Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review

OBJECTIVES Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. STUDY DESIGN AND SETTING We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. RESULTS We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. CONCLUSION Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics.

IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial

BACKGROUND The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate "patient-centric" outcomes of functional limb preservation, mobility and quality of life (QoL). METHODS/DESIGN IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI. DISCUSSION This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are discussed. IN.PACT DEEP is a milestone, prospective, randomized, robust, independent core lab-adjudicated CLI trial that will evaluate the role of a new infrapopliteal revascularization technology, the IA-DEB, compared to PTA. It will assess the overall impact on infrapopliteal artery patency, limb salvage, wound healing, pain control, QoL, and patient mobility. The 1-year results of the adjudicated co-primary and secondary endpoints will be available in 2014. TRIAL REGISTRATION NCT00941733

Federally regulated institutional review boards: The aspects of a "model" IRB---Is the current system in need of a tune up or complete overhaul?

Institutional Review Boards (IRBs) are the primary gatekeepers for the protection of ethical standards of federally regulated research on human subjects in this country. This paper focuses on what general, broad measures that may be instituted or enhanced to exemplify a "model IRB". This is done by examining the current regulatory standards of federally regulated IRBs, not private or commercial boards, and how many of those standards have been found either inadequate or not generally understood or followed. The analysis includes suggestions on how to bring about changes in order to make the IRB process more efficient, less subject to litigation, and create standardized educational protocols for members. The paper also considers how to include better oversight for multi-center research, increased centralization of IRBs, utilization of Data Safety Monitoring Boards when necessary, payment for research protocol review, voluntary accreditation, and the institution of evaluation/quality assurance programs. ^ This is a policy study utilizing secondary analysis of publicly available data. Therefore, the research for this paper focuses on scholarly medical/legal journals, web information from the Department of Health and Human Services, Federal Drug Administration, and the Office of the Inspector General, Accreditation Programs, law review articles, and current regulations applicable to the relevant portions of the paper. ^ Two issues are found to be consistently cited by the literature as major concerns. One is a need for basic, standardized educational requirements across all IRBs and its members, and secondly, much stricter and more informed management of continuing research. There is no federally regulated formal education system currently in place for IRB members, except for certain NIH-based trials. Also, IRBs are not keeping up with research once a study has begun, and although regulated to do so, it does not appear to be a great priority. This is the area most in danger of increased litigation. Other issues such as voluntary accreditation and outcomes evaluation are slowing gaining steam as the processes are becoming more available and more sought after, such as JCAHO accrediting of hospitals. ^ Adopting the principles discussed in this paper should promote better use of a local IRBs time, money, and expertise for protecting the vulnerable population in their care. Without further improvements to the system, there is concern that private and commercial IRBs will attempt to create a monopoly on much of the clinical research in the future as they are not as heavily regulated and can therefore offer companies quicker and more convenient reviews. IRBs need to consider the advantages of charging for their unique and important services as a cost of doing business. More importantly, there must be a minimum standard of education for all IRB members in the area of the ethical standards of human research and a greater emphasis placed on the follow-up of ongoing research as this is the most critical time for study participants and may soon lead to the largest area for litigation. Additionally, there should be a centralized IRB for multi-site trials or a study website with important information affecting the trial in real time. There needs to be development of standards and metrics to assess the performance of the IRBs for quality assurance and outcome evaluations. The boards should not be content to run the business of human subjects' research without determining how well that function is actually being carried out. It is important that federally regulated IRBs provide excellence in human research and promote those values most important to the public at large.^

Various ratios of C1-C5 hydrocarbons, gas composition and computed temperature at DSDP Leg 64 Holes

I have evaluated shipboard data and preliminary interpretations related to organic geochemistry in light of additional shore-based analyses. Data on interstitial gas, the C/N ratio, and fluorescence indicate that organic matter was altered by sills and that these were all single intrusions except the upper sill complex at Site 481, which was a multiple emplacement. Site 477 had the highest in situ temperature, estimated from interstitial gas composition to be 225°C.

