Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation. PMID:20626885
Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials.
This chapter is concerned with some of the more mundane aspects of the day to day design, planning, documentation, and management of clinical trials, rather than with the finer points of trial design which are dealt with in detail elsewhere. The points considered here, taken individually, seem obvious and trivial but it is hoped that some may be helpful in obtaining the maximum return for the work invested in running a trial. PMID:7104166
Bose, Anindya; Das, Suman
Prolonged timelines and large expenses associated with clinical trials have prompted a new focus on improving the operational efficiency of clinical trials by use of Clinical Trial Management Systems (CTMS) in order to improve managerial control in trial conduct. However, current CTMS systems are not able to meet the expectations due to various shortcomings like inability of timely reporting and trend visualization within/beyond an organization. To overcome these shortcomings of CTMS, clinical researchers can apply a business intelligence (BI) framework to create Clinical Research Intelligence (CLRI) for optimization of data collection and analytics. This paper proposes the usage of an innovative and collaborative visualization tool (CTA) as CTMS "add-on" to help overwhelm these deficiencies of traditional CTMS, with suitable examples.
Goodarzynejad, Hamidreza; Babamahmoodi, Abdolreza
Context: A well-structured protocol for a clinical trial may be able to answer clinical questions, but it cannot be deemed enough to ensure success in the face of incompetent management of time as well as human and economic resources. To address this problem, in this article, we present our literature review on evidence as to how a good knowledge of proper management among researchers can enhance the likelihood of the success of clinical trial projects. Evidence Acquisition: Using multiple search strategies, we conducted a literature review on published studies in the English language from 2002 to 2012 by searching the Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE. Results: Our review suggests that a successful trial requires a work plan or work scope as well as a timeline. The trial manager should subsequently manage the study in accordance with the plan and the timeline. Many research units have called for a clinical project manager with scientific background and regulatory skills to effect coordination among various aspects of a clinical trial. Conclusions: Project management may benefit both the managerial and scientific aspects of medical projects and reduce fund waste. However, little has been written to date on project management in the context of clinical research. The suggestions represent the views of the individual authors. To provide a high level of evidence in this regard, we recommend that a randomized controlled trial be performed to compare trial projects progressed with and without the use of project management. PMID:26430517
Mathura, Venkatarajan S; Rangareddy, Mahendiranath; Gupta, Pankaj; Mullan, Michael
Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment. Availability http://www.rfdn.org/bioinfo/CTMS/ctms.html. PMID:21670796
Starren, Justin B; Payne, Philip R O; Kaufman, David R
Clinical trials increasingly rely upon web-based Clinical Trials Management Systems (CTMS). As with clinical care systems, Human Computer Interaction (HCI) issues can greatly affect the usefulness of such systems. Evaluation of the user interface of one web-based CTMS revealed a number of potential human-computer interaction problems, in particular, increased workflow complexity associated with a web application delivery model and potential usability problems resulting from the use of ambiguous icons. Because these design features are shared by a large fraction of current CTMS, the implications extend beyond this individual system.
Starren, Justin B.; Payne, Philip R.O.; Kaufman, David R.
Clinical trials increasingly rely upon web-based Clinical Trials Management Systems (CTMS). As with clinical care systems, Human Computer Interaction (HCI) issues can greatly affect the usefulness of such systems. Evaluation of the user interface of one web-based CTMS revealed a number of potential human-computer interaction problems, in particular, increased workflow complexity associated with a web application delivery model and potential usability problems resulting from the use of ambiguous icons. Because these design features are shared by a large fraction of current CTMS, the implications extend beyond this individual system. PMID:17238728
Chen, Zhao-hua; Huang, Qin; Deng, Ya-zhong; Zhang, Yue; Xu, Yu; Yu, Hao; Liu, Zong-fan
Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.
... Sponsors Why Are They Important How Do They Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites What Are Clinical ...
Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G
The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.
Shankar, Ravi D; Martins, Susana B; O'Connor, Martin; Parrish, David B; Das, Amar K
Management of complex clinical trials involves coordinated-use of a myriad of software applications by trial personnel. The applications typically use distinct knowledge representations and generate enormous amount of information during the course of a trial. It becomes vital that the applications exchange trial semantics in order for efficient management of the trials and subsequent analysis of clinical trial data. Existing model-based frameworks do not address the requirements of semantic integration of heterogeneous applications. We have built an ontology-based architecture to support interoperation of clinical trial software applications. Central to our approach is a suite of clinical trial ontologies, which we call Epoch, that define the vocabulary and semantics necessary to represent information on clinical trials. We are continuing to demonstrate and validate our approach with different clinical trials management applications and with growing number of clinical trials.
Shankar, Ravi D.; Martins, Susana B.; O’Connor, Martin; Parrish, David B.; Das, Amar K.
Management of complex clinical trials involves coordinated-use of a myriad of software applications by trial personnel. The applications typically use distinct knowledge representations and generate enormous amount of information during the course of a trial. It becomes vital that the applications exchange trial semantics in order for efficient management of the trials and subsequent analysis of clinical trial data. Existing model-based frameworks do not address the requirements of semantic integration of heterogeneous applications. We have built an ontology-based architecture to support interoperation of clinical trial software applications. Central to our approach is a suite of clinical trial ontologies, which we call Epoch, that define the vocabulary and semantics necessary to represent information on clinical trials. We are continuing to demonstrate and validate our approach with different clinical trials management applications and with growing number of clinical trials. PMID:18693919
Clinical trials are research studies that test how well new medical approaches work in people. Each study answers scientific ... screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...
Park, Yu Rang; Kim*, Ju Han
Standardized management of data elements (DEs) for Case Report Form (CRF) is crucial in Clinical Trials Information System (CTIS). Traditional CTISs utilize organization-specific definitions and storage methods for Des and CRFs. We developed metadata-based DE management system for clinical trials, Clinical and Histopathological Metadata Registry (CHMR), using international standard for metadata registry (ISO 11179) for the management of cancer clinical trials information. CHMR was evaluated in cancer clinical trials with 1625 DEs extracted from the College of American Pathologists Cancer Protocols for 20 major cancers. PMID:17238675
Singhal, Richa; Rana, Rakesh
Missing data is frequently encountered in clinical studies. Unfortunately, they are often neglected or not properly handled during data analysis and this may significantly bias the results of the study, reduce study power and lead to invalid conclusions. Substantial instances of missing data are a serious problem that undermines the scientific trustworthiness of causal conclusions from clinical trials. The assumption that statistical analysis methods can compensate for such missing data is not justified. Hence aspects of clinical trial design that limit the probability of missing data should be an important objective, while planning a clinical trial. In addition to specific aspects of trial design, many components of clinical trial conduct can also limit the extent of missing data. The topic of missing data is often not a major concern until it is time for data collection and data analysis. This article discusses some basic issues about missing data as well as prospective "watch outs" which could reduce the occurrence of missing data. It provides some possible design considerations that should be considered in order to alleviate patients from dropping out of a clinical trial. In addition to these the concept of the missing data mechanism has also been discussed. Three types of missing data mechanisms missing completely at random, missing at random and not missing at random have been discussed in detail.
Zhao, Wenle; Durkalski, Valerie; Pauls, Keith; Dillon, Catherine; Kim, Jaemyung; Kolk, Deneil; Silbergleit, Robert; Stevenson, Valerie; Palesch, Yuko
A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials. The latter causes a possible redundancy in document collection and management. To address these and other related challenges, a central regulatory document management system was designed. This manuscript shares the design of the system as well as examples of it use in current studies. Copyright (c) 2009 Elsevier Inc. All rights reserved.
Schöbel, Martin; Stäubert, Sebastian; Löbe, Matthias; Meinel, Kirsti; Winter, Alfred
As a part of the introduction of a Clinical Trial Management System (CTMS) for an Academic Site Management Organization (SMO) we had to determine the requirements such a system has to meet. By performing extensive Requirements Engineering, we aimed at raising the success of the future system and the user satisfaction. Investigations revealed the existence of TORE (Task and Object-oriented Requirements Engineering), a task-driven approach for determining requirements on user interface- and information-intensive systems. In this paper, we present an adoption of this method for our purposes, resulting in a reasonable list of requirements for CTMS acquisition.
Payne, Philip R.O.; Greaves, Andrew W.; Kipps, Thomas J.
The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. To enable the CRC’s clinical research efforts, a system providing for real-time collaboration was required. CTMS provides such functionality, and demonstrates that the use of novel data modeling, web-application platforms, and management strategies provides for the deployment of an extensible, cost effective solution in such an environment. PMID:14728471
Tellez, M; Potter, C M; Kinner, D G; Jensen, D; Waldron, E; Heimberg, R G; Myers Virtue, S; Zhao, H; Ismail, A I
Anxiety regarding dental and physical health is a common and potentially distressing problem, for both patients and health care providers. Anxiety has been identified as a barrier to regular dental visits and as an important target for enhancement of oral health-related quality of life. The study aimed to develop and evaluate a computerized cognitive-behavioral therapy dental anxiety intervention that could be easily implemented in dental health care settings. A cognitive-behavioral protocol based on psychoeducation, exposure to feared dental procedures, and cognitive restructuring was developed. A randomized controlled trial was conducted (N = 151) to test its efficacy. Consenting adult dental patients who met inclusion criteria (e.g., high dental anxiety) were randomized to 1 of 2 groups: immediate treatment (n = 74) or a wait-list control (n = 77). Analyses of covariance based on intention-to-treat analyses were used to compare the 2 groups on dental anxiety, fear, avoidance, and overall severity of dental phobia. Baseline scores on these outcomes were entered into the analyses as covariates. Groups were equivalent at baseline but differed at 1-mo follow-up. Both groups showed improvement in outcomes, but analyses of covariance demonstrated significant differences in dental anxiety, fear, avoidance, and overall severity of dental phobia in favor of immediate treatment at the follow-up assessment. Of the patients who met diagnostic criteria for phobia at baseline, fewer patients in the immediate treatment group continued to meet criteria for dental phobia at follow-up as compared with the wait-list group. A new computer-based tool seems to be efficacious in reducing dental anxiety and fear/avoidance of dental procedures. Examination of its effectiveness when administered in dental offices under less controlled conditions is warranted (ClinicalTrials.gov NCT02081365).
James, Pam; Bebee, Patty; Beekman, Linda; Browning, David; Innes, Mathew; Kain, Jeannie; Royce-Westcott, Theresa; Waldinger, Marcy
Quantifying data management and regulatory workload for clinical research is a difficult task that would benefit from a robust tool to assess and allocate effort. As in most clinical research environments, The University of Michigan Comprehensive Cancer Center (UMCCC) Clinical Trials Office (CTO) struggled to effectively allocate data management and regulatory time with frequently inaccurate estimates of how much time was required to complete the specific tasks performed by each role. In a dynamic clinical research environment in which volume and intensity of work ebbs and flows, determining requisite effort to meet study objectives was challenging. In addition, a data-driven understanding of how much staff time was required to complete a clinical trial was desired to ensure accurate trial budget development and effective cost recovery. Accordingly, the UMCCC CTO developed and implemented a Web-based effort-tracking application with the goal of determining the true costs of data management and regulatory staff effort in clinical trials. This tool was developed, implemented, and refined over a 3-year period. This article describes the process improvement and subsequent leveling of workload within data management and regulatory that enhanced the efficiency of UMCCC's clinical trials operation.
Kyte, Derek; Ives, Jonathan; Draper, Heather; Calvert, Melanie
Assessment of patient-reported outcomes (PROs) provides valuable information to inform patient-centered care, but may also reveal 'PRO alerts': psychological distress or physical symptoms that may require an immediate response. Ad-hoc management of PRO alerts in clinical trials may result in suboptimal patient care or potentially bias trial results. To gain greater understanding of current practice in PRO alert management we conducted a national survey of personnel involved in clinical trials with a PRO endpoint. We conducted a national cross-sectional survey of 767 UK-based research nurses, data managers/coordinators, trial managers and chief/principal investigators involved in clinical trials using PROs. Respondents were self-selected volunteers from a non-randomised sample of eligible individuals recruited via 55 UK Clinical Research Collaboration Registered Clinical Trials Units and 19 Comprehensive Local Research Networks. Questions centred on the proportion of trial personnel encountering alerts, how staff responded to PRO alerts and whether current guidance was deemed sufficient to support research personnel. We undertook descriptive analyses of the quantitative data and directed thematic analysis of free-text comments. 20% of research nurses did not view completed PRO questionnaires and were not in a position to discover alerts, 39-50% of the remaining respondent group participants reported encountering PRO alerts. Of these, 83% of research nurses and 54% of data managers/trial coordinators reported taking action to assist the trial participant, but less than half were able to record the intervention in the trial documentation. Research personnel reported current PRO alert guidance/training was insufficient. Research personnel are intermittently exposed to PRO alerts. Some intervene to help trial participants, but are not able to record this intervention in the trial documentation, risking co-intervention bias. Other staff do not check PRO information
James, Pam; Bebee, Patricia; Beekman, Linda; Browning, David; Innes, Mathew; Kain, Jeannie; Royce-Westcott, Theresa; Waldinger, Marcy
Clinical trials operations struggle to achieve optimal distribution of workload in a dynamic data management and regulatory environment, and to achieve adequate cost recovery for personnel costs. The University of Michigan Comprehensive Cancer Center developed and implemented an effort tracking application to quantify data management and regulatory workload to more effectively assess and allocate work while improving charge capture. Staff recorded how much time they spend each day performing specific study-related and general office tasks. Aggregated data on staff use of the application from 2006 through 2009 were analyzed to gain a better understanding of what trial characteristics require the most data management and regulatory effort. Analysis revealed 4 major determinants of staff effort: 1) study volume (actual accrual), 2) study accrual rate, 3) study enrollment status, and 4) study sponsor type. Effort tracking also confirms that trials that accrued at a faster rate used fewer resources on a per-patient basis than slow-accruing trials. In general, industry-sponsored trials required the most data management and regulatory support, outweighing other sponsor types. Although it is widely assumed that most data management efforts are expended while a trial is actively accruing, the authors learned that 25% to 30% of a data manager's effort is expended while the study is either not yet open or closed to enrollment. Through the use of a data-driven effort tracking tool, clinical research operations can more efficiently allocate workload and ensure that study budgets are negotiated to adequately cover study-related expenses.
Background A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials. Methods International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials. Results The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit. Section
McCain, Nancy L.; Gray, D. Patricia; Elswick, R. K., Jr.; Robins, Jolynne W.; Tuck, Inez; Walter, Jeanne M.; Rausch, Sarah M.; Ketchum, Jessica McKinney
Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of…
McCain, Nancy L.; Gray, D. Patricia; Elswick, R. K., Jr.; Robins, Jolynne W.; Tuck, Inez; Walter, Jeanne M.; Rausch, Sarah M.; Ketchum, Jessica McKinney
Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of…
Elbogen, Eric B; Hamer, Robert M; Swanson, Jeffrey W; Swartz, Marvin S
The study evaluated an intervention to help veterans with psychiatric disabilities, who face a unique set of challenges concerning money management. A randomized clinical trial was conducted of a brief (one to three hours) psychoeducational, recovery-oriented money management intervention called $teps for Achieving Financial Empowerment ($AFE). Analyses revealed no main effects on outcomes of random assignment to $AFE (N=67) or a control condition consisting of usual care (N=77). Veterans who reported using $AFE skills showed significantly lower impulsive buying, more responsible spending, higher rates of engaging in vocational activities, and greater number of work hours compared with veterans in the control condition. Findings have clinical implications for case management services involving informal money management assistance. Offering veterans with psychiatric disabilities a one-time money management intervention is unlikely to lead to substantial changes. Results imply that efforts to improve psychosocial outcomes among veterans must not only teach but also increase use of money management skills.
Ngari, Moses M; Waithira, Naomi; Chilengi, Roma; Njuguna, Patricia; Lang, Trudie; Fegan, Greg
Clinical trials data management (CTDM) remains one of the many challenges in running state of the art trials in resource-poor settings since most trials do not allocate, or have available, sufficient resources for CTDM and because of poor internet connectivity. Open-source software like OpenClinica could be a solution in such scenarios. In 2007, the KEMRI-Wellcome Trust Research Programme (KWTRP) adopted OpenClinica (OC) community edition, an open-source software system and we share our experience and lessons learnt since its adoption. We have used OC in three different modes; direct remote data entry from sites through Global System for Mobile Communications (GSM) modems, a centralized data centre approach where all data from paper records were entered at a central location and an off-line approach where data entry was done from a copy of database hosted on a field-site server laptop, then data uploaded to a centralized server later. We have used OC in eleven trials/studies with a cumulative number of participants in excess of 6000. These include large and complex trials, with multiple sites recruiting in different regions of East Africa. In the process, we have developed substantial local capacity through hands-on training and mentorship, which we have now begun to share with other institutions in the region. Our experience demonstrates that an open source data management system to manage trials' data can be utilized to international industry standards in resource-poor countries.
Rico-Villademoros, Fernando; Hernando, Teresa; Sanz, Juan-Luis; López-Alonso, Antonio; Salamanca, Oscar; Camps, Carlos; Rosell, Rafael
Background The purpose of this study was to determine the standard tasks performed by clinical research coordinators (CRCs) in oncology clinical trials. Methods Forty-one CRCs were anonymously surveyed, using a four-page self-administered questionnaire focused on demographics, qualifications, and professional experience. The survey questions on responsibilities consisted of an ad-hoc 32-item questionnaire where respondents had to rate the frequency of involvement in the listed activities using a 3-point scale. We defined as "standard" a task that was rated as "in all or nearly all trials" by at least half of the respondents. Results A response rate of 90% (37 out of 41) was achieved after two mailings. Less than half of the respondents had received additional training in oncology, clinical research or Good Clinical Practices (GCP). Overall, all standard tasks performed by CRCs were in the category of "monitoring activities" (those usually performed by a Clinical Research Associate "CRA") and included patient registration/randomization, recruitment follow-up, case report form completion, collaboration with the CRA, serious adverse events reporting, handling of investigator files, and preparing the site for and/or attending audits. Conclusions CRCs play a key role in the implementation of oncology clinical trials, which goes far beyond mere data collection and/or administrative support, and directly contributes to the gathering of good quality data. PMID:15043760
Brandt, C A; Nadkarni, P; Marenco, L; Karras, B T; Lu, C; Schacter, L; Fisk, J M; Miller, P L
This paper describes the process of enhancing Trial/DB, a database system for clinical studies management. The system's enhancements have been driven by the need to maximize the effectiveness of developer personnel in supporting numerous and diverse users, of study designers in setting up new studies, and of administrators in managing ongoing studies. Trial/DB was originally designed to work over a local area network within a single institution, and basic architectural changes were necessary to make it work over the Internet efficiently as well as securely. Further, as its use spread to diverse communities of users, changes were made to let the processes of study design and project management adapt to the working styles of the principal investigators and administrators for each study. The lessons learned in the process should prove instructive for system architects as well as managers of electronic patient record systems.
Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Contoreggi, Carlo; Leff, Michelle
A clinical recruiting management system with qualification decision support systems was developed to increase the efficiency of screening and evaluation of participants during a recruiting process whereby recruiting for various protocols are conducted at multiple sites by different groups with process interdependencies. This system is seamlessly integrated into our enterprise-scale Human Research Information System (HuRIS), encompassing research participants' electronic health records (EHR), with real-time access to the clinical trial data.
Women are under-represented in landmark clinical trials that form the basis of evidence based management of cardiovascular diseases. Differences among male and female patients emerged in effectiveness and safety of therapeutics in some diseases. Especially in dyslipidemia, ischemic heart diseases and heart failure, trials in which women are better represented and guidelines that evaluate findings in women more detailed are needed. This article evaluates differences among men and women in some landmark trials that are used among main references in management guidelines.
Reynolds, Penny S; Michael, Mary J; Spiess, Bruce D
Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the 'gold standard' management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be
Recently reported results of well-designed prospective clinical trials for extranodal NK/T-cell lymphoma, nasal type (ENKL) have rapidly changed the management of ENKL. This review will focus on the evidence obtained from prospective clinical trials for ENKL and discuss the most highly recommended current management and future directions for the better management of ENKL. For patients with nasal NK/T-cell lymphoma of stage IE or contiguous stage IIE with cervical node involvement, concurrent chemoradiotherapy with radiotherapy (RT) and a two-thirds dose of DeVIC chemotherapy is recommended as a first-line treatment. To obtain the expected clinical outcome, performing RT following the same procedure as that reported is important. For the other patients with newly diagnosed ENKL, SMILE chemotherapy is recommended as an induction therapy. The Epstein-Barr virus DNA load in peripheral blood is useful for both prognostication and monitoring during the follow-up after treatment. Other L-asparaginase-containing chemotherapies and chemotherapies containing non-multidrug resistance-related agents and etoposide are good options for elderly patients or patients with impaired organ function. As in the cases of other aggressive lymphomas, prospective clinical trials with adequate statistical considerations should be conducted to improve the prognosis of patients with ENKL.
Inouye, Jillian; Braginsky, Nafanua; Kataoka-Yahiro, Merle
Little has been reported in the literature about self-management strategies of chronic conditions in Asian and Pacific Islanders (APIs). The purpose of this systematic review was to investigate randomized clinical trials (RCTs) of self-management strategies of chronic conditions in APIs. Twenty-one studies were included in the final review, published between 1997 and 2010. Initially, the Jadad Scoring of Quality of Reports of Randomized Clinical Trials (JSQRRC) was used to determine the quality of RCT studies. The researchers then did a systematic review of each of the RCTs based on the JSQRRC criteria. JSQRRC scores ranged from 8 to 12, M = 9.6. Descriptive analysis indicated cognitive behavioral interventions as an effective treatment methodology for APIs. The results underscore the importance of clarifying the methodological components and reporting of RCTs. Interventions appropriate for APIs using disaggregated ethnic groups are essential to determine specific cultural responses to treatments and outcomes.
Sittig, Dean F.
Acute Respiratory Distress Syndrome (ARDS) is often not responsive to conventional supportive therapy and the mortality rate may exceed 90%. A new form of supportive care, Extracorporeal Carbon Dioxide Removal (ECCO2R), has shown a dramatic increase in survival (48%). A controlled clinical trial of the new ECCO2R therapy versus conventional Continuous Positive Pressure Ventilation (CPPV) is being initiated. Detailed care protocols have been developed by “expert” critical care physicians for the management of patients. Using a blackboard control architecture, the protocols have been implemented on an existing hospital information system and will direct patient care and help manage the controlled clinical trial. Therapeutic instructions are automatically generated by the computer from data input by physicians, nurses, respiratory therapists, and the laboratory. Preliminary results show that the computerized protocol system can direct therapy for acutely ill patients.
Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164). PMID:24886378
Baum, M; Edwards, M H; Magarey, C J
From a study of the organization of a national clinical trial on the management of early cancer of the breast in women there appear to be overwhelming advantages in studying large numbers of patients. To this end centres abroad have been encouraged to join. All the evidence at present suggests that it is feasible to organize a study on this scale, that the documentation and follow-up are accurate, and that the enthusiasm of the participants can be successfully fostered and maintained.
Buchsbaum, Richard; Kaufmann, Petra; Barsdorf, Alexandra I; Arbing, Rachel; Montes, Jacqueline; Thompson, John L P
The objective was to report on the creation, features and performance of a web-based data management system for a two-stage phase II randomized clinical trial of Co-Enzyme Q10 in ALS. We created a relatively comprehensive web-based data system that provided electronic data entry; patient management utilities; adverse event reporting, safety monitoring, and invoice generation; and standardized coding for medications and adverse events. In stage 1, clinical sites submitted 7207 forms reporting on 105 patients followed for 10 months. Less than 0.7% of submitted forms contained errors. At the time of the delivery of the analysis data set, only four errors remained unresolved. Data were available quickly, with a median time from event to data posting of two days. The data set was locked and the analysis data set produced nine days after the final patient visit. A survey of trial personnel yielded generally positive feedback, with 75% of respondents wishing to use a similar system in the future. Given sufficient resources, a comprehensive web-based data management system can meet the need for clean, available data in clinical trials in ALS and similar diseases, and can contribute significantly to their efficient execution.
Luo, Xiaolong; Chen, Peng; Wu, Alan Chengqing; Pan, Guohua; Li, Mingyu; Chen, Guang; Dong, Qian; Cline, Gary A; Dornseif, Bruce E; Jin, Zhezhen
Planned and unplanned subgroup analyses of large clinical trials are frequently performed and the results are sometimes difficult to interpret. The source of a nominal significant finding may come from a true signal, variation of the clinical trial outcome or the observed data structure. Quantitative assessment is critical to the interpretation of the totality of the clinical data. In this article we provide a general framework to manage subgroup analyses and to interpret the findings through a set of supplement analyses to planned main (primary and secondary) analyses, as an alternative to the commonly used multiple comparison framework. The proposed approach collectively and coherently utilizes several quantitative methods and enhances the credibility and interpretability of subgroup analyses. A case study is used to illustrate the application of the proposed method.
... existing treatments. Some may study new forms of psychotherapy (talk therapy). Others may study a combination of ... period. In trials that test new forms of psychotherapy, one group may be randomly assigned to a ...
Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.
Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748
Smith, David H; Johnson, Eric S; Thorp, Micah L; Crispell, Kathy A; Yang, Xiuhai; Petrik, Amanda F
Heart failure case management programs have been shown in clinical trials to be highly effective at preventing future hospitalizations. But the absolute benefits of these programs depend on the baseline risk of outcome in the treated population. Because baseline risks of hospitalization in trials are often higher than community-based samples, translating trial results to the community setting may be misleading. One solution is to identify subgroups for intervention that have sufficiently high baseline risk. Using estimates of hospitalizations averted from a previously published systematic review of heart failure management, we estimated a program's efficiency based on level of predicted risk. Medical history and demographic data on heart failure patients from a large integrated US health plan were used to build a logistic regression-based prognostic risk score for cardiovascular-related hospitalization over 1 year. We calculated the crude rate of hospitalizations for comparison with trial data. We also calculated the program's potential dollar savings from averting hospitalizations. The average risk of hospitalization in the systematic review's trials was 45%; our population's average observed risk was 18% and the risk among the highest risk patients was 33%. After accounting for the assumed annual intervention cost of $700, the base-case analysis (at $6000 per hospitalization) shows a savings of $122/patient at highest risk; failing to intervene according to predicted risk (no targeting) would actually cost $211/patient. Our findings illustrate how clinical trial findings can be efficiently integrated into community settings by using a prognostic risk score to focus attention on high-risk subgroups.
... your information private 5. What happens when the study ends The Possible Risks and Benefits The trial may provide treatments or screenings, but there is no promise that your health will get better. The medicine, test, or treatment may not work for you. 6. The benefits of the treatments ...
Buchan, I.; Covvey, H.D.; Mylopoulos, J.; DiMarco, C.; Wigle, E.D.
There is an intrinsic simplicity and similarity in clinical trials, despite their apparent overwhelming variety. Their basic processes, in investigating the cause and effect relationship between some intervention and its outcome, are the same. They also share common problems. Through the enforcement of the proper procedures we can ensure the quality of the clinical experiment. The expense and commitment of time and resources to the carrying out of clinical trials demands attention to these matters... if for no other reasons than to achieve some result given the funds invested and to ensure the safety of participating patients. Research at the University of Toronto into the problems of interactive information systems design has resulted in the development of a high-level programming language and design environment called TAXIS. It is our contention that the application of the TAXIS tools and methodology to the clinical trial management domain will result in easier-to-write systems that are more understandable, modifiable, extensible, reliable, transportable and, in the long run, less costly.
Oshakbayev, Kuat; Dukenbayeva, Bibazhar; Otarbayev, Nurzhan; Togizbayeva, Gulnar; Tabynbayev, Nariman; Gazaliyeva, Meruyert; Idrisov, Alisher; Oshakbayev, Pernekul
The prevalence and burden of atherosclerotic (AS) diseases are increasing during the last twenty years. Some studies show a close relationship between overweight and AS, but influence on AS diseases of different weight loss methods are still studying. The purpose of the research was to study the effectiveness of a weight loss program in AS patients in randomized controlled trial, and to develop a conception of evolution of AS. A randomized controlled prospective clinical trial including 97 people, from them 71 patients with various AS manifestations. Patients were divided in 2 subgroups for non-drug weight loss program, and conventional drug therapy. The weight loss program included calorie restriction with 100-150 kcal/day, fat-free vegetables, salt diet, and optimum physical activity. Statistical analysis was performed using SPSS for Windows version 17.0. The weight loss subgroup lost ranging between 7-20% from an initial weight (P = 0.016). Weight loss was achieved due to fatty mass reduction only (P = 0.005). Hemoglobin levels (P < 0.001), bone mineral density (P < 0.001), percentages of water (P = 0.006) and muscle masses (P = 0.0038) were increased in weight loss subgroup. Ejection fraction (P < 0.0001), systolic output (P < 0.0001) were increased in patients with coronary artery disease. The weight loss program led to a decrease in symptomatic drugs doses up to total abolition. A conception of AS was developed. The weight loss program treated the AS diseases; improved laboratory and instrumental parameters, decreased symptomatic drugs doses. AS development is a logical way of ontogenetic ageing of body fat. ClinicalTrials.gov NCT01700075. State registration is # 0109RK000079, code is O.0475 at the National Center for Scientific and Technical Information of the Republic of Kazakhstan.
Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |
... Tiếng Việt) Arabic (العربية) Expand Section Clinical Trials - English Clinical Trials - العربية (Arabic) PDF American Cancer Society ... Traditional (Cantonese dialect) (繁體中文) Expand Section Clinical Trials - English Clinical Trials - 繁體中文 (Chinese, Traditional (Cantonese dialect)) PDF ...
McCain, Nancy L; Gray, D Patricia; Elswick, R K; Robins, Jolynne W; Tuck, Inez; Walter, Jeanne M; Rausch, Sarah M; Ketchum, Jessica McKinney
Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of three 10-week stress management approaches--cognitive-behavioral relaxation training (RLXN), focused tai chi training (TCHI), and spiritual growth groups (SPRT)--in comparison to a wait-listed control group (CTRL) among 252 individuals with HIV infection. Using repeated measures mixed modeling, the authors found that in comparison to the CTRL group, (a) both the RLXN and TCHI groups used less emotion-focused coping, and (b) all treatment groups had augmented lymphocyte proliferative function. Despite modest effects of the interventions on psychosocial functioning, robust findings of improved immune function have important clinical implications, particularly for persons with immune-mediated illnesses. (c) 2008 APA, all rights reserved
McCain, Nancy L.; Gray, D. Patricia; Elswick, R. K.; Robins, Jolynne W.; Tuck, Inez; Walter, Jeanne M.; Rausch, Sarah M.; Ketchum, Jessica McKinney
Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of three 10-week stress management approaches—cognitive–behavioral relaxation training (RLXN), focused tai chi training (TCHI), and spiritual growth groups (SPRT)—in comparison to a wait-listed control group (CTRL) among 252 individuals with HIV infection. Using repeated measures mixed modeling, the authors found that in comparison to the CTRL group, (a) both the RLXN and TCHI groups used less emotion-focused coping, and (b) all treatment groups had augmented lymphocyte proliferative function. Despite modest effects of the interventions on psychosocial functioning, robust findings of improved immune function have important clinical implications, particularly for persons with immune-mediated illnesses. PMID:18540736
Chauvie, Stéphane; Biggi, Alberto; Stancu, Alexandru; Cerello, Piergiorgio; Cavallo, Anna; Fallanca, Federico; Ficola, Umberto; Gregianin, Michele; Guerra, Ugo Paolo; Chiaravalloti, Agostino; Schillaci, Orazio; Gallamini, Andrea
Background It has been proposed that in clinical trials in which the therapeutic strategy is driven by functional imaging, central review of the images should be done in real time. Purpose We report our experience with a new tool for image exchange and review, called Web-Based Imaging Diagnosis by Expert Network (WIDEN), which we implemented for the HD0607 prospective multicenter Italian clinical trial in which Hodgkin lymphoma treatment was adapted based on results of an interim positron emission tomography (PET) scan performed after the first two cycles of chemotherapy. Methods We used WIDEN for general management of the clinical trial, site imaging qualification, image exchange, workflow control, blinded independent central review, inter-observer variability assessment, consensus creation, audit, and statistical analysis. Results As of February 2013, the interim PET was available for 512 patients; upon central review, 103 of the scans were judged to be positive and 409 to be negative. The median scan uploading and downloading times were 1 min, 25 s and 1 min, 55 s, respectively; the average and median times for diagnosis exchange were 47 h, 53 min and 37 h, 43 min, respectively. The binary concordance between pairs of reviewers (Cohen's kappa) ranged from 0.72 to 0.85. The 5-point scale concordance among all reviewers (Krippendorf's alpha) was 0.77. Conclusions WIDEN proved to be an effective tool for medical imaging exchange and online review. Data security, simplicity, feasibility, and prompt scan review were demonstrated. Central reviews were completed promptly.
Background The use of Clinical Data Management Systems (CDMS) has become essential in clinical trials to handle the increasing amount of data that must be collected and analyzed. With a CDMS trial data are captured at investigator sites with "electronic Case Report Forms". Although more and more of these electronic data management systems are used in academic research centres an overview of CDMS products and of available data management and quality management resources for academic clinical trials in Europe is missing. Methods The ECRIN (European Clinical Research Infrastructure Network) data management working group conducted a two-part standardized survey on data management, software tools, and quality management for clinical trials. The questionnaires were answered by nearly 80 centres/units (with an overall response rate of 47% and 43%) from 12 European countries and EORTC. Results Our survey shows that about 90% of centres have a CDMS in routine use. Of these CDMS nearly 50% are commercial systems; Open Source solutions don't play a major role. In general, solutions used for clinical data management are very heterogeneous: 20 different commercial CDMS products (7 Open Source solutions) in addition to 17/18 proprietary systems are in use. The most widely employed CDMS products are MACRO™ and Capture System™, followed by solutions that are used in at least 3 centres: eResearch Network™, CleanWeb™, GCP Base™ and SAS™. Although quality management systems for data management are in place in most centres/units, there exist some deficits in the area of system validation. Conclusions Because the considerable heterogeneity of data management software solutions may be a hindrance to cooperation based on trial data exchange, standards like CDISC (Clinical Data Interchange Standard Consortium) should be implemented more widely. In a heterogeneous environment the use of data standards can simplify data exchange, increase the quality of data and prepare centres
... Content ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ... This Site ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking ...
... Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ...
Creutzig, Ursula; Zimmermann, Martin; Hannemann, Julia; Krämer, Irene; Pfistner, Beate; Herold, Ralf; Henze, Günter
The German 'Competence Network Paediatric Oncology and Haematology' aims at improving the structure of paediatric oncology and haematology as a whole, focussing in particular on the quality of clinical trials and study co-ordinating centres. This comprises the following measures: (1) Employment of research and trial assistants in order to improve the quality of documentation and study management in the participating hospitals. (2) Development of an internet portal to provide medical information for non-professionals, for patients and their families as well as for health professionals. (3) The project group 'Central Trial Support' supports study centres during the process of writing and examining new treatment protocols so that they are in compliance with the Good Clinical Practice criteria, formal criteria, legal requirements and statutory provisions. This group currently produces a structural standardisation of study protocols and case record forms in order to improve their usability. The 'Competence Network Malignant Lymphomas' is a project with similar aims and will be outlined for comparison.
Zhang, Shuyu; Mou, Jiani; Hackett, Andy P.; Raymond, Stephen A.; Chang, Annette M.
Abstract Background: This report describes the performance of a wireless electronic diary (e-diary) system for data collection and enhanced patient–investigator interactions during intensive insulin management in diabetes clinical trials. Materials and Methods: We implemented a customized electronic communication system featuring an e-diary and a Web portal in three global, randomized, controlled Phase 3 clinical trials testing basal insulin peglispro compared with insulin glargine, both combined with prandial insulin lispro, in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively). We collected data during 28 weeks of study e-diary use for the report. Results: Patients (n=2,938) in 31 countries used e-diaries to transmit 2,439,087 blood glucose (BG) values, 96% of which were associated by the patient with a protocol time point during the 72-h response window. Of 208,192 hypoglycemia events captured, 96% had a BG value, and 95% had treatments and outcomes entered by patients within the 72-h window. Patients recorded administration of 1,964,477 insulin doses; 93% of basal insulin doses were adherent with the investigator prescription. Investigators adjusted 13 basal and 92 bolus insulin prescriptions per patient-year using the e-diary system. After 26 weeks of treatment and e-diary use in the combined study arms, hemoglobin A1c values decreased by 0.6% or 1.6% and fasting BG decreased by 7.8 or 28 mg/dL in patients with T1DM or T2DM, respectively. Conclusions: The e-diary system enabled comprehensive data collection and facilitated communication between investigators and patients for intensive insulin management in three global clinical trials testing basal insulins. PMID:25826466
Kastner, Monika; Straus, Sharon E
Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management.
Straus, Sharon E.
BACKGROUND Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. OBJECTIVE To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. DATA SOURCES Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. REVIEW METHODS Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. RESULTS Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). CONCLUSION Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management. Electronic supplementary material The online version of this article (doi:10.1007/s11606-008-0812-9) contains supplementary material, which is available to authorized users. PMID:18836782
Goldfien, Robert; Pressman, Alice; Jacobson, Alice; Ng, Michele; Avins, Andrew
Context: Relatively few patients with gout receive appropriate treatment. Objective: To determine whether a pharmacist-staffed gout management program is more effective than usual care in achieving target serum uric acid (sUA) levels in gout patients. Design: A parallel-group, randomized controlled trial of a pharmacist-staffed, telephone-based program for managing hyperuricemia vs usual care. Trial duration was 26 weeks. Main Outcome Measures: Primary outcome measure was achieving sUA levels at or below 6 mg/dL at the 26-week visit. Secondary outcome was mean change in sUA levels in the control and intervention groups. Participants were adults with recurrent gout and sUA levels above 6.0 mg/dL. Participants were randomly assigned to management by a clinical pharmacist following protocol or to monitoring of sUA levels but management of their gout by their usual treating physician. Results: Of 102 patients who met eligibility criteria, 77 subjects obtained a baseline sUA measurement and were entered into the trial. Among 37 participants in the intervention group, 13 (35%) had sUA levels at or below 6.0 mg/dL at 26 weeks, compared with 5 (13%) of 40 participants in the control group (risk ratio = 2.8, 95% confidence interval [CI] = 1.1 to 7.1, p = 0.03). The mean change in sUA levels among controls was +0.1 mg/dL compared with −1.5 mg/dL in the intervention group (sUA difference = −1.6, 95% CI = −0.9 to −2.4, p < 0.001). Conclusions: A structured pharmacist-staffed program was more effective than usual care for achieving target sUA levels. These results suggest a structured program could greatly improve gout management. PMID:27352414
Rabeh, Wissam; Akel, Samir; Eid, Toufic; Muwakkit, Samar; Abboud, Miguel; El Solh, Hassan; Saab, Raya
Management of Wilms tumor (WT) in children depends on a multidisciplinary approach to treatment, and outcomes have significantly improved as reported by cooperative group clinical trials. Here, we review the clinical outcomes of patients with WT and identify challenges and barriers encountered in multidisciplinary management outside of cooperative clinical trials. We retrospectively reviewed the clinical records of 35 children with WT treated between April 2002 and June 2013 at the Children's Cancer Institute in Lebanon. Upfront resection was performed in 23 cases. Biopsies were performed for Stage V tumors (n=4), those with unresectable tumors or inferior vena caval thrombus (n=5), and patients who had partial surgery performed elsewhere prior to presentation (n=2). One patient died due to toxicity prior to surgery. The tumor was Stage I in eight patients, Stage II in five patients, Stages III and IV in nine patients each, and bilateral (Stage V) in four patients. Adherence to The National Wilms Tumor Study-5 recommendations was adequate. At the time of analysis, 30 patients were free of disease and four patients had relapse-all having metastatic disease initially. The National Wilms Tumor Study-5 therapy resulted in favorable outcomes in children with nonmetastatic Wilms tumor in the setting of a multidisciplinary approach to therapy and resolution of financial barriers to medical care. Upstaging due to prior intervention and lung radiation therapy to all those with computed tomography-detected lung nodules may both have resulted in overtreatment of a subset of patients. Finally, the relatively high incidence of bilateral tumors suggests the need for further genetic and molecular studies in this patient population. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.
Edinger, Jack D.; Grubber, Janet; Ulmer, Christi; Zervakis, Jennifer; Olsen, Maren
Objectives: To test a collaborative care model for interfacing sleep specialists with primary care providers to enhance patients' sleep disorders management. Methods: This study used a randomized, parallel group, clinical intervention trial design. A total of 137 adult (29 women) VA outpatients with sleep complaints were enrolled and randomly assigned to (1) an intervention (INT) consisting of a one-time consultation with a sleep specialist who provided diagnostic feedback and treatment recommendations to the patient and the patient's primary care provider; or (2) a control condition consisting of their usual primary care (UPC). Provider-focused outcomes included rates of adherence to recommended diagnostic procedures and sleep-focused interventions. Patient-focused outcomes included measures taken from sleep diaries and actigraphy; Pittsburgh Sleep Quality Index (PSQI) scores; and self-report measures of sleepiness, fatigue, mood, quality of life, and satisfaction with health care. Results: The proportions of provider-initiated sleep-focused interventions were significantly higher in the INT group than in the UPC group for polysomnography referrals (49% versus 6%; P < 0.001) and mental health clinic referrals (19% versus 6%; P = 0.02). At the 10-mo follow up, INT recipients showed greater estimated mean reductions in diary total wake time (−17.0 min; 95% confidence interval [CI]: −30.9, −3.1; P = 0.02) and greater increases in sleep efficiency (+3.7%; 95% CI: 0.8, 6.5; P = 0.01) than did UPC participants. A greater proportion of the INT group showed ≥ 1 standard deviation decline on the PSQI from baseline to the 10-mo follow-up (41% versus 21%; P = 0.02). Moreover, 69% of the INT group had normal (≤ 10) Epworth Sleepiness Scale scores at the 10-mo follow-up, whereas only 50% of the UPC group fell below this clinical cutoff (P = 0.03). Conclusions: A one-time sleep consultation significantly increased healthcare providers' attention to sleep problems and
Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.
Allen, Kelli D.; Yancy, William S.; Bosworth, Hayden B.; Coffman, Cynthia J.; Jeffreys, Amy S.; Datta, Santanu K.; McDuffie, Jennifer; Strauss, Jennifer L.; Oddone, Eugene Z.
Background Management of osteoarthritis (OA) requires both medical and behavioral strategies, but there is low use of some recommended therapies. Objectives This study examined the effectiveness of a combined patient and provider intervention for improving OA outcomes. Design Cluster randomized clinical trial with assignment to OA Intervention and Usual Care arms. Setting Department of Veterans Affairs Medical Center (VA) in Durham, NC, USA. Participants 30 providers (clusters) and 300 outpatients with symptomatic hip and / or knee OA Interventions The telephone-based patient intervention focused on weight management, physical activity, and cognitive behavioral pain management. The provider intervention involved delivery of patient-specific OA treatment recommendations to primary care providers through the electronic medical record. Measurements Primary outcome: Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) total score (range: 0-96) at 12 months. Secondary outcomes: WOMAC function subscale (range: 0-68), WOMAC pain subscale (0-20), physical performance (Short Physical Performance Battery) and depressive symptoms (Patient Health Questionnaire-8). Linear mixed models adjusted for clustering of providers assessed the difference in improvement in outcomes between arms. Results At 12-month follow-up, WOMAC scores were 4.1 points lower (indicating improvement) in the OA Intervention arm vs. Usual Care [95% confidence interval (CI) = −7.2, −1.1; p=0.009]. The WOMAC function subscale was 3.3 points lower in the intervention arm [95% CI = −5.7, −1.0; p=0.005]. There was no difference in WOMAC pain subscale scores between arms (p=0.126). Physical performance and depressive symptoms did not differ between the two arms. Limitations The study was conducted in one VA medical center. Conclusions The combined patient and provider intervention resulted in modest improvement in self-reported physical function in patients with hip and knee OA
Whellan, David J; Hasselblad, Vic; Peterson, Eric; O'Connor, Christopher M; Schulman, Kevin A
The medical community has turned to disease management (DM) to bridge the gap between proven therapies and clinical practice for patients with heart failure (HF). The aim of this study was to assess the effectiveness of DM programs in reducing hospitalization and mortality in patients with HF on the basis of the results of existing trials. We compared the published results from 19 randomized controlled clinical trials evaluating HF DM programs. A random effects model was used to combine the hazards ratio for all-cause hospitalization across the studies evaluating specific types of HF DM programs. We identified 19 relevant studies, with 5752 enrolled patients, which assessed the benefits of HF DM programs. The overall effect was a significant decrease in all-cause hospitalization for patients with HF. There was significant heterogeneity in the results (P < .0001). The results of this analysis indicate that HF DM is an intervention that could significantly decrease hospitalization for patients with HF. However, due to differences in the types of strategies and the variety of health care settings in which they were evaluated, further studies of HF DM programs with multiple participating centers are required.
Moreira, Ricardo Castanho; Mantovani, Maria de Fátima; Soriano, José Verdú
Type 2 diabetes mellitus is a chronic condition that requires ongoing, life-long care in order to be controlled. The aims of the study were to assess the effect of nursing case management on glycated hemoglobin (HbA1c) levels compared to usual care in people with type 2 diabetes mellitus and to determine if effects of nursing case management varied by gender, age, duration of disease, education, and income. This is a pragmatic clinical trial, conducted in the municipality of Bandeirantes, Paraná, Brazil, in 2011 and 2012. Eighty individuals were recruited and randomized equally to receive nursing case management or usual care. Covariates were sociodemographic and clinical factors. The outcome was HbA1c measured at baseline, 6 months, and 12 months. The sample consisted predominately of women; most had been diagnosed with type 2 diabetes mellitus within the previous 5 years. Mean age was 50.14 (SD = 7.00), with 5.27 (SD = 4.39) years of schooling and an average HbA1c of 9.90% (SD = 2.49). Hemoglobin A1c was reduced from an average of 10.33% to 9.0% (p < .01) in the nursing case management group and from 9.57% to 8.93% (p = .05) in the usual care group; the group by time effect was not significant. Case management effects varied by younger age (p = .05), duration of type 2 diabetes less than 5 years (p = .03), up to 4 years of schooling (p = .04), and being in the lowest-income stratum (p = .02). Both groups showed a statistically significant reduction of HbA1c at 6 and 12 months following baseline. The difference in proportional reduction of HbA1c between groups was not statistically significant.
