Projecting future drug expenditures--2009.

PubMed

Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

2009-02-01

Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

Preclinical drug development.

PubMed

Brodniewicz, Teresa; Grynkiewicz, Grzegorz

2010-01-01

Life sciences provide reasonably sound prognosis for a number and nature of therapeutic targets on which drug design could be based, and search for new chemical entities--future new drugs, is now more than ever based on scientific principles. Nevertheless, current very long and incredibly costly drug discovery and development process is very inefficient, with attrition rate spanning from many thousands of new chemical structures, through a handful of validated drug leads, to single successful new drug launches, achieved in average after 13 years, with compounded cost estimates from hundreds of thousands to over one billion US dollars. Since radical pharmaceutical innovation is critically needed, number of new research projects concerning this area is steeply rising outside of big pharma industry--both in academic environment and in small private companies. Their prospective success will critically depend on project management, which requires combined knowledge of scientific, technical and legal matters, comprising regulations concerning admission of new drug candidates to be subjects of clinical studies. This paper attempts to explain basic rules and requirements of drug development within preclinical study period, in case of new chemical entities of natural or synthetic origin, which belong to low molecular weight category.

24 CFR 247.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... CERTAIN SUBSIDIZED AND HUD-OWNED PROJECTS Subsidized Projects § 247.2 Definitions. Drug-related criminal... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Definitions. 247.2 Section 247.2 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF...

INTEGRATING HEALTH TECHNOLOGY ASSESSMENT PRINCIPLES IN FORMULARY MANAGEMENT.

PubMed

Teng, Monica; Khoo, Ai Leng; Zhao, Ying Jiao; Lin, Liang; Lim, Boon Peng

2016-01-01

Effective formulary management in healthcare institutions safeguards rational drug use and optimizes health outcomes. We implemented a formulary management program integrating the principles of health technology assessment (HTA) to improve the safe, appropriate, and cost-effective use of medicine in Singapore. A 3-year formulary management program was initiated in 2011 in five public healthcare institutions. This program was managed by a project team comprising HTA researchers. The project team worked with institutional pharmacy and therapeutics (P&T) committees to: (i) develop tools for formulary drug review and decision making; (ii) enhance the HTA knowledge and skills of formulary pharmacists and members of P&T committees; (iii) devise a prioritization framework to overcome resource constraints and time pressure; and (iv) conceptualize and implement a framework to review existing formulary. Tools that facilitate drug request submission, drug review, and decision making were developed for formulary drug inclusion. A systematic framework to review existing formulary was also developed and tested in selected institutions. A competency development plan was rolled out over 2 years to enhance formulary pharmacists' proficiency in systematic literature search and review, meta-analysis, and pharmacoeconomic evaluation. The plan comprised training workshops and on-the-job knowledge transfer between the project team and institutional formulary pharmacists through collaborating on selected drug reviews. A resource guide that consolidated the tools and templates was published to encourage the adoption of best practices in formulary management. Based on the concepts of HTA, we implemented an evidence-based approach to optimize formulary management.

Accessing external innovation in drug discovery and development.

PubMed

Tufféry, Pierre

2015-06-01

A decline in the productivity of the pharmaceutical industry research and development (R&D) pipeline has highlighted the need to reconsider the classical strategies of drug discovery and development, which are based on internal resources, and to identify new means to improve the drug discovery process. Accepting that the combination of internal and external ideas can improve innovation, ways to access external innovation, that is, opening projects to external contributions, have recently been sought. In this review, the authors look at a number of external innovation opportunities. These include increased interactions with academia via academic centers of excellence/innovation centers, better communication on projects using crowdsourcing or social media and new models centered on external providers such as built-to-buy startups or virtual pharmaceutical companies. The buzz for accessing external innovation relies on the pharmaceutical industry's major challenge to improve R&D productivity, a conjuncture favorable to increase interactions with academia and new business models supporting access to external innovation. So far, access to external innovation has mostly been considered during early stages of drug development, and there is room for enhancement. First outcomes suggest that external innovation should become part of drug development in the long term. However, the balance between internal and external developments in drug discovery can vary largely depending on the company strategies.

Antiviral drug research proposal activity.

PubMed

Injaian, Lisa; Smith, Ann C; Shipley, Jennifer German; Marbach-Ad, Gili; Fredericksen, Brenda

2011-01-01

The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an "expert" in one aspect of the project. The Antiviral Drug Research Proposal (ADRP) culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity.

Antiviral Drug Research Proposal Activity †

PubMed Central

Injaian, Lisa; Smith, Ann C.; Shipley, Jennifer German; Marbach-Ad, Gili; Fredericksen, Brenda

2011-01-01

The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an “expert” in one aspect of the project. The Antiviral Drug Research Proposal (ADRP) culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity. PMID:23653735

Inroads to predict in vivo toxicology-an introduction to the eTOX Project.

PubMed

Briggs, Katharine; Cases, Montserrat; Heard, David J; Pastor, Manuel; Pognan, François; Sanz, Ferran; Schwab, Christof H; Steger-Hartmann, Thomas; Sutter, Andreas; Watson, David K; Wichard, Jörg D

2012-01-01

There is a widespread awareness that the wealth of preclinical toxicity data that the pharmaceutical industry has generated in recent decades is not exploited as efficiently as it could be. Enhanced data availability for compound comparison ("read-across"), or for data mining to build predictive tools, should lead to a more efficient drug development process and contribute to the reduction of animal use (3Rs principle). In order to achieve these goals, a consortium approach, grouping numbers of relevant partners, is required. The eTOX ("electronic toxicity") consortium represents such a project and is a public-private partnership within the framework of the European Innovative Medicines Initiative (IMI). The project aims at the development of in silico prediction systems for organ and in vivo toxicity. The backbone of the project will be a database consisting of preclinical toxicity data for drug compounds or candidates extracted from previously unpublished, legacy reports from thirteen European and European operation-based pharmaceutical companies. The database will be enhanced by incorporation of publically available, high quality toxicology data. Seven academic institutes and five small-to-medium size enterprises (SMEs) contribute with their expertise in data gathering, database curation, data mining, chemoinformatics and predictive systems development. The outcome of the project will be a predictive system contributing to early potential hazard identification and risk assessment during the drug development process. The concept and strategy of the eTOX project is described here, together with current achievements and future deliverables.

[New drugs of abuse on the Web: the role of the Psychonaut Web Mapping Project].

PubMed

Schifano, Fabrizio; Ricciardi, Alessandra; Corazza, Ornella; Deluca, Paolo; Davey, Zoe; Rafanelli, Chiara

2010-01-01

In the rapid change of drug scenarios, as the powerful development in the drug market, particularly in the number and the kind of the compound available, Internet plays a dominant role to become one of the major "drug market". The European Commission funded the Psychonaut Web Mapping Project (carried out in the time-frame January 2008-December 2009), with the aim to start/implement an Early Warning System (through the data/information collected from the Web virtual market), to identify and categorise novel recreational drugs/psychoactive compounds (synthetical/herbal drugs), and new trends in drug use to provide information for immediate and prevention intervention. The Psychonaut is a multi-site research project involving 8 research centres (De Sleutel, Belgium; University of Hertfordshire School of Pharmacy, St George's University of London, England; A-klinikkasäätiö, Finlandia; Klinik für Psychiatrie und Psychotherapie, Germany; Assessorato Salute Regione Marche, Italy; Drug Abuse Unit, Spain; Centre of Competence Bergen Clinics Foundation, Norway) based in 7 European Countries (England, Italy, Belgium, Finland, Germany, Spain, Norway).

78 FR 63481 - Therapeutic Area Standards Initiative Project Plan; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

...] Therapeutic Area Standards Initiative Project Plan; Availability AGENCY: Food and Drug Administration, HHS... Therapeutic Area Standards Initiative Project Plan. This therapeutic area (TA) Project Plan will be the primary document for guiding all major aspects of FDA's multi-year initiative to develop and implement TA...

Drug Repurposing from an Academic Perspective.

PubMed

Oprea, Tudor I; Bauman, Julie E; Bologa, Cristian G; Buranda, Tione; Chigaev, Alexandre; Edwards, Bruce S; Jarvik, Jonathan W; Gresham, Hattie D; Haynes, Mark K; Hjelle, Brian; Hromas, Robert; Hudson, Laurie; Mackenzie, Debra A; Muller, Carolyn Y; Reed, John C; Simons, Peter C; Smagley, Yelena; Strouse, Juan; Surviladze, Zurab; Thompson, Todd; Ursu, Oleg; Waller, Anna; Wandinger-Ness, Angela; Winter, Stuart S; Wu, Yang; Young, Susan M; Larson, Richard S; Willman, Cheryl; Sklar, Larry A

2011-01-01

Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the "valley of death" by bridging basic to clinical sciences.

Drug Repurposing from an Academic Perspective

PubMed Central

Oprea, Tudor I.; Bauman, Julie E.; Bologa, Cristian G.; Buranda, Tione; Chigaev, Alexandre; Edwards, Bruce S.; Jarvik, Jonathan W.; Gresham, Hattie D.; Haynes, Mark K.; Hjelle, Brian; Hromas, Robert; Hudson, Laurie; Mackenzie, Debra A.; Muller, Carolyn Y.; Reed, John C.; Simons, Peter C.; Smagley, Yelena; Strouse, Juan; Surviladze, Zurab; Thompson, Todd; Ursu, Oleg; Waller, Anna; Wandinger-Ness, Angela; Winter, Stuart S.; Wu, Yang; Young, Susan M.; Larson, Richard S.; Willman, Cheryl; Sklar, Larry A.

2011-01-01

Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the “valley of death” by bridging basic to clinical sciences. PMID:22368688

Common characteristics of open source software development and applicability for drug discovery: a systematic review

PubMed Central

2011-01-01

Background Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery. Methods A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project. Results Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined. Conclusions We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents. PMID:21955914

Comprehensive summary--Predict-IV: A systems toxicology approach to improve pharmaceutical drug safety testing.

PubMed

Mueller, Stefan O; Dekant, Wolfgang; Jennings, Paul; Testai, Emanuela; Bois, Frederic

2015-12-25

This special issue of Toxicology in Vitro is dedicated to disseminating the results of the EU-funded collaborative project "Profiling the toxicity of new drugs: a non animal-based approach integrating toxicodynamics and biokinetics" (Predict-IV; Grant 202222). The project's overall aim was to develop strategies to improve the assessment of drug safety in the early stage of development and late discovery phase, by an intelligent combination of non animal-based test systems, cell biology, mechanistic toxicology and in silico modeling, in a rapid and cost effective manner. This overview introduces the scope and overall achievements of Predict-IV. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advanced Research Projects Agency counterdrug program

NASA Astrophysics Data System (ADS)

Pennella, John J.

1994-03-01

The Department of Defense (DoD), in support of the National Drug Control Strategy, has designated that detecting and countering the production, trafficking and use of illegal drugs is a high priority national security mission. The Advanced Research Projects Agency (ARPA) Counterdrug Program is assisting DoD in this objective by developing technology and prototype systems to enhance the capabilities of the DoD and civilian law enforcement agencies, consistent with the DoD mission and the supply reduction goals of the National Drug Control Strategy. The objective of this paper is to summarize the current ARPA Counterdrug Program, with special emphasis on the current efforts and future plans for developing technology to meet the National needs for Non-Intrusive Inspection.

Portfolio management in early stage drug discovery - a traveler's guide through uncharted territory.

PubMed

Betz, Ulrich A K

2011-07-01

Portfolio management in drug development has become a best practice in the pharmaceutical industry. By contrast, early on in the value chain - the discovery phase - portfolio management is still in its infancy. Nevertheless, owing to the attrition of R&D projects from phase to phase and the cost of capital involved, these early phases of drug discovery play a significant part for the overall cost of bringing new, innovative drugs to the market. This paper describes various approaches to manage a portfolio of projects in early-stage drug discovery and provides crucial factors that determine the success of such an approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

Factors that enable and hinder the implementation of projects in the alcohol and other drug field.

PubMed

MacLean, Sarah; Berends, Lynda; Hunter, Barbara; Roberts, Bridget; Mugavin, Janette

2012-02-01

Few studies systematically explore elements of successful project implementation across a range of alcohol and other drug (AOD) activities. This paper provides an evidence base to inform project implementation in the AOD field. We accessed records for 127 completed projects funded by the Alcohol, Education and Rehabilitation Foundation from 2002 to 2008. An adapted realist synthesis methodology enabled us to develop categories of enablers and barriers to successful project implementation, and to identify factors statistically associated with successful project implementation, defined as meeting all funding objectives. Thematic analysis of eight case study projects allowed detailed exploration of findings. Nine enabler and 10 barrier categories were identified. Those most frequently reported as both barriers and enablers concerned partnerships with external agencies and communities, staffing and project design. Achieving supportive relationships with partner agencies and communities, employing skilled staff and implementing consumer or participant input mechanisms were statistically associated with successful project implementation. The framework described here will support development of evidence-based project funding guidelines and project performance indicators. The study provides evidence that investing project hours and resources to develop robust relationships with project partners and communities, implementing mechanisms for consumer or participant input and attracting skilled staff are legitimate and important activities, not just in themselves but because they potentially influence achievement of project funding objectives. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.

Impact of biomarker development on drug safety assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marrer, Estelle, E-mail: estelle.marrer@novartis.co; Dieterle, Frank

2010-03-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative andmore » 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.« less

Value of shared preclinical safety studies - The eTOX database.

PubMed

Briggs, Katharine; Barber, Chris; Cases, Montserrat; Marc, Philippe; Steger-Hartmann, Thomas

2015-01-01

A first analysis of a database of shared preclinical safety data for 1214 small molecule drugs and drug candidates extracted from 3970 reports donated by thirteen pharmaceutical companies for the eTOX project (www.etoxproject.eu) is presented. Species, duration of exposure and administration route data were analysed to assess if large enough subsets of homogenous data are available for building in silico predictive models. Prevalence of treatment related effects for the different types of findings recorded were analysed. The eTOX ontology was used to determine the most common treatment-related clinical chemistry and histopathology findings reported in the database. The data were then mined to evaluate sensitivity of established in vivo biomarkers for liver toxicity risk assessment. The value of the database to inform other drug development projects during early drug development is illustrated by a case study.

A Research Strategy Case Study of Alcohol and Drug Prevention by Non-Governmental Organizations in Sweden 2003-2009

PubMed Central

2011-01-01

Background Alcohol and drug prevention is high on the public health agenda in many countries. An increasing trend is the call for evidence-based practice. In Sweden in 2002 an innovative project portfolio including an integrated research and competence-building strategy for non-governmental organisations (NGOs) was designed by the National Board of Health and Welfare (NBHW). This research strategy case study is based on this initiative. Methods The embedded case study includes 135 projects in 69 organisations and 14 in-depth process or effect studies. The data in the case study has been compiled using multiple methods - administrative data; interviews and questionnaires to project leaders; focus group discussions and seminars; direct and participatory observations, interviews, and documentation of implementation; consultations with the NBHW and the NGOs; and a literature review. Annual reports have been submitted each year and three bi-national conferences Reflections on preventions have been held. Results A broad range of organisations have been included in the NBHW project portfolio. A minority of the project were run by Alcohol or drug organisations, while a majority has children or adolescents as target groups. In order to develop a trustful partnership between practitioners, national agencies and researchers a series of measures were developed and implemented: meeting with project leaders, project dialogues and consultations, competence strengthening, support to documentation, in-depth studies and national conferences. A common element was that the projects were program-driven and not research-driven interventions. The role of researchers-as-technical advisors was suitable for the fostering of a trustful partnership for research and development. The independence of the NGOs was regarded as important for the momentum in the project implementation. The research strategy also includes elements of participatory research. Conclusions This research strategy case study shows that it is possible to integrate research into alcohol and drug prevention programs run by NGOs, and thereby contribute to a more evidence-based practice. A core element is developing a trustful partnership between the researchers and the organisations. Moreover, the funding agency must acknowledge the importance of knowledge development and allocating resources to research groups that is capable of cooperating with practitioners and NGOs. PMID:21492442

OpenZika: An IBM World Community Grid Project to Accelerate Zika Virus Drug Discovery

PubMed Central

Perryman, Alexander L.; Horta Andrade, Carolina

2016-01-01

The Zika virus outbreak in the Americas has caused global concern. To help accelerate this fight against Zika, we launched the OpenZika project. OpenZika is an IBM World Community Grid Project that uses distributed computing on millions of computers and Android devices to run docking experiments, in order to dock tens of millions of drug-like compounds against crystal structures and homology models of Zika proteins (and other related flavivirus targets). This will enable the identification of new candidates that can then be tested in vitro, to advance the discovery and development of new antiviral drugs against the Zika virus. The docking data is being made openly accessible so that all members of the global research community can use it to further advance drug discovery studies against Zika and other related flaviviruses. PMID:27764115

OpenZika: An IBM World Community Grid Project to Accelerate Zika Virus Drug Discovery.

PubMed

Ekins, Sean; Perryman, Alexander L; Horta Andrade, Carolina

2016-10-01

The Zika virus outbreak in the Americas has caused global concern. To help accelerate this fight against Zika, we launched the OpenZika project. OpenZika is an IBM World Community Grid Project that uses distributed computing on millions of computers and Android devices to run docking experiments, in order to dock tens of millions of drug-like compounds against crystal structures and homology models of Zika proteins (and other related flavivirus targets). This will enable the identification of new candidates that can then be tested in vitro, to advance the discovery and development of new antiviral drugs against the Zika virus. The docking data is being made openly accessible so that all members of the global research community can use it to further advance drug discovery studies against Zika and other related flaviviruses.

A Practical Approach to Rural Drug Abuse Programming.

ERIC Educational Resources Information Center

Rozelle, George R.; And Others

1980-01-01

Reviews characteristics of rural drug abuse and general considerations for rural service delivery. Describes the Prevention Project, a rural drug abuse program in Florida, and explains its development, philosophy, and teaching techniques, including a basic educational module for use with rural youth. Includes recommendations for similar programs.…

Using Realist Synthesis to Develop an Evidence Base from an Identified Data Set on Enablers and Barriers for Alcohol and Drug Program Implementation

ERIC Educational Resources Information Center

Hunter, Barbara; MacLean, Sarah; Berends, Lynda

2012-01-01

The purpose of this paper is to show how "realist synthesis" methodology (Pawson, 2002) was adapted to review a large sample of community based projects addressing alcohol and drug use problems. Our study drew on a highly varied sample of 127 projects receiving funding from a national non-government organisation in Australia between 2002…

Projecting future drug expenditures--2012.

PubMed

Hoffman, James M; Li, Edward; Doloresco, Fred; Matusiak, Linda; Hunkler, Robert J; Shah, Nilay D; Vermeulen, Lee C; Schumock, Glen T

2012-03-01

Factors likely to influence drug expenditures, drug expenditure trends in 2010 and 2011, and projected drug expenditures for 2012 are discussed. Data were analyzed to provide drug expenditure trends for total drug expenditures and the hospital and clinic sectors. Data were obtained from the IMS Health National Sales Perspectives database. From 2009 to 2010, total U.S. drug expenditures increased by 2.7%, with total spending rising from $299.2 billion to $307.5 billion. Drug expenditures in clinics grew by 6.0% from 2009 to 2010. Hospital drug expenditures increased at the moderate rate of 1.5% from 2009 to 2010; through the first nine months of 2011, hospital drug expenditures increased by only 0.3% compared with the same period in 2010. The dominant trend over the past several years is substantial moderation in expenditure growth for widely used drugs, primarily due to the ongoing introduction and wide use of generic versions of high-cost, frequently used medications. At the end of 2010, generic drugs accounted for 78% of all retail prescriptions dispensed. Another pattern is substantial increases in expenditures for specialized medications, particularly in the outpatient setting as growth in prescription drug expenditures for clinic-administered drugs consistently outpaces growth in total expenditures. Various factors are likely to influence drug expenditures in 2012, including drugs in development, the diffusion of new drugs, generic drugs, drug shortages, and biosimilars. For 2012, we project a 3-5% increase in total drug expenditures across all settings, a 5-7% increase in expenditures for clinic-administered drugs, and a 0-2% increase in hospital drug expenditures.

Decision-making in product portfolios of pharmaceutical research and development – managing streams of innovation in highly regulated markets

PubMed Central

Jekunen, Antti

2014-01-01

Decision-making is a core function of any drug development firm. Developing drugs demands a firm to be highly innovative, while at the same time the activity is strictly regulated. Successful drug development offers the right to apply for a long-term patent that confers exclusive marketing rights. This article addresses the issue of what constitutes an adequate portfolio of drugs for a drug development firm and how it might be managed successfully. The paper investigates decision-making in the industry and specifically in the development of oncology drugs from various perspectives: the need for decisions, their timing, decision-making at the project level, the optimal portfolio, tools for portfolio analysis, the evaluation of patents, and finally the importance of the drug portfolio. Drug development decisions as important organizational elements should get more emphasis, and decisions in drug portfolio using modern decision-making methods should be used more widely than what currently happens. Structured, informed decisions would help avoiding late terminations of drugs in Phase III development. An improved research and development pipeline and drug portfolio management are the major elements in the general strategy targeting success. PMID:25364229

Decision-making in product portfolios of pharmaceutical research and development--managing streams of innovation in highly regulated markets.

PubMed

Jekunen, Antti

2014-01-01

Decision-making is a core function of any drug development firm. Developing drugs demands a firm to be highly innovative, while at the same time the activity is strictly regulated. Successful drug development offers the right to apply for a long-term patent that confers exclusive marketing rights. This article addresses the issue of what constitutes an adequate portfolio of drugs for a drug development firm and how it might be managed successfully. The paper investigates decision-making in the industry and specifically in the development of oncology drugs from various perspectives: the need for decisions, their timing, decision-making at the project level, the optimal portfolio, tools for portfolio analysis, the evaluation of patents, and finally the importance of the drug portfolio. Drug development decisions as important organizational elements should get more emphasis, and decisions in drug portfolio using modern decision-making methods should be used more widely than what currently happens. Structured, informed decisions would help avoiding late terminations of drugs in Phase III development. An improved research and development pipeline and drug portfolio management are the major elements in the general strategy targeting success.

Establishing Good Practices for Exposure–Response Analysis of Clinical Endpoints in Drug Development

PubMed Central

Overgaard, RV; Ingwersen, SH; Tornøe, CW

2015-01-01

This tutorial aims at promoting good practices for exposure–response (E-R) analyses of clinical endpoints in drug development. The focus is on practical aspects of E-R analyses to assist modeling scientists with a process of performing such analyses in a consistent manner across individuals and projects and tailored to typical clinical drug development decisions. This includes general considerations for planning, conducting, and visualizing E-R analyses, and how these are linked to key questions. PMID:26535157

Pharmacogenomic Approaches for Automated Medication Risk Assessment in People with Polypharmacy

PubMed Central

Liu, Jiazhen; Friedman, Carol; Finkelstein, Joseph

2018-01-01

Abstract Medication regimen may be optimized based on individual drug efficacy identified by pharmacogenomic testing. However, majority of current pharmacogenomic decision support tools provide assessment only of single drug-gene interactions without taking into account complex drug-drug and drug-drug-gene interactions which are prevalent in people with polypharmacy and can result in adverse drug events or insufficient drug efficacy. The main objective of this project was to develop comprehensive pharmacogenomic decision support for medication risk assessment in people with polypharmacy that simultaneously accounts for multiple drug and gene effects. To achieve this goal, the project addressed two aims: (1) development of comprehensive knowledge repository of actionable pharmacogenes; (2) introduction of scoring approaches reflecting potential adverse effect risk levels of complex medication regimens accounting for pharmacogenomic polymorphisms and multiple drug metabolizing pathways. After pharmacogenomic knowledge repository was introduced, a scoring algorithm has been built and pilot-tested using a limited data set. The resulting total risk score for frequently hospitalized older adults with polypharmacy (72.04±17.84) was statistically significantly different (p<0.05) from the total risk score for older adults with polypharmacy with low hospitalization rate (8.98±2.37). An initial prototype assessment demonstrated feasibility of our approach and identified steps for improving risk scoring algorithms.

Assessing the Financial Benefits of Faster Development Times: The Case of Single-source Versus Multi-vendor Outsourced Biopharmaceutical Manufacturing.

PubMed

DiMasi, Joseph A; Smith, Zachary; Getz, Kenneth A

2018-05-10

The extent to which new drug developers can benefit financially from shorter development times has implications for development efficiency and innovation incentives. We provided a real-world example of such gains by using recent estimates of drug development costs and returns. Time and fee data were obtained on 5 single-source manufacturing projects. Time and fees were modeled for these projects as if the drug substance and drug product processes had been contracted separately from 2 vendors. The multi-vendor model was taken as the base case, and financial impacts from single-source contracting were determined relative to the base case. The mean and median after-tax financial benefits of shorter development times from single-source contracting were $44.7 million and $34.9 million, respectively (2016 dollars). The after-tax increases in sponsor fees from single-source contracting were small in comparison (mean and median of $0.65 million and $0.25 million). For the data we examined, single-source contracting yielded substantial financial benefits over multi-source contracting, even after accounting for somewhat higher sponsor fees. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Drug Abuse Assessment, Program Planning and Resource Development in the Black Community.

ERIC Educational Resources Information Center

Gunn, Karen S.

This paper presents a needs assessment project developed to establish drug-related services in a small black community. A literature review reveals the influence of social issues relevant to the population on research methodology, program planning, and social action. The convergent analysis approach used in the needs assessment is explained and…

Improving the translation in Europe of nanomedicines (a.k.a. drug delivery) from academia to industry.

PubMed

Eaton, Michael A W

2012-12-28

Over the last decade the involvement of European academic scientists in the translation of Nanomedicines and Drug Delivery into useful therapeutics has been modest. Funders have become increasingly concerned and some attempts have been made in Europe to improve impact. While the consequences are minimal at present for stakeholders, the eventual impact at national and political levels could be serious and is likely to lead to reverse innovation - the import of healthcare products from developing economies - if not addressed. Some knowledge of industrial drug development is critical for innovation in this regulated sector - this information being not easily obtained outside Pharma. While peer review has failings, more important is project inception, since once started research takes on a life of its own. This paper aims to encourage healthcare researchers to take a more translational approach to selecting (applied) drug delivery projects. Copyright © 2012 Elsevier B.V. All rights reserved.

3 CFR - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

Code of Federal Regulations, 2013 CFR

2013-01-01

... is the combination of geographic, commercial, and economic factors that allow drugs to transit or be... economic opportunity, security, and the ability of the Afghan government to project the rule of law... country's wide-ranging national objectives to improve peace, security, and economic development. This year...

Data Mining Approaches for Genomic Biomarker Development: Applications Using Drug Screening Data from the Cancer Genome Project and the Cancer Cell Line Encyclopedia.

