Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Guidance

  • TRU guidance
  • anticipatory guidance
  • attentional guidance
  • cell guidance
  • detailed guidance
  • draft guidance
  • endoscopic guidance
  • ethical guidance
  • fda guidance
  • fluoroscopic guidance
  • image guidance
  • little guidance
  • national guidance
  • new guidance
  • nice guidance
  • offer guidance
  • policy guidance
  • practical guidance
  • regulatory guidance
  • sonographic guidance
  • specific guidance
  • ultrasonographic guidance
  • ultrasound guidance
  • us guidance
  • useful guidance
  • valuable guidance

  • Terms modified by Guidance

  • guidance cue
  • guidance document
  • guidance law
  • guidance molecule
  • guidance system
  • guidance technique

  • Selected Abstracts


    Marco Caliendo
    Abstract Propensity score matching (PSM) has become a popular approach to estimate causal treatment effects. It is widely applied when evaluating labour market policies, but empirical examples can be found in very diverse fields of study. Once the researcher has decided to use PSM, he is confronted with a lot of questions regarding its implementation. To begin with, a first decision has to be made concerning the estimation of the propensity score. Following that one has to decide which matching algorithm to choose and determine the region of common support. Subsequently, the matching quality has to be assessed and treatment effects and their standard errors have to be estimated. Furthermore, questions like ,what to do if there is choice-based sampling?' or ,when to measure effects?' can be important in empirical studies. Finally, one might also want to test the sensitivity of estimated treatment effects with respect to unobserved heterogeneity or failure of the common support condition. Each implementation step involves a lot of decisions and different approaches can be thought of. The aim of this paper is to discuss these implementation issues and give some guidance to researchers who want to use PSM for evaluation purposes. [source]


    Jeng-Yu Wang
    ABSTRACT In this paper, we present various linear analyses of the linearized lateral dynamics of heavy-duty vehicles (HDVs) (tractor-semitrailer type), which include time domain, frequency domain and pole/zero analyses. These analyses are conducted to examine the vehicle response to the steering input subjected to variations of speed, road adhesion coefficient, cargo load in the trailer, and look-ahead distance for the lateral deviation sensor. These parameters (uncertainties) have significant influence on vehicle dynamics. It has been shown that redefining the look-ahead lateral error as the controlled output has a favorable impact on the lateral control problem. Based on these analyses, a robust steering controller using H, loop-shaping procedure is designed for a tractor semitrailer combination to follow the road center line on both curved and straight highway sections. The proposed controller ensures the robust performance under model uncertainties which include varying vehicle longitudinal speed, road adhesion coefficient, and cargo load in the trailer. The performance of the designed controller is evaluated by simulations and validated by experiments. [source]

    Guidance for non-gynaecological cytology , a platform for the future

    CYTOPATHOLOGY, Issue 5 2009
    S. Slater
    No abstract is available for this article. [source]

    Microgeographic genetic isolation in chub (Cyprinidae: Squalius cephalus) population of the Durance River: estimating fragmentation by dams

    C. Dehais
    Dehais C, Eudeline R, Berrebi P, Argillier C. Microgeographic genetic isolation in chub (Cyprinidae: Squalius cephalus) population of the Durance River: estimating fragmentation by dams. Ecology of Freshwater Fish 2010: 19: 267,278. 2010 John Wiley & Sons A/S Abstract ,, Weirs and dams are wide spread throughout the world's river systems. The most direct effect of these barriers is the limitation of organism movements, i.e., the alteration of connectivity by fragmentation of the aquatic habitat. Whereas the impact of fragmentation on migratory fish species has been well studied, insights on nonmigratory species are still needed. In particular, knowledge on the effects of dams on cyprinid populations at the watershed scale is lacking. Therefore, we studied the genetic structure of eleven chub (Squalius cephalus) samples lined up in the highly fragmented Durance River (France). Using five microsatellite loci, we show that even if the overall genetic differentiation is low, isolation by distance does occur and that genetic diversity increases from upstream to downstream. Dams seem to participate jointly with waterway distance in the explanation of this pattern. However more precise conclusions cannot be made. Guidance for future studies are given. [source]

