to stratospheric ozone depletion. Rather than a highly improbable coincidence, circulation and climate changes extending from the Antarctic Peninsula to the subtropics-similar to those associated with modern stratospheric ozone depletion over Antarctica-plausibly link the Mount Takahe eruptions to the onset of accelerated Southern Hemisphere deglaciation ∼17.7 ka

Southern Hemisphere climate variability forced by Northern Hemisphere ice-sheet topography

The presence of large Northern Hemisphere ice sheets and reduced greenhouse gas concentrations during the Last Glacial Maximum fundamentally altered global ocean–atmosphere climate dynamics1. Model simulations and palaeoclimate records suggest that glacial boundary conditions affected the El Niño–Southern Oscillation2,3, a dominant source of short-term global climate variability. Yet little is known about changes in short-term climate variability at mid- to high latitudes. Here we use a high-resolution water isotope record from West Antarctica to demonstrate that interannual to decadal climate variability at high southern latitudes was almost twice as large at the Last Glacial Maximum as during the ensuing Holocene epoch (the past 11,700 years). Climate model simulations indicate that this increased variability reflects an increase in the teleconnection strength between the tropical Pacific and West Antarctica, owing to a shift in the mean location of tropical convection. This shift, in turn, can be attributed to the influence of topography and albedo of the North American ice sheets on atmospheric circulation. As the planet deglaciated, the largest and most abrupt decline in teleconnection strength occurred between approximately 16,000 years and 15,000 years ago, followed by a slower decline into the early Holocene

Carbonyl sulfide hydrolysis in antarctic ice cores and an atmospheric history for the last 8000 years

Carbonyl sulfide (COS) was measured in Antarctic ice core samples from the Byrd, Siple Dome, Taylor Dome, and West Antarctic Ice Sheet Divide sites covering the last 8000 years of the Holocene. COS levels decrease downcore in most of these ice cores. The magnitude of the downcore trends varies among the different ice cores and is related to the thermal histories of the ice sheet at each site. We hypothesize that this is due to the temperature-dependent hydrolysis of COS that occurs in situ. We use a one-dimensional ice flow and heat flux model to infer temperature histories for the ice core samples from different sites and empirically determine the kinetic parameters for COS hydrolysis. We estimate e-folding lifetimes for COS hydrolysis ranging from 102 years to 106 years over a temperature range of 0°C to - 50°C. The reaction kinetics are used to estimate and correct for the in situ COS loss, allowing us to reconstruct paleoatmospheric COS trends during the mid-to-late Holocene. The results suggest a slow, long-term increase in atmospheric COS that may have started as early as 5000 years ago. Given that the largest term in the COS budget is uptake by terrestrial plants, this could indicate a decline in terrestrial productivity during the late Holocene

Changes in atmospheric carbonyl sulfide over the last 54,000years inferred from measurements in Antarctic ice cores

We measured carbonyl sulfide (COS) in air extracted from ice core samples from the West Antarctic Ice Sheet (WAIS) Divide, Antarctica, with the deepest sample dated to 54,300 years before present. These are the first ice core COS measurements spanning the Last Glacial Maximum (LGM), the last glacial/interglacial transition, and the early Holocene. The WAIS Divide measurements from the LGM and the last transition are the first COS measurements in air extracted from full clathrate (bubble-free) ice. This study also includes new COS measurements from Taylor Dome, Antarctica, including some in bubbly glacial ice that are concurrent with the WAIS Divide data from clathrate glacial ice. COS hydrolyzes in ice core air bubbles, and the recovery of an atmospheric record requires correcting for this loss. The data presented here suggest that the in situ hydrolysis of COS is significantly slower in clathrate ice than in bubbly ice. The clathrate ice measurements are corrected for the hydrolysis loss during the time spent as bubbly ice only. The corrected WAIS Divide record indicates that atmospheric COS was 250–300 parts per trillion (ppt) during the LGM and declined by 80–100 ppt during the last glacial/interglacial transition to a minimum of 160–210 ppt at the beginning of the Holocene. This decline was likely caused by an increase in the gross primary productivity of terrestrial plants, with a possible contribution from a reduction in ocean sources. COS levels were above 300 ppt in the late Holocene, indicating that large changes in the COS biogeochemical cycle occurred during the Holocene