Jiang, Dongsheng; Kong, Weihong; Jiang, Joanna J
Many people seek alternative treatments to reduce stress and to manage anxiety. To counsel people appropriately, physicians need to understand current evidence and recognize both the value and defects in the facts. To review the effect of Tai Chi interventions on improvement of mental health and to learn lessons from current evidence through various clinical studies. A literature search was performed to identify research studies that assessed Tai Chi's mental health benefits. Selected studies were classified according to research design, outcome measures, and results. They were qualitatively assessed based on Tai Chi's significant influence on mental health in the areas of mood, stress, and anxiety level. After screening in citations that mentioned Tai Chi as an intervention, we found 21 clinical studies, all of which included at least one outcome measure of mental health or a testing system that included a mental health component. Our results show low evidence of recommending Tai Chi intervention to all patients who seek improvement in mental health despite that many positive effects of Tai Chi practice on mood and anxiety were found in different clinical trials. Considering the fact that Tai Chi is a gentle exercise, well suited for people with various physical capabilities, especially the elderly, health care providers may consider recommending it to people with mental health issues and seek alternative treatment besides routine medical care. Nonetheless, clinicians should be aware of the limitations due to incomplete understanding of Tai Chi as an intervention. Better evidence and stronger clinical trial designs are needed to further investigate Tai Chi's role in improving mental health.
Peterson, Magnus; Byrom, Bill; Dowlman, Nikki; McEntegart, Damian
Computer-controlled systems are commonly used in clinical trials to control dispensing and manage site inventories of trial supplies. Typically such systems are used with an interactive telephone or web system that provide an interface with the study site. Realizing the maximum savings in medication associated with this approach has, in the past, been problematic as it has been difficult to fully estimate medication requirements due to the complexities of these algorithms and the inherent variation in the clinical trial recruitment process. We describe the traditional and automated methods of supplying sites. We detail a simulation approach that models the automated system. We design a number of simulation experiments using this model to investigate the supply strategy properties that influence medication overage and other strategy performance metrics. The computer-controlled medication system gave superior performance to the traditional method. In one example, a 75% overage of wasted medication in the traditional system was associated with higher supply failure than an automated system strategy with an overage of 47%. In a further example, we demonstrate that the impact of using a country stratified as opposed to site stratified scheme affects the number of deliveries and probability of supply failures more than the amount of drug wasted with respective increases of 20, 2300 and 4%. Medication savings with automated systems are particularly significant in repeat dispensing designs. We show that the number of packs required can fall by as much as 50% if one uses a predictive medication algorithm. We conclude that a computer-controlled supply chain enables medication savings to be realized and that it is possible to quantify the distribution of these savings using a simulation model. The simulation model can be used to optimize the prestudy medication supply strategy and for midstudy monitoring using real-time data contained in the study database.
Jensen, Chad D; Aylward, Brandon S; Steele, Ric G
The objective of this study was to evaluate demographic and psychosocial predictors of attendance in a family-based behavioral weight management clinical trial. Ninety-three children and adolescents aged 7-17 (Mean age = 11.59, s.d. = 2.6) who were either overweight or obese (Mean BMI percentile = 98.2) and their parents received either a 10-session behavioral treatment or a three-session brief family intervention in the context of a randomized clinical trial (10). Psychosocial and anthropometric measures were obtained before enrollment and at the end of 10 weeks for both treatment groups. Univariate linear regression and hierarchical multiple regression analyses were used to identify predictors of attendance to treatment from an a priori set of hypothesized predictors. Three variables demonstrated significant associations with the dependent variable, percent of treatment sessions attended. Specifically, distance from participant's home to treatment site, lower gross family income, and youth self-report of depressive symptoms were each associated with lower percent attendance (all Ps < 0.05). These results corroborate (i.e., income, depressive symptoms) and expand (i.e., distance from treatment site) previous reports in the literature of potential barriers to effective treatment for pediatric obesity, and suggest the need for research on treatment delivery methods that could increase participation among low-income families (e.g., eHealth, mHealth options). Depressive symptoms could represent an additional barrier to treatment attendance, suggesting that assessment and treatment for these symptoms may be appropriate before commencing weight management treatment.
Allen, Kelli D; Bosworth, Hayden B; Chatterjee, Ranee; Coffman, Cynthia J; Corsino, Leonor; Jeffreys, Amy S; Oddone, Eugene Z; Stanwyck, Catherine; Yancy, William S; Dolor, Rowena J
The Patient and PRovider Interventions for Managing Osteoarthritis (OA) in Primary Care (PRIMO) study is one of the first health services trials targeting OA in a multi-site, primary care network. This multi-site approach is important for assessing generalizability of the interventions. These analyses describe heterogeneity in clinic and patient characteristics, as well as recruitment metrics, across PRIMO study clinics. Baseline data were obtained from the PRIMO study, which enrolled n = 537 patients from ten Duke Primary Care practices. The following items were examined across clinics with descriptive statistics: (1) Practice Characteristics, including primary care specialty, numbers and specialties of providers, numbers of patients age 55+, urban/rural location and county poverty level; (2) Recruitment Metrics, including rates of eligibility, refusal and randomization; (3) Participants' Characteristics, including demographic and clinical data (general and OA-related); and (4) Participants' Self-Reported OA Treatment Use, including pharmacological and non-pharmacological therapies. Intraclass correlation coefficients (ICCs) were computed for participant characteristics and OA treatment use to describe between-clinic variation. Study clinics varied considerably across all measures, with notable differences in numbers of patients age 55+ (1,507-5,400), urban/rural location (ranging from "rural" to "small city"), and proportion of county households below poverty level (12%-26%). Among all medical records reviewed, 19% of patients were initially eligible (10%-31% across clinics), and among these, 17% were randomized into the study (13%-21% across clinics). There was considerable between-clinic variation, as measured by the ICC (>0.01), for the following patient characteristics and OA treatment use variables: age (means: 60.4-66.1 years), gender (66%-88% female), race (16%-61% non-white), low income status (5%-27%), presence of hip OA (26%-68%), presence both knee
Wang, Fusheng; Lee, Rubao; Zhang, Xiaodong; Saltz, Joel
Medical image based biomarkers are being established for therapeutic cancer clinical trials, where image assessment is among the essential tasks. Large scale image assessment is often performed by a large group of experts by retrieving images from a centralized image repository to workstations to markup and annotate images. In such environment, it is critical to provide a high performance image management system that supports efficient concurrent image retrievals in a distributed environment. There are several major challenges: high throughput of large scale image data over the Internet from the server for multiple concurrent client users, efficient communication protocols for transporting data, and effective management of versioning of data for audit trails. We study the major bottlenecks for such a system, propose and evaluate a solution by using a hybrid image storage with solid state drives and hard disk drives, RESTful Web Services based protocols for exchanging image data, and a database based versioning scheme for efficient archive of image revision history. Our experiments show promising results of our methods, and our work provides a guideline for building enterprise level high performance medical image management systems. PMID:21603096
Wang, Fusheng; Lee, Rubao; Zhang, Xiaodong; Saltz, Joel
Medical image based biomarkers are being established for therapeutic cancer clinical trials, where image assessment is among the essential tasks. Large scale image assessment is often performed by a large group of experts by retrieving images from a centralized image repository to workstations to markup and annotate images. In such environment, it is critical to provide a high performance image management system that supports efficient concurrent image retrievals in a distributed environment. There are several major challenges: high throughput of large scale image data over the Internet from the server for multiple concurrent client users, efficient communication protocols for transporting data, and effective management of versioning of data for audit trails. We study the major bottlenecks for such a system, propose and evaluate a solution by using a hybrid image storage with solid state drives and hard disk drives, RESTful Web Services based protocols for exchanging image data, and a database based versioning scheme for efficient archive of image revision history. Our experiments show promising results of our methods, and our work provides a guideline for building enterprise level high performance medical image management systems.
Forouzan, Arash; Barzegari, Hassan; Motamed, Hassan; Khavanin, Ali; Shiri, Hamideh
Introduction: Considering the existing contradictions regarding effectiveness of intravenous (IV) lidocaine, especially in emergency department (ED), the present study was designed to compare the analgesic effect of IV lidocaine and morphine sulfate in pain management for extremity bone fractures. Method: In this triple blind clinical trial, 15 to 65 year-old patients with extremity fractures and in need of pain management were randomly allocated to either IV lidocaine or morphine sulfate group and were compared regarding severity of pain 5, 10, 15, 20, 25, and 30 minutes after infusion via intention to treat analysis. The absolute risk reduction, number needed to treat and relative risk of IV lidocaine after 30 minutes were 0.40 (95%CI: 0.25 – 0.64), 7 (95%CI: 3.7 – 23.1), and 20.71 (95%CI: 10.91 – 30.51), respectively. Results: 280 patients with the mean age of 32.50 ± 12.77 years were randomly divided into 2 equal groups of 140 (73.9% male). The 2 groups had similar baseline characteristics. 15 minutes after injection success rate was 49.28% in lidocaine and 33.57% in morphine sulfate group (p = 0.011), and after 30 minutes it reached 85.71% and 65.00%, respectively (p < 0.001). Conclusion: Based on the results of the present study, IV lidocaine could be considered as a reasonable alternative choice for pain management in ED. PMID:28894783
Wang, Fusheng; Lee, Rubao; Zhang, Xiaodong; Saltz, Joel
Medical image based biomarkers are being established for therapeutic cancer clinical trials, where image assessment is among the essential tasks. Large scale image assessment is often performed by a large group of experts by retrieving images from a centralized image repository to workstations to markup and annotate images. In such environment, it is critical to provide a high performance image management system that supports efficient concurrent image retrievals in a distributed environment. There are several major challenges: high throughput of large scale image data over the Internet from the server for multiple concurrent client users, efficient communication protocols for transporting data, and effective management of versioning of data for audit trails. We study the major bottlenecks for such a system, propose and evaluate a solution by using a hybrid image storage with solid state drives and hard disk drives, RESTfulWeb Services based protocols for exchanging image data, and a database based versioning scheme for efficient archive of image revision history. Our experiments show promising results of our methods, and our work provides a guideline for building enterprise level high performance medical image management systems.
Krishnan, Jerry A; Bender, Bruce G; Wamboldt, Frederick S; Szefler, Stanley J; Adkinson, N Franklin; Zeiger, Robert S; Wise, Robert A; Bilderback, Andrew L; Rand, Cynthia S
Information comparing subjective and objective measurements of adherence to study medications and the effects of adherence on treatment-related differences in asthma clinical trials are limited. We sought to compare subjective and objective measurements of children's adherence to inhaled corticosteroids or placebo and to determine whether adherence to study medications modified treatment-related differences in outcomes. In an ancillary study conducted in 3 of 8 Childhood Asthma Management Program Clinical Centers, adherence was assessed by using self-reported and objective data in 5- to 12-year-old children with mild or moderate asthma who were randomly assigned to 200 μg of inhaled budesonide twice per day (n = 84) or placebo (n = 56) for 4 years. The κ statistic was used to evaluate agreement between self-reported adherence (daily diary cards) and objectively measured adherence (number of doses left in study inhalers). Multivariable analyses were used to determine whether adherence to study treatment modified treatment-related differences in outcomes. Adherence of less than 80% was seen in 75% of 140 children when adherence was measured objectively but only in 6% of children when measured by means of self-report. There was poor agreement between objective and subjective measurements of adherence of at least 80% (κ = 0.00; 95% CI, -0.05 to 0.04); self-reported adherence over the 4-year period generally overestimated objectively measured adherence (93.6% vs 60.8%, P < .0001). There was little evidence to indicate that adherence modified treatment-related differences in outcomes. Researchers should use objective rather than self-reported adherence data to identify clinical trial participants with low levels of adherence to study treatment. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Kroenke, Kurt; Krebs, Erin E; Wu, Jingwei; Yu, Zhangsheng; Chumbler, Neale R; Bair, Matthew J
Chronic musculoskeletal pain is among the most prevalent, costly, and disabling medical disorders. However, few clinical trials have examined interventions to improve chronic pain in primary care. To determine the effectiveness of a telecare intervention for chronic pain. The Stepped Care to Optimize Pain Care Effectiveness (SCOPE) study was a randomized trial comparing a telephone-delivered collaborative care management intervention vs usual care in 250 patients with chronic (≥3 months) musculoskeletal pain of at least moderate intensity (Brief Pain Inventory [BPI] score ≥5). Patients were enrolled from 5 primary care clinics in a single Veterans Affairs medical center from June 2010 through May 2012, with 12-month follow-up completed by June 2013. Patients were randomized either to an intervention group (n = 124) or to a usual care group whose members received all pain care as usual from their primary care physicians (n = 126). The intervention group received 12 months of telecare management that coupled automated symptom monitoring with an algorithm-guided stepped care approach to optimizing analgesics. Primary outcome was the BPI total score, which ranges from 0 ("no pain") to 10 ("pain as bad as you can imagine") and for which a 1-point change is considered clinically important. Secondary pain outcomes included BPI interference and severity, global pain improvement, treatment satisfaction, and use of opioids and other analgesics. Overall, mean (SD) baseline BPI scores in the intervention and control groups were 5.31 (1.81) and 5.12 (1.80), respectively. Compared with usual care, the intervention group had a 1.02-point lower (95% CI, -1.58 to -0.47) BPI score at 12 months (3.57 vs 4.59). Patients in the intervention group were nearly twice as likely to report at least a 30% improvement in their pain score by 12 months (51.7% vs 27.1%; relative risk, 1.9 [95% CI, 1.4 to 2.7]), with a number needed to treat of 4.1 (95% CI, 3.0 to 6.4) for a 30
Cortés-Puch, Irene; Wesley, Robert A.; Carome, Michael A.; Danner, Robert L.; Wolfe, Sidney M.; Natanson, Charles
Objective The adequacy of informed consent in the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial (SUPPORT) has been questioned. SUPPORT investigators and publishing editors, heads of government study funding agencies, and many ethicists have argued that informed consent was adequate because the two oxygen saturation target ranges studied fell within a range commonly recommended in guidelines. We sought to determine whether each oxygen target as studied in SUPPORT and four similar randomized controlled trials (RCTs) was consistent with usual care. Design/Participants/Setting PubMed, EMBASE, Web of Science, and Scopus were searched for English articles back to 1990 providing information on usual care oxygen management in extremely premature infants. Data were extracted on intended and achieved oxygen saturation levels as determined by pulse oximetry. Twenty-two SUPPORT consent forms were examined for statements about oxygen interventions. Results While the high oxygen saturation target range (91 to 95%) was consistent with usual care, the low range (85 to 89%) was not used outside of the SUPPORT trial according to surveys and clinical studies of usual care. During usual care, similar lower limits (< 88%) were universally paired with higher upper limits (≥ 92%) and providers skewed achieved oxygen saturations toward the upper-end of these intended ranges. Blinded targeting of a low narrow range resulted in significantly lower achieved oxygen saturations and a doubling of time spent below the lower limit of the intended range compared to usual care practices. The SUPPORT consent forms suggested that the low oxygen saturation arm was a widely practiced subset of usual care. Conclusions SUPPORT does not exemplify comparative effectiveness research studying practices or therapies in common use. Descriptions of major differences between the interventions studied and commonly practiced usual care, as well as potential risks associated with these
Amini, Leila; Tehranian, Najmeh; Movahedin, Mansoureh; Ramezani Tehrani, Fahimeh; Ziaee, Saeedeh
Background: Recently there is a focus on the antioxidants as adjuvant treatment of polycystic ovary syndrome (PCOS), the most endocrinopathy in reproductive age women. Objective: The aim of this review is answer to the question whether antioxidants are effective for managing of hormonal and metabolic problems in women with PCOS based on first degree evidences from Iran. Materials and Methods: A systematic review of clinical trials was done in Persian and international databases including PubMed, Scientific Information Database, Google Scholar, Iran Medex, and Magiran up to 2013. Keywords were including polycystic ovary syndrome, Iran, vitamin, antioxidant. From 440 potential studies found electronically, 11 studies; including 444 women in intervention and 390 women in control groups. Intervention in three studies was Calcium-vitamin D or calcitriol; in three studies was ω-3 fatty acids; in two studies was N-acetyl cysteine; in one study was folic acid; in one study was Zinc; and in one study was Soy. Results: Finally, 11 studies that were relevant and met the inclusion criteria reviewed. There were 7 studies in English and 4 studies in Persian. We couldn’t include all studies because all full texts were not accessible. Conclusion: The results showed that antioxidants and vitamins have positive effects on management of PCOS women. Although it seems more studies is necessary in this field. PMID:25653669
Henry, James A.; Thielman, Emily J.; Zaugg, Tara L.; Kaelin, Christine; Schmidt, Caroline J.; Griest, Susan; McMillan, Garnett P.; Myers, Paula; Rivera, Izel; Baldwin, Robert; Carlson, Kathleen
Purpose: This randomized controlled trial evaluated, within clinical settings, the effectiveness of coping skills education that is provided with progressive tinnitus management (PTM). Method: At 2 Veterans Affairs medical centers, N = 300 veterans were randomized to either PTM intervention or 6-month wait-list control. The PTM intervention…
Clinical trials/research are conducted to examine the clinical questions of practicing physicians. It is important to design trials appropriately in advance, taking their feasibility into account. A randomized, controlled trial is the ultimate design for treatment comparisons at the final confirmatory stage. However, randomized trials do not necessarily provide all answers to clinical questions. This article summarizes fundamental points of clinical trial design and the important role of randomization and contrasts superiority and noninferiority trials. In addition, it focuses on propensity score matching, a useful method to compare two treatment arms, especially in the context where randomization is infeasible. The propensity score-matching method is increasingly used in surgical clinical research.
Griffin, Hayley J; O'Connor, Helen T; Rooney, Kieron B; Steinbeck, Katharine S
Limited research in young overweight and obese women indicates that they are difficult to recruit to weight management trials, with attrition higher and weight loss success lower than middle to older age participants. This study aimed to evaluate the effectiveness of different recruitment strategies for a clinical weight loss trial in overweight and obese Generation Y women. Overweight and obese (BMI >=27.5 kg/m-2) women aged 18-25 years (n=70) were required for a 12 month clinical weight management trial including diet, exercise and behaviour modification. Contact with researchers and eventual recruitment are reported for the various strategies employed to engage participants. Data reported as % or mean±SE. Recruitment was challenging with only 50 of the total 70 participants recruited within the scheduled time frame (24 months). Just over one quarter (27%) of volunteers assessed were recruited. Flyers posted around local tertiary education campuses were the most successful method, yielding 36% of included participants. This was followed by advertisements on the local area health service intranet (26%) and in local and metropolitan newspapers (16%). Recruitment of overweight and obese Generation Y women for a clinical weight loss trial was difficult. Multiple strategies targeted at this age and gender group were required. Less rigorous selection criteria and reduced face-to-face intervention time may improve recruitment and retention rates into clinical trials for this age group.
Blumenthal, James A.; Sherwood, Andrew; Smith, Patrick J.; Watkins, Lana; Mabe, Stephanie; Kraus, William E.; Ingle, Krista; Miller, Paula; Hinderliter, Alan
Background Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease (CHD). Despite considerable epidemiologic evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. Methods and Results 151 outpatients with CHD aged 36 to 84 years were randomized to 12-weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and CHD biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR comprised a No-CR comparison group. All participants were followed for up to 5.3 years (median = 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P = 0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in CHD biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with CR alone (18% vs. 33%, HR = 0.49 [0.25, 0.95], P = 0.035) and both CR groups had lower event rates compared to the No-CR group (47%, HR = 0.44 [0.27, 0.71], P < .001). Conclusions CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. Clinical Trial Registration Information www.Clinicaltrials.gov. Identifier: NCT00981253. PMID:27045127
Rollo, David; Machado, Sanjay; Ceschin, Mauro
Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports.
Neri-Mejía, M; Pedraza-Avilés, A G
To compare the effectiveness of intramuscular oxytocin against intravenous oxytocin against intravenous traditional oxytocin infusion, in the active management of the third period of the delayed impingement labor work and controlled cord traction. Randomized controlled blinded clinical trial. In women age 14 to 40 with full term pregnancy, childbirth attended by ISSSTE's Regional Hospital "Gral. Ignacio Zaragoza", in the period from August to December 2015. 152 deliveries were attended, from which 66 fulfill with selection criteria. Group 1 = 22 patients, group 2 = 21 patients and Group 3 = 23 patients. The total age average was 26.92 + 5.8. For blood volume, statistical differences were significant among the three groups (p = 0.000). Adverse reactions were presented in 1 .5%, without difference between the groups. (P = 0.337). The differences in hemoglobin values and final and initial hematocrit presented differences with statistical significance (p = 0.000 for both). Nonetheless, the differences obtained in the analysis of the diverse variables among the three types of treatment, the three schemes are effective on the obstetrical hemorrhage prevention.
Evans, Scott R.
Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. The selection of a clinical trial design structure requires logic and creativity. Common structural designs are discussed. PMID:21423788
Liu, Yan; deSouza, Nandita M; Shankar, Lalitha K; Kauczor, Hans-Ulrich; Trattnig, Siegfried; Collette, Sandra; Chiti, Arturo
Imaging has steadily evolved in clinical cancer research as a result of improved conventional imaging methods and the innovation of new functional and molecular imaging techniques. Despite this evolution, the design and data quality derived from imaging within clinical trials are not ideal and gaps exist with paucity of optimised methods, constraints of trial operational support, and scarce resources. Difficulties associated with integrating imaging biomarkers into trials have been neglected compared with inclusion of tissue and blood biomarkers, largely because of inherent challenges in the complexity of imaging technologies, safety issues related to new imaging contrast media, standardisation of image acquisition across multivendor platforms, and various postprocessing options available with advanced software. Ignorance of these pitfalls directly affects the quality of the imaging read-out, leading to trial failure, particularly when imaging is a primary endpoint. Therefore, we propose a practical risk-based framework and recommendations for trials driven by imaging biomarkers, which allow identification of risks at trial initiation to better allocate resources and prioritise key tasks. Copyright © 2015 Elsevier Ltd. All rights reserved.
Arab, Lenore; Hahn, Harry; Henry, Judith; Chacko, Sara; Winter, Ashley; Cambou, Mary C
Screening and tracking subjects and data management in clinical trials require significant investments in manpower that can be reduced through the use of web-based systems. To support a validation trial of various dietary assessment tools that required multiple clinic visits and eight repeats of online assessments, we developed an interactive web-based system to automate all levels of management of a biomarker-based clinical trial. The "Energetics System" was developed to support 1) the work of the study coordinator in recruiting, screening and tracking subject flow, 2) the need of the principal investigator to review study progress, and 3) continuous data analysis. The system was designed to automate web-based self-screening into the trial. It supported scheduling tasks and triggered tailored messaging for late and non-responders. For the investigators, it provided real-time status overviews on all subjects, created electronic case reports, supported data queries and prepared analytic data files. Encryption and multi-level password protection were used to insure data privacy. The system was programmed iteratively and required six months of a web programmer's time along with active team engagement. In this study the enhancement in speed and efficiency of recruitment and quality of data collection as a result of this system outweighed the initial investment. Web-based systems have the potential to streamline the process of recruitment and day-to-day management of clinical trials in addition to improving efficiency and quality. Because of their added value they should be considered for trials of moderate size or complexity.
Kleijnen, J; Knipschild, P; ter Riet, G
OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800
Data generated in all clinical trial are recorded on the data collection instrument Case report Form / Electronic Case Report Form by investigators located at various sites in various countries. In multicentric clinical trials since different investigator or medically qualified experts are from different sites / centers recording the medical term(s) uniformly is a big challenge. Medical coders from clinical data management team process these terms and perform medical coding. Medical coding is performed to categorize the medical terms reported appropriately so that they can be analyzed/reviewed. This article describes process which is used for medical coding in clinical data management and two most commonly used medical dictionaries MedDRA and WHO-DDE in brief. It is expected to help medical coders to understand the process of medical coding in clinical data management. Few common issues which the medical coder faces while performing medical coding, are also highlighted.
McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John
The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one ‘parallel outcomes’ model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β = 0.060, p < 0.05). In the second trial, CM predicted negative urinalysis (−UA) over the 12-week treatment period (β = 0.069, p < 0.05). In both trials, there was a significant, positive relationship between attendance and −UA submission, but in the first trial a −UA at both baseline and over time was related to attendance over time (r = 0.117; r = 0.013, respectively) and in the second trial, a −UA submission at baseline was associated with increased attendance over time (r = 0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This ‘indirect reinforcement’ between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. PMID:26456717
McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John
The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials.
Howard, Virginia J; Meschia, James F; Lal, Brajesh K; Turan, Tanya N; Roubin, Gary S; Brown, Robert D; Voeks, Jenifer H; Barrett, Kevin M; Demaerschalk, Bart M; Huston, John; Lazar, Ronald M; Moore, Wesley S; Wadley, Virginia G; Chaturvedi, Seemant; Moy, Claudia S; Chimowitz, Marc; Howard, George; Brott, Thomas G
Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone
Solak, Okan; Oz, Gürhan; Kokulu, Serdar; Solak, Ozlem; Doğan, Gökçen; Esme, Hıdır; Ocalan, Kubilay; Baki, Elif Doğan
The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. To investigate the effectiveness of intramuscular opioid (IMO), intravenous patient-controlled analgesia (IVPCA) and the Fentanyl transdermal therapeutic system (TTS) in the management of rib fracture pain. Prospective randomized clinical trial. In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB) in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15), 4×40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15) this was 5 μg/mL continuous intravenous fentanyl and was 50 μg fentanyl TTS in Group TTS (n=15). The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS). The pain during lying down (VASl) and mobilisation (VASm) was detected. There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05). We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p<0.05). The mean VASl and VASm scores measured on the 1(st), 2(nd), 3(rd), 4(th) and 5(th) days were found to be higher in Group IMO than in Groups IVPCA and TTS; however, these differences were not statistically significant (p>0.05). In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA
Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann
Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484
Murphy, Sean C; Shott, Joseph P; Parikh, Sunil; Etter, Paige; Prescott, William R; Stewart, V Ann
Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests.
Edinger, Jack D; Grubber, Janet; Ulmer, Christi; Zervakis, Jennifer; Olsen, Maren
To test a collaborative care model for interfacing sleep specialists with primary care providers to enhance patients' sleep disorders management. This study used a randomized, parallel group, clinical intervention trial design. A total of 137 adult (29 women) VA outpatients with sleep complaints were enrolled and randomly assigned to (1) an intervention (INT) consisting of a one-time consultation with a sleep specialist who provided diagnostic feedback and treatment recommendations to the patient and the patient's primary care provider; or (2) a control condition consisting of their usual primary care (UPC). Provider-focused outcomes included rates of adherence to recommended diagnostic procedures and sleep-focused interventions. Patient-focused outcomes included measures taken from sleep diaries and actigraphy; Pittsburgh Sleep Quality Index (PSQI) scores; and self-report measures of sleepiness, fatigue, mood, quality of life, and satisfaction with health care. The proportions of provider-initiated sleep-focused interventions were significantly higher in the INT group than in the UPC group for polysomnography referrals (49% versus 6%; P < 0.001) and mental health clinic referrals (19% versus 6%; P = 0.02). At the 10-mo follow up, INT recipients showed greater estimated mean reductions in diary total wake time (-17.0 min; 95% confidence interval [CI]: -30.9, -3.1; P = 0.02) and greater increases in sleep efficiency (+3.7%; 95% CI: 0.8, 6.5; P = 0.01) than did UPC participants. A greater proportion of the INT group showed ≥ 1 standard deviation decline on the PSQI from baseline to the 10-mo follow-up (41% versus 21%; P = 0.02). Moreover, 69% of the INT group had normal (≤ 10) Epworth Sleepiness Scale scores at the 10-mo follow-up, whereas only 50% of the UPC group fell below this clinical cutoff (P = 0.03). A one-time sleep consultation significantly increased healthcare providers' attention to sleep problems and resulted in benefits to patients' sleep
Emami Ardestani, Mohammad; Kalantary, Elham; Samaiy, Vajihe; Taherian, Keramat
Introduction: Corticosteroids are routinely used in management of chronic obstructive pulmonary disease (COPD) exacerbation. The main purpose of present study was to compare the efficacy of methyl prednisolone (MP) and dexamethasone (DXM) for this purpose. Methods: Adult COPD patients entered the present clinical trial. All patients received standard treatment on admission and were then divided into 2 groups of intravenous MP and DXM. Patients were asked to rate their shortness of breath; sputum volume and viscosity; dyspnea; cough; and general wellbeing on a 0-5 scale. Baseline parameters such as O2 saturation, arterial blood gas parameters, and white blood cell (WBC) count were compared on admission and day 7 and 14 of therapy using SPSS 22. Results: 68 patients were randomly allocated to 2 groups of 34 (82.4% male). The baseline characteristics of the two groups were similar (p < 0.05). Comparison of treatment outcomes for the 7th day showed a significant difference between the 2 groups only regarding cough (p = 0.047), HCO3 (p < 0.001), and O2 saturation (p = 0.042). On day 14 the 2 groups were different only regarding cough (p = 0.048) and sputum viscosity (p = 0.011). There was a significant difference between the two groups regarding trend of changes in dyspnea (p = 0.02; DXM >> MP) and cough (p = 0.035; MP >> DXM). There were no significant differences between the two medications regarding side effects on 7th and 14th day after treatment. Conclusion: It seems that MP and DXM have similar efficacy and side effects in treatment of COPD exacerbation and selecting drug of choice would better be based on the most prominent symptoms of patients on admission. PMID:28286842
Geyer, John; Myers, Kathleen; Vander Stoep, Ann; McCarty, Carolyn; Palmer, Nancy; DeSalvo, Amy
Clinical trials with multiple intervention locations and a single research coordinating center can be logistically difficult to implement. Increasingly, web-based systems are used to provide clinical trial support with many commercial, open source, and proprietary systems in use. New web-based tools are available which can be customized without programming expertise to deliver web-based clinical trial management and data collection functions. To demonstrate the feasibility of utilizing low-cost configurable applications to create a customized web-based data collection and study management system for a five intervention site randomized clinical trial establishing the efficacy of providing evidence-based treatment via teleconferencing to children with attention-deficit hyperactivity disorder. The sites are small communities that would not usually be included in traditional randomized trials. A major goal was to develop database that participants could access from computers in their home communities for direct data entry. Discussed is the selection process leading to the identification and utilization of a cost-effective and user-friendly set of tools capable of customization for data collection and study management tasks. An online assessment collection application, template-based web portal creation application, and web-accessible Access 2007 database were selected and customized to provide the following features: schedule appointments, administer and monitor online secure assessments, issue subject incentives, and securely transmit electronic documents between sites. Each tool was configured by users with limited programming expertise. As of June 2011, the system has successfully been used with 125 participants in 5 communities, who have completed 536 sets of assessment questionnaires, 8 community therapists, and 11 research staff at the research coordinating center. Total automation of processes is not possible with the current set of tools as each is loosely
Burke, Lora E.; Styn, Mindi A.; Glanz, Karen; Ewing, Linda J.; Elci, Okan U.; Conroy, Margaret B.; Sereika, Susan M.; Acharya, Sushama D.; Music, Edvin; Keating, Alison L.; Sevick, Mary Ann
Background The primary form of treatment for obesity today is behavioral therapy. Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change. The SMART weight loss trial examined the impact of replacing the standard paper record used for self-monitoring with a personal digital assistant (PDA). This paper describes the design, methods, intervention, and baseline sample characteristics of the SMART trial. Methods The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention. Participants were randomized to one of three conditions (1) use of a standard paper record (PR); (2) use of a PDA with dietary and physical activity software (PDA); or (3), use of a PDA with the same software plus a customized feedback program (PDA + FB). Results We screened 704 individuals and randomized 210. There were statistically but not clinically significant differences among the three cohorts in age, education, HDL cholesterol, blood glucose and systolic blood pressure. At 24 months, retention rate for the first of three cohorts was 90%. Conclusions To the best of our knowledge, the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records. This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component. PMID:19665588
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Morais, Ítalo; Lemos, Andréa; Katz, Leila; Melo, Lorena Fernandes Rosendo de; Maciel, Mariano Maia; Amorim, Melania Maria Ramos de
Introduction Systematic reviews that evaluate the perineal cryotherapy to reduce pain in the vaginal postpartum are inconclusive. Purpose To evaluate clinical effectiveness of cryotherapy in the management of humanized postpartum perineal pain and vaginal edema. Methods A double-bind randomized controlled clinical trial (UTN number: U1111-1131-8433) was conducted in a hospital in Northeastern, Brazil. Women were included following humanized childbirth. All had vaginal deliveries of a single, full-term pregnancy with cephalic presentation. Exclusion criteria included previous perineal lesion, episiotomy during the current delivery, instrumental delivery, uterine curettage and postpartum hemorrhage. In the experimental group, an ice pack was applied six times on the perineum for 20 minutes, reducing the temperature between 10 and 15 ° C, then 60 minutes without exposure to cold. In the non-cryotherapy, a water bag unable to reduce the temperature to this extent was used, compliance with the same application protocol of the first group. Perineal temperature was monitored at zero, 10 and 20 minutes for application in both groups. Evaluations were made immediately before and after the applications and 24 hours after delivery spontaneous, to determine the association between variables. Results A total of 80 women were included in the study, 40 in each group. There was no significant difference in scores of perineal pain and edema between the groups with or without cryotherapy until 24 hours after childbirth. There was no difference between groups when accomplished repeated measures analysis over the 24 hours after delivery, considering the median perineal pain (p = 0.3) and edema (p = 0.9). Perineal cryotherapy did not influence the amount of analgesics used (p = 0.07) and no adverse effect was registered. Conclusion The use of cryotherapy following normal vaginal delivery within the concept of humanized minimally interventionist childbirth had no
Miller, Rachel E; Block, Joel A; Malfait, Anne-Marie
Anti-nerve growth factor (NGF) antibodies hold tremendous potential for the management of osteoarthritis pain, but clinical trials have revealed serious adverse effects that are incompletely understood. This review discusses clinical trial results along with preclinical studies that have assessed NGF blockade in experimental osteoarthritis, in order to provide insight for future studies. Systematic reviews have revealed that anti-NGF therapy, including tanezumab, is efficacious in improving pain and function, but serious adverse events, including rapidly progressive osteoarthritis and osteonecrosis, resulted in a moratorium on trials that was only recently lifted. Within the past year, preclinical testing has revealed effects of NGF blockade on both pain behaviors and joint structure in experimental models of osteoarthritis. Similar to clinical trial results, these studies in laboratory animals demonstrated analgesic efficacy of NGF blockade. Interestingly, several animal studies have suggested detrimental effects on joint integrity as a result of treatment, particularly when treatment is started early in the disease, when joint damage is mild to moderate. NGF blockade continues to represent a promising new approach for the treatment of osteoarthritis pain, but the actual benefits and risks remain to be fully elucidated. Preclinical models may suggest patient populations that could be best served while limiting side-effects, but future work should further investigate the mechanisms of benefits and unwanted side-effects.
Wilson, S. Jo-Anne; Wells, Philip S.; Kovacs, Michael J.; Lewis, Geoffrey M.; Martin, Janet; Burton, Erica; Anderson, David R.
Background There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care. Methods We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range ± 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups. Results Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by
Akaza, Hideyuki; Fukuoka, Masahiro; Ohtsu, Atsushi; Usami, Michiyuki; Ikeda, Tadashi; Aiba, Keisuke; Isonishi, Seiji; Ohashi, Yasuo; Saijo, Nagahiro; Sone, Saburo; Tsukagoshi, Shigeru; Tsuruo, Takashi; Kato, Masuhiro; Mikami, Osamu; Dong, Rui-Ping; von Euler, Mikael; Blackledge, George; Stribling, Don
Based on reviews of the Japanese clinical trial situation in lung cancer, gastric cancer, prostate cancer and breast cancer, it was clear that much progress has been made in short time. There are considerable differences between Japan and the West and also differences between clinical areas in Japan. For regulatory purposes bridging studies have become increasingly important. Use of identical protocols are required for effective bridging. Participations in global phase III trials is the best way of achieving registration in Japan. For successful global trials in Japan it is important to include Japanese investigators in the preparation of the protocol and to recognise the challenges facing such a project. Clinical practice in diagnosis and treatment have many differences, thus it is recommended to have clear and detailed information in the protocol. Hard end points like survival are important since they are not biased by cultural differences. There are clear difficulties with HE or QOL outcomes. The emergence of focus on evidence based medicine is also happening in Japan and will help to harmonize documentation across the world. For large adjuvant or prevention cancer global trials are essential. To facilitate global studies further development of infrastructure is necessary in Japan. Use of electronic data capture web based communication etc. will help overcome communication difficulties. Other improvements that will make Japanese participation in global trials easier and better include establishment of clinical trial centre at each hospital, introduction of trial coordinators or study nurses and an improved collaboration with company staff. A critical issue that also need addressing is agreement of centre target recruitment. We need to introduce a new flexible system in Japan if participation in global trial is to be optimised. If we can address these issues Japanese investigators and collaborative groups should be able to initiate and lead global trials in the
Aspry, Karen E; Furman, Roy; Karalis, Dean G; Jacobson, Terry A; Zhang, Audrey M; Liptak, Gregory S; Cohen, Jerome D
Large gaps in lipid treatment and medication adherence persist in high-risk outpatients in the United States. Health information technology (HIT) is being applied to close quality gaps in chronic illness care, but its utility for lipid management has not been widely studied. To perform a qualitative review of the impact of HIT interventions on lipid management processes of care (screening or testing; drug initiation, titration or adherence; or referrals) or clinical outcomes (percent at low density lipoprotein cholesterol goal; absolute lipid levels; absolute risk scores; or cardiac hospitalizations) in outpatients with coronary heart disease or at increased risk. PubMed and Google Scholar databases were searched using Medical Subject Headings related to clinical informatics and cholesterol or lipid management. English language articles that described a randomized controlled design, tested at least one HIT tool in high risk outpatients, and reported at least 1 lipid management process measure or clinical outcome, were included. Thirty-four studies that enrolled 87,874 persons were identified. Study ratings, outcomes, and magnitude of effects varied widely. Twenty-three trials reported a significant positive effect from a HIT tool on lipid management, but only 14 showed evidence that HIT interventions improve clinical outcomes. There was mixed evidence that provider-level computerized decision support improves outcomes. There was more evidence in support of patient-level tools that provide connectivity to the healthcare system, as well as system-level interventions that involve database monitoring and outreach by centralized care teams. Randomized controlled trials show wide variability in the effects of HIT on lipid management outcomes. Evidence suggests that multilevel HIT approaches that target not only providers but include patients and systems approaches will be needed to improve lipid treatment, adherence and quality. Copyright © 2013 National Lipid
Chen, Yin-Ying; Wu, Ping; Wang, Jie
Drug clinical trial is an important link in the chain of new drug research and development. The results of drug discovery and development directly depend on the extent of standardization of clinical trials. Therefore, improving the quality of drug clinical trials is of great importance, and drug clinical trial institutions play a crucial role in the quality management of drug clinical trials. After years of development, the overall level of drug clinical trials has advanced rapidly in China, and a large number of clinical trials of traditional Chinese medicine have also been carried out. However, there is still a big gap between our country and developed countries. Therefore, for the construction and management of Chinese drug clinical trial institutions, there is still a long way to go. This study aims to analyze the current development of drug clinical trial institutions in China and explore the existing problems from three aspects, including current situations of institutional organization and management, regional and professional distributions, and quality control. And some suggestions are put forward finally, including support of traditional Chinese medicine, introduction of drug-risk management system, and construction of information management.
Marchant, Gary E; Lindor, Rachel A
Clinical trials of nanotechnology medical products present complex risk management challenges that involve many uncertainties and important risk-risk trade-offs. This paper inquires whether the precautionary principle can help to inform risk management approaches to nanomedicine clinical trials. It concludes that prudent precaution may be appropriate for ensuring the safety of such trials, but that the precautionary principle itself, especially in its more extreme forms, does not provide useful guidance for specific safety measures.
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, 101M, AAV-AADC, AGN-201904-Z; Agomelatine, AN-0128, AN-2690, Arginine butyrate, Asenapine maleate; Belinostat, Bortezomib, BQ-123, BQ-788; Bucindolol hydrochloride; Certolizumab pegol; Dasatinib, Denosumab, Desvenlafaxine succinate; Ecogramostim, Esomeprazole magnesium; Homoharringtonine; huN901-DM1, Hyaluronic acid; Incyclinide; L-Arginine hydrochloride; Mepolizumab; Nematode anticoagulant protein c2, Nilotinib; Oblimersen sodium; R-115866, Raltegravir potassium, Retapamulin, Romidepsin, Rusalatide acetate; Sarcosine, SCIO-469, Soblidotin, Sorivudine; Tilarginine hydrochloride, Tipifarnib; Uracil; Vildagliptin. (c) 2007 Prous Science. All rights reserved.
Haak, Daniel; Page, Charles-E.; Deserno, Thomas M.
Providing eligibility, efficacy and security evaluation by quantitative and qualitative disease findings, medical imaging has become increasingly important in clinical trials. Here, subject's data is today captured in electronic case reports forms (eCRFs), which are offered by electronic data capture (EDC) systems. However, integration of subject's medical image data into eCRFs is insufficiently supported. Neither integration of subject's digital imaging and communications in medicine (DICOM) data, nor communication with picture archiving and communication systems (PACS), is possible. This aggravates the workflow of the study personnel, in special regarding studies with distributed data capture in multiple sites. Hence, in this work, a system architecture is presented, which connects an EDC system, a PACS and a DICOM viewer via the web access to DICOM objects (WADO) protocol. The architecture is implemented using the open source tools OpenClinica, DCM4CHEE and Weasis. The eCRF forms the primary endpoint for the study personnel, where subject's image data is stored and retrieved. Background communication with the PACS is completely hidden for the users. Data privacy and consistency is ensured by automatic de-identification and re-labelling of DICOM data with context information (e.g. study and subject identifiers), respectively. The system is exemplarily demonstrated in a clinical trial, where computer tomography (CT) data is de-centrally captured from the subjects and centrally read by a chief radiologists to decide on inclusion of the subjects in the trial. Errors, latency and costs in the EDC workflow are reduced, while, a research database is implicitly built up in the background.
Irritable bowel syndrome (IBS) is a common disorder of the gastrointestinal tract, about which there has been considerable recent research. The aim of this article is to briefly review the aspects of IBS pathogenesis that involve the gastrointestinal microbiota, and then to critically appraise the recent and emerging evidence for the use of probiotics and prebiotics in its management. The increased risk of developing IBS following gastroenteritis and the co-existence of dysbiosis, elevated luminal gas production and immune activation, indicate that the gastrointestinal microbiota may be a therapeutic target in IBS. Most systematic reviews indicate that probiotics have a beneficial impact on global IBS symptoms, abdominal pain and flatulence. However, recent trials indicate that different probiotics can improve, have no effect, or even worsen symptoms, confirming that benefits are likely to be strain and symptom-specific. There are no recent clinical trials of prebiotics in IBS, although previous studies indicate potential benefit at lower doses. Clearly, some probiotics have considerable potential in the management of IBS; however, the benefits are likely to be strain-specific. Preliminary studies suggest low doses of prebiotics may improve symptoms of IBS, although further robust clinical trials are required.
Jacobsen, Paul B; Le-Rademacher, Jennifer; Jim, Heather; Syrjala, Karen; Wingard, John R; Logan, Brent; Wu, Juan; Majhail, Navneet S; Wood, William; Rizzo, J Douglas; Geller, Nancy L; Kitko, Carrie; Faber, Edward; Abidi, Muneer H; Slater, Susan; Horowitz, Mary M; Lee, Stephanie J
Studies show that engaging patients in exercise and/or stress management techniques during hematopoietic cell transplantation (HCT) improves quality of life. The Blood and Marrow Transplant Clinical Trials Network tested the efficacy of training patients to engage in self-directed exercise and stress management during HCT. The study randomized 711 patients at 21 centers to receive 1 of 4 training interventions before HCT: a self-directed exercise program, a self-administered stress management program, both, or neither. Participants completed self-reported assessments at enrollment and up to 180 days after HCT. Randomization was stratified by center and transplant type. There were no differences in the primary endpoints of the Physical Component Summary and Mental Component Summary scales of the Medical Outcomes Study Short Form 36 at day +100 among the groups, based on an intention-to-treat analysis. There also were no differences in overall survival, days of hospitalization through day +100 post-HCT, or in other patient-reported outcomes, including treatment-related distress, sleep quality, pain, and nausea. Patients randomized to training in stress management reported more use of those techniques, but patients randomized to training in exercise did not report more physical activity. Although other studies have reported efficacy of more intensive interventions, brief training in an easy-to-disseminate format for either self-directed exercise or stress management was not effective in our trial.
Loane, M A; Gore, H E; Bloomer, S E; Corbett, R; Eedy, D J; Mathews, C; Steele, K; Wootton, R
Results from phase 1 of the UK Multicentre Teledermatology Trial demonstrated the diagnostic accuracy of realtime teledermatology using low-cost equipment. Phase 2 of the trial aimed to assess its effectiveness as a management tool for dermatological disease. Teledermatology consultations were organized between two health centres and two hospitals in Northern Ireland using low-cost videoconferencing equipment. For 205 patients seen by a dermatologist over the video-link a diagnosis and management plan were recorded. A subsequent face-to-face consultation was arranged on the same day to confirm the diagnosis and treatment regime. A comparison of these management plans revealed that the same plan was recommended in 64% of cases; the teledermatologist was unable to advocate a suitable management plan in 19% of cases; a suboptimal treatment plan was suggested by the teledermatologist in 6% of cases; and in 11% of cases, the teledermatologist suggested an inappropriate treatment plan. These findings indicate that appropriate clinical management was possible in approximately two-thirds of dermatology consultations via the video-link.
Choong, Miew Keen; Tsafnat, Guy; Hibbert, Peter; Runciman, William B; Coiera, Enrico
Clinical quality indicators are necessary to monitor the performance of healthcare services. The development of indicators should, wherever possible, be based on research evidence to minimise the risk of bias which may be introduced during their development, because of logistic, ethical or financial constraints alone. The development of automated methods to identify the evidence base for candidate indicators should improve the process of indicator development. The objective of this study is to explore the relationship between clinical quality indicators for asthma management in children with outcome and process measurements extracted from randomised controlled clinical trial reports. National-level indicators for asthma management in children will be extracted from the National Quality Measures Clearinghouse (NQMC) database and the National Institute for Health and Care Excellence (NICE) quality standards. Outcome measures will be extracted from published English language randomised controlled trial (RCT) reports for asthma management in children aged below 12 years. The two sets of measures will be compared to assess any overlap. The study will provide insights into the relationship between clinical quality indicators and measurements in RCTs. This study will also yield a list of measurements used in RCTs for asthma management in children, and will find RCT evidence for indicators used in practice. Ethical approval is not necessary because this study will not include patient data. Findings will be disseminated through peer-reviewed publications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Rodrigues, Filipe B; Wild, Edward J
Clinical Trials Corner of Journal of Huntington's Disease will regularly review ongoing and recently completed clinical trials in Huntington's disease. In this inaugural issue, we list all currently registered and ongoing clinical trials, expand on LEGATO-HD and IONIS-HTTRx, and cover two recently finished trials: Amaryllis and Pride-HD.
Logemann, Jeri A.
Recent importance placed upon efficacy research has spawned the development of the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG). This group, funded by the National Institutes of Health (NIH), was organized by the American Speech Language and Hearing Association to address the need for more treatment efficacy research…
In recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provide the investigators a second chance to modify or redesign the trial while the study is still ongoing. However, it is a concern that a shift in target patient population may occur after significant adaptations are made. In addition, the overall type I error rate may not be preserved. Moreover, the results may not be reliable and hence are difficult to interpret. As indicated by the US Food and Drug Administration draft guidance on adaptive design clinical trials, the adaptive design has to be a prospectively planned opportunity and should be based on information collected within the study, with or without formal statistical hypothesis testing. This article reviews the relative advantages, limitations, and feasibility of commonly considered adaptive designs in clinical trials. Statistical concerns when implementing adaptive designs are also discussed.