    Emergency Nurses' Utilization of Ultrasound Guidance for Placement of Peripheral Intravenous Lines in Difficult-access Patients

    Larry Brannam MD
    Objectives: Emergency nurses (ENs) typically place peripheral intravenous (IV) lines, but if repeated attempts fail, emergency physicians have to obtain peripheral or central access. The authors describe the patient population for which ultrasound (US)-guided peripheral IVs are used and evaluate the success rates for such lines by ENs. Methods: This was a prospective observational study of ENs in a Level I trauma center with a census of 75,000, performing US-guided IV line placement on difficult-to-stick patients (repeated blind IV placement failure or established history). ENs were trained on an inanimate model after a 45-minute lecture. Surveys were filled out after each US-guided IV attempt on a patient. ENs could decline to fill out surveys, which recorded the reason for use of US, type of patient, and success. Successful cannulation was confirmed by drawing blood and flushing fluids. Descriptive statistics were used to evaluated data. Results: A total of 321 surveys were collected in a five-month period no ENs declined to participate. There were 280 (87%) successful attempts. Twelve (29%) of the 41 failure patients required central lines, 9 (22%) received external jugular IVs, and 20 (49%) had peripheral IV access placed under US guidance by another nurse or physician. Twenty-eight percent (90) of all patients were obese, 18% (57) had sickle cell anemia, 10% (31) were renal dialysis patients, 12% (40) were IV drug abusers, and 19% (61) had unspecified chronic illness. The remainder had no reason for difficult access given. There were four arterial punctures. Conclusions: ENs had a high success rate and few complications with use of US guidance for vascular access in a variety of difficult-access patients. [source]

    Cognitive Processes in Eye Guidance

    K. A. Jellinger
    No abstract is available for this article. [source]

    Stable Non-Covalent Large Area Patterning of Inert Teflon-AF Surface: A New Approach to Multiscale Cell Guidance,

    Francesco Valle
    Micro- and nano-patterning of cell adhesion proteins is demonstrated to direct the growth of neural cells, viz. human neuroblastoma SHSY5Y, at precise positions on a strongly antifouling substrate of technolological interest. We adopt a soft-lithographic approach with oxygen plasma modified PDMS stamps to pattern human laminin on Teflon-AF films. These patterns are based on the interplay of capillary forces within the stamp and non-covalent intermolecular and surface interactions. Remarkably, they remain stable for several days upon cell culture conditions. The fabrication of substrates with adjacent antifouling and adhesion-promoting regions allows us to reach absolute spatial control in the positioning of neuroblastoma cells on the Teflon-AF films. This patterning approach of a technologically-relevant substrate can be of interest in tissue engineering and biosensing. [source]

    An International Comparison of Materiality Guidance for Governments, Public Services and Charities

    Rene Price
    This article compares international and country,specific guidance associated with the materiality concept as it applies to the public sector and charitable entities. The proliferation of multiple terms with similar meanings is evidenced in Australia, Canada, New Zealand, the United Kingdom , England, Ireland and Scotland , and international guidance. Alignment of terminology could enhance harmonization of standards and increase the chances that application of standards is comparable. Conceptual dimensions of materiality in the public sector emphasize qualitative considerations such as legal compliance, fiduciary responsibility, timeliness, and follow,up. [source]

    Correction: High-Resolution Patterning of Hydrogels in Three Dimensions using Direct-Write Photofabrication for Cell Guidance

    Stephanie K. Seidlits
    No abstract is available for this article. [source]

    High-Resolution Patterning of Hydrogels in Three Dimensions using Direct-Write Photofabrication for Cell Guidance