An Inquiry Into The Theory, Causes And Consequences Of Monitoring Indicators Of Health And Safety At Work

This paper engages in an interdisciplinary survey of the current state of knowledge related to the theory, determinants and consequences of occupational safety and health (OSH). First, it synthesizes the available theoretical frameworks used by economists and psychologists to understand the issues related to the optimal provision of OSH in the labour market. Second, it reviews the academic literature investigating the correlates of a comprehensive set of OSH indicators, which portray the state of OSH infrastructure (social security expenditure, prevention, regulations), inputs (chemical and physical agents, ergonomics, working time, violence) and outcomes (injuries, illnesses, absenteeism, job satisfaction) within workplaces. Third, it explores the implications of the lack of OSH in terms of the economic and social costs that are entailed. Finally, the survey identifies areas of future research interests and suggests priorities for policy initiatives that can improve the health and safety of workers.

Roadway Lighting and Safety: Phase II – Monitoring Quality, Durability and Efficiency, November 2011

This Phase II project follows a previous project titled Strategies to Address Nighttime Crashes at Rural, Unsignalized Intersections. Based on the results of the previous study, the Iowa Highway Research Board (IHRB) indicated interest in pursuing further research to address the quality of lighting, rather than just the presence of light, with respect to safety. The research team supplemented the literature review from the previous study, specifically addressing lighting level in terms of measurement, the relationship between light levels and safety, and lamp durability and efficiency. The Center for Transportation Research and Education (CTRE) teamed with a national research leader in roadway lighting, Virginia Tech Transportation Institute (VTTI) to collect the data. An integral instrument to the data collection efforts was the creation of the Roadway Monitoring System (RMS). The RMS allowed the research team to collect lighting data and approach information for each rural intersection identified in the previous phase. After data cleanup, the final data set contained illuminance data for 101 lighted intersections (of 137 lighted intersections in the first study). Data analysis included a robust statistical analysis based on Bayesian techniques. Average illuminance, average glare, and average uniformity ratio values were used to classify quality of lighting at the intersections.

Roadway Lighting and Safety: Phase II – Monitoring Quality, Durability and Efficiency, November 2011

This Phase II project follows a previous project titled Strategies to Address Nighttime Crashes at Rural, Unsignalized Intersections. Based on the results of the previous study, the Iowa Highway Research Board (IHRB) indicated interest in pursuing further research to address the quality of lighting, rather than just the presence of light, with respect to safety. The research team supplemented the literature review from the previous study, specifically addressing lighting level in terms of measurement, the relationship between light levels and safety, and lamp durability and efficiency. The Center for Transportation Research and Education (CTRE) teamed with a national research leader in roadway lighting, Virginia Tech Transportation Institute (VTTI) to collect the data. An integral instrument to the data collection efforts was the creation of the Roadway Monitoring System (RMS). The RMS allowed the research team to collect lighting data and approach information for each rural intersection identified in the previous phase. After data cleanup, the final data set contained illuminance data for 101 lighted intersections (of 137 lighted intersections in the first study). Data analysis included a robust statistical analysis based on Bayesian techniques. Average illuminance, average glare, and average uniformity ratio values were used to classify quality of lighting at the intersections.

Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods, [and] Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes

Rapport de synthèse1. Partie de laboratoireCette première étude décrit le développement et la validation, selon les standards internationaux, de deux techniques de mesure des concentrations sanguines de voriconazole, un nouvel agent antifongique à large spectre: 1) la chromatographic en phase liquide à haute pression et 2) le bio-essai utilisant une souche mutante de Candida hypersensible au voriconazole. Ce travail a aussi permis de mettre en évidence une importante et imprévisible variabilité inter- et intra-individuelle des concentrations sanguines de voriconazole malgré l'utilisation des doses recommandées par le fabriquant. Ce travail a été publié dans un journal avec "peer-review": "Variability of voriconazole plasma levels measured by new high- performance liquid chromatography and bioassay methods" by A. Pascual, V. Nieth, T. Calandra, J. Bille, S. Bolay, L.A. Decosterd, T. Buclin, P.A. Majcherczyk, D. Sanglard, 0. Marchetti. Antimicrobial Agents Chemotherapy, 2007; 51:137-432. Partie CliniqueCette deuxième étude a évalué de façon prospective l'impact clinique des concentrations sanguines de voriconazole sur l'efficacité et sécurité thérapeutique chez des patients atteints d'infections fongiques. Des concentrations sanguines élevées étaient significativement associés à la survenue d'une toxicité neurologique (encéphalopathie avec confusion, hallucinations et myoclonies) et des concentrations sanguines basses à une réponse insuffisante au traitement antifongique (persistance ou progression des signes cliniques et radiologiques de l'infection). Dans la majorité des cas, un ajustement de la dose de voriconazole, sur la base des concentrations mesurées, a abouti à une récupération neurologique complète ou à une résolution de l'infection, respectivement. Ce travail a été publié dans un journal avec "peer-review": " Voriconazole Therapeutic Drug Monitoring in Patients with Invasive Mycoses Improves Efficacy and Safety Outcomes" by A. Pascual, T. Calandra, S. Bolay, T. Buclin, J. Bille, and O. Marchetti. Clinical Infectious Diseases, 2008 January 15; 46(2): 201-11.Ces deux études, financées de façon conjointe par un "grant" international de la Société suisse d'infectiologie et la Société internationale de maladies infectieuses et par la Fondation pour le progrès en microbiologie médicale et maladies infectieuses (FAMMID, Lausanne), ont été réalisées au sein du Service des Maladies Infectieuses, Département de Médecine, au CHUV, en étroite collaboration avec la Division de Pharmacologie Clinique, Département de Médecine, au CHUV et l'Institut de Microbiologie du CHUV et de l'Université de Lausanne.