Rosenberg, S.A.; Kaplan, H.S.
This is a summary report of the Stanford randomized clinical trials of the management of Hodgkin's disease, initiated in 1962. There have been four major changes in the treatment protocols during this 22 year period. Between 1962-67, 132 patients with CS I, II and III disease were enrolled on various radiation trials. Between 1968-74, 367 patients were enrolled on studies primarily evaluating the role of adjuvant MOPP chemotherapy. Between 1974-80, variations in the chemotherapy regimen and the sequences of the combined modality programs were studied. The current studies, initiated in 1980, have enrolled 102 patients, and test a new mild adjuvant chemotherapy, VBM, (vinblastine, bleomycin and methotrexate) and utilizes ABVD in combined modality and alternating regimens. During the two decades of these studies, involving more than 800 patients, the initial remission rate and duration and the survival of all patients treated have progressively improved.
HIV/AIDS researchers are finding it increasingly difficult to recruit volunteers for their studies, and are working on designing studies that are more broadly applicable and palatable to the volunteers. Studies offer both opportunities and risks for people who volunteer. This overview describes the basics of trial design and practice, with the purposes of each trial phase clearly described. Participation requires informed consent, and before entering a study patients should ask, among other things, what side effects they can expect, and who will manage their treatment.
Chassany, O; Duracinský, M
The current reference guideline about ethics in clinical trials is the Declaration of Helsinki of human rights in medical research. Three major principles are emphasised: respect of the patient to accept or not to participate in a trial, the constraints and the presumed risks must be acceptable for patients included in a study, and vulnerable subjects should not participate in studies. The investigator is responsible for obtaining a free and well-informed consent from patients before their inclusion in a study. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. Else, a small-sized trial comparing a new drug versus a reference treatment can lead to an erroneous conclusion of absence of difference. Moreover, good results or improvement are obtained in at least 30% of cases with placebo, whatever the disease. The use of placebo is unethical in life-threatening diseases and when an effective proved drug exists. The use of placebo is ethical in severe diseases with no efficient drug, in some severe diseases even when an active reference treatment is available, and in all moderate and functional diseases. In order to detect flawed studies, most journals now ask for any manuscript submitted and reporting results of a randomised clinical trial to join a checklist in order to verify the quality of the trial. Finally, it remains the responsibility of the doctor to decide whether or not a protocol is ethical, to participate or not and to include patients or not.
Scheen, A J; Radermecker, R P; Philips, J C
The 64th scientific congress of the American Diabetes Association had a special session devoted to the presentation of the results from three clinical trials: 1) the first multicentre international trial of pancreatic islet transplantation according to the so-called Edmonton protocol with the primary endpoint of restoring insulin independence in type 1 diabetic patients; 2) three pivotal studies of 30 weeks testing both the efficacy and safety of exenatide (exendin-4), a new insulin secretagogue that is a long-acting analogue of glucagon-like peptide-1, in patients with type 2 diabetes treated with either metformin, or a sulfonylurea, or a metformin-sulfonylurea combination; and 3) the "Collaborative AtoRvastatin Diabetes Study" (CARDS), a placebo-controlled primary prevention trial of cardiovascular complications using atorvastatin 10 mg in 2 838 at risk patients with type 2 diabetes. The main results and conclusions of these trials are briefly presented as they open new perspectives in the management of patients with type 1 or type 2 diabetes mellitus.
Elfgren, Kristina; Elfström, K Miriam; Naucler, Pontus; Arnheim-Dahlström, Lisen; Dillner, Joakim
Introduction of human papillomavirus-based screening is ongoing in many countries, given its higher sensitivity and longer-lasting protection compared with cytology-based screening. However, optimal clinical management of human papillomavirus-positive but cytology-negative women is unclear, and additional studies with clinical follow-up are warranted. The aim of the current study was to investigate the long-term outcomes of the clinical management used in a double-blind, randomized clinical trial of human papillomavirus screening conducted in the context of the routine, organized screening program in Sweden. Among 12,527 women aged 32-38 years enrolled in the trial, we followed up the 195 women who attended the colposcopy screening who were cytologically normal but persistently human papillomavirus positive (at least 12 months later; median, 19 months) in the human papillomavirus testing arm (n = 100) or were randomly selected from the control arm (n = 95). Women in the human papillomavirus testing arm were followed up with repeated human papillomavirus testing, cytologies, and colposcopies if persistently human papillomavirus-positive without cervical intraepithelial neoplasia grade 2 or worse. A similar number of random colposcopies and tests were carried out in the control arm. Women were followed up over 13 years for the main outcome measures: cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse and cervical intraepithelial neoplasia grade 3 or worse. Among women who continued to attend and had continuous human papillomavirus persistence, all (40 of 40, 100% [95% confidence interval, 91-100%]) developed cervical intraepithelial neoplasia grade 2 or worse. There were no cases among women who cleared their human papillomavirus persistence (0 of 35, 0% (95% confidence interval, 0-10%) (P < .001). Among women who had had human papillomavirus persistence but did not continue with repeated human papillomavirus tests (unknown persistence
Background UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Methods/Design Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. Discussion This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD. Trial registration Current Controlled Trials: ISRCTN73535163. Date of registration: 5 April 2011 PMID:25011730
Gordon, Paul H.
Amyotrophic lateral sclerosis (ALS), first described by Jean-Martin Charcot in the 1870s, is an age-related disorder that leads to degeneration of motor neurons. The disease begins focally in the central nervous system and then spreads relentlessly. The clinical diagnosis, defined by progressive signs and symptoms of upper and lower motor neuron dysfunction, is confirmed by electromyography. Additional testing excludes other conditions. The disease is heterogeneous, but most patients die of respiratory muscle weakness less than 3 years from symptom-onset. Like other age-related neurodegenerative diseases, ALS has genetic and environmental triggers. Of the five to 10% of cases that are inherited, mutations have been discovered for a high proportion. In addition to genetic factors, age, tobacco use, and athleticism may contribute to sporadic ALS, but important etiologies are unidentified for most patients. Complex pathophysiological processes, including mitochondrial dysfunction, aggregation of misfolded protein, oxidative stress, excitotoxicity, inflammation and apoptosis, involve both motor neurons and surrounding glial cells. There is clinical and pathological overlap with other neurodegenerative diseases, particularly frontotemporal dementia. The mechanisms leading to disease propagation in the brain are a current focus of research. To date, one medication, riluzole, licensed in 1996, has been proved to prolong survival in ALS. Numerous clinical trials have so far been unable to identify another neuroprotective agent. Researchers now aim to slow disease progression by targeting known pathophysiological pathways or genetic defects. Current approaches are directed at muscle proteins such as Nogo, energetic balance, cell replacement, and abnormal gene products resulting from mutations. Until better understanding of the causes and mechanisms underlying progression lead to more robust neuroprotective agents, symptomatic therapies can extend life and improve quality of
Gordon, Paul H
Amyotrophic lateral sclerosis (ALS), first described by Jean-Martin Charcot in the 1870s, is an age-related disorder that leads to degeneration of motor neurons. The disease begins focally in the central nervous system and then spreads relentlessly. The clinical diagnosis, defined by progressive signs and symptoms of upper and lower motor neuron dysfunction, is confirmed by electromyography. Additional testing excludes other conditions. The disease is heterogeneous, but most patients die of respiratory muscle weakness less than 3 years from symptom-onset. Like other age-related neurodegenerative diseases, ALS has genetic and environmental triggers. Of the five to 10% of cases that are inherited, mutations have been discovered for a high proportion. In addition to genetic factors, age, tobacco use, and athleticism may contribute to sporadic ALS, but important etiologies are unidentified for most patients. Complex pathophysiological processes, including mitochondrial dysfunction, aggregation of misfolded protein, oxidative stress, excitotoxicity, inflammation and apoptosis, involve both motor neurons and surrounding glial cells. There is clinical and pathological overlap with other neurodegenerative diseases, particularly frontotemporal dementia. The mechanisms leading to disease propagation in the brain are a current focus of research. To date, one medication, riluzole, licensed in 1996, has been proved to prolong survival in ALS. Numerous clinical trials have so far been unable to identify another neuroprotective agent. Researchers now aim to slow disease progression by targeting known pathophysiological pathways or genetic defects. Current approaches are directed at muscle proteins such as Nogo, energetic balance, cell replacement, and abnormal gene products resulting from mutations. Until better understanding of the causes and mechanisms underlying progression lead to more robust neuroprotective agents, symptomatic therapies can extend life and improve quality of
NICHOLSON, James M.; PARRY, Samuel; CAUGHEY, Aaron B.; ROSEN, Sarah; KEEN, Allison; MACONES, George A.
Objective To compare birth outcomes resulting from the active management of risk in pregnancy at term (AMOR-IPAT) to those resulting from standard management. Methods Randomized clinical trial with 270 women of mixed parity. AMOR-IPAT used preventive labor induction to ensure delivery before the end of an estimated optimal time of delivery. Rates of four adverse obstetric events, and two composite measures, were used to evaluate birth outcomes. Results The AMOR-IPAT-exposed group had a similar cesarean delivery rate (10.3% vs. 14.9%, p=0.25), but a lower NICU admission rate (1.5% vs. 6.7%, p = 0.03), a higher uncomplicated vaginal birth rate (73.5% vs. 62.8%, p=0.046), and a lower mean Adverse Outcome Index score (1.4 vs. 8.6, p=0.03). Conclusion AMOR-IPAT exposure improved the pattern of birth outcomes. Larger randomized clinical trials are needed to further explore the impact of AMOR-IPAT on birth outcomes and to determine the best methods of preventive labor induction. PMID:18455526
Alexopoulos, George S.; Raue, Patrick J.; McCulloch, Charles; Kanellopoulos, Dora; Seirup, Joanna K.; Sirey, Jo Anne; Banerjee, Samprit; Kiosses, Dimitris N.; Areán, Patricia A.
Objective To test the hypotheses that (1) clinical case management integrated with problem-solving therapy (CM-PST) is more effective than clinical case management alone (CM) in reducing depressive symptoms of depressed, disabled, impoverished patients and that (2) development of problem-solving skills mediates improvement of depression. Methods This randomized clinical trial with a parallel design allocated participants to CM or CM-PST at 1:1 ratio. Raters were blind to patients’ assignments. Two hundred seventy-one individuals were screened and 171 were randomized to 12 weekly sessions of either CM or CM-PST. Participants were at least 60 years old with major depression measured with the 24-item Hamilton Depression Rating Scale (HAM-D), had at least one disability, were eligible for home-based meals services, and had income no more than 30% of their counties’ median. Results CM and CM-PST led to similar declines in HAM-D over 12 weeks (t = 0.37, df = 547, p = 0.71); CM was noninferior to CM-PST. The entire study group (CM plus CM-PST) had a 9.6-point decline in HAM-D (t = 18.7, df = 547, p <0.0001). The response (42.5% versus 33.3%) and remission (37.9% versus 31.0%) rates were similar (χ2 = 1.5, df = 1, p = 0.22 and χ2 = 0.9, df = 1, p = 0.34, respectively). Development of problem-solving skills did not mediate treatment outcomes. There was no significant increase in depression between the end of interventions and 12 weeks later (0.7 HAM-D point increase) (t = 1.36, df = 719, p = 0.17). Conclusion Organizations offering CM are available across the nation. With training in CM, their social workers can serve the many depressed, disabled, low-income patients, most of whom have poor response to antidepressants even when combined with psychotherapy. PMID:25794636
Alexopoulos, George S; Raue, Patrick J; McCulloch, Charles; Kanellopoulos, Dora; Seirup, Joanna K; Sirey, Jo Anne; Banerjee, Samprit; Kiosses, Dimitris N; Areán, Patricia A
To test the hypotheses that (1) clinical case management integrated with problem-solving therapy (CM-PST) is more effective than clinical case management alone (CM) in reducing depressive symptoms of depressed, disabled, impoverished patients and that (2) development of problem-solving skills mediates improvement of depression. This randomized clinical trial with a parallel design allocated participants to CM or CM-PST at 1:1 ratio. Raters were blind to patients' assignments. Two hundred seventy-one individuals were screened and 171 were randomized to 12 weekly sessions of either CM or CM-PST. Participants were at least 60 years old with major depression measured with the 24-item Hamilton Depression Rating Scale (HAM-D), had at least one disability, were eligible for home-based meals services, and had income no more than 30% of their counties' median. CM and CM-PST led to similar declines in HAM-D over 12 weeks (t = 0.37, df = 547, p = 0.71); CM was noninferior to CM-PST. The entire study group (CM plus CM-PST) had a 9.6-point decline in HAM-D (t = 18.7, df = 547, p <0.0001). The response (42.5% versus 33.3%) and remission (37.9% versus 31.0%) rates were similar (χ(2) = 1.5, df = 1, p = 0.22 and χ(2) = 0.9, df = 1, p = 0.34, respectively). Development of problem-solving skills did not mediate treatment outcomes. There was no significant increase in depression between the end of interventions and 12 weeks later (0.7 HAM-D point increase) (t = 1.36, df = 719, p = 0.17). Organizations offering CM are available across the nation. With training in CM, their social workers can serve the many depressed, disabled, low-income patients, most of whom have poor response to antidepressants even when combined with psychotherapy. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Robbins, William L.; Conklin, James J.
Medical images (angiography, CT, MRI, nuclear medicine, ultrasound, x ray) play an increasingly important role in the clinical development and regulatory review process for pharmaceuticals and medical devices. Since medical images are increasingly acquired and archived digitally, or are readily digitized from film, they can be visualized, processed and analyzed in a variety of ways using digital image processing and display technology. Moreover, with image-based data management and data visualization tools, medical images can be electronically organized and submitted to the U.S. Food and Drug Administration (FDA) for review. The collection, processing, analysis, archival, and submission of medical images in a digital format versus an analog (film-based) format presents both challenges and opportunities for the clinical and regulatory information management specialist. The medical imaging 'core laboratory' is an important resource for clinical trials and regulatory submissions involving medical imaging data. Use of digital imaging technology within a core laboratory can increase efficiency and decrease overall costs in the image data management and regulatory review process.
Butts, Sydney C; Floyd, Elizabeth; Lai, Erica; Rosenfeld, Richard M; Doerr, Timothy
The control of pain associated with mandibular fractures is an important treatment outcome that affects function, adherence to treatment regimens, and patient comfort and satisfaction. To explore the pain management protocols reported in studies of mandibular fractures, including the reporting of quality-of-life measures. PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, and clinicaltrials.gov were searched for randomized clinical trials published from 1970 to July 2014. We followed PRISMA reporting standards to assess study eligibility and extract data. Studies of patients older than 16 years who underwent operative mandibular fracture management were included. The primary data collected included the type of analgesic prescribed, associated adverse effects of the analgesic, method of pain assessment, and use of quality-of-life measures. A pain attentiveness score was assigned to studies based on the comprehensiveness of the information reported. Several variables were reviewed to determine the factors that predict reporting of pain-related data. Assessments of risk for bias were performed using the Cochrane Collaboration's domain-based evaluation method. The initial search identified 111 articles, of which 38 met inclusion criteria. Among the 38 reviewed articles, there were 38 trials and 1808 unique patients represented. Among the 38 articles, the procedures reported included maxillomandibular fixation only in 6 (16%), open reduction with internal fixation only in 20 (53%), and both in 12 (32%). Specific analgesics prescribed were reported in only 5 of the 38 studies (13%), and 3 of these used a combination of nonsteroidal anti-inflammatory drugs and acetaminophen (paracetamol). Thirteen studies (34%) reported pain assessments and 5 (13%) included quality-of-life measures. Geographic region was the only variable that predicted pain attentiveness, with studies from Europe (3 of 11 studies [27%]) and Asia (6 of 16 studies [38%]) most likely to have a high pain
Palacio, Carlos; Masri, Ghania; Mooradian, Arshag D
Alternative medicine preparations represent a significant industry worldwide. Black cohosh (Cimicifuga racemosa), a buttercup plant grown in North America, is one such popular preparation for the treatment of menopausal symptoms. Because the proportion of women experiencing climacteric symptoms is high, black cohosh merits further study as to its efficacy and safety. Convincing evidence for its efficacy in this setting remains to be demonstrated. The purpose of this systematic review was to assess the current literature on the benefits of black cohosh for women experiencing climacteric symptoms. To this end, a PubMed search was conducted on 1 November 2007 using the search terms 'black cohosh' AND 'menopause'. The search was limited to randomized controlled trials in the English language involving adults. Several additional reviews dealing with alternative therapies for menopause were included to capture additional older and non-English language literature. Ultimately, 16 studies eligible for review were identified. Many of the studies had conflicting results. Methodological flaws included lack of uniformity of the drug preparation used, variable outcome measures and lack of a placebo group. The benefits of black cohosh in the management of climacteric symptoms remain to be proven. Case studies suggest an additional unexplored area of adverse events that also needs to be addressed.
Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.
New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765
McClellan, Carey Middleton; Cramp, Fiona; Powell, Jane; Benger, Jonathan Richard
Objectives To evaluate the clinical effectiveness of soft tissue injury management by emergency nurse practitioners (ENPs) and extended scope physiotherapists (ESPs) compared to the routine care provided by doctors in a UK emergency department (ED). Design Randomised, pragmatic trial of equivalence. Setting One adult ED in England. Participants 372 patients were randomised; 126 to the ESP group, 123 to the ENP group and 123 to the doctor group. Participants were adults (older than 16 years) presenting to the ED with a peripheral soft tissue injury eligible for management by any of the three professional groups. Patients were excluded if they had any of the following: injury greater than 72 hours old; systemic disease; dislocated joints; recent surgery; unable to give informed consent (eg, dementia), open wounds; major deformities; opiate analgesia required; concurrent chest/rib injury; neurovascular deficits and associated fracture. Interventions Patients were randomised to treatment by ESPs, ENPs or routine care provided by doctors (of all grades). Main outcome measures Upper-limb and lower-limb functional scores, quality of life, physical well-being, preference-based health measures and the number of days off work. Results The clinical outcomes of soft tissue injury treated by ESPs and ENPs in the ED were equivalent to routine care provided by doctors. Conclusions As all groups were clinically equivalent it is other factors such as cost, workforce sustainability, service provision and skill mix that become important. This result validates the role of the ENP, which is becoming established as an integral part of minor injuries care, and demonstrates that the ESP should be considered as part of the clinical skill mix without detriment to outcomes. ISRCTN-ISRCTN trials register number 70891354. PMID:23144256
McClellan, Carey Middleton; Cramp, Fiona; Powell, Jane; Benger, Jonathan Richard
To evaluate the clinical effectiveness of soft tissue injury management by emergency nurse practitioners (ENPs) and extended scope physiotherapists (ESPs) compared to the routine care provided by doctors in a UK emergency department (ED). Randomised, pragmatic trial of equivalence. One adult ED in England. 372 patients were randomised; 126 to the ESP group, 123 to the ENP group and 123 to the doctor group. Participants were adults (older than 16 years) presenting to the ED with a peripheral soft tissue injury eligible for management by any of the three professional groups. Patients were excluded if they had any of the following: injury greater than 72 hours old; systemic disease; dislocated joints; recent surgery; unable to give informed consent (eg, dementia), open wounds; major deformities; opiate analgesia required; concurrent chest/rib injury; neurovascular deficits and associated fracture. Patients were randomised to treatment by ESPs, ENPs or routine care provided by doctors (of all grades). Upper-limb and lower-limb functional scores, quality of life, physical well-being, preference-based health measures and the number of days off work. The clinical outcomes of soft tissue injury treated by ESPs and ENPs in the ED were equivalent to routine care provided by doctors. As all groups were clinically equivalent it is other factors such as cost, workforce sustainability, service provision and skill mix that become important. This result validates the role of the ENP, which is becoming established as an integral part of minor injuries care, and demonstrates that the ESP should be considered as part of the clinical skill mix without detriment to outcomes. ISRCTN-ISRCTN TRIALS REGISTER NUMBER: 70891354.
Lavori, Philip W.
Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID:26140056
... Initiative Grant Finder Therapy Acceleration Program Academic Concierge Biotechnology Accelerator Clinical Trials Division Special Projects Beat AML ... Initiative Grant Finder Therapy Acceleration Program Academic Concierge Biotechnology Accelerator Clinical Trials Division Special Projects Beat AML ...
... the right choice for you. What are the costs of a clinical trial? All medical care provided ... Clinical trials conducted at other locations may involve costs related to standard medical care. These may or ...
Smith, Carol E.; Piamjariyakul, Ubolrat; Wick, Jo A.; Spertus, John A.; Russell, Christy; Dalton, Kathleen M.; Elyachar, Andrea; Vacek, James L.; Reeder, Katherine M.; Nazir, Niaman; Ellerbeck, Edward F.
Background This trial tested the effects of multidisciplinary group clinic appointments on the primary outcome of time to first HF rehospitalization or death. Methods and Results HF patients (N=198) were randomly assigned to standard care or standard care plus multidisciplinary group clinics. The group intervention consisted of 4 weekly clinic appointments and one booster clinic at month 6, where multidisciplinary professionals engaged patients in HF self-management skills. Data were collected prospectively for 12 months beginning after completion of the first four group clinic appointments (2 months post randomization). The intervention was associated with greater adherence to recommended vasodilators (p=0.04). The primary outcome (first HF-related hospitalization or death) was experienced by 22 (24%) in the intervention group and 30 (28%) in standard care. The total HF-related hospitalizations, including repeat hospitalizations after the first time; were 28 in the intervention group and 45 among those receiving standard care. The effects of treatment on rehospitalization varied significantly over time. From 2-7 months post randomization, there was a significantly longer hospitalization-free time in the intervention group (Cox proportional HR = 0.45 (95% CI = 0.21, 0.98; p=0.04). No significant difference between groups was found from month 8 through 12 (HR = 1.7, 95% CI = 0.7, 4.1). Conclusions Multidisciplinary group clinic appointments were associated with greater adherence to selected heart failure medications and longer hospitalization-free survival during the time that the intervention was underway. Larger studies will be needed to confirm the benefits seen in this trial and identify methods to sustain these benefits. PMID:25236883
Stephens, Janna; Patel, Angel
Abstract Introduction: More than one-third of U.S. adults are obese, which greatly increases their risks for type 2 diabetes, cardiovascular disease, and some types of cancer. Busy healthcare professionals need effective tools and strategies to facilitate healthy eating and increase physical activity, thus promoting weight loss in their patients. Communication technologies such as the Internet and mobile devices offer potentially powerful methodologies to deliver behavioral weight loss interventions, and researchers have studied a variety of technology-assisted approaches. Materials and Methods: The literature from 2002 to 2012 was systematically reviewed by examining clinical trials of technology-assisted interventions for weight loss or weight maintenance among overweight and obese adults. Results: In total, 2,011 citations from electronic databases were identified; 39 articles were eligible for inclusion. Findings suggest that the use of technology-assisted behavioral interventions, particularly those that incorporate text messaging or e-mail, may be effective for producing weight loss among overweight and obese adults. Conclusions: Only a small percentage of the 39 studies reviewed used mobile platforms such as Android® (Google, Mountain View, CA) phones or the iPhone® (Apple, Cupertino, CA), only two studies incorporated cost analysis, none was able to identify which features were most responsible for changes in outcomes, and few reported long-term outcomes. All of these areas are important foci for future research. PMID:25409001
Allen, Jerilyn K; Stephens, Janna; Patel, Angel
More than one-third of U.S. adults are obese, which greatly increases their risks for type 2 diabetes, cardiovascular disease, and some types of cancer. Busy healthcare professionals need effective tools and strategies to facilitate healthy eating and increase physical activity, thus promoting weight loss in their patients. Communication technologies such as the Internet and mobile devices offer potentially powerful methodologies to deliver behavioral weight loss interventions, and researchers have studied a variety of technology-assisted approaches. The literature from 2002 to 2012 was systematically reviewed by examining clinical trials of technology-assisted interventions for weight loss or weight maintenance among overweight and obese adults. In total, 2,011 citations from electronic databases were identified; 39 articles were eligible for inclusion. Findings suggest that the use of technology-assisted behavioral interventions, particularly those that incorporate text messaging or e-mail, may be effective for producing weight loss among overweight and obese adults. Only a small percentage of the 39 studies reviewed used mobile platforms such as Android(®) (Google, Mountain View, CA) phones or the iPhone(®) (Apple, Cupertino, CA), only two studies incorporated cost analysis, none was able to identify which features were most responsible for changes in outcomes, and few reported long-term outcomes. All of these areas are important foci for future research.
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. Copyright 2005 Prous Science. All rights reserved.
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5-methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA-794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155.
Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity. Recent research suggests that interventions designed for parents exclusively, which have been named parents as agents of change (PAC) approaches, have yielded positive outcomes for managing pediatric obesity. To date, no research has combined a PAC intervention approach with cognitive behavioural therapy (CBT) to examine whether these combined elements enhance intervention effectiveness. This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management. We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors, lifestyle behaviours, and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention (PEP). Methods/Design This study is a pragmatic, two-armed, parallel, single-blinded, superiority, randomized clinical trial. The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children’s BMI z-score (primary outcome). Secondary objectives are to assess intervention-mediated changes in cardiometabolic, lifestyle, and psychosocial variables in children and parents. Both interventions are similar in frequency of contact, session duration, group facilitation, lifestyle behaviour goals, and educational content. However, the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts, feelings, and behaviours; these cognitive activities are enabled by group leaders who possess formal training in CBT. Mothers and fathers of children (8–12 years of age; BMI ≥85th percentile) are eligible to participate if they are proficient in English (written and spoken) and agree for at least one parent to attend
Semrad, Thomas J.; Fahrni, Ana Rodriguez; Gong, I-Yeh; Khatri, Vijay P.
Purpose With the use of case presentations, we present a review of the role of systemic chemotherapy in oligometastatic colorectal cancer and suggest ways to integrate clinical research findings into the interdisciplinary management of this potentially curable subset of patients. Methods This educational review discusses the role of chemotherapy in the management of oligometastatic metastatic colorectal cancer. Results In initially resectable oligometastatic colorectal cancer, the goal of chemotherapy is to eradicate micrometastatic disease. Perioperative 5-fluorouracil and oxaliplatin along with surgical resection can result in 5-year survival rates as high as 57%. With the development of increasingly successful chemotherapy regimens, attention is being paid to the use of chemotherapy to convert patients with initially unresectable metastasis into patients with a chance of surgical cure. The choice of chemotherapy regimen requires consideration of the goals of therapy and assessment of both tumor and patient-specific factors. Discussion Herein we discuss the choice and timing of chemotherapy in patients with initially resectable and borderline resectable metastatic colorectal cancer. Coordinated multidisciplinary care of such patients can optimize survival outcomes and result in the cure of patients with this otherwise lethal disease. PMID:26100816
Sakamaki, Kentaro; Yamanaka, Takeharu
Clinical trials are conducted based on the development of surgical technology and are designed to answer specific research questions. In planning clinical trials population, intervention, comparison, and outcome are important elements. Sample size calculation is also central to the design of clinical trials, especially randomized, controlled ones. This article outlines study phases, four important elements of design, and sample size calculation.
Charalambous, M; Bhatti, S F M; Van Ham, L; Platt, S; Jeffery, N D; Tipold, A; Siedenburg, J; Volk, H A; Hasegawa, D; Gallucci, A; Gandini, G; Musteata, M; Ives, E; Vanhaesebrouck, A E
Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05. IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Fransen, Marlene; Nairn, Lillias; Winstanley, Julie; Lam, Paul; Edmonds, John
To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis (OA) result in measurable clinical benefits. A randomized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA. Participants were randomly allocated for 12 weeks to hydrotherapy classes (n = 55), Tai Chi classes (n = 56), or a waiting list control group (n = 41). Outcomes were assessed 12 and 24 weeks after randomization and included pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index), general health status (Medical Outcomes Study Short Form 12 Health Survey [SF-12], version 2), psychological well-being, and physical performance (Up and Go test, 50-foot walk time, timed stair climb). At 12 weeks, compared with controls, participants allocated to hydrotherapy classes demonstrated mean improvements (95% confidence interval) of 6.5 (0.4, 12.7) and 10.5 (3.6, 14.5) for pain and physical function scores (range 0-100), respectively, whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 (-0.8, 11.1) and 9.7 (2.8, 16.7), respectively. Both class allocations achieved significant improvements in the SF-12 physical component summary score, but only allocation to hydrotherapy achieved significant improvements in the physical performance measures. All significant improvements were sustained at 24 weeks. In this almost exclusively white sample, class attendance was higher for hydrotherapy, with 81% attending at least half of the available 24 classes, compared with 61% for Tai Chi. Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older, sedentary individuals with chronic hip or knee OA.
Vigil-De Gracia, Paulino; Ruiz, Esteban; López, Juan C; de Jaramillo, Ilka Alveo; Vega-Maleck, Juan C; Pinzón, Jaime
To compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in the puerperium. Randomized clinical trial. Critical care unit of gynecology and obstetrics department in the Complejo hospitalario "Dr. AAM" de la Caja de Seguro Social in Panama. Eighty-two women with severe hypertension during the postpartum period. Patients were randomized to receive hydralazine (5 mg as a slow bolus dose given intravenously, and repeated every 20 minutes to a maximum of five doses) or labetalol (20 mg in an intravenous bolus dose followed by 40 mg if not effective within 20 minutes, followed by 80 mg every 20 minutes to a maximum dose of 300 mg). The primary endpoint was the successful lowering of blood pressure. Secondary endpoints were maternal complications and side-effects. Forty-two women were enrolled in the hydralazine group and 40 in the labetalol group. Women were similar with respect to characteristics at randomization. No significant differences were observed for persistent severe hypertension or maternal side-effects. There was only one case of persistent severe hypertension in the labetalol group. There were no maternal deaths in any of the women studied. This randomized clinical trial shows that intravenous hydralazine and intravenous labetalol are effective and safe in the management of severe hypertension in the postpartum period.
Goodman, Steven N.
This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.
Blumenthal, James A; Sherwood, Andrew; Smith, Patrick J; Watkins, Lana; Mabe, Stephanie; Kraus, William E; Ingle, Krista; Miller, Paula; Hinderliter, Alan
Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease. Despite considerable epidemiological evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. One hundred fifty-one outpatients with coronary heart disease who were 36 to 84 years of age were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group. All participants were followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P=0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in coronary heart disease biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group (18% versus 33%; hazard ratio=0.49; 95% confidence interval, 0.25-0.95; P=0.035), and both CR groups had lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95% confidence interval, 0.27-0.71; P<0.001). CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00981253. © 2016 American Heart Association, Inc.
Kirk, Shelley; Brehm, Bonnie; Saelens, Brian E; Woo, Jessica G; Kissel, Elizabeth; D'Alessio, David; Bolling, Christopher; Daniels, Stephen R
To compare the effectiveness and safety of carbohydrate (CHO)-modified diets with a standard portion-controlled (PC) diet in obese children. Obese children (n=102) aged 7-12 years were randomly assigned to a 3-month intervention of a low-CHO (LC), reduced glycemic load (RGL), or standard PC diet, along with weekly dietary counseling and biweekly group exercise. Anthropometry, dietary adherence, and clinical measures were evaluated at baseline and 3, 6, and 12 months. Analyses applied intention-to-treat longitudinal mixed models. Eighty-five children (83%) completed the 12-month assessment. Daily caloric intake decreased from baseline to all time points for all diet groups (P<.0001), although LC diet adherence was persistently lower (P<.0002). At 3 months, body mass index z score was lower in all diet groups (LC, -0.27 ± 0.04; RGL, -0.20 ± 0.04; PC, -0.21 ± 0.04; P<.0001) and was maintained at 6 months, with similar results for waist circumference and percent body fat. At 12 months, participants in all diet groups had lower body mass index z scores than at baseline (LC, -0.21 ± 0.04; RGL, -0.28 ± 0.04; PC, -0.31 ± 0.04; P<.0001), and lower percent body fat, but no reductions in waist circumference were maintained. All diets demonstrated some improved clinical measures. Diets with modified CHO intake were as effective as a PC diet for weight management in obese children. However, the lower adherence to the LC diet suggests that this regimen is more difficult for children to follow, particularly in the long term. Copyright © 2012 Mosby, Inc. All rights reserved.
Anand, Vibha; Cahan, Amos; Ghosh, Soumya
ClinicalTrials.gov was established as a web-based registry for clinical trials of human participants in 2000. Mandatory registration started in 2008. Given more than a decade of registered trials, it's important to understand the "topic" areas and their evolution over time from this resource. This information may help in identifying current knowledge gaps. We use dynamic topic model (DTM) methods to discover topics and their evolution over last 17 years. Our model suggests that there are disease or organ specific trials such as 'Cardiovascular disorders', Heart & Brain conditions', or 'Breast & Prostate cancer' as well as trials registered for general health. General health trials are less likely to be FDA regulated, but both health and pain management, as well as surgical, heart, and brain trials have upward trend in recent years while advanced cancer trials have downward trended. Our model derives unique insights from metadata associated with each topic area.
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran.
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337. (c) 2003 Prous Science
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007, adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra, aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1 vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate, bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride, cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997, epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib, everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1 cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132, ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride, miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP, parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000, prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan, ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306, stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib, trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AdGVVEGF121.10, anakinra, andolast, anidulafungin, APC-2059, l-arginine hydrochloride, aripiprazole, arzoxifene hydrochloride, asimadoline; Bexarotene, bimatoprost, bimosiamose, bizelesin, BMS-188667, botulinum toxin type B, bromfenac sodium, bryostatin 1; Cannabidiol, cariporide mesilate, CCI-1004, CDP-571, cerivastatin sodium, clevudine; Dalbavancin, darbepoetin alfa, decitabine, deligoparin sodium, diethylnorspermine, drotrecogin alfa (activated), DTaP-HBV-IPV/Hib-vaccine; E-5564, eculizumab, edodekin alfa, emtricitabine, enfuvirtide, (-)-epigallocatechin gallate, eplerenone, esomeprazole magnesium, etaquine, etoricoxib, ezetimibe; Fesoterodine, fipamezole hydrochloride, fondaparinux sodium, fosamprenavir calcium, frovatriptan, fulvestrant; Gadofosveset sodium, galiximab, ghrelin (human), glufosfamide; Homoharringtonine; Idraparinux sodium, imatinib mesylate, INS-37217; KRN-7000; L-651582, lafutidine, lanthanum carbonate, lenercept, levetiracetam, lusupultide; Magnesium sulfate, melatonin, mepolizumab, midostaurin, morphine hydrochloride, mozavaptan; Natalizumab, nesiritide; OPC-51803, oregovomab, oritavancin; Peginterferon alfa-2(a), pleconaril, plevitrexed, prasterone, pregabalin; Ranibizumab, Ro-31-7453, roxifiban acetate, rubitecan; SCV-07, SHL-749, sho-saiko-to, soblidotin, solifenacin succinate; Tegaserod maleate, telithromycin, tenecteplase, theraCIM, tipifarnib, travoprost; Valdecoxib, vardenafil hydrochloride hydrate, voriconazole; Ximelagatran; Ziprasidone hydrochloride, ZYC-00101. (c) 2003 Prous Science. All rights reserved.
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abciximab, acetylcysteine, adefovir dipivoxil, alfuzosin hydrochloride, aliskiren fumarate, alosetron hydrochloride, amlodipine besilate, apomorphine hydrochloride, atazanavir, atorvastatin, atorvastatin calcium, atrasentan; Basiliximab, beraprost sodium, bevacizumab, bivalirudin, botulinum toxin type A, botulinum toxin type B; Celecoxib, cetuximab, cilansetron, cilomilast; Daclizumab, darbepoetin alfa, docetaxel, duloxetine hydrochloride; Efalizumab, efavirenz, eletriptan,, entecavir, eplerenone, epoetin alfa, eptifibatide, esomeprazole magnesium. ezetimibe; Filgrastim, finasteride, fluvastatin sodium, follitropin alfa; Gemcitabine, gemeprost, ghrelin (human); HE-2000; Infliximab, 111In-Pentetreotide, interferon alfa-2 alpha, interferon alfa-2 beta, interferon beta-1 alpha, irbesartan, irinotecan hydrochloride; Ketamine hydrochloride; L-778123, lafutidine, lamivudine, lamivudine/zidovudine, latanoprost, letrozole, licofelone, lopinavir, losartan potassium, loxiglumide, lubeluzole; Magnesium sulfate, MeGLA, meloxicam, mycophenolate mofetil; NBI-6024, nelfinavir mesilate, nesiritide, nevirapine, niacin, NN-2211; Octreotide, orlistat; PC-515, peginterferon alfa-2 alpha, peginterferon alfa-2b, pemetrexed disodium, pibrozelesin hydrochloride, pimagedine, pirfenidone, pitavastatin calcium, premarin/trimegestone, prucalopride; Rabeprazole sodium; reboxetine, risedronate sodium, ritonavir, rituximab, rofecoxib, roflumilast, rosuvastatin calcium; Sertraline, sibutramine hydrochloride monohydrate, sildenafil citrate, spironolactone, stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b
Tomillero, A; Moral, M A
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort
Tomillero, A; Moral, M A
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5-Methyltetrahydrofolate, 9-aminocamptothecin; AdPEDF.11, AE-37, albumin interferon alfa, alicaforsen sodium, alvocidib hydrochloride, AMG-706, arginine butyrate, avanafil, axitinib, azimilide hydrochloride; BAY-579352, belagenpumatucel-L, beta-lapachone, BHT-3009, BIBW-2992, bremelanotide, BX-471; Casopitant mesylate, cediranib, certolizumab pegol, CH-1504, ChimeriVax-West Nile, clofazimine, CpG-7909, curcumin, Cypher; Dapoxetine hydrochloride, darusentan, diflomotecan, D-methionine, dnaJP1, D-serine, DTPw-HB Hib-MenAC, DTPw-HepB-Hib; E-7010, ecogramostim, edodekin alfa, EGFRvlll peptide vaccine, elcometrine, elcometrine/ethinylestradiol, elsilimomab, enrasentan, ertumaxomab, etalocib sodium, exisulind; Fenretinide, fesoterodine, fingolimod hydrochloride, fontolizumab; Gefitinib, gemtuzumab ozogamicin, ghrelin (human), GV-1001; HTU-PA, human papillomavirus vaccine; Indacaterol, indiplon, interleukin-21, intranasal insulin, irinotecan hydrochloride/floxuridine, ISIS-301012, ispinesib mesylate, ixabepilone; K562/GM-CSF; Lapatinib, L-BLP-25, linezolid, liposome encapsulated paclitaxel, LY-2124275; MC-1, MC-1/lisinopril, MDX-066, melanoma vaccine, MMR-V, multivalent (ACYW) meningitis vaccine; Nilotinib, nobori, nociceptin; Oblimersen sodium, orbofiban acetate, ospemifene; Paliperidone, panitumumab, PEG-filgrastim, PEGylated interferon alfacon-1, perflubutane, pertuzumab, phenserine tartrate, phVEGF-A165, pleconaril, prasugrel, prednisolone sodium metasulfobenzoate; R-411, recombinant malaria vaccine, rhGM-CSF, roflumilast, romidepsin, ruboxistaurin mesilate hydrate; Sirolimus-eluting stent, SR-4554, St. John
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide
Moral, M A; Tomillero, A
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus
Bayés, M; Rabasseda, X
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir
Hill, G; Forbes, W; Kozak, J; MacNeill, I
The history of the application of statistical theory to the analysis of clinical trials is reviewed. The current orthodoxy is a somewhat illogical hybrid of the original theory of significance tests of Edgeworth, Karl Pearson, and Fisher, and the subsequent decision theory approach of Neyman, Egon Pearson, and Wald. This hegemony is under threat from Bayesian statisticians. A third approach is that of likelihood, stemming from the work of Fisher and Barnard. This approach is illustrated using hypothetical data from the Lancet articles by Bradford Hill, which introduced clinicians to statistical theory.
Bekelman, David B; Plomondon, Mary E; Carey, Evan P; Sullivan, Mark D; Nelson, Karin M; Hattler, Brack; McBryde, Connor F; Lehmann, Kenneth G; Gianola, Katherine; Heidenreich, Paul A; Rumsfeld, John S
Heart failure (HF) has a major effect on patients' health status, including their symptom burden, functional status, and health-related quality of life. To determine the effectiveness of a collaborative care patient-centered disease management (PCDM) intervention to improve the health status of patients with HF. The Patient-Centered Disease Management (PCDM) trial was a multisite randomized clinical trial comparing a collaborative care PCDM intervention with usual care in patients with HF. A population-based sample of 392 patients with an HF diagnosis from 4 Veterans Affairs centers who had a Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score of less than 60 (heavy symptom burden and impaired functional status and quality of life) were enrolled between May 2009 and June 2011. The PCDM intervention included collaborative care by a multidisciplinary care team consisting of a nurse coordinator, cardiologist, psychiatrist, and primary care physician; home telemonitoring and patient self-management support; and screening and treatment for comorbid depression. The primary outcome was change in the KCCQ overall summary score at 1 year (a 5-point change is clinically significant). Mortality, hospitalization, and depressive symptoms (Patient Health Questionnaire 9) were secondary outcomes. There were no significant differences in baseline characteristics between patients randomized to the PCDM intervention (n=187) vs usual care (n=197); baseline mean KCCQ overall summary scores were 37.9 vs 36.9 (P=.48). There was significant improvement in the KCCQ overall summary scores in both groups after 1 year (mean change, 13.5 points in each group), with no significant difference between groups (P=.97). The intervention was not associated with greater improvement in the KCCQ overall summary scores when the effect over time was estimated using 3-month, 6-month, and 12-month data (P=.74). Among secondary outcomes, there were significantly fewer deaths at 1 year in
Coluzzi, Flaminia; Taylor, Robert; Pergolizzi, Joseph V; Mattia, Consalvo; Raffa, Robert B
Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial) during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation). Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring). Finally, for those patients for whom transition (tapering) from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's): titration (or trial), tweaking (or tailoring), and transition (or tapering). Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non-pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Gellatly, Judith; Bower, Peter; McMillan, Dean; Roberts, Christopher; Byford, Sarah; Bee, Penny; Gilbody, Simon; Arundel, Catherine; Hardy, Gillian; Barkham, Michael; Reynolds, Shirley; Gega, Lina; Mottram, Patricia; Lidbetter, Nicola; Pedley, Rebecca; Peckham, Emily; Connell, Janice; Molle, Jo; O'Leary, Neil; Lovell, Karina
UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD. Current Controlled Trials: ISRCTN73535163. Date of registration: 5 April 2011.
Vaiman, Michael; Krakovski, Daniel; Haitov, Zoe
Summary Background Surface electromyographic (sEMG) study of post-tonsillectomy swallow-evoked muscular reactions was performed in order to evaluate the efficacy and safety of oxycodone and dexamethasone in pain management after tonsillectomy. Material/Methods 90 randomly chosen operated adults were divided into three groups. Group 1 (n=30) was treated with OxyContin (Oxycodone) injections; Group 2 (n=30) was treated with Dexacort (Dexamethasone), and Group 3 (n=30) was a placebo group. Pain assessment included visual analogue scale (VAS) pain score and the EMG data like the timing, electric amplitude and graphic patterns of muscular activity during deglutition. We investigated masseter, infrahyoid and submental-submandibular muscles. Records from trapezius muscle were used for control. The results were compared with previously established normative database. The patients were tested 24 h after surgery. The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients. Results Analgesia with oxycodone smoothed the recorded sEMG swallow peaks and increases time of deglutition. Dexamethasone normalized muscular activity in deglutition in cases with edema as detected by the EMG records. Statistically significant difference in muscle reactions was detected between the two Groups and the placebo group. Conclusions Application of oxycodone significantly reduces the postoperative pain. Application of dexamethasone after tonsillectomy is advisable because of the reduction of postoperative morbidity while the reduction of the postoperative pain is secondary to the reduction of edema. SEMG might be used as an adjunctive measure of pain behavior via assessment of muscular reactions to pain and to analgesia. PMID:21959624
Vaiman, Michael; Krakovski, Daniel; Haitov, Zoe
Surface electromyographic (sEMG) study of post-tonsillectomy swallow-evoked muscular reactions was performed in order to evaluate the efficacy and safety of oxycodone and dexamethasone in pain management after tonsillectomy. 90 randomly chosen operated adults were divided into three groups. Group 1 (n = 30) was treated with OxyContin (Oxycodone) injections; Group 2 (n = 30) was treated with Dexacort (Dexamethasone), and Group 3 (n = 30) was a placebo group. Pain assessment included visual analogue scale (VAS) pain score and the EMG data like the timing, electric amplitude and graphic patterns of muscular activity during deglutition. We investigated masseter, infrahyoid and submental-submandibular muscles. Records from trapezius muscle were used for control. The results were compared with previously established normative database. The patients were tested 24 h after surgery. The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients. Analgesia with oxycodone smoothed the recorded sEMG swallow peaks and increases time of deglutition. Dexamethasone normalized muscular activity in deglutition in cases with edema as detected by the EMG records. Statistically significant difference in muscle reactions was detected between the two Groups and the placebo group. Application of oxycodone significantly reduces the postoperative pain. Application of dexamethasone after tonsillectomy is advisable because of the reduction of postoperative morbidity while the reduction of the postoperative pain is secondary to the reduction of edema. SEMG might be used as an adjunctive measure of pain behavior via assessment of muscular reactions to pain and to analgesia.
Tomillero, A; Moral, M A
Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar
Lobach, David F; Kawamoto, Kensaku; Anstrom, Kevin J; Silvey, Garry M; Willis, Janese M; Johnson, Fred S; Edwards, Rex; Simo, Jessica; Phillips, Pam; Crosslin, David R; Eisenstein, Eric L
To determine whether a clinical decision support system can favorably impact the delivery of emergency department and hospital services. Randomized clinical trial of three clinical decision support delivery modalities: email messages to care managers (email), printed reports to clinic administrators (report) and letters to patients (letter) conducted among 20,180 Medicaid beneficiaries in Durham County, North Carolina with follow-up through 9 months. Patients in the email group had fewer low-severity emergency department encounters vs. controls (8.1 vs. 10.6/100 enrollees, p < 0.001) with no increase in outpatient encounters or medical costs. Patients in the letter group had more outpatient encounters and greater outpatient and total medical costs. There were no treatment-related differences for patients in the reports group. Among patients <18 years, those in the email group had fewer low severity (7.6 vs. 10.6/100 enrollees, p < 0.001) and total emergency department encounters (18.3 vs. 23.5/100 enrollees, p < 0.001), and lower emergency department ($63 vs. $89, p = 0.002) and total medical costs ($1,736 vs. $2,207, p = 0.009). Patients who were ≥18 years in the letter group had greater outpatient medical costs. There were no intervention-related differences in patient-reported assessments of quality of life and medical care received. The effectiveness of clinical decision support messaging depended upon the delivery modality and patient age. Health IT interventions must be carefully evaluated to ensure that the resultant outcomes are aligned with expectations as interventions can have differing effects on clinical and economic outcomes.