    Stephanie K. Seidlits
    Abstract The development of three-dimensional, spatially defined neuronal cultures that mimic chemical and physical attributes of native tissue is of considerable interest for various applications, including the development of tailored neuronal networks and clinical repair of damaged nerves. Here, the use of multiphoton excitation to photocrosslink protein microstructures within three-dimensional, optically transparent hydrogel materials, such as those based on hyaluronic acid, is reported. Multiphoton excitation confines photocrosslinking to a three-dimensional voxel with submicron spatial resolution, enabling fabrication of protein matrices with low- to sub-micrometer feature sizes by scanning the focus of a laser relative to the reagent solution. These methods can be used to create complex three-dimensional architectures that provide both chemical and topographical cues for cell culture and guidance, providing for the first time a means to direct cell adhesion and migration on size scales relevant to in vivo environments. Using this approach, guidance of both dorsal root ganglion cells (DRGs) and hippocampal neural progenitor cells (NPCs) along arbitrary, three-dimensional paths is demonstrated. [source]

    Disabled children (0,3 years) and integrated services , the impact of Early Support

    Alys Young PhD MSc BA(Hons) CQSW
    Abstract Early Support (ES) is the flagship government programme aimed at improving multi-agency working with, and supporting enhanced outcomes for, children with a disability 0,3 years and their families. This paper draws on results from the recently completed Department for Education and Skills commissioned national evaluation of ES involving 46 pathfinder projects throughout England. Data were collected by survey at two points in time (9 months apart), by focus groups with service providers and parents, and through secondary data analyses, including exploratory economic evaluation. This paper outlines some of the key findings pertaining to the relationship between integrated children's services and the impact of ES. As such, we address three concerns: what the evidence from ES can tell us about the relationships between universal and targeted provision within integrated children's service structures, the relationship between specific short-term initiatives and their longer-term sustainability within integrated children's services structures and the potential costs and benefits of ES looking forward to its implementation on a national basis within an integrated children's services environment. Although focused primarily on children with a disability in the early years, implications will be drawn for the implementation of Lead Professional Guidance and the Common Assessment Framework more generically. [source]

    Developing evidence-based recommendations in public health , incorporating the views of practitioners, service users and user representatives

    Mary J Renfrew
    Abstract Background Guidance based on a systematic assessment of the evidence base has become a fundamental tool in the cycle of evidence-based practice and policy internationally. The process of moving from the formal evidence base derived from research studies to the formation and agreement of recommendations is however acknowledged to be problematic, especially in public health; and the involvement of practitioners, service commissioners and service users in that process is both important and methodologically challenging. Aim To test a structured process of developing evidence-based recommendations in public health while involving a broad constituency of practitioners, service commissioners and service user representatives. Methods As part of the development of national public health recommendations to promote and support breastfeeding in England, the methodological challenges of involving stakeholders were examined and addressed. There were three main stages: (i) an assessment of the formal evidence base (210 studies graded); (ii) electronic and fieldwork-based consultation with practitioners, service commissioners and service user representatives (563 participants), and an in-depth analytical consultation in three ,diagonal slice' workshops (89 participants); (iii) synthesis of the previous two stages. Results and conclusions The process resulted in widely agreed recommendations together with suggestions for implementation. It was very positively evaluated by participants and those likely to use the recommendations. Service users had a strong voice throughout and participated actively. This mix of methods allowed a transparent, accountable process for formulating recommendations based on scientific, theoretical, practical and expert evidence, with the added potential to enhance implementation. [source]

    Nerve Repair: A Conducting-Polymer Platform with Biodegradable Fibers for Stimulation and Guidance of Axonal Growth (Adv. Mater.

    ADVANCED MATERIALS, Issue 43 2009
    Effective functional innervation of medical bionic devices, as well as re-innervation of target tissue in nerve and spinal cord injuries, requires a platform that can stimulate and orientate neural growth. Gordon Wallace and co-workers report on p. 4393 that conducting and nonconducting biodegradable polymers show excellent potential as suitable hybrid substrata for neural regeneration and may form the basis of electrically active conduits designed to accelerate nerve repair. [source]

    A Conducting-Polymer Platform with Biodegradable Fibers for Stimulation and Guidance of Axonal Growth

    ADVANCED MATERIALS, Issue 43 2009
    Anita F. Quigley
    A biosynthetic platform composed of a conducting polypyrrole sheet embedded with unidirectional biodegradable polymer fibers is described (see image; scale bar,=,50 m). Such hybrid systems can promote rapid directional nerve growth for neuro-regenerative scaffolds and act as interfaces between the electronic circuitry of medical bionic devices and the nervous system. [source]