PubMed

Covell, David G

2015-01-01

Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE) and Sanger Cancer Genome Project (CGP). The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a) evaluate drug responses of compounds with similar mechanism of action (MOA), b) examine measures of gene expression (GE), copy number (CN) and mutation status (MUT) biomarkers, combined with gene set enrichment analysis (GSEA), for hypothesizing biological processes important for drug response, c) conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d) assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions.

Fragment-based hit identification: thinking in 3D.

PubMed

Morley, Andrew D; Pugliese, Angelo; Birchall, Kristian; Bower, Justin; Brennan, Paul; Brown, Nathan; Chapman, Tim; Drysdale, Martin; Gilbert, Ian H; Hoelder, Swen; Jordan, Allan; Ley, Steven V; Merritt, Andy; Miller, David; Swarbrick, Martin E; Wyatt, Paul G

2013-12-01

The identification of high-quality hits during the early phases of drug discovery is essential if projects are to have a realistic chance of progressing into clinical development and delivering marketed drugs. As the pharmaceutical industry goes through unprecedented change, there are increasing opportunities to collaborate via pre-competitive networks to marshal multifunctional resources and knowledge to drive impactful, innovative science. The 3D Fragment Consortium is developing fragment-screening libraries with enhanced 3D characteristics and evaluating their effect on the quality of fragment-based hit identification (FBHI) projects. Copyright © 2013 Elsevier Ltd. All rights reserved.

An assessment of collections at the University of Wisconsin-Madison Health Sciences Libraries: drug resistance.

PubMed

Bergen, P L; Nemec, D

1999-01-01

In December 1997, the authors completed an in-depth collection assessment project at the University of Wisconsin-Madison Health Sciences Libraries. The purpose was to develop a framework for future collection assessment projects by completing a multifaceted evaluation of the libraries' monograph and serial collections in the subject area of drug resistance. Evaluators adapted and synthesized several traditional collection assessment tools, including shelflist measurement, bibliography and standard list checking, and citation analysis. Throughout the project, evaluators explored strategies to overcome some of the problems inherent in the application of traditional collection assessment methods to the evaluation of biomedical collections. Their efforts resulted in the identification of standard monographs and core journals for the subject area, a measurement of the collections' strength relative to the collections of benchmark libraries, and a foundation for future collection development within the subject area. The project's primary outcome was a collection assessment methodology that has potential application to both internal and cooperative collection development in medical, pharmaceutical, and other health sciences libraries.

DNAPrint Genomics, Inc.: better drugs for segmented markets.

PubMed

Frudakis, Tony

2008-02-01

The postgenome era promises more efficient drug-development cycles and medications targeted to compatible populations, resulting in improved outcomes, fewer drug-company failures, less litigation, fewer recalls and a refurbished image of 'pharma' in the mind of the customer. DNAPrint was founded to help precipitate these changes. Since 1999, we have developed and optimized novel methods for assessing patient response proclivities as individuals but also as constituents of populations, and we have introduced a computational platform for modeling drug biology. We expect these tools will allow us to maximize the efficiency of our clinical trials and, more importantly, ensure better postmarket performance parameters. With these tools, we are now carefully engineering select drug-development projects in an attempt to illustrate the viability of a novel drug-development model - one based on the application of intelligence and new technologies for superior drug performance in segmented markets.

The Role of VET in Alcohol and Other Drugs Workforce Development: Survey Technical Report

ERIC Educational Resources Information Center

Pidd, Ken; Carne, Amanda; Roche, Ann

2010-01-01

To examine the effectiveness of vocational education and training qualifications as a workforce development strategy in the community services and health industries, a case study was undertaken of the alcohol and other drug sector. The project comprised of two parts: (1) An online survey to gain an understanding of employer's perceptions of and…

Role of pharmacoeconomic analysis in R&D decision making: when, where, how?

PubMed

Miller, Paul

2005-01-01

Pharmacoeconomics is vitally important to drug manufacturers in terms of communicating to external decision-makers (payers, prescribers, patients) the value of their products, achieving regulatory and reimbursement approval and contributing to commercial success. Since development of new drugs is long, costly and risky, and decisions must be made how to allocate considerable research and development (R&D) resources, pharmacoeconomics also has an essential role informing internal decision-making (within a company) during drug development. The use of pharmacoeconomics in early development phases is likely to enhance the efficiency of R&D resource use and also provide a solid foundation for communicating product value to external decision-makers further downstream, increasing the likelihood of regulatory (reimbursement) approval and commercial success. This paper puts the case for use of pharmacoeconomic analyses earlier in the development process and outlines five techniques (clinical trial simulation [CTS], option pricing [OP], investment appraisal [IA], threshold analysis [TA] and value of information [VOI] analysis) that can provide useful input into the design of clinical development programmes, portfolio management and optimal pricing strategy. CTS can estimate efficacy and tolerability profiles before clinical data are available. OP can show the value of different clinical programme designs, sequencing of studies and stop decisions. IA can compare expected net present value (NPV) of different product profiles or study designs. TA can be used to understand development drug profile requirements given partial data. VOI can assist risk management by quantifying uncertainty and assessing the economic viability of gathering further information on the development drug. No amount of pharmacoeconomic data can make a bad drug good; what it can do is enhance the drug developers understanding of the characteristics of that drug. Decision-making, in light of this information, is likely to be better than that without it, whether it leads to faster termination of uneconomic projects or the allocation of more appropriate resources to attractive projects.

Orphan drugs: trends and issues in drug development.

PubMed

Rana, Proteesh; Chawla, Shalini

2018-04-12

Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

Novel Hypoxia-Directed Cancer Therapeutics

DTIC Science & Technology

2017-07-01

as anti-cancer therapies. 15. SUBJECT TERMS Hypoxia-inducible factors, mass-spectrometry, drug discovery, kidney cancer 16. SECURITY CLASSIFICATION...programs required for driving solid tumor growth in cancers of kidney , pancreas, stomach, colon and skin. We seek the discovery of drug-like...drug discovery, kidney cancer. 5 What opportunities for training and professional development has the project provided? How were the

How the bioanalytical scientist plays a key role in interdisciplinary project teams in the development of biotherapeutics - a reflection of the European Bioanalysis Forum.

PubMed

Dudal, Sherri; Staack, Roland F; Stoellner, Daniela; Fjording, Marianne Scheel; Vieser, Eva; Pascual, Marie-Hélène; Brudny-Kloeppel, Margarete; Golob, Michaela

2014-05-01

The bioanalytical scientist plays a key role in the project team for the drug development of biotherapeutics from the discovery to the marketing phase. Information from the project team members is required for assay development and sample analysis during the discovery, preclinical and clinical phases of the project and input is needed from the bioanalytical scientist to help data interpretation. The European Bioanalysis Forum target team 20 discussed many of the gaps in information and communication between the bioanalytical scientist and project team members as a base for providing a perspective on the bioanalytical scientist's role and interactions within the project team.

The science of laboratory and project management in regulated bioanalysis.

PubMed

Unger, Steve; Lloyd, Thomas; Tan, Melvin; Hou, Jingguo; Wells, Edward

2014-05-01

Pharmaceutical drug development is a complex and lengthy process, requiring excellent project and laboratory management skills. Bioanalysis anchors drug safety and efficacy with systemic and site of action exposures. Development of scientific talent and a willingness to innovate or adopt new technology is essential. Taking unnecessary risks, however, should be avoided. Scientists must strategically assess all risks and find means to minimize or negate them. Laboratory Managers must keep abreast of ever-changing technology. Investments in instrumentation and laboratory design are critical catalysts to efficiency and safety. Matrix management requires regular communication between Project Managers and Laboratory Managers. When properly executed, it aligns the best resources at the right times for a successful outcome. Attention to detail is a critical aspect that separates excellent laboratories. Each assay is unique and requires attention in its development, validation and execution. Methods, training and facilities are the foundation of a bioanalytical laboratory.

Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project.

PubMed

Moreno, Lucas; Caron, Hubert; Geoerger, Birgit; Eggert, Angelika; Schleiermacher, Gudrun; Brock, Penelope; Valteau-Couanet, Dominique; Chesler, Louis; Schulte, Johannes H; De Preter, Katleen; Molenaar, Jan; Schramm, Alexander; Eilers, Martin; Van Maerken, Tom; Johnsen, John Inge; Garrett, Michelle; George, Sally L; Tweddle, Deborah A; Kogner, Per; Berthold, Frank; Koster, Jan; Barone, Giuseppe; Tucker, Elizabeth R; Marshall, Lynley; Herold, Ralf; Sterba, Jaroslav; Norga, Koen; Vassal, Gilles; Pearson, Andrew Dj

2017-08-01

Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies.

Search for Novel Antibacterial Compounds and Targets.

PubMed

Kuroda, Teruo; Ogawa, Wakano

2017-01-01

Drug-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa, and vancomycin-resistant enterococci (VRE) have been spreading; however, the development of new antibacterial drugs has not progressed accordingly. Novel antibacterial drugs or their candidate seeds need to be developed for effective antibiotic therapy. Under these conditions, the search for novel compounds and novel targets is important. In Okayama University, as a part of the Drug Discovery for Intractable Infectious Diseases project, we are proceeding with the development of antibacterial drugs for the treatment of drug-resistant bacterial infections. We found that riccardin C (a natural product of liverwort) and 6,6'-dihydroxythiobinupharidine (from the crude drug Senkotsu) exhibited strong antibacterial activities, particularly against Gram-positive bacteria. We showed that riccardin C induced cell membrane leakage and that 6,6'-dihydroxythiobinupharidine inhibited DNA topoisomerase IV. Moreover, 6,6'-dihydroxythiobinupharidine exerted synergistic effects with already known anti-MRSA drugs as well as with vancomycin for VRE.

Brazilian Federal Police drug chemical profiling - the PeQui project.

PubMed

Zacca, Jorge J; Botelho, Elvio Dias; Vieira, Maurício L; Almeida, Fernanda L A; Ferreira, Luciana S; Maldaner, Adriano O

2014-07-01

Over the past six years the Brazilian Federal Police has undertaken major efforts in order to implement and to develop its own drug chemical profiling program. This paper aims to provide a broad perspective regarding the managerial strategies and some examples of subsequent technical issues involved in the implementation of such a project. Close collaboration with local drug enforcement and investigation teams, establishment of proper worldwide partnerships with well recognized institutions in the field of drug analysis and the attainment of suitable funding and human resources are shown to be key success factors. Some preliminary results concerning the chemical profile of cocaine seizures in Brazil during this process are presented. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

The "Flavor" of the Social Ecology Paradigm in Use: Building on Mutual Social Support in Preventing Drug Abuse.

ERIC Educational Resources Information Center

Thorsheim, Howard I.; Roberts, Bruce B.

The "Bottled Pain" project, a drug abuse prevention program in 24 Lutheran congregations in southern Minnesota, is based on a social ecology paradigm designed to prevent drug abuse through the development of socially supportive relationshps and through using the environment as a natural strength within the community. According to the…

National trends in prescription drug expenditures and projections for 2014.

PubMed

Schumock, Glen T; Li, Edward C; Suda, Katie J; Matusiak, Linda M; Hunkler, Robert J; Vermeulen, Lee C; Hoffman, James M

2014-03-15

An analysis of trends in U.S. pharmaceutical spending is presented, including projections for drug expenditures in nonfederal hospital and clinic settings in 2014. Trends in pharmaceutical expenditures and developments likely to influence future spending, including new drug approvals and patent expirations, were analyzed using data from the IMS Health National Sales Perspectives database. Projections were based on a combination of quantitative and qualitative analyses and expert opinion. Total prescription sales for the 12 months ending September 2013 were approximately $326 billion, 0.7% lower than sales during the previous 12 months; pharmaceutical spending by clinics and nonfederal hospitals grew by 4.5% and 1.8%, respectively. Vaccines were among the products driving large sales increases in clinic settings, with alteplase and pegfilgrastim topping the list of fast-growing drugs by hospital expenditures. Few new drug approvals anticipated in 2014 are expected to result in major expenditures by hospitals and clinics. Expansion of access to health care and other changes related to the Patient Protection and Affordable Care Act, as well as continued improvement in the U.S. economy, may drive growth in pharmaceutical spending over the next 12-24 months. Growth in U.S. prescription drug expenditures is expected to rebound in 2014, with a projected 3-5% increase in total drug expenditures across all settings this year, including a 5-7% increase in clinic spending and a 1-3% increase in hospital spending. Health-system pharmacy leaders should carefully examine local drug-utilization patterns to determine their respective organization's anticipated spending in 2014.

Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics

PubMed Central

Shirey-Rice, Jana K.; Lavieri, Robert R.; Jerome, Rebecca N.; Zaleski, Nicole M.; Aronoff, David M.; Bastarache, Lisa; Niu, Xinnan; Holroyd, Kenneth J.; Roden, Dan M.; Skaar, Eric P.; Niswender, Colleen M.; Marnett, Lawrence J.; Lindsley, Craig W.; Ekstrom, Leeland B.; Bentley, Alan R.; Bernard, Gordon R.; Hong, Charles C.; Denny, Joshua C.

2017-01-01

Abstract The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains. The Incubator supports a diverse pipeline of drug indication finding projects, leveraging the natural experiment of human genetics. PMID:28379727

An assessment of collections at the University of Wisconsin-Madison Health Sciences Libraries: drug resistance.

PubMed Central

Bergen, P L; Nemec, D

1999-01-01

In December 1997, the authors completed an in-depth collection assessment project at the University of Wisconsin-Madison Health Sciences Libraries. The purpose was to develop a framework for future collection assessment projects by completing a multifaceted evaluation of the libraries' monograph and serial collections in the subject area of drug resistance. Evaluators adapted and synthesized several traditional collection assessment tools, including shelflist measurement, bibliography and standard list checking, and citation analysis. Throughout the project, evaluators explored strategies to overcome some of the problems inherent in the application of traditional collection assessment methods to the evaluation of biomedical collections. Their efforts resulted in the identification of standard monographs and core journals for the subject area, a measurement of the collections' strength relative to the collections of benchmark libraries, and a foundation for future collection development within the subject area. The project's primary outcome was a collection assessment methodology that has potential application to both internal and cooperative collection development in medical, pharmaceutical, and other health sciences libraries. PMID:9934527

CNS drug development: part III: future directions.

PubMed

Preskorn, Sheldon H

2011-01-01

This column, the third in a series on central nervous system (CNS) drug development, discusses advances during the first decade of the 21st century and directions the field may take in the next 10 years. By identifying many possible new drug targets, the human genome project has created the potential to develop novel central nervous system (CNS) drugs with new mechanisms of action. At the same time, this proliferation of possible new targets has complicated the drug development process, since research has not yet provided guidance as to which targets may be most fruitful. This and other factors (eg, increasing regulatory requirements) have increased the cost and complexity of the drug development process. In addition, as more is learned about the biology of psychiatric illnesses, syndromes may be subdivided into more specific entities that are better understood from a pathophysiological and pathoetiological perspective. This is likely to lead to development of more targeted treatments focused on underlying causes of illness as well as prevention. The development of drugs for Alzheimer's disease is discussed as a possible model for future CNS drug development. We are at the beginning of an era when it is likely that the way in which CNS drugs are developed will need to be rethought, which will call for flexibility and creativity on the part of both drug developers and clinical researchers.

[Structural Study in the Platform for Drug Discovery, Informatics, and Structural Life Science].

PubMed

Senda, Toshiya

2016-01-01

The Platform for Drug Discovery, Informatics, and Structural Life Science (PDIS), which has been launched since FY2012, is a national project in the field of structural biology. The PDIS consists of three cores - structural analysis, control, and informatics - and aims to support life science researchers who are not familiar with structural biology. The PDIS project is able to provide full-scale support for structural biology research. The support provided by the PDIS project includes protein purification with various expression systems, large scale protein crystallization, crystal structure determination, small angle scattering (SAXS), NMR, electron microscopy, bioinformatics, etc. In order to utilize these methods of support, PDIS users need to submit an application form to the one-stop service office. Submitted applications will be reviewed by three referees. It is strongly encouraged that PDIS users have sufficient discussion with researchers in the PDIS project before submitting the application. This discussion is very useful in the process of project design, particularly for beginners in structural biology. In addition to this user support, the PDIS project has conducted R&D, which includes the development of synchrotron beamlines. In the PDIS project, PF and SPring-8 have developed beamlines for micro-crystallography, high-throughput data collection, supramolecular assembly, and native single anomalous dispersion (SAD) phasing. The newly developed beamlines have been open to all users, and have accelerated structural biology research. Beamlines for SAXS have also been developed, which has dramatically increased bio-SAXS users.

wHospital: a web-based application with digital signature for drugs dispensing management.

PubMed

Rossi, Lorenzo; Margola, Lorenzo; Manzelli, Vacia; Bandera, Alessandra

2006-01-01

wHospital is the result of an information technology research project, based on the utilization of a web based application for managing the hospital drugs dispensing. Part of wHospital back bone and its key distinguishing characteristic is the adoption of the digital signature system,initially deployed by the Government of Lombardia, a Northern Italy Region, throughout the distribution of smart cards to all the healthcare and hospital staffs. The developed system is a web-based application with a proposed Health Records Digital Signature (HReDS) handshake to comply with the national law and with the Joint Commission International Standards. The prototype application, for a single hospital Operative Unit (OU), has focused on data and process management, related to drug therapy. Following a multi-faceted selection process, the Infective Disease OU of the Hospital in Busto Arsizio, Lombardia, was chosen for the development and prototype implementation. The project lead time, from user requirement analysis to training and deployment was approximately 8 months. This paper highlights the applied project methodology, the system architecture, and the achieved preliminary results.

The development of guidelines for drug and alcohol dependence treatment: affecting policy and practice.

PubMed

Heather, N; Mattick, R P

1994-01-01

The rationale and methodology behind the Australian Quality Assurance Project is described. The Project aimed to develop guidelines for treatment content based on three sources of information: research findings, current practice and expert opinion. The issue of the gap between research and practice is discussed, as well as the role of dissemination in altering clinician behaviour.

Advancing Drug Discovery through Enhanced Free Energy Calculations.

PubMed

Abel, Robert; Wang, Lingle; Harder, Edward D; Berne, B J; Friesner, Richard A

2017-07-18

A principal goal of drug discovery project is to design molecules that can tightly and selectively bind to the target protein receptor. Accurate prediction of protein-ligand binding free energies is therefore of central importance in computational chemistry and computer aided drug design. Multiple recent improvements in computing power, classical force field accuracy, enhanced sampling methods, and simulation setup have enabled accurate and reliable calculations of protein-ligands binding free energies, and position free energy calculations to play a guiding role in small molecule drug discovery. In this Account, we outline the relevant methodological advances, including the REST2 (Replica Exchange with Solute Temperting) enhanced sampling, the incorporation of REST2 sampling with convential FEP (Free Energy Perturbation) through FEP/REST, the OPLS3 force field, and the advanced simulation setup that constitute our FEP+ approach, followed by the presentation of extensive comparisons with experiment, demonstrating sufficient accuracy in potency prediction (better than 1 kcal/mol) to substantially impact lead optimization campaigns. The limitations of the current FEP+ implementation and best practices in drug discovery applications are also discussed followed by the future methodology development plans to address those limitations. We then report results from a recent drug discovery project, in which several thousand FEP+ calculations were successfully deployed to simultaneously optimize potency, selectivity, and solubility, illustrating the power of the approach to solve challenging drug design problems. The capabilities of free energy calculations to accurately predict potency and selectivity have led to the advance of ongoing drug discovery projects, in challenging situations where alternative approaches would have great difficulties. The ability to effectively carry out projects evaluating tens of thousands, or hundreds of thousands, of proposed drug candidates, is potentially transformative in enabling hard to drug targets to be attacked, and in facilitating the development of superior compounds, in various dimensions, for a wide range of targets. More effective integration of FEP+ calculations into the drug discovery process will ensure that the results are deployed in an optimal fashion for yielding the best possible compounds entering the clinic; this is where the greatest payoff is in the exploitation of computer driven design capabilities. A key conclusion from the work described is the surprisingly robust and accurate results that are attainable within the conventional classical simulation, fixed charge paradigm. No doubt there are individual cases that would benefit from a more sophisticated energy model or dynamical treatment, and properties other than protein-ligand binding energies may be more sensitive to these approximations. We conclude that an inflection point in the ability of MD simulations to impact drug discovery has now been attained, due to the confluence of hardware and software development along with the formulation of "good enough" theoretical methods and models.

From a Viewpoint of Clinical Settings: Pharmacoepidemiology as Reverse Translational Research (rTR).

PubMed

Kawakami, Junichi

2017-01-01

Clinical pharmacology and pharmacoepidemiology research may converge in practise. Pharmacoepidemiology is the study of pharmacotherapy and risk management in patient groups. For many drugs, adverse reaction(s) that were not seen and/or clarified during research and development stages have been reported in the real world. Pharmacoepidemiology can detect and verify adverse drug reactions as reverse translational research. Recently, development and effective use of medical information databases (MID) have been conducted in Japan and elsewhere for the purpose of post-marketing safety of drugs. The Ministry of Health, Labour and Welfare, Japan has been promoting the development of 10-million scale database in 10 hospitals and hospital groups as "the infrastructure project of medical information database (MID-NET)". This project enables estimation of the frequency of adverse reactions, the distinction between drug-induced reactions and basal health-condition changes, and usefulness verification of administrative measures of drug safety. However, because the database information is different from detailed medical records, construction of methodologies for the detection and evaluation of adverse reactions is required. We have been performing database research using medical information system in some hospitals to establish and demonstrate useful methods for post-marketing safety. In this symposium, we aim to discuss the possibility of reverse translational research from clinical settings and provide an introduction to our research.

Bringing the DERP to consumers: 'Consumer Reports Best Buy Drugs'.

PubMed

Findlay, Steven D

2006-01-01

Consumers Union, publisher of Consumer Reports magazine, has used the drug class reviews of the Drug Effectiveness Review Project (DERP) as one critical component of a free public information project on the comparative effectiveness, safety, and cost of prescription drugs. The project translates the DERP findings for consumers. Drawing on other sources and adding information on drug costs, the project chooses Best Buy drugs in each category it evaluates. This guidance can help consumers save up to thousands of dollars per year, and it has the potential to reduce overall drug spending.

Oral biopharmaceutics tools - time for a new initiative - an introduction to the IMI project OrBiTo.

PubMed

Lennernäs, H; Aarons, L; Augustijns, P; Beato, S; Bolger, M; Box, K; Brewster, M; Butler, J; Dressman, J; Holm, R; Julia Frank, K; Kendall, R; Langguth, P; Sydor, J; Lindahl, A; McAllister, M; Muenster, U; Müllertz, A; Ojala, K; Pepin, X; Reppas, C; Rostami-Hodjegan, A; Verwei, M; Weitschies, W; Wilson, C; Karlsson, C; Abrahamsson, B

2014-06-16

OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of clinical pharmacy in Belgian hospitals through pilot projects funded by the government.

PubMed

Somers, A; Spinewine, A; Spriet, I; Steurbaut, S; Tulkens, P; Hecq, J D; Willems, L; Robays, H; Dhoore, M; Yaras, H; Vanden Bremt, I; Haelterman, M

2018-04-30

Objectives The goal is to develop clinical pharmacy in the Belgian hospitals to improve drug efficacy and to reduce drug-related problems. Methods From 2007 to 2014, financial support was provided by the Belgian federal government for the development of clinical pharmacy in Belgian hospitals. This project was guided by a national Advisory Working Group. Each funded hospital was obliged to describe yearly its clinical pharmacy activities. Results In 2007, 20 pharmacists were funded in 28 pilot hospitals; this number was doubled in 2009 to 40 pharmacists over 54 institutions, representing more than half of all acute Belgian hospitals. Most projects (72%) considered patient-related activities, whereas some projects (28%) had a hospital-wide approach. The projects targeted patients at admission (30%), during hospital stay (52%) or at discharge (18%). During hospital stay, actions were mainly focused on geriatric patients (20%), surgical patients (15%), and oncology patients (9%). Experiences, methods, and tools were shared during meetings and workshops. Structure, process, and outcome indicators were reported and strengths, weaknesses, opportunities, and threats were described. The yearly reports revealed that the hospital board was engaged in the project in 87% of the cases, and developed a vision on clinical pharmacy in 75% of the hospitals. In 2014, the pilot phase was replaced by structural financing for clinical pharmacy in all acute Belgian hospitals. Conclusion The pilot projects in clinical pharmacy funded by the federal government provided a unique opportunity to launch clinical pharmacy activities on a broad scale in Belgium. The results of the pilot projects showed clear implementation through case reports, time registrations, and indicators. Tools for clinical pharmacy activities were developed to overcome identified barriers. The engagement of hospital boards and the results of clinical pharmacy activities persuaded the government to start structural financing of clinical pharmacy.

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Miscellaneous.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven developed by the "Infusion Project," offers information and miscellaneous lessons on drug use prevention for integration into an existing seventh-grade middle school curriculum. The module, based on a type of interactive learning called infusion learning contains seven lessons each providing…

Project YES: A Break from Tradition.

ERIC Educational Resources Information Center

Jones, Dennis Floyd; And Others

1995-01-01

To aid at-risk children, summer intervention programs must emphasize links between physical well-being and drug awareness, nutrition, health, and safety. West Virginia's Project YES (Youth Enrichment Services) is a comprehensive, community-based program highlighting many aspects of child development. The article describes the program's history,…

A matrix approach to guide IHC-based tissue biomarker development in oncology drug discovery.

PubMed

Smith, Neil R; Womack, Christopher

2014-01-01

Immunohistochemistry (IHC) is a core platform for the analysis of tissue samples, and there is an increasing demand for reliable and quantitative IHC-based tissue biomarkers in oncology clinical research and development (R&D) environments. Biomarker assay and drug development proceed in parallel. Furthermore, biomarker assay requirements change with each phase of drug development. We have therefore developed a matrix tool to enable researchers to evaluate whether a particular IHC biomarker assay is fit for purpose. Experience gained from the development of 130 IHC biomarkers, supporting a large number of oncology drug projects, was used to formulate a practical approach to IHC assay development. The resultant matrix grid and accompanying work flow incorporates 16 core decision points that link antibody and assay specificity and sensitivity, and assay performance in preclinical and clinical samples, with stages of drug development. The matrix provides a means to ensure that relevant information on an IHC assay in development is recorded and communicated consistently and that minimum assay validation requirements are met. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Competencies for the provision of comprehensive medication management services in an experiential learning project

PubMed Central

de Freitas, Erika Lourenço; Ramalho de Oliveira, Djenane

2017-01-01

Objective To understand students’ and tutors’ perceptions of the development of clinical competencies for the delivery of comprehensive medication management services in an experiential learning project linked to a Brazilian school of pharmacy. Methods An autoethnographic qualitative study was carried out based on participant observation, focus groups and individual interviews with students and tutors involved in an experiential learning project. Results The study revealed the development of competencies related to the philosophy of practice, the pharmacotherapy workup of drug therapy and interprofessional relationships. Conclusions The experiential learning project contributed to the professional development of pharmacy students in pharmaceutical care practice, pointing to its potential benefits for incorporation into professional pharmacy curricula. PMID:28950021

Competencies for the provision of comprehensive medication management services in an experiential learning project.