Gupta, Anjali; Calfas, Karen J.; Marshall, Simon J.; Robinson, Thomas N.; Rock, Cheryl L.; Huang, Jeannie S.; Epstein-Corbin, Melanie; Servetas, Christina; Donohue, Michael C.; Norman, Gregory J.; Raab, Fredric; Merchant, Gina; Fowler, James H.; Griswold, William G.; Fogg, B.J.; Patrick, Kevin
Advances in information technology and near ubiquity of the Internet have spawned novel modes of communication and unprecedented insights into human behavior via the digital footprint. Health behavior randomized controlled trials (RCTs), especially technology-based, can leverage these advances to improve the overall clinical trials management process and benefit from improvements at every stage, from recruitment and enrollment to engagement and retention. In this paper, we report the results for recruitment and retention of participants in the SMART study and introduce a new model for clinical trials management that is a result of interdisciplinary team science. The MARKIT model brings together best practices from information technology, marketing, and clinical research into a single framework to maximize efforts for recruitment, enrollment, engagement, and retention of participants into a RCT. These practices may have contributed to the study’s on-time recruitment that was within budget, 86% retention at 24 months, and a minimum of 57% engagement with the intervention over the 2-year RCT. Use of technology in combination with marketing practices may enable investigators to reach a larger and more diverse community of participants to take part in technology-based clinical trials, help maximize limited resources, and lead to more cost-effective and efficient clinical trial management of study participants as modes of communication evolve among the target population of participants. PMID:25866383
Gupta, Anjali; Calfas, Karen J; Marshall, Simon J; Robinson, Thomas N; Rock, Cheryl L; Huang, Jeannie S; Epstein-Corbin, Melanie; Servetas, Christina; Donohue, Michael C; Norman, Gregory J; Raab, Fredric; Merchant, Gina; Fowler, James H; Griswold, William G; Fogg, B J; Patrick, Kevin
Advances in information technology and near ubiquity of the Internet have spawned novel modes of communication and unprecedented insights into human behavior via the digital footprint. Health behavior randomized controlled trials (RCTs), especially technology-based, can leverage these advances to improve the overall clinical trials management process and benefit from improvements at every stage, from recruitment and enrollment to engagement and retention. In this paper, we report the results for recruitment and retention of participants in the SMART study and introduce a new model for clinical trials management that is a result of interdisciplinary team science. The MARKIT model brings together best practices from information technology, marketing, and clinical research into a single framework to maximize efforts for recruitment, enrollment, engagement, and retention of participants into a RCT. These practices may have contributed to the study's on-time recruitment that was within budget, 86% retention at 24 months, and a minimum of 57% engagement with the intervention over the 2-year RCT. Use of technology in combination with marketing practices may enable investigators to reach a larger and more diverse community of participants to take part in technology-based clinical trials, help maximize limited resources, and lead to more cost-effective and efficient clinical trial management of study participants as modes of communication evolve among the target population of participants. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
van der Sanden, Wil J M; Mettes, Dirk G; Plasschaert, Alphons J M; Grol, Richard P T M; Mulder, Jan; Verdonschot, Emiel H
The objective of this study was twofold, namely to evaluate the effectiveness of a dental clinical practice guideline on the management of asymptomatic impacted lower third molars (i) on referral rates and (ii) on dentists' change in knowledge. A two-arm cluster randomized controlled trial, with pre- and post-test assessments, was conducted. A guideline was implemented by multifaceted interventions (i.e. feedback, reminders, and an interactive meeting). The effect was evaluated after 1 yr by repeating the baseline questionnaire and by monitoring the number of patients who were referred for removal of their asymptomatic impacted mandibular third molars. Instruments were questionnaires for detecting changes in knowledge, patient records, and panoramic radiographs. The knowledge of dentists regarding asymptomatic mandibular third molar management was found to increase significantly in the intervention group as compared to the control group. There was no statistically significant difference between the groups in guideline-consistent patient referral rates at the post-test assessment. It was concluded that the methodology employed for dissemination and implementation of a clinical practice guideline on asymptomatic mandibular third molar management improves dentists' knowledge on this topic and is effective in improving decision-making in simulated cases; however, no clinical effect was demonstrated.
Bateman, Anthony; Fonagy, Peter
This randomized controlled trial tested the effectiveness of an 18-month mentalization-based treatment (MBT) approach in an outpatient context against a structured clinical management (SCM) outpatient approach for treatment of borderline personality disorder. Patients (N=134) consecutively referred to a specialist personality disorder treatment center and meeting selection criteria were randomly allocated to MBT or SCM. Eleven mental health professionals equal in years of experience and training served as therapists. Independent evaluators blind to treatment allocation conducted assessments every 6 months. The primary outcome was the occurrence of crisis events, a composite of suicidal and severe self-injurious behaviors and hospitalization. Secondary outcomes included social and interpersonal functioning and self-reported symptoms. Outcome measures, assessed at 6-month intervals, were analyzed using mixed effects logistic regressions for binary data, Poisson regression models for count data, and mixed effects linear growth curve models for self-report variables. Substantial improvements were observed in both conditions across all outcome variables. Patients randomly assigned to MBT showed a steeper decline of both self-reported and clinically significant problems, including suicide attempts and hospitalization. Structured treatments improve outcomes for individuals with borderline personality disorder. A focus on specific psychological processes brings additional benefits to structured clinical support. Mentalization-based treatment is relatively undemanding in terms of training so it may be useful for implementation into general mental health services. Further evaluations by independent research groups are now required.
Henry, James A; Thielman, Emily J; Zaugg, Tara L; Kaelin, Christine; Schmidt, Caroline J; Griest, Susan; McMillan, Garnett P; Myers, Paula; Rivera, Izel; Baldwin, Robert; Carlson, Kathleen
This randomized controlled trial evaluated, within clinical settings, the effectiveness of coping skills education that is provided with progressive tinnitus management (PTM). At 2 Veterans Affairs medical centers, N = 300 veterans were randomized to either PTM intervention or 6-month wait-list control. The PTM intervention involved 5 group workshops: 2 led by an audiologist (teaching how to use sound as therapy) and 3 by a psychologist (teaching coping skills derived from cognitive behavioral therapy). It was hypothesized that PTM would be more effective than wait-list control in reducing functional effects of tinnitus and that there would be no differences in effectiveness between sites. At both sites, a statistically significant improvement in mean Tinnitus Functional Index scores was seen at 6 months for the PTM group. Combined data across sites revealed a statistically significant improvement in Tinnitus Functional Index relative to wait-list control. The effect size for PTM using the Tinnitus Functional Index was 0.36 (small). Results suggest that PTM is effective at reducing tinnitus-related functional distress in clinical settings. Although effect sizes were small, they provide evidence of clinical effectiveness of PTM in the absence of stringent research-related inclusion criteria and with a relatively small number of sessions of cognitive behavioral therapy.
Klimt, C R
Long-term clinical trials often include more than one active treatment group. These may be discontinued independently if found to be ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet another kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.
The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy. We examined weight changes among ...
Ortega Moreno, A
Clinical management (CM) as a concept includes different innovating experiences in health care services management among developed countries, which were initiated during the late eighties and the first nineties. They were mostly due to the concern that political leaders had about their financial viability. CM, as far as it is understood in Spain, is an organizing model which considers the patient as the centre of the health system. It is guided towards disease, looking for continuous assistance and facilitates an autonomous management together with decentralization at the time of taking decisions. It involves professionals whose clinical practice, based on guides, medical records and care planning, incorporate the knowledge and methodology of "evidence based medicine". Clinical management units (CMU) are organizational types of CM, which implantation is spreading rapidly in the different national health care systems. They include a person who assumes responsibility for them, who act as the hospital directorship interlocutor and are autonomous at the time of managing the allocated resources related to their medical programmes and services. They have an information system adapted to their own needs and an outcome evaluation system which allows them "process" re-engineering. CMU's strengths and weaknesses are highly dependent on the professionals that integrate them. The CMU responsible carries out a management contract with the hospital directorship in which CMU competences, directorship's obligations, essential aspects to meet agreed goals, an outcome evaluation system and an incentives scheme are included.
Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K
Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537
Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K
Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331.
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T
Tomillero, A; Moral, M A
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium
Gupta, P. R.
Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease of unknown etiology. Its pathogenesis remains poorly elucidated but aberrant wound healing is central to its pathology. It has a median survival time of 3 to 5 years. None of the treatment modality or drugs tried in its management has so far changed the overall outcome. Recent in vitro and experimental studies have shown that ambroxol hydrochloride exerts several newer actions, namely the surfactant stimulatory, anti-imflammatory and anti-oxidant actions, in addition to its being a secrrtolytic and mucokinetic agent. The anti inflammatory and anti-fibrotic properties of the drug are due to its ability to block the release of oxidant stress markers, cytokines, leukotrienes, MPO activity, hydroxyproline content, nitic oxide and/or collagen I & III mRNA in the local milieu while preserving the SOD and GSH-PX activities. In human studies also, the agent was able to block the expression of TGF-beta and TNF-alpha in plasma and preserving the carbon monoxide diffusion capacity of the lungs in lung cancer patients on radiation therapy. Thus, ambroxol may have the potential to check the dysregulated healing process that is typical of IPF. This, coupled with its safety profile for human use, warrants clinical trials of the drug in the management of IPF. PMID:24669082
Nadkarni, Prakash M.; Brandt, Cynthia; Frawley, Sandra; Sayward, Frederick G.; Einbinder, Robin; Zelterman, Daniel; Schacter, Lee; Miller, Perry L.
ACT/DB is a client—server database application for storing clinical trials and outcomes data, which is currently undergoing initial pilot use. It stores most of its data in entity—attribute—value form. Such data are segregated according to data type to allow indexing by value when possible, and binary large object data are managed in the same way as other data. ACT/DB lets an investigator design a study rapidly by defining the parameters (or attributes) that are to be gathered, as well as their logical grouping for purposes of display and data entry. ACT/DB generates customizable data entry. The data can be viewed through several standard reports as well as exported as text to external analysis programs. ACT/DB is designed to encourage reuse of parameters across multiple studies and has facilities for dictionary search and maintenance. It uses a Microsoft Access client running on Windows 95 machines, which communicates with an Oracle server running on a UNIX platform. ACT/DB is being used to manage the data for seven studies in its initial deployment. PMID:9524347
Nadkarni, P M; Brandt, C; Frawley, S; Sayward, F G; Einbinder, R; Zelterman, D; Schacter, L; Miller, P L
ACT/DB is a client-server database application for storing clinical trials and outcomes data, which is currently undergoing initial pilot use. It stores most of its data in entity-attribute-value form. Such data are segregated according to data type to allow indexing by value when possible, and binary large object data are managed in the same way as other data. ACT/DB lets an investigator design a study rapidly by defining the parameters (or attributes) that are to be gathered, as well as their logical grouping for purposes of display and data entry. ACT/DB generates customizable data entry. The data can be viewed through several standard reports as well as exported as text to external analysis programs. ACT/DB is designed to encourage reuse of parameters across multiple studies and has facilities for dictionary search and maintenance. It uses a Microsoft Access client running on Windows 95 machines, which communicates with an Oracle server running on a UNIX platform. ACT/DB is being used to manage the data for seven studies in its initial deployment.
Gupta, Sandeep K.
There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464
Aptel, F; Cucherat, M; Blumen-Ohana, E; Denis, P
Clinical trials are playing an increasingly crucial role in modern evidence based medicine, allowing for rigorous scientific evaluation of treatment strategies and validation of patient care. The results of clinical trials often form the rational basis from which physicians draw information used to adapt their therapeutic practices. Critical reading and analysis of trials involves the assessment of whether the available data provide enough credible evidence that the treatment will result in a clinically significant and relevant improvement. Evaluating the quality of a clinical trial is a process that draws upon sometimes complex methodological and statistical concepts, with which the reader should nonetheless be familiar in order to come to impartial conclusions regarding the raw data presented in the clinical trials. The goal of the current article is to review the methodological and statistical concepts required for the design and interpretation of clinical trials, so as to allow for a critical analysis of publications or presentations of clinical trials. The first section describes the major methodological principles of clinical trial design required for a rigorous evaluation of the treatment benefit, as well as the various pitfalls or biases that could lead to erroneous conclusions. The second section briefly describes the main statistical tests used in clinical trials, as well as certain situations that may increase the risk of false positive findings (type 1 error), such as multiple, subgroup, intermediate and non-inferiority analysis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Plotnikoff, Gregory A; Watanabe, Kenji; Torkelson, Carolyn; La Valleur, June; Radosevich, David M
The aim of this study was to assess the efficacy of TU-025, keishibukuryogan, a Japanese prescription herbal medicine used for hot flash management, in American women. This randomized, double-blind, placebo-controlled, phase II trial enrolled 178 postmenopausal women aged 45 to 58 years with a Mayo hot flash score greater than 28 per week who met other inclusion criteria. After a 1-week placebo run-in period, participants were randomly assigned placebo, or 7.5 g/day, or 12.5 g/day groups, for 12 weeks. Primary and secondary outcomes were measured using the Mayo Clinic Hot Flash Diary, the Greene Climacteric Index, and the Pittsburgh Sleep Quality Index. At 3 months, hot flash scores, climacteric symptoms, and sleep quality improved by 34% in the placebo group, 40% in the 7.5 g/day group, and 38% in the 12.5 g/day group. (P < 0.001). However, the differences in changes between groups were not statistically significant (P = 0.990). Diarrhea unexpectedly developed in 20% of participants receiving active medication. For American women, unlike the clinical experience for Japanese women, TU-025 did not significantly reduce the frequency and severity of hot flash symptoms, improve climacteric symptoms, or benefit sleep quality. This study identified several potentially significant methodological factors to be considered in future scientific assessments of traditional Asian medicines.
Farhat, Grace; Drummond, Sandra; Al-Dujaili, Emad A S
Polyphenols have been suggested to reduce body weight and modify body composition through different mechanisms. These effects have been extensively studied in animals and in vitro and to a lesser extent in humans. The aim of this review is to consider the association between polyphenols and body weight status by focusing on human intervention studies. We conducted a systematic literature search in MEDLINE (via EBSCOhost), ProQuest CENTRAL, and Cochrane CENTRAL without time restrictions. Randomized controlled trials assessing the effect of polyphenols on weight and/or body composition in the overweight and/or obese population were included. Nineteen studies met our inclusion criteria. Results suggest that further research is required before supporting a potential role of polyphenols in reducing weight in overweight and obese individuals (nine studies showed a significant decrease in weight by a mean of 1.47 ± 0.58 kg). Nevertheless, several studies indicated that polyphenols might be effective in preventing small increases in weight during periods of overfeeding rather than reducing weight as such. The outcomes noted do not yet support polyphenol supplementation as a complementary approach in weight loss diets. Further larger trials with a duration of 12 months or more are needed to elucidate the effect of polyphenols on body weight status. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
... Trials Phases of Clinical Trials Randomization Use of Placebos Research Team Members Paying for Clinical Trials Insurance ... types of clinical trials. Also, explains phases, randomization, placebo, and members of the research team. Paying for ...
Recent data reveal that subtle selective publication affects critical aspects of trial reporting, in some cases altering the interpretation of results. Timely prospective registration could help deter selective reporting and clinical trial stakeholders from government authorities to journal editors should work together to foster prospective registration of trials.
Chalkeidis, Omiros; Kotsovolis, Georgios; Kalakonas, Apostolos; Filippidou, Maria; Triantafyllou, Christos; Vaikos, Dimitris; Koutsioumpas, Epaminondas
The Airtraq Optical Laryngoscope is a new type of laryngoscope that provides a direct view of the glottis without alignment of the mouth, pharynx and trachea. Data show that it has advantages over the Macintosh laryngoscope. The aim of this study was to compare the use of the Airtraq laryngo-scope versus the No. 3 Macintosh blade for routine airway management in terms of intubation time, complications during and after laryngoscopy, and ease of use. In this single-center, randomized, clinical trial, 63 patients scheduled for elective operation were randomly allocated to two groups. Thirty-five patients were intubated with the Airtraq laryngoscope and 28 with the traditional Macintosh laryngoscope. All intubations were performed by experienced anesthesiologists who had a similar level of experience with the Airtraq laryngoscope. The time needed for intubation, any assistance required, complications during and after laryngoscopy and intubation, and the number of unsuccessful intubation attempts were documented and compared between the groups. Intubation with the Macintosh laryngoscope was quicker (mean+/-standard deviation: 23.7+/-5.9 seconds) than with the Airtraq laryngoscope (29.6+/-8.5 seconds). Although the difference (5.9 seconds) was statistically significant (p<0.05), it was not clinically significant. The anesthesiologists who used the Airtraq laryngo-scope less frequently required assistance (p<0.05) to place the endotracheal tube. No differences were found regarding complications during and after laryngoscopy and intubation. There were no differences in any of the outcomes in patients with Mallampati class > 2. The Airtraq laryngoscope is easier to use but it does not have any significant advantages compared with the Macintosh laryngoscope for routine airway management. More studies are needed to evaluate its use in patients with a difficult airway, and in emergency procedures. 2010 Taiwan Society of Anesthesiologists. Published by Elsevier B.V. All rights
Bruce, Martha L.; Raue, Patrick J.; Reilly, Catherine F.; Greenberg, Rebecca L.; Meyers, Barnett S.; Banerjee, Samprit; Pickett, Yolonda R.; Sheeran, Thomas F.; Ghesquiere, Angela; Zukowski, Diane; Rosas, Vianca H.; McLaughlin, Jeanne; Pledger, Lori; Doyle, Joan; Joachim, Pamela; Leon, Andrew C.
at any follow-up. Among 208 participants with HDRS≥10, CAREPATH demonstrated effectiveness (P=0.02) with lower HDRS at three (14.1 vs 16.1; P=0.04), six (12.0 vs 14.7; P=0.02) and twelve months (11.8 vs 15.7; P=0.005). Exploratory analyses found no differences in number or length of home visits. Conclusion and Relevance Home health nurses can effectively integrate depression care management into routine practice. However, clinical benefit appears limited to only patients with moderate to severe depression. Trial Registration Clinicaltrials.gov Identifier: NCT01979302 http://clinicaltrials.gov/ct2/show/NCT01979302 PMID:25384017
Bisoffi, Zeno; Sirima, Bienvenu Sodiomon; Angheben, Andrea; Lodesani, Claudia; Gobbi, Federico; Tinto, Halidou; Van den Ende, Jef
To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria (RDT) is at least equivalent to that of controls (treated presumptively without test) and to determine the impact of the introduction of a malaria RDT on clinical decisions. Randomized, multi-centre, open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso: one arm with use of RDT before treatment decision, one arm managed clinically. Primary endpoint: persistence of fever at day 4. Secondary endpoints: frequency of malaria treatment and of antibiotic treatment. A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season, and randomized either to be submitted to RDT (P_RTD) or to be managed presumptively (P_CLIN). In both seasons, no significant difference was found between the two randomized groups in the frequency of antimalarial treatment, nor of antibiotic prescription. In the dry season, 80.8% and 79.8% of patients with a negative RDT were nevertheless diagnosed and treated for malaria, and so were 85.0% and 82.6% negative patients in the rainy season. In the rainy season only, both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9%, P = 0.00 and 0.00, respectively). Our study was inconclusive on RDT safety (clinical outcome in the two randomized groups), because of an exceedingly and unexpectedly low compliance with the negative test result. Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current, presumptive treatment strategy.
Kanai, Masatoshi; Suzuki-Nishimura, Tamiko
Part of the revision of the Pharmaceutical Affairs Law in 2002 included the establishment of a system for independent clinical trials. According to the partial revision of the Guideline for Good Clinical Practice (GCP), MHLW Ministerial Ordinance No. 106 dated June 12, 2003, independent clinical trials are now recognized in Japan. MHLW promotes to resolve the issues about compliance with good clinical practice (GCP) guideline and the management of the clinical trials, including independent clinical trials. For our nation, more effective and safer new drug applications based on domestic independent clinical trial documents will soon be reviewed by the Pharmaceuticals and Medical Devices Agency (PMDA). For the protection of human rights, important issues about quality control and quality assurance raised by GCP Audit consist of both GCP on-site review and Document-based Conformity Review by the Office of Conformity Audit of the PMDA are studied.
Klimt, C R; Canner, P L
Long-term trials often include more than one active treatment group. These may be discontinued independently if found ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet anouther kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.
The pilot phase of the ECRIN (European Clinical Research Infrastructure Network) certification programme for European data centres, in late 2011, led to a substantial revision of the original ECRIN standards, completed by June 2012. The pilot phase, the conclusions drawn from it and the revised set of standards are described. Issues concerning the further development of standards and related material are discussed, as are the methods available to best support that development. A strategy is outlined based on short-lived specific task groups, established as necessary by a steering group drawn from ECRIN-ERIC. A final section discusses possible future developments. PMID:23561034
Ohmann, Christian; Canham, Steve; Cornu, Catherine; Dreß, Jochen; Gueyffier, François; Kuchinke, Wolfgang; Nicolis, Enrico B; Wittenberg, Michael
The pilot phase of the ECRIN (European Clinical Research Infrastructure Network) certification programme for European data centres, in late 2011, led to a substantial revision of the original ECRIN standards, completed by June 2012. The pilot phase, the conclusions drawn from it and the revised set of standards are described. Issues concerning the further development of standards and related material are discussed, as are the methods available to best support that development. A strategy is outlined based on short-lived specific task groups, established as necessary by a steering group drawn from ECRIN-ERIC. A final section discusses possible future developments.
Ayres, Thomas R.
The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)
Gist, Peter; Langley, David
PRINCE2, which stands for Projects in Controlled Environments, is a project management method covering the organisation, management, and control of projects and is widely used in both government and commercial IT and building projects in the UK. This paper describes the application of PRINCE2 to the management of large clinical trials…
Smith, Clayton A; Kachnic, Lisa A
Management of anal carcinoma began as abdominoperineal resection and has evolved to combined chemotherapy and radiation. Early randomized trials demonstrated superior clinical outcomes of combined modality therapy over radiotherapy alone. Subsequent trials investigated alterations in the standard backbone of radiotherapy concurrent with 5-fluorouracil and mitomycin C with intent to maintain clinical outcomes while reducing treatment-related morbidity. The addition of intensity-modulated radiotherapy to radiation planning and delivery has subsequently reduced acute toxicity and detrimental treatment breaks. Ongoing and future trials are aimed at reducing therapy in favorable patient populations to decrease morbidity while intensifying treatment in patients with negative prognostic factors. Copyright © 2017 Elsevier Inc. All rights reserved.
Marcus, M. D.; Wilfley, D. E.; El ghormli, L.; Zeitler, P.; Linder, B.; Hirst, K.; Ievers-Landis, C. E.; van Buren, D. J.; Walders-Abramson, N.
Summary Background The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy. Objectives We examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms. Methods The 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11–17 years) completed assessments of weight-related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time. Results Lifestyle intervention did not enhance outcome relative to metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥7% in overweight were associated with significant benefits over 24 months. Conclusions Although adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM. PMID:27161901
Saatsaz, Sussan; Rezaei, Rozita; Alipour, Abbas; Beheshti, Zahra
The present study was conducted to determine the effect of massage on post-cesarean pain and anxiety. The present single-blind clinical trial was conducted on 156 primiparous women undergone elective cesarean section. The participants were randomly divided into three groups, including a hand and foot massage group, a foot massage group and a control group (n = 52 per group). The patients' intensity of pain, vital signs and anxiety level were measured before, immediately after and 90 min after the massage. A significant reduction was observed in the intensity of pain immediately and 90 min after massage (P < 0.001). Moreover, changes in some of the physiological parameters, including blood pressure and respiration rate, were significant after massage (P < 0.001); however, this change was not significant for pulse rate. A significant reduction was also observed in the level of anxiety (P < 0.001) and a significant increase in the frequency of breastfeeding (P < 0.001) after massage. As an effective nursing intervention presenting no side-effects, hand and foot massage can be helpful in the management of postoperative pain and stress. Copyright © 2016 Elsevier Ltd. All rights reserved.
Gehan, E A
This is a review paper which gives a discussion of various aspects of clinical trials in cancer research. Since the conduct of the first randomized controlled clinical trial in cancer patients in the mid-1950's, substantial progress has been made in the utilization of the clinical trial technique for the evaluation of therapeutic efficiacy. The important elements of a protocol are given with some discussion of items to be considered in designing a protocol. The types of clinical trial (phase I, II, III) are defined, and the place of each phase of study in the context of the search for new treatments is delineated. A comprehensive discussion is given of the elements in the comparative clinical trial (phase III), including objectives, consierations in planning (comparability of treatment groups stratification of patients, feasibility and size of study, and prospective versus retrospective studies). Brief descriptions are given of designs for comparative clinical trials and a trial in oat cell lung carcinoma is discussed in some detail. Finally, some comments and references are given concerning the analysis of clinical trials. PMID:232043
O'Brien, J. R.
Results of treatment of 151 cases of vaginitis in patients attending a leukorrhea clinic were studied. The incidence of each type of vaginitis is recorded. Analysis of results of treatment with six compounds currently used in the therapy of vaginitis indicated that acetarsol or pimaricin compounds, with their broader spectra of activity, appeared to be most useful, prior to establishment of a definite diagnosis by means of cultures. Chlordantoin is an effective antifungal agent and is associated with a high percentage of “culture cures”. Resistant cases should be investigated for diabetes mellitus, and many are aided by a low carbohydrate diet. Metronidazole was used only for resistant cases of trichomoniasis, with a cure rate of over 80% when both partners were treated simultaneously. Triple-sulfa vaginal cream was effective in over 80% of patients with nonspecific vaginitis; no cases of resistant bacterial infections were encountered. Dienestrol cream was effective in relieving the symptoms of atrophic vaginitis. PMID:14144540
Satheeshkumar, P S; Chamba, Moideen Sha; Balan, Anita; Sreelatha, K T; Bhatathiri, V N; Bose, Tinky
Oral care in cancer patients is an important aspect in the quality of life of patients undergoing cancer therapy. Mucositis, trismus, salivary gland dysfunction are the main complications of the cancer therapy, which lead to long-term complications such as radiation caries, poor oral hygiene and osteoradionecrosis. A timely oral evaluation and intervention in these patients can reduce the severity of the potential complications. Triclosan is an antibacterial agent widely used in periodontal therapy, the effectiveness of triclosan in the management of radiation induced oral mucositis is evaluated here. 1) To determine the effectiveness of triclosan in the management of radiation-induced oral mucositis. 2) To compare the effectiveness of triclosan mouth rinse with conventional sodium bicarbonate mouth rinse. Twenty-four patients who underwent radiation therapy for oral cancer and subsequently developed oral mucositis were included in the study. They were randomly allocated into two groups on noticing grade I mucositis (erythema). The study group was advised to use triclosan mouthwash containing triclosan 0.03% W/V and sodium bicarbonate 2 mg mouth wash for the control group. A weekly follow-up evaluation of body weight, food intake, pain and grading of mucositis were made during the radiation treatment period and post radiation treatment period. Both the groups were statistically identical. All the 24 patients in both the groups passed through grade 3 mucositis on the last day of radiotherapy. However, 10 patients in the control group and only one patient in the study group entered to grade 4 mucositis. A definite change was noticed in the severity of the mucositis, food intake and weight loss. The control group took more than 45 days to resolve while the study group took only less than 28 days. The results of the study were evaluated and tried to formulate a hypothesis so as to explain the less severity and early resolution of mucositis in the study group. Triclosan
Dalal, Krishna; Maran, V Bharathi; Pandey, Ravindra M; Tripathi, Manjari
Background. The restricted usage of existing pharmacological methods which do not seem to provide the treatment of diabetic neuropathy may lead to exploring the efficacy of a complementary therapy. In this context, this paper was devoted to evaluate the efficacy of foot reflexology. This health science works on the hypothesis that the dysfunctional states of body parts could be identified by observing certain skin features and be rectified by stimulating certain specific areas mapped on feet. Method. Subjects (N = 58) with diagnosed diabetic neuropathy were randomly distributed into reflexology and control groups in which both group patients were treated with ongoing pharmacological drugs. Reflexology group patients were additionally treated holistically with the hypothesis that this therapy would bring homeostasis among body organ functions. This was a caregiver-based study with a follow-up period of 6 months. The outcome measures were pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities. The skin features leading to the detection of the abnormal functional states of body parts were also recorded and analyzed. Results. Reflexology group showed more improvements in all outcome measures than those of control subjects with statistical significance. Conclusion. This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy.
Dalal, Krishna; Maran, V. Bharathi; Pandey, Ravindra M.; Tripathi, Manjari
Background. The restricted usage of existing pharmacological methods which do not seem to provide the treatment of diabetic neuropathy may lead to exploring the efficacy of a complementary therapy. In this context, this paper was devoted to evaluate the efficacy of foot reflexology. This health science works on the hypothesis that the dysfunctional states of body parts could be identified by observing certain skin features and be rectified by stimulating certain specific areas mapped on feet. Method. Subjects (N = 58) with diagnosed diabetic neuropathy were randomly distributed into reflexology and control groups in which both group patients were treated with ongoing pharmacological drugs. Reflexology group patients were additionally treated holistically with the hypothesis that this therapy would bring homeostasis among body organ functions. This was a caregiver-based study with a follow-up period of 6 months. The outcome measures were pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities. The skin features leading to the detection of the abnormal functional states of body parts were also recorded and analyzed. Results. Reflexology group showed more improvements in all outcome measures than those of control subjects with statistical significance. Conclusion. This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy. PMID:24527055
McKenzie, Joanne E; French, Simon D; O'Connor, Denise A; Grimshaw, Jeremy M; Mortimer, Duncan; Michie, Susan; Francis, Jill; Spike, Neil; Schattner, Peter; Kent, Peter M; Buchbinder, Rachelle; Green, Sally E
Background Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidence-based clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access
Lee, J. Jack; Chu, Caleb T.
Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. The alternative Bayesian paradigm has been greatly enhanced by advancements in computational algorithms and computer hardware. Compared to its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and for studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation, and analysis, and Web-based applications, which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More such trials should be designed and conducted to refine the approach and demonstrate its real benefit in action. PMID:22711340
Lee, J Jack; Chu, Caleb T
Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More Bayesian trials should be designed and conducted to refine the approach and demonstrate their real benefit in action.
Miaskowski, Christine; Dodd, Marylin; West, Claudia; Schumacher, Karen; Paul, Steven M; Tripathy, Debu; Koo, Peter
This randomized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with standard care in decreasing pain intensity scores, increasing appropriate analgesic prescriptions, and increasing analgesic intake in oncology outpatients with pain from bone metastasis. Patients were randomly assigned to the PRO-SELF intervention (n = 93) or standard care (n = 81). Patients in the standard care arm were seen by a research nurse three times and were called three times by phone between the home visits. PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention, were taught how to use a pillbox, and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions. Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management. Pain intensity scores decreased significantly from baseline (all P <.0001) in the PRO-SELF group (ie, least pain, 28.4%; average pain, 32.5%; and worst pain, 27.0%) compared with the standard care group (ie, least increased by 14.6%, average increased by 1.9%, and worst decreased by 1.2%). The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3% to 37.0% (P =.008) compared with a change from 29.6% to 32.5% in the standard care group. The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain.
Garcia, Alexis; De Sanctis, Juan B
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: nonsteroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus antiinflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BlyS plays a key role in the selection, maturation and survival of B cells and it has a significant role in the pathogenesis of SLE. In this review, we analyzed the role of BLyS as a diagnostic/prognostic marker and/or therapeutic target for lupus patients, and the different clinical studies published using belimumab.
Kumar, Tarun; Arora, Neha; Puri, Gagan; Aravinda, Konidena; Dixit, Avani; Jatti, Deepa
The oral cavity is an open ecosystem that shows a dynamic balance between the entrance of microorganisms (bacterial, viral or fungal), colonization modalities, nutritional balance, and host defenses against their removal. The oral lesions including aphthous ulcerations, herpes labialis, oral candidiasis, oral lichen planus, and angular cheilitis some of the common entities encountered in the clinical practice. A variety of treatment options is available in the literature for all of these lesions and conditions. Topical ozone therapy is a minimally invasive technique that can be used for these conditions without any side effects. Aim and Objectives: To evaluate the efficacy of ozonized olive oil in the treatment of oral lesions and conditions. Materials and Methods: A longitudinal study was carried out on 50 patients (aphthous ulcerations, herpes labialis, oral candidiasis, oral lichen planus, and angular cheilitis). The ozonized olive oil was applied twice daily until the lesion regresses for a maximum of 6 months. Results: All the lesions regress in patients with aphthous ulcerations, herpes labialis, oral candidiasis and angular cheilitis or showed improvement in the signs and symptoms in oral lichen planus patients. No toxicity or side effect was observed in any of the patients. Conclusion: Ozone therapy though requires a gaseous form to be more effective, but topical form can also bring out the positive results without any toxicity or side effect. Hence, it can be considered as a minimally invasive therapy for the oral infective and immunological conditions. PMID:27041901
Chahal, Nita; Rush, Janet; Manlhiot, Cedric; Boydell, Katherine M; Jelen, Ahlexxi; McCrindle, Brian W
Lifestyle management for dyslipidemic adolescents often occurs in the context of family-centered care, which necessitates adaptation of counseling strategies. To determine the effectiveness of motivational interviewing for lifestyle behavior change for dyslipidemic adolescents in a dyad with a parent versus alone. A total number of 32 adolescents were randomized 1:1 to receive a series of motivational interviewing sessions either together with a parent or alone for a 6-month intervention, with both quantitative and qualitative assessment of outcomes. Both groups were similar at baseline. Following the intervention, there were no significant differences between groups in physical, laboratory, lifestyle or psychosocial measures, except for a reduction in dietary fats/sugars (p = 0.02) and in screen time (p = 0.02) in the alone group. When both groups were combined, significant reductions at 6 months were noted for body mass index (p < 0.001), waist circumference (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.001), triglycerides (p = 0.01), non-high-density lipoprotein cholesterol (p < 0.001), fasting insulin (p = 0.01), and homeostatic model (p = 0.02). Reduced screen time and increased fruit and vegetable intake were also noted for both groups combined. These changes were also reflected in self-efficacy (p = 0.004), self-esteem (p = 0.03), and improvement in quality of life measures. Interview data provided insights into the utility and acceptability of the motivational interviewing intervention. Motivational interviewing was an efficient strategy for inspiring healthy lifestyle and physiological changes among adolescents in both groups. Family centered pediatric approaches should consider the autonomy and individual preferences of the adolescent prior to counseling.
Chahal, Nita; Rush, Janet; Manlhiot, Cedric; Boydell, Katherine M; Jelen, Ahlexxi; McCrindle, Brian W
Background: Lifestyle management for dyslipidemic adolescents often occurs in the context of family-centered care, which necessitates adaptation of counseling strategies. Objective: To determine the effectiveness of motivational interviewing for lifestyle behavior change for dyslipidemic adolescents in a dyad with a parent versus alone. Methods: A total number of 32 adolescents were randomized 1:1 to receive a series of motivational interviewing sessions either together with a parent or alone for a 6-month intervention, with both quantitative and qualitative assessment of outcomes. Results: Both groups were similar at baseline. Following the intervention, there were no significant differences between groups in physical, laboratory, lifestyle or psychosocial measures, except for a reduction in dietary fats/sugars (p = 0.02) and in screen time (p = 0.02) in the alone group. When both groups were combined, significant reductions at 6 months were noted for body mass index (p < 0.001), waist circumference (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.001), triglycerides (p = 0.01), non–high-density lipoprotein cholesterol (p < 0.001), fasting insulin (p = 0.01), and homeostatic model (p = 0.02). Reduced screen time and increased fruit and vegetable intake were also noted for both groups combined. These changes were also reflected in self-efficacy (p = 0.004), self-esteem (p = 0.03), and improvement in quality of life measures. Interview data provided insights into the utility and acceptability of the motivational interviewing intervention. Conclusion: Motivational interviewing was an efficient strategy for inspiring healthy lifestyle and physiological changes among adolescents in both groups. Family centered pediatric approaches should consider the autonomy and individual preferences of the adolescent prior to counseling. PMID:28567283
Masoudi, Mohammad S; Haghnegahdar, Ali; Ghaffarpasand, Fariborz; Ilami, Ghazal
A randomized clinical trial. To compare the functional recovery between early kyphoplasty and conservative care in paratroopers with stable thoracolumbar fractures. Treatment of traumatic stable thoracolumbar fractures in young individuals is still a debate. Conservative management and kyphoplasty are options of therapy. But enough data are not available for supporting each. We included 70 paratroopers with stable thoracolumbar fractures (A1 and A2 classification according to AOSpine thoracolumbar spine injury classification system) presenting <60 days after trauma and hyperintensity in T2-weighted magnetic resonance imaging. Old fractures and those requiring fixation were excluded. Patients were randomly assigned to 2 study groups to undergo percutaneous balloon kyphoplasty (n=34) or conservative care (n=36) by applying orthosis for 2 months. Patients were followed for 12 months and were evaluated clinically using visual analogue scale (VAS) and Oswestry disability index (ODI). The baseline characteristics were comparable between 2 study groups. The VAS score and ODI decreased significantly in both study groups after 12 months of treatment. The VAS score was significantly lower in kyphoplasty group after the intervention (P<0.001), 1 month (P<0.001), 3 months (P<0.001), 6 months (P<0.001), and 12 months (P<0.001) after the intervention. In addition, the ODI was significantly lower after the intervention (P<0.001), 1 month (P<0.001), 3 months (P<0.001), 6 months (P<0.001), and 12 months (P<0.001) after the intervention. Kyphoplasty was associated with shorter duration of returning to parachuting (P<0.001) and shorter duration of absence from work (P<0.001). Early kyphoplasty in stable thoracolumbar fractures after parachute jumping is associated with less pain, better functional recovery, less days of absence from work, and shorter duration of returning to parachuting.
Mascarin, Naryana Cristina; Vancini, Rodrigo Luiz; Andrade, Marã Lia Dos Santos; Magalhães, Eduardo de Paiva; de Lira, Claudio Andre Barbosa; Coimbra, Ibsen Bellini
Although recent advances in knee osteoarthritis (OA) treatment and evaluation were achieved, to the best of our knowledge, few studies have evaluated the longitudinal effect of therapeutic modalities on the functional exercise capacity of patients with knee OA. The purpose was to investigate the effects of kinesiotherapy and electrotherapy on functional exercise capacity, evaluated using the six-minute walk test (6-MWT) in patients with bilateral knee OA. Secondary measurements included range of motion (ROM), severity of knee pain (VAS), and a measure of perceived health and physical function, evaluated using the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. A total of 40 women with bilateral knee OA were assigned to three groups: kinesiotherapy (KIN, n = 16), transcutaneous electrical nerve stimulation (TENS, n = 12), or ultrasound (US, n = 10). The groups underwent 12 weeks of intervention twice per week. The participants were subjected to the 6-MWT, ROM, VAS and WOMAC index. These tests were performed before and after the intervention. The study was focused on outpatients and was carried out at Universidade Estadual de Campinas, Brazil. At follow-up, the KIN and US groups had significantly higher 6-MWT distances (19.8 ± 21.7 and 14.1 ± 22.5%, respectively) compared with their respective pre-intervention values. All treatments were effective for reducing pain and improving the WOMAC index. We demonstrated that the 6-MWT is a tool that can be used to evaluate improvements in the functional exercise capacity of patients submitted to a clinical intervention.
Background Although recent advances in knee osteoarthritis (OA) treatment and evaluation were achieved, to the best of our knowledge, few studies have evaluated the longitudinal effect of therapeutic modalities on the functional exercise capacity of patients with knee OA. The purpose was to investigate the effects of kinesiotherapy and electrotherapy on functional exercise capacity, evaluated using the six-minute walk test (6-MWT) in patients with bilateral knee OA. Secondary measurements included range of motion (ROM), severity of knee pain (VAS), and a measure of perceived health and physical function, evaluated using the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. Methods A total of 40 women with bilateral knee OA were assigned to three groups: kinesiotherapy (KIN, n = 16), transcutaneous electrical nerve stimulation (TENS, n = 12), or ultrasound (US, n = 10). The groups underwent 12 weeks of intervention twice per week. The participants were subjected to the 6-MWT, ROM, VAS and WOMAC index. These tests were performed before and after the intervention. The study was focused on outpatients and was carried out at Universidade Estadual de Campinas, Brazil. Results At follow-up, the KIN and US groups had significantly higher 6-MWT distances (19.8 ± 21.7 and 14.1 ± 22.5%, respectively) compared with their respective pre-intervention values. All treatments were effective for reducing pain and improving the WOMAC index. Conclusions We demonstrated that the 6-MWT is a tool that can be used to evaluate improvements in the functional exercise capacity of patients submitted to a clinical intervention. PMID:22999098
Thompson, Michael A
Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.
Holmes, Jonathan M.
Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. PMID:25752747
Holmes, Jonathan M
Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. Copyright © 2015 Elsevier Ltd. All rights reserved.
George, Stephen L; Buyse, Marc
Highly publicized cases of fabrication or falsification of data in clinical trials have occurred in recent years and it is likely that there are additional undetected or unreported cases. We review the available evidence on the incidence of data fraud in clinical trials, describe several prominent cases, present information on motivation and contributing factors and discuss cost-effective ways of early detection of data fraud as part of routine central statistical monitoring of data quality. Adoption of these clinical trial monitoring procedures can identify potential data fraud not detected by conventional on-site monitoring and can improve overall data quality. PMID:25729561
Oeser, Clarissa; Lutsar, Irja; Metsvaht, Tuuli; Turner, Mark A; Heath, Paul T; Sharland, Mike
Antibiotic licensing studies remain a problem in neonates. The classical adult clinical syndrome-based licensing studies do not apply to neonates, where sepsis is the most common infection. The main obstacle to conducting neonatal antibiotic trials is a lack of consensus on the definition of neonatal sepsis itself and the selection of appropriate endpoints. This article describes the difficulties of the clinical and laboratory definitions of neonatal sepsis and reviews the varying designs of previous neonatal sepsis trials. The optimal design of future trials of new antibiotics will need to be based on pharmacokinetic/pharmacodynamic parameters, combined with adequately powered clinical studies to determine safety and efficacy.
Chavannes, Niels H; Grijsen, Marlous; van den Akker, Marjan; Schepers, Huub; Nijdam, Maddy; Tiep, Brian; Muris, Jean
AIMD: To assess the long-term effectiveness of an integrated disease management (IDM) program (consisting of optimal medication, reactivation, education, and exacerbation management) in primary care patients with chronic obstructive pulmonary disease (COPD). Controlled trial comparing the effects of IDM on quality of life--assessed by the St. George's Respiratory Questionnaire (SGRQ)--in primary care COPD patients. The minimal clinically important change on the SGRQ was accepted as being -4 points. Baseline and one year differences were compared using paired sample T-tests. The differential effects of an FEV1/FVC ratio <0.7 and dyspnoea as assessed by the Medical Research Council (MRC) Dyspnoea scale were investigated. The average age of subjects was 63 years, with an average post-bronchodilator FEV1 of 67% predicted, average FEV1/FVC ratio of 0.65, a mean of 35 pack-years smoking, and 63% were male. No significant differences existed between groups at baseline. After one year of IDM, SGRQ had improved by -4.6 points (95% CI, -7.2 to -2.0; p=0.001) in the intervention group, versus -0.7 points (95% CI, - 3.0 to 1.6; p=0.6) in the usual care group. In patients with an FEV1/FVC ratio <0.7, SGRQ improved by -5.9 points (95% CI, -9.6 to -2.2; p=0.002) in the IDM group, while in the usual care group SGRQ improved by -0.8 points (95% CI, -4.1 to 2.4; p=0.6). In patients with an MRC Dyspnoea score >2 and FEV1/FVC <0.7, SGRQ improved by -13.4 points (95% CI, -20.8 to -6.1; p=0.002) in the IDM group, versus -0.3 points (95% CI, -5.5 to 4.9; p=0.9) in the usual care group. In this study, IDM improved one-year quality of life in primary care COPD patients, compared to usual care. The improvement in SGRQ was both clinically relevant and statistically significant, and was greatest in patients with FEV1/FVC <0.7 and MRC Dyspnoea score >2.
Chen, Haiyong; Ning, Zhipeng; Lam, Wing Lok; Lam, Wai-Yee; Zhao, Ying Ke; Yeung, Jerry Wing Fai; Ng, Bacon Fung-Leung; Ziea, Eric Tat-Chi; Lao, Lixing
Analgesic effects of acupuncture have been extensively studied in various clinical trials. However, the conclusion remains controversial, even among large scale randomized controlled trials. This study aimed to evaluate the association between the conclusion of the trials and the types of control used in those trials via systematic review. Published randomized controlled trials of acupuncture for pain were retrieved from electronic databases (Medline, AMED, Cochrane libraries, EMBASE, PsycINFO, Clinicaltrials.gov, and CAB Abstracts) using a prespecified search strategy. One hundred and thirty-nine studies leading to 166 pairs of acupuncture-control treatment effect comparisons (26 studies comprised of 53 intervention-control pairs) were analyzed based on the proportion of positive conclusions in different control designs. We found that treatment effects of acupuncture compared with nontreatment controls had the highest tendency to yield a positive conclusion (84.3%), compared with nonneedle-insertion controls (53.3%). Whereas with needle-insertion controls, the lowest tendency of positive conclusions was observed (37.8%). Consistently, in studies reporting successful blinding, a higher tendency of positive findings on the treatment effect of acupuncture was found in the noninsertion sham controls compared with that in the insertion sham controls. We conclude that the type of control is likely to affect the conclusion in acupuncture analgesic trials. Appropriate control should be chosen according to the aims of studies. Copyright © 2016. Published by Elsevier B.V.
... Credit: National Cancer Institute Informed consent is a process through which you learn details about the trial before deciding whether to take part. This includes learning about the trial’s purpose and possible risks and ...
Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.
Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352
Gjorgov, A N
There are two major approaches to medical investigations: observational studies and experimental trials. The classical application of the experimental design to studies of human populations is the randomized clinical trial of the efficacy of a new drug or treatment. A further application of the experimental studies is to the testing of hypotheses about the etiology of a disease, already tested and corroborated from various forms of observational studies. Ethical considerations and requirements for consent of the experimental subjects are of primary concern in the clinical trials, and those concerns set the first and final limits for implementing a trial. General moral principles in research with human and animal beings, defined by the "Nuremberg Code," deal with strict criteria for approval, endorsement and evaluation of a clinical trial.
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Rigo, Flavia Karine; Trevisan, Gabriela; Godoy, Maria C; Rossato, Mateus Fortes; Dalmolin, Gerusa D; Silva, Mariane A; Menezes, Mirian S; Caumo, Wolnei; Ferreira, Juliano
Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. We conducted a randomized, double blind, active-controlled parallel-group clinical trial. Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain.Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid.