    Evaluation of Bioaccumulation Using In Vivo Laboratory and Field Studies,

    Annie V Weisbrod
    Abstract A primary consideration in the evaluation of chemicals is the potential for substances to be absorbed and retained in an organism's tissues (i.e., bioaccumulated) at concentrations sufficient to pose health concerns. Substances that exhibit properties that enable biomagnification in the food chain (i.e., amplification of tissue concentrations at successive trophic levels) are of particular concern due to the elevated long-term exposures these substances pose to higher trophic organisms, including humans. Historically, biomarkers of in vivo chemical exposure (e.g., eggshell thinning, bill deformities) retrospectively led to the identification of such compounds, which were later categorized as persistent organic pollutants. Today, multiple bioaccumulation metrics are available to quantitatively assess the bioaccumulation potential of new and existing chemicals and identify substances that, upon or before environmental release, may be characterized as persistent organic pollutants. This paper reviews the various in vivo measurement approaches that can be used to assess the bioaccumulation of chemicals in aquatic or terrestrial species using laboratory-exposed, field-deployed, or collected organisms. Important issues associated with laboratory measurements of bioaccumulation include appropriate test species selection, test chemical dosing methods, exposure duration, and chemical and statistical analyses. Measuring bioaccumulation at a particular field site requires consideration of which test species to use and whether to examine natural populations or to use field-deployed populations. Both laboratory and field methods also require reliable determination of chemical concentrations in exposure media of interest (i.e., water, sediment, food or prey, etc.), accumulated body residues, or both. The advantages and disadvantages of various laboratory and field bioaccumulation metrics for assessing biomagnification potential in aquatic or terrestrial food chains are discussed. Guidance is provided on how to consider the uncertainty in these metrics and develop a weight-of-evidence evaluation that supports technically sound and consistent persistent organic pollutant and persistent, bioaccumulative, and toxic chemical identification. Based on the bioaccumulation information shared in 8 draft risk profiles submitted for review under the United Nations Stockholm Convention, recommendations are given for the information that is most critical to aid transparency and consistency in decision making. [source]

    Biopsy site selection for endobronchial ultrasound guide-sheath transbronchial biopsy of peripheral lung lesions

    D. I. K. Fielding
    Abstract Background: Choice of biopsy method for peripheral lung lesions is usually between CT-guided fine-needle aspiration biopsy (CT FNA) and bronchoscopy. Endobronchial ultrasound guide-sheath biopsy (EBUS GS) is a new method to improve the yield of bronchoscopy. Guidance on which lesions would be appropriate for either method is needed. The aim of the study was to compare the diagnostic yields and pneumothorax rate of EBUS GS and CT FNA in terms of the location of the lesion needing biopsy, in particular, whether the lesion is touching the pleura. Methods: Prospective series of EBUS GS were compared to retrospective review of CT FNA carried out simultaneously in a large teaching hospital. Results: For EBUS GS 140 cases were carried out with mean lesion size 29 mm. Overall diagnostic sensitivity was 66%. For lesions not touching visceral pleura it was 74% compared with 35% where it was on the pleura (P < 0.01). For CT FNA 121 cases were carried out with mean lesion size 37 mm. The overall diagnostic sensitivity was 64%. Rate of pneumothorax and ICC placement in EBUS GS was 1 and 0% and in CTFNA was 28 and 6%, with P < 0.001 for both. Conclusion: Lesion location, in particular, connection to the visceral pleura, can improve decision-making in referral for either CT FNA or EBUS GS to maximize diagnostic yield and minimize pneumothorax rate. [source]

    Implementing Quality Improvement Strategies in Brazilian Hospitals: A Model for Guidance of the Initial Stage of Implementation