PubMed

Mendonça, Simone de Araújo Medina; Freitas, Erika Lourenço de; Ramalho de Oliveira, Djenane

2017-01-01

To understand students' and tutors' perceptions of the development of clinical competencies for the delivery of comprehensive medication management services in an experiential learning project linked to a Brazilian school of pharmacy. An autoethnographic qualitative study was carried out based on participant observation, focus groups and individual interviews with students and tutors involved in an experiential learning project. The study revealed the development of competencies related to the philosophy of practice, the pharmacotherapy workup of drug therapy and interprofessional relationships. The experiential learning project contributed to the professional development of pharmacy students in pharmaceutical care practice, pointing to its potential benefits for incorporation into professional pharmacy curricula.

Projecting future drug expenditures--2006.

PubMed

Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Schumock, Glen T; Grim, Penny; Hunkler, Robert J; Hontz, Karrie M

2006-01-15

Drug expenditure trends in 2004 and 2005, projected drug expenditures for 2006, and factors likely to influence drug costs are discussed. Various factors are likely to affect drug costs, including drug prices, drugs in development, and generic drugs. In 2004 there was a continued moderation of the increase in drug expenditures. Drug expenditures increased by 8.7% from 2003 to 2004. Through the first nine months of 2005, expenditures increased by only 8.1% compared with 2004. This moderation can be attributed to several factors, including the continued trend toward higher prescription drug cost sharing for insured consumers, growing availability of generic drugs, and lack of "blockbuster" new drugs in recent years. Drug expenditures in 2006 will likely be influenced by similar factors, with few costly new products reaching the market, increased concern over product safety slowing the diffusion of those new agents that do reach the market, and several important patent expirations, leading to slower growth in expenditures. Forecasting and managing rising drug expenditures remains a challenge. Pharmacy managers must remain vigilant in monitoring drug costs in their health system and take a proactive role in pursuing efficient drug utilization. The dynamic health policy environment further complicates drug budgeting and must be considered, especially in integrated health systems responsible for managing inpatient, outpatient, and clinic drug costs. The comparison of health-system-specific data and trends with the national information presented in this article may provide a useful context when presenting institutional drug costs to senior management.

Development of a gastrointestinal tract microscale cell culture analog to predict drug transport

USDA-ARS?s Scientific Manuscript database

Microscale cell culture analogs (uCCAs) are used to study the metabolism and toxicity of a chemical or drug. These in vitro devices are physical replicas of physiologically based pharmacokinetic models that combine microfabrication and cell culture. The goal of this project is to add an independent ...

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Science.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven developed by the "Infusion Project," offers information and lessons on drug use prevention for integration into an existing seventh-grade middle school science curriculum. The module, based on a type of interactive learning called infusion learning, contains 12 lessons, each providing objectives, a…

Evaluation of a Peer-Led Drug Abuse Risk Reduction Project for Runaway/Homeless Youths.

ERIC Educational Resources Information Center

Fors, Stuart W.; Jarvis, Sara

1995-01-01

Evaluates the Drug Prevention in Youth risk reduction program that was implemented in shelters for runaway/homeless youths in the southeastern United States. An evaluation strategy was developed allowing for comparisons between peer-led, adult-led and nonintervention groups. Well-trained and motivated peer/near-peer leaders made particularly…

Children and Drug Education: The P.I.E.D. Pipers.

ERIC Educational Resources Information Center

Gloss, Elizabeth

1995-01-01

Developing coping skills for preventing substance abuse and promoting interaction and role modeling among older and younger children were the goals of the P.I.E.D. (People Involved in Education about Drugs) Pipers project. Nurses taught content to student trainees who presented information to peers and younger children. (SK)

Infusing Alcohol and Drug Prevention with Existing Classroom Study Units: Exceptional Education.

ERIC Educational Resources Information Center

Valencia Community Coll., Orlando, FL.

This curriculum module, one of seven developed by the "Infusion Project," offers information and lessons on drug use prevention for integration into an existing seventh-grade exceptional education middle school curriculum for social skills, mathematics, science and language arts. The module, based on a type of interactive learning called…

Toxins and drug discovery.

PubMed

Harvey, Alan L

2014-12-15

Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Drug targets for resistant malaria: Historic to future perspectives.

PubMed

Kumar, Sahil; Bhardwaj, T R; Prasad, D N; Singh, Rajesh K

2018-05-11

New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development. The development of resistance has highlighted the need for the search of novel antimalarial molecules. The pharmaceutical industries are committed to new drug development due to the global recognition of this life threatening resistance to the currently available antimalarial therapy. The recent developments in the understanding of parasite biology are exhilarating this resistance issue which is further being ignited by malaria genome project. With this background of information, this review was aimed to highlights and provides useful information on various present and promising treatment approaches for resistant malaria, new progresses, pursued by some innovative targets that have been explored till date. This review also discusses modern and futuristic multiple approaches to antimalarial drug discovery and development with pictorial presentations highlighting the various targets, that could be exploited for generating promising new drugs in the future for drug resistant malaria. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

NASA Technical Reports Server (NTRS)

Wu, L.; Tam, V.; Chow, Diana S. L.; Putcha, Lakshmi

2014-01-01

An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND). The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial with INSCOP.

Pseudohallucinations associated with moclobemide: a case report.

PubMed

Degner, D; Kropp, S; Porzig, J; Grohmann, R; Rüther, E

2005-07-01

The goal of the multicenter drug surveillance project AMSP ("Arzneimittelsicherheit in der Psychiatrie") is the monitoring, assessment and analysis of adverse drug reactions (ADR) of psychopharmalogical drugs. We report about a 23 year-old patient with a depressive episode. He developed severe pseudohallucinations under a treatment with moclobemide. The symptoms occur 6 days after starting the medication and decline within two days after stopping moclobemide. The term "pseudohallucinations" is discussed controversially but still of high interest.

Financing drug discovery for orphan diseases.

PubMed

Fagnan, David E; Gromatzky, Austin A; Stein, Roger M; Fernandez, Jose-Maria; Lo, Andrew W

2014-05-01

Recently proposed 'megafund' financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures among disease targets) the amount of capital needed to de-risk such portfolios is much lower in this field. Numerical simulations suggest that an orphan disease megafund of only US$575 million can yield double-digit expected rates of return with only 10-20 projects in the portfolio. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

The SULSA Assay Development Fund: accelerating translation of new biology from academia to pharma.

PubMed

McElroy, Stuart P; Jones, Philip S; Barrault, Denise V

2017-02-01

With industry increasingly sourcing preclinical drug discovery projects from academia it is important that new academic discoveries are enabled through translation with HTS-ready assays. However, many scientifically interesting, novel molecular targets lack associated high-quality, robust assays suitable for hit finding and development. To bridge this gap, the Scottish Universities Life Sciences Alliance (SULSA) established a fund to develop assays to meet quality criteria such as those of the European Lead Factory. A diverse project portfolio was quickly assembled, and a review of the learnings and successful outcomes showed this fund as a new highly cost-effective model for leveraging significant follow-on resources, training early-career scientists and establishing a culture of translational drug discovery in the academic community. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The worldwide trend of using botanical drugs and strategies for developing global drugs.

PubMed

Ahn, Kyungseop

2017-03-01

Natural product drugs, or botanical drugs, are drugs composed of natural substances which have constituents with healthenhancing or medicinal activities. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards for approving drug sales vary by countries. And also, thorough standardization, certification, clinical studies and data of these will be required as well as data confirming safety and effectiveness. Meanwhile, as an international exchange in botanical drug market continues, the importance of plant resources was emphasized. Thus countries' ownership of domestic natural resources became vital. Not only establishing a systematic method to secure domestic plant resources, but also cooperation with other countries on sharing natural resources is essential to procure natural resources effectively. Korea started to show visible results with botanical drugs, and asthma/COPD treatment made out of speedwell is one example. Sufficient investment and government's active support for basic infrastructure for global botanical drugs will bring Korea to much higher level of botanical drug development. [BMB Reports 2017; 50(3): 111-116].

Explaining drug policy: Towards an historical sociology of policy change.

PubMed

Seddon, Toby

2011-11-01

The goal of seeking to understand the development over time of drug policies is a specific version of the more general intellectual project of finding ways of explaining social change. The latter has been a preoccupation of some of the greatest thinkers within the social sciences of the last 200 years, from Foucault all the way back to the three nineteenth-century pioneers, Marx, Durkheim and Weber. I describe this body of work as 'historical sociology'. In this paper, I outline how a particular approach to historical sociology can be fruitfully drawn upon to understand the development of drug policy, using by way of illustration the example of the analysis of a recent transformation in British drug policy: the rise of the criminal justice agenda. I conclude by arguing that by looking at developments in drug policy in this way, some new insights are opened up. Copyright © 2011 Elsevier B.V. All rights reserved.

Applying Principles of Visual Literacy to the Design of Distance Education Materials for Correctional Use.

ERIC Educational Resources Information Center

Lenze, James S.

This paper examines the conceptualization and design of the Pennsylvania Audiographics Distance Education Project's (PADEP) Life Skills and Drug Education Course, and discusses the successes and difficulties of the project based on results from formative evaluation. Educators from Harrisburg, Pennsylvania, developed new courses that could be…

Going the Distance: Delivery of High School Drug Prevention via Distance Education

ERIC Educational Resources Information Center

Wyrick, David L.; Fearnow-Kenney, Melodie; Wyrick, Cheryl Haworth; Orsini, Muhsin Michael; Strack, Robert W.; Milroy, Jeffrey J.

2010-01-01

The purpose of this project was to develop a technology that can be used in schools where there are insufficient resources to implement a quality drug prevention program. The specific technology--distance education via teleconferencing--allows a highly qualified teacher to deliver programs in such settings with increased quality. A promising high…

An Interdisciplinary Approach for the Integration and Diffusion of Substance Abuse Prevention Programs

ERIC Educational Resources Information Center

Bechtel, Lori J.; Vicary, Judith; Swisher, John; Smith, Edward; Hopkins, Abigail; Henry, Kimberly; Minner, Daphne

2006-01-01

Effective substance abuse prevention programs help students develop knowledge as well as psychosocial competencies that can help them resist or delay the initiation of alcohol, tobacco and other drug (ATOD) use. This paper describes the integration process used in a five-year project, Adoption of Drug Abuse Prevention Training (ADAPT), to study…

The University of New Mexico Center for Molecular Discovery

PubMed Central

Edwards, Bruce S.; Gouveia, Kristine; Oprea, Tudor I.; Sklar, Larry A.

2015-01-01

The University of New Mexico Center for Molecular Discovery (UNMCMD) is an academic research center that specializes in discovery using high throughput flow cytometry (HTFC) integrated with virtual screening, as well as knowledge mining and drug informatics. With a primary focus on identifying small molecules that can be used as chemical probes and as leads for drug discovery, it is a central core resource for research and translational activities at UNM that supports implementation and management of funded screening projects as well as “up-front” services such as consulting for project design and implementation, assistance in assay development and generation of preliminary data for pilot projects in support of competitive grant applications. The HTFC platform in current use represents advanced, proprietary technology developed at UNM that is now routinely capable of processing bioassays arrayed in 96-, 384- and 1536-well formats at throughputs of 60,000 or more wells per day. Key programs at UNMCMD include screening of research targets submitted by the international community through NIH’s Molecular Libraries Program; a multi-year effort involving translational partnerships at UNM directed towards drug repurposing - identifying new uses for clinically approved drugs; and a recently established personalized medicine initiative for advancing cancer therapy by the application of “smart” oncology drugs in selected patients based on response patterns of their cancer cells in vitro. UNMCMD discoveries, innovation, and translation have contributed to a wealth of inventions, patents, licenses and publications, as well as startup companies, clinical trials and a multiplicity of domestic and international collaborative partnerships to further the research enterprise. PMID:24409953

The University of New Mexico Center for Molecular Discovery.

PubMed

Edwards, Bruce S; Gouveia, Kristine; Oprea, Tudor I; Sklar, Larry A

2014-03-01

The University of New Mexico Center for Molecular Discovery (UNMCMD) is an academic research center that specializes in discovery using high throughput flow cytometry (HTFC) integrated with virtual screening, as well as knowledge mining and drug informatics. With a primary focus on identifying small molecules that can be used as chemical probes and as leads for drug discovery, it is a central core resource for research and translational activities at UNM that supports implementation and management of funded screening projects as well as "up-front" services such as consulting for project design and implementation, assistance in assay development and generation of preliminary data for pilot projects in support of competitive grant applications. The HTFC platform in current use represents advanced, proprietary technology developed at UNM that is now routinely capable of processing bioassays arrayed in 96-, 384- and 1536-well formats at throughputs of 60,000 or more wells per day. Key programs at UNMCMD include screening of research targets submitted by the international community through NIH's Molecular Libraries Program; a multi-year effort involving translational partnerships at UNM directed towards drug repurposing - identifying new uses for clinically approved drugs; and a recently established personalized medicine initiative for advancing cancer therapy by the application of "smart" oncology drugs in selected patients based on response patterns of their cancer cells in vitro. UNMCMD discoveries, innovation, and translation have contributed to a wealth of inventions, patents, licenses and publications, as well as startup companies, clinical trials and a multiplicity of domestic and international collaborative partnerships to further the research enterprise.

Advancing tuberculosis drug regimen development through innovative quantitative translational pharmacology methods and approaches.

PubMed

Hanna, Debra; Romero, Klaus; Schito, Marco

2017-03-01

The development of novel tuberculosis (TB) multi-drug regimens that are more efficacious and of shorter duration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens. This perspective article highlights the work of seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making, dose selection, trial design, and safety assessments, in order to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health. Copyright © 2016. Published by Elsevier Ltd.

Coupling computer-interpretable guidelines with a drug-database through a web-based system – The PRESGUID project

PubMed Central

Dufour, Jean-Charles; Fieschi, Dominique; Fieschi, Marius

2004-01-01

Background Clinical Practice Guidelines (CPGs) available today are not extensively used due to lack of proper integration into clinical settings, knowledge-related information resources, and lack of decision support at the point of care in a particular clinical context. Objective The PRESGUID project (PREScription and GUIDelines) aims to improve the assistance provided by guidelines. The project proposes an online service enabling physicians to consult computerized CPGs linked to drug databases for easier integration into the healthcare process. Methods Computable CPGs are structured as decision trees and coded in XML format. Recommendations related to drug classes are tagged with ATC codes. We use a mapping module to enhance computerized guidelines coupling with a drug database, which contains detailed information about each usable specific medication. In this way, therapeutic recommendations are backed up with current and up-to-date information from the database. Results Two authoritative CPGs, originally diffused as static textual documents, have been implemented to validate the computerization process and to illustrate the usefulness of the resulting automated CPGs and their coupling with a drug database. We discuss the advantages of this approach for practitioners and the implications for both guideline developers and drug database providers. Other CPGs will be implemented and evaluated in real conditions by clinicians working in different health institutions. PMID:15053828

Understanding drug targets: no such thing as bad news.

PubMed

Roberts, Ruth A

2018-05-24

How can small-to-medium pharma and biotech companies enhance the chances of running a successful drug project and maximise the return on a limited number of assets? Having a full appreciation of the safety risks associated with proposed drug targets is a crucial element in understanding the unwanted side-effects that might stop a project in its tracks. Having this information is necessary to complement knowledge about the probable efficacy of a future drug. However, the lack of data-rich insight into drug-target safety is one of the major causes of drug-project failure today. Conducting comprehensive target-safety reviews early in the drug discovery process enables project teams to make the right decisions about which drug targets to take forward. Copyright © 2018 Elsevier Ltd. All rights reserved.

Medicinal Chemistry Projects Requiring Imaginative Structure-Based Drug Design Methods.

PubMed

Moitessier, Nicolas; Pottel, Joshua; Therrien, Eric; Englebienne, Pablo; Liu, Zhaomin; Tomberg, Anna; Corbeil, Christopher R

2016-09-20

Computational methods for docking small molecules to proteins are prominent in drug discovery. There are hundreds, if not thousands, of documented examples-and several pertinent cases within our research program. Fifteen years ago, our first docking-guided drug design project yielded nanomolar metalloproteinase inhibitors and illustrated the potential of structure-based drug design. Subsequent applications of docking programs to the design of integrin antagonists, BACE-1 inhibitors, and aminoglycosides binding to bacterial RNA demonstrated that available docking programs needed significant improvement. At that time, docking programs primarily considered flexible ligands and rigid proteins. We demonstrated that accounting for protein flexibility, employing displaceable water molecules, and using ligand-based pharmacophores improved the docking accuracy of existing methods-enabling the design of bioactive molecules. The success prompted the development of our own program, Fitted, implementing all of these aspects. The primary motivation has always been to respond to the needs of drug design studies; the majority of the concepts behind the evolution of Fitted are rooted in medicinal chemistry projects and collaborations. Several examples follow: (1) Searching for HDAC inhibitors led us to develop methods considering drug-zinc coordination and its effect on the pKa of surrounding residues. (2) Targeting covalent prolyl oligopeptidase (POP) inhibitors prompted an update to Fitted to identify reactive groups and form bonds with a given residue (e.g., a catalytic residue) when the geometry allows it. Fitted-the first fully automated covalent docking program-was successfully applied to the discovery of four new classes of covalent POP inhibitors. As a result, efficient stereoselective syntheses of a few screening hits were prioritized rather than synthesizing large chemical libraries-yielding nanomolar inhibitors. (3) In order to study the metabolism of POP inhibitors by cytochrome P450 enzymes (CYPs)-for toxicology studies-the program Impacts was derived from Fitted and helped us to reveal a complex metabolism with unforeseen stereocenter isomerizations. These efforts, combined with those of other docking software developers, have strengthened our understanding of the complex drug-protein binding process while providing the medicinal chemistry community with useful tools that have led to drug discoveries. In this Account, we describe our contributions over the past 15 years-within their historical context-to the design of drug candidates, including BACE-1 inhibitors, POP covalent inhibitors, G-quadruplex binders, and aminoglycosides binding to nucleic acids. We also remark the necessary developments of docking programs, specifically Fitted, that enabled structure-based design to flourish and yielded multiple fruitful, rational medicinal chemistry campaigns.

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

PubMed

Kiyosawa, Naoki; Manabe, Sunao

2016-01-01

Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

Cardiovascular Organ-on-a-Chip Platforms for Drug Discovery and Development

PubMed Central

Ribas, João; Sadeghi, Hossein; Manbachi, Amir; Leijten, Jeroen; Brinegar, Katelyn; Zhang, Yu Shrike; Ferreira, Lino

2016-01-01

Abstract Cardiovascular diseases are prevalent worldwide and are the most frequent causes of death in the United States. Although spending in drug discovery/development has increased, the amount of drug approvals has seen a progressive decline. Particularly, adverse side effects to the heart and general vasculature have become common causes for preclinical project closures, and preclinical models do not fully recapitulate human in vivo dynamics. Recently, organs-on-a-chip technologies have been proposed to mimic the dynamic conditions of the cardiovascular system—in particular, heart and general vasculature. These systems pay particular attention to mimicking structural organization, shear stress, transmural pressure, mechanical stretching, and electrical stimulation. Heart- and vasculature-on-a-chip platforms have been successfully generated to study a variety of physiological phenomena, model diseases, and probe the effects of drugs. Here, we review and discuss recent breakthroughs in the development of cardiovascular organs-on-a-chip platforms, and their current and future applications in the area of drug discovery and development. PMID:28971113

Strategy of Daiichi Sankyo discovery research in oncology.

PubMed

Akahane, Kouichi; Hirokawa, Kazunori

2014-02-01

We would like to introduce Daiichi Sankyo's approach to developing cancer targeted medicines with special reference to the drug discovery strategy, global discovery activities and external research collaboration leading to generation of innovative drugs for cancer patients. We are developing 14 clinical projects for cancer treatment and three of them have been previously approved. These are mostly targeted for growth and survival signals of cancer cells. To overcome the drug resistance mechanism derived from the heterogeneous nature of cancer, we are developing selective inhibitors in three major clusters of signal pathways which may allow future rational combinations of oncology products. In addition to the main research facility in Japan, research sites in the EU and the USA provide us with different technical expertise and diversified ideas of drug discovery. To access novel drug targets, we are facilitating research collaboration with leading academia and successful cancer research scientists. In conclusion, we intend to focus more on developing innovative personalized medicines for better treatment of cancer.

Toxin Inhibition - Deconvolution Strategies and Assay Screening of Combinatorial Peptide Libraries

DTIC Science & Technology

2007-08-01

that could serve as lead compounds in the development of drug therapies to toxins. The libraries have typical structures of X I - X2 - hinge - X3 - X4...or passive vaccines have limited efficacies. There are no drug prophylaxes or therapies available. This technical report describes research to provide...broadly applicable drug discovery methods for a wide range of toxins. Future Work: The work conducted in the TIF project raised and renewed interest in

How to promote adverse drug reaction reports using information systems - a systematic review and meta-analysis.

PubMed

Ribeiro-Vaz, Inês; Silva, Ana-Marta; Costa Santos, Cristina; Cruz-Correia, Ricardo

2016-03-01

Adverse drug reactions (ADRs) are a well-recognized public health problem and a major cause of death and hospitalization in developed countries. The safety of a new drug cannot be established until it has been on the market for several years. Keeping drug reactions under surveillance through pharmacovigilance systems is indispensable. However, underreporting is a major issue that undermines the effectiveness of spontaneous reports. Our work presents a systematic review on the use of information systems for the promotion of ADR reporting. The aim of this work is to describe the state of the art information systems used to promote adverse drug reaction reporting. A systematic review was performed with quantitative analysis of studies describing or evaluating the use of information systems to promote adverse drug reaction reporting. Studies with data related to the number of ADRs reported before and after each intervention and the follow-up period were included in the quantitative analysis. From a total of 3865 articles, 33 articles were included in the analysis; these articles described 29 different projects. Most of the projects were on a regional scale (62 %) and were performed in a hospital context (52 %). A total of 76 % performed passive promotion of ADR reporting and used web-based software (55 %). A total of 72 % targeted healthcare professionals and 24 % were oriented to patient ADR reporting. We performed a meta-analysis of 7 of the 29 projects to calculate the aggregated measure of the ADR reporting increase, which had an overall measure of 2.1 (indicating that the interventions doubled the number of ADRs reported). We found that most of the projects performed passive promotion of ADR reporting (i.e., facilitating the process). They were developed in hospitals and were tailored to healthcare professionals. These interventions doubled the number of ADR reports. We believe that it would be useful to develop systems to assist healthcare professionals with completing ADR reporting within electronic health records because this approach seems to be an efficient method to increase the ADR reporting rate. When this approach is not possible, it is essential to have a tool that is easily accessible on the web to report ADRs. This tool can be promoted by sending emails or through the inclusion of direct hyperlinks on healthcare professionals' desktops.

A re-evaluation of project pride, a redesigned school-based drug abuse prevention program.

PubMed

LoSciuto, Leonard; Steinman, Ross B

2004-01-01

The present study examined the effectiveness of Project PRIDE, a school-based, counselor-administered, drug and alcohol prevention program. The study is presented in the context of Project PRIDE'S efforts to keep itself current and effective via continual evaluation-based development. In this outcome evaluation, Project PRIDE participants demonstrated greater pretest to posttest gains on five of six outcome measures compared to control students, although many of the changes were small or moderate and only two were statistically significant. Further, as predicted, gains in more factual or objective areas of the program were greater than in more subjective areas dealing with student perceptions and feelings. The limitations and implications of the findings are discussed. Also discussed are the advantages of the Binomial Effect Size Display as a data presentation mode that promotes both client and general audience understanding of results.

Project K.I.C.K., A School-Based Drug Education Research Project--Peers, Parents and Kids.

ERIC Educational Resources Information Center

Rollin, Stephen A.; And Others

1994-01-01

Evaluated first phase of three-phase research project, Project KICK (Kids in Cooperation with Kids) by examining interaction between parent education, positive peer role modeling, and drug education for third graders. Hypothesized that intervention would lead to increase in self-esteem, improved attitudes, increased knowledge regarding drugs, and…

Development of a replicated database of DHCP data for evaluation of drug use.

PubMed Central

Graber, S E; Seneker, J A; Stahl, A A; Franklin, K O; Neel, T E; Miller, R A

1996-01-01

This case report describes development and testing of a method to extract clinical information stored in the Veterans Affairs (VA) Decentralized Hospital Computer System (DHCP) for the purpose of analyzing data about groups of patients. The authors used a microcomputer-based, structured query language (SQL)-compatible, relational database system to replicate a subset of the Nashville VA Hospital's DHCP patient database. This replicated database contained the complete current Nashville DHCP prescription, provider, patient, and drug data sets, and a subset of the laboratory data. A pilot project employed this replicated database to answer questions that might arise in drug-use evaluation, such as identification of cases of polypharmacy, suboptimal drug regimens, and inadequate laboratory monitoring of drug therapy. These database queries included as candidates for review all prescriptions for all outpatients. The queries demonstrated that specific drug-use events could be identified for any time interval represented in the replicated database. PMID:8653451

Development of a replicated database of DHCP data for evaluation of drug use.

PubMed

Graber, S E; Seneker, J A; Stahl, A A; Franklin, K O; Neel, T E; Miller, R A

1996-01-01

This case report describes development and testing of a method to extract clinical information stored in the Veterans Affairs (VA) Decentralized Hospital Computer System (DHCP) for the purpose of analyzing data about groups of patients. The authors used a microcomputer-based, structured query language (SQL)-compatible, relational database system to replicate a subset of the Nashville VA Hospital's DHCP patient database. This replicated database contained the complete current Nashville DHCP prescription, provider, patient, and drug data sets, and a subset of the laboratory data. A pilot project employed this replicated database to answer questions that might arise in drug-use evaluation, such as identification of cases of polypharmacy, suboptimal drug regimens, and inadequate laboratory monitoring of drug therapy. These database queries included as candidates for review all prescriptions for all outpatients. The queries demonstrated that specific drug-use events could be identified for any time interval represented in the replicated database.

Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years

PubMed Central

Panczyk, Mariusz

2014-01-01

During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation, as a result of large international research projects (Human Genome Project, the 1000 Genomes Project International HapMap Project, and Programs for Genomic Applications NHLBI-PGA). This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of cancer. For clinical use in the treatment of patients with colorectal cancer (CRC), in addition to fluoropyrimidines, another two new cytostatic drugs were allowed: irinotecan and oxaliplatin. Intensive research into new treatment regimens and a new generation of drugs used in targeted therapy has also been conducted. The last 20 years was a time of numerous in vitro and in vivo studies on the molecular basis of drug resistance. One of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer cells. Understanding the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized medicine. Scientists hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/pharmacogenomics. Over the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application potential. This review is a synthetic presentation of drug resistance in the context of CRC patient chemotherapy. The multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review. PMID:25110414

Discovery and development of antiviral drugs for biodefense: experience of a small biotechnology company.

PubMed

Bolken, Tove C; Hruby, Dennis E

2008-01-01

The unmet need for effective antivirals against potential agents of bioterrorism and emerging infections is obvious; however, the challenges to develop such drugs are daunting. Even with the passage of Project BioShield and more recently the BARDA legislation, there is still not a clear market for these types of drugs and limited federal funding available to support expensive drug development studies. SIGA Technologies, Inc. is a small biotech company committed to developing novel products for the prevention and treatment of severe infectious diseases, with an emphasis on products for diseases that could result from bioterrorism. Through trials and error SIGA has developed an approach to this problem in order to establish the infrastructure necessary to successfully advance new antiviral drugs from the discovery stage on through to licensure. The approach that we have taken to drug development is biology driven and dependent on a dispersive development model utilizing essential collaborations with academic, federal, and private sector partners. This consortium approach requires success in acquiring grants and contracts as well as iterative communication with the government and regulatory agencies. However, it can work as evidenced by the rapid progress of our lead antiviral against smallpox, ST-246, and should serve as the template for development of new antivirals against important biological pathogens.

[Clinical-pharmacological aspects to accelerate the development process from the preclinical to the clinical phase/1st communication: The contribution of clinical pharmacology].

PubMed

Kuhlmann, Jochen

2004-01-01

To improve the transition from research to development a critical evaluation of the individual project by research and disease area teams is required to include input from pharmacology, toxicology, pharmacokinetics, galenics, clinical pharmacology, clinical as well as regulatory experts and marketing. Decisions on the individual development strategy should be made prior to the start of development and all projects should be reviewed at predefined stages throughout the product development life cycle. This ensures consistency of decision-making not only during the development of individual products but throughout the entire development pipeline. Studies in the exploratory stage of drug development should be designed for decision making in contrast to later clinical trials in the confirmatory stage that require power for proof-of-safety and proof-of-efficacy. The more thorough and profound studies have been carried out during this exploratory stage of drug development, the earlier a decision can be made on the continuation or discontinuation of further development, thus saving development time and money and assessing and considerably reducing the risk for the patients and increasing the success rate of the project in the later confirmatory effectiveness trial with an adequate number of subjects receiving the new therapy under typical conditions of use. Strategies which may be helpful to improve the quality of decisions in drug discovery and drug development are: discovery experiments should be done to critically evaluate the compound, the "killer" experiments should be done as early as possible, continuous effort on preclinical disease models is necessary to improve predictability of efficacy in patients ("humanized" research): genomic technology should be used to identify novel, disease-related targets and to characterise preclinical test systems, improvement of knowledge and experience concerning the relevance of new technologies for the clinical picture; genotyping of clinical trial patients to select patient groups which are likely to respond to treatment (pharmacogenomics), modelling and simulation of preclinical and clinical trials, integration of pharmacokinetic and pharmacodynamic principles into drug development, assessment of the interaction potential (CYP-450, trasporter proteins and others), increasing use of biomarker/surrogate marker for rapid clinical feedback, involvement of the target population as soon as possible, applying statistical data analysis techniques for proving effectiveness, co-operation with high quality centers. To reach this goal clinical pharmacology must be fully integrated in the whole process from the candidate selection to its positioning within the market.

[Clinical-pharmacological aspects to accelerate the development process from the preclinical to the clinical phase/2nd communication: promising strategies].

PubMed

Kuhlmann, Jochen

2004-01-01

To improve the transition from research to development a critical evaluation of the individual project by research and disease area teams is required to include input from pharmacology, toxicology, pharmacokinetics, galenics, clinical pharmacology, clinical as well as regulatory experts and marketing. Decisions on the individual development strategy should be made prior to the start of development and all projects should be reviewed at predefined stages throughout the product development life cycle. This ensures consistency of decision-making not only during the development of individual products but throughout the entire development pipeline. Studies in the exploratory stage of drug development should be designed for decision making in contrast to later clinical trials in the confirmatory stage that require power for proof-of-safety and proof-of-efficacy. The more thorough and profound studies have been carried out during this exploratory stage of drug development, the earlier a decision can be made on the continuation or discontinuation of further development, thus saving development time and money and assessing and considerably reducing the risk for the patients and increasing the success rate of the project in the later confirmatory effectiveness trial with an adequate number of subjects receiving the new therapy under typical conditions of use. Strategies which may be helpful to improve the quality of decisions in drug discovery and drug development are: discovery experiments should be done to critically evaluate the compound, the "killer" experiments should be done as early as possible, continuous effort on preclinical disease models is necessary to improve predictability of efficacy in patients ("humanized" research): genomic technology should be used to identify novel, disease-related targets and to characterise preclinical test systems, improvement of knowledge and experience concerning the relevance of new technologies for the clinical picture, genotyping of clinical trial patients to select patient groups which are likely to respond to treatment (pharmacogenomics), modelling and simulation of preclinical and clinical trials, integration of pharmacokinetic and pharmacodynamic principles into drug development, assessment of the interaction potential (CYP-450, trasporter proteins and others), increasing use of biomarker/surrogate marker for rapid clinical feedback, involvement of the target population as soon as possible, applying statistical data analysis techniques for proving effectiveness, co-operation with high quality centers. To reach this goal clinical pharmacology must be fully integrated in the whole process from the candidate selection to its positioning within the market.

Managing intellectual property to develop medicines for the world's poorest.

PubMed

Fonteilles-Drabek, Sylvie; Reddy, David; Wells, Timothy N C

2017-04-01

It has been argued that patents impede the development and access of medicines for tropical diseases such as malaria. However, we believe that intellectual property can be a key tool to enable timely progression of drug development projects involving multiple partners and to ensure equitable access to successful products.

Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers

DTIC Science & Technology

2016-10-01

previous rat ARdbd-DNA crystals and may represent a new crystal form. Key outcome 2: We have carried out followup crystallization screening...to VPC-14449 as a model drug to assist on other related projects. 1. Tam, K., Dalal, K., Hsing, M., Cheng, C.W., Chiang , Y.T., Sharma, A., Peacock

Discovery of Bioactive Compounds by the UIC-ICBG Drug Discovery Program in the 18 Years Since 1998.

PubMed

Zhang, Hong-Jie; Li, Wan-Fei; Fong, Harry H S; Soejarto, Djaja Doel

2016-10-31

The International Cooperative Biodiversity Groups (ICBG) Program based at the University of Illinois at Chicago (UIC) is a program aimed to address the interdependent issues of inventory and conservation of biodiversity, drug discovery and sustained economic growth in both developing and developed countries. It is an interdisciplinary program involving the extensive synergies and collaborative efforts of botanists, chemists and biologists in the countries of Vietnam, Laos and the USA. The UIC-ICBG drug discovery efforts over the past 18 years have resulted in the collection of a cumulative total of more than 5500 plant samples (representing more than 2000 species), that were evaluated for their potential biological effects against cancer, HIV, bird flu, tuberculosis and malaria. The bioassay-guided fractionation and separation of the bioactive plant leads resulted in the isolation of approximately 300 compounds of varying degrees of structural complexity and/or biological activity. The present paper summarizes the significant drug discovery achievements made by the UIC-ICBG team of multidisciplinary collaborators in the project over the period of 1998-2012 and the projects carried on in the subsequent years by involving the researchers in Hong Kong.

Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients.

PubMed

Thom, Claire

2015-09-01

Claire Thom speaks to Gemma Westcott, Commissioning Editor: Claire Thom joined Astellas in 2013 as the Therapeutic Area Head for Oncology in Global Development. In that role, she also serves as the STAR leader for Oncology for Astellas. Prior to Astellas, she spent 12 years with Takeda. Her last position was Senior Vice President, Portfolio Management, Drug Development Management and Medical Informatics and Strategic Operations within the Medical Division (the Division within Millennium responsible for oncology clinical drug development within Takeda). During her 4 years at Millennium, at various times, she had responsibility within the Medical Division for leading portfolio management, business operations (medical finance, annual and mid-range financial planning, space planning and operations, headcount resourcing, development goals process), clinical development operations (clinical operations, programming, data management, statistics, medical writing, clinical outsourcing), drug development management (project management), medical informatics (technology support for the division) and the strategic project management office for the division. Prior to joining Millennium, Claire Thom spent 18 months working in Osaka, Japan, during which she was responsible for developing the oncology strategy for Takeda that culminated in the acquisition of Millennium. Before going to Japan, she held positions of varying responsibility within the Takeda US development organization including the management of regulatory affairs, safety, biometrics and data management, clinical research and quality assurance. Claire Thom has particular expertise in organizational design and efficiency; she has successfully worked through integrations across multiple functions and redesigned business processes. She has a PharmD from University of Illinois (IL, USA) and over 20 years of pharmaceutical experience including positions in medical affairs and new product planning (over 11 years at Searle) and drug development (over 12 years at Takeda/Millennium).

Coexistence of passive and carrier-mediated processes in drug transport.

PubMed

Sugano, Kiyohiko; Kansy, Manfred; Artursson, Per; Avdeef, Alex; Bendels, Stefanie; Di, Li; Ecker, Gerhard F; Faller, Bernard; Fischer, Holger; Gerebtzoff, Grégori; Lennernaes, Hans; Senner, Frank

2010-08-01

The permeability of biological membranes is one of the most important determinants of the pharmacokinetic processes of a drug. Although it is often accepted that many drug substances are transported across biological membranes by passive transcellular diffusion, a recent hypothesis speculated that carrier-mediated mechanisms might account for the majority of membrane drug transport processes in biological systems. Based on evidence of the physicochemical characteristics and of in vitro and in vivo findings for marketed drugs, as well as results from real-life discovery and development projects, we present the view that both passive transcellular processes and carrier-mediated processes coexist and contribute to drug transport activities across biological membranes.

Is Project Towards No Drug Abuse (Project TND) an evidence-based drug and violence prevention program? A review and reappraisal of the evaluation studies.

PubMed

Gorman, Dennis M

2014-08-01

This paper critically reviews the published evidence pertaining to Project Towards No Drug Abuse (Project TND). Publications from seven evaluation studies of Project TND are reviewed, and the results from these are discussed as related to the following outcomes: main effects on the use of cigarettes, alcohol and marijuana; main effects on the use of "hard drugs," defined in the evaluations as cocaine, hallucinogens, stimulants, inhalants, ecstasy and other drugs (e.g., depressants, PCP, steroids and heroin); subgroup and interaction analyses of drug use; and violence-related behaviors. Very few main effects have been found for cigarette, alcohol and marijuana use in the Project TND evaluations. While studies do report main effects for hard drug use, these findings are subject to numerous threats to validity and may be attributable to the data analyses employed. Similarly, while isolated subgroup and interaction effects were found for alcohol use among baseline nonusers and some violence-related behaviors in the early Project TND evaluations, these findings have not been replicated in more recent studies and may result from multiple comparisons between study conditions. In conclusion, there is little evidence to support the assertion that Project TND is an effective drug or violence prevention program. The broader implications of these findings for prevention science are discussed and suggestions are made as to how the quality of research in the field might be improved.

PBPK models for the prediction of in vivo performance of oral dosage forms.

PubMed

Kostewicz, Edmund S; Aarons, Leon; Bergstrand, Martin; Bolger, Michael B; Galetin, Aleksandra; Hatley, Oliver; Jamei, Masoud; Lloyd, Richard; Pepin, Xavier; Rostami-Hodjegan, Amin; Sjögren, Erik; Tannergren, Christer; Turner, David B; Wagner, Christian; Weitschies, Werner; Dressman, Jennifer

2014-06-16

Drug absorption from the gastrointestinal (GI) tract is a highly complex process dependent upon numerous factors including the physicochemical properties of the drug, characteristics of the formulation and interplay with the underlying physiological properties of the GI tract. The ability to accurately predict oral drug absorption during drug product development is becoming more relevant given the current challenges facing the pharmaceutical industry. Physiologically-based pharmacokinetic (PBPK) modeling provides an approach that enables the plasma concentration-time profiles to be predicted from preclinical in vitro and in vivo data and can thus provide a valuable resource to support decisions at various stages of the drug development process. Whilst there have been quite a few successes with PBPK models identifying key issues in the development of new drugs in vivo, there are still many aspects that need to be addressed in order to maximize the utility of the PBPK models to predict drug absorption, including improving our understanding of conditions in the lower small intestine and colon, taking the influence of disease on GI physiology into account and further exploring the reasons behind population variability. Importantly, there is also a need to create more appropriate in vitro models for testing dosage form performance and to streamline data input from these into the PBPK models. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the current status of PBPK models available. The current challenges in PBPK set-ups for oral drug absorption including the composition of GI luminal contents, transit and hydrodynamics, permeability and intestinal wall metabolism are discussed in detail. Further, the challenges regarding the appropriate integration of results from in vitro models, such as consideration of appropriate integration/estimation of solubility and the complexity of the in vitro release and precipitation data, are also highlighted as important steps to advancing the application of PBPK models in drug development. It is expected that the "innovative" integration of in vitro data from more appropriate in vitro models and the enhancement of the GI physiology component of PBPK models, arising from the OrBiTo project, will lead to a significant enhancement in the ability of PBPK models to successfully predict oral drug absorption and advance their role in preclinical and clinical development, as well as for regulatory applications. Copyright © 2013 Elsevier B.V. All rights reserved.

The Drug Resistance Strategies Project as Translational Research

ERIC Educational Resources Information Center

Hecht, Michael L.; Miller-Day, Michelle

2007-01-01

This paper tells the story of the multi-layered translational process of the Drug Resistance Strategies Project. The Drug Resistance Strategies Project provides an exemplar of translational scholarship, translating adolescent narratives about their substance use experiences into an efficacious, substance abuse prevention middle school curriculum.…

Improving Conduct and Feasibility of Clinical Trials to Evaluate Antibacterial Drugs to Treat Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team.

PubMed

Knirsch, Charles; Alemayehu, Demissie; Botgros, Radu; Comic-Savic, Sabrina; Friedland, David; Holland, Thomas L; Merchant, Kunal; Noel, Gary J; Pelfrene, Eric; Reith, Christina; Santiago, Jonas; Tiernan, Rosemary; Tenearts, Pamela; Goldsack, Jennifer C; Fowler, Vance G

2016-08-15

The etiology of hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is often multidrug-resistant infections. The evaluation of new antibacterial drugs for efficacy in this population is important, as many antibacterial drugs have demonstrated limitations when studied in this population. HABP/VABP trials are expensive and challenging to conduct due to protocol complexity and low patient enrollment, among other factors. The Clinical Trials Transformation Initiative (CTTI) seeks to advance antibacterial drug development by streamlining HABP/VABP clinical trials to improve efficiency and feasibility while maintaining ethical rigor, patient safety, information value, and scientific validity. In 2013, CTTI engaged a multidisciplinary group of experts to discuss challenges impeding the conduct of HABP/VABP trials. Separate workstreams identified challenges associated with HABP/VABP protocol complexity. The Project Team developed potential solutions to streamline HABP/VABP trials using a Quality by Design approach. CTTI recommendations focus on 4 key areas to improve HABP/VABP trials: informed consent processes/practices, protocol design, choice of an institutional review board (IRB), and trial outcomes. Informed consent processes should include legally authorized representatives. Protocol design decisions should focus on eligibility criteria, prestudy antibacterial therapy considerations, use of new diagnostics, and sample size. CTTI recommends that sponsors use a central IRB and discuss trial endpoints with regulators, including defining a clinical failure and evaluating the impact of concomitant antibacterial drugs. Streamlining HABP/VABP trials by addressing key protocol elements can improve trial startup and patient recruitment/retention, reduce trial complexity and costs, and ensure patient safety while advancing antibacterial drug development. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

On the bridge over the translational valley of death: interview with Per I Arvidsson.

PubMed

Arvidsson, Per I

2017-06-01

Per I Arvidsson speaks to Francesca Lake, Managing Editor: Per received his PhD in organic chemistry from Gothenburg University (Sweden) in 1999, where he continued as a lecturer for a short time. Following 2 years at the ETH Zurich (Switzerland) as a postdoctoral fellow, he went on to establish an independent research group at the Department of Biochemistry and Organic Chemistry at Uppsala University (Sweden). In 2006, he joined AstraZeneca R&D Södertälje (Sweden). After 1-year in-house training for future leaders in drug discovery and development, he became team leader in Medicinal Chemistry in 2007. In 2008, he was appointed Candidate Drug Delivery team leader with responsibility for preclinical drug discoveries in several CNS and pain projects. In 2010, he became Project Director at the innovative medicine unit for CNS & Pain research in Södertälje with responsibility from lead optimization to end of Phase II for projects in the neurodegeneration area. After joining AstraZeneca, he continued to pursue academic research as Adjunct Professor in bioorganic chemistry at the Department of Biochemistry and Organic Chemistry, Uppsala University (2007-2010), and the Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University (2010-2013). In 2010, he was appointed honorary professor in Pharmacy and Pharmacology at the University of KwaZulu Natal (South Africa). In 2013, he was recruited to the Karolinska Institute in Stockholm as Director of Drug Discovery & Development, to build up the National Swedish infrastructure for Drug Discovery & Development at the Science for Life Laboratory (SciLifeLab). Since 2013, he has been a part-time research professor at the College of Health Science at the University of KwaZulu Natal. He is named inventor on over 15 patent applications, and coauthor to over 100 publications, two of which have won 'most cited papers' awards.

On the bridge over the translational valley of death: interview with Per I Arvidsson

PubMed Central

Arvidsson, Per I

2017-01-01

Per I Arvidsson speaks to Francesca Lake, Managing Editor: Per received his PhD in organic chemistry from Gothenburg University (Sweden) in 1999, where he continued as a lecturer for a short time. Following 2 years at the ETH Zurich (Switzerland) as a postdoctoral fellow, he went on to establish an independent research group at the Department of Biochemistry and Organic Chemistry at Uppsala University (Sweden). In 2006, he joined AstraZeneca R&D Södertälje (Sweden). After 1-year in-house training for future leaders in drug discovery and development, he became team leader in Medicinal Chemistry in 2007. In 2008, he was appointed Candidate Drug Delivery team leader with responsibility for preclinical drug discoveries in several CNS and pain projects. In 2010, he became Project Director at the innovative medicine unit for CNS & Pain research in Södertälje with responsibility from lead optimization to end of Phase II for projects in the neurodegeneration area. After joining AstraZeneca, he continued to pursue academic research as Adjunct Professor in bioorganic chemistry at the Department of Biochemistry and Organic Chemistry, Uppsala University (2007–2010), and the Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University (2010–2013). In 2010, he was appointed honorary professor in Pharmacy and Pharmacology at the University of KwaZulu Natal (South Africa). In 2013, he was recruited to the Karolinska Institute in Stockholm as Director of Drug Discovery & Development, to build up the National Swedish infrastructure for Drug Discovery & Development at the Science for Life Laboratory (SciLifeLab). Since 2013, he has been a part-time research professor at the College of Health Science at the University of KwaZulu Natal. He is named inventor on over 15 patent applications, and coauthor to over 100 publications, two of which have won ‘most cited papers’ awards. PMID:28670474

Simulating the drug discovery pipeline: a Monte Carlo approach

PubMed Central

2012-01-01

Background The early drug discovery phase in pharmaceutical research and development marks the beginning of a long, complex and costly process of bringing a new molecular entity to market. As such, it plays a critical role in helping to maintain a robust downstream clinical development pipeline. Despite its importance, however, to our knowledge there are no published in silico models to simulate the progression of discrete virtual projects through a discovery milestone system. Results Multiple variables were tested and their impact on productivity metrics examined. Simulations predict that there is an optimum number of scientists for a given drug discovery portfolio, beyond which output in the form of preclinical candidates per year will remain flat. The model further predicts that the frequency of compounds to successfully pass the candidate selection milestone as a function of time will be irregular, with projects entering preclinical development in clusters marked by periods of low apparent productivity. Conclusions The model may be useful as a tool to facilitate analysis of historical growth and achievement over time, help gauge current working group progress against future performance expectations, and provide the basis for dialogue regarding working group best practices and resource deployment strategies. PMID:23186040

Design and implementation of a cost-accounting system in hospital pharmacy.

PubMed

Gouveia, W A; Anderson, E R; Decker, E L; Backer, K

1988-03-01

The design and implementation of a cost-accounting system in a hospital pharmacy department is described. Pharmacy resource use (labor, drugs, supplies, and overhead), or pharmacy's intermediate products, was clearly defined in terms of dosage forms (10 groupings representing variable labor and supplies) and drug products (more than 100 categories that incorporate cost and volume of use for 3000 line items). Costs were defined as variable or nonvariable (fixed), based on whether they were related to a specific medication order. Labor was divided into variable and fixed components. Time standards were developed using time and motion studies. Variable labor hours were determined as follows: specified hours (the volume of each dosage form multiplied by the standard time for each dosage form); nonspecified hours (time not directly associated with production); hours worked (specified plus nonspecified hours); and hours paid (hours worked plus sick leave and vacation). A standard cost for each drug product was based on the weighted average of volume and cost of the individual line items. The total drug budget was constructed by multiplying the standard cost for each drug product times the projected volume for each drug product. The pharmacy budget was developed by calculating the number and mix of pharmacy products used in association with the projected number and type of cases for the fiscal year. The monthly pharmacy budget reports were assembled with data from the payroll, billing, and cost-accounting systems.(ABSTRACT TRUNCATED AT 250 WORDS)

The La Salle University FIPSE Grant: A Review and Evaluation of the Alcohol and Other Drug Program, 1 September 88 through 30 September 90.

ERIC Educational Resources Information Center

Chapman, Robert J.

This report presents descriptive and evaluative information on the Alcohol and Other Drug Program (A & D Program) developed at Pennsylvania's La Salle University and supported by the Fund for the Improvement of Postsecondary Education. The program includes an alcohol awareness project, a peer education program, a resident educator with A &…

A Pilot Project to Develop a Tool to Assess Gain in Knowledge in Third Graders Participating in a Science Based Drug Prevention Education Curriculum

ERIC Educational Resources Information Center

Butler, Miriam

2013-01-01

Drug use and abuse presents a significant problem to individuals, families, and law enforcement in communities across the United States. Methamphetamine is a particular concern in one rural eastern Missouri county. Much work being done in this county by multiple agencies to decrease methamphetamine production and use. Little attention, however,…

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2013-08-01

This project is to use cutting-edge technologies to characterize novel RSR genes and their functions in tumor suppression; identify gene signature...and membrane proteins associated with defective RSR; identify drugs that target these defects; and develop RSR-defect-targeting nanoparticles for...screening and validation of drugs that target RSR-defect cells. The progress of our third year research is described below. BODY The tasks

United Nations Office on Drugs and Crime International Network of Drug Dependence Treatment and Rehabilitation Resource Centres: Treatnet.

PubMed

Tomás-Rosselló, Juana; Rawson, Richard A; Zarza, Maria J; Bellows, Anne; Busse, Anja; Saenz, Elizabeth; Freese, Thomas; Shawkey, Mansour; Carise, Deni; Ali, Robert; Ling, Walter

2010-10-01

Key to the dissemination of evidence-based addiction treatments is the exchange of experiences and mutual support among treatment practitioners, as well as the availability of accurate addiction training materials and effective trainers. To address the shortage of such resources, the United Nations Office on Drugs and Crime (UNODC) created Treatnet, a network of 20 drug dependence treatment resource centers around the world. Treatnet's primary goal is to promote the use of effective addiction treatment practices. Phase I of this project included (1) selecting and establishing a network of geographically distributed centers; (2) conducting a capacity-building program consisting of a training needs assessment, development of training packages, and the training of 2 trainers per center in 1 content area each; and (3) creating good-practice documents. Data on the training activities conducted by the trainers during their first 6 months in the field are presented. Plans for Phase II of the Treatnet project are also discussed.

Stroma Breaking Theranostic Nanoparticles for Targeted Pancreatic Cancer Therapy

Cancer.gov

This project develops a dual-targeted and stroma breaking theranostic nanoparticle platform to address an unmet, clinical challenge of poor drug delivery efficiency in the application of nanomedicine to cancer therapy.

Improving pharmaceutical innovation by building a more comprehensive database on drug development and use.

PubMed

Daniel, Gregory W; Cazé, Alexis; Romine, Morgan H; Audibert, Céline; Leff, Jonathan S; McClellan, Mark B

2015-02-01

New drugs and biologics have had a tremendous impact on the treatment of many diseases. However, available measures suggest that pharmaceutical innovation has remained relatively flat, despite substantial growth in research and development spending. We review recent literature on pharmaceutical innovation to identify limitations in measuring and assessing innovation, and we describe the framework and collaborative approach we are using to develop more comprehensive, publicly available metrics for innovation. Our research teams at the Brookings Institution and Deerfield Institute are collaborating with experts from multiple areas of drug development and regulatory review to identify and collect comprehensive data elements related to key development and regulatory characteristics for each new molecular entity approved over the past several decades in the United States and the European Union. Subsequent phases of our effort will add data on downstream product use and patient outcomes and will also include drugs that have failed or been abandoned in development. Such a database will enable researchers to better analyze the drivers of drug innovation, trends in the output of new medicines, and the effect of policy efforts designed to improve innovation. Project HOPE—The People-to-People Health Foundation, Inc.

The Community Pulling Together: A Tribal Community-University Partnership Project to Reduce Substance Abuse and Promote Good Health in a Reservation Tribal Community

PubMed Central

Thomas, Lisa R.; Donovan, Dennis M.; Sigo, Robin LW.; Austin, Lisette; Marlatt, G. Alan

2010-01-01

Alcohol and drug abuse are major areas of concern for many American Indian/Alaska Native communities. Research on these problems has often been less than successful, in part because many researchers are not sensitive to the culture and traditions of the tribes and communities with which they are working. They also often fail to incorporate tribal customs, traditions, and values into the interventions developed to deal with substance abuse. We describe the use of Community-Based Participatory Research (CBPR) and Tribal Participatory Research (TPR) approaches to develop a culturally sensitive substance abuse prevention program for Native youth. This project, The Community Pulling Together: Healing of the Canoe, is a collaboration between the Suquamish Tribe and the Alcohol and Drug Abuse Institute at the University of Washington. PMID:20157631

“Applied” Aspects of the Drug Resistance Strategies Project

PubMed Central

Hecht, Michael L.; Miller-Day, Michelle A.