Albrecht, T L; Blanchard, C; Ruckdeschel, J C; Coovert, M; Strongbow, R
Clinical trials are the primary means for determining new, effective treatments for cancer patients, yet the number of patients that accrue is relatively limited. The purpose of this study was to explore the relationship between physician behavior and patient accrual to a clinical trial by videotaping the interaction. Forty-eight patient-physician interactions involving 12 different oncologists were videotaped in several clinics at the H. Lee Moffitt Cancer Center and Research Institute (Tampa, FL). The purpose of each interaction was to present the possibility of a clinical trial to the patient. A coding system, the Moffitt Accrual Analysis System, was developed by the authors to code behaviors that represented both the legal-informational and social influence models of communication behavior. Thirty-two patients agreed to participate in the clinical trial. Videotaping was found to be a viable, valid, and reliable method for studying the interaction. Physicians who were observed to use both models of influence were found to enroll more patients. Thus, patients were more likely to accrue to the trial when their physician verbally presented items normally included in an informed consent document and when they behaved in a reflective, patient-centered, supportive, and responsive manner. Discussion of benefits, side effects, patient concerns and resources to manage the concerns were all associated with accrual. This research has implications for modifying physician behavior and, thus, increasing the numbers of patients accruing to oncology clinical trials.
McDuffie, Roberta; Summerson, John; Reilly, Patricia; Blackwell, Caroline; Goff, David; Kimel, Angela R.; Crago, Lenore; Fonseca, Vivian
Hurricane Katrina was one of the most catastrophic natural disasters to hit the United States. It had a major impact on health care in New Orleans, LA and the surrounding region, not only in relation to acute illness but also chronic disease. When Hurricane Katrina struck New Orleans on August 29, 2005, there were 193 participants being followed in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial at Tulane University Health Sciences Center. In the immediate aftermath of the storm, the Tulane University ACCORD Study site, in collaboration with the Study Coordinating Center and the Southeast Clinical Center Network office of the trial at Wake Forest University Health Sciences in North Carolina, took several actions in order to locate the participants, ensure their safety, and maintain the scientific integrity of the trial. We describe the actions taken and the relative success/failure of such actions. PMID:18577469
Interventional oncology has great potential to be a good treatment modality in the field of oncology, because its procedures are minimally invasive and fairly quick. However, except for a few procedures such as percutaneous radiofrequency ablation and trans-catheter arterial chemo-embolization that have been recognized as standard treatments for hepatocellular carcinoma, most procedures have not been established as the standard treatment modality due to the limited number of clinical trials with compelling evidence. There are several common problems when performing clinical trials of interventional oncology. The first is that the outcomes of clinical trials are greatly influenced by the level of technical skill of the physicians. The second is that equipment and devices vary widely in countries and regions, and they also influence the outcomes. The third is that the methodology of clinical trials for techniques such as interventional oncology has not yet been established. The fourth is the difficulty of setting appropriate endpoints; quality of life is suitable for evaluating interventional oncology in palliative care, but it is not easy to set as the endpoint. The fifth is the difficulty of employing a blinded design, because the procedure cannot be performed without the physician's awareness. Despite such difficult situations, many multi-institutional clinical trials of interventional oncology have been carried out in Japan, with some challenging results. Establishing evidence is critical to making interventional oncology the standard treatment. Interventional radiologists should know the importance of clinical trials, and should move ahead in this direction in a step-by-step manner.
Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.
The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398
Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials.
Howlett, Jonathan G; McKelvie, Robert S; Arnold, J Malcolm O; Costigan, Jeannine; Dorian, Paul; Ducharme, Anique; Estrella-Holder, Estrellita; Ezekowitz, Justin A; Giannetti, Nadia; Haddad, Haissam; Heckman, George A; Herd, Anthony M; Isaac, Debra; Jong, Philip; Kouz, Simon; Liu, Peter; Mann, Elizabeth; Moe, Gordon W; Tsuyuki, Ross T; Ross, Heather J; White, Michel
The Canadian Cardiovascular Society published a comprehensive set of recommendations on the diagnosis and management of heart failure in January 2006. Based on feedback obtained through a national program of heart failure workshops and through active solicitation of stakeholders, several topics were identified because of their importance to the practicing clinician. Topics chosen for the present update include best practices for the diagnosis and management of right-sided heart failure, myocarditis and device therapy, and a review of recent important or landmark clinical trials. These recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. The present update has been written from a clinical perspective to provide a user-friendly and practical approach. Specific clinical questions that are addressed include: What is right-sided heart failure and how should one approach the diagnostic work-up? What other clinical entities may masquerade as this nebulous condition and how can we tell them apart? When should we be concerned about the presence of myocarditis and how quickly should patients with this condition be referred to an experienced centre? Among the myriad of recently published landmark clinical trials, which ones will impact our standards of clinical care? The goals are to aid physicians and other health care providers to optimally treat heart failure patients, resulting in a measurable impact on patient health and clinical outcomes in Canada.
Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: Diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials
Howlett, Jonathan G; McKelvie, Robert S; Arnold, J Malcolm O; Costigan, Jeannine; Dorian, Paul; Ducharme, Anique; Estrella-Holder, Estrellita; Ezekowitz, Justin A; Giannetti, Nadia; Haddad, Haissam; Heckman, George A; Herd, Anthony M; Isaac, Debra; Jong, Philip; Kouz, Simon; Liu, Peter; Mann, Elizabeth; Moe, Gordon W; Tsuyuki, Ross T; Ross, Heather J; White, Michel
The Canadian Cardiovascular Society published a comprehensive set of recommendations on the diagnosis and management of heart failure in January 2006. Based on feedback obtained through a national program of heart failure workshops and through active solicitation of stakeholders, several topics were identified because of their importance to the practicing clinician. Topics chosen for the present update include best practices for the diagnosis and management of right-sided heart failure, myocarditis and device therapy, and a review of recent important or landmark clinical trials. These recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. The present update has been written from a clinical perspective to provide a user-friendly and practical approach. Specific clinical questions that are addressed include: What is right-sided heart failure and how should one approach the diagnostic work-up? What other clinical entities may masquerade as this nebulous condition and how can we tell them apart? When should we be concerned about the presence of myocarditis and how quickly should patients with this condition be referred to an experienced centre? Among the myriad of recently published landmark clinical trials, which ones will impact our standards of clinical care? The goals are to aid physicians and other health care providers to optimally treat heart failure patients, resulting in a measurable impact on patient health and clinical outcomes in Canada. PMID:19214293
MacRae, Catharine Siân; Lewis, Jeremy S; Shortland, Adam P; Morrissey, Matthew C; Critchley, Duncan
Multicenter, assessor-blind, randomized, clinical trial. To compare the effectiveness of rocker sole footwear to traditional flat sole footwear as part of the management for people with low back pain (LBP). During the past decade, persistent advertising has claimed that footwear constructed with a rocker sole will reduce LBP. However, there is no robust evidence to support these claims. One hundred fifteen people with chronic LBP were randomized to wear rocker sole shoes or flat sole shoes for a minimum of 2 hours each day while standing and walking. Primary outcome was the Roland Morris Disability Questionnaire (RMDQ). In addition, participants attended an exercise and education program once a week for 4 weeks and wore their assigned shoes during these sessions. Participants were assessed without their knowledge of group allocation prerandomization, and at 6 weeks, 6 months, and 1 year (main outcome point). Analysis was by intention-to-treat method. At 12 months, data from 44 of 58 (77.2%) of the rocker sole group and 49 of 57 (84.5%) of the flat sole group were available for analysis. In the rocker sole group, mean reduction in RMDQ was -3.1 (95% CI [confidence interval], -4.5 to -1.6), and in the flat sole group, it was -4.4 (95% CI, -5.8 to -3.1) (a greater negative value represents a greater reduction in disability). At 6 months, more people wearing flat shoes compared with those wearing rocker shoes demonstrated a minimal clinically important improvement in disability (53.2% and 31.1%, respectively; P = 0.03). Between-group differences were not significant for RMDQ or any secondary outcomes (e.g., pain) at any time. People reporting pain when standing and walking at baseline (n = 59) reported a greater reduction in RMDQ at 12 months in the flat sole group (-4.4 [95% CI, -6.0 to -2.8], n = 29) than the rocker sole group (-2.0 [95% CI, -3.6 to -0.4], n = 30) (P < 0.05). Rocker sole shoes seem to be no more beneficial than flat sole shoes in affecting disability
Demchuk, Andrew M; Goyal, Mayank; Yeatts, Sharon D; Carrozzella, Janice; Foster, Lydia D; Qazi, Emmad; Hill, Michael D; Jovin, Tudor G; Ribo, Marc; Yan, Bernard; Zaidat, Osama O; Frei, Donald; von Kummer, Rüdiger; Cockroft, Kevin M; Khatri, Pooja; Liebeskind, David S; Tomsick, Thomas A; Palesch, Yuko Y; Broderick, Joseph P
To use baseline computed tomographic (CT) angiography to analyze imaging and clinical end points in an Interventional Management of Stroke III cohort to identify patients who would benefit from endovascular stroke therapy. The primary clinical end point was 90-day dichotomized modified Rankin Scale (mRS) score. Secondary end points were 90-day mRS score distribution and 24-hour recanalization. Prespecified subgroup was baseline proximal occlusions (internal carotid, M1, or basilar arteries). Exploratory analyses were subsets with any occlusion and specific sites of occlusion (two-sided α = .01). Of 656 subjects, 306 (47%) underwent baseline CT angiography or magnetic resonance angiography. Of 306, 282 (92%) had arterial occlusions. At baseline CT angiography, proximal occlusions (n = 220) demonstrated no difference in primary outcome (41.3% [62 of 150] endovascular vs 38% [27 of 70] intravenous [IV] tissue-plasminogen activator [tPA]; relative risk, 1.07 [99% confidence interval: 0.67, 1.70]; P = .70); however, 24-hour recanalization rate was higher for endovascular treatment (n = 167; 84.3% [97 of 115] endovascular vs 56% [29 of 52] IV tPA; P < .001). Exploratory subgroup analysis for any occlusion at baseline CT angiography did not demonstrate significant differences between endovascular and IV tPA arms for primary outcome (44.7% [85 of 190] vs 38% [35 of 92], P = .29), although ordinal shift analysis of full mRS distribution demonstrated a trend toward more favorable outcome (P = .011). Carotid T- or L-type occlusion (terminal internal carotid artery [ICA] with M1 middle cerebral artery and/or A1 anterior cerebral artery involvement) or tandem (extracranial or intracranial) ICA and M1 occlusion subgroup also showed a trend favoring endovascular treatment over IV tPA alone for primary outcome (26% [12 of 46] vs 4% [one of 23], P = .047). Significant differences were identified between treatment arms for 24-hour recanalization in proximal occlusions; carotid T
Mould, R F
The design of clinical trials in cancer is a subject which features reasonably often among FRCR (Part 1) examination questions, and as such should be of more than passing interest to oncologists. It is also a subject which is gaining in relevance since the number of trials is increasing annually due in part to the many chemotherapeutic regimes which are being proposed. This paper which is based on a lecture given in Cambridge at the Hospital Physicists' Association Annual Conference in September 1978, is intended to act as an introduction to clinical trial design. References for further reading are given and, in particular, the extensive report on randomised clinical trials to the Medical Research Council's Leukaemia Steering Committee (Peto et al., 1977, 1978) is recommended.
Fraccaro, Paolo; Pupella, Valeria; Gazzarata, Roberta; Dentone, Chiara; Cenderello, Giovanni; De Leo, Pasqualina; Bozzano, Federica; Casalino Finocchio, Giorgetta; De Maria, Andrea; Fenoglio, Daniela; Filaci, Gilberto; Guerra, Michele; Di Biagio, Antonio; Mantia, Eugenio; Orofino, Giancarlo; Ferrea, Giuseppe; Viscoli, Claudio; Giacomini, Mauro
In recent years, Highly-Active Anti-Retroviral Therapies (HAARTs) have modified the Human Immunodeficiency Virus (HIV) life-cycle and the disease is now considered chronic. Consequently, a longitudinal and complex follow-up is now required for HIV positive patients during their lifetime. Moreover, patients often encounter various complications due to comorbidities, related to the immunodeficiency state and HAARTs' side effects. Thus, HIV positive patients are involved in multicenter clinical trials (MCTs) to improve treatments and discover a preventive vaccine. Therefore, physicians require proper instruments to access comprehensive patient data for managing patients during follow-ups, and tools for data collection and analysis in MCTs. The Ligurian HIV Clinical Network aims to provide physicians with a Web-tool to administrate HIV positive patients' data within primary-care and to reuse the collected clinical information to perform MCTs in Northern Italy. The key aspect of the system is a relational database which allows the storage of various types of clinical information (eg, related to HIV, cardiovascular, or hepatic diseases) in multiple formats. The modular design of the database permits a rapid insertion of new parameters without requiring any changes in the database structure. Furthermore, codes from biomedical ontologies controlled vocabularies ("Logical Observation Identifier Names and Codes", and "International Classification of Diseases 9") and ontologies ("Systematized Nomenclature of Medicine Clinical Terms"), units and normality ranges used by all partners participating in the project were collected to achieve a complete semantic interoperability. Accordingly, data can be automatically normalized through the z score formula and physicians can extract and correctly compare information with external statistical tools. Moreover, to respect patients' privacy and legal issues, a local identifier, determined through an HASH cryptography algorithm, is
Cox, K; Wilson, E; Arthur, A; Elkan, R; Armstrong, S
The effect of a nurse-managed intervention, for early phase cancer trial participants at trial conclusion, on psychosocial outcomes was evaluated at two cancer centres in the Midlands, England using a randomised controlled trial. It involved 117 patients who were participating in an early phase cancer clinical trial. It was a nurse-managed trial exit, which included a trial exit interview, trial feedback information leaflet and telephone follow-up compared with standard care at trial conclusion. Psychological distress at 1 week and 4-6 weeks post-trial conclusion, patient's knowledge and understanding and patient's satisfaction were assessed. The results showed there was no significant difference between the two groups regarding scores for anxiety and depression at time one and time two. There is some suggestion that the intervention reduced anxiety from trial conclusion to follow-up (P=0.27). Patients in both groups felt they had contributed to cancer research through trial participation. However, intervention patients were more likely to feel that they knew how the trial was going (P<0.001), knew how other people in the trial were doing (P=0.001), had all the feedback they needed about the trial they took part in (P<0.01) and knew how they would be followed up (P=0.02). Patient satisfaction with the intervention was high (median score=4.5 where 5 is greatest satisfaction). In conclusion, nurse-managed trial conclusion led to positive outcomes for patients who had recently completed a clinical trial.
Resnik, David B.; Tinkle, Sally S.
Nanomedicine shows tremendous promise for improving medical diagnosis, treatment, and prevention, but it also raises a variety of ethical concerns. Because of the paucity of data on the physicochemical properties of nanoscale materials in biological systems, clinical trials of nanomedicine products present some unique challenges related to risk minimization, management and communication involving human subjects. Although these clinical trials do not raise any truly novel ethical issues, the rapid development of nanotechnology and its potentially profound social and environmental impacts, add a sense of urgency to the problems that arise. PMID:17166777
Lemaire, Jane B; Wallace, Jean E; Lewin, Adriane M; de Grood, Jill; Schaefer, Jeffrey P
Background Physicians often experience work-related stress that may lead to personal harm and impaired professional performance. Biofeedback has been used to manage stress in various populations. Objective To determine whether a biofeedback-based stress management tool, consisting of rhythmic breathing, actively self-generated positive emotions and a portable biofeedback device, reduces physician stress. Design Randomized controlled trial measuring efficacy of a stress-reduction intervention over 28 days, with a 28-day open-label trial extension to assess effectiveness. Setting Urban tertiary care hospital. Participants Forty staff physicians (23 men and 17 women) from various medical practices (1 from primary care, 30 from a medical specialty and 9 from a surgical specialty) were recruited by means of electronic mail, regular mail and posters placed in the physicians’ lounge and throughout the hospital. Intervention Physicians in the intervention group were instructed to use a biofeedback-based stress management tool three times daily. Participants in both the control and intervention groups received twice-weekly support visits from the research team over 28 days, with the intervention group also receiving re-inforcement in the use of the stress management tool during these support visits. During the 28-day extension period, both the control and the intervention groups received the intervention, but without intensive support from the research team. Main outcome measure Stress was measured with a scale developed to capture short-term changes in global perceptions of stress for physicians (maximum score 200). Results During the randomized controlled trial (days 0 to 28), the mean stress score declined significantly for the intervention group (change –14.7, standard deviation [SD] 23.8; p = 0.013) but not for the control group (change –2.2, SD 8.4; p = 0.30). The difference in mean score change between the groups was 12.5 (p = 0.048). The lower mean stress
The Conducting Clinical Trials in Europe meeting, held in London, included topics covering new developments in the field of clinical trials and recommendations on how to best conduct a trial. This conference report highlights selected presentations on the state of affairs of trials in Europe, conducting trials in emerging markets, strategies for improving trials, trial design options, peri-approval and pediatric trials, and the role of key players, such as physicians. Company perspectives from Pfizer Inc and Nycomed are also included.
effectiveness of a novel clinical intervention developed by the PI called the Collaborative Assessment and Management of Suicidality (CAMS). CAMS is not a... effectiveness of CAMS versus Enhanced Care As Usual (E-CAU) in a sample of n = 148 active-duty US Army Soldiers who are experiencing suicidal ideation and/or...sources at the ARS to include the behavioral health clinic and the inpatient unit. The goal of this study is to determine if CAMS is more effective
Buchanan, David R; White, Jeffrey D; O'Mara, Ann M; Kelaghan, Joseph W; Smith, Wendy B; Minasian, Lori M
To identify major research-design issues in proposals submitted by investigators in the Community Clinical Oncology Program (CCOP) for clinical trials of complementary and alternative medicine (CAM) for cancer-symptom management. We conducted content analysis of all scientific reviews of concepts and protocols submitted by the CCOP to the National Cancer Institute (NCI) to identify research challenges in conducting clinical trials designed to evaluate CAM interventions for cancer-symptom management. Since the inception of the NCI Office of Cancer Complementary and Alternative Medicine in 1998, a total of 46 symptom-management studies using CAM interventions have been proposed by CCOP investigators, with 20 studies now in progress comprising 22% of the current total CCOP symptom-management portfolio. Proposals fell into four categories: complex natural products; nutritional therapeutics; mind-body interventions; and alternative medical systems. The most significant research-design issues arose as a consequence of the lack of preclinical data for CAM interventions and the lack of quality-control standards comparable with those used in regulating new pharmaceutical agents. Across the different types of CAM interventions, the most common problems found in proposed research designs are related to unwarranted assumptions about the consistency and standardization of CAM interventions, the need for data-based justifications for the study hypotheses, and the need to implement appropriate quality control and monitoring procedures during the course of the trial. To advance the state of the science, future research must address these critical issues if CAM interventions are to be evaluated rigorously and have a consequent impact on clinical practice and general public awareness.
... Watch: Addictive Behaviors : Carl Lejuez, Professor of Clinical Psychology at the University of Maryland, College Park, and Director of the Center for Addictions, Personality & Emotional Research, discusses translational research — studying the basic internal processes ...
Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D
Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Loane, M A; Corbett, R; Bloomer, S E; Eedy, D J; Gore, H E; Mathews, C; Steele, K; Wootton, R
Diagnostic accuracy and management recommendations of realtime teledermatology consultations using low-cost telemedicine equipment were evaluated. Patients were seen by a dermatologist over a video-link and a diagnosis and treatment plan were recorded. This was followed by a face-to-face consultation on the same day to confirm the earlier diagnosis and management plan. A total of 351 patients with 427 diagnoses participated. Sixty-seven per cent of the diagnoses made over the video-link agreed with the face-to-face diagnosis. Clinical management plans were recorded for 214 patients with 252 diagnoses. For this cohort, 44% of the patients were seen by the same dermatologist at both consultations, while 56% were seen by a different dermatologist. In 64% of cases the same management plan was recommended at both consultations; a sub-optimum treatment plan was recommended in 8% of cases; and in 9% of cases the video-link management plans were judged to be inappropriate. In 20% of cases the dermatologist was unable to recommend a suitable management plan by video-link. There were significant differences in the ability to recommend an optimum management plan by video-link when a different dermatologist made the reference management plan. The results indicate that a high proportion of dermatological conditions can be successfully managed by realtime teledermatology.
Choudhury, Khushboo; Ghooi, Ravindra
The rules for compensation for injury and death in clinical trials have recently been notified. These rules clarify that medical management of all injuries in clinical trials is mandatory and in cases in which injury or death is related to the clinical trial, the subject (or nominee) is entitled to compensation over and above the medical management. They also specify procedures and timelines for reporting serious adverse events. These require simplification. The rules will hopefully make clinical trial safer for subjects and investigators alike. However, they suffer from certain inconsistencies that should be reconsidered. They need to be modified so that they do not damage the industry.
Badesch, D B
Progress in treatment of pulmonary hypertension has been impaired by the lack of formal clinical trials. This is now beginning to change, and the impact on our approach to treating patients with pulmonary hypertension in substantial. As with other relatively uncommon medical disorders, randomized, controlled, multi-center trials are needed to assess the safety and efficacy of potential therapeutic modalities. Treatments showing promise at the level of small pilot studies within a single center should be studied more rigorously.
Wing, J K
In summary, the discussion by Professors Helmchen and Müller-Oerlinghausen of the morality of clinical trials has emphasized a point that is frequently overlooked. It is an essential to consider those situations in which it might be unethical not to conduct a trial as it is to be concerned about the ways in which trials might restrict the rights of the individuals taking part in them. They and I have dealt mainly with the first of these two issues because it has been relatively neglected. The second is, of course, equally important and has rightly received much attention. Both matters deserve further public discussion. PMID:775090
Wing, J K
In summary, the discussion by Professors Helmchen and Müller-Oerlinghausen of the morality of clinical trials has emphasized a point that is frequently overlooked. It is an essential to consider those situations in which it might be unethical not to conduct a trial as it is to be concerned about the ways in which trials might restrict the rights of the individuals taking part in them. They and I have dealt mainly with the first of these two issues because it has been relatively neglected. The second is, of course, equally important and has rightly received much attention. Both matters deserve further public discussion.
Atwater, Brett D; Oujiri, James; Wolff, Matthew R
The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial confirmed that percutaneous coronary intervention is no better than optimal medical therapy for the prevention of major adverse cardiac events in patients with stable angina. The impact of these findings on clinical practice remains unknown. Clinicians may more frequently opt for medical rather than procedural therapy of stable angina in response to the COURAGE trial. Clinical information was collected from patients with stable angina referred to our hospital for cardiac catheterization between January 1, 2007 and June 18, 2007 (n = 332). Catheterization referral volume and the use of medications and coronary revascularization were compared before and after the release of the COURAGE trial. There was a significant increase in anti-ischemia medication use prior to catheterization referral following the COURAGE trial (mean = 1.31 [SD 0.83] medications pre-COURAGE, mean = 1.54 [SD 0.84] medications post-COURAGE, P = 0.012). Among 217 patients with coronary disease on catheterization, treatment with medication rather than percutaneous or surgical revascularization increased after COURAGE (11.1% pre-COURAGE vs 23.0% post-COURAGE, P = 0.03). There was also a significant decrease in referral volume following the COURAGE trial (3.12 referrals/day pre-COURAGE vs 2.51 referrals/day post-COURAGE, P = 0.034). The COURAGE trial immediately impacted the management of stable angina. Catheterization referral volume decreased, medication use increased, and the use of medical therapy rather than revascularization increased among patients with coronary disease.
Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122
Strauss, David G.; Blinova, Ksenia
Clinical trials ‘in a dish’ involve testing medical therapies for safety or effectiveness in the laboratory with human tissue. This has become possible owing to recent biotechnology advances including induced pluripotent stem cells, organs-on-a-chip, and whole-genome sequencing. We provide here an overview of the landscape and highlight steps the FDA is taking to advance the science of clinical trials in a dish and to support the development and validation of new regulatory paradigms to assess drug safety using these new technologies. PMID:27876286
Bergmann, J F; Chassany, O
To improve medical knowledge by reading clinical trial reports it is necessary to check for the respect of the methodological rules, and to analyze and criticize the results. A control group and a randomisation are always necessary. Double blind assessment, sample size calculation, intention to treat analysis, a unique primary end point are also important. The conclusions of the trial are valid only for the population included and the clinical signification of the results, depending on the control treatment, has to be evaluated. Respect of the reading rules is necessary to assess the reliability of the conclusions, in order to promote evidence-based practice.
Developments in biotechnology and genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians. The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials. In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine. We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are Phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction-based approach to the analysis of randomized clinical trials that both preserves the Type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen.
Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, C. Oliver; Walsh, Karin S.; Wolters, Pamela L.; Widemann, Brigitte C.
The neurofibromatoses (NF)—including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis—are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801
Jung, Sin-Ho; Sargent, Daniel J
Traditionally, Phase II trials have been conducted as single-arm trials to compare the response probabilities between an experimental therapy and a historical control. Historical control data, however, often have a small sample size, are collected from a different patient population, or use a different response assessment method, so that a direct comparison between a historical control and an experimental therapy may be severely biased. Randomized Phase II trials entering patients prospectively to both experimental and control arms have been proposed to avoid any bias in such cases. The small sample sizes for typical Phase II clinical trials imply that the use of exact statistical methods for their design and analysis is appropriate. In this article, we propose two-stage randomized Phase II trials based on Fisher's exact test, which does not require specification of the response probability of the control arm for testing. Through numerical studies, we observe that the proposed method controls the type I error accurately and maintains a high power. If we specify the response probabilities of the two arms under the alternative hypothesis, we can identify good randomized Phase II trial designs by adopting the Simon's minimax and optimal design concepts that were developed for single-arm Phase II trials.
Before any clinical trial begins, a detailed trial protocol must be prepared. The authority of the trial results will depend on the quality of this document. In many protocols, a key component is a plan for a series of interim analyses of the accumulating trial data, and a 'stopping rule' based on them. Such a rule might be intended to prevent participants from continuing to receive a drug that already seems to be unsafe, or to allow a successful drug to become generally available as soon as sufficient evidence of its advantages has been collected. There has been considerable misunderstanding of these rules, and controversies associated with them. Here, I discuss why this might be, and what can be done to promote their successful and beneficial use in the future.
Chan, Kam Wa; Ip, Tai Pang; Kwong, Alfred Siu Kei; Lui, Sing Leung; Chan, Gary Chi Wang; Cowling, Benjamin John; Yiu, Wai Han; Wong, Dickson Wai Leong; Liu, Yang; Feng, Yibin; Tan, Kathryn Choon Beng; Chan, Loretta Yuk Yee; Leung, Joseph Chi Kam; Lai, Kar Neng; Tang, Sydney Chi Wai
Introduction Diabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin–angiotensin system has only achieved limited effect in preserving renal function. Recent observational data show that the use of Chinese medicine (CM), a major form of traditional medicine used extensively in Asia, could reduce the risk of end-stage kidney disease. However, existing clinical practice guidelines are weakly evidence-based and the effect of CM remains unclear. This trial explores the effect of an existing integrative Chinese–Western medicine protocol for the management of DN. Objective To optimise parameters and assess the feasibility for a subsequent phase III randomised controlled trial through preliminary evaluation on the effect of an adjuvant semi-individualised CM treatment protocol on patients with type 2 diabetes with stages 2–3 chronic kidney disease and macroalbuminuria. Methods and analysis This is an assessor-blind, add-on, randomised, controlled, parallel, multicentre, open-label pilot pragmatic clinical trial. 148 patients diagnosed with DN will be recruited and randomised 1:1 to a 48-week additional semi-individualised CM treatment programme or standard medical care. Primary end points are the changes in estimated glomerular filtration rate and spot urine albumin-to-creatinine ratio between baseline and treatment end point. Secondary end points include fasting blood glucose, glycated haemoglobin, brain natriuretic peptide, fasting insulin, C peptide, fibroblast growth factor 23, urinary monocyte chemotactic protein-1, cystatin C, nephrin, transforming growth factor-β1 and vascular endothelial growth factor. Adverse events are monitored through self-completed questionnaire and clinical visits. Outcomes will be analysed by regression models. Enrolment started in July 2015. Ethics and registration This protocol is approved by the Institutional
Cook, John; Drummond, Michael; Heyse, Joseph F
Healthcare decision makers are increasingly requesting information on the cost and cost-effectiveness of new medicines at the time of product launch. In order to provide this information, data on healthcare resource utilization and, in some cases, costs, may be collected in clinical trials. In this paper, we discuss some of the issues statisticians need to address when it is appropriate to include these economic endpoints in the trial. Several design issues are discussed, including the alternative types of and methods for collecting economic endpoint data, sample size and generalizability. Alternative approaches in the analysis of resource utilization, cost and cost-effectiveness are also presented. Finally, several of the analytic approaches are applied to actual data from a clinical trial.
Lambourne, Kate; Washburn, Richard A.; Gibson, Cheryl; Sullivan, Debra K.; Goetz, Jeannine; Lee, Robert; Smith, Bryan K.; Mayo, Matthew S.; Donnelly, Joseph E.
State-of-the-art treatment for weight management consists of a behavioral intervention to facilitate decreased energy intake and increased physical activity. These interventions are typically delivered face-to-face (FTF) by a health educator to a small group of participants. There are numerous barriers to participation in FTF clinics including availability, scheduling, the expense and time required to travel to the clinic site, and possible need for dependent care. Weight management clinics delivered by conference call have the potential to diminish or eliminate these barriers. The conference call approach may also reduce burden on providers, who could conduct clinic groups from almost any location without the expenses associated with maintaining FTF clinic space. A randomized trial will be conducted in 395 overweight/obese adults (BMI 25–39.9 kg/m2) to determine if weight loss (6 months) and weight maintenance (12 months) are equivalent between weight management interventions utilizing behavioral strategies and pre-packaged meals delivered by either a conference call or the traditional FTF approach. The primary outcome, body weight, will be assessed at baseline, 6, 12 and 18 months. Secondary outcomes including waist circumference, energy and macronutrient intake, and physical activity and will be assessed on the same schedule. In addition, a cost analysis and extensive process evaluation will be completed. PMID:22664647
Lambourne, Kate; Washburn, Richard A; Gibson, Cheryl; Sullivan, Debra K; Goetz, Jeannine; Lee, Robert; Smith, Bryan K; Mayo, Matthew S; Donnelly, Joseph E
State-of-the-art treatment for weight management consists of a behavioral intervention to facilitate decreased energy intake and increased physical activity. These interventions are typically delivered face-to-face (FTF) by a health educator to a small group of participants. There are numerous barriers to participation in FTF clinics including availability, scheduling, the expense and time required to travel to the clinic site, and possible need for dependent care. Weight management clinics delivered by conference call have the potential to diminish or eliminate these barriers. The conference call approach may also reduce burden on providers, who could conduct clinic groups from almost any location without the expenses associated with maintaining FTF clinic space. A randomized trial will be conducted in 395 overweight/obese adults (BMI 25-39.9 kg/m(2)) to determine if weight loss (6 months) and weight maintenance (12 months) are equivalent between weight management interventions utilizing behavioral strategies and pre-packaged meals delivered by either a conference call or the traditional FTF approach. The primary outcome, body weight, will be assessed at baseline, 6, 12 and 18 months. Secondary outcomes including waist circumference, energy and macronutrient intake, and physical activity and will be assessed on the same schedule. In addition, a cost analysis and extensive process evaluation will be completed. Copyright © 2012 Elsevier Inc. All rights reserved.
The NCI Community Oncology Research Program (NCORP) is a national network of investigators, cancer care providers, academic institutions, and other organizations. NCORP conducts multi-site cancer clinical trials and studies in diverse populations in community-based healthcare systems across the United States and Puerto Rico.
Morales, Daniel R; Donnan, Peter T; Daly, Fergus; Staa, Tjeerd Van; Sullivan, Frank M
Objectives To measure the incidence of Bell's palsy and determine the impact of clinical trial findings on Bell's palsy management in the UK. Design Interrupted time series regression analysis and incidence measures. Setting General practices in the UK contributing to the Clinical Practice Research Datalink (CPRD). Participants Patients ≥16 years with a diagnosis of Bell's palsy between 2001 and 2012. Interventions (1) Publication of the 2004 Cochrane reviews of clinical trials on corticosteroids and antivirals for Bell's palsy, which made no clear recommendation on their use and (2) publication of the 2007 Scottish Bell's Palsy Study (SBPS), which made a clear recommendation that treatment with prednisolone alone improves chances for complete recovery. Main outcome measures Incidence of Bell's palsy per 100 000 person-years. Changes in the management of Bell's palsy with either prednisolone therapy, antiviral therapy, combination therapy (prednisolone with antiviral therapy) or untreated cases. Results During the 12-year period, 14 460 cases of Bell's palsy were identified with an overall incidence of 37.7/100 000 person-years. The 2004 Cochrane reviews were associated with immediate falls in prednisolone therapy (−6.3% (−11.0 to −1.6)), rising trends in combination therapy (1.1% per quarter (0.5 to 1.7)) and falling trends for untreated cases (−0.8% per quarter (−1.4 to −0.3)). SBPS was associated with immediate increases in prednisolone therapy (5.1% (0.9 to 9.3)) and rising trends in prednisolone therapy (0.7% per quarter (0.4 to 1.2)); falling trends in combination therapy (−1.7% per quarter (−2.2 to −1.3)); and rising trends for untreated cases (1.2% per quarter (0.8 to 1.6)). Despite improvements, 44% still remain untreated. Conclusions SBPS was clearly associated with change in management, but a significant proportion of patients failed to receive effective treatment, which cannot be fully explained. Clarity and uncertainty in
Morales, Daniel R; Donnan, Peter T; Daly, Fergus; Staa, Tjeerd Van; Sullivan, Frank M
To measure the incidence of Bell's palsy and determine the impact of clinical trial findings on Bell's palsy management in the UK. Interrupted time series regression analysis and incidence measures. General practices in the UK contributing to the Clinical Practice Research Datalink (CPRD). Patients ≥16 years with a diagnosis of Bell's palsy between 2001 and 2012. (1) Publication of the 2004 Cochrane reviews of clinical trials on corticosteroids and antivirals for Bell's palsy, which made no clear recommendation on their use and (2) publication of the 2007 Scottish Bell's Palsy Study (SBPS), which made a clear recommendation that treatment with prednisolone alone improves chances for complete recovery. Incidence of Bell's palsy per 100 000 person-years. Changes in the management of Bell's palsy with either prednisolone therapy, antiviral therapy, combination therapy (prednisolone with antiviral therapy) or untreated cases. During the 12-year period, 14 460 cases of Bell's palsy were identified with an overall incidence of 37.7/100 000 person-years. The 2004 Cochrane reviews were associated with immediate falls in prednisolone therapy (-6.3% (-11.0 to -1.6)), rising trends in combination therapy (1.1% per quarter (0.5 to 1.7)) and falling trends for untreated cases (-0.8% per quarter (-1.4 to -0.3)). SBPS was associated with immediate increases in prednisolone therapy (5.1% (0.9 to 9.3)) and rising trends in prednisolone therapy (0.7% per quarter (0.4 to 1.2)); falling trends in combination therapy (-1.7% per quarter (-2.2 to -1.3)); and rising trends for untreated cases (1.2% per quarter (0.8 to 1.6)). Despite improvements, 44% still remain untreated. SBPS was clearly associated with change in management, but a significant proportion of patients failed to receive effective treatment, which cannot be fully explained. Clarity and uncertainty in clinical trial recommendations may change clinical practice. However, better ways are needed to understand and circumvent
Background Patients with hypertension continue to have less than optimal blood pressure control, with nearly one in five Canadian adults having hypertension. Pharmacist prescribing is gaining favor as a potential clinically efficacious and cost-effective means to improve both access and quality of care. With Alberta being the first province in Canada to have independent prescribing by pharmacists, it offers a unique opportunity to evaluate outcomes in patients who are prescribed antihypertensive therapy by pharmacists. Methods The study is a randomized controlled trial of enhanced pharmacist care, with the unit of randomization being the patient. Participants will be randomized to enhanced pharmacist care (patient identification, assessment, education, close follow-up, and prescribing/titration of antihypertensive medications) or usual care. Participants are patients in rural Alberta with undiagnosed/uncontrolled blood pressure, as defined by the Canadian Hypertension Education Program. The primary outcome is the change in systolic blood pressure between baseline and 24 weeks in the enhanced-care versus usual-care arms. There are also three substudies running in conjunction with the project examining different remuneration models, investigating patient knowledge, and assessing health-resource utilization amongst patients in each group. Discussion To date, one-third of the required sample size has been recruited. There are 15 communities and 17 pharmacists actively screening, recruiting, and following patients. This study will provide high-level evidence regarding pharmacist prescribing. Trial Registration Clinicaltrials.gov NCT00878566. PMID:21834970
Background Osteoarthritis (OA) is a prevalent chronic disease and a leading cause of disability in adults. For people with knee and hip OA, symptoms (e.g., pain and fatigue) can interfere with mobility and physical activity. Whereas symptom management is a cornerstone of treatment for knee and hip OA, limited evidence exists for behavioral interventions delivered by rehabilitation professionals within the context of clinical care that address how symptoms affect participation in daily activities. Activity pacing, a strategy in which people learn to preplan rest breaks to avoid symptom exacerbations, has been effective as part of multi-component interventions, but hasn't been tested as a stand-alone intervention in OA or as a tailored treatment using accelerometers. In a pilot study, we found that participants who underwent a tailored activity pacing intervention had reduced fatigue interference with daily activities. We are now conducting a full-scale trial. Methods/Design This paper provides a description of our methods and rationale for a trial that evaluates a tailored activity pacing intervention led by occupational therapists for adults with knee and hip OA. The intervention uses a wrist accelerometer worn during the baseline home monitoring period to glean recent symptom and physical activity patterns and to tailor activity pacing instruction based on how symptoms relate to physical activity. At 10 weeks and 6 months post baseline, we will examine the effectiveness of a tailored activity pacing intervention on fatigue, pain, and physical function compared to general activity pacing and usual care groups. We will also evaluate the effect of tailored activity pacing on physical activity (PA). Discussion Managing OA symptoms during daily life activity performance can be challenging to people with knee and hip OA, yet few clinical interventions address this issue. The activity pacing intervention tested in this trial is designed to help people modulate their
Dexheimer, Judith W; Abramo, Thomas J; Arnold, Donald H; Johnson, Kevin; Shyr, Yu; Ye, Fei; Fan, Kang-Hsien; Patel, Neal; Aronsky, Dominik
The use of evidence-based guidelines can improve the care for asthma patients. We implemented a computerized asthma management system in a pediatric emergency department (ED) to integrate national guidelines. Our objective was to determine whether patient eligibility identification by a probabilistic disease detection system (Bayesian network) combined with an asthma management system embedded in the workflow decreases time to disposition decision. We performed a prospective, randomized controlled trial in an urban, tertiary care pediatric ED. All patients 2-18 years of age presenting to the ED between October 2010 and February 2011 were screened for inclusion by the disease detection system. Patients identified to have an asthma exacerbation were randomized to intervention or control. For intervention patients, asthma management was computer-driven and workflow-integrated including computer-based asthma scoring in triage, and time-driven display of asthma-related reminders for re-scoring on the electronic patient status board combined with guideline-compliant order sets. Control patients received standard asthma management. The primary outcome measure was the time from triage to disposition decision. The Bayesian network identified 1339 patients with asthma exacerbations, of which 788 had an asthma diagnosis determined by an ED physician-established reference standard (positive predictive value 69.9%). The median time to disposition decision did not differ among the intervention (228 min; IQR=(141, 326)) and control group (223 min; IQR=(129, 316)); (p=0.362). The hospital admission rate was unchanged between intervention (25%) and control groups (26%); (p=0.867). ED length of stay did not differ among intervention (262 min; IQR=(165, 410)) and control group (247 min; IQR=(163, 379)); (p=0.818). The control and intervention groups were similar in regards to time to disposition; the computerized management system did not add additional wait time. The time to
Dexheimer, Judith W; Abramo, Thomas J; Arnold, Donald H; Johnson, Kevin; Shyr, Yu; Ye, Fei; Fan, Kang-Hsien; Patel, Neal; Aronsky, Dominik
Objective The use of evidence-based guidelines can improve the care for asthma patients. We implemented a computerized asthma management system in a pediatric emergency department (ED) to integrate national guidelines. Our objective was to determine whether patient eligibility identification by a probabilistic disease detection system (Bayesian network) combined with an asthma management system embedded in the workflow decreases time to disposition decision. Methods We performed a prospective, randomized controlled trial in an urban, tertiary care pediatric ED. All patients 2–18 years of age presenting to the ED between October 2010 and February 2011 were screened for inclusion by the disease detection system. Patients identified to have an asthma exacerbation were randomized to intervention or control. For intervention patients, asthma management was computer-driven and workflow-integrated including computer-based asthma scoring in triage, and time-driven display of asthma-related reminders for re-scoring on the electronic patient status board combined with guideline-compliant order sets. Control patients received standard asthma management. The primary outcome measure was the time from triage to disposition decision. Results The Bayesian network identified 1,339 patients with asthma exacerbations, of which 788 had an asthma diagnosis determined by an ED physician-established reference standard (positive predictive value 69.9%). The median time to disposition decision did not differ among the intervention (228 minutes; IQR=(141, 326)) and control group (223 minutes; IQR= (129, 316));(p=0.362). The hospital admission rate was unchanged between intervention (25%) and control groups (26%); (p=0.867). ED length of stay did not differ among intervention (262 minutes; IQR=(165, 410)) and control group (247 minutes; IQR=(163, 379));(p=0.818). Conclusions The control and intervention groups were similar in regards to time to disposition; the computerized management
Tubiana, M; Henry-Amar, M; Carde, P; Burgers, J M; Hayat, M; Van der Schueren, E; Noordijk, E M; Tanguy, A; Meerwaldt, J H; Thomas, J
From 1964 to 1987, the EORTC Lymphoma Group conducted four consecutive controlled clinical trials on clinical stages I and II Hodgkin's disease in which 1,579 patients were entered. From the onset the main aim of these trials was to identify the subsets of patients who could be treated safely by regional radiotherapy (RT). Therefore, several prognostic indicators were prospectively registered and progressively used in the trial protocols for the delineation of the favorable and unfavorable subgroups as soon as they were recognized of high predictive value. In the H2 trial (1972 to 1976), the histologic subtype was the only variable taken into account for the therapeutic strategy and the staging laparotomy findings were found to be of prognostic value only in patients with favorable prognostic indicators. In the H5 trial (1977 to 1982), patients were subdivided into two subgroups according to six prognostic indicators. Patients with favorable features were submitted to a staging laparotomy (lap); lap negative patients were randomized between mantle field RT and mantle field plus paraaortic RT. Disease free survival (DFS) and total survival (S) were similar in the two arms. Among patients with unfavorable features, DFS and S were significantly higher in the arm treated by combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) chemotherapy (CT) and RT than in the arm treated by total nodal irradiation. Nevertheless, in patients below the age of 40, the overall survival rates were equivalent in the two arms. In the H6 trial, the delineation of the favorable subgroup was based on (a) absence of systemic symptoms and elevated ESR, (b) no more than one or two lymph node areas involved. The aim of the study was to assess the impact on survival of a therapeutic strategy including staging laparotomy. At a 4-year follow-up, no difference in survival was evidenced. In patients with unfavorable prognostic indicators, 3 MOPP-RT-3 MOPP were compared with 3
A 6-month clinical trial in the Philippines sought to determine the efficacy of coconut oil and of "monolaurin," a coconut oil byproduct, in killing HIV by breaking down its coating. This research is based on the theory that medium-chain fatty acids, like monolaurin, can have this effect on certain viruses. The trial involves 12 women and 3 men in the early stage of HIV infection. 10 patients will take different doses of monolaurin, and 5 will consume coconut oil. It is hypothesized that the regimen will lead to higher CD4 counts and a lower viral load. The trial was almost abandoned because it received only lukewarm approval from the Health Secretary.
Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida
The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763
Demirtas, Yener; Yagmur, Caglayan; Soylemez, Fatih; Ozturk, Nuray; Demir, Ahmet
Split-thickness skin grafting (STSG) is a frequently used reconstructive technique but is associated with a large variation regarding the management of the donor site. The aim of this study is to compare five different dressings for management of the STSG donor site in a prospective trial. 100 consecutive patients, in whom reconstruction with STSG was performed, were included into the study. The grafts are harvested in a standard manner and the donor sites were dressed with one of the following materials: Aquacel® Ag, Bactigras® with Melolin®, Comfeel® Plus Transparent, Opsite® Flexigrid and Adaptic®. The materials are compared regarding to the time required for complete epithelialization, pain sensed by the patients, incidence of infection, scar formation, ease of application and the cost. The earliest complete epithelialization was observed for Aquacel® Ag and the latest for Bactigras® with Melolin®·Comfeel® Plus Transparent was the most painless dressing and Bactigras® with Melolin® was the most painful. The incidence of infection was highest for Bactigras® with Melolin®·Opsite® Flexigrid was the most economical dressing and Aquacel® Ag was the most expensive one. The aim is to provide the earliest complete epithelialization with minimal patient discomfort and lower cost in management of the STSG donor sites. None of the tested materials were ideal regarding these criteria, but Comfeel® Plus Transparent, as the least painful and one of the most economical materials, may be offered as the dressing of choice among the tested materials. Copyright © 2009 Elsevier Ltd and ISBI. All rights reserved.
Rogers, Joseph G; Boyle, Andrew J; O'Connell, John B; Horstmanshof, Douglas A; Haas, Donald C; Slaughter, Mark S; Park, Soon J; Farrar, David J; Starling, Randall C
Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. The objective of this study is to examine the impact of mechanically assisted circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration-defined criteria for treatment but are not yet receiving intravenous inotropic therapy. This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy. Copyright © 2014 Elsevier Inc. All rights reserved.
Zamłyński, Jacek; Horzelska, Ewa; Zamłyński, Mateusz; Olszak-Wąsik, Katarzyna; Nowak, Leszek; Bodzek, Piotr; Horzelski, Tomasz; Bablok, Rafał; Olejek, Anita
Myelomeningocele (MMC) is the most frequent congenital defect of the central nervous system for which there is no satisfactory alternative to postnatal treatment. On the contrary prenatal MMC surgery is conducting before birth and is aimed at protecting from Chiari II malformation. The main goal of fetal MMC repair is to improve development and life quality of children with Chiari II malformation. Management of Myelomeningocele Study (MOMS) which was published in 2011 clearly confirmed effectiveness of prenatal surgery. In this paper we compare MOMS results with our own clinical experience. Thanks to high effectiveness and significant improvement in safety of maternal-fetal surgery prenatal MMC surgery become a new standard of treatment.