    T. Diana.
    Since the early 1990s, Brazilian hospitals have increasingly adopted quality improvement strategies with a view to attending more demanding customers and to the higher performance standards required by the Ministry of Health. However, most efforts have not been successful, partly because hospitals lack adequate methodologies, namely implementation models. This paper presents a two-stage model to help Brazilian hospitals deploy such strategies more effectively. It focusses on the development and pilot-test of the model for the buy-in stage. Distinctive features of the model were found to be critical for results at this stage: 1) An ad hoc structure to manage the changes involved; 2) A performance measurement system to lever and monitor its implementation, while aligning the actions taken with strategy objectives. Other aspects found to be crucial for success were creative application of model elements to the culture of the hospital and to Brazilian contingencies. [source]

    Accounting Standards, Implementation Guidance, and Example-Based Reasoning

    ABSTRACT This paper examines interpretation of accounting standards that provide implementation guidance via affirmative or counter examples. Based on prior psychology research, we predict that practitioners engage in "example-based reasoning" such that they are more likely to conclude that their case qualifies for the same treatment as the example. We test our predictions in two experiments in which participants judge the appropriateness of income-statement recognition. Experiment 1 uses Masters of Business Administration (MBA) students and varies example type (affirmative, counter) and case (revenue recognition, expense recognition) in a 2 2 design. Experiment 1 supports our predictions. Experiment 2 uses more experienced practitioners, and varies example type (affirmative, counter, both) in a 1 3 design. Experiment 2 supports the use of example-based reasoning, and indicates that practitioners in the "both" condition respond as if they had only received an affirmative example. These results have implications for understanding how guidance that accompanies accounting standards can result in aggressive or conservative application of standards. [source]

    Spatiotemporal Delivery Strategies for Promoting Musculoskeletal Tissue Regeneration,,

    Robert E Guldberg PhD
    Abstract A primary regenerative medicine strategy is to stimulate or augment endogenous repair mechanisms that promote functional restoration of damaged or degenerated tissues. There is increasing evidence that maximizing the potency of tissue regenerative therapies will require design and development of delivery approaches that provide controlled spatiotemporal release of key signaling molecules. Guidance on which factors to deliver and the timing of delivery is emerging from advances in understanding of critical pathways involved in the development of integrated musculoskeletal tissues. A broad range of biomaterials-based deployment technologies are becoming available that allow controlled spatial presentation and release kinetics of biological cues. The purpose of this perspective article is to review promising spatiotemporal delivery strategies designed to promote functional tissue regeneration with an emphasis on vascularized bone repair. [source]

    Flood risk management and planning policy in a time of policy transition: the case of the Wapshott Road Planning Inquiry, Surrey, England

    S. Tunstall
    Abstract This paper focuses on an English case study example of decision making on development and flood risk. It was carried out through qualitative document analysis and 13 in-depth interviews with flood risk professionals and others in the Lower Thames Valley. It illustrates the recent shift in policy in England from flood defence to a flood risk management approach with an increased emphasis on spatial planning and development control. It shows that decision makers take time to come to terms with new government policy. Despite the more prescriptive government guidance on development and flood risk in Planning Policy Guidance 25 and later documents, there remains scope for disagreements, for example, over what constitutes ,safe' development in flood risk areas. Other sustainability objectives can still weigh heavily against flood risk in local decision making. The potential contributions of modelling, and new visualisation techniques in the flood risk management and planning context are considered. [source]

    The impact of the 1999 CAP reforms on the efficiency of the COP sector in Spain

    Fatima Lambarraa
    Agenda 2000; Distance function; Efficiency; Spanish COP sector Abstract The cereal, oilseeds, and protein crop sector (COP) occupies a prominent position within the European Union's agricultural sector. Within Spain, the COP sector accounts for almost a third of total Agricultural Guidance and Guarantee Fund expenses, and half of the utilized agricultural area (UAA). The COP sector is not only relevant because of its physical and economic magnitude, but also because of the political attention it receives. The Common Agricultural Policy (CAP) reforms that occurred during the 1990s paid special attention to this sector. This article aims to determine the impacts of Agenda 2000 on a sample of Spanish COP farmers' production decisions by using an output-oriented stochastic distance function. The distance function allows for an assessment of the reform-motivated changes on total output, input used, input composition, and crop mix. It also permits an assessment of the impacts of the reform on farms' technical efficiency. Results show that the reform has shifted the production frontier inward and changed output composition in favor of voluntary set-aside land. With respect to input composition, Agenda 2000 induced a decrease in land, fertilizers, pesticides, and other inputs in favor of labor. In addition, Agenda 2000 has had a negative impact on technical efficiency. [source]