2010-01-01

This paper discusses the applied aspects of our Drug Resistance Strategies Project. We argue that a new definitional distinction is needed to expand the notion of “applied” from the traditional notion of utilizing theory, which we call “applied.1”, in order to consider theory-grounded, theory testing and theory developing applied research. We label this new definition “applied.2” research. We then explain that our descriptive work describing the social processes of adolescent substance use, identity and use, and drug norms, as well as the subsequent development and dissemination of our keepin’ it REAL middle school substance use curriculum are examples of “applied.1” work. In the “applied.2” realm, we include our theory testing (e.g., tests of multiculturalism, narrative and performance theories, the Focus Theory of Norms) and theory-developing (e.g., parent-child communication, cultural grounding) research as well our new directions in theory development (e.g., adaptation processes). We conclude with a call for space in the discipline for “applied.2” work that builds and tests theory through application to significant social issues that contribute to our communities. We note obstacles in departmental and scholarly norms but express optimism about the prospects for “applied.2” research in the future of communication research. PMID:20711485

Positron emission tomography imaging as a key enabling technology in drug development.

PubMed

McCarthy, T J

2007-01-01

The use of positron emission tomography (PET) in drug development has become more common in the pharmaceutical industry in recent years. One of the biggest challenges to gaining acceptance of this technology is for project teams to understand when to use PET. This chapter reviews the usage of PET in drug development in the context of target, mechanism and efficacy biomarkers. Examples are drawn from a number of therapeutic areas, but we also show that the relative penetration of this technology beyond CNS and oncology applications has been relatively small. However, with the increasing availability of PET and development of novel radiotracers it is expected that the utilization will be much broader in future years, with the additional expectation that the use of PET as an efficacy biomarker will also become more evident.

USING PHOTOVOICE WITH YOUTH TO DEVELOP A DRUG PREVENTION PROGRAM IN A RURAL HAWAIIAN COMMUNITY

PubMed Central

Helm, Susana; Lee, Wayde; Hanakahi, Vanda; Gleason, Krissy; McCarthy, Kayne

2015-01-01

Introduction Substance use represents a significant and persistent health disparity among Native Hawaiian youth and communities. A community-university participatory action research project was conducted to develop a Native Hawaiian model of drug prevention. Methods Ten youth participated in eight Photovoice focus groups. Focus group transcripts and the youths’ SHOWED (see, happening, our, why, empower, do) worksheets were analyzed. Results Emergent analyses are described regarding focus group theme identification and the meaning of each theme. Youth-selected exemplary photographs and researcher-selected exemplary quotations are provided. Implications Native Hawaiian drug prevention will be place-based in culturally significant community locations, experiential, and guided by multigenerational teaching and learning. PMID:25768388

Open source drug discovery--a new paradigm of collaborative research in tuberculosis drug development.

PubMed

Bhardwaj, Anshu; Scaria, Vinod; Raghava, Gajendra Pal Singh; Lynn, Andrew Michael; Chandra, Nagasuma; Banerjee, Sulagna; Raghunandanan, Muthukurussi V; Pandey, Vikas; Taneja, Bhupesh; Yadav, Jyoti; Dash, Debasis; Bhattacharya, Jaijit; Misra, Amit; Kumar, Anil; Ramachandran, Srinivasan; Thomas, Zakir; Brahmachari, Samir K

2011-09-01

It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. Copyright © 2011 Elsevier Ltd. All rights reserved.

The IMI PROTECT project: purpose, organizational structure, and procedures.

PubMed

Reynolds, Robert F; Kurz, Xavier; de Groot, Mark C H; Schlienger, Raymond G; Grimaldi-Bensouda, Lamiae; Tcherny-Lessenot, Stephanie; Klungel, Olaf H

2016-03-01

The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty-five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two work packages within PROTECT implemented research examining the extent to which differences in the study design, methodology, and choice of data source can contribute to producing discrepant results from observational studies on drug safety. To evaluate the effect of these differences, the project applied different designs and analytic methodology for six drug-adverse event pairs across several electronic healthcare databases and registries. This papers introduces the organizational structure and procedures of PROTECT, including how drug-adverse event and data sources were selected, study design and analyses documents were developed, and results managed centrally. Copyright © 2016 John Wiley & Sons, Ltd.

O8.10A MODEL FOR RESEARCH INITIATIVES FOR RARE CANCERS: THE COLLABORATIVE EPENDYMOMA RESEARCH NETWORK (CERN)

PubMed Central

Armstrong, T.S.; Aldape, K.; Gajjar, A.; Haynes, C.; Hirakawa, D.; Gilbertson, R.; Gilbert, M.R.

2014-01-01

Ependymoma represents less than 5% of adult central nervous system (CNS) tumors and a higher percentage of pediatric CNS tumors, but it remains an orphan disease. The majority of the laboratory-based research and clinical trials have been conducted in the pediatric setting, a reflection of the relative incidence and funding opportunities. CERN, created in 2006, was designed to establish a collaborative effort between laboratory and clinical research and pediatric and adult investigators. The organization of CERN is based on integration and collaboration among five projects. Project 1 contains the clinical trials network encompassing both adult and pediatric centers. This group has completed 2 clinical trials with more underway. Project 2 is focused on molecular classification of human ependymoma tumor tissues and also contains the tumor repository which has now collected over 600 fully clinically annotated CNS ependymomas from adults and children. Project 3 is focused on drug discovery utilizing robust laboratory models of ependymoma to perform high throughput screening of drug libraries, then taking promising agents through extensive preclinical testing including monitoring of drug delivery to tumor using state of the art microdialysis. Project 4 contains the basic research efforts evaluating the molecular pathogenesis of ependymoma and has successfully translated these findings by generating the first mouse models of ependymoma that are employed in preclinical drug development in Project 3. Project 5 studies patient outcomes, including the incorporation of these measures in the clinical trials. This project also contains an online Ependymoma Outcomes survey, collecting data on the consequences of the disease and its treatment. These projects have been highly successful and collaborative. For example, the serial measurement of symptom burden (Project 5) has greatly contributed to the evaluation of treatment efficacy of a clinical trial (Project 1) and investigators from Project 2 are evaluating potential predictive markers from tumor tissue from the same clinical trial. Results from genomic and molecular discoveries generated by Project 4 were evaluated using the clinical material from the Tumor Registry (Project 2). Agents identified from the high throughput screening in Project 3 are being used to create novel clinical trials (Project 1). As a complimentary effort, CERN's community outreach efforts provide a major gateway to patients, families, caregivers and healthcare providers, contributing to greater awareness of ependymoma, and supporting clinical trial accrual in Project 1. In summary, CERN has successfully created a collaborative, multi-national integrated effort combining pediatric- and adult-focused investigators spanning from basic science to patient outcomes measures. This research paradigm may be an effective approach for other rare cancers.

Construction of an Integrated Positive Youth Development Conceptual Framework for the Prevention of the Use of Psychotropic Drugs among Adolescents

PubMed Central

Lee, Tak Yan

2011-01-01

This is a theoretical paper with an aim to construct an integrated conceptual framework for the prevention of adolescents' use and abuse of psychotropic drugs. This paper first reports the subjective reasons for adolescents' drug use and abuse in Hong Kong and reviews the theoretical underpinnings. Theories of drug use and abuse, including neurological, pharmacological, genetic predisposition, psychological, and sociological theories, were reviewed. It provides a critical re-examination of crucial factors that support the construction of a conceptual framework for primary prevention of adolescents' drug use and abuse building on, with minor revision, the model of victimization and substance abuse among women presented by Logan et al. This revised model provides a comprehensive and coherent framework synthesized from theories of drug abuse. This paper then provides empirical support for integrating a positive youth development perspective in the revised model. It further explains how the 15 empirically sound constructs identified by Catalano et al. and used in a positive youth development program, the Project P.A.T.H.S., relate generally to the components of the revised model to formulate an integrated positive youth development conceptual framework for primary prevention of adolescent drug use. Theoretical and practical implications as well as limitations and recommendations are discussed. PMID:22194671

Open Source Drug Discovery in Practice: A Case Study

PubMed Central

Årdal, Christine; Røttingen, John-Arne

2012-01-01

Background Open source drug discovery offers potential for developing new and inexpensive drugs to combat diseases that disproportionally affect the poor. The concept borrows two principle aspects from open source computing (i.e., collaboration and open access) and applies them to pharmaceutical innovation. By opening a project to external contributors, its research capacity may increase significantly. To date there are only a handful of open source R&D projects focusing on neglected diseases. We wanted to learn from these first movers, their successes and failures, in order to generate a better understanding of how a much-discussed theoretical concept works in practice and may be implemented. Methodology/Principal Findings A descriptive case study was performed, evaluating two specific R&D projects focused on neglected diseases. CSIR Team India Consortium's Open Source Drug Discovery project (CSIR OSDD) and The Synaptic Leap's Schistosomiasis project (TSLS). Data were gathered from four sources: interviews of participating members (n = 14), a survey of potential members (n = 61), an analysis of the websites and a literature review. Both cases have made significant achievements; however, they have done so in very different ways. CSIR OSDD encourages international collaboration, but its process facilitates contributions from mostly Indian researchers and students. Its processes are formal with each task being reviewed by a mentor (almost always offline) before a result is made public. TSLS, on the other hand, has attracted contributors internationally, albeit significantly fewer than CSIR OSDD. Both have obtained funding used to pay for access to facilities, physical resources and, at times, labor costs. TSLS releases its results into the public domain, whereas CSIR OSDD asserts ownership over its results. Conclusions/Significance Technically TSLS is an open source project, whereas CSIR OSDD is a crowdsourced project. However, both have enabled high quality research at low cost. The critical success factors appear to be clearly defined entry points, transparency and funding to cover core material costs. PMID:23029588

Optimizing the discovery organization for innovation.

PubMed

Sams-Dodd, Frank

2005-08-01

Strategic management is the process of adapting organizational structure and management principles to fit the strategic goal of the business unit. The pharmaceutical industry has generally been expert at optimizing its organizations for drug development, but has rarely implemented different structures for the early discovery process, where the objective is innovation and the transformation of innovation into drug projects. Here, a set of strategic management methods is proposed, covering team composition, organizational structure, management principles and portfolio management, which are designed to increase the level of innovation in the early drug discovery process.

Reducing HIV infection among new injecting drug users in the China-Vietnam Cross Border Project.

PubMed

Des Jarlais, Don C; Kling, Ryan; Hammett, Theodore M; Ngu, Doan; Liu, Wei; Chen, Yi; Binh, Kieu Thanh; Friedmann, Patricia

2007-12-01

To assess an HIV prevention programme for injecting drug users (IDU) in the crossborder area between China and Vietnam. Serial cross-sectional surveys (0, 6, 12, 18, 24 and 36 months) of community-recruited current IDU. The project included peer educator outreach and the large-scale distribution of sterile injection equipment. Serial cross-sectional surveys with HIV testing of community recruited IDU were conducted at baseline (before implementation) and 6, 12, 18, 24 and 36 months post-baseline. HIV prevalence and estimated HIV incidence among new injectors (individuals injecting drugs for < 3 years) in each survey wave were the primary outcome measures. The percentages of new injectors among all subjects declined across each survey waves in both Ning Ming and Lang Son. HIV prevalence and estimated incidence fell by approximately half at the 24-month survey and by approximately three quarters at the 36-month survey in both areas (all P < 0.01). The implementation of large-scale outreach and syringe access programmes was followed by substantial reductions in HIV infection among new injectors, with no evidence of any increase in individuals beginning to inject drugs. This project may serve as a model for large-scale HIV prevention programming for IDU in China, Vietnam, and other developing/transitional countries.

Effective visualization of integrated knowledge and data to enable informed decisions in drug development and translational medicine

PubMed Central

2013-01-01

Integrative understanding of preclinical and clinical data is imperative to enable informed decisions and reduce the attrition rate during drug development. The volume and variety of data generated during drug development have increased tremendously. A new information model and visualization tool was developed to effectively utilize all available data and current knowledge. The Knowledge Plot integrates preclinical, clinical, efficacy and safety data by adding two concepts: knowledge from the different disciplines and protein binding. Internal and public available data were gathered and processed to allow flexible and interactive visualizations. The exposure was expressed as the unbound concentration of the compound and the treatment effect was normalized and scaled by including expert opinion on what a biologically meaningful treatment effect would be. The Knowledge Plot has been applied both retrospectively and prospectively in project teams in a number of different therapeutic areas, resulting in closer collaboration between multiple disciplines discussing both preclinical and clinical data. The Plot allows head to head comparisons of compounds and was used to support Candidate Drug selections and differentiation from comparators and competitors, back translation of clinical data, understanding the predictability of preclinical models and assays, reviewing drift in primary endpoints over the years, and evaluate or benchmark compounds in due diligence comparing multiple attributes. The Knowledge Plot concept allows flexible integration and visualization of relevant data for interpretation in order to enable scientific and informed decision-making in various stages of drug development. The concept can be used for communication, decision-making, knowledge management, and as a forward and back translational tool, that will result in an improved understanding of the competitive edge for a particular project or disease area portfolio. In addition, it also builds up a knowledge and translational continuum, which in turn will reduce the attrition rate and costs of clinical development by identifying poor candidates early. PMID:24098919

[Improve the accessibility of essential drugs for the populations of one medical region in Burkina Faso].

PubMed

Ridde, Valéry; Nitièma, Abdoulaye P; Dadjoari, Moussa

2005-01-01

Despite the formulation of the Bamako initiative in 1992 in Burkina Faso, not until 2001 and the launching of a project by a nongovernmental organization was the policy really implemented in a region of the country. One of the goals of this policy is to improve access to health care by using generic essential drugs. The objective of this article is to summarize the results of the evaluation of the project's ability to improve the population's access to drugs. The project lasted three years (2001-2003) and the interventions took place in 41 basic health centres of three districts. According to WHO, improving access to drugs requires consideration of four essential factors: rational use, affordable prices, financial viability, and effectiveness of the distribution. The average number of drugs prescribed per prescription sheet (n = 1061) was 2.4; 93% of the drugs were prescribed by their generic name (international non-proprietary names); 44% of infant diarrheas were treated with oral rehydration salt. National drug prices were respected but not the directives aiming at exempting from payment or subsidizing certain population sub-groups (children, indigents). The average annual cash flow of the basic health centres was 1.2 million F CFA and it increased by 854% compared to the beginning of the project. The cost-recovery scheme for administrative expenses was 106%. The average annual availability of the 10 essential drugs was 89%. Utilization rates increased (0.13 in 1999 to 0.21 in 2003) but not significantly differently than in other basic health centres of the area not supported by the project (p = 0.084). The project succeeded in improving access to these drugs for the overall population but not for the worst-off. The drugs are now geographically available for all and financially accessible for those who can afford to pay. The intervention strategy supported the sustainability of the project's activities but much remains to be done to provide the poorest with access to drugs.

The Impact of the 5E Teaching Model on Changes in Neuroscience, Drug Addiction, and Research Methods Knowledge of Science Teachers Attending California's ARISE Professional Development Workshops

ERIC Educational Resources Information Center

Manzo, Rosa D.; Whent, Linda; Liets, Lauren; de la Torre, Adela; Gomez-Camacho, Rosa

2016-01-01

This study examined how science teachers' knowledge of research methods, neuroscience and drug addiction changed through their participation in a 5-day summer science institute. The data for this study evolved from a four-year NIH funded science education project called Addiction Research and Investigation for Science Educators (ARISE). Findings…

Experimental and clinical psychopharmacology: National Institute on Drug Abuse's clinical research agenda.

PubMed

Leshner, Alan I

2002-08-01

Studies of drugs and behavior are a core component of virtually every portfolio within the broad purview of the National Institute on Drug Abuse (NIDA). Moreover, psychopharmacological research is an important vehicle for advancing understanding of how drugs of abuse produce their effects, particularly including addiction. However, as with all major public health issues, simply understanding the issue is not enough. NIDA's psychopharmacology projects, therefore, span basic, clinical, and applied (e.g., medication development) research activities. These include the establishment of a nationwide clinical trials network designed to provide an infrastructure to test both behavioral and psychopharmacological treatments in a real-life practice setting with diverse patients.

78 FR 57623 - TRICARE Over-the-Counter Drug Demonstration Project

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-19

... DEPARTMENT OF DEFENSE Office of the Secretary TRICARE Over-the-Counter Drug Demonstration Project AGENCY: Office of the Secretary, DoD. ACTION: Notice of modification to the TRICARE Over-the-Counter Drug...) drugs to be included on the TRICARE uniform formulary. The Department has been engaged in a...

75 FR 10806 - Training Program for Regulatory Project Managers; Information Available to Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0108] Training Program for Regulatory Project Managers; Information Available to Industry AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) Center for Drug Evaluation...

78 FR 8544 - Training Program for Regulatory Project Managers; Information Available to Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2003-N-0453] Training Program for Regulatory Project Managers; Information Available to Industry AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration's (FDA's) Center for Drug...

[Optimization of information on the medication of polypharmacy patients in primary care].

PubMed

Nicieza-García, María Luisa; Salgueiro-Vázquez, María Esther; Jimeno-Demuth, Francisco José; Manso, Gloria

2016-01-01

As part of the protocol of the Health Service of the Principality of Asturias (Spain), primary care physicians periodically receive listings of the treatments of patients of any age taking 10 or more drugs/day for 6 months. Currently, the Health Service of the Principality of Asturias is developing a project that aims to assess the medications of polypharmacy patients. The aim is to identify: 1) the consumption of medicines of low therapeutic usefulness, 2) the consumption of potentially nephrotoxic drugs in patients with a low glomerular filtration rate, and 3) potentially inappropriate prescribing in patients aged 65 years or older. The project was started in Health Area II and the aim is to extend it to the remaining health areas. In our opinion, its automation and general implementation could be useful to optimize drug prescription. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.

Detection System of the First Rapidly Relocatable Tagged Neutron Inspection System (RRTNIS), Developed in the Framework of the European H2020 C-BORD Project

NASA Astrophysics Data System (ADS)

Fontana, Cristiano Lino; Carnera, Alberto; Lunardon, Marcello; Pino, Felix; Sada, Cinzia; Soramel, Francesca; Stevanato, Luca; Nebbia, Giancarlo; Carasco, Cédric; Perot, Bertrand; Sardet, Alix; Sannie, Guillaume; Iovene, Alessandro; Tintori, Carlo; Grodzicki, Krystian; Moszyński, Marek; Sibczyński, Paweł; Swiderski, Lukasz; Moretto, Sandra

The European project entitled ;effective Container inspection at BORDer control points; (C-BORD) focuses on the development and in-situ tests of a comprehensive cost-effective solution for the generalized Non-Intrusive Inspection (NII) of containers and large-volume freight at the European Union (EU) border. It copes with a large range of targets, including explosives, chemical warfare agents, illicit drugs, tobacco and Special Nuclear Materials. Within the C-BORD project, a new generation of Tagged Neutron Inspection System (TNIS) for cargo containers is foreseen. Unlike its predecessors, this system would be the first Rapidly Relocatable TNIS (RRTNIS). It will be a second-line defense system, to be used on sealed containers in order to detect explosives, illicit drugs and chemical agents in a suspect voxel (elementary volume unit). We report on the status of the RRTNIS system, in particular the overall design, the characterization of the large-volume NaI(Tl) gamma detectors, the digital analysis of the time measurements and the Data Acquisition System (DAQ).

Optimizing DMPK Properties: Experiences from a Big Pharma DMPK Department.

PubMed

Sohlenius-Sternbeck, Anna-Karin; Janson, Juliette; Bylund, Johan; Baranczewski, Pawel; Breitholtz-Emanuelsson, Anna; Hu, Yin; Tsoi, Carrie; Lindgren, Anders; Gissberg, Olle; Bueters, Tjerk; Briem, Sveinn; Juric, Sanja; Johansson, Jenny; Bergh, Margareta; Hoogstraate, Janet

2016-01-01

The disposition of a drug is dependent on interactions between the body and the drug, its molecular properties and the physical and biological barriers presented in the body. In order for a drug to have a desired pharmacological effect it has to have the right properties to be able to reach the target site in sufficient concentration. This review details how drug metabolism and pharmacokinetics (DMPK) and physicochemical deliveries played an important role in data interpretation and compound optimization at AstraZeneca R&D in Södertälje, Sweden. A selection of assays central in the evaluation of the DMPK properties of new chemical entities is presented, with guidance and consideration on assay outcome interpretation. Early in projects, solubility, LogD, permeability and metabolic stability were measured to support effective optimization of DMPK properties. Changes made to facilitate high throughput, efficient bioanalysis and the handling of large amounts of samples are described. Already early in drug discovery, we used an integrated approach for the prediction of the fate of drugs in human (early dose to man) based on data obtained from in vitro experiments. The early dose to man was refined with project progression, which triggered more intricate assays and experiments. At later stages, preclinical in vivo pharmacokinetic (PK) data was integrated with pharmacodynamics (PD) to allow predictions of required dose, dose intervals and exposure profile to achieve the desired effect in man. A well-defined work flow of DMPK activities from early lead identification up to the selection of a candidate drug was developed. This resulted in a cost effective and efficient optimization of chemical series, and facilitated informed decision making throughout project progress.

Identification of novel psychoactive drug use in Sweden based on laboratory analysis--initial experiences from the STRIDA project.

PubMed

Helander, Anders; Beck, Olof; Hägerkvist, Robert; Hultén, Peter

2013-08-01

The study aimed to collect information concerning the increasing use of new psychoactive substances, commonly sold through online shops as 'Internet drugs' or 'legal highs', or in terms of masked products such as 'bath salts' and 'plant food'. The Karolinska Institutet and Karolinska University Laboratory and the Swedish Poisons Information Centre have initiated a project called 'STRIDA' aiming to monitor the occurrence and trends of new psychoactive substances in Sweden, and collect information about their clinical symptoms, toxicity and associated health risks. A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-component method has been developed, currently allowing for the determination of > 80 novel psychoactive compounds or metabolites thereof. This study focused mainly on the particular drug substances identified and the population demographics of the initial STRIDA cases. In urine and/or blood samples obtained from 103 consecutive cases of admitted or suspected recreational drug intoxications in mostly young subjects (78% were ≤ 25 years, and 81% were males) presenting at emergency departments all over the country, psychoactive substances were detected in 82%. The substances comprised synthetic cannabinoids ('Spice'; JWH analogues), substituted cathinones ('bath salts'; e.g. butylone, MDPV and methylone) and tryptamines (4-HO-MET), plant-based substances (mitragynine and psilocin), as well as conventional drugs-of-abuse. In 44% of the cases, more than one new psychoactive substance, or a mixture of new and/or conventional drugs were detected. The initial results of the STRIDA project have documented use of a broad variety of new psychoactive substances among mainly young people all over Sweden.

Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

ERIC Educational Resources Information Center

Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

2010-01-01

A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

Best Practices in Prevention: A Curriculum on Alcohol, Tobacco and Other Drugs, and Violence. Grades 6 and 7. Drug Education Component. Project Oz.

ERIC Educational Resources Information Center

Bilyk-Glancy, Joanne; Caison, Shelia; Campbell, Melissa; Carlton, Chris; Dobbins, Mike; Menkhaus, Lisa; Nappi, Beth; Payne, Sue; Rankaitis, Peter; Sutton, Arthur; Wisted, Nancy

Project Oz is a not-for-profit special services agency providing drug education and crisis intervention services. Project Oz curricula provide compact and well-researched information for teachers, supplemented by student learning activities that reinforce the lecture portions of the topic. These activities are grade-appropriate and incorporate…

75 FR 79379 - Defense Advanced Research Projects Agency and Food and Drug Administration Expanding In Vivo...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... need special accommodations due to a disability, please contact Jenifer Schimmenti (see Contact) at... toxins. Owing to the typical paradigm for development of diagnostic devices, these next generation class...

Implications of pharmacogenomics for drug development and clinical practice.

PubMed

Ginsburg, Geoffrey S; Konstance, Richard P; Allsbrook, Jennifer S; Schulman, Kevin A

2005-11-14

Pharmacogenomics is likely to be among the first clinical applications of the Human Genome Project and is certain to have an enormous impact on the clinical practice of medicine. Herein, we discuss the potential implications of pharmacogenomics on the drug development process, including drug safety, productivity, market segmentation, market expansion, differentiation, and personalized health care. We also review 3 challenges facing the translation of pharmacogenomics into clinical practice: dependence on information technology, limited health care financing, and the scientific uncertainty surrounding validation of specific applications of the technology. To our knowledge, there is currently no formal agenda to promote and cultivate innovation, to develop progressive information technology, or to obtain the financing that would be required to advance the use of pharmacogenomic technologies in patient care. Although the potential of these technologies is driving change in the development of clinical sciences, it remains to be seen which health care systems level needs will be addressed.

National trends in prescription drug expenditures and projections for 2016.

PubMed

Schumock, Glen T; Li, Edward C; Suda, Katie J; Wiest, Michelle D; Stubbings, JoAnn; Matusiak, Linda M; Hunkler, Robert J; Vermeulen, Lee C

2016-07-15

Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2016 in nonfederal hospitals, clinics, and overall (all sectors). Drug expenditure data through calendar year 2015 were obtained from the IMS Health National Sales Perspectives database and analyzed. Other factors that may influence drug spending in hospitals and clinics in 2016, including new drug approvals and patent expirations, were also reviewed. Expenditure projections for 2016 were based on a combination of quantitative analyses and expert opinion. Total U.S. prescription sales in the 2015 calendar year were $419.4 billion, which was 11.7% higher than sales in 2014. Prescription expenditures in clinics and nonfederal hospitals totaled $56.7 billion (a 15.9% increase) and $33.6 billion (a 10.7% increase), respectively, in 2015. In nonfederal hospitals, growth in spending was driven primarily by increased prices for existing drugs. The hepatitis C combination drug ledipasvir-sofosbuvir was the top drug overall in terms of 2015 expenditures ($14.3 billion); in both clinics and nonfederal hospitals, infliximab was the top drug. Individual drugs with the greatest increases in expenditures in 2015 were specialty agents and older generics; these agents are likely to continue to influence total spending in 2016. We project an 11-13% increase in total drug expenditures overall in 2016, with a 15-17% increase in clinic spending and a 10-12% increase in hospital spending. Health-system pharmacy leaders should carefully examine local drug utilization patterns in projecting their own organization's drug spending in 2016. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

An Evaluation of Immediate Outcomes and Fidelity of a Drug Abuse Prevention Program in Continuation High Schools: Project towards No Drug Abuse (TND)

ERIC Educational Resources Information Center

Lisha, Nadra E.; Sun, Ping; Rohrbach, Louise A.; Spruijt-Metz, Donna; Unger, Jennifer B.; Sussman, Steve

2012-01-01

The present study provides an implementation fidelity, process, and immediate outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention program targeting continuation high school youth (n = 1426) at risk for drug abuse. A total of 24 schools participated in three randomized conditions: TND Only, TND and motivational…

Analyzing compound and project progress through multi-objective-based compound quality assessment.