A European survey on current practices in epilepsy monitoring units and implications for patients' safety.

OBJECTIVE: This study aimed to survey current practices in European epilepsy monitoring units (EMUs) with emphasis on safety issues. METHODS: A 37-item questionnaire investigating characteristics and organization of EMUs, including measures for prevention and management of seizure-related serious adverse events (SAEs), was distributed to all identified European EMUs plus one located in Israel (N=150). RESULTS: Forty-eight (32%) EMUs, located in 18 countries, completed the questionnaire. Epilepsy monitoring unit beds are 1-2 in 43%, 3-4 in 34%, and 5-6 in 19% of EMUs; staff physicians are 1-2 in 32%, 3-4 in 34%, and 5-6 in 19% of EMUs. Personnel operating in EMUs include epileptologists (in 69% of EMUs), clinical neurophysiologists trained in epilepsy (in 46% of EMUs), child neurologists (in 35% of EMUs), neurology and clinical neurophysiology residents (in 46% and in 8% of EMUs, respectively), and neurologists not trained in epilepsy (in 27% of EMUs). In 20% of EMUs, patients' observation is only intermittent or during the daytime and primarily carried out by neurophysiology technicians and/or nurses (in 71% of EMUs) or by patients' relatives (in 40% of EMUs). Automatic detection systems for seizures are used in 15%, for body movements in 8%, for oxygen desaturation in 33%, and for ECG abnormalities in 17% of EMUs. Protocols for management of acute seizures are lacking in 27%, of status epilepticus in 21%, and of postictal psychoses in 87% of EMUs. Injury prevention consists of bed protections in 96% of EMUs, whereas antisuffocation pillows are employed in 21%, and environmental protections in monitoring rooms and in bathrooms are implemented in 38% and in 25% of EMUs, respectively. The most common SAEs were status epilepticus reported by 79%, injuries by 73%, and postictal psychoses by 67% of EMUs. CONCLUSIONS: All EMUs have faced different types of SAEs. Wide variation in practice patterns and lack of protocols and of precautions to ensure patients' safety might promote the occurrence and severity of SAEs. Our findings highlight the need for standardized and shared protocols for an effective and safe management of patients in EMUs.

Leading Safety Indicators: Proactively Monitoring Safety Performance

Traditional measures or indicators of workplace safety performance reflect unrecognized hazards, unsafe conditions, reckless behavior, and other safety program shortcomings only after a worker is injured or falls ill. In contrast to traditional or lagging indicators, leading indicators can predict poor safety performance to ensure that safety program failings are addressed before an occupational injury or illness actually occurs. This Capstone Project identified a variety of proactive safety management practices, policies, and activities shown to have a positive impact on workplace safety as leading safety indicators. The end result is a comprehensive framework of leading safety indicators that employers can use to proactively gauge safety program performance and address unrecognized hazards, unsafe conditions, reckless behavior, and other safety program deficiencies.

High speed image techniques for construction safety net monitoring in outdoor conditions

Póster presentado en SPIE Photonics Europe, Brussels, 16-19 April 2012.