    Sex in Health Education: Official Guidance for Schools in England, 1928,1977

    Jane Pilcher
    The article begins with an account of the origins of sex education in schools, and of why, in the early twentieth century, its inclusion in the health education curriculum was problematical. In the main section, the article examines the content of consecutive editions of the government published "handbooks of health education", and of an important supplementary guidance pamphlet, published during the Second World War. It traces the gradual shifts over time in official discourses of "sex education", and in the sets of understandings about children, sexuality and the role of parents, for example, which underlay them. The shifts in official guidance discourses on sex within the health education curriculum of schools are explained through locating changes in their broader social and political contexts, especially the impact of the Second World War on sexual morality and the post-war emergence of youth as a significant social grouping. The article concludes by evaluating the handbooks as a source for the history of school-based health and sex education and by drawing attention to the wider historical and sociological significance of official discourses on sex education. [source]

    Financial Decision-Making: Guidance for Supporting Financial Decision-Making by People with Learning Disabilities

    Nick Gore

    Fairly Bland: an alternative view of a supposed new ,Death Ethic' and the BMA guidelines

    LEGAL STUDIES, Issue 4 2001
    David Price
    Recently in this journal John Keown attacked the BMA Guidance published on ,Withholding and Withdrawing Life-prolonging Medical Treatment', arguing that it was, fundamentally at odds with the sanctity of life doctrine as properly understood, condemning the intentional termination of individuals' lives. In riposte it is asserted that even this modified version of the doctrine cannot support a defensible moral or legal standard for decision-making here, being founded upon an excessive emphasis on the mental state of the clinician and an inappropriately narrow focus on the effects of the proposed treatment on the ,health' of the patient, as opposed to being primarily driven by the (best) interests of the patient. The attempt to divorce treatment decisions from broader evaluations of the net benefit or other otherwise able to be attained by the patient from such treatment, including the taking into account of the individual's handicapped state, accordingly fails. Acceptance of such reality is, at the least, the first step toward a common language for further dialogue even between those with polar opposite opinions in this sphere. [source]

    The reveal: ABA ethics opinion highlights civil practice mediator confidentiality

    Russ Bleemer
    A new opinion by the ABA's Committee on Mediator Ethical Guidance investigates how mediators can introduce essential information to parties where the adversary would be prohibited from doing so. [source]

    Food Guides Reflect Similarities and Differences in Dietary Guidance in Three Countries (Japan, Canada, and the United States)

    NUTRITION REVIEWS, Issue 4 2007
    Suzanne P. Murphy PhD
    Food guides to help consumers make healthy choices have recently been released in three countries: Japan, Canada, and the United States. The visual symbol that introduces key concepts is a spinning top in Japan, a rainbow in Canada, and a pyramid in the United States. The main features of the new guides are given in printed consumer resources, and more detailed information is available at related websites. Although the process of developing the guides varied among the countries, the resulting recommended food patterns are remarkably consistent [source]

    The Brief Pain Inventory and Its "Pain At Its Worst in the Last 24 Hours" Item: Clinical Trial Endpoint Considerations

    PAIN MEDICINE, Issue 3 2010
    Thomas M. Atkinson PhD
    Abstract Context., In 2006, the United States Food and Drug Administration (FDA) released a draft Guidance for Industry on the use of patient-reported outcomes (PRO) Measures in Medical Product Development to Support Labeling Claims. This draft guidance outlines psychometric aspects that should be considered when designing a PRO measure, including conceptual framework, content validity, construct validity, reliability, and the ability to detect clinically meaningful score changes. When finalized, it may provide a blueprint for evaluations of PRO measures that can be considered by sponsors and investigators involved in PRO research and drug registration trials. Objective., In this review we examine the short form of the Brief Pain Inventory (BPI) and particularly the "pain at its worst in the last 24 hours" item in the context of the FDA draft guidance, to assess its utility in clinical trials that include pain as a PRO endpoint. Results and Conclusions., After a systematic evaluation of the psychometric aspects of the BPI, we conclude that the BPI and its "pain at its worst in the last 24 hours" item generically satisfy most key recommendations outlined in the draft guidance for assessing a pain-reduction treatment effect. Nonetheless, when the BPI is being considered for assessment of pain endpoints in a registration trial, sponsors and investigators should consult with the appropriate FDA division early during research design to discuss whether there is sufficient precedent to use the instrument in the population of interest or whether additional evaluations of measurement properties are advisable. [source]