PubMed

Nissink, J Willem M; Degorce, Sébastien

2013-05-01

Compound-quality scoring methods designed to evaluate multiple drug properties concurrently are useful to analyze and prioritize output from drug-design efforts. However, formalized multiparameter optimization approaches are not widely used in drug design. We rank molecules synthesized in drug-discovery projects using simple and aggregated desirability functions reflecting medicinal chemistry 'rules'. Our quality score deals transparently with missing data, a key requirement in drug-hunting projects where data availability is often limited. We further estimate confidence in the interpretation of such a compound-quality measure. Scores and associated confidences provide systematic insight in the quality of emerging chemical equity. Tracking quality of synthetic output over time yields valuable insight into the progress of drug-design teams, with potential applications in risk and resource management of a drug portfolio.

Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

PubMed Central

Mfuh, Adelphe M.; Larionov, Oleg V.

2016-01-01

Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab

PubMed Central

Arvidsson, Per I; Sandberg, Kristian; Sakariassen, Kjell S

2017-01-01

The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants. PMID:28670468

Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab.

PubMed

Arvidsson, Per I; Sandberg, Kristian; Sakariassen, Kjell S

2017-06-01

The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants.

Developing Novel Therapeutics Targeting Undifferentiated and Castration-Resistant Prostate Cancer Stem Cells

DTIC Science & Technology

2016-10-01

identify PCSC- specific homing peptides ; and 2) To perform unbiased drug library screening to identify novel PCSC-targeting chemicals. In the past...display library (PDL) screening in PSA-/lo PCa cells to identify PCSC- specific homing peptides ; and 2) To perform unbiased drug library screening to...Goals of the Project (SOW): Aim 1: To perform phage display library (PDL) screening in PSA-/lo PCa cells to identify PCSC- specific homing peptides

Specific issues, exact locations: case study of a community mapping project to improve safety in a disadvantaged community.

PubMed

Qummouh, Rana; Rose, Vanessa; Hall, Pat

2012-12-01

Safety is a health issue and a significant concern in disadvantaged communities. This paper describes an example of community-initiated action to address perceptions of fear and safety in a suburb in south-west Sydney which led to the development of a local, community-driven research project. As a first step in developing community capacity to take action on issues of safety, a joint resident-agency group implemented a community safety mapping project to identify the extent of safety issues in the community and their exact geographical location. Two aerial maps of the suburb, measuring one metre by two metres, were placed on display at different locations for four months. Residents used coloured stickers to identify specific issues and exact locations where crime and safety were a concern. Residents identified 294 specific safety issues in the suburb, 41.9% (n=123) associated with public infrastructure, such as poor lighting and pathways, and 31.9% (n=94) associated with drug-related issues such as drug activity and discarded syringes. Good health promotion practice reflects community need. In a very practical sense, this project responded to community calls for action by mapping resident knowledge on specific safety issues and exact locations and presenting these maps to local decision makers for further action.

The incidence of drugs in fatally injured drivers

DOT National Transportation Integrated Search

1972-09-01

Method for the collection of blood, urine, bile and alcohol washes of face and fingers from fatally injured drivershave been developed. Specimens have been collected ffom Alcohol Safety ALtion Project areas and other cooperating areas. The samples we...

Pharmacokinetic properties and in silico ADME modeling in drug discovery.

PubMed

Honório, Kathia M; Moda, Tiago L; Andricopulo, Adriano D

2013-03-01

The discovery and development of a new drug are time-consuming, difficult and expensive. This complex process has evolved from classical methods into an integration of modern technologies and innovative strategies addressed to the design of new chemical entities to treat a variety of diseases. The development of new drug candidates is often limited by initial compounds lacking reasonable chemical and biological properties for further lead optimization. Huge libraries of compounds are frequently selected for biological screening using a variety of techniques and standard models to assess potency, affinity and selectivity. In this context, it is very important to study the pharmacokinetic profile of the compounds under investigation. Recent advances have been made in the collection of data and the development of models to assess and predict pharmacokinetic properties (ADME--absorption, distribution, metabolism and excretion) of bioactive compounds in the early stages of drug discovery projects. This paper provides a brief perspective on the evolution of in silico ADME tools, addressing challenges, limitations, and opportunities in medicinal chemistry.

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women's Health.

PubMed

Thomas, Mark P; Potter, Barry V L

2015-10-08

In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have led to steroidal and nonsteroidal drugs in numerous preclinical and clinical trials, with promising results in oncology and women's health, including endometriosis. Drugs have been designed to inhibit STS, e.g., Irosustat, as innovative dual-targeting aromatase-steroid sulfatase inhibitors (DASIs) and as multitargeting agents for hormone-independent tumors, such as the steroidal STX140 and nonsteroidal counterparts, acting inter alia through microtubule disruption. The aryl sulfamate pharmacophore is highly versatile, operating via three distinct mechanisms of action, and imbues attractive pharmaceutical properties. This Perspective gives a personal view of the work leading both to the therapeutic concepts and these drugs, their current status, and how they might develop in the future.

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

PubMed Central

Thomas, Mark P.; Potter, Barry V. L.

2016-01-01

In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some twenty years, have led to steroidal and non-steroidal drugs in numerous pre-clinical and clinical trials, with promising results in oncology and women’s health, including endometriosis. Drugs have been designed to inhibit STS e.g. Irosustat, as innovative dual-targeting aromatase-steroid sulfatase inhibitors (DASIs) and as multi-targeting agents for hormone-independent tumors, such as the steroidal STX140 and non-steroidal counterparts, acting inter alia through microtubule disruption. The aryl sulfamate pharmacophore is highly versatile, operating via three distinct mechanisms of action and imbues attractive pharmaceutical properties. This Perspectives article gives a personal view of the work leading both to the therapeutic concepts and these drugs, their current status and how they might develop in the future. PMID:25992880

[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs].

PubMed

Ozawa, Hikaru; Abiko, Yasushi; Akimoto, Takeshi

2003-01-01

The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)

Budget Impact Analysis of Biosimilar Trastuzumab for the Treatment of Breast Cancer in Croatia.

PubMed

Cesarec, August; Likić, Robert

2017-04-01

Breast cancer is the most common cancer in women and has considerable impact on healthcare budgets and patients' quality of life. Trastuzumab (Herceptin ® ) is a monoclonal antibody directed against the human epidermal growth factor receptor (HER2) for the treatment of breast cancer. Several trastuzumab biosimilars are currently in development. In 2015, trastuzumab was the drug with the highest financial consumption among all drugs in Croatia. This model estimates the 1-year budget impact of the introduction of biosimilar trastuzumab in Croatia. A budget impact model, based on approvals for trastuzumab treatment in 2015, was developed for the introduction of biosimilars. Two biosimilar scenarios were developed: biosimilar scenario 1, based on all approvals in 2015, and biosimilar scenario 2, based on approvals after February 2015 and the reimbursement of the subcutaneous formulation of trastuzumab in Croatia. Only trastuzumab-naïve patients and drug-acquisition costs were used in the model. Uptake of biosimilar was assumed at 50 %. Scenarios were calculated with price discounts of 15, 25 and 35 %. The robustness of the model was tested by extensive sensitivity analyses. The projected drug cost savings from the introduction of biosimilar trastuzumab range from €0.26 million (scenario 2, 15 % price discount) to €0.69 million (scenario 1, 35 % price discount). If budget savings were reinvested to treat additional patients with trastuzumab, 14 (scenario 2, 15 % price discount) to 47 (scenario 1, 35 % price discount) additional patients could be treated. Sensitivity analyses showed that the incidence of breast cancer had the highest impact on the model, with a 10 % decrease in incidence leading to an 11.3 % decrease in projected savings. The introduction of biosimilar trastuzumab could lead to significant drug cost savings in Croatia.

Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

NASA Technical Reports Server (NTRS)

Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

2015-01-01

An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

Factors associated with failure of oncology drugs in late-stage clinical development: A systematic review.

PubMed

Jardim, Denis L; Groves, Eric S; Breitfeld, Philip P; Kurzrock, Razelle

2017-01-01

We aimed to describe the reasons for failure of experimental anticancer drugs in late-stage clinical development. We searched the PharmaProjects database (https://citeline.com/products/pharmaprojects/) for anticancer drugs discontinued between 01/01/2009 and 06/30/2014. Drug programs that reached phase III trials, but never gained Food and Drug Administration (FDA) approval were compared to 37 anti-cancer drugs achieving FDA approval in this time period. Forty-two drugs fit our criteria for development failures. These failed drugs (49% targeted, 23% cytotoxics, and 28% other) were tested in 43 cancer indications (drug programs). Only 16% (7/43) of failed drug programs adopted a biomarker-driven rationale for patient selection versus 57% (21/37) of successful drug programs (P<0.001). Phase II trial information was available in 32 of 43 failed drug programs and in 32 of 37 successful programs. Nine of the 32 trials (28%) of failed drugs versus 28 of 32 trials (87%) of successful drugs (P<0.001) achieved proof of concept (single agent response rate (RR) ⩾20% or combination therapy showing a ⩾20% RR increase above the median historical RR without the experimental agent (with a minimal absolute increase of 5%) or a randomized phase II trial showing significance (P⩽0.05) for its primary outcome). No pattern of study sites, trial design or funding characteristics emerged from the failed drug analysis. For drugs that reached Phase III, lack of a biomarker-driven strategy and failure to attain proof of concept in phase II are potential risk factors for later discontinuation, especially for targeted agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

[International Partnership for Therapeutic Drug Development of NTDs by DNDi].

PubMed

Yamada, Haruki; Hirabayashi, Fumiko; Brünger, Chris

2016-01-01

The Drugs for Neglected Diseases initiative (DNDi), with headquarters in Geneva, is a non-profit drug research and development (R&D) organization and Product Development Partnership (PDP) which was established in 2003 by 7 founding organizations such as Médecins Sans Frontières (MSF), the Pasteur Institute, The Specific Programme for Research and Training in Tropical Diseases (WHO-TDR), etc. DNDi has worked mainly on the development of new treatments for neglected tropical diseases (NTDs), which is difficult to achieve under market economy conditions. DNDi has promoted overall drug discovery research including the screening of drug candidates, hit to lead, lead optimization, pre-clinical and clinical studies in the area of infectious diseases with a focus on malaria, sleeping sickness (human African trypanosomiasis; HAT), Chagas disease, leishmaniasis, filarial diseases and pediatric formulations for HIV treatment. DNDi's achievements include the development of novel therapies based on patient needs through innovative partnerships with over 130 organizations in industry, government, academia, and public institutions around the world. To date, DNDi has registered 6 novel treatments adapted to the needs of patients in poor countries, and has another 12 novel entities in development. DNDi Japan is a Japanese non-profit organization (NPO) based on the global principles of DNDi and, as the only PDP in Japan, is supporting NTD drug discovery projects in collaboration with Japanese pharmaceutical companies, academic institutions and government agencies by utilizing Japan's excellent R&D capabilities to develop new treatments for NTDs in order to contribute to global health.

Applications of chemogenomic library screening in drug discovery.

PubMed

Jones, Lyn H; Bunnage, Mark E

2017-04-01

The allure of phenotypic screening, combined with the industry preference for target-based approaches, has prompted the development of innovative chemical biology technologies that facilitate the identification of new therapeutic targets for accelerated drug discovery. A chemogenomic library is a collection of selective small-molecule pharmacological agents, and a hit from such a set in a phenotypic screen suggests that the annotated target or targets of that pharmacological agent may be involved in perturbing the observable phenotype. In this Review, we describe opportunities for chemogenomic screening to considerably expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Other applications are explored, including drug repositioning, predictive toxicology and the discovery of novel pharmacological modalities.

A Drug-Centric View of Drug Development: How Drugs Spread from Disease to Disease.

PubMed

Rodriguez-Esteban, Raul

2016-04-01

Drugs are often seen as ancillary to the purpose of fighting diseases. Here an alternative view is proposed in which they occupy a spearheading role. In this view, drugs are technologies with an inherent therapeutic potential. Once created, they can spread from disease to disease independently of the drug creator's original intentions. Through the analysis of extensive literature and clinical trial records, it can be observed that successful drugs follow a life cycle in which they are studied at an increasing rate, and for the treatment of an increasing number of diseases, leading to clinical advancement. Such initial growth, following a power law on average, has a degree of momentum, but eventually decelerates, leading to stagnation and decay. A network model can describe the propagation of drugs from disease to disease in which diseases communicate with each other by receiving and sending drugs. Within this model, some diseases appear more prone to influence other diseases than be influenced, and vice versa. Diseases can also be organized into a drug-centric disease taxonomy based on the drugs that each adopts. This taxonomy reflects not only biological similarities across diseases, but also the level of differentiation of existing therapies. In sum, this study shows that drugs can become contagious technologies playing a driving role in the fight against disease. By better understanding such dynamics, pharmaceutical developers may be able to manage drug projects more effectively.

ATHENA, the Desktop Human "Body"

ScienceCinema

Iyer, Rashi; Harris, Jennifer

2018-05-18

Creating surrogate human organs, coupled with insights from highly sensitive mass spectrometry technologies, a new project is on the brink of revolutionizing the way we screen new drugs and toxic agents. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is developing four human organ constructs - liver, heart, lung and kidney - that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA "body" of interconnected organs would fit neatly on a desk. "By developing this 'homo minutus,' we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs," said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort. The project is supported by the Defense Threat Reduction Agency (DTRA). Some 40 percent of pharmaceuticals fail their clinical trials, Iyer noted, and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success.

ATHENA, the Desktop Human "Body"

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iyer, Rashi; Harris, Jennifer

2014-09-29

Creating surrogate human organs, coupled with insights from highly sensitive mass spectrometry technologies, a new project is on the brink of revolutionizing the way we screen new drugs and toxic agents. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is developing four human organ constructs - liver, heart, lung and kidney - that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA "body" of interconnected organs would fit neatly on a desk. "By developing this 'homo minutus,' we are stepping beyond the need formore » animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs," said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort. The project is supported by the Defense Threat Reduction Agency (DTRA). Some 40 percent of pharmaceuticals fail their clinical trials, Iyer noted, and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success.« less

Biosensor technology for the detection of illegal drugs I: objectives, preparatory work, and drug enrichment

NASA Astrophysics Data System (ADS)

Hilpert, Reinhold; Binder, Florian; Grol, Michael; Hallermayer, Klaus; Josel, Hans-Peter; Klein, Christian; Maier, Josef; Oberpriller, Helmut; Ritter, Josef; Scheller, Frieder W.

1994-10-01

In a joint project of Deutsche Aerospace, Boehringer Mannheim and the University of Potsdam portable devices for the detection of illegal drugs, based on biosensor technology, are being developed. The concept enrichment of the drug from the gas phase and detection by immunological means. This publication covers the description of our objectives, preparatory work and results concerning enrichment of drugs from the gas phase. Vapor pressures of cocaine and cannabinoids have been determined. A test gas generator has been constructed which allows for reproducible preparation of cocaine concentrations between 2 ng/l and 2 pg/l. Coupling of a thermodesorption unit with GC/MS has been established for reference analysis. As another analytical tool, an ELISA with a lower detection limit of about 0,5 pg cocaine/assay has been developed. Applying fleece-type adsorbers, enrichment factors for cocaine in the range of 105 have been realized. No significant interference was found with potentially disturbing substances.

FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects.

PubMed

Lagorce, David; Sperandio, Olivier; Galons, Hervé; Miteva, Maria A; Villoutreix, Bruno O

2008-09-24

Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses) and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making. This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python) based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries. We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after) experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules) that can be easily tuned.

Definition of variables required for comprehensive description of drug dosage and clinical pharmacokinetics.

PubMed

Medem, Anna V; Seidling, Hanna M; Eichler, Hans-Georg; Kaltschmidt, Jens; Metzner, Michael; Hubert, Carina M; Czock, David; Haefeli, Walter E

2017-05-01

Electronic clinical decision support systems (CDSS) require drug information that can be processed by computers. The goal of this project was to determine and evaluate a compilation of variables that comprehensively capture the information contained in the summary of product characteristic (SmPC) and unequivocally describe the drug, its dosage options, and clinical pharmacokinetics. An expert panel defined and structured a set of variables and drafted a guideline to extract and enter information on dosage and clinical pharmacokinetics from textual SmPCs as published by the European Medicines Agency (EMA). The set of variables was iteratively revised and evaluated by data extraction and variable allocation of roughly 7% of all centrally approved drugs. The information contained in the SmPC was allocated to three information clusters consisting of 260 variables. The cluster "drug characterization" specifies the nature of the drug. The cluster "dosage" provides information on approved drug dosages and defines corresponding specific conditions. The cluster "clinical pharmacokinetics" includes pharmacokinetic parameters of relevance for dosing in clinical practice. A first evaluation demonstrated that, despite the complexity of the current free text SmPCs, dosage and pharmacokinetic information can be reliably extracted from the SmPCs and comprehensively described by a limited set of variables. By proposing a compilation of variables well describing drug dosage and clinical pharmacokinetics, the project represents a step forward towards the development of a comprehensive database system serving as information source for sophisticated CDSS.

Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

NASA Astrophysics Data System (ADS)

Becker, Holger; Hansen-Hagge, Thomas; Kurtz, Andreas; Mrowka, Ralf; Wölfl, Stefan; Gärtner, Claudia

2017-02-01

The development of new drugs is time-consuming, extremely expensive and often promising drug candidates fail in late stages of the development process due to the lack of suitable tools to either predict toxicological effects or to test drug candidates in physiologically relevant environments prior to clinical tests. We therefore try to develop diagnostic multiorgan microfluidic chips based on patient specific induced pluripotent stem cell (iPS) technology to explore liver dependent toxic effects of drugs on individual human tissues such as liver or kidney cells. Based initially on standardized microfluidic modules for cell culture, we have developed integrated microfluidic devices which contain different chambers for cell/tissue cultivation. The devices are manufactured using injection molding of thermoplastic polymers such as polystyrene or cyclo-olefin polymer. In the project, suitable surface modification methods of the used materials had to be explored. We have been able to successfully demonstrate the seeding, cultivation and further differentiation of modified iPS, as shown by the use of differentiation markers, thus providing a suitable platform for toxicity testing and potential tissue-tissue interactions.

Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms

PubMed Central

Lopez, Felipe L; Ernest, Terry B; Tuleu, Catherine; Gul, Mine Orlu

2015-01-01

Introduction: Most conventional drug delivery systems are not acceptable for pediatric patients as they differ in their developmental status and dosing requirements from other subsets of the population. Technology platforms are required to aid the development of age-appropriate medicines to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability. Areas covered: The current approaches and novel developments in the field of age-appropriate drug delivery for pediatric patients are critically discussed including patient-centric formulations, administration devices and packaging systems. Expert opinion: Despite the incentives provided by recent regulatory modifications and the efforts of formulation scientists, there is still a need for implementation of pharmaceutical technologies that enable the manufacture of licensed age-appropriate formulations. Harmonization of endeavors from regulators, industry and academia by sharing learning associated with data obtained from pediatric investigation plans, product development pathways and scientific projects would be the way forward to speed up bench-to-market age appropriate formulation development. A collaborative approach will benefit not only pediatrics, but other patient populations such as geriatrics would also benefit from an accelerated patient-centric approach to drug delivery. PMID:26165848

Extreme-Scale Computing Project Aims to Advance Precision Oncology | Poster

Cancer.gov

Two government agencies and five national laboratories are collaborating to develop extremely high-performance computing capabilities that will analyze mountains of research and clinical data to improve scientific understanding of cancer, predict drug response, and improve treatments for patients.

Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations.

PubMed

Doherty, Kathleen; Essajee, Shaffiq; Penazzato, Martina; Holmes, Charles; Resch, Stephen; Ciaranello, Andrea

2014-05-02

Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0-13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments.

Design Considerations for the Development of Interactive Video (IV) in Nurse Education.

ERIC Educational Resources Information Center

Chandra, Peter; And Others

A computer assisted learning (CAL) program in the area of intravenous drug administration developed by the Nightingale Project is currently being used in a number of nursing schools and hospitals throughout the United Kingdom. The success of this program and the emergence of interactive video as a significant training medium persuaded the…

Biopharmaceutics data management system for anonymised data sharing and curation: First application with orbito IMI project.

PubMed

Lacy-Jones, Kristin; Hayward, Philip; Andrews, Steve; Gledhill, Ian; McAllister, Mark; Abrahamsson, Bertil; Rostami-Hodjegan, Amin; Pepin, Xavier

2017-03-01

The OrBiTo IMI project was designed to improve the understanding and modelling of how drugs are absorbed. To achieve this 13 pharmaceutical companies agreed to share biopharmaceutics drug properties and performance data, as long as they were able to hide certain aspects of their dataset if required. This data was then used in simulations to test how three in silico Physiological Based Pharmacokinetic (PBPK) tools performed. A unique database system was designed and implemented to store the drug data. The database system was unique, in that it had the ability to make different sections of a dataset visible or hidden depending on the stage of the project. Users were also given the option to hide identifying API attributes, to help prevent identification of project members from previously published data. This was achieved by applying blinding strategies to data parameters and the adoption of a unique numbering system. An anonymous communication tool was proposed to exchange comments about data, which enabled its curation and evolution. This paper describes the strategy adopted for numbering and blinding of the data, the tools developed to gather and search data as well as the tools used for communicating around the data with the aim of publicising the approach for other pre-competitive research between organisations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Translating New Science Into the Drug Review Process

PubMed Central

Rouse, Rodney; Kruhlak, Naomi; Weaver, James; Burkhart, Keith; Patel, Vikram; Strauss, David G.

2017-01-01

In 2011, the US Food and drug Administration (FDA) developed a strategic plan for regulatory science that focuses on developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. In line with this, the Division of Applied Regulatory Science was created to move new science into the Center for Drug Evaluation and Research (CDER) review process and close the gap between scientific innovation and drug review. The Division, located in the Office of Clinical Pharmacology, is unique in that it performs mission-critical applied research and review across the translational research spectrum including in vitro and in vivo laboratory research, in silico computational modeling and informatics, and integrated clinical research covering clinical pharmacology, experimental medicine, and postmarket analyses. The Division collaborates with Offices throughout CDER, across the FDA, other government agencies, academia, and industry. The Division is able to rapidly form interdisciplinary teams of pharmacologists, biologists, chemists, computational scientists, and clinicians to respond to challenging regulatory questions for specific review issues and for longer-range projects requiring the development of predictive models, tools, and biomarkers to speed the development and regulatory evaluation of safe and effective drugs. This article reviews the Division’s recent work and future directions, highlighting development and validation of biomarkers; novel humanized animal models; translational predictive safety combining in vitro, in silico, and in vivo clinical biomarkers; chemical and biomedical informatics tools for safety predictions; novel approaches to speed the development of complex generic drugs, biosimilars, and antibiotics; and precision medicine. PMID:29568713

Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future.

PubMed

Hol, Wim G J

2015-05-01

Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. Presented here is an overview of the evolution over the last three to four decades of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa. Target selection is a crucial and multi-faceted aspect of structure-guided drug design. The major impact of advances in molecular biology, genome sequencing and high-throughput screening is touched upon. The most advanced crystallographic techniques, including XFEL, have already been applied to structure determinations of drug targets from parasitic protozoa. Even cryo-electron microscopy is contributing to our understanding of the mode of binding of inhibitors to parasite ribosomes. A number of projects have been selected to illustrate how structural information has assisted in arriving at promising compounds that are currently being evaluated by pharmacological, pharmacodynamic and safety tests to assess their suitability as pharmaceutical agents. Structure-guided approaches are also applied to incorporate properties into compounds such that they are less likely to become the victim of resistance mechanisms. A great increase in the number of novel antiparasitic compounds will be needed in the future. These should then be combined into various multi-compound therapeutics to circumvent the diverse resistance mechanisms that render single-compound, or even multi-compound, drugs ineffective. The future should also see (i) an increase in the number of projects with a tight integration of structural biology, medicinal chemistry, parasitology and pharmaceutical sciences; (ii) the education of more `medicinal structural biologists' who are familiar with the properties that compounds need to have for a high probability of success in the later steps of the drug-development process; and (iii) the expansion of drug-development capabilities in middle- and low-income countries.

Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future

PubMed Central

Hol, Wim G. J.

2015-01-01

Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. Presented here is an overview of the evolution over the last three to four decades of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa. Target selection is a crucial and multi-faceted aspect of structure-guided drug design. The major impact of advances in molecular biology, genome sequencing and high-throughput screening is touched upon. The most advanced crystallographic techniques, including XFEL, have already been applied to structure determinations of drug targets from parasitic protozoa. Even cryo-electron microscopy is contributing to our understanding of the mode of binding of inhibitors to parasite ribosomes. A number of projects have been selected to illustrate how structural information has assisted in arriving at promising compounds that are currently being evaluated by pharmacological, pharmacodynamic and safety tests to assess their suitability as pharmaceutical agents. Structure-guided approaches are also applied to incorporate properties into compounds such that they are less likely to become the victim of resistance mechanisms. A great increase in the number of novel antiparasitic compounds will be needed in the future. These should then be combined into various multi-compound therapeutics to circumvent the diverse resistance mechanisms that render single-compound, or even multi-compound, drugs ineffective. The future should also see (i) an increase in the number of projects with a tight integration of structural biology, medicinal chemistry, parasitology and pharmaceutical sciences; (ii) the education of more ‘medicinal structural biologists’ who are familiar with the properties that compounds need to have for a high probability of success in the later steps of the drug-development process; and (iii) the expansion of drug-development capabilities in middle- and low-income countries. PMID:25945701

The third annual BRDS on research and development of nucleic acid-based nanomedicines

PubMed Central

Chaudhary, Amit Kumar

2017-01-01

The completion of human genome project, decrease in the sequencing cost, and correlation of genome sequencing data with specific diseases led to the exponential rise in the nucleic acid-based therapeutic approaches. In the third annual Biopharmaceutical Research and Development Symposium (BRDS) held at the Center for Drug Discovery and Lozier Center for Pharmacy Sciences and Education at the University of Nebraska Medical Center (UNMC), we highlighted the remarkable features of the nucleic acid-based nanomedicines, their significance, NIH funding opportunities on nanomedicines and gene therapy research, challenges and opportunities in the clinical translation of nucleic acids into therapeutics, and the role of intellectual property (IP) in drug discovery and development. PMID:27848223

Hit and lead criteria in drug discovery for infectious diseases of the developing world.

PubMed

Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

2015-11-01

Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

PubMed

Ioset, Jean-Robert; Chang, Shing

2011-09-01

The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

Developing and Implementing a Positive Behavioral Reinforcement Intervention in Prison-Based Drug Treatment: Project BRITE

PubMed Central

Burdon, William M.; De Lore, Jef St.; Prendergast, Michael L.