Fritz, Julie M; Kim, Minchul; Magel, John S; Asche, Carl V
Economic evaluation of a randomized clinical trial. Compare costs and cost-effectiveness of usual primary care management for patients with acute low back pain (LBP) with or without the addition of early physical therapy. Low back pain is among the most common and costly conditions encountered in primary care. Early physical therapy after a new primary care consultation for acute LBP results in small clinical improvement but cost-effectiveness of a strategy of early physical therapy is unknown. Economic evaluation was conducted alongside a randomized clinical trial of patients with acute, nonspecific LBP consulting a primary care provider. All patients received usual primary care management and education, and were randomly assigned to receive four sessions of physical therapy or usual care of delaying referral consideration to permit spontaneous recovery. Data were collected in a randomized trial involving 220 participants age 18 to 60 with LBP <16 days duration without red flags or signs of nerve root compression. The EuroQoL EQ-5D health states were collected at baseline and after 1-year and used to compute the quality adjusted life year (QALY) gained. Direct (health care utilization) and indirect (work absence or reduced productivity) costs related to LBP were collected monthly and valued using standard costs. The incremental cost-effectiveness ratio was computed as incremental total costs divided by incremental QALYs. Early physical therapy resulted in higher total 1-year costs (mean difference in adjusted total costs = $580, 95% CI: $175, $984, P = 0.005) and better quality of life (mean difference in QALYs = 0.02, 95% CI: 0.005, 0.35, P = 0.008) after 1-year. The incremental cost-effectiveness ratio was $32,058 (95% CI: $10,629, $151,161) per QALY. Our results support early physical therapy as cost-effective relative to usual primary care after 1 year for patients with acute, nonspecific LBP. 2.
Palesch, Yuko Y.; Yeatts, Sharon D.; Tomsick, Thomas A; Foster, Lydia D.; Demchuk, Andrew M.; Khatri, Pooja; Hill, Michael D.; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Simpson, Annie; Simpson, Kit N.; Broderick, Joseph P.
Background and Purpose Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months but data regarding outcomes at 12 months are currently lacking. Methods We compared functional and quality of life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous (IV) tissue plasminogen activator (t-PA) followed by endovascular treatment as compared to IV t-PA alone in the Interventional Management of Stroke (IMS) III Trial. The key outcome measures were a modified Rankin Scale (mRS) score ≤ 2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure (HRQoL). Results 656 subjects with moderate to severe stroke (National Institutes of Health Stroke Scale ≥ 8) were enrolled at 58 centers in the United States (41 sites), Canada (7), Australia (4), and Europe (6). There was an interaction between treatment group and stroke severity in the repeated measures analysis of mRS ≤ 2 outcome (p=0.039). In the 204 participants with severe stroke (NIHSS ≥ 20), a greater proportion of the endovascular group had a mRS ≤ 2 (32.5%) at 12 months as compared to the IV t-PA group (18.6%, p=0.037); no difference was seen for the 452 participants with moderately-severe strokes (55.6% vs. 57.7%). In participants with severe stroke, the endovascular group had 35.2 (95% CI: 2.1, 73.3) more quality-adjusted-days over 12 months as compared to IV t-PA alone. Conclusions Endovascular therapy improves functional outcome and HRQoL at 12 months after severe ischemic stroke. PMID:25858239
Hannon, Tamara S; Dugan, Tamara M; Saha, Chandan K; McKee, Steven J; Downs, Stephen M; Carroll, Aaron E
Type 2 diabetes (T2D) is increasingly common in young individuals. Primary prevention and screening among children and adolescents who are at substantial risk for T2D are recommended, but implementation of T2D screening practices in the pediatric primary care setting is uncommon. To determine the feasibility and effectiveness of a computerized clinical decision support system to identify pediatric patients at high risk for T2D and to coordinate screening for and diagnosis of prediabetes and T2D. This cluster-randomized clinical trial included patients from 4 primary care pediatric clinics. Two clinics were randomized to the computerized clinical decision support intervention, aimed at physicians, and 2 were randomized to the control condition. Patients of interest included children, adolescents, and young adults 10 years or older. Data were collected from January 1, 2013, through December 1, 2016. Comparison of physician screening and follow-up practices after adding a T2D module to an existing computer decision support system. Electronic medical record (EMR) data from patients 10 years or older were reviewed to determine the rates at which pediatric patients were identified as having a body mass index (BMI) at or above the 85th percentile and 2 or more risk factors for T2D and underwent screening for T2D. Medical records were reviewed for 1369 eligible children (712 boys [52.0%] and 657 girls [48.0%]; median [interquartile range] age, 12.9 [11.2-15.3]), of whom 684 were randomized to the control group and 685 to the intervention group. Of these, 663 (48.4%) had a BMI at or above the 85th percentile. Five hundred sixty-five patients (41.3%) met T2D screening criteria, with no difference between control and intervention sites. The T2D module led to a significant increase in the percentage of patients undergoing screening for T2D (89 of 283 [31.4%] vs 26 of 282 [9.2%]; adjusted odds ratio, 4.6; 95% CI, 1.5-14.7) and a greater proportion attending a scheduled follow
Over the past decades, randomised controlled trials (RCTs) have prevailed over clinical judgement, case reports, and observational studies and became the gold evidential standard in medicine. Furthermore, during the same time frame, RCTs became a crucial part of the regulatory process whereby a new therapeutic can gain access to the drug market. Today, clinical trials are large and tightly regulated enterprises that have to comply with ethical requirements while maintaining high epistemic standards, a balance that becomes increasingly difficult as the research questions become more sophisticated. In this review, the author will discuss some of the most important ethical issues surrounding RCTs, with an eye to the most recent debates and the context of oncological research in particular. PMID:24482672
Swanson, Barbara; Keithley, Joyce K.; Sha, Beverly E.; Fogg, Louis; Nerad, Judith; Novak, Richard M.; Adeyemi, Oluwatoyin; Spear, Gregory T.
Background Human immunodeficiency virus (HIV) infection is associated with dyslipidemia and increased risk for cardiovascular events; however, the use of statins in HIV-infected people is complicated by pharmacokinetic interactions and overlapping toxicities with antiretroviral medications. Policosanol is a dietary supplement derived from sugar cane that is widely used as a statin alternative in Latin America. Primary Study Objective To collect feasibility data on sugar cane–derived policosanol to normalize dyslipidemic profiles in a sample of medically underserved HIV-infected people. Methods/design Randomized, controlled, double-blind clinical trial. Setting Two infectious disease outpatient clinics located in a Health Resources Service Administration–designated medically underserved neighborhood in Chicago, Illinois. Participants Fifty-four clinically stable HIV-infected people (91% black) with at least one lipid abnormality that warranted dietary modifications and/or drug therapy. Intervention Participants received either 20 mg/day of policosanol or placebo for 12 weeks, followed by a 4-week washout and crossover to the other arm. Primary Outcome Measures Efficacy measures included the standard lipid panel (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides) and nuclear magnetic resonance (NMR)–derived lipoprotein particle profiles. Safety measures included CD4+ T lymphocyte counts, plasma HIV ribonucleic acid levels, serum creatinine, and liver function tests. Results Policosanol supplementation was not associated with normalization of any dyslipidemic parameters as measured by the standard lipid panel or NMR spectroscopy–measured lipoprotein size or concentration. The supplement was well tolerated and was not associated with any changes in parameters of HIV disease progression. Conclusions Our findings corroborate recent studies conducted outside Cuba that have failed to find any lipid modulatory effects for
Shen, Tong; Liu, Yan
With worldwide improvements in the regulations of international and domestic clinical trial conductions, the quality of clinical trials and trial data management are receiving a great deal of attention. To ensure the quality of clinical trials, maintain business flexibilities and effectively utilize internal and external resources, the outsourcing model is used in the management of clinical data in operation of pharmaceutical companies. The essential criteria of a successful outsourcing mode in clinical trial are selection of qualified contract research organizations (CRO); establishment of appropriate outsourcing model, and generation of effective quality control systems to ensure the authenticity, integrity and accuracy of the clinical trial data.
Stewart, Simon; Carrington, Melinda J; Horowitz, John D; Marwick, Thomas H; Newton, Phillip J; Davidson, Patricia M; Macdonald, Peter; Thompson, David R; Chan, Yih-Kai; Krum, Henry; Reid, Christopher; Scuffham, Paul A
We compared the longer-term impact of the two most commonly applied forms of post-discharge management designed to minimize recurrent hospitalization and prolong survival in typically older patients with chronic heart failure (CHF). We followed a multi-center randomized controlled trial cohort of Australian patients hospitalized with CHF and initially allocated to home-based or specialized CHF clinic-based intervention for 1368 ± 216 days. Blinded endpoints included event-free survival from all-cause emergency hospitalization or death, all-cause mortality and rate of all-cause hospitalization and stay. 280 patients (73% male, aged 71 ± 14 years and 73% left ventricular systolic dysfunction) were initially randomized to home-based (n=143) or clinic-based (n=137) intervention. During extended follow-up (complete for 274 patients), 1139 all-cause hospitalizations (7477 days of hospital stay) and 121 (43.2%) deaths occurred. There was no difference in the primary endpoint; 20 (14.0%) home-based versus 13 (7.4%) clinic-based patients remained event-free (adjusted HR 0.89, 95% CI 0.70 to 1.15; p=0.378). Significantly fewer home-based (51/143, 35.7%) than clinic-based intervention (71/137, 51.8%) patients died (adjusted HR 0.62, 95% CI 0.42 to 0.90: p=0.012). Home-based versus clinic-based intervention patients accumulated 592 and 547 all-cause hospitalizations (p=0.087) associated with 3067 (median 4.0, IQR 2.0 to 6.8) versus 4410 (6.0, IQR 3.0 to 12.0) days of hospital stay (p<0.01 for rate and duration of hospital stay). Relative to clinic-based intervention, home-based intervention was not associated with prolonged event-free survival. Home-based intervention was, however, associated with significantly fewer all-cause deaths and significantly fewer days of hospital stay in the longer-term. Australian New Zealand Clinical Trials Registry number 12607000069459 (http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81803). Copyright © 2013 Elsevier Ireland
Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven
To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding
NARAYAN, RAJ K.; MICHEL, MARY ELLEN; Ansell, Beth; Baethmann, Alex; Biegon, Anat; Bracken, Michael B.; Bullock, M. Ross; Choi, Sung C.; Clifton, Guy L.; Contant, Charles F.; Coplin, William M.; Dietrich, W. Dalton; Ghajar, Jamshid; Grady, Sean M.; Grossman, Robert G.; Hall, Edward D.; Heetderks, William; Hovda, David A.; Jallo, Jack; Katz, Russell L.; Knoller, Nachshon; Kochanek, Patrick M.; Maas, Andrew I.; Majde, Jeannine; Marion, Donald W.; Marmarou, Anthony; Marshall, Lawrence F.; McIntosh, Tracy K.; Miller, Emmy; Mohberg, Noel; Muizelaar, J. Paul; Pitts, Lawrence H.; Quinn, Peter; Riesenfeld, Gad; Robertson, Claudia S.; Strauss, Kenneth I.; Teasdale, Graham; Temkin, Nancy; Tuma, Ronald; Wade, Charles; Walker, Michael D.; Weinrich, Michael; Whyte, John; Wilberger, Jack; Young, A. Byron; Yurkewicz, Lorraine
Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research. PMID:12042091
Summary HPP is a rare disease that manifests in different ways across the life course. Accurate diagnosis depends upon the use of appropriate age-related normative data. A new therapy is undergoing clinical trials; the preliminary published data is encouraging, but the scope of clinical application remains to be determined. PMID:26604944
Ell, Kathleen; Aranda, María P; Wu, Shinyi; Oh, Hyunsung; Lee, Pey-Jiuan; Guterman, Jeffrey
The study evaluated depression and self-care management among patients with diabetes and/or heart disease in a 12-month randomized trial conducted in Los Angeles County Department of Health Services (LAC-DHS) community clinics. We compared LAC-DHS clinic usual care (UC) versus A-Helping-Hand (AHH) intervention in which bilingual promotoras, hired and supervised by the research project, provided 6 weekly psychoeducational sessions followed by boosters. Of 1957 screened, 348 depressed patients (PHQ-9 score≥10) were enrolled, randomized to AHH (n=178) or UC (n=170) after baseline interview assessing mental health, treatment receipt, co-morbid illness, self-care management, and environmental stressors. Comprehensive assessments were repeated at 6 and 12months by an independent interviewer blind to the study group. Patients (85% diabetes, 4% heart disease, 11% both) were predominantly female (85%), Latino (99%), born outside of the US (91%). Study attrition at 12months was 30% (AHH 31%, UC 28%, P=0.51). No baseline characteristics were associated with attrition. Half of AHH patients received 4 or more sessions. Intend-to-treat analysis found study groups did not vary significantly at 6 and 12months. Before-after paired t-tests showed significant improvements in most measures in each group. During the trial, LAC-DHS activated healthcare improvements including depression screening, referral to clinic staff including community health workers (with the same role as the promotoras) to improve patient care management. Both patient groups performed equally well which may be a function of the enhanced healthcare model. Future research should replicate the promotora-integrated care model with other groups and care settings with similar comorbid conditions. Copyright © 2017 Elsevier Inc. All rights reserved.
Refolo, P; Sacchini, D; Minacori, R; Spagnolo, A G
Recruiting patients is a critical point of today's clinical research and, along the years, several solutions have been proposed, even if their efficacy seems to be doubtful. On the other hand, nowadays, Internet represents a great opportunity for improving clinical trial recruitments. Nevertheless, on-line recruitment services (e-recruitment) could ensure some advantages (such as facilitating interaction between supply and demand of clinical research, time and money savings/optimizations, data entry errors reduction), but also raise some issues (such as those related to sampling, information, consent, real identity of participants and risks for data breaches). The article debates on the difficulties to recruit patients for clinical research, in general, and e-recruitment particularly, discussing some ethical issues raised by internet enrolment.
Patil, Rajan R
The Indian Council of Medical Research had, on May 31, 2011, called for research proposals on severely acute malnourished (SAM) children to generate evidence for the development of practical and scalable regimens to medically rehabilitate children suffering from SAM, without serious complications, at the home/community level and/or peripheral inpatient facilities. The primary outcomes of the proposed research study are recovery from SAM in the short term, as well as sustenance of recovery (for at least six months after the initiation of treatment). The secondary outcomes are the acceptability, feasibility and safety of the regimes being tested. It was suggested that the studies be designed as individual or cluster randomised or quasi randomised controlled trials (RCTs). This paper analyses the methodological, operational, and most importantly, ethical challenges and implications of conducting community-based RCTs involving SAM children. The paper dwells in detail on why and how the RCT design is inappropriate and unsuitable for studying the effectiveness of home-based management of SAM children in the community.
Federman, Alex D; Martynenko, Melissa; O'Conor, Rachel; Kannry, Joseph; Karp, Adam; Lurio, Joseph; Hoy-Rosas, Jamillah; Lopez, Ray; Obiapi, Rosemary; Young, Edwin; Wolf, Michael S; Wisnivesky, Juan P
Older adults with asthma face numerous barriers to effective self-management and asthma control, and experience worse outcomes than younger asthmatics. Yet, there have been no controlled trials of interventions specifically designed to improve their care and outcomes. Through a multi-stakeholder collaboration (patients, academia, community-based organizations, a state department of health, and an advocacy organization) we developed a multi-component asthma self-management support intervention to address the myriad psychosocial, functional, health status, and cognitive barriers to effective asthma self-management in adults ages 60 and older. We are recruiting 425 New Yorkers in Manhattan and the Bronx for a pragmatic randomized controlled trial with 3 arms: the intervention delivered in primary care settings or in their home, or usual care. In the intervention, care coaches use a novel screening tool to identify the specific barriers to asthma control and self-management they experience. Once identified, the coach and patient choose from a menu of actions to address it. The intervention emphasizes efficiency, flexibility, shared decision making and goal setting, communication strategies appropriate for individuals with limited cognition and literacy skills, and ongoing reinforcement and support. Additionally, we introduced asthma-specific enhancements to the electronic health records of all participating clinical practices, including an asthma severity assessment, clinical decision support, and a patient-tailored asthma action plan. Patients will be followed for 12months and interviewed at baseline, 3, 6, and 12months and data on emergency department visits and hospitalizations will be obtained through the New York State Statewide Planning and Research Cooperative System. Copyright © 2015 Elsevier Inc. All rights reserved.
Elbourne, Diana; Dezateux, Carol; Arthur, Rosemary; Clarke, N M P; Gray, Alastair; King, Andy; Quinn, Anne; Gardner, Frances; Russell, Glynn
Clinical screening aims to identify and treat neonatal hip instability associated with increased risk of hip displacement, but risks failures of diagnosis and treatment (abduction splinting), iatrogenic effects, and costs to parents and health services. Our objectives were to assess clinical effectiveness and net cost of ultrasonography compared with clinical assessment alone, to provide guidance for management of infants with clinical hip instability. Infants with clinical hip instability were recruited from 33 centres in UK and Ireland and randomised to either ultrasonographic hip examination (n=314) or clinical assessment alone (n=315). The primary outcome was appearance on hip radiographs by 2 years. Secondary outcomes included surgical treatment, abduction splinting, level of mobility, resource use, and costs. Analysis was by intention to treat. Protocol compliance was high, and radiographic information was available for 91% of children by 12-14 months and 85% by 2 years. By age 2 years, subluxation, dislocation, or acetabular dysplasia were identified by radiography on one or both hips of 21 children in each of the groups (relative risk 1.00; 95% CI 0.56-1.80). Fewer children in the ultrasonography group had abduction splinting in the first 2 years than did those in the no-ultrasonography group (0.78; 0.65-0.94; p=0.01). Surgical treatment was required by 21 infants in the ultrasonography group (6.7%) and 25 (7.9%) in the no-ultrasonography group (0.84; 0.48-1.47). One child from the ultrasonography group and four from the no-ultrasonography group were not walking by 2 years (0.25; 0.03-2.53; p=0.37). Infants in the ultrasonography group incurred significantly higher ultrasound costs over the first 2 years (pound 42 vs pound 23, mean difference pound 19, 95% CI 11-27); total hospital costs were lower for those infants, but the difference was not significant. The use of ultrasonography in infants with screen-detected clinical hip instability allows abduction
Zhang, Xiu-lai; Chen, Meng; Zhu, Ling-ling
Despite increased awareness of the potential of herb-drug interactions (HDIs), the lack of rigorous clinical evidence regarding the significance provides a challenge for clinicians and consumers to make rational decisions about the safe combination of herbal and conventional medicines. This review addressed HDIs based on evidence from randomized controlled trials (RCTs). Literature was identified by performing a PubMed search till January 2017. Risk description and clinical risk management were described. Among 74 finally included RCTs, 17 RCTs (22.97%) simply addressed pharmacodynamic HDIs. Fifty-seven RCTs (77.03%) investigated pharmacokinetic HDIs and twenty-eight of them showed potential or actual clinical relevance. The extent of an HDI may be associated with the factors such as pharmacogenomics, dose of active ingredients in herbs, time course of interaction, characteristics of the object drugs (e.g., administration routes and pharmacokinetic profiles), modification of herbal prescription compositions, and coexistence of inducers and inhibitors. Clinical professionals should enhance risk management on HDIs such as increasing awareness of potential changes in therapeutic risk and benefits, inquiring patients about all currently used conventional medicines and herbal medicines and supplements, automatically detecting highly substantial significant HDI by computerized reminder system, selecting the alternatives, adjusting dose, reviewing the appropriateness of physician orders, educating patients to monitor for drug-interaction symptoms, and paying attention to follow-up visit and consultation. PMID:28491115
To make clinicians aware of potential sources of error in ophthalmic pharmaceutical clinical trials that can lead to erroneous interpretation of results, a critical review of the study design of various pharmaceutical ophthalmic clinical trials was completed. Discrepancies as a result of study shortcomings may explain observed differences between reported ophthalmic trial data and observed clinical results. PMID:19668731
Charrois, Theresa L; McAlister, Finlay A; Cooney, Dale; Lewanczuk, Richard; Kolber, Michael R; Campbell, Norman Rc; Rosenthal, Meagen; Houle, Sherilyn Kd; Tsuyuki, Ross T
Patients with hypertension continue to have less than optimal blood pressure control, with nearly one in five Canadian adults having hypertension. Pharmacist prescribing is gaining favor as a potential clinically efficacious and cost-effective means to improve both access and quality of care. With Alberta being the first province in Canada to have independent prescribing by pharmacists, it offers a unique opportunity to evaluate outcomes in patients who are prescribed antihypertensive therapy by pharmacists. The study is a randomized controlled trial of enhanced pharmacist care, with the unit of randomization being the patient. Participants will be randomized to enhanced pharmacist care (patient identification, assessment, education, close follow-up, and prescribing/titration of antihypertensive medications) or usual care. Participants are patients in rural Alberta with undiagnosed/uncontrolled blood pressure, as defined by the Canadian Hypertension Education Program. The primary outcome is the change in systolic blood pressure between baseline and 24 weeks in the enhanced-care versus usual-care arms. There are also three substudies running in conjunction with the project examining different remuneration models, investigating patient knowledge, and assessing health-resource utilization amongst patients in each group. To date, one-third of the required sample size has been recruited. There are 15 communities and 17 pharmacists actively screening, recruiting, and following patients. This study will provide high-level evidence regarding pharmacist prescribing. Clinicaltrials.gov NCT00878566.
Pendleton, A; Arden, N; Dougados, M; Doherty, M; Bannwarth, B; Bijlsma, J; Cluzeau, F; Cooper, C; Dieppe, P; Gunther, K; Hauselmann, H; Herrero-Beaumont, G; Kaklamanis, P; Leeb, B; Lequesne, M; Lohmander, S; Mazieres, B; Mola, E; Pavelka, K; Serni, U; Swoboda, B; Verbruggen, A; Weseloh, G; Zimmermann-Gorska, I
BACKGROUND—Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in 1998 to determine the methodological and logistical approach required for the development of evidence based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. METHODS—The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and keywords. All European language publications in the form of systematic reviews, meta-analyses, randomised controlled trials, controlled trials, and observational studies were included. During stage three all the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and, where practical, the numbers needed to treat and the effect size for each treatment were calculated. In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach. The final stage ranked these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. RESULTS—Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. CONCLUSIONS—These are the first clinical guidelines on knee
Cai, Tommaso; Verze, Paolo; La Rocca, Roberto; Anceschi, Umberto; De Nunzio, Cosimo; Mirone, Vincenzo
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still a challenge to manage for all physicians. We feel that a summary of the current literature and a systematic review to evaluate the therapeutic efficacy of flower pollen extract would be helpful for physicians who are considering a phytotherapeutic approach to treating patients with CP/CPPS. A comprehensive search of the PubMed and Embase databases up to June 2016 was performed. This comprehensive analysis included both pre-clinical and clinical trials on the role of flower pollen extract in CP/CPPS patients. Moreover, a meta-analysis of available randomized controlled trials (RCTs) was performed. The NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and Quality of Life related questionnaires (QoL) were the most commonly used tools to evaluate the therapeutic efficacy of pollen extract. Pre-clinical studies demonstrated the anti-inflammatory and anti-proliferative role of pollen extract. 6 clinical, non-controlled studies including 206 patients, and 4 RCTs including 384 patients were conducted. The mean response rate in non-controlled studies was 83.6% (62.2%-96.0%). The meta-analysis revealed that flower pollen extract could significantly improve patients' quality of life [OR 0.52 (0.34-.0.81); p = 0.02]. No significant adverse events were reported. Most of these studies presented encouraging results in terms of variations in NIH-CPSI and QoL scores. These studies suggest that the use of flower pollen extract for the management of CP/CPPS patients is beneficial. Future publications of robust evidence from additional RCTs and longer-term follow-up would provide more support encouraging the use of flower pollen extracts for CP/CPPS patients.
Featherstone, J.D.B.; White, J.M; Hoover, C.I.; Rapozo-Hilo, M.; Weintraub, J.A.; Wilson, R.S.; Zhan, L.; Gansky, S.A.
This randomized parallel group clinical trial assessed whether combined antibacterial and fluoride therapy benefits the balance between caries pathological and protective factors. Eligible, enrolled adults (n = 231), with 1–7 baseline cavitated teeth, attending a dental school clinic were randomly assigned to a control or intervention group. Salivary mutans streptococci (MS), lactobacilli (LB), fluoride (F) level, and resulting caries risk status (low or high) assays were determined at baseline and every 6 months. After baseline, all cavitated teeth were restored. An examiner masked to group conducted caries exams at baseline and 2 years after completing restorations. The intervention group used fluoride dentifrice (1,100 ppm F as NaF), 0.12% chlorhexidine gluconate rinse based upon bacterial challenge (MS and LB), and 0.05% NaF rinse based upon salivary F. For the primary outcome, mean caries increment, no statistically significant difference was observed (24% difference between control and intervention groups, p = 0.101). However, the supplemental adjusted zero-inflated Poisson caries increment (change in DMFS) model showed the intervention group had a statistically significantly 24% lower mean than the control group (p = 0.020). Overall, caries risk reduced significantly in intervention versus control over 2 years (baseline adjusted generalized linear mixed models odds ratio, aOR = 3.45; 95% CI: 1.67, 7.13). Change in MS bacterial challenge differed significantly between groups (aOR = 6.70; 95% CI: 2.96, 15.13) but not for LB or F. Targeted antibacterial and fluoride therapy based on salivary microbial and fluoride levels favorably altered the balance between pathological and protective caries risk factors. PMID:22472515
Background Psychological treatments have been successful in treating chronic low back pain (CLBP). However, the effect sizes are still modest and there is room for improvement. A way to progress is by enhancing treatment adherence and self-management using information and communication technologies (ICTs). Therefore, the objective of this study was to design a trial investigating the short- and long-term efficacy of cognitive behavioural treatment (CBT) for CLBP using or not ICTs. A secondary objective of this trial will be to evaluate the influence of relevant variables on treatment response. Possible barriers in the implementation of CBT with and without ICT will also be investigated. Methods A randomised controlled trial with 180 CLBP patients recruited from specialised care will be conducted. Participants will be randomly assigned to three conditions: Control group (CG), CBT, and CBT supported by ICTs (CBT + ICT). Participants belonging to the three conditions will receive a conventional rehabilitation program (back school). The CBT group program will last six sessions. The CBT + ICT group will use the internet and SMS to practice the therapeutic strategies between sessions and in the follow-ups at their homes. Primary outcome variables will be self-reported disability and pain intensity. Assessment will be carried out by blinded assessors in five moments: pre-treatment, post-treatment and 3-, 6-, and 12-month follow-ups. The influence of catastrophizing, fear-avoidance beliefs, anxiety and depression in response to treatment in the primary outcomes will also be analysed. Discussion This study will show data of the possible benefits of using ICTs in the improvement of CBT for treating CLBP. Trial registration ClinicalTrials.gov, NCT01802671 PMID:23607895
Gómez-Arámbula, Hansel; Hidalgo-Hurtado, Antonio; Rodríguez-Flores, Rosaura; González-Amaro, Ana-María; Garrocho-Rangel, Arturo
Background The aim of this study was to compare the days of hospitalization length between patients treated with Moxifloxacin with that of patients treated with a Clindamycin/Ceftriaxone combination and additionally, to isolate and identify the oral pathogens involved in orofacial odontogenic infections. Material and Methods A pilot-controlled-clinical-trial was carried out on hospitalized patients with cervicofacial odontogenic abscesses or cellulitis, who were randomly asigned to two study groups: 1) patients who received Moxifloxacin, and 2) patients receiving Clindamycin/Ceftriaxone combination. Infiltrate samples were collected through transdermic or transmucosal punction and later cultured on a media specific for aerobic and anaerobic microorganisms. Mean hospitalization duration in days until hospital discharge and susceptibility assessment in rates were established. Results Mean hospitalization time in days of patients treated with Moxifloxacin was 7.0 ± 1.6 days, while in the Clindamycin/Ceftriaxone group, this was 8.4 ± 1.8 days, although significant difference could not be demonstrated (p=0.074). A total of 43 strains were isolated, all of these Gram-positive. These strains appeared to be highly sensitive to Moxifloxacin (97.5%) and Ceftriaxone (92.5%). Conclusions Moxifloxacin and Ceftriaxone appear to be potential convenient and rational alternatives to traditional antibiotics, for treating severe odontogenic infections, in conjunction with surgical extraoral incision, debridement, and drainage. Key words:Orofacial odontogenic infections, antimicrobial susceptibility, antimicrobial resistance. PMID:26644841
Wirz, Stefan; Wartenberg, Hans Christian; Elsen, Christian; Wittmann, Maria; Diederichs, Marta; Nadstawek, Joachim
In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical Rating Scales (NRS)], or as categorical parameters, and analyzed by descriptive and confirmatory statistics (ANOVA, Wilcoxon, chi). Rotation was successful in 64% of patients experiencing pain (60%), and gastrointestinal (32%) and central (26%) symptoms under oral morphine (38%), transdermal fentanyl (22%), tramadol (20%), oxycodone (12%), or sublingual buprenorphine (8%). NRS of pain (4.1 to 3.2; P=0.015), gastrointestinal symptoms, especially defecation rates (P=0.04), and incidence of insomnia improved after an increase in morphine-equivalent doses from 108.9 to 137.6 mg/d without modifying concomitant analgesics or coanalgesics. Switching the opioid to oral hydromorphone may be a helpful technique to alleviate pain and several symptoms, but it is still not clear to what extent the underlying mechanisms, such as the technique of rotation itself, better dose adjustment, or using a different opioid have an impact.
Azadbakht, Leila; Haghighatdoost, Fahimeh; Karimi, Golgis; Esmaillzadeh, Ahmad
Few investigations reported the reductive effect of preload consuming on energy intake. The objective of the study was to compare the effects of consuming a mix of low glycaemic index foods such as vegetable salad, yogurt and water before or with meal on anthropometric measures and cardio vascular diseases (CVD) risks. In this randomized controlled clinical trial, 25 men and 35 women were recruited to consume similar amounts of macronutrients within a hypocaloric diet for 3 months. Although subjects in the preload group consumed preload 15 min before the main meal, subjects in the control group consumed them with meal. The results showed that body weight, waist circumference, triglyceride, total cholesterol and systolic blood pressure decreased in more amount in the preload group ( - 7.8 ± 0.5%, - 2.7 ± 0.2%, - 5.7 ± 1.1%, - 3.1 ± 0.53% and - 4.4 ± 0.4%, respectively; p < 0.05 for all). Fasting blood sugar and low density lipoprotein (LDL)-cholesterol decreased significantly only in the preload group. Consuming vegetable salad, yogurt and water as preload leads to greater changes in anthropometric measures and CVD risks.
Sadler, G R; Lantz, J M; Fullerton, J T; Dault, Y
Nurses are in an ideal position to promote patients' awareness of the role played by clinical trials in the advancement of health science and the subsequent improvement of patient care. The history of clinical trials and the four phases of clinical trials are described. Nurses' professional roles in clinical trial participation, such as helping the patient to identify open clinical trials and acting as clinical interpreter and patient advocate during the patient's participation in a trial, are detailed. Professional considerations that must be addressed by the nurse are reviewed and include ensuring that the trial has received approval from an Institutional Review Board for the participation of human subjects; that the responsibilities of participation are congruent with the nurse's personal values and workplace obligations; and that once engaged, the nurse can make the commitment to sustain participation in the trial. Most important, the nurse must keep the patient's needs and values uppermost in mind during the evaluation of potential clinical trials. Nurses have a critical role to play in the promotion of clinical trials, the recruitment of patients for clinical trial participation, the education of the patient and family, and the clinical care and support of patients throughout their participation in clinical trials.
Downe, S; Finlayson, K; Melvin, C; Spiby, H; Ali, S; Diggle, P; Gyte, G; Hinder, S; Miller, V; Slade, P; Trepel, D; Weeks, A; Whorwell, P; Williamson, M
Objective (Primary) To establish the effect of antenatal group self-hypnosis for nulliparous women on intra-partum epidural use. Design Multi-method randomised control trial (RCT). Setting Three NHS Trusts. Population Nulliparous women not planning elective caesarean, without medication for hypertension and without psychological illness. Methods Randomisation at 28–32 weeks’ gestation to usual care, or to usual care plus brief self-hypnosis training (two × 90-minute groups at around 32 and 35 weeks’ gestation; daily audio self-hypnosis CD). Follow up at 2 and 6 weeks postnatal. Main outcome measures Primary: epidural analgesia. Secondary: associated clinical and psychological outcomes; cost analysis. Results Six hundred and eighty women were randomised. There was no statistically significant difference in epidural use: 27.9% (intervention), 30.3% (control), odds ratio (OR) 0.89 [95% confidence interval (CI): 0.64–1.24], or in 27 of 29 pre-specified secondary clinical and psychological outcomes. Women in the intervention group had lower actual than anticipated levels of fear and anxiety between baseline and 2 weeks post natal (anxiety: mean difference −0.72, 95% CI −1.16 to −0.28, P = 0.001); fear (mean difference −0.62, 95% CI −1.08 to −0.16, P = 0.009) [Correction added on 7 July 2015, after first online publication: ‘Mean difference’ replaced ‘Odds ratio (OR)’ in the preceding sentence.]. Postnatal response rates were 67% overall at 2 weeks. The additional cost in the intervention arm per woman was £4.83 (CI −£257.93 to £267.59). Conclusions Allocation to two-third-trimester group self-hypnosis training sessions did not significantly reduce intra-partum epidural analgesia use or a range of other clinical and psychological variables. The impact of women's anxiety and fear about childbirth needs further investigation. Tweetable abstract Going to 2 prenatal self-hypnosis groups didn't reduce labour epidural use but did
Downe, S; Finlayson, K; Melvin, C; Spiby, H; Ali, S; Diggle, P; Gyte, G; Hinder, S; Miller, V; Slade, P; Trepel, D; Weeks, A; Whorwell, P; Williamson, M
(Primary) To establish the effect of antenatal group self-hypnosis for nulliparous women on intra-partum epidural use. Multi-method randomised control trial (RCT). Three NHS Trusts. Nulliparous women not planning elective caesarean, without medication for hypertension and without psychological illness. Randomisation at 28-32 weeks' gestation to usual care, or to usual care plus brief self-hypnosis training (two × 90-minute groups at around 32 and 35 weeks' gestation; daily audio self-hypnosis CD). Follow up at 2 and 6 weeks postnatal. Primary: epidural analgesia. Secondary: associated clinical and psychological outcomes; cost analysis. Six hundred and eighty women were randomised. There was no statistically significant difference in epidural use: 27.9% (intervention), 30.3% (control), odds ratio (OR) 0.89 [95% confidence interval (CI): 0.64-1.24], or in 27 of 29 pre-specified secondary clinical and psychological outcomes. Women in the intervention group had lower actual than anticipated levels of fear and anxiety between baseline and 2 weeks post natal (anxiety: mean difference -0.72, 95% CI -1.16 to -0.28, P = 0.001); fear (mean difference -0.62, 95% CI -1.08 to -0.16, P = 0.009) [Correction added on 7 July 2015, after first online publication: 'Mean difference' replaced 'Odds ratio (OR)' in the preceding sentence.]. Postnatal response rates were 67% overall at 2 weeks. The additional cost in the intervention arm per woman was £4.83 (CI -£257.93 to £267.59). Allocation to two-third-trimester group self-hypnosis training sessions did not significantly reduce intra-partum epidural analgesia use or a range of other clinical and psychological variables. The impact of women's anxiety and fear about childbirth needs further investigation. © 2015 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
Roukema, Jolt; Steyerberg, Ewout W; van der Lei, Johan; Moll, Henriëtte A
To assess compliance with a clinical decision support system (CDSS) for diagnostic management of children with fever without apparent source and to study the effects of application of the CDSS on time spent in the emergency department (ED) and number of laboratory tests. The CDSS was used by ED nursing staff to register children presenting with fever. The CDSS identified children that met inclusion criteria (1-36 months and fever without apparent source (FWS)) and provided patient-specific diagnostic management advice. Children at high risk for serious bacterial infection were randomized for the 'intervention' (n = 74) or the 'control' (n = 90) group. In the intervention group, the CDSS provided the advice to immediately order laboratory tests and in the control group the ED physician first assessed the children and then decided on ordering laboratory tests. Compliance with registration of febrile children was 50% (683/1,399). Adherence to the advice to order laboratory tests was 82% (61/74). Children in the intervention group had a median (25(th)-75(th) percentile) length of stay at the ED of 138 (104-181) minutes. The median length of stay at the ED in the control group was 123 (83-179) minutes. Laboratory tests were significantly more frequently ordered in the intervention group (82%) than in the control group (44%, p < 0.001, chi(2) test). Implementation of a CDSS for diagnostic management of young children with fever without apparent source was successful regarding compliance and adherence to CDSS recommendations, but had unexpected effects on patient outcome in terms of ED length of stay and number of laboratory tests. The use of the current CDSS was discontinued.
Webster, Joan; Bucknall, Tracey; Wallis, Marianne; McInnes, Elizabeth; Roberts, Shelley; Chaboyer, Wendy
Participation in a clinical trial is believed to benefit patients but little is known about the post-trial effects on routine hospital-based care. To describe (1) hospital-based, pressure ulcer care-processes after patients were discharged from a pressure ulcer prevention, cluster randomised controlled trial; and (2) to investigate if the trial intervention had any impact on subsequent hospital-based care. We conducted a retrospective analysis of 133 trial participants who developed a pressure ulcer during the clinical trial. We compared outcomes and care processes between participants who received the pressure ulcer prevention intervention and those in the usual care, control group. We also compared care processes according to the pressure ulcer stage. A repositioning schedule was reported for 19 (14.3%) patients; 33 (24.8%) had a dressing applied to the pressure ulcer; 17 (12.8) patients were assessed by a wound care team; and 20 (15.0%) were seen by an occupational therapist. Patients in the trial's intervention group were more likely to have the presence of a pressure ulcer documented in their chart (odds ratio (OR) 8.18, 95% confidence intervals (CI) 3.64-18.36); to be referred to an occupational therapist OR 0.92 (95% CI 0.07; 0.54); to receive a pressure relieving device OR 0.31 (95% CI 0.14; 0.69); or a pressure relieving mattress OR 0.44 (95% CI 0.20; 0.96). Participants with Stage 2 or unstageable ulcers were more likely than others to have dressings applied to their wounds (p=<0.001) and to be referred to an occupational therapist for protective devices (p=0.022). Participants in the intervention group of a clinical trial were more likely to receive additional post trial care and improved documentation compared with those in the control group but documentation of pressure ulcer status and care is poor. Copyright © 2017 Elsevier Ltd. All rights reserved.
An embedded longitudinal multi-faceted qualitative evaluation of a complex cluster randomized controlled trial aiming to reduce clinically important errors in medicines management in general practice.
Cresswell, Kathrin M; Sadler, Stacey; Rodgers, Sarah; Avery, Anthony; Cantrill, Judith; Murray, Scott A; Sheikh, Aziz
There is a need to shed light on the pathways through which complex interventions mediate their effects in order to enable critical reflection on their transferability. We sought to explore and understand key stakeholder accounts of the acceptability, likely impact and strategies for optimizing and rolling-out a successful pharmacist-led information technology-enabled (PINCER) intervention, which substantially reduced the risk of clinically important errors in medicines management in primary care. Data were collected at two geographical locations in central England through a combination of one-to-one longitudinal semi-structured telephone interviews (one at the beginning of the trial and another when the trial was well underway), relevant documents, and focus group discussions following delivery of the PINCER intervention. Participants included PINCER pharmacists, general practice staff, researchers involved in the running of the trial, and primary care trust staff. PINCER pharmacists were interviewed at three different time-points during the delivery of the PINCER intervention. Analysis was thematic with diffusion of innovation theory providing a theoretical framework. We conducted 52 semi-structured telephone interviews and six focus group discussions with 30 additional participants. In addition, documentary data were collected from six pharmacist diaries, along with notes from four meetings of the PINCER pharmacists and feedback meetings from 34 practices. Key findings that helped to explain the success of the PINCER intervention included the perceived importance of focusing on prescribing errors to all stakeholders, and the credibility and appropriateness of a pharmacist-led intervention to address these shortcomings. Central to this was the face-to-face contact and relationship building between pharmacists and a range of practice staff, and pharmacists' explicitly designated role as a change agent. However, important concerns were identified about the likely
Background There is a need to shed light on the pathways through which complex interventions mediate their effects in order to enable critical reflection on their transferability. We sought to explore and understand key stakeholder accounts of the acceptability, likely impact and strategies for optimizing and rolling-out a successful pharmacist-led information technology-enabled (PINCER) intervention, which substantially reduced the risk of clinically important errors in medicines management in primary care. Methods Data were collected at two geographical locations in central England through a combination of one-to-one longitudinal semi-structured telephone interviews (one at the beginning of the trial and another when the trial was well underway), relevant documents, and focus group discussions following delivery of the PINCER intervention. Participants included PINCER pharmacists, general practice staff, researchers involved in the running of the trial, and primary care trust staff. PINCER pharmacists were interviewed at three different time-points during the delivery of the PINCER intervention. Analysis was thematic with diffusion of innovation theory providing a theoretical framework. Results We conducted 52 semi-structured telephone interviews and six focus group discussions with 30 additional participants. In addition, documentary data were collected from six pharmacist diaries, along with notes from four meetings of the PINCER pharmacists and feedback meetings from 34 practices. Key findings that helped to explain the success of the PINCER intervention included the perceived importance of focusing on prescribing errors to all stakeholders, and the credibility and appropriateness of a pharmacist-led intervention to address these shortcomings. Central to this was the face-to-face contact and relationship building between pharmacists and a range of practice staff, and pharmacists’ explicitly designated role as a change agent. However, important concerns were
Chappell, Lucy C; Gurung, Vinita; Seed, Paul T; Chambers, Jenny; Williamson, Catherine
Objectives To test whether ursodeoxycholic acid reduces pruritus in women with intrahepatic cholestasis of pregnancy, whether early term delivery does not increase the incidence of caesarean section, and the feasibility of recruiting women with intrahepatic cholestasis of pregnancy to trials of these interventions. Design First phase of a semifactorial randomised controlled trial. Setting Nine consultant led maternity units, United Kingdom. Participants 125 women with intrahepatic cholestasis of pregnancy (pruritus and raised levels of serum bile acids) or pruritus and raised alanine transaminase levels (>100 IU/L) recruited after 24 weeks’ gestation and followed until delivery. 56 women were randomised to ursodeoxycholic acid, 55 to placebo, 30 to early term delivery, and 32 to expectant management. Interventions Ursodeoxycholic acid 500 mg twice daily or placebo increased as necessary for symptomatic or biochemical improvement until delivery; early term delivery (induction or delivery started between 37+0 and 37+6) or expectant management (spontaneous labour awaited until 40 weeks’ gestation or caesarean section undertaken by normal obstetric guidelines, usually after 39 weeks’ gestation). Main outcome measures The primary outcome for ursodeoxycholic acid was maternal itch (arithmetic mean of measures (100 mm visual analogue scale) of worst itch in past 24 hours) and for the timing of delivery was caesarean section. Secondary outcomes were other maternal and perinatal outcomes and recruitment rates. Results Ursodeoxycholic acid reduced itching by −16 mm (95% confidence interval −27 mm to −6 mm), less than the 30 mm difference prespecified by clinicians and women as clinically meaningful. 32% (14/44) of women randomised to ursodeoxycholic acid experienced a reduction in worst itching by at least 30 mm compared with 16% (6/37) randomised to placebo. The difference of 16% (95% confidence interval −3 to 34); this would represent a number needed to treat
Clinical trials, particularly large cooperative group trials, establish the standards that we use to treat many of our cancer patients. The process by which multi-institutional clinical trials are developed, performed and peer-reviewed in the United States is equaled by few other countries around the world. Our clinical cooperative groups should be considered an important national resource. However, they stand at an embattled crossroads. Traditionally, only two to three percent of cancer patients have been entered onto clinical trials. In the past few years, national accrual has declined even further-from approximately 22,000 to 16,000 patients annually. The reasons for this decline are unclear. Although it could simply reflect a hiatus in the activity of some groups (such as the recent reorganization of the National Surgical Adjuvant Breast and Bowel Project [NSABP]), it more likely reflects changes in our health care environment. Few managed care insurance plans permit patient entry into clinical studies on the premise that trials increase patient care costs. Yet, individualized patient care not delivered according to strict peer-reviewed standards may cost more. While this remains undetermined, oncologists in both academic and private practice are being pressured to work harder for fewer rewards. They are being told that investigational treatments are not allowed even if trials evaluating these treatments may ultimately lead to better and more cost-effective patient care. This is a sad state of affairs at a time when, on one hand, treatment for many solid tumors remains desperately inadequate and, on the other hand, new insights into tumor biology promise to alter fundamentally our approach to cancer care. Where do surgeons fit into this picture? The cooperative groups were initiated in the mid-1950s, primarily to evaluate the potential role of chemotherapy in cancer treatment. During the past forty years, surgeons have usually played a supporting role in
Kaló, Zoltán; Antal, János; Pénzes, Miklós; Pozsgay, Csilla; Szepezdi, Zsuzsanna; Nagyjánosi, László
To determine the contribution of clinical trials to the gross domestic product (GDP) in Hungary. An anonymous survey of pharmaceutical companies and clinical research organizations (CROs) was conducted to estimate their clinical trial-related employment and revenues. Clinical trial documents at the National Institute of Pharmacy (NIP) were analyzed to estimate trial-related revenues at health care institutions and the value of investigational medical products (IMPs) based on avoided drug costs. Financial benefits were calculated as 2010 US $ purchasing power parity (PPP) values. Clinical trials increased the revenue of Hungarian health care providers by 1 US $65.6 million. The value of IMPs was US $67.0 million. Clinical trial operation and management activities generated 900 jobs and US $166.9 million in revenue among CROs and pharmaceutical companies. The contribution of clinical trials to the Hungarian GDP in 2010 amounted to 0.2%. Participation in international clinical trials may result in health, financial, and intangible benefits that contribute to the sustainability of health care systems, especially in countries with severe resource constraints. Although a conservative approach was employed to estimate the economic benefits of clinical trials, further research is necessary to improve the generalizability of our findings.
Kaló, Zoltán; Antal, János; Pénzes, Miklós; Pozsgay, Csilla; Szepezdi, Zsuzsanna; Nagyjánosi, László
Aim To determine the contribution of clinical trials to the gross domestic product (GDP) in Hungary. Methods An anonymous survey of pharmaceutical companies and clinical research organizations (CROs) was conducted to estimate their clinical trial-related employment and revenues. Clinical trial documents at the National Institute of Pharmacy (NIP) were analyzed to estimate trial-related revenues at health care institutions and the value of investigational medical products (IMPs) based on avoided drug costs. Financial benefits were calculated as 2010 US $ purchasing power parity (PPP) values. Results Clinical trials increased the revenue of Hungarian health care providers by US $165.6 million. The value of IMPs was US $67.0 million. Clinical trial operation and management activities generated 900 jobs and US $166.9 million in revenue among CROs and pharmaceutical companies. Conclusions The contribution of clinical trials to the Hungarian GDP in 2010 amounted to 0.2%. Participation in international clinical trials may result in health, financial, and intangible benefits that contribute to the sustainability of health care systems, especially in countries with severe resource constraints. Although a conservative approach was employed to estimate the economic benefits of clinical trials, further research is necessary to improve the generalizability of our findings. PMID:25358877
Fraccaro, Paolo; Dentone, Chiara; Fenoglio, Daniela; Giacomini, Mauro
Clinical Trials (CTs) are indispensable instruments for evidence-based medicine and frequently necessitate the management, sharing and analysis of large amounts of data amongst partners in different locations. To effectively satisfy these requirements, the proposed solution combines a web platform and a Clinical Data Management System (CDMS) to exploit the strengths of Electronic Health Records (EHR) and Electronic Data Capture (EDC) systems. The core of the proposal is a relational database which has high data structuring characteristics and utilises biomedical controlled vocabularies (e.g. LOINC and ICD). In addition, units and normality ranges were collected for data comparison through the application of the Z-score transformation. The obtained CDMS preserves the EDC's flexibility and user autonomy and permits the creation of patient cohorts, as in the EHR. Accordingly, clinical information, after the initial recording, is available for different simultaneous multicentre CTs. Furthermore, interface runtime controls guarantee high data quality during data entering processes. Currently, the proposed system has been developed in the HIV and eye diseases fields in Italy. The proposed solution is flexible and suitable to perform multicentre research within a varying range of medical domains. In the future, the automatic importation of information from hospitals has been planned through an HL7 standard interface which would improve both data quantity and quality.