    Persons With Developmental Disabilities Exposed to Interpersonal Violence and Crime: Strategies and Guidance for Assessment

    CDDN, Ginny Focht-New APRN
    PURPOSE.,Persons with developmental disabilities are frequently exposed to interpersonal violence and crime, directed at themselves and others, and are in need of specific interventions tailored to their unique needs. CONCLUSIONS.,What may be different in comparison to other survivors are the ways therapeutic interventions are adapted so that fears and ongoing concerns can be effectively expressed and addressed. PRACTICE IMPLICATIONS.,Persons with developmental disabilities may benefit from a variety of interventions in the treatment of intrapsychic trauma after exposure to interpersonal violence and crime. [source]

    Impact of baseline ECG collection on the planning, analysis and interpretation of ,thorough' QT trials

    Venkat Sethuraman
    Abstract The current guidelines, ICH E14, for the evaluation of non-antiarrhythmic compounds require a ,thorough' QT study (TQT) conducted during clinical development (ICH Guidance for Industry E14, 2005). Owing to the regulatory choice of margin (10,ms), the TQT studies must be conducted to rigorous standards to ensure that variability is minimized. Some of the key sources of variation can be controlled by use of randomization, crossover design, standardization of electrocardiogram (ECG) recording conditions and collection of replicate ECGs at each time point. However, one of the key factors in these studies is the baseline measurement, which if not controlled and consistent across studies could lead to significant misinterpretation. In this article, we examine three types of baseline methods widely used in the TQT studies to derive a change from baseline in QTc (time-matched, time-averaged and pre-dose-averaged baseline). We discuss the impact of the baseline values on the guidance-recommended ,largest time-matched' analyses. Using simulation we have shown the impact of these baseline approaches on the type I error and power for both crossover and parallel group designs. In this article, we show that the power of study decreases as the number of time points tested in TQT study increases. A time-matched baseline method is recommended by several authors (Drug Saf. 2005; 28(2):115,125, Health Canada guidance document: guide for the analysis and review of QT/QTc interval data, 2006) due to the existence of the circadian rhythm in QT. However, the impact of the time-matched baseline method on statistical inference and sample size should be considered carefully during the design of TQT study. The time-averaged baseline had the highest power in comparison with other baseline approaches. Copyright 2008 John Wiley & Sons, Ltd. [source]

    Simulation assessments of statistical aspects of bioequivalence in the pharmaceutical industry

    Scott D. Patterson
    Abstract An Erratum has been published for this article in Pharmaceutical Statistics 2004; 3(3): 232 Since the early 1990s, average bioequivalence (ABE) has served as the international standard for demonstrating that two formulations of drug product will provide the same therapeutic benefit and safety profile. Population (PBE) and individual (IBE) bioequivalence have been the subject of intense international debate since methods for their assessment were proposed in the late 1980s. Guidance has been proposed by the Food and Drug Administration (FDA) for the implementation of these techniques in the pioneer and generic pharmaceutical industries. Hitherto no consensus among regulators, academia and industry has been established on the use of the IBE and PBE metrics. The need for more stringent bioequivalence criteria has not been demonstrated, and it is known that the PBE and IBE criteria proposed by the FDA are actually less stringent under certain conditions. The statistical properties of method of moments and restricted maximum likelihood modelling in replicate designs will be summarized, and the application of these techniques in the assessment of ABE, IBE and PBE will be considered based on a database of 51 replicate design studies and using simulation. Copyright 2004 John Wiley & Sons, Ltd. [source]