Greber, Katarzyna E; Dawgul, Małgorzata
Today microbial drug resistance has become a serious problem not only within inpatient setting but also within outpatient setting. Repeated intake and unnecessary usage of antibiotics as well as the transfer of resistance genes are the most important factors that make the microorganisms resistant to conventional antibiotics. A large number of antimicrobials successfully used for prophylaxis and therapeutic purposes have now become ineffective [1, 2]. Therefore, new molecules are being studied to be used in the treatment of various diseases. Some of these molecules are structural compounds based on a combination of peptides, for example, naturally occurring endogenous peptide antibiotics and their synthetic analogues or molecules designed de novo using QSAR (quantitative structureproperty relationships)-based methods . Trying to exploit numerous advantages of antimicrobial peptides such as high potency and selectivity, broad range of targets, potentially low toxicity and low accumulation in tissues, pharmaceutical industry aims to develop them as commercially available drugs and appropriate clinical trials are being conducted . In this paper we define clinical trials steps and describe current status of several antimicrobial peptides under clinical development as well as briefly depict peptide drug formulation.
Followill, David S.; Urie, Marcia; Galvin, James M.; Ulin, Kenneth; Xiao, Ying; FitzGerald, Thomas J.
The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials. PMID:23272300
Pflugfelder, Stephen C; Karpecki, Paul M; Perez, Victor L
Blepharitis is a chronic inflammatory disease of the eyelids that is frequently encountered in clinical practice. The etiology of the disorder is complex and not fully understood, but the general consensus is that bacteria and inflammation contribute to the pathology. Blepharitis can be classified into anterior blepharitis, involving the anterior lid margin and eyelashes, and posterior blepharitis, characterized by dysfunction of the meibomian glands. Long-term management of symptoms may include daily eyelid cleansing routines and the use of therapeutic agents that reduce infection and inflammation. A cure is not possible in most cases, and subjective symptoms may persist even when a clinical assessment of signs indicates that the condition has improved. There are no established guidelines regarding therapeutic regimens, but recent clinical trials have shown that antibiotics and topical corticosteroids can produce significant improvement in signs and symptoms of blepharitis. Fixed combinations of a topical antibiotic and a corticosteroid offer an effective and convenient treatment modality that addresses both infectious and inflammatory components of the disease. Further clinical trials are needed to determine optimal therapies for managing blepharitis. Copyright © 2014 Elsevier Inc. All rights reserved.
A cluster randomised controlled trial of the clinical and cost-effectiveness of a 'whole systems' model of self-management support for the management of long- term conditions in primary care: trial protocol
Background Patients with long-term conditions are increasingly the focus of quality improvement activities in health services to reduce the impact of these conditions on quality of life and to reduce the burden on care utilisation. There is significant interest in the potential for self-management support to improve health and reduce utilisation in these patient populations, but little consensus concerning the optimal model that would best provide such support. We describe the implementation and evaluation of self-management support through an evidence-based 'whole systems' model involving patient support, training for primary care teams, and service re-organisation, all integrated into routine delivery within primary care. Methods The evaluation involves a large-scale, multi-site study of the implementation, effectiveness, and cost-effectiveness of this model of self-management support using a cluster randomised controlled trial in patients with three long-term conditions of diabetes, chronic obstructive pulmonary disease (COPD), and irritable bowel syndrome (IBS). The outcome measures include healthcare utilisation and quality of life. We describe the methods of the cluster randomised trial. Discussion If the 'whole systems' model proves effective and cost-effective, it will provide decision-makers with a model for the delivery of self-management support for populations with long-term conditions that can be implemented widely to maximise 'reach' across the wider patient population. Trial registration number ISRCTN: ISRCTN90940049 PMID:22280501
Beach, J E
When contract research organizations (CROs) were first formed, pharmaceutical companies outsourced to them only certain aspects of the conduct of their clinical trials. At first CROs were highly specialized entities, providing, for example, either biostatistical advice, clinical research associates who monitored investigational sites for regulatory compliance, or regulatory support. Gradually, full service CROs emerged, offering a full range of services for clinical trials, including the selection of investigators and investigational sites, assistance with patient recruitment, safety surveillance and reporting, site audits, and data management and biostatistics. This evolving relationship between CROs and the pharmaceutical and medical device industries has resulted in CROs assuming more and more of the regulatory and ethical risks and responsibilities inherent in the conduct of clinical trials. In this full service role, CROs, unlike sponsors, are not interested in the outcome of study, but like sponsors, are subject to heavy regulation by the federal government, must follow applicable state laws, must respect international guidelines, and are obliged to follow their own operating procedures. Moreover, they are judged by the industry on the basis of the scope and quality of services provided, including the degree of adherence to the research protocol, regulatory requirements, and timelines; the quality of the professional working relationships with investigators and institutions, both academic and community-based; and the validity of the data. Further, CROs are subject to comprehensive audits by sponsoring companies, FDA, and other regulatory authorities. For all these reasons, CROs are being tasked with strict vigilance of all stages of the clinical trial process to ensure that the laws, regulations, and industry standards designed for the protection of human subjects and data integrity are maintained.
Matsui, Elizabeth C; Perzanowski, Matthew; Peng, Roger D; Wise, Robert A; Balcer-Whaley, Susan; Newman, Michelle; Cunningham, Amparito; Divjan, Adnan; Bollinger, Mary E; Zhai, Shuyan; Chew, Ginger; Miller, Rachel L; Phipatanakul, Wanda
Professionally delivered integrated pest management (IPM) interventions can reduce home mouse allergen concentrations, but whether they reduce asthma morbidity among mouse-sensitized and exposed children and adolescents is unknown. To determine the effect of an IPM intervention on asthma morbidity among mouse-sensitized and exposed children and adolescents with asthma. Randomized clinical trial conducted in Baltimore, Maryland, and Boston, Massachusetts. Participants were mouse-sensitized and exposed children and adolescents (aged 5-17 years) with asthma randomized to receive professionally delivered IPM plus pest management education or pest management education alone. Enrollment occurred between May 2010 and August 2014; the final follow-up visit occurred on September 25, 2015. Integrated pest management consisted of application of rodenticide, sealing of holes that could serve as entry points for mice, trap placement, targeted cleaning, allergen-proof mattress and pillow encasements, and portable air purifiers. Infestation was assessed every 3 months, and if infestation persisted or recurred, additional treatments were delivered. All participants received pest management education, which consisted of written material and demonstration of the materials needed to set traps and seal holes. The primary outcome was maximal symptom days defined as the highest number of days of symptoms in the previous 2 weeks among 3 types of symptoms (days of slowed activity due to asthma; number of nights of waking with asthma symptoms; and days of coughing, wheezing, or chest tightness) across 6, 9, and 12 months. Of 361 children and adolescents who were randomized (mean [SD] age, 9.8 [3.2] years; 38% female; 181 in IPM plus pest management education group and 180 in pest management education alone group), 334 were included in the primary analysis. For the primary outcome, there was no statistically significant between-group difference for maximal symptom days across 6, 9, and 12
Quinn, Charlene C; Clough, Suzanne Sysko; Minor, James M; Lender, Dan; Okafor, Maria C; Gruber-Baldini, Ann
Less than 63% of individuals with diabetes meet professional guidelines target of hemoglobin A1c <7.0%, and only 7% meet combined glycemic, lipid, and blood pressure goals. The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools. Secondary aims examined health care provider (HCP) adherence to prescribing guidelines and assessed HCPs' adoption of the technology. Thirty patients with type 2 diabetes were recruited from three community physician practices for a 3-month study and evenly randomized. The intervention group received cell phone-based software designed by endocrinologists and CDEs (WellDoc Communications, Inc., Baltimore, MD). The software provided real-time feedback on patients' blood glucose levels, displayed patients' medication regimens, incorporated hypo- and hyperglycemia treatment algorithms, and requested additional data needed to evaluate diabetes management. Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms. The system sent computer-generated logbooks (with suggested treatment plans) to intervention patients' HCPs. The average decrease in A1c for intervention patients was 2.03%, compared to 0.68% (P < 0.02, one-tailed) for control patients. Of the intervention patients, 84% had medications titrated or changed by their HCP compared to controls (23%, P = 0.002). Intervention patients' HCPs reported the system facilitated treatment decisions, provided organized data, and reduced logbook review time. Adults with type 2 diabetes using WellDoc's software achieved statistically significant improvements in A1c. HCP and patient satisfaction with the system was clinically and statistically significant.
Cassese, Mariarita; Zuber, Veronica
Women use more medicines than men because they fall ill more often and suffer more from chronic diseases, but also because women pay more attention to their health and have more consciousness and care about themselves. Although medicines can have different effects on women and men, women still represent a small percentage in the first phases of trials (22%) which are essential to verify drugs dosage, side effects, and safety. Even though women are more present in trials, studies results are not presented with a gender approach. This situation is due to educational, social, ethical and economical factors. The scientific research must increase feminine presence in clinical trials in order to be equal and correct, and all the key stakeholder should be involved in this process. We still have a long way to cover and it doesn't concern only women but also children and old people. The aim is to have a medicine not only illness-focused but patient-focused: a medicine able to take into consideration all the patient characteristics and so to produce a really personalized therapy. What above described is part of the reasons why in 2005 was founded the National Observatory for Women's Health (Osservatorio Nazionale sulla Salute della Donna, ONDa) which promotes a gender health awareness and culture in Italy, at all the levels of the civil and scientific society.
Domenech, Julio; Baños, Rosa; Peñalver, Lourdes; Garcia-Palacios, Azucena; Herrero, Rocio; Ezzedine, Aida; Martinez-Diaz, Monica; Ballester, Javier; Horta, Jaime; Botella, Cristina
Psychological treatments have been successful in treating chronic low back pain (CLBP). However, the effect sizes are still modest and there is room for improvement. A way to progress is by enhancing treatment adherence and self-management using information and communication technologies (ICTs). Therefore, the objective of this study was to design a trial investigating the short- and long-term efficacy of cognitive behavioural treatment (CBT) for CLBP using or not ICTs. A secondary objective of this trial will be to evaluate the influence of relevant variables on treatment response. Possible barriers in the implementation of CBT with and without ICT will also be investigated. A randomised controlled trial with 180 CLBP patients recruited from specialised care will be conducted. Participants will be randomly assigned to three conditions: Control group (CG), CBT, and CBT supported by ICTs (CBT + ICT). Participants belonging to the three conditions will receive a conventional rehabilitation program (back school). The CBT group program will last six sessions. The CBT + ICT group will use the internet and SMS to practice the therapeutic strategies between sessions and in the follow-ups at their homes. Primary outcome variables will be self-reported disability and pain intensity. Assessment will be carried out by blinded assessors in five moments: pre-treatment, post-treatment and 3-, 6-, and 12-month follow-ups. The influence of catastrophizing, fear-avoidance beliefs, anxiety and depression in response to treatment in the primary outcomes will also be analysed. This study will show data of the possible benefits of using ICTs in the improvement of CBT for treating CLBP. ClinicalTrials.gov, NCT01802671.
Hegana, Rahul; Toshikhane, Hemant Devaraj; Toshikhane, Sangeeta; Amin, Hetal
Introduction: Post-operative pain is Nociceptive i.e., anticipated unavoidable physiological pain which is caused due to tissue trauma. Drugs such as NSAIDs (Non Steroidal Anti Inflammatory Drugs) and Opioids are used for post-operative pain management but are associated with their own drawbacks. Karamardādi Yoga has been in use in Ayurvedic practice for analgesia. It is known to relieve pain and can be used to supplement anaesthesia and also get rid of adverse effect of modern analgesic drugs. Aims and Objective: To study the comparative effect of Karamardādi Yoga and Diclofenac sodium in post-operative pain management. Materials and Methods: Randomized clinical trial with Group A (Control Group: Tab Diclofenac sodium 50 mg as a single dose) and Group B (Trial Group: Cap Karamardādi Yoga 500 mg as a single dose). Those who had undergone haemorrhoidectomy operation under local anaesthesia were selected as per inclusion criteria. Vitals, desirable effect and undesirable effect, total surgical time, requirement of 1st dose of analgesic, requirement of rescue analgesic and pain determined by VAS (Visual Analog Scale) were the assessment criteria and were observed and recorded. Results: Karamardādi Yoga does not show any undesirable or serious ill effects and altered values of vitals as per statistical analysis. As per VAS scale, pain felt by Trial group was earlier than control group. Conclusions: Karamardādi Yoga has analgesic property but its analgesic property and pain threshold capacity is lesser than those of Diclofenac sodium. PMID:27621519
O'Neal, Heather A.; Blair, Steven N.
Discusses exercise adherence from the perspective of adhering to an exercise treatment in a controlled trial, focusing on: adherence (to intervention and measurement); the development of randomized clinical trials; exemplary randomized clinical trials in exercise science (exercise training studies and physical activity interventions); and study…
Ross, Joseph S.; Mulvey, Gregory K.; Hines, Elizabeth M.; Nissen, Steven E.; Krumholz, Harlan M.
Background ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. Methods and Findings We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Conclusions Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low
Ross, Joseph S; Mulvey, Gregory K; Hines, Elizabeth M; Nissen, Steven E; Krumholz, Harlan M
ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements
Rowland, Rosalind; McShane, Helen
Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985
Mackillop, Lucy H; Bartlett, Katy; Birks, Jacqueline; Farmer, Andrew J; Gibson, Oliver J; Kevat, Dev A; Kenworthy, Yvonne; Levy, Jonathan C; Loerup, Lise; Tarassenko, Lionel; Velardo, Carmelo; Hirst, Jane E
Introduction The prevalence of gestational diabetes mellitus (GDM) is rising in the UK. Good glycaemic control improves maternal and neonatal outcomes. Frequent clinical review of patients with GDM by healthcare professionals is required owing to the rapidly changing physiology of pregnancy and its unpredictable course. Novel technologies that allow home blood glucose (BG) monitoring with results transmitted in real time to a healthcare professional have the potential to deliver good-quality healthcare to women more conveniently and at a lower cost to the patient and the healthcare provider compared to the conventional face-to-face or telephone-based consultation. We have developed an integrated GDm-health management system and aim to test the impact of using this system on maternal glycaemic control, costs, patient satisfaction and maternal and neonatal outcomes compared to standard clinic care in a single large publicly funded (National Health Service (NHS)) maternity unit. Methods and analysis Women with confirmed gestational diabetes in a current pregnancy are individually randomised to either the GDm-health system and half the normal clinic visits or normal clinic care. Primary outcome is mean BG in each group from recruitment to delivery calculated, with adjustments made for number of BG measurements, proportion of preprandial and postprandial readings and length of time in study, and compared between the groups. The secondary objective will be to compare the two groups for compliance to the allocated BG monitoring regime, maternal and neonatal outcomes, glycaemic control using glycated haemoglobin (HbA1c) and other BG metrics, and patient attitudes to care assessed using a questionnaire and resource use. Ethics and dissemination Thresholds for treatment, dietary advice and clinical management are the same in both groups. The results of the study will be published in a peer-reviewed journal and disseminated electronically and in print. Trial registration
Zhao, Ting; Wu, Ping; Li, Yong; Lian, Feng-mei; Liu, Ping; Qiao, Jie
The quality control of new drug cilnical trial is the effective guaranty for the pharmaceutical safety and effective after available on market. Enhancing the inspection and quality control of new drug clinical trials provide the crucial importance to achieve a persistent profitable standard. This paper mainly discussed the problems of current clinical trials based on annual check of drug clinical trial institution.
Liaw, Sok Ying; Chan, Sally Wai-Chi; Chen, Fun-Gee; Hooi, Shing Chuan; Siau, Chiang
Virtual patient simulation has grown substantially in health care education. A virtual patient simulation was developed as a refresher training course to reinforce nursing clinical performance in assessing and managing deteriorating patients. The objective of this study was to describe the development of the virtual patient simulation and evaluate its efficacy, by comparing with a conventional mannequin-based simulation, for improving the nursing students' performances in assessing and managing patients with clinical deterioration. A randomized controlled study was conducted with 57 third-year nursing students who were recruited through email. After a baseline evaluation of all participants' clinical performance in a simulated environment, the experimental group received a 2-hour fully automated virtual patient simulation while the control group received 2-hour facilitator-led mannequin-based simulation training. All participants were then re-tested one day (first posttest) and 2.5 months (second posttest) after the intervention. The participants from the experimental group completed a survey to evaluate their learning experiences with the newly developed virtual patient simulation. Compared to their baseline scores, both experimental and control groups demonstrated significant improvements (P<.001) in first and second post-test scores. While the experimental group had significantly lower (P<.05) second post-test scores compared with the first post-test scores, no significant difference (P=.94) was found between these two scores for the control group. The scores between groups did not differ significantly over time (P=.17). The virtual patient simulation was rated positively. A virtual patient simulation for a refreshing training course on assessing and managing clinical deterioration was developed. Although the randomized controlled study did not show that the virtual patient simulation was superior to mannequin-based simulation, both simulations have demonstrated
... performed globally, greater use of contract research organizations (CROs), participation of vulnerable... research, obtain informed consent). FDA has also heard from clinical trial sponsors and CROs that sponsors and CROs are reluctant to change their processes related to clinical trial oversight and management...
Bucur, Anca; Van Leeuwen, Jasper; Chen, Njin-Zu; Claerhout, Brecht; De Schepper, Kristof; Perez-Rey, David; Alonso-Calvo, Raul; Pugliano, Lina; Saini, Kamal
To support the efficient execution of post-genomic multi-centric clinical trials in breast cancer we propose a solution that streamlines the assessment of the eligibility of patients for available trials. The assessment of the eligibility of a patient for a trial requires evaluating whether each eligibility criterion is satisfied and is often a time consuming and manual task. The main focus in the literature has been on proposing different methods for modelling and formalizing the eligibility criteria. However the current adoption of these approaches in clinical care is limited. Less effort has been dedicated to the automatic matching of criteria to the patient data managed in clinical care. We address both aspects and propose a scalable, efficient and pragmatic patient screening solution enabling automatic evaluation of eligibility of patients for a relevant set of trials. This covers the flexible formalization of criteria and of other relevant trial metadata and the efficient management of these representations.
Background US Latinos have greater prevalence of type 2 diabetes (diabetes), uncontrolled diabetes and diabetes co-morbidities compared to non-Latino Whites. They also have lower literacy levels and are more likely to live in poverty. Interventions are needed to improve diabetes control among low-income Latinos. Methods and design This randomized clinical trial tested the efficacy of a culturally- and literacy-tailored diabetes self-management intervention (Latinos en Control) on glycemic control among low-income Latinos with diabetes, compared to usual care (control). Participants were recruited from five community health centers (CHCs) in Massachusetts. The theory-based intervention included an intensive phase of 12 weekly sessions and a follow-up maintenance phase of 8 monthly sessions. Assessments occurred at baseline, and at 4 and 12 months. The primary outcome was glycosylated hemoglobin (HbA1c). Secondary outcomes were self-management behaviors, weight, lipids and blood pressure. Additional outcomes included diabetes knowledge, self-efficacy, depression and quality of life. The study was designed for recruitment of 250 participants (estimated 20% dropout rate) to provide 90% power for detecting a 7% or greater change in HbA1c between the intervention and control groups. This is a difference in change of HbA1c of 0.5 to 0.6%. Discussion Low-income Latinos bear a great burden of uncontrolled diabetes and are an understudied population. Theory-based interventions that are tailored to the needs of this high-risk population have potential for improving diabetes self-management and reduce health disparities. This article describes the design and methods of a theory driven intervention aimed at addressing this need. Trial registration http://www.clinicaltrials.gov # NCT00848315 PMID:20003208
Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). The Fiber Study, a randomized controlled trial on symptom management for FI, successfully enrolled 189 community-living adu...
Boorsma, Marijke; van Hout, Hein PJ; Frijters, Dinnus H; Ribbe, Miel W; Nijpels, Giel
Background The objective of this article is to describe the design of a study to evaluate the clinical and economic effects of a Disease Management model on functional health, quality of care and quality of life of persons living in homes for the elderly. Methods This study concerns a cluster randomized controlled clinical trial among five intervention homes and five usual care homes in the North-West of the Netherlands with a total of over 500 residents. All persons who are not terminally ill, are able to be interviewed and sign informed consent are included. For cognitively impaired persons family proxies will be approached to provide outcome information. The Disease Management Model consists of several elements: (1) Trained staff carries out a multidimensional assessment of the patients functional health and care needs with the interRAI Long Term Care Facilities instrument (LTCF). Computerization of the LTCF produces immediate identification of problem areas and thereby guides individualized care planning. (2) The assessment outcomes are discussed in a Multidisciplinary Meeting (MM) with the nurse, primary care physician, nursing home physician and Psychotherapist and if necessary other members of the care team. The MM presents individualized care plans to manage or treat modifiable disabilities and risk factors. (3) Consultation by an nursing home physician and psychotherapist is offered to the frailest residents at risk for nursing home admission (according to the interRAI LTCF). Outcome measures are Quality of Care indicators (LTCF based), Quality Adjusted Life Years (Euroqol), Functional health (SF12, COOP-WONCA), Disability (GARS), Patients care satisfaction (QUOTE), hospital and nursing home days and mortality, health care utilization and costs. Discussion This design is unique because no earlier studies were performed to evaluate the effects and costs of this Disease Management Model for disabled persons in homes for the elderly on functional health and
Boorsma, Marijke; van Hout, Hein P J; Frijters, Dinnus H; Ribbe, Miel W; Nijpels, Giel
The objective of this article is to describe the design of a study to evaluate the clinical and economic effects of a Disease Management model on functional health, quality of care and quality of life of persons living in homes for the elderly. This study concerns a cluster randomized controlled clinical trial among five intervention homes and five usual care homes in the North-West of the Netherlands with a total of over 500 residents. All persons who are not terminally ill, are able to be interviewed and sign informed consent are included. For cognitively impaired persons family proxies will be approached to provide outcome information. The Disease Management Model consists of several elements: (1) Trained staff carries out a multidimensional assessment of the patients functional health and care needs with the interRAI Long Term Care Facilities instrument (LTCF). Computerization of the LTCF produces immediate identification of problem areas and thereby guides individualized care planning. (2) The assessment outcomes are discussed in a Multidisciplinary Meeting (MM) with the nurse, primary care physician, nursing home physician and Psychotherapist and if necessary other members of the care team. The MM presents individualized care plans to manage or treat modifiable disabilities and risk factors. (3) Consultation by an nursing home physician and psychotherapist is offered to the frailest residents at risk for nursing home admission (according to the interRAI LTCF). Outcome measures are Quality of Care indicators (LTCF based), Quality Adjusted Life Years (Euroqol), Functional health (SF12, COOP-WONCA), Disability (GARS), Patients care satisfaction (QUOTE), hospital and nursing home days and mortality, health care utilization and costs. This design is unique because no earlier studies were performed to evaluate the effects and costs of this Disease Management Model for disabled persons in homes for the elderly on functional health and quality of care. TRAIL
16 Table 3. HBO Clinical Trials: Multiple Sclerosis ..... 17 Table 4. HBO Clinical Trials: Diabetic Foot Ulcers.. .17 Table 5. HBO...treatment of multiple sclerosis (MS) (table 3), and two reported on diabetic foot ulcers (table 4). The remaining seven reported on seven different...group of MS trials is convincing that HBO was not effective for MS. The diabetic foot ulcer trials are difficult to compare. They used different HBO
Brown, Sharon A; García, Alexandra A; Orlander, Philip R; Hanis, Craig L
Objectives: Studies of social support in diabetes have focused on the effects of support on the person with type 2 diabetes. We explored diabetes prevention effects of a culturally tailored diabetes self-management intervention in individuals without diabetes who were supporters of intervention participants. Methods: This is a secondary analysis of data from a randomized clinical trial that involved 256 Mexican Americans with diabetes. Each study participant designated a supporter—spouse, relative, friend—who attended intervention sessions and assisted participants in attaining effective diabetes self-management. Supporter’s glycosylated hemoglobin (A1C) data were tracked for 1 year to determine diabetes conversion rates in supporters without diabetes at baseline. Results: Fewer individuals in the intervention group (n = 9) converted to an A1C above the 7% threshold, compared to the 1-year wait-listed control group (n = 16). We found a statistically significant difference (p = .021) at 12 months in the number of individuals whose A1C was ⩽8%, with fewer supporters above threshold in the intervention group (reduction of 48%). Supporters in the intervention group with prediabetes, based on baseline A1C, experienced a slight reduction in A1C, while control group supporters with prediabetes experienced an increase. Discussion: The results suggest that there are potential benefits for family members and other supporters of persons with diabetes who participated in diabetes self-management programs. PMID:28228947
Espinoza, Magdalena; Hsieh, Antony; Hsiehchen, David
Clinical guidelines are commonly based on inadequate evidence, suggesting deficiencies in the present portfolio of clinical research. To investigate characteristics of clinical trials examining gastrointestinal (GI) diseases registered in ClinicalTrials.gov. A cross-sectional analysis of 13,647 GI trials and 111,535 non-GI trials initiated between January 1997 and September 2013 was performed. Entries were sorted by operational status, purpose, interventions, trial design, and epochs to identify trends and interactions in trial properties. The global production of GI trials has remained static in recent years and a majority of research efforts are focused on a few diseases. While GI trials are generally produced by highly populated US states and countries, they are also seldom larger than 500 patients. The likelihood of using data monitoring committees, randomization, and double blinding in GI trials has increased over time, though a substantial fraction of GI trials still do not employ rigorous trial designs. While levels of GI trials correlate with disease burden, the explained variance of GI trials by disease burden worldwide is poor. GI trials are chiefly concentrated in few diseases and highly populated regions, exhibit heterogeneous trends and methodologies, and are sensitive to disease burdens, though more so within North America than worldwide. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Azzopardi, D; Strohm, B; Edwards, A D; Halliday, H; Juszczak, E; Levene, M; Thoresen, M; Whitelaw, A; Brocklehurst, P
This is a phase 4 study of infants registered with the UK TOBY Cooling Register from December 2006 to February 2008. The registry was established on completion of enrolLment to the TOBY randomised trial of treatment with whole body hypothermia following perinatal asphyxia at the end of November 2006. We collected information about patient characteristics, condition at birth, resuscitation details, severity of encephalopathy, hourly temperature record, clinical complications and outcomes before hospital discharge. 120 infants born at a median of 40 (IQR 38-41) weeks' gestation and weighing a median of 3287 (IQR 2895-3710) g at birth were studied. Cooling was started at a median of 3 h 54 min (IQR 2 h-5 h 32 min) after birth. All but three infants underwent whole body cooling. The mean (SD) rectal temperature from 6 to 72 h of the cooling period was 33.57 degrees C (0.51 degrees C). The daily encephalopathy score fell: median (IQR) 11 (6-15), 9.7 (5-14), 8 (5-13) and 7 (2-12) on days 1-4 after birth, respectively. 51% of the infants established full oral feeding at a median (range) of 9 (4-24) days. 26% of the study infants died. MRI was consistent with hypoxia-ischaemia in most cases. Clinical complications were not considered to be due to hypothermia. In the UK, therapeutic hypothermia following perinatal asphyxia is increasingly being provided. The target body temperature is successfully achieved and the clinical complications observed were not attributed to hypothermia. Treatment with hypothermia may have prevented the worsening of the encephalopathy that is commonly observed following asphyxia.
Recently, the complexity and costs of clinical trials have increased dramatically, especially in the area of new drug development. Risk-based monitoring (RBM) has been attracting attention as an efficient and effective trial monitoring approach, which can be applied irrespectively of the trial sponsor, i.e., academic institution or pharmaceutical company. In the RBM paradigm, it is expected that a statistical approach to central monitoring can help improve the effectiveness of on-site monitoring by prioritizing and guiding site visits according to central statistical data checks, as evidenced by examples of actual trial datasets. In this review, several statistical methods for central monitoring are presented. It is important to share knowledge about the role and performance capabilities of statistical methodology among clinical trial team members (i.e., sponsors, investigators, data managers, monitors, and biostatisticians) in order to adopt central statistical monitoring for assessing data quality in the actual clinical trial.
Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L
There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.
Heyden, Robin; Mejilla, Roanne; Capelson, Roberta; Chalmers, Karen A; Rizzo DePaoli, Maria; Veerappa, Chetty; Wiecha, John M
intervention costs were US $1117 versus US $931 for face-to-face. Conclusions It is feasible to deliver diabetes self-management interventions to inner city African American women via virtual worlds, and outcomes may be comparable to those of face-to-face interventions. Further effectiveness research is warranted. Trial Registration ClinicalTrials.gov NCT01340079; http://clinicaltrials.gov/show/NCT01340079 (Archived by WebCite at http://www.webcitation.org/6T2aSvmka). PMID:25344620
Mattingly, William A; Kelley, Robert R; Wiemken, Timothy L; Chariker, Julia H; Peyrani, Paula; Guinn, Brian E; Binford, Laura E; Buckner, Kimberley; Ramirez, Julio
Objective Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. Materials and Methods We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. Results The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. Conclusion We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system. PMID:26878068
Perino, L J; Apley, M D
As mentioned at the outset, the ultimate test of a product or procedure must be under field conditions and is best obtained from controlled studies of field use. Economic justification for use is based on this information. Each producer places a different value on attributable benefits such as improved health or growth performance. These values also change with fluctuating market values of cattle and feed. This makes determining the cost-benefit ratio of any procedure or product a moving target. Addressing this issue requires the clinically relevant and statistically significant differences that practitioners should be able to generate if they follow the guidelines presented here. There already exists a number of unusable studies. We suggest that those interested in undertaking this challenge be uncompromising in their experimental design. To be reliable, studies must follow the recommendations outlined above. Without sound field trial design and execution which ensures that the information is reliable and statistical significance which ensures that the differences are real, clinical outcomes cannot be extrapolated to economic justification. Any other course leads to making less than optimal recommendations on product use because of a lack of clinically relevant information.
Vieira, Jean Mendes de Lucena; Lima, Elisangela da Costa; Land, Marcelo Gerardin Poirot; Ventura, Miriam; Coelho, Helena Lutescia Luna
This study aimed to characterize the clinical trials with medicines enrolling Brazilian children and adolescents, registered in the databases of Clinical Trials and the Brazilian Clinical Trials Network (ReBEC) from 1994 to 2014. Only 462 clinical trials enrolled Brazilian children and adolescents. There was an increase in registrations beginning in 2003, with an important drop in 2011. Among these trials, 35.5% were hosted in Brazil. The international clinical trials were mostly conducted by North American companies. In both cases, multinational industry was the principal source of funding. The clinical trials were predominantly phase III with injectable and solid oral pharmaceutical forms of antiviral drugs. Domestic clinical trials showed wider variation in the pharmaceutical forms and higher percentage of liquid formulations, when compared to the international trials. In addition to heavy external dependence for conducting clinical trials, the study emphasized the challenge for pediatric care in Brazil, which presents epidemiological peculiarities in an environment prone to the use of unlicensed medicines for children.
Zang, Yong; Lee, J. Jack
Adaptive designs have become popular in clinical trial and drug development. Unlike traditional trial designs, adaptive designs use accumulating data to modify the ongoing trial without undermining the integrity and validity of the trial. As a result, adaptive designs provide a flexible and effective way to conduct clinical trials. The designs have potential advantages of improving the study power, reducing sample size and total cost, treating more patients with more effective treatments, identifying efficacious drugs for specific subgroups of patients based on their biomarker profiles, and shortening the time for drug development. In this article, we review adaptive designs commonly used in clinical trials and investigate several aspects of the designs, including the dose-finding scheme, interim analysis, adaptive randomization, biomarker-guided randomization, and seamless designs. For illustration, we provide examples of real trials conducted with adaptive designs. We also discuss practical issues from the perspective of using adaptive designs in oncology trials. PMID:25811018
Senator Specter, Honorable Members of the Committee, it is my high privilege to speak on behalf of a subject near and dear to my heart. I have been involved in the care of patients with cancer and in cancer clinical trials for the past 34 years. I chair the Southwest Oncology Group, the largest National Cancer Institute-supported cancer clinical research organization. In 1996, this Group enrolled 6,359 patients to therapeutic cancer clinical trials from all 50 states (Fig. 1), and completed the randomization of 18,867 normal, healthy men into the intergroup Prostate Cancer Prevention Trial. Cancer clinical trials are always designed to improve the outcomes of cancer patients. However, only 2%-3% of all eligible cancer patients in this country are treated on these cutting-edge trials. It is clear that this number must increase dramatically in order for us to be able to translate the monumental advances emanating from the basic cancer research laboratories into effective diagnosis, prevention and treatment strategies for patients with and at high risk for cancer. This low accrual is related to multiple factors: First, managed care has had a negative impact related to its refusal to reimburse for the clinical care aspects of patients on cancer clinical trials. During my presentation to the President's Cancer Panel in San Antonio in September, I shared three thoughts as to what the Panel should be asking as they pursue the question of "Managed Care's Role in the War on Cancer": &bul; "Should managed care bear a portion of the costs of clinical research as a form of R & D?" &bul; "What State or Federal legislation is needed to assure that managed care patients have access to cancer clinical research?" &bul; "Will there be any future for cancer clinical research when the managed care tidal wave finally reaches Chicago and New York?" The NCI-Department of Defense and the NCI-Department of Veterans Affairs Interagency Agreements are superb models of what needs to be done
Morgenstern, Jon; Hogue, Aaron; Dauber, Sarah; Dasaro, Christopher; McKay, James R.
This study tested whether coordinated care management (CCM), a continuity of care intervention for substance use disorders (SUD), improved rates of abstinence when compared with usual welfare management for substance-using single adults and adults with dependent children applying for public assistance. The study was designed as a practical…
Morgenstern, Jon; Hogue, Aaron; Dauber, Sarah; Dasaro, Christopher; McKay, James R.
This study tested whether coordinated care management (CCM), a continuity of care intervention for substance use disorders (SUD), improved rates of abstinence when compared with usual welfare management for substance-using single adults and adults with dependent children applying for public assistance. The study was designed as a practical…
Cher, Daniel J; Capobianco, Robyn A
Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.
A Randomized Controlled Trial Protocol to Evaluate the Effectiveness of an Integrated Care Management Approach to Improve Adherence Among HIV-Infected Patients in Routine Clinical Care: Rationale and Design
Fredericksen, Rob J; Church, Anna; Harrington, Anna; Ciechanowski, Paul; Magnani, Jennifer; Nasby, Kari; Brown, Tyler; Dhanireddy, Shireesha; Harrington, Robert D; Lober, William B; Simoni, Jane; Safren, Stevan A; Edwards, Todd C; Patrick, Donald L; Saag, Michael S; Crane, Paul K; Kitahata, Mari M
Background Adherence to antiretroviral medications is a key determinant of clinical outcomes. Many adherence intervention trials investigated the effects of time-intensive or costly interventions that are not feasible in most clinical care settings. Objective We set out to evaluate a collaborative care approach as a feasible intervention applicable to patients in clinical care including those with mental illness and/or substance use issues. Methods We developed a randomized controlled trial (RCT) investigating an integrated, clinic-based care management approach to improve clinical outcomes that could be integrated into the clinical care setting. This is based on the routine integration and systematic follow-up of a clinical assessment of patient-reported outcomes targeting adherence, depression, and substance use, and adapts previously developed and tested care management approaches. The primary health coach or care management role is provided by clinic case managers allowing the intervention to be generalized to other human immunodeficiency virus (HIV) clinics that have case managers. We used a stepped-care approach to target interventions to those at greatest need who are most likely to benefit rather than to everyone to maintain feasibility in a busy clinical care setting. Results The National Institutes of Health funded this study and had no role in study design, data collection, or decisions regarding whether or not to submit manuscripts for publication. This trial is currently underway, enrollment was completed in 2015, and follow-up time still accruing. First results are expected to be ready for publication in early 2017. Discussion This paper describes the protocol for an ongoing clinical trial including the design and the rationale for key methodological decisions. There is a need to identify best practices for implementing evidence-based collaborative care models that are effective and feasible in clinical care. Adherence efficacy trials have not led to
Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial
tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. Trial registration ClinicalTrials.gov Identifier: NCT01149590 PMID:23036114
The clinical and cost-effectiveness of the BRinging Information and Guided Help Together (BRIGHT) intervention for the self-management support of people with stage 3 chronic kidney disease in primary care: study protocol for a randomized controlled trial
Background Improving the quality of care for people with vascular disease is a key priority. Chronic kidney disease (CKD) has recently been included as a target condition for general practices to add to registers of chronic conditions as part of the Quality and Outcome Framework. This paper outlines the implementation and evaluation of a self-management intervention involving an information guidebook, tailored access to local resources and telephone support for people with stage 3 chronic kidney disease. Methods/Design The study involves a multi-site, longitudinal patient-level randomized controlled trial. The study will evaluate the clinical use and cost-effectiveness of a complex self-management intervention for people with stage 3 chronic kidney disease in terms of self-management capacity, health-related quality of life and blood pressure control compared to care as usual. We describe the methods of the patient-level randomized controlled trial. Discussion The management of chronic kidney disease is a developing area of research. The BRinging Information and Guided Help Together (BRIGHT) trial aims to provide evidence that a complementary package of support for people with vascular disease that targets both clinical and social need broadens the opportunities of self-management support by addressing problems related to social disadvantage. Trial registration Trial registration reference: ISRCTN45433299 PMID:23356861
Fitzmaurice, D A; Murray, E T; McCahon, D; Holder, R; Raftery, J P; Hussain, S; Sandhar, H; Hobbs, F D R
Objective To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. Design Multicentre open randomised controlled trial. Setting Midlands region of the UK. Participants 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. Intervention Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. Main outcome measure Percentage of time spent within the therapeutic range of international normalised ratio. Results No significant differences were found in percentage of time in the therapeutic range between self managment and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (χ2(df = 1) = 0.02, P = 0.89). Conclusion With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375. PMID:16216821
Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J
Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the
Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed
Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa.
Gallo, Joseph J; Hwang, Seungyoung; Joo, Jin Hui; Bogner, Hillary R; Morales, Knashawn H; Bruce, Martha L; Reynolds, Charles F
Two-thirds of older adults have two or more medical conditions that often take precedence over depression in primary care. We evaluated whether evidence-based depression care management would improve the long-term mortality risk among older adults with increasing levels of medical comorbidity. Longitudinal analyses of the practice-randomized Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT). Twenty primary care practices randomized to intervention or usual care. The sample included 1204 older primary care patients completing the Charlson Comorbidity Index (CCI) and other interview questions at baseline. For 2 years, a depression care manager worked with primary care physicians to provide algorithm-based care for depression, offering psychotherapy, increasing the antidepressant dose if indicated, and monitoring symptoms, medication adverse effects, and treatment adherence. Depression status based on clinical interview, CCI to evaluate medical comorbidity, and vital status at 8 years (National Death Index). In the usual care condition, patients with the highest levels of medical comorbidity and depression were at increased risk of mortality over the course of the follow-up compared to depressed patients with minimal medical comorbidity [hazard ratio 3.02 (95% CI, 1.32 to 8.72)]. In contrast, in intervention practices, patients with the highest level of medical comorbidity and depression compared to depressed patients with minimal medical comorbidity were not at significantly increased risk [hazard ratio 1.73 (95% CI, 0.86 to 3.96)]. Nondepressed patients in intervention and usual care practices had similar mortality risk. Depression management mitigated the combined effect of multimorbidity and depression on mortality. Depression management should be integral to optimal patient care, not a secondary focus.
Hall, Jacqueline Anne; Salgado, Roberto; Lively, Tracy; Sweep, Fred; Schuh, Anna
Clinical cancer research today often includes testing the value of biomarkers to direct treatment and for drug development. However, the practical challenges of integration of molecular information into clinical trial protocols are increasingly appreciated. Inherent difficulties include evidence gaps in available biomarker data, a paucity of robust assay methods, and the design of appropriate studies within the constraints of feasible trial operations, and finite resources. Scalable and proportionate approaches are needed to systematically cope with these challenges. Therefore, we assembled international experts from three clinical trials organisations to identify the common challenges and common solutions. We present a practical risk-assessment framework allowing targeting of scarce resources to crucial issues coupled with a library of useful resources and a simple actionable checklist of recommendations. We hope that these practical methods will be useful for running biomarker-driven trials and ultimately help to develop biomarkers that are ready for integration in routine practice. Copyright © 2014 Elsevier Ltd. All rights reserved.
Viergever, Roderik F.; Ghersi, Davina
Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991
Ellenberg, Susan S; Culbertson, Richard; Gillen, Daniel L; Goodman, Steven; Schrandt, Suzanne; Zirkle, Maryan
In any clinical trial, it is essential to monitor the accumulating data to be sure that the trial continues to be safe for participants and that the trial is being conducted properly. Data monitoring committees, independent expert panels who undertake regular reviews of the data as the trial progresses, serve an important role in safeguarding the interests of research participants and ensuring trial integrity in many trials. Many pragmatic clinical trials, which aim to inform healthcare decisions by comparing alternate interventions in heterogeneous healthcare delivery settings, will warrant review by an independent data monitoring committee due to their potential impact on clinical practice. However, the very features that make a trial "pragmatic" may pose challenges in terms of which aspects of a trial to monitor and when it is appropriate for a data monitoring committee to intervene. Using the Pragmatic-Explanatory Continuum Indicator Summary tool that draws distinctions between pragmatic and explanatory clinical trials, we review characteristics of pragmatic clinical trials that may have implications for data monitoring committees and interim monitoring plans. These include broad eligibility criteria, a focus on subjective patient-centered outcomes, and in some cases a lack of standardized follow-up procedures across study sites. Additionally, protocol adherence is often purposefully not addressed in pragmatic trials in order to accurately represent the clinical practice setting and maintain practicability of implementation; there are differing viewpoints as to whether adherence should be assessed and acted upon by data monitoring committees in these trials. Some other issues not specifically related to the Pragmatic-Explanatory Continuum Indicator Summary criteria may also merit special consideration in pragmatic trials. Thresholds for early termination of a pragmatic clinical trial might be controversial. The distinguishing features of pragmatic clinical
Salari, Soheila; Khomand, Payam; Arasteh, Modabber; Yousefzamani, Bahareh; Hassanzadeh, Kambiz
Major Depressive Disorder (MDD) is known as one of the most common psychiatric disorders in patients with multiple sclerosis (MS). In recent years, zinc has been found to have beneficial effects on psychopathology and the therapy of depression. The aim of the present study was to examine the effect of zinc supplement on depression and neurological signs in patients with MS. The present randomized, double-blind, placebo-controlled clinical trial was performed on 43 patients with MS and who also demonstrated MDD based on the Beck questionnaire. These patients were randomly selected and were divided into two groups: the placebo group (n=22) and the intervention group (n=21). The patients received either zinc sulphate (220 mg containing 50mg zinc element) or a placebo for 12 weeks. Clinical examinations were obtained in terms of abnormal ocular movement, muscle power, and gait disorder. The results indicated that in the patients who received the zinc supplement, the mean score of depression was reduced compared to those in the placebo group, whereas the neurological examinations revealed that there were no differences between the treatment and control groups. Therefore, the zinc supplementation is an appropriate choice for the depression management in patients with MS. Copyright © 2015. Published by Elsevier Urban & Partner Sp. z o.o.
Meeker-O’Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J
Background: Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. Methods: The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials (“quality-by-design”), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. Conclusion: The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of
Okonta, Patrick I.
The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247
Okonta, Patrick I
The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.
Study Protocol for a randomized controlled trial of mentalization based therapy against specialist supportive clinical management in patients with both eating disorders and symptoms of borderline personality disorder
Background The NOURISHED study: Nice OUtcomes for Referrals with Impulsivity, Self Harm and Eating Disorders. Eating Disorders (ED) and Borderline Personality Disorder (BPD) are both difficult to treat and the combination presents particular challenges. Both are associated with vulnerability to loss of mentalization (awareness of one’s own and others’ emotional state). In BPD, Mentalization Based therapy (MBT) has been found effective in reducing symptoms. In this trial we investigate the effectiveness and cost-effectiveness of MBT adapted for Eating disorders (Mentalization Based Therapy for Eating Disorders (MBT-ED)) compared to a standard comparison treatment, Specialist Supportive Clinical Management (SSCM-ED) in patients with a combination of an Eating Disorder and either a diagnosis of BPD or a history of self-harm and impulsivity in the previous 12 months. Methods/Design We will complete a multi-site single-blind randomized controlled trial (RCT) of MBT-ED vs SSCM-ED. Participants will be recruited from three Eating Disorder Services and two Borderline Personality Disorder Services in London. Participants allocated to MBT-ED will receive one year of weekly group and individual therapy and participants allocated to SSCM-ED will receive 20 sessions of individual therapy over 1 year. In addition, participants in both groups will have access to up to 5 hours of dietetic advice. The primary outcome measure is the global score on the Eating Disorders Examination. Secondary outcome measures include total score on the Zanarini BPD scale, the Object Relations Inventory, the Depression Anxiety Stress Scales, quality of life and cost-effectiveness. Measures are taken at recruitment and at 6 month intervals up to 18 months. Discussion This is the first Randomised Controlled Trial of MBT-ED in patients with eating disorders and symptoms of BPD and will provide evidence to inform therapy decisions in this group of patients. During MBT-ED mentalization is
Laughon, Matthew M; Benjamin, Daniel K; Capparelli, Edmund V; Kearns, Gregory L; Berezny, Katherine; Paul, Ian M; Wade, Kelly; Barrett, Jeff; Smith, Phillip Brian; Cohen-Wolkowiez, Michael
Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and ‘opportunistic’ studies, have addressed some of the historical challenges associated with clinical trials in children. PMID:21980319
Hester, Reid K.; Delaney, Harold D.; Campbell, William
Objective: To evaluate the effectiveness of a web-based protocol, ModerateDrinking.com (MD; "www.moderatedrinking.com") combined with use of the online resources of Moderation Management (MM; "www.moderation.org") as opposed to the use of the online resources of MM alone. Method: We randomly assigned 80 problem drinkers to…
Brown, Sarah R; Sherratt, Debbie; Booth, Gill; Brown, Julia; Collinson, Fiona; Gregory, Walter; Flanagan, Louise
Early phase trials are essential in drug development, determining appropriate dose levels and assessing preliminary activity. These trials are undertaken by industry and academia, with increasing collaborations between the two. There is pressure to perform these trials quickly, safely, and robustly. However, there are inherent differences between developing and managing early phase, compared to late phase, drug trials. This article describes an approach to establishing an academically led early phase trial portfolio, highlighting lessons learned and sharing experiences. In 2009, the University of Leeds Clinical Trials Research Unit became the Clinical Trials Coordinating Office for Myeloma UK's phase I and II trials. We embarked on a transition from working extensively in phase III to early phase trials development and conduct. This involved evaluating and revising our well-established standard operating procedures, visiting other academic early phase units, and developing essential new documentation and processes. A core team of trial and data managers and statisticians was established to facilitate expertise and knowledge retention. A detailed training plan was implemented focussing on essential standard practices for early phase. These included pharmacovigilance, recruitment, trial design and set-up, data and site monitoring, and oversight committees. Training in statistical methods for early phase trials was incorporated. Initial scoping of early phase trial management and conduct was essential in establishing this early phase portfolio. Many of the processes developed were successful. However, regular review and evaluation were implemented to enable changes and ensure efficiencies. It is recommended that others embarking on this venture build on the experiences described in this article.
A Randomized Controlled Trial Protocol to Evaluate the Effectiveness of an Integrated Care Management Approach to Improve Adherence Among HIV-Infected Patients in Routine Clinical Care: Rationale and Design.
Crane, Heidi M; Fredericksen, Rob J; Church, Anna; Harrington, Anna; Ciechanowski, Paul; Magnani, Jennifer; Nasby, Kari; Brown, Tyler; Dhanireddy, Shireesha; Harrington, Robert D; Lober, William B; Simoni, Jane; Safren, Stevan A; Edwards, Todd C; Patrick, Donald L; Saag, Michael S; Crane, Paul K; Kitahata, Mari M
Adherence to antiretroviral medications is a key determinant of clinical outcomes. Many adherence intervention trials investigated the effects of time-intensive or costly interventions that are not feasible in most clinical care settings. We set out to evaluate a collaborative care approach as a feasible intervention applicable to patients in clinical care including those with mental illness and/or substance use issues. We developed a randomized controlled trial (RCT) investigating an integrated, clinic-based care management approach to improve clinical outcomes that could be integrated into the clinical care setting. This is based on the routine integration and systematic follow-up of a clinical assessment of patient-reported outcomes targeting adherence, depression, and substance use, and adapts previously developed and tested care management approaches. The primary health coach or care management role is provided by clinic case managers allowing the intervention to be generalized to other human immunodeficiency virus (HIV) clinics that have case managers. We used a stepped-care approach to target interventions to those at greatest need who are most likely to benefit rather than to everyone to maintain feasibility in a busy clinical care setting. The National Institutes of Health funded this study and had no role in study design, data collection, or decisions regarding whether or not to submit manuscripts for publication. This trial is currently underway, enrollment was completed in 2015, and follow-up time still accruing. First results are expected to be ready for publication in early 2017. This paper describes the protocol for an ongoing clinical trial including the design and the rationale for key methodological decisions. There is a need to identify best practices for implementing evidence-based collaborative care models that are effective and feasible in clinical care. Adherence efficacy trials have not led to sufficient improvements, and there remains
Ananthakrishnan, Revathi; Menon, Sandeep
Cancer is a disease that occurs due to the uncontrolled multiplication of cells that invade nearby tissues and can spread to other parts of the body. An increased incidence of cancer in the world has led to an increase in oncology research and in the number of oncology trials. Well designed oncology clinical trials are a key part of developing effective anti-cancer drugs. This review focuses on statistical considerations in the design and analysis of oncology clinical trials.
... to control high blood pressure. There are clinical trials going on all the time in nearly every area of medical research. To Find Out More To find out more about clinical trials and how to participate, go to: www.clinicaltrials. ...
Liu, Fei-Fei; Okunieff, Paul; Bernhard, Eric J.; Stone, Helen B.; Yoo, Stephen; Coleman, C. Norman; Vikram, Bhadrasain; Brown, Martin; Buatti, John; Guha, Chandan
A Workshop entitled “Lessons Learned from Radiation Oncology Trials” was held on December 7–8th, 2011 in Bethesda, MD, to present and discuss some of the recently conducted Radiation Oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this Workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the pre-clinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions, including the: a) opportunities to learn from null-hypothesis trials through tissue and imaging studies; b) value of pre-clinical data supporting the design of combinatorial therapies; c) significance of validated biomarkers; d) necessity of quality assurance in radiotherapy delivery; e) conduct of sufficiently-powered studies to address the central hypothesis; and f) importance of publishing results of the trials regardless of the outcome. The fact that well-designed hypothesis-driven clinical trials produce null or negative results is expected given the limitations of trial design, and complexities of cancer biology. It is important to understand the reasons underlying such null results however, in order to effectively merge the technological innovations with the rapidly evolving biology for maximal patient benefit, through the design of future clinical trials. PMID:24043463
Lora-Tamayo, Jaime; Euba, Gorane; Cobo, Javier; Horcajada, Juan Pablo; Soriano, Alex; Sandoval, Enrique; Pigrau, Carles; Benito, Natividad; Falgueras, Luis; Palomino, Julián; Del Toro, María Dolores; Jover-Sáenz, Alfredo; Iribarren, José Antonio; Sánchez-Somolinos, Mar; Ramos, Antonio; Fernández-Sampedro, Marta; Riera, Melchor; Baraia-Etxaburu, Josu Mirena; Ariza, Javier
Levofloxacin plus rifampicin (L+R) is the treatment of choice for acute staphylococcal prosthetic joint infection (PJI) managed with debridement and implant retention (DAIR). Long courses have been empirically recommended, but some studies have suggested that shorter treatments could be as effective. Our aim was to prove that a short treatment schedule was non-inferior to the standard long schedule. An open-label, multicentre, randomised clinical trial (RCT) was performed. Patients with an early post-surgical or haematogenous staphylococcal PJI, managed with DAIR and initiated on L+R were randomised to receive 8 weeks of treatment (short schedule) versus a long schedule (3 months or 6 months for hip or knee prostheses, respectively). The primary endpoint was cure rate. From 175 eligible patients, 63 were included (52% women; median age, 72 years): 33 patients (52%) received the long schedule and 30 (48%) received the short schedule. There were no differences between the two groups except for a higher rate of polymicrobial infection in the long-schedule group (27% vs. 7%; P = 0.031). Median follow-up was 540 days. In the intention-to-treat analysis, cure rates were 58% and 73% in patients receiving the long and short schedules, respectively (difference -15.7%, 95% CI -39.2% to 7.8%). Forty-four patients (70%) were evaluable per-protocol: cure rates were 95.0% and 91.7% for the long and short schedules, respectively (difference 3.3%, 95% CI -11.7% to 18.3%). This is the first RCT suggesting that 8 weeks of L+R could be non-inferior to longer standard treatments for acute staphylococcal PJI managed with DAIR.
Reznik, Robert S.; Ichim, Thomas E.; Petrov, Vladimir; Reznik, Boris N.
The Russian population offers a unique opportunity for conducting clinical trials in general, and specifically in the area of Medical Devices. Although the regulatory framework for approval of clinical trials and eventual marketing registration is based on an American-style format, details of operating in the Russian framework are very different. Understanding and leveraging the unique characteristics of the Russian system on the patient side, the investigator side, and the regulatory side is important in extracting optimum value out of clinical trials in Russia. Having performed Medical Device research and clinical trials in Russia, the authors overview the present system and describe various strategies for working in this growing but still under-utilized clinical trials arena.
Freund, Tobias; Peters-Klimm, Frank; Boyd, Cynthia M; Mahler, Cornelia; Gensichen, Jochen; Erler, Antje; Beyer, Martin; Gondan, Matthias; Rochon, Justine; Gerlach, Ferdinand M; Szecsenyi, Joachim
Patients with multiple chronic conditions are at high risk for potentially avoidable hospitalizations, which may be reduced by care coordination and self-management support. Medical assistants are an increasingly available resource for patient care in primary care practices. To determine whether protocol-based care management delivered by medical assistants improves care in patients at high risk for future hospitalization in primary care. Two-year cluster randomized clinical trial. (Current Controlled Trials: ISRCTN56104508). 115 primary care practices in Germany. 2076 patients with type 2 diabetes, chronic obstructive pulmonary disease, or chronic heart failure and a likelihood of hospitalization in the upper quartile of the population, as predicted by an analysis of insurance data. Protocol-based care management, including structured assessment, action planning, and monitoring delivered by medical assistants, compared with usual care. All-cause hospitalizations at 12 months (primary outcome) and quality-of-life scores (12-Item Short Form Health Survey [SF-12] and EuroQol instrument [EQ-5D]). Included patients had an average of 4 co-occurring chronic conditions. All-cause hospitalizations did not differ between groups at 12 months (risk ratio [RR], 1.01 [95% CI, 0.87 to 1.18]) and 24 months (RR, 0.98 [CI, 0.85 to 1.12]). Quality of life (differences, 1.16 [CI, 0.24 to 2.08] on SF-12 physical component and 1.68 [CI, 0.60 to 2.77] on SF-12 mental component) and general health (difference on EQ-5D, 0.03 [CI, 0.00 to 0.05]) improved significantly at 24 months. Intervention costs totaled $10 per patient per month. Small number of primary care practices and low intensity of intervention. This low-intensity intervention did not reduce all-cause hospitalizations but showed positive effects on quality of life at reasonable costs in high-risk multimorbid patients. AOK Baden-Württemberg and AOK Bundesverband.
data quality in this study, a review of the military electronic health record for the relevant time period was conducted prior to each assessment and...unique qualities of suicidal drivers. 78 2016 Military Health Systems Research Symposium (Orlando, FL) Presentation title: Operation Worth...Active-Duty Soldiers who presented to a military outpatient behavioral health clinic. There were 73 Soldiers received CAMS; 75 Soldiers received E
Soldiers who are experiencing suicidal ideation and/or behaviors. Research clinicians for both treatment conditions were recruited from the Army...staff. Participants were recruited from a number of sources at the ARS including the outpatient behavioral health clinic and the inpatient unit...Approvals from all IRB committees involved in the study have been obtained. Participant recruitment began in MAY 2012 for the training phase of the
Setia, Maninder Singh
In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184
Weng, Chunhua; Kahn, Michael; Gennari, John
Clinical trial protocols include detailed temporal constraints on treatment and associated tasks. Unlike health-care guidelines, protocols are highly prescriptive. Therefore, informatics applications that enforce such temporal constraints are more directly useful with protocols than with guidelines. Although there are some temporal knowledge representation efforts for health-care guidelines, we find these to be insufficiently expressive for clinical trial protocols. In this paper, we focus on temporal knowledge representation for clinical trial protocols and the task of patient-specific scheduling in protocols. We define a temporal ontology, use it to encode clinical trial protocols, and describe a prototype tool to carry out patient-specific scheduling for the tasks in protocols. We predict that an expressive temporal knowledge representation can support a number of scheduling and management tasks for protocol-based care. PMID:12463951
FitzGerald, T J; Urie, Marcia; Ulin, Kenneth; Laurie, Fran; Yorty, Jeffrey; Hanusik, Richard; Kessel, Sandy; Jodoin, Maryann Bishop; Osagie, Gani; Cicchetti, M Giulia; Pieters, Richard; McCarten, Kathleen; Rosen, Nancy
Quality assurance in radiotherapy (RT) has been an integral aspect of cooperative group clinical trials since 1970. In early clinical trials, data acquisition was nonuniform and inconsistent and computational models for radiation dose calculation varied significantly. Process improvements developed for data acquisition, credentialing, and data management have provided the necessary infrastructure for uniform data. With continued improvement in the technology and delivery of RT, evaluation processes for target definition, RT planning, and execution undergo constant review. As we move to multimodality image-based definitions of target volumes for protocols, future clinical trials will require near real-time image analysis and feedback to field investigators. The ability of quality assurance centers to meet these real-time challenges with robust electronic interaction platforms for imaging acquisition, review, archiving, and quantitative review of volumetric RT plans will be the primary challenge for future successful clinical trials.
Klimt, C R
The subject of varied acceptance of clinical trial results is discussed in the context of review of trials with which I have been involved and my subjective evaluation of their impact on the practice of clinical medicine. My experience goes back to 1949 and a World Health Organization trial of hyperimmune gamma globulin against rabies. This was followed by a large trial of secondary prevention of poliomyelitis. I participated in the planning and initiation of the first chronic disease trial, the University Group Diabetes Program (UGDP). The latter lasted for 15 years and its ramifications continue to this day. My next trial was the Coronary Drug Project (CDP), a complex trial with more than 8,000 patients. The trials of aspirin and aspirin combined with persantine (the CDPA, AMIS, PARIS I, and PARIS II) followed. My last three trials were a trial of photocoagulation in diabetic retinopathy (DRS), a six-country trial of the antiarrhythmic drug mexiletine (IMPACT), and a study involving two diagnostic procedures for pulmonary embolism (PIOPED). When one considers, in retrospect, the plethora of trials one is struck by the uniform absence of a priori considerations of the impact on medical practice, or likely lack thereof, of possible outcomes.
Boutrand, J P
A clinical trial is designed to provide clinical evidence of compliance with the medical device Directives. Clinical evidence can also be based on systematic and objective literature review. This article highlights when to use the clinical or the literature route to demonstrate the safety and performance of a medical device.
Seow, Hsien-Yeang; Whelan, Patrick; Levine, Mark N; Cowan, Kathryn; Lysakowski, Barbara; Kowaleski, Brenda; Snider, Anne; Xu, Rebecca Y; Arnold, Andrew
Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD. We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data. Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry). The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.
Razzaghi, Mohammad Reza; Razi, Abdollah; Mazloomfard, Mohammad Mohsen; Golmohammadi Taklimi, Amin; Valipour, Reza; Razzaghi, Zahra
To compare efficacy and safety of holmium:YAG laser and pneumatic lithotripter in the management of ureteral stones. One hundred and twelve patients with 1 to 2 cm ureteral calculi were selected for pneumatic or holmium:YAG laser transurethral ureterolithotripsy (56 patients in each group). Ultrasonography and plain abdominal x-ray were performed for all the patients before the operation. The pneumatic lithoclast was Swiss LithoClast, while in laser lithotripsy, holmium:YAG laser frequency was used, which was usually set between 5 and 10 Hz at a power of 10 to 15 Watt. Intravenous urography was performed for all the patients at 3 months to assess functional status and to delineate the ureteral anatomy. The mean patients' age and stones' size were the same in both groups, and there were no statistical differences. Mean duration of lithotripsy was 13.7 ± 12.6 minutes in laser group and 7.9 ± 4.2 minutes in pneumatic lithotripsy group. Immediate stone-free rate was 100% and 82.1% in the laser and pneumatic groups, respectively (P = .001). Stone pushing back occurred only in 10 (17.9%) patients in pneumatic group. In terms of complications, such as perforation, mucosal injury, and bleeding, there were no differences between the two groups. No intravenous pyelography related complication was seen at 3-month follow-up. Laser lithotripsy is a superior approach for the management of upper ureteral stones of 1 to 2 cm in size due to its higher rate of stone clearance.
Scott, Christy K; Dennis, Michael L.
Aims Post-discharge monitoring and early re-intervention have become standard practice when managing numerous chronic conditions. These two experiments tested the effectiveness of Recovery Management Checkup (RMC) protocols for adult chronic substance users. Intervention RMC included quarterly monitoring; motivational interviewing to provide personalized feedback and to resolve ambivalence about substance use; treatment linkage, engagement, and retention protocols to increase the amount of treatment received. Participants and Setting Recruited from sequential addiction treatment admissions, participants in the two experiments were on average 36 and 38 years of age, mostly female (59% vs. 46%), African American (85% vs. 80%), and met past-year criteria for dependence (87% vs. 76%). Design Participants in both experiments were randomly assigned to the RMC or control condition and interviewed quarterly for 2 years. Measurement The Global Appraisal of Individual Needs (GAIN) was the main assessment instrument. Findings RMC participant outcomes were better than control participants in both experiments. Effect sizes were larger in the second experiment in terms of reducing days to readmission (Cohen’s d=0.41 vs. d=0.22), successive quarters in the community using substances (d= −0.32 vs. −0.19), past-month symptoms of abuse/dependence (d=−0.23 vs. −0.02) and increasing the days of abstinence over 2 years (d=+0.29 vs. 0.04). Conclusion RMC, which provided ongoing monitoring and linkage, is feasible to conduct and is effective for adults with chronic substance dependence. PMID:19344441
Sakpal, Tushar Vijay
Every clinical trial should be planned. This plan should include the objective of trial, primary and secondary end-point, method of collecting data, sample to be included, sample size with scientific justification, method of handling data, statistical methods and assumptions. This plan is termed as clinical trial protocol. One of the key aspects of this protocol is sample size estimation. The aim of this article is to discuss how important sample size estimation is for a clinical trial, and also to understand the effects of sample size over- estimation or under-estimation on outcome of a trial. Also an attempt is made to understand importance of minimum sample to detect a clinically important difference. This article is also an attempt to provide inputs on different parameters that impact sample size and basic rules for these parameters with the help of some simple examples. PMID:21829786
Study Protocol for a randomized controlled trial of mentalization based therapy against specialist supportive clinical management in patients with both eating disorders and symptoms of borderline personality disorder.
Robinson, Paul; Barrett, Barbara; Bateman, Anthony; Hakeem, Az; Hellier, Jennifer; Lemonsky, Fenella; Rutterford, Clare; Schmidt, Ulrike; Fonagy, Peter
The NOURISHED study: Nice OUtcomes for Referrals with Impulsivity, Self Harm and Eating Disorders.Eating Disorders (ED) and Borderline Personality Disorder (BPD) are both difficult to treat and the combination presents particular challenges. Both are associated with vulnerability to loss of mentalization (awareness of one's own and others' emotional state). In BPD, Mentalization Based therapy (MBT) has been found effective in reducing symptoms. In this trial we investigate the effectiveness and cost-effectiveness of MBT adapted for Eating disorders (Mentalization Based Therapy for Eating Disorders (MBT-ED)) compared to a standard comparison treatment, Specialist Supportive Clinical Management (SSCM-ED) in patients with a combination of an Eating Disorder and either a diagnosis of BPD or a history of self-harm and impulsivity in the previous 12 months. We will complete a multi-site single-blind randomized controlled trial (RCT) of MBT-ED vs SSCM-ED. Participants will be recruited from three Eating Disorder Services and two Borderline Personality Disorder Services in London. Participants allocated to MBT-ED will receive one year of weekly group and individual therapy and participants allocated to SSCM-ED will receive 20 sessions of individual therapy over 1 year. In addition, participants in both groups will have access to up to 5 hours of dietetic advice. The primary outcome measure is the global score on the Eating Disorders Examination. Secondary outcome measures include total score on the Zanarini BPD scale, the Object Relations Inventory, the Depression Anxiety Stress Scales, quality of life and cost-effectiveness. Measures are taken at recruitment and at 6 month intervals up to 18 months. This is the first Randomised Controlled Trial of MBT-ED in patients with eating disorders and symptoms of BPD and will provide evidence to inform therapy decisions in this group of patients. During MBT-ED mentalization is encouraged, while in SSCM-ED it is not overtly
Berger, Lee; Speare, Rick; Pessier, Allan; Voyles, Jamie; Skerratt, Lee F
Effective and safe treatments of amphibian chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd), are needed to prevent mortality in captive programs, reduce the risk of disease spread, and better manage the disease in threatened wild populations. Bd is susceptible to a range of antifungal agents and low levels of heat (>30 degrees C) when tested in vitro, but there are few proven methods for clearing adult amphibians of Bd, and acute drug toxicity is a problem for tadpoles and juveniles. In postmetamorphic animals, heat (32 and 37 degrees C) is the only well-supported treatment. Antifungal drugs have not undergone rigorous testing--for example, trials were small or lacked controls and thorough post-treatment testing. In addition, pharmacokinetic studies have not been performed so there are no data on blood or tissue levels of antifungal agents. However, itraconazole baths have been widely used in amphibian rescue and conservation programs and anecdotal evidence suggests that they are effective for adults and subadults. In an experimental trial with tadpoles, a low dose of itraconazole cleared Bd but may have been associated with cutaneous depigmentation. Fluconazole appeared safe for tadpoles as it did not cause mortality, and future attempts to find an effective dose may be worthwhile. Palliative restoration of blood sodium and potassium levels by administration of electrolyte solutions appears useful in frogs with clinical chytridiomycosis. Randomised and blinded clinical trials, which include basic pharmacological studies, are urgently needed to provide comparable evidence for the safety and efficacy of treatment options which are likely to vary with amphibian species. Priorities are to validate and optimize the use of heat and itraconazole regimes.
Kornmehl, Heather; Singh, Sanminder; Johnson, Mary Ann; Armstrong, April W
Atopic dermatitis (AD) is a chronic disease requiring regular follow-up. To increase access to dermatological care, online management of AD is being studied. However, a critical knowledge gap exists in determining AD patients' quality of life in direct-to-patient online models. In this study, we examined quality of life in AD patients managed through a direct-access online model. We randomized 156 patients to receiving care through a direct-access online platform or in person. Patients were seen for six visits over 12 months. At each visit, the patients completed Dermatology Life Quality Index/Children's Dermatology Life Quality Index (DLQI/CDLQI), and Short Form (SF-12). Between baseline and 12 months, the mean (standard deviation, SD) within-group difference in DLQI score in the online group was 4.1 (±2.3); for the in-person group, the within-group difference was 4.8 (±2.7). The mean (SD) within-group difference in CDLQI score in the online group was 4.7 (±2.8); for the in-person group, the within-group difference was 4.9 (±3.1). The mean (SD) within-group difference in physical component score (PCS) and mental component score (MCS) SF-12 scores in the online group was 6.5 (±3.8) and 8.6 (±4.3); for the in-person group, it was 6.8 (±3.2) and 9.1(±3.8), respectively. The difference in the change in DLQI, CDLQI, SF-12 PCS, and SF-12 MCS scores between the two groups was 0.72 (95% confidence interval [90% CI], -0.97 to 2.41), 0.23 (90% CI, -2.21 to 2.67), 0.34 (90% CI, -1.16 to 1.84), and 0.51 (90% CI, -1.11 to 2.13), respectively. All differences were contained within their equivalence margins. Adult and pediatric AD patients receiving direct-access online care had equivalent quality of life outcomes as those see in person. The direct-access online model has the potential to increase access to care for patients with chronic skin diseases.
Camilleri, Michael; Parkman, Henry P.; Shafi, Mehnaz A.; Abell, Thomas L.; Gerson, Lauren
This guideline presents recommendations for the evaluation and management of patients with gastroparesis. Gastroparesis is identified in clinical practice through the recognition of the clinical symptoms and documentation of delayed gastric emptying. Symptoms from gastroparesis include nausea, vomiting, early satiety, postprandial fullness, bloating, and upper abdominal pain. Management of gastroparesis should include assessment and correction of nutritional state, relief of symptoms, improvement of gastric emptying and, in diabetics, glycemic control. Patient nutritional state should be managed by oral dietary modifications. If oral intake is not adequate, then enteral nutrition via jejunostomy tube needs to be considered. Parenteral nutrition is rarely required when hydration and nutritional state cannot be maintained. Medical treatment entails use of prokinetic and antiemetic therapies. Current approved treatment options, including metoclopramide and gastric electrical stimulation (GES, approved on a humanitarian device exemption), do not adequately address clinical need. Antiemetics have not been specifically tested in gastroparesis, but they may relieve nausea and vomiting. Other medications aimed at symptom relief include unapproved medications or off-label indications, and include domperidone, erythromycin (primarily over a short term), and centrally acting antidepressants used as symptom modulators. GES may relieve symptoms, including weekly vomiting frequency, and the need for nutritional supplementation, based on open-label studies. Second-line approaches include venting gastrostomy or feeding jejunostomy; intrapyloric botulinum toxin injection was not effective in randomized controlled trials. Most of these treatments are based on open-label treatment trials and small numbers. Partial gastrectomy and pyloroplasty should be used rarely, only in carefully selected patients. Attention should be given to the development of new effective therapies for
Graham, Michael M
The Clinical Trials Network of the Society of Nuclear Medicine was formed to provide quality assurance of both imaging and radiopharmaceutical manufacturing in clinical trials. The intention is to register and qualify a large number (>200) of sites, both in the United States and internationally, to be able to do the positron emission tomography imaging part of clinical trials. Initially, the types of trials to be supported include evaluation of novel radiopharmaceuticals and trials that use approved or experimental radiopharmaceuticals for early assessment of tumor response to novel chemotherapy agents. The Clinical Trials Network is organized into 7 committees that provide overall oversight and strategic guidance, database management, site qualification and monitoring, scanner validation, clinical site orientation, technologist education, trial design, and a manufacturer's registry. At the end of the first year, more than 200 potential clinical trial sites and more than 125 manufacturing sites have expressed interest in participating. The qualification process is well underway. Funding is being provided by 3 large pharmaceutical companies. An investigational new drug application has been obtained for F-18 fluorothymidine that is held by Society of Nuclear Medicine to allow simplification of data management during multisite trials with F-18 fluorothymidine. A second investigational new drug application is in preparation for F-18 fluoromisonidazole. A supply of oncology chest phantoms has been manufactured and have been shipped to numerous sites for scanner validation. Educational materials are being developed for the physicians, technologists, and research coordinators at the sites. This is an important initiative that is likely to help significantly expand the role of molecular imaging and will help bring the right treatment to the right patient at the right time. Copyright 2010 Elsevier Inc. All rights reserved.
Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabeth; McCormack, Sheena
After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs. PMID:23561044
Chen, Jane; Wilkoff, Bruce L; Choucair, Wassim; Cohen, Todd J; Crossley, George H; Johnson, W Ben; Mongeon, Luc R; Serwer, Gerald A; Sherfesee, Lou
Background Although pacemakers are primarily used for the treatment of bradycardia, diagnostic data available in current pacemakers allow them to be also used as sophisticated, continuous monitoring devices. Easy access to these stored data may assist clinicians in making diagnostic and therapeutic decisions sooner, thus avoiding potential long-term sequelae due to untreated clinical disorders. Internet-based remote device interrogation systems provide clinicians with frequent and complete access to stored data in pacemakers. In addition to monitoring device function, remote monitors may be a helpful tool in assisting physicians in the management of common arrhythmia disorders. Methods The Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial is a prospective, randomized, parallel, unblinded, multicenter, open label clinical trial to determine the utility of remote pacemaker interrogation in the earlier diagnosis of clinically actionable events compared to the existing practice of transtelephonic monitoring. There have been 980 patients enrolled and randomized to receive pacemaker follow up with either remote interrogation using the Medtronic CareLink® Network (CareLink) versus the conventional method of transtelephonic monitoring (TTM) in addition to periodic in-person interrogation and programming evaluations. The purpose of this manuscript is to describe the design of the PREFER trial. The results, to be presented separately, will characterize the number of clinically actionable events as a result of pacemaker follow-up using remote interrogation instead of TTM. Trial registration ClinicalTrials.gov: NCT00294645. PMID:18387185
Gatsonis, C; Greenhouse, J B
Phase I clinical trials are conducted to determine the dose-response curve of a new drug with respect to toxic side effects and, in particular, to estimate the maximum tolerated dose (MTD). In this paper we take a Bayesian approach to the problem of making inferences about the MTD. Working with broad classes of priors, we obtain the posterior distribution of the MTD and study its properties. We also address the question of providing updated assessments of the risk of toxicity for new patients entering the study at a specific dose level. These assessments would be useful in deciding issues of study management and ethics. Our analysis pays particular attention to the sensitivity of the inferences and risk assessments to the choice of prior and the choice of model for the dose-response relationship.
Conroy, Elizabeth J; Harman, Nicola L; Lane, J Athene; Lewis, Steff C; Murray, Gordon; Norrie, John; Sydes, Matt R; Gamble, Carrol
The Medical Research Council Guidelines for Good Clinical Practice outlines a three-committee trial oversight structure--the day-to-day Trial Management Group, the Data Monitoring Committee and the Trial Steering Committee. In this model, the Trial Steering Committee is the executive committee that oversees the trial and considers the recommendations from the Data Monitoring Committee. There is yet to be in-depth consideration establishing the Trial Steering Committee's role and functionality. A survey to establish Trial Steering Committee's current practices, role and the use and opinion on the Medical Research Council guidelines was undertaken within UK Clinical Research Collaborative registered Clinical Trials Units. Completed surveys were obtained from 38 of 47 fully and partially registered Units. Individual items in the survey were analysed and reported spanning current Trial Steering Committee practices including its role, requirement and experience required for membership; methods to identify members; and meeting frequency. Terms (a document describing the committee's remit, objectives and functionality) were obtained and analysed from 21 of 33 Units with documents in place at their Unit. A total of 20 responders suggested aspects of the current Medical Research Council Guidelines that need improvement. We present the first survey reporting on practices within UK Clinical Research Collaborative registered Clinical Trials Units on the experience and remits of Trial Steering Committees. We have identified a widespread adoption of Medical Research Council Guidelines for Trial Steering Committees in the United Kingdom, but limitations in this existing provision have been identified that need to be addressed. © The Author(s) 2015.
Aragonès, Enric; López-Cortacans, Germán; Caballero, Antonia; Piñol, Josep Ll; Sánchez-Rodríguez, Elisabet; Rambla, Concepció; Tomé-Pires, Catarina; Miró, Jordi
Chronic musculoskeletal pain and depression are very common in primary care patients. Furthermore, they often appear as comorbid conditions, resulting in additive effect on adverse health outcomes. On the basis of previous studies, we hypothesise that depression and chronic musculoskeletal pain may benefit from an integrated management programme at primary care level. We expect positive effects on both physical and psychological distress of patients. To determine whether a new programme for an integrated approach to chronic musculoskeletal pain and depression leads to better outcomes than usual care. Cluster-randomised controlled trial involving two arms: a) control arm (usual care); and b) intervention arm, where patients participate in a programme for an integrated approach to the pain-depression dyad. Primary care centres in the province of Tarragona, Catalonia, Spain, Participants: We will recruit 330 patients aged 18-80 with moderate or severe musculoskeletal pain (Brief Pain Inventory, average pain subscale ≥5) for at least 3 months, and with criteria for major depression (DSM-IV). A multicomponent programme according to the chronic care model. The main components are care management, optimised antidepressant treatment, and a psychoeducational group action. Blind measurements: The patients will be monitored through blind telephone interviews held at 0, 3, 6 and 12 months. Severity of pain and depressive symptoms, pain and depression treatment response rates, and depression remission rates. The outcomes will be analysed on an intent-to-treat basis and the analysis units will be the individual patients. This analysis will consider the effect of the study design on any potential lack of independence between observations made within the same cluster. The protocol was approved by the Research Ethics Committee of the Jordi Gol Primary Care Research Institute (IDIAP), Barcelona, (P14/142). This project strengthens and improves treatment approaches for a major
Mitchell, Rick; Shah, Maitri; Ahmad, Sushma; Rogers, Audrey Smith; Ellenberg, Jonas H
Even after intensive review, interpretative questions, ambiguities, contradictions, or errors, will arise once the protocol is scrutinized by site IRBs and implemented at sites. This will occur despite preparation and implementation of site protocol training, and provision of well crafted case report forms for the reporting of clinical and laboratory evaluations and adverse events. Since many staff are involved in each protocol, site investigators or study coordinators might direct protocol queries, participant management, or IRB queries to different network participants, resulting in inconsistent responses. It is important to establish a response mechanism that ensures consistent responses and their systematic documentation. For reporting of adverse events, and the submission of or documentation of completion of regulatory requirements, an easily accessible and structured communications system is also required. This paper describes the development and implementation of a user-friendly web-based query and notification system (QNS) for subject management, adverse events, regulatory, and IRB components. This system was created in the Adolescent Trials Network for HIV/AIDS Interventions (ATN), using existing web based tools with minor modifications and minimal cost. The query and notification system is interactive and allows for free flow of information among the site coordinators and both the protocol teams and the regulatory group. The process of the system is transparent to users at the sites, although its use and maintenance is controlled by Data Operations Center staff, to assure that ATN requirements for review and approval are met. This results in consistency of and timeliness of responses to queries, timeliness and accuracy of adverse event reporting and the ability for the data operations center regulatory staff to provide notification of pending or delinquent regulatory submissions.
Fernández-González, Felipe J.; Cabero-López, Jorge; Brizuela, Aritza; Suazo, Ivan; Pérez-Pevida, Esteban; Cobo, Teresa; Montalban, Oier; Diéguez-Pereira, Markel; Chávarri-Prado, David; de la Pinta, Iker Bellanco; Jiménez-Garrudo, Antonio
Background: For patients whose centric relation (CR) has not been considered at the start and during treatment, the task of achieving an occlusal scheme that works together with the temporomandibular joint, the muscles, and the structures of the stomatognathic apparatus becomes a major concern. Objective: This study aims to describe a reproducible, predictable and to date unreported procedure of selective grinding guided by an occlusal splint and to analyze condylar position (CP) based on the skeletal pattern. Methods: A total of 72 symptomatic patients (38 females and 34 males) were classified into three groups: hyperdivergent, intermediate and hypodivergent. CP was quantified by mounted casts on a measures condyle displacement (MCD) device. Helkimo index was also performed in order to assess the severity of the temporomandibular joint (TMJ) disorders attending to clinical dysfunction, occlusal state and anamnestic dysfunction. Once the stability had been obtained, the splint was progressively reduced until the maximum intercuspation (MIC) was achieved. Results: The vertical displacement was found to be significantly different between the hyperdivergent and other two groups (p<0.01). Comparisons of MCD analysis before and after the selective grinding procedure identified a statistically significant difference in the horizontal and vertical CP (p<0.01) between the different groups whereas the Helkimo Index showed a clear improvement of TMJ disorders. Conclusion: All facial types, specially the hyperdivergent face type, showed a reduction in condylar displacement (CD) and less craniomandibular symptoms using this procedure, making it an excellent technique for clinicians. PMID:28839479
Hollander, Priscilla; Bays, Harold E; Rosenstock, Julio; Frustaci, Mary Ellen; Fung, Albert; Vercruysse, Frank; Erondu, Ngozi
To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes (N = 335, aged 18-65 years, BMI ≥30 to <50 kg/m(2) or BMI ≥27 to <50 kg/m(2) with hypertension and/or dyslipidemia). Participants were randomized (1:1:1:1) to receive PBO, CANA 300 mg, PHEN 15 mg, or coadministration of CANA 300 mg and PHEN 15 mg (CANA/PHEN) orally once daily. The primary end point was percent change in body weight from baseline to week 26; key secondary end points were the proportion of participants achieving weight loss ≥5% and change from baseline in systolic blood pressure. CANA/PHEN provided statistically superior weight loss from baseline versus PBO at week 26 (least squares mean difference -6.9% [95% CI -8.6 to -5.2]; P < 0.001). CANA/PHEN also provided statistically superior achievement of weight loss ≥5% and reduction in systolic blood pressure compared with PBO. CANA/PHEN was generally well tolerated, with a safety and tolerability profile consistent with that of the individual components. CANA/PHEN produced meaningful reductions in body weight and was generally well tolerated in individuals who were overweight or obese without type 2 diabetes. Further studies are warranted to evaluate potential use of this combination for long-term weight management. © 2017 by the American Diabetes Association.
Ness, Elizabeth A; Royce, Cheryl
Clinical trials are paramount to improving human health. New trial designs and informed consent issues are emerging as a result of genomic profiling and the development of molecularly targeted agents. Many groups and individuals are responsible for ensuring the protection of research participants and the quality of the data produced. The specialty role of the clinical trials nurse (CTN) is critical to clinical trials. Oncology CTNs have competencies that can help guide their practice; however, not all oncology clinical trials are supervised by a nurse. Using the process of engagement, one organization has restructured oncology CTNs under a nurse-supervised model.
Held, Claes; Hylek, Elaine M; Alexander, John H; Hanna, Michael; Lopes, Renato D; Wojdyla, Daniel M; Thomas, Laine; Al-Khalidi, Hussein; Alings, Marco; Xavier, Dennis; Ansell, Jack; Goto, Shinya; Ruzyllo, Witold; Rosenqvist, Mårten; Verheugt, Freek W A; Zhu, Jun; Granger, Christopher B; Wallentin, Lars
In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the
Reed, Richard L; Barton, Christopher A; Isherwood, Linda M; Baxter, Jodie M Oliver; Roeger, Leigh
A robust research base is required in General Practice. The research output for General Practice is much less than those of other clinical disciplines. A major impediment to more research in this sector is difficulty with recruitment. Much of the research in this area focuses on barriers to effective recruitment and many projects have great difficulty with this process. This paper seeks to describe a systematic approach to recruitment for a randomized controlled trial that allowed the study team to recruit a substantial number of subjects from General Practice over a brief time period. A systematic approach to recruitment in this setting based on prior literature and the experience of the investigator team was incorporated into the design and implementation of the study. Five strategies were used to facilitate this process. These included designing the study to minimize the impact of the research on the day-to-day operations of the clinics, engagement of general practitioners in the research, making the research attractive to subjects, minimizing attrition and ensuring recruitment was a major focus of the management of the study. Outcomes of the recruitment process were measured as the proportion of practices that agreed to participate, the proportion of potentially eligible subjects who consented to take part in the trial and the attrition rate of subjects. Qualitative interviews with a subset of successfully recruited participants were done to determine why they chose to participate in the study; data were analyzed using thematic analysis. Five out of the six general practices contacted agreed to take part in the study. Thirty-eight per cent of the 1663 subjects who received a letter of invitation contacted the university study personnel regarding their interest in the project. Recruitment of the required number of eligible participants (n = 256) was accomplished in seven months. Thematic analysis of interviews with 30 participants regarding key factors in their
Haase, G M
Prospective clinical trials are used to evaluate therapeutic interventions. Because surgery is involved in the diagnosis, staging, and therapy of solid malignancies, active surgical leadership in these cancer studies is important. There are currently barriers to widespread surgical participation in clinical trials. This report defines the obstacles as well as documents efforts to overcome them and improve surgical quality assurance in cooperative group research. The surgical leadership of several clinical cooperative groups sponsored by the National Cancer Institute (NCI) were interviewed. Cooperative group reports were analyzed with respect to internal audits, quality assurance and activities of surgical monitoring committees. Minutes from meetings of the NCI's workshops on "Surgeons in Clinical Trials" were reviewed. Six concerns present impediments to surgical quality in clinical trials. To address these, substantive surgical leadership is being developed throughout the cooperative group system. Surgical co-principal investigators for institutions and protocols are being appointed. Uniform surgical standards and operative guidelines are being developed. Surgical data review occur at the local institution as well as through central audits and surgical monitoring committees. Coordinators in surgical data management are being trained. Surgical education is organized at cooperative group meetings and disseminated to the surgical community by seminars, workshops, audiovisual teaching sessions, and scientific publications. Surgeons are playing increasing leadership roles in the cancer trials performed by cooperative groups. Surgical leaders are dedicated to a broad-scale quality assurance effort. Enhanced surgical commitment, widespread clinical participation, and focused leadership should affect a high level of surgical quality care in clinical trials research.
Javidan, Abbas Norouzi; Shahbazian, Heshmatollah; Emami, Amirhossein; Yekaninejad, Mir Saeed; Emami-Razavi, Hassan; Farhadkhani, Masoumeh; Ahmadzadeh, Ahmad; Gorjipour, Fazel
Recombinant human erythropoietin (rHuEPO) is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2) years. 48.7% of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43) g/dL at beginning of the study and reached 10.96 (±2.23) g/dL after 4 months and showed significant increase overall (P<0.001). PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL). Anemia were successfully corrected in 49% of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis.
AD-AIN 354 STANFORD UNIV CA DEPT OF STATISTICS F/V 12/1 ALLOCATION RULES FOR SEQUENTIAL CLINICAL TRIALS .(U) JUL 82 D SIEGMUND N00V11577-C-V306...UNCLASSIFIED TR 18 NL ALLOCATION RULES FOR SEQUENTIAL CLINICAL TRIALS BY D. SIEGMUND TECHNICAL REPORT NO. 18 JULY 1982 PREPARED UNDER CONTRACT N00014-77-C...at all. Rere me. discuss (I) and (11) or mes"s 9f a Monte Carlo experiment. The advantages of randomization in clinical trials has been discussed at
Ellimoottil, Chad; Vijan, Sandeep; Flanigan, Robert C
A well-designed and executed clinical trial is the gold standard of evidence-based medicine. It is important for readers to understand the rationale for the study design, identify common pitfalls, and scrutinize limitations. Herein, we present a brief overview of types of designs used for clinical trials and discuss the use of appropriate end points, the selection of study participants, randomization, sample size calculation, blinding, and analysis of data. Finally, we emphasize the importance of accurate and transparent reporting. Our goal is to provide a primer for practicing urologists to enhance their understanding of the clinical trial literature.
González-Moreno, María; Saborido, Cristian; Teira, David
Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple.
Smed, Marie; Getz, Kenneth A
Knowledge generated by site representatives through their participation in clinical trials is valuable for testing new products in use and obtaining final market approval. The leverage of this important knowledge is however challenged as the former direct relationships between in-house staff in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract Research Organization) and thereby adding another link in the relationships between site and sponsor. These changes are intended to optimize the time-consuming and costly trial phases; however, there is a need to study whether valuable knowledge and experience is compromised in the process. Limited research exists on the full range of clinical practice insights obtained by investigators during and after clinical trials and how well these insights are transferred to study sponsors. This study explores the important knowledge-transfer processes between sites and sponsors and to what extent sites' knowledge gained in clinical trials is utilized by the industry. Responses from 451 global investigative site representatives are included in the study. The analysis of the extensive dataset reveals that the current processes of collaboration between sites and the industry restrict the leverage of valuable knowledge gained by physicians in the process of clinical trials. These restrictions to knowledge-transfer between site and sponsor are further challenged if CRO partners are integrated in the trial process.
Ellis, Cara E; Korbutt, Gregory S
The development of the Edmonton Protocol encouraged a great deal of optimism that a cell-based cure for type I diabetes could be achieved. However, donor organ shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Consequently, it is important to consider whether the current science meets the ethical requirements for moving toward clinical trials. Despite the potential risks and the scientific unknowns that remain to be investigated, there is optimism regarding the xenotransplantation of some types of tissue, and enough evidence has been gathered to ethically justify clinical trials for the most safe and advanced area of research, porcine islet transplantation. Researchers must make a concerted effort to maintain a positive image for xenotransplantation, as a few well-publicized failed trials could irrevocably damage public perception of xenotransplantation. Because all of society carries the burden of risk, it is important that the public be involved in the decision to proceed. As new information from preclinical and clinical trials develops, policy decisions should be frequently updated. If at any point evidence shows that islet xenotransplantation is unsafe, then clinical trials will no longer be justified and they should be halted. However, as of now, the expected benefit of an unlimited supply of islets, combined with adequate informed consent, justifies clinical trials for islet xenotransplantation.
Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L
A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well.
Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy
The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.
... Sponsors Why Are They Important How Do They Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites What Are the ...
Gadde, Kishore M; Pritham Raj, Y
This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0 mg-which have been approved by the US Food and Drug Administration (FDA) for long-term management of obesity since 2012. Topics discussed in this paper include rationale for pharmacotherapy, history of antiobesity drugs, and efficacy and safety data from randomized controlled trials with implications for clinical practice. Weight loss achieved by currently approved drugs ranges from approximately 3 to 9%, above and beyond weight loss with lifestyle counseling alone, after a year. Response and attrition rates in clinical trials indicate that the benefits of pharmacotherapy range from substantial for some patients, modest for others, and no benefits for others still. Decisions regarding selection of a suitable drug from the available pharmacotherapy options and duration of treatment should be based on the expected and observed benefit-to-risk balance and tailored to the needs of each individual patient using the principles of shared decision-making.
Urooj, Mohd; Husain, Gulam Mohammed; Khan, Mohammad Ahmed; Kazmi, Munawwar Husain
The recent amendments notified by the Government of India, for conducting clinical trial, is greatly appreciable as promoting safety and well-being of human subjects. These rules clearly state that medical management of injuries in clinical trials is mandatory, and clinical trial-related injury or death needs to be compensated over and above the medical management. These rules need to be reconsidered for simplification and better understanding of issues regarding compensation. There is a need of clarity at some points which should be discussed with all stakeholders for better understanding of current regulations. In our view, attention must also be given to academic investigators, during discussion to promote availability of cost-effective treatment in India. PMID:28929045
Allen, K D; Bierma-Zeinstra, S M A; Foster, N E; Golightly, Y M; Hawker, G
Rigorous implementation research is important for testing strategies to improve the delivery of effective osteoarthritis (OA) interventions. The objective of this manuscript is to describe principles of implementation research, including conceptual frameworks, study designs and methodology, with specific recommendations for randomized clinical trials of OA treatment and management. This manuscript includes a comprehensive review of prior research and recommendations for implementation trials. The review of literature included identification of seminal articles on implementation research methods, as well as examples of previous exemplar studies using these methods. In addition to a comprehensive summary of this literature, this manuscript provides key recommendations for OA implementation trials. This review concluded that to date there have been relatively few implementation trials of OA interventions, but this is an emerging area of research. Future OA clinical trials should routinely consider incorporation of implementation aims to enhance translation of findings.
Panakanti, Tandava Krishnan; Chhablani, Jay
Branch retinal vein occlusion (BRVO) is the second most common retinal vascular disorder. The management of macular edema has changed considerably over time. The laser is considered the gold standard treatment for over two decades. However, visual recovery with laser is usually slow and incomplete. The advent of intravitreal agents, specifically anti-vascular endothelial growth factors (VEGF) have heralded a new era which promises rapid recovery of vision and quality of vision. Randomized clinical trials have reported optimal results with anti-VEGF agents (ranibizumab, bevacizumab, and aflibercept) compared to laser therapy or steroids. However, nearly 50% of the patients require repeat intravitreal anti-VEGF therapy up to 4 years after initiating therapy to sustain the visual gains. The adverse events (systemic and ocular) of these agents are minimal. Monotherapy with anti-VEGF agents have been found to provide better results than any combination with laser. This review article summarizes evidence from randomized controlled trials evaluating treatment options for the treatment of macular edema secondary to BRVO with a special focus on anti-VEGF therapy. PMID:26957837
Melo, J A
This article provides an overview of the main problems that ethics committees deal with when analysing clinical trials. Some characteristics of the different phases are discussed as well as some particular problems of the Portuguese law.
Geller, Nancy L; Kim, Dong-Yun; Tian, Xin
This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.
Molloy, Síle F; Henley, Patricia
This article describes the processes and procedures involved in planning, conducting and reporting monitoring activities for large Clinical Trials of Investigational Medicinal Products (CTIMPs), focusing on those conducted in resource-limited settings. © 2016 John Wiley & Sons Ltd.
Scientific review ensures that studies are based on sound science, which contributes to the safety of clinical trial participants. Learn about the role of Institutional Review Boards (IRBs), Data and Safety Monitoring Boards (DSMBs), and government agenci
Wang, Philip S.; Simon, Gregory E.; Avorn, Jerry; Azocar, Francisca; Ludman, Evette J.; McCulloch, Joyce; Petukhova, Maria Z.; Kessler, Ronald C.