2012-01-01

Within prison settings, the reliance on punishment for controlling inappropriate or non-compliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention. PMID:22185038

Developing and implementing a positive behavioral reinforcement intervention in prison-based drug treatment: Project BRITE.

PubMed

Burdon, William M; St De Lore, Jef; Prendergast, Michael L

2011-09-01

Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention.

Manifestations of integrated public health policy in Dutch municipalities.

PubMed

Peters, Dorothee; Harting, Janneke; van Oers, Hans; Schuit, Jantine; de Vries, Nanne; Stronks, Karien

2016-06-01

Integrated public health policy (IPHP) aims at integrating health considerations into policies of other sectors. Since the limited empirical evidence available may hamper its further development, we systematically analysed empirical manifestations of IPHP, by placing policy strategies along a continuum of less-to-more policy integration, going from intersectoral action (IA) to healthy public policy (HPP) to health in all policies (HiAP). Our case study included 34 municipal projects of the Dutch Gezonde Slagkracht Programme (2009-15), which supports the development and implementation of IPHP on overweight, alcohol and drug abuse, and smoking. Our content analysis of project application forms and interviews with all project leaders used a framework approach involving the policy strategies and the following policy variables: initiator, actors, policy goals, determinants and policy instruments. Most projects showed a combination of policy strategies. However, manifestations of IPHP in overweight projects predominantly involved IA. More policy integration was apparent in alcohol/drugs projects (HPP) and in all-theme projects (HiAP). More policy integration was related to broad goal definitions, which allowed for the involvement of actors representing several policy sectors. This enabled the implementation of a mix of policy instruments. Determinants of health were not explicitly used as a starting point of the policy process. If a policy problem justifies policy integration beyond IA, it might be helpful to start from the determinants of health (epidemiological reality), systematically transform them into policy (policy reality) and set broad policy goals, since this gives actors from other sectors the opportunity to participate. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

77 FR 66182 - TRICARE Over-the-Counter Drug Demonstration Project

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-02

... costs/benefits and beneficiary satisfaction of providing OTC drugs under the pharmacy benefits program... (TPharm) which was on November 4, 2009. In order to more thoroughly evaluate the clinical and cost effectiveness of OTC drugs as well as beneficiary satisfaction with the project, the Department published a...

24 CFR 882.410 - Rent adjustments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SUPPORTIVE HOUSING FOR THE ELDERLY PROGRAM AND SECTION 811 SUPPORTIVE HOUSING FOR PERSONS WITH DISABILITIES... drug-related criminal activity is generally prevalent, and not specific to a particular project, and... primarily as a result of the prevalence of such drug-related activity. HUD may, on a project-by-project...

Employing a youth-led adult-guided framework: "Why Drive High?" social marketing campaign.

PubMed

Marko, Terry-Lynne; Watt, Tyler

2011-01-01

The "Drugged Driving Kills project: Why Drive High?" social marketing campaign was developed and implemented by youth leaders and adult facilitators from public and community health to increase youth awareness of the adverse effects of marijuana on driving. The youth-led adult-guided project was founded on the Holden's youth empowerment conceptual model. This article reports on the results of the focus group evaluation, conducted to determine to what extent the tailored youth-led adult-guided framework for the "Why Drive High?" social marketing campaign provided an environment for youth leadership development.

The eTOX data-sharing project to advance in silico drug-induced toxicity prediction.

PubMed

Cases, Montserrat; Briggs, Katharine; Steger-Hartmann, Thomas; Pognan, François; Marc, Philippe; Kleinöder, Thomas; Schwab, Christof H; Pastor, Manuel; Wichard, Jörg; Sanz, Ferran

2014-11-14

The high-quality in vivo preclinical safety data produced by the pharmaceutical industry during drug development, which follows numerous strict guidelines, are mostly not available in the public domain. These safety data are sometimes published as a condensed summary for the few compounds that reach the market, but the majority of studies are never made public and are often difficult to access in an automated way, even sometimes within the owning company itself. It is evident from many academic and industrial examples, that useful data mining and model development requires large and representative data sets and careful curation of the collected data. In 2010, under the auspices of the Innovative Medicines Initiative, the eTOX project started with the objective of extracting and sharing preclinical study data from paper or pdf archives of toxicology departments of the 13 participating pharmaceutical companies and using such data for establishing a detailed, well-curated database, which could then serve as source for read-across approaches (early assessment of the potential toxicity of a drug candidate by comparison of similar structure and/or effects) and training of predictive models. The paper describes the efforts undertaken to allow effective data sharing intellectual property (IP) protection and set up of adequate controlled vocabularies) and to establish the database (currently with over 4000 studies contributed by the pharma companies corresponding to more than 1400 compounds). In addition, the status of predictive models building and some specific features of the eTOX predictive system (eTOXsys) are presented as decision support knowledge-based tools for drug development process at an early stage.

In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context.

PubMed

Lennernäs, H; Lindahl, A; Van Peer, A; Ollier, C; Flanagan, T; Lionberger, R; Nordmark, A; Yamashita, S; Yu, L; Amidon, G L; Fischer, V; Sjögren, E; Zane, P; McAllister, M; Abrahamsson, B

2017-04-03

The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the interindividual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.

Early repositioning through compound set enrichment analysis: a knowledge-recycling strategy.

PubMed

Temesi, Gergely; Bolgár, Bence; Arany, Adám; Szalai, Csaba; Antal, Péter; Mátyus, Péter

2014-04-01

Despite famous serendipitous drug repositioning success stories, systematic projects have not yet delivered the expected results. However, repositioning technologies are gaining ground in different phases of routine drug development, together with new adaptive strategies. We demonstrate the power of the compound information pool, the ever-growing heterogeneous information repertoire of approved drugs and candidates as an invaluable catalyzer in this transition. Systematic, computational utilization of this information pool for candidates in early phases is an open research problem; we propose a novel application of the enrichment analysis statistical framework for fusion of this information pool, specifically for the prediction of indications. Pharmaceutical consequences are formulated for a systematic and continuous knowledge recycling strategy, utilizing this information pool throughout the drug-discovery pipeline.

A unified approach to computational drug discovery.

PubMed

Tseng, Chih-Yuan; Tuszynski, Jack

2015-11-01

It has been reported that a slowdown in the development of new medical therapies is affecting clinical outcomes. The FDA has thus initiated the Critical Path Initiative project investigating better approaches. We review the current strategies in drug discovery and focus on the advantages of the maximum entropy method being introduced in this area. The maximum entropy principle is derived from statistical thermodynamics and has been demonstrated to be an inductive inference tool. We propose a unified method to drug discovery that hinges on robust information processing using entropic inductive inference. Increasingly, applications of maximum entropy in drug discovery employ this unified approach and demonstrate the usefulness of the concept in the area of pharmaceutical sciences. Copyright © 2015. Published by Elsevier Ltd.

Gold nanoparticles for high-throughput genotyping of long-range haplotypes

NASA Astrophysics Data System (ADS)

Chen, Peng; Pan, Dun; Fan, Chunhai; Chen, Jianhua; Huang, Ke; Wang, Dongfang; Zhang, Honglu; Li, You; Feng, Guoyin; Liang, Peiji; He, Lin; Shi, Yongyong

2011-10-01

Completion of the Human Genome Project and the HapMap Project has led to increasing demands for mapping complex traits in humans to understand the aetiology of diseases. Identifying variations in the DNA sequence, which affect how we develop disease and respond to pathogens and drugs, is important for this purpose, but it is difficult to identify these variations in large sample sets. Here we show that through a combination of capillary sequencing and polymerase chain reaction assisted by gold nanoparticles, it is possible to identify several DNA variations that are associated with age-related macular degeneration and psoriasis on significant regions of human genomic DNA. Our method is accurate and promising for large-scale and high-throughput genetic analysis of susceptibility towards disease and drug resistance.

Community Commons Program Development Manual.

ERIC Educational Resources Information Center

Culp, Kieta Osteen

Community Commons (CC) is a collaborative partnership among Brevard Community College (BCC) (Florida) and over 40 social service organizations and agencies in Florida dedicated to providing education, job training, social services, recreation, and a drug free environment to communities of low income families. The project specifically seeks to…

A Drug-Centric View of Drug Development: How Drugs Spread from Disease to Disease

PubMed Central

Rodriguez-Esteban, Raul

2016-01-01

Drugs are often seen as ancillary to the purpose of fighting diseases. Here an alternative view is proposed in which they occupy a spearheading role. In this view, drugs are technologies with an inherent therapeutic potential. Once created, they can spread from disease to disease independently of the drug creator’s original intentions. Through the analysis of extensive literature and clinical trial records, it can be observed that successful drugs follow a life cycle in which they are studied at an increasing rate, and for the treatment of an increasing number of diseases, leading to clinical advancement. Such initial growth, following a power law on average, has a degree of momentum, but eventually decelerates, leading to stagnation and decay. A network model can describe the propagation of drugs from disease to disease in which diseases communicate with each other by receiving and sending drugs. Within this model, some diseases appear more prone to influence other diseases than be influenced, and vice versa. Diseases can also be organized into a drug-centric disease taxonomy based on the drugs that each adopts. This taxonomy reflects not only biological similarities across diseases, but also the level of differentiation of existing therapies. In sum, this study shows that drugs can become contagious technologies playing a driving role in the fight against disease. By better understanding such dynamics, pharmaceutical developers may be able to manage drug projects more effectively. PMID:27124390

The Commercial Market For Priority Review Vouchers.

PubMed

Ridley, David B; Régnier, Stephane A

2016-05-01

In 2007 the US Congress created the priority review voucher program to encourage the development of drugs for neglected diseases. Under the program, the developer of a drug that treats a neglected disease receives both a faster review of the drug by the Food and Drug Administration and a voucher for a faster review of a different drug. The developer can sell the voucher. We estimated the commercial value of the voucher using US sales of new treatments approved in the period 2007-09. A third of the commercial value of a voucher comes from capturing market share from competitors, nearly half from the value of earlier sales because of the expedited review, and less than a quarter from lengthening the time between approval and the launch of a generic competitor. We estimate that if only one priority review voucher is available in a year, it will be worth more than $200 million, but if four vouchers are available, the value could fall below $100 million. Congress should be cautious about expanding the voucher program, because increasing the number of vouchers sharply decreases the expected price. Lower voucher prices could undermine the incentive to develop new medicines for neglected diseases. Project HOPE—The People-to-People Health Foundation, Inc.

Global vision of druggability issues: applications and perspectives.

PubMed

Abi Hussein, Hiba; Geneix, Colette; Petitjean, Michel; Borrel, Alexandre; Flatters, Delphine; Camproux, Anne-Claude

2017-02-01

During the preliminary stage of a drug discovery project, the lack of druggability information and poor target selection are the main causes of frequent failures. Elaborating on accurate computational druggability prediction methods is a requirement for prioritizing target selection, designing new drugs and avoiding side effects. In this review, we describe a survey of recently reported druggability prediction methods mainly based on networks, statistical pocket druggability predictions and virtual screening. An application for a frequent mutation of p53 tumor suppressor is presented, illustrating the complementarity of druggability prediction approaches, the remaining challenges and potential new drug development perspectives. Copyright © 2016 Elsevier Ltd. All rights reserved.

75 FR 53701 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0394] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01); Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug...

Alcohol and Drug Research in California 1987.

ERIC Educational Resources Information Center

Lowe, Lois L., Comp.

Abstracts of 130 research projects in alcohol and drug programs in California are presented in this document. The projects described in this directory show the extent and diversity of current alcohol and drug research within the state. Each abstract lists the principal investigator with his or her title, institution, and address; co-principal…

Applications of microarray technology in breast cancer research

PubMed Central

Cooper, Colin S

2001-01-01

Microarrays provide a versatile platform for utilizing information from the Human Genome Project to benefit human health. This article reviews the ways in which microarray technology may be used in breast cancer research. Its diverse applications include monitoring chromosome gains and losses, tumour classification, drug discovery and development, DNA resequencing, mutation detection and investigating the mechanism of tumour development. PMID:11305951

Longitudinal impact of the project PATHS on adolescent risk behavior: what happened after five years?

PubMed

Shek, Daniel T L; Yu, Lu

2012-01-01

The present study investigated the longitudinal impact of the Project PATHS, a large-scale curriculum-based positive youth development program in Hong Kong, on the development of adolescents' risk behavior over a period of five years. Using a longitudinal randomized controlled design, eight waves of data were collected from 19 experimental schools in which students participated in the Project PATHS (N = 2,850 at Wave 8) and 24 control schools without joining the Project PATHS (N = 3,640 at Wave 8). At each wave, students responded to measures assessing their current risk behaviors, including delinquency, use of different types of drug, and their intentions of participating in risk behaviors in the future. Results demonstrated that adolescents receiving the program exhibited significantly slower increases in delinquent behaviors and substance use as compared to the control participants. During two years after the completion of the program, differences in youth risk behaviors in the two groups still existed. These results suggest that the Project PATHS has long-term effect in preventing adolescent problem behavior through promoting positive youth development.

NATIONAL POLICIES TO MEET THE CHALLENGE OF SUBSTANCE ABUSE : PROGRAMMES AND IMPLEMENTATION

PubMed Central

Malhotra, Anil; Mohan, Ashwin

2000-01-01

Drug abuse has become a growing issue of concern to humanity. India has a large consumer base of drug and alcohol abusers. This has serious repercussions in terms of morbidity & mortality. Hence the need for a national policy. In India, the Narcotic Drugs and Psychotropic Substances Act. 1985 (NDPS) provides the framework for drug abuse control in the country. A large number of measures have been undertaken as part of demand reduction activities. These include framing policies and programmes, setting up of centres, developing pilot projects, etc. However, the implementation still needs a lot to be desired. The efforts have not yet been streamlined and no revision of policies has taken place based on experience. This paper critically reviews the initiatives taken thus far to control drug abuse in our country. PMID:21407973

Polydrug use among club-going young adults recruited through time-space sampling

PubMed Central

Grov, Christian; Kelly, Brian C.; Parsons, Jeffrey T.

2009-01-01

Though some researchers have indicated club drug users are more likely to be polydrug users, there remains little known about the prevalence and specific combinations of the substances they use. Between 2004-2006, and using time-space sampling, a stratified sample of 400 18-29 year old New York City club-going drug-using young adults were recruited into the Club Drugs and Health Project. Most participants (91.7%) had engaged in polydrug use and 1,670 combinations of drugs were reported. Ecstasy (86.6% of users) and cocaine (85.7% of users) were the two most frequently reported club drugs used in combination with other substances. In terms of poly-club-drug combinations, ecstasy appeared to be the “universal compliment” as this drug was most often cited in combinations with other club drugs (specifically ecstasy + ketamine, ecstasy + cocaine, ecstasy + GHB). Other frequently cited drug combinations included cocaine and marijuana, ecstasy and marijuana, LSD and marijuana, and cocaine and alcohol. These data highlight the need to develop drug health education and prevention messages targeted at polydrug use. PMID:19444726

Traditional Medicine Collection Tracking System (TM-CTS): a database for ethnobotanically driven drug-discovery programs.

PubMed

Harris, Eric S J; Erickson, Sean D; Tolopko, Andrew N; Cao, Shugeng; Craycroft, Jane A; Scholten, Robert; Fu, Yanling; Wang, Wenquan; Liu, Yong; Zhao, Zhongzhen; Clardy, Jon; Shamu, Caroline E; Eisenberg, David M

2011-05-17

Ethnobotanically driven drug-discovery programs include data related to many aspects of the preparation of botanical medicines, from initial plant collection to chemical extraction and fractionation. The Traditional Medicine Collection Tracking System (TM-CTS) was created to organize and store data of this type for an international collaborative project involving the systematic evaluation of commonly used Traditional Chinese Medicinal plants. The system was developed using domain-driven design techniques, and is implemented using Java, Hibernate, PostgreSQL, Business Intelligence and Reporting Tools (BIRT), and Apache Tomcat. The TM-CTS relational database schema contains over 70 data types, comprising over 500 data fields. The system incorporates a number of unique features that are useful in the context of ethnobotanical projects such as support for information about botanical collection, method of processing, quality tests for plants with existing pharmacopoeia standards, chemical extraction and fractionation, and historical uses of the plants. The database also accommodates data provided in multiple languages and integration with a database system built to support high throughput screening based drug discovery efforts. It is accessed via a web-based application that provides extensive, multi-format reporting capabilities. This new database system was designed to support a project evaluating the bioactivity of Chinese medicinal plants. The software used to create the database is open source, freely available, and could potentially be applied to other ethnobotanically driven natural product collection and drug-discovery programs. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Traditional Medicine Collection Tracking System (TM-CTS): A Database for Ethnobotanically-Driven Drug-Discovery Programs

PubMed Central

Harris, Eric S. J.; Erickson, Sean D.; Tolopko, Andrew N.; Cao, Shugeng; Craycroft, Jane A.; Scholten, Robert; Fu, Yanling; Wang, Wenquan; Liu, Yong; Zhao, Zhongzhen; Clardy, Jon; Shamu, Caroline E.; Eisenberg, David M.

2011-01-01

Aim of the study. Ethnobotanically-driven drug-discovery programs include data related to many aspects of the preparation of botanical medicines, from initial plant collection to chemical extraction and fractionation. The Traditional Medicine-Collection Tracking System (TM-CTS) was created to organize and store data of this type for an international collaborative project involving the systematic evaluation of commonly used Traditional Chinese Medicinal plants. Materials and Methods. The system was developed using domain-driven design techniques, and is implemented using Java, Hibernate, PostgreSQL, Business Intelligence and Reporting Tools (BIRT), and Apache Tomcat. Results. The TM-CTS relational database schema contains over 70 data types, comprising over 500 data fields. The system incorporates a number of unique features that are useful in the context of ethnobotanical projects such as support for information about botanical collection, method of processing, quality tests for plants with existing pharmacopoeia standards, chemical extraction and fractionation, and historical uses of the plants. The database also accommodates data provided in multiple languages and integration with a database system built to support high throughput screening based drug discovery efforts. It is accessed via a web-based application that provides extensive, multi-format reporting capabilities. Conclusions. This new database system was designed to support a project evaluating the bioactivity of Chinese medicinal plants. The software used to create the database is open source, freely available, and could potentially be applied to other ethnobotanically-driven natural product collection and drug-discovery programs. PMID:21420479

Implementation of mechanism of action biology-driven early drug development for children with cancer.

PubMed

Pearson, Andrew D J; Herold, Ralf; Rousseau, Raphaël; Copland, Chris; Bradley-Garelik, Brigid; Binner, Debbie; Capdeville, Renaud; Caron, Hubert; Carleer, Jacqueline; Chesler, Louis; Geoerger, Birgit; Kearns, Pamela; Marshall, Lynley V; Pfister, Stefan M; Schleiermacher, Gudrun; Skolnik, Jeffrey; Spadoni, Cesare; Sterba, Jaroslav; van den Berg, Hendrick; Uttenreuther-Fischer, Martina; Witt, Olaf; Norga, Koen; Vassal, Gilles

2016-07-01

An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large-scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric malignancies, are evaluated in early phase clinical trials, and that this approach to generate pre-clinical and clinical data is systematically pursued by academia, sponsors, industry, and regulatory bodies to bring new paediatric oncology drugs to front-line therapy more rapidly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB)

PubMed Central

Ekins, Sean; Spektor, Anna Coulon; Clark, Alex M.; Dole, Krishna; Bunin, Barry A.

2016-01-01

Neglected disease drug discovery is generally poorly funded compared with major diseases and hence there is an increasing focus on collaboration and precompetitive efforts such as public–private partnerships (PPPs). The More Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by the EU with the goal of discovering new drugs for tuberculosis. Collaborative Drug Discovery has provided a commercial web-based platform called CDD Vault which is a hosted collaborative solution for securely sharing diverse chemistry and biology data. Using CDD Vault alongside other commercial and free cheminformatics tools has enabled support of this and other large collaborative projects, aiding drug discovery efforts and fostering collaboration. We will describe CDD's efforts in assisting with the MM4TB project. PMID:27884746

Projecting future drug expenditures in U.S. nonfederal hospitals and clinics--2013.

PubMed

Hoffman, James M; Li, Edward; Doloresco, Fred; Matusiak, Linda; Hunkler, Robert J; Shah, Nilay D; Vermeulen, Lee C; Schumock, Glen T

2013-03-15

Factors likely to influence drug expenditures, drug expenditure trends in 2012, and projected drug expenditures for U.S. nonfederal hospitals and clinics in 2013 are discussed. Prescription drug expenditure data for 2011 through September 2012 were obtained from the IMS Health National Sales Perspectives database. Expenditure projections were based on a combination of quantitative and qualitative analyses, combined with expert opinion. Total prescription sales in the United States for the 12-month period ending September 2012 were $326.0 billion, a 0.8% increase from the previous 12 months. This rate of growth was the lowest in recent history and can be attributed to modest increases in expenditures for new products (3.3%) and the prices of existing products (5.9%), coupled with a marked decline in overall volume and mix (-8.4%). For the 9 months ending in September 2012, total prescription expenditures grew 2.7% when compared with the same period in 2011. Oncology products remained important expenditures for hospitals and clinics. Antineoplastic agents were the top medication class for expenditures in nonfederal hospitals, and oncology products accounted for 32.2% of drug expenditures in the clinic setting in the first 9 months of 2012. For 2013, we project a 1-3% increase in total drug expenditures across all settings, a 2-4% increase in expenditures for clinic-administered drugs, and a 0.5% decline to 1.5% increase in hospital drug expenditures. Health-system pharmacy leaders should carefully examine their own local drug-utilization patterns to determine their own organization's drug expenditure forecast.

Institute for Molecular Medicine Research Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, Michael E

2012-12-14

The objectives of the project are the development of new Positron Emission Tomography (PET) imaging instrumentation, chemistry technology platforms and new molecular imaging probes to examine the transformations from normal cellular and biological processes to those of disease in pre-clinical animal models. These technology platforms and imaging probes provide the means to: 1. Study the biology of disease using pre-clinical mouse models and cells. 2. Develop molecular imaging probes for imaging assays of proteins in pre-clinical models. 3. Develop imaging assays in pre-clinical models to provide to other scientists the means to guide and improve the processes for discovering newmore » drugs. 4. Develop imaging assays in pre-clinical models for others to use in judging the impact of drugs on the biology of disease.« less

["When the ad is good, the product is sold." The MonitorACAO Project and drug advertising in Brazil].

PubMed

Soares, Jussara Calmon Reis de Souza

2008-04-01

This paper presents an analysis on drug advertising in Brazil, based on the final report of the MonitorACAO Project, by the group from the Universidade Federal Fluminense, Niterói, Rio de Janeiro. Due to a partnership between the university and the National Agency for Health Surveillance (ANVISA), drug advertisements were monitored and analyzed for one year, according to the methodology defined by the Agency. The samples were collected in medical practices and hospitals, drugstores, pharmacies and in scientific magazines. TV and radio programs were monitored, in the case of OTC drugs. 159 advertisements referring to pharmaceuticals were sent to ANVISA,from a total of 263 irregular ads analyzed between October 2004 and August 2005. The main problems found were the poor quality of drug information to health professionals, as well as misleading drug use to lay population. Based on the results of this project and on other studies, the banning of drug advertising in Brazil is proposed.

An Integrated Curriculum of Nursing, Nutrition, Exercise, and Drugs for Health Care Providers of the Elderly (Project NNED).

ERIC Educational Resources Information Center

Summit-Portage Area Health Education Network, Akron, OH.

This document is intended to give health care providers interdisciplinary information concerning drugs, nutrition, and exercise to help them enhance health maintenance of the elderly. Prepared as part of Project NNED, (Nursing, Nutrition, Exercise, and Drugs), an integrated curriculum for health care providers of the elderly, the document includes…

A Short-Term Evaluation of Project DARE (Drug Abuse Resistance Education): Preliminary Indications of Effectiveness.

ERIC Educational Resources Information Center

DeJong, William

1987-01-01

Assessed impact of Project DARE (Drug Abuse Resistance Education) on knowledge, attitudes, and self-reported behavior of seventh graders who received DARE curriculum in sixth grade. Compared to controls, DARE students reported significantly lower use of alcohol, cigarettes, and other drugs. Findings were especially strong for boys. (Author/NB)

Modifying Pro-Drug Risk Factors in Adolescents: Results from Project ALERT

ERIC Educational Resources Information Center

Ghosh-Dastidar, Bonnie; Longshore, Douglas L.; Ellickson, Phyllis L.; McCaffrey, Daniel F.

2004-01-01

The objective of this study was to evaluate the impact of a revised state-of-the-art drug prevention program, Project ALERT, on risk factors for drug use in mostly rural midwestern schools and communities. Fifty-five middle schools from South Dakota were randomly assigned to treatment or control conditions. Treatment-group students received 11…

A randomized evaluation of a computer-based physician's workstation: design considerations and baseline results.

PubMed Central

Rotman, B. L.; Sullivan, A. N.; McDonald, T.; DeSmedt, P.; Goodnature, D.; Higgins, M.; Suermondt, H. J.; Young, C. Y.; Owens, D. K.

1995-01-01

We are performing a randomized, controlled trial of a Physician's Workstation (PWS), an ambulatory care information system, developed for use in the General Medical Clinic (GMC) of the Palo Alto VA. Goals for the project include selecting appropriate outcome variables and developing a statistically powerful experimental design with a limited number of subjects. As PWS provides real-time drug-ordering advice, we retrospectively examined drug costs and drug-drug interactions in order to select outcome variables sensitive to our short-term intervention as well as to estimate the statistical efficiency of alternative design possibilities. Drug cost data revealed the mean daily cost per physician per patient was 99.3 cents +/- 13.4 cents, with a range from 0.77 cent to 1.37 cents. The rate of major interactions per prescription for each physician was 2.9% +/- 1%, with a range from 1.5% to 4.8%. Based on these baseline analyses, we selected a two-period parallel design for the evaluation, which maximized statistical power while minimizing sources of bias. PMID:8563376

Qualification of imaging biomarkers for oncology drug development.

PubMed

Waterton, John C; Pylkkanen, Liisa

2012-03-01

Although many imaging biomarkers have been described for cancer research, few are sufficiently robust, reliable and well-characterised to be used as routine tools in clinical cancer research. In particular, biomarkers which show that investigational therapies have reduced tumour cell proliferation, or induced necrotic or apoptotic cell death are not commonly used to support decision-making in drug development, even though such pharmacodynamic effects are common goals of many classes of investigational drugs. Moreover we lack well-qualified biomarkers of propensity to metastasise. The qualification and technical validation of imaging biomarkers poses unique challenges not always encountered when validating biospecimen biomarkers. These include standardisation of acquisition and analysis, imaging-pathology correlation, cross-sectional clinical-biomarker correlations and correlation with outcome. Such work is ideally suited to precompetitive research and public-private partnerships, and this has been recognised within the Innovative Medicines Initiative (IMI), a Joint Undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations, which has initiated projects in the areas of drug safety, drug efficacy, knowledge management and training. Copyright © 2011 Elsevier Ltd. All rights reserved.

Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations

PubMed Central

2014-01-01

Background Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. Methods We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0–13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. Results The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. Conclusions The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments. PMID:24885453

Methods in Clinical Pharmacology Series

PubMed Central

Beaumont, Claire; Young, Graeme C; Cavalier, Tom; Young, Malcolm A

2014-01-01

Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical ADME and pharmacokinetic (PK) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. These recently developed approaches are described here together with relevant examples primarily from experiences gained in support of drug development projects at GlaxoSmithKline. The advantages of these study designs together with their limitations are described. We also discuss special considerations which should be made for a successful outcome to these new approaches and also to the more traditional human radiolabel study in order to maximize knowledge around the human ADME properties of drug molecules. PMID:25041729

Developing strategies for AIDS prevention research with black and Hispanic drug users.

PubMed Central

Schilling, R F; Schinke, S P; Nichols, S E; Zayas, L H; Miller, S O; Orlandi, M A; Botvin, G J

1989-01-01

More than 8 of 10 intravenous drug users infected with the human immunodeficiency virus (HIV) are black or Hispanic. Recognizing that sociocultural factors affect HIV transmission, public health officials have called for interventions designed for ethnic-racial minority groups. Considered in this paper are the nature and extent of AIDS among ethnic-racial minorities and the cultural aspects of drug use and sexual behavior related to HIV transmission. That drug users and their associates are practicing safer needle use is evident; that they are changing their sexual behavior is less so. Calling for rapid advances in knowledge and expanded efforts in intervention, Federal agencies have instituted numerous programs to support innovative research and demonstration projects in ethnic-racial minority communities. Needed are studies that (a) describe the phenomena of drug use and sexual behavior among ethnic-racial minority populations, (b) establish the efficacy of culturally specific AIDS prevention strategies in drug treatment and community settings, and (c) demonstrate new ways of recruiting, treating, and reducing relapse among drug users. PMID:2493660

[Is the price of cancer drugs related to the cost of develo-pment and production or to the economic value of their clincal efficacy?].

PubMed

Russi, Alberto; Serena, Marta; Palozzo, Angelo C

2016-04-01

In the past years, the expenditure for cancer drugs has quickly increased, especially for biologic agents. Pharmaceutical companies and national health systems have different approaches in handling the issue of drug reimbursement. Companies support a price based on research and development (R&D) expenditures including those for unsuccessful drug projects while national health systems generally argue that pricing should be based on the incremental benefit generated by the agent under examination (value-based pricing - VBP). Nevertheless, current oncologic drugs prices are too high and not really justified by their incremental benefits or innovation, nor can they demonstrate that higher thresholds in QALYs could bring wider societal benefits. In this article we discuss these two points of view in the light of the most recent national and international literature. In Italy, drug reimbursement is currently managed through a mixed approach between the recognition of R&D expenditures and VBP. Reimbursement is also integrated with post-marketing patient-based national registries, particularly in the field of anti-cancer agents, that provide rebates based on financial risk sharing, cost-sharing, payment by results and success fee methods.

Developing community networks to deliver HIV prevention interventions.

PubMed Central

Guenther-Grey, C; Noroian, D; Fonseka, J; Higgins, D

1996-01-01

Outreach has a long history in health and social service programs as an important method for reaching at-risk persons within their communities. One method of "outreach" is based on the recruitment of networks of community members (or "networkers") to deliver HIV prevention messages and materials in the context of their social networks and everyday lives. This paper documents the experiences of the AIDS Community Demonstration Projects in recruiting networkers to deliver HIV prevention interventions to high-risk populations, including injecting drug users not in treatment; female sex partners of injecting drug users; female sex traders; men who have sex with men but do not self-identify as gay; and youth in high-risk situations. The authors interviewed project staff and reviewed project records of the implementation of community networks in five cities. Across cities, the projects successfully recruited persons into one or more community networks to distribute small media materials, condoms, and bleach kits, and encourage risk-reduction behaviors among community members. Networkers' continuing participation was enlisted through a variety of monetary and nonmonetary incentives. While continuous recruitment of networkers was necessary due to attrition, most interventions reported maintaining a core group of networkers. In addition, the projects appeared to serve as a starting point for some networkers to become more active in other community events and issues. PMID:8862156

Enabling drug discovery project decisions with integrated computational chemistry and informatics

NASA Astrophysics Data System (ADS)

Tsui, Vickie; Ortwine, Daniel F.; Blaney, Jeffrey M.

2017-03-01

Computational chemistry/informatics scientists and software engineers in Genentech Small Molecule Drug Discovery collaborate with experimental scientists in a therapeutic project-centric environment. Our mission is to enable and improve pre-clinical drug discovery design and decisions. Our goal is to deliver timely data, analysis, and modeling to our therapeutic project teams using best-in-class software tools. We describe our strategy, the organization of our group, and our approaches to reach this goal. We conclude with a summary of the interdisciplinary skills required for computational scientists and recommendations for their training.

Meaningful engagement of people living with HIV who use drugs: methodology for the design of a Peer Research Associate (PRA) hiring model.

PubMed

Closson, K; McNeil, R; McDougall, P; Fernando, S; Collins, A B; Baltzer Turje, R; Howard, T; Parashar, S

2016-10-07

Community-based HIV, harm reduction, and addiction research increasingly involve members of affected communities as Peer Research Associates (PRAs)-individuals with common experiences to the participant population (e.g. people who use drugs, people living with HIV [PLHIV]). However, there is a paucity of literature detailing the operationalization of PRA hiring and thus limited understanding regarding how affected communities can be meaningfully involved through low-barrier engagement in paid positions within community-based participatory research (CBPR) projects. We aim to address this gap by describing a low-threshold PRA hiring process. In 2012, the BC Centre for Excellence in HIV/AIDS and the Dr. Peter AIDS Foundation collaborated to develop a mixed-method CBPR project evaluating the effectiveness of the Dr. Peter Centre (DPC)-an integrative HIV care facility in Vancouver, Canada. A primary objective of the study was to assess the impact of DPC services among clients who have a history of illicit drug use. In keeping with CBPR principles, affected populations, community-based organizations, and key stakeholders guided the development and dissemination of a low-barrier PRA hiring process to meaningfully engage affected communities (e.g. PLHIV who have a history of illicit drug use) in all aspects of the research project. The hiring model was implemented in a number of stages, including (1) the establishment of a hiring team; (2) the development and dissemination of the job posting; (3) interviewing applicants; and (4) the selection of participants. The hiring model presented in this paper demonstrates the benefits of hiring vulnerable PLHIV who use drugs as PRAs in community-based research. The provision of low-barrier access to meaningful research employment described herein attempts to engage affected communities beyond tokenistic involvement in research. Our hiring model was successful at engaging five PRAs over a 2-year period and fostered opportunities for future paid employment or volunteer opportunities through ongoing collaboration between PRAs and a diverse range of stakeholders working in HIV/AIDS and addictions. Additionally, this model has the potential to be used across a range of studies and community-based settings interested in meaningfully engaging communities in all stages of the research process.

Machine learning algorithms for the prediction of hERG and CYP450 binding in drug development.

PubMed

Klon, Anthony E

2010-07-01

The cost of developing new drugs is estimated at approximately $1 billion; the withdrawal of a marketed compound due to toxicity can result in serious financial loss for a pharmaceutical company. There has been a greater interest in the development of in silico tools that can identify compounds with metabolic liabilities before they are brought to market. The two largest classes of machine learning (ML) models, which will be discussed in this review, have been developed to predict binding to the human ether-a-go-go related gene (hERG) ion channel protein and the various CYP isoforms. Being able to identify potentially toxic compounds before they are made would greatly reduce the number of compound failures and the costs associated with drug development. This review summarizes the state of modeling hERG and CYP binding towards this goal since 2003 using ML algorithms. A wide variety of ML algorithms that are comparable in their overall performance are available. These ML methods may be applied regularly in discovery projects to flag compounds with potential metabolic liabilities.

Club drug use and dependence among young adults recruited through time-space sampling.

PubMed

Parsons, Jeffrey T; Grov, Christian; Kelly, Brian C

2009-01-01

Ketamine, methylenedioxymethamphetamine (MDMA/ecstasy), cocaine, gamma-hydroxybutyrate (GHB), methamphetamine, and d-lysergic acid diethylamide (LSD/acid) have been identified as "club drugs" because of their link to club culture among young adults. Yet little is known about users' demographic differences in the prevalence of club drugs. This study sought to provide a comprehensive profile of users' demographic differences in prevalence of club drug use and dependence. Using time-space sampling, a stratified sample of 400 18- to 29-year-old club-going young adults was recruited into the Club Drugs and Health Project. Though participants reported using an array of club drugs, almost all participants (90.0%) were cocaine users. Although there were several sexual orientation and gender differences in recent drug exposure, patterns of use (measured in days) were fairly similar across gender, sexual orientation, and age. Finally, a majority of individuals (58.5%) met or exceeded criteria for club drug dependence, with most (61.7%) indicating cocaine was the one drug causing them significant problems. Cocaine is a major drug in club culture. It is essential to develop culturally appropriate drug education and prevention initiatives for young adults using club drugs.

Adaptation of Alcohol and Drug Screening, Brief Intervention and Referral to Treatment (SBIRT) to a Department of Intercollegiate Athletics: The COMPASS Project

ERIC Educational Resources Information Center

Agley, Jon; Walker, Barbara B.; Gassman, Ruth A.

2013-01-01

Objective: To develop and implement an intervention for problem alcohol and substance use among student athletes at a large Midwestern department of intercollegiate athletics in the USA, by use of screening, a brief intervention, referral to treatment (SBIRT) and motivational interviewing (MI). This paper outlines the development of the protocol,…

Modelling Drug Administration Regimes for Asthma: A Romanian Experience

ERIC Educational Resources Information Center

Andras, Szilard; Szilagyi, Judit

2010-01-01

In this article, we present a modelling activity, which was a part of the project DQME II (Developing Quality in Mathematics Education, for more details see http://www.dqime.uni-dortmund.de) and some general observations regarding the maladjustments and rational errors arising in such type of activities.

Citizen Me: An Experiential Curriculum for Citizenship Education. Level: Six.

ERIC Educational Resources Information Center

Lantz, Jean

The Citizen Me Level Six guide incorporates the project's goal of providing a curriculum which integrates concepts of basic citizenship education with community involvement through gaining an understanding of rights, liberties, and obligations of citizens, developing an awareness of outcomes identified in crime and drug education, understanding…

76 FR 9562 - Safe Schools/Healthy Students Program; Catalog of Federal Domestic Assistance (CFDA) Numbers: 84...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-18

... projects resulted in-- Fewer students witnessing violence; Fewer students involved in violent incidents... related to the five comprehensive plan elements: Element One: Safe school environments and violence... related to early childhood social and emotional learning and development; drug, alcohol, and violence...

Method Development for Clinical Comprehensive Evaluation of Pediatric Drugs Based on Multi-Criteria Decision Analysis: Application to Inhaled Corticosteroids for Children with Asthma.

PubMed

Yu, Yuncui; Jia, Lulu; Meng, Yao; Hu, Lihua; Liu, Yiwei; Nie, Xiaolu; Zhang, Meng; Zhang, Xuan; Han, Sheng; Peng, Xiaoxia; Wang, Xiaoling

2018-04-01

Establishing a comprehensive clinical evaluation system is critical in enacting national drug policy and promoting rational drug use. In China, the 'Clinical Comprehensive Evaluation System for Pediatric Drugs' (CCES-P) project, which aims to compare drugs based on clinical efficacy and cost effectiveness to help decision makers, was recently proposed; therefore, a systematic and objective method is required to guide the process. An evidence-based multi-criteria decision analysis model that involved an analytic hierarchy process (AHP) was developed, consisting of nine steps: (1) select the drugs to be reviewed; (2) establish the evaluation criterion system; (3) determine the criterion weight based on the AHP; (4) construct the evidence body for each drug under evaluation; (5) select comparative measures and calculate the original utility score; (6) place a common utility scale and calculate the standardized utility score; (7) calculate the comprehensive utility score; (8) rank the drugs; and (9) perform a sensitivity analysis. The model was applied to the evaluation of three different inhaled corticosteroids (ICSs) used for asthma management in children (a total of 16 drugs with different dosage forms and strengths or different manufacturers). By applying the drug analysis model, the 16 ICSs under review were successfully scored and evaluated. Budesonide suspension for inhalation (drug ID number: 7) ranked the highest, with comprehensive utility score of 80.23, followed by fluticasone propionate inhaled aerosol (drug ID number: 16), with a score of 79.59, and budesonide inhalation powder (drug ID number: 6), with a score of 78.98. In the sensitivity analysis, the ranking of the top five and lowest five drugs remains unchanged, suggesting this model is generally robust. An evidence-based drug evaluation model based on AHP was successfully developed. The model incorporates sufficient utility and flexibility for aiding the decision-making process, and can be a useful tool for the CCES-P.

In silico fragment-based drug design.

PubMed

Konteatis, Zenon D

2010-11-01

In silico fragment-based drug design (FBDD) is a relatively new approach inspired by the success of the biophysical fragment-based drug discovery field. Here, we review the progress made by this approach in the last decade and showcase how it complements and expands the capabilities of biophysical FBDD and structure-based drug design to generate diverse, efficient drug candidates. Advancements in several areas of research that have enabled the development of in silico FBDD and some applications in drug discovery projects are reviewed. The reader is introduced to various computational methods that are used for in silico FBDD, the fragment library composition for this technique, special applications used to identify binding sites on the surface of proteins and how to assess the druggability of these sites. In addition, the reader will gain insight into the proper application of this approach from examples of successful programs. In silico FBDD captures a much larger chemical space than high-throughput screening and biophysical FBDD increasing the probability of developing more diverse, patentable and efficient molecules that can become oral drugs. The application of in silico FBDD holds great promise for historically challenging targets such as protein-protein interactions. Future advances in force fields, scoring functions and automated methods for determining synthetic accessibility will all aid in delivering more successes with in silico FBDD.

Molecular Dynamics: New Frontier in Personalized Medicine.

PubMed

Sneha, P; Doss, C George Priya

2016-01-01

The field of drug discovery has witnessed infinite development over the last decade with the demand for discovery of novel efficient lead compounds. Although the development of novel compounds in this field has seen large failure, a breakthrough in this area might be the establishment of personalized medicine. The trend of personalized medicine has shown stupendous growth being a hot topic after the successful completion of Human Genome Project and 1000 genomes pilot project. Genomic variant such as SNPs play a vital role with respect to inter individual's disease susceptibility and drug response. Hence, identification of such genetic variants has to be performed before administration of a drug. This process requires high-end techniques to understand the complexity of the molecules which might bring an insight to understand the compounds at their molecular level. To sustenance this, field of bioinformatics plays a crucial role in revealing the molecular mechanism of the mutation and thereby designing a drug for an individual in fast and affordable manner. High-end computational methods, such as molecular dynamics (MD) simulation has proved to be a constitutive approach to detecting the minor changes associated with an SNP for better understanding of the structural and functional relationship. The parameters used in molecular dynamic simulation elucidate different properties of a macromolecule, such as protein stability and flexibility. MD along with docking analysis can reveal the synergetic effect of an SNP in protein-ligand interaction and provides a foundation for designing a particular drug molecule for an individual. This compelling application of computational power and the advent of other technologies have paved a promising way toward personalized medicine. In this in-depth review, we tried to highlight the different wings of MD toward personalized medicine. © 2016 Elsevier Inc. All rights reserved.

Characterization of 12 GnRH peptide agonists - a kinetic perspective.

PubMed

Nederpelt, Indira; Georgi, Victoria; Schiele, Felix; Nowak-Reppel, Katrin; Fernández-Montalván, Amaury E; IJzerman, Adriaan P; Heitman, Laura H

2016-01-01

Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin-releasing hormone (GnRH) receptor for the treatment of hormone-dependent diseases. Surprisingly, the kinetic receptor-binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor-binding kinetics of 12 GnRH peptide agonists, including many marketed drugs. A novel radioligand-binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [(125) I]-triptorelin. In addition to radioligand-binding studies, a homogeneous time-resolved FRET Tag-lite™ method was developed as an alternative assay for the same purpose. Two novel competition association assays were successfully developed and applied to determine the kinetic receptor-binding characteristics of 12 high-affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin). Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor. © 2015 The British Pharmacological Society.

Making care affordable.

PubMed

Solomon, S

1999-01-01

The YRG Centre for AIDS Research and Education (CARE) in Chennai, India runs an integrated care program ensuring appropriate and affordable care to everyone who needs it. The program includes both voluntary counseling/testing and hospital/home-based care. YRG CARE developed several strategies for the care program, which include 1) different fees for an HIV test, 2) free counseling service, 3) different charges for other care services, 4) a subsidized pharmacy (involving purchasing drugs directly from manufacturers and wholesalers, ordering free samples from manufacturers, and acquiring drugs through the drug component of its clinical research projects, from overseas hospitals, and from YRG CARE hospital and community-based patients who have not used them), and 5) subsidized meals.

Application of chemical biology in target identification and drug discovery.

PubMed

Zhu, Yue; Xiao, Ting; Lei, Saifei; Zhou, Fulai; Wang, Ming-Wei

2015-09-01

Drug discovery and development is vital to the well-being of mankind and sustainability of the pharmaceutical industry. Using chemical biology approaches to discover drug leads has become a widely accepted path partially because of the completion of the Human Genome Project. Chemical biology mainly solves biological problems through searching previously unknown targets for pharmacologically active small molecules or finding ligands for well-defined drug targets. It is a powerful tool to study how these small molecules interact with their respective targets, as well as their roles in signal transduction, molecular recognition and cell functions. There have been an increasing number of new therapeutic targets being identified and subsequently validated as a result of advances in functional genomics, which in turn led to the discovery of numerous active small molecules via a variety of high-throughput screening initiatives. In this review, we highlight some applications of chemical biology in the context of drug discovery.

Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation

PubMed Central

Quirke, Viviane M.

2017-01-01

Today, tamoxifen is one of the world's best-selling hormonal breast cancer drugs. However, it was not always so. Compound ICI 46,474 (as it was first known) was synthesized in 1962 within a project to develop a contraceptive pill in the pharmaceutical laboratories of ICI (now part of AstraZeneca). Although designed to act as an anti-estrogen, the compound stimulated, rather than suppressed ovulation in women. This, and the fact that it could not be patented in the USA, its largest potential market, meant that ICI nearly stopped the project. It was saved partly because the team's leader, Arthur Walpole, threatened to resign, and pressed on with another project: to develop tamoxifen as a treatment for breast cancer. Even then, its market appeared small, because at first it was mainly used as a palliative treatment for advanced breast cancer. An important turning point in tamoxifen's journey from orphan drug to best-selling medicine occurred in the 1980s, when clinical trials showed that it was also useful as an adjuvant to surgery and chemotherapy in the early stages of the disease. Later, trials demonstrated that it could prevent its occurrence or re-occurrence in women at high risk of breast cancer. Thus, it became the first preventive for any cancer, helping to establish the broader principles of chemoprevention, and extending the market for tamoxifen and similar drugs further still. Using tamoxifen as a case study, this paper discusses the limits of the rational approach to drug design, the role of human actors, and the series of feedback loops between bench and bedside that underpins pharmaceutical innovation. The paper also highlights the complex evaluation and management of risk that are involved in all therapies, but more especially perhaps in life-threatening and emotion-laden diseases like cancer. PMID:28955226

Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation.

PubMed

Quirke, Viviane M

2017-01-01

Today, tamoxifen is one of the world's best-selling hormonal breast cancer drugs. However, it was not always so. Compound ICI 46,474 (as it was first known) was synthesized in 1962 within a project to develop a contraceptive pill in the pharmaceutical laboratories of ICI (now part of AstraZeneca). Although designed to act as an anti-estrogen, the compound stimulated, rather than suppressed ovulation in women. This, and the fact that it could not be patented in the USA, its largest potential market, meant that ICI nearly stopped the project. It was saved partly because the team's leader, Arthur Walpole, threatened to resign, and pressed on with another project: to develop tamoxifen as a treatment for breast cancer. Even then, its market appeared small, because at first it was mainly used as a palliative treatment for advanced breast cancer. An important turning point in tamoxifen's journey from orphan drug to best-selling medicine occurred in the 1980s, when clinical trials showed that it was also useful as an adjuvant to surgery and chemotherapy in the early stages of the disease. Later, trials demonstrated that it could prevent its occurrence or re-occurrence in women at high risk of breast cancer. Thus, it became the first preventive for any cancer, helping to establish the broader principles of chemoprevention, and extending the market for tamoxifen and similar drugs further still. Using tamoxifen as a case study, this paper discusses the limits of the rational approach to drug design, the role of human actors, and the series of feedback loops between bench and bedside that underpins pharmaceutical innovation. The paper also highlights the complex evaluation and management of risk that are involved in all therapies, but more especially perhaps in life-threatening and emotion-laden diseases like cancer.

Community-based participatory research in a heavily researched inner city neighbourhood: Perspectives of people who use drugs on their experiences as peer researchers

PubMed Central

Damon, Will; Callon, Cody; Wiebe, Lee; Small, Will; Kerr, Thomas; McNeil, Ryan

2017-01-01

Community based participatory research (CBPR) has become an increasingly common approach to research involving people who use(d) drugs (PWUD), who are often employed as Peer Researchers on these projects. This paper seeks to understand the impact of CBPR on PWUD, particularly those living in heavily researched and stigmatized neighbourhoods where CBPR projects are often located. This study draws on 14 in-depth interviews with PWUD who had previous experience as both peer researchers and research participants in CBPR projects conducted between July 2010 and February 2011. The study employed a CBPR approach in its study design, recruitment, interviewing, and analysis. Our analysis indicates that participants were supportive of CBPR in principle and described the ways in which it helped contest stigmatizing assumptions and researcher bias. Participants also reported positive personal gains from participation in CBPR projects. However, many participants had negative experiences with CBPR projects, especially when CBPR principles were implemented in a superficial or incomplete manner. Participants emphasized the importance of inclusiveness and active deconstruction of hierarchy between researchers and community members to successful CBPR among drug using populations. CBPR has been widely adopted as a research approach within marginalized communities but has often been implemented inconsistently. Still, CBPR can empower communities to contest forms of social stigma that are often reproduced through academic research on marginalized communities. Our findings describe how the benefits of CBPR are maximized when CBPR principles are consistently applied and when community based researchers are supported in ways that reduce hierarchies of power. This suggests a need for capacity building within affected communities to develop independent support, training, and grievance processes for peer researchers. PMID:28135693

Community-based participatory research in a heavily researched inner city neighbourhood: Perspectives of people who use drugs on their experiences as peer researchers.

PubMed

Damon, Will; Callon, Cody; Wiebe, Lee; Small, Will; Kerr, Thomas; McNeil, Ryan

2017-03-01

Community-based participatory research (CBPR) has become an increasingly common approach to research involving people who use(d) drugs (PWUD), who are often employed as peer researchers on these projects. This paper seeks to understand the impact of CBPR on PWUD, particularly those living in heavily researched and stigmatized neighbourhoods where CBPR projects are often located. This study draws on 14 in-depth interviews with PWUD who had previous experience as both peer researchers and research participants in CBPR projects conducted between July 2010 and February 2011. The study employed a CBPR approach in its study design, recruitment, interviewing, and analysis. Our analysis indicates that participants were supportive of CBPR in principle and described the ways in which it helped contest stigmatizing assumptions and researcher bias. Participants also reported positive personal gains from participation in CBPR projects. However, many participants had negative experiences with CBPR projects, especially when CBPR principles were implemented in a superficial or incomplete manner. Participants emphasized the importance of inclusiveness and active deconstruction of hierarchy between researchers and community members to successful CBPR among drug using populations. CBPR has been widely adopted as a research approach within marginalized communities but has often been implemented inconsistently. Still, CBPR can empower communities to contest forms of social stigma that are often reproduced through academic research on marginalized communities. Our findings describe how the benefits of CBPR are maximized when CBPR principles are consistently applied and when community-based researchers are supported in ways that reduce power hierarchies. This suggests a need for capacity building within affected communities to develop independent support, training, and grievance processes for peer researchers. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Health Intervention Project: HIV risk reduction among African American women drug users.

PubMed Central

Sterk, Claire E.

2002-01-01

OBJECTIVE: This article describes the Health Intervention Project, an intervention for African American women in Atlanta, Georgia, who are crack cocaine users. METHODS:A formative phase involved ethnographic mapping of the physical and social infrastructure of the study communities and in-depth interviews with women crack cocaine users. Key findings that were incorporated into the intervention program included the exchange of sex for money or drugs, the women's experience with trauma and abuse, the role of men and male partners, the women's roles as mothers and members of extended families, their identity as African Americans, and their desire to reduce their risk for HIV/AIDS related to their drug use and sexual behavior. Individualized intervention sessions were designed to meet the women's needs. The motivation intervention emphasized self-motivation for behavioral change with the assistance of the interventionist, who facilitated the women's goal identification, action plan, and problem-solving skills. The negotiation intervention focused on improving technical and assertive communication skills. An action plan was developed, and the women worked on negotiation skills, self-control regarding sexual and drug-use encounters, assertiveness in sexual and drug-use interactions, and conflict resolution. CONCLUSION: Effective prevention and intervention programs must be framed within an appropriate racial, ethnic, and cultural context. Future research is needed to better understand risk in its social context, including the impact of community factors. PMID:12435832

The Health Intervention Project: HIV risk reduction among African American women drug users.

PubMed

Sterk, Claire E

2002-01-01

This article describes the Health Intervention Project, an intervention for African American women in Atlanta, Georgia, who are crack cocaine users. A formative phase involved ethnographic mapping of the physical and social infrastructure of the study communities and in-depth interviews with women crack cocaine users. Key findings that were incorporated into the intervention program included the exchange of sex for money or drugs, the women's experience with trauma and abuse, the role of men and male partners, the women's roles as mothers and members of extended families, their identity as African Americans, and their desire to reduce their risk for HIV/AIDS related to their drug use and sexual behavior. Individualized intervention sessions were designed to meet the women's needs. The motivation intervention emphasized self-motivation for behavioral change with the assistance of the interventionist, who facilitated the women's goal identification, action plan, and problem-solving skills. The negotiation intervention focused on improving technical and assertive communication skills. An action plan was developed, and the women worked on negotiation skills, self-control regarding sexual and drug-use encounters, assertiveness in sexual and drug-use interactions, and conflict resolution. Effective prevention and intervention programs must be framed within an appropriate racial, ethnic, and cultural context. Future research is needed to better understand risk in its social context, including the impact of community factors.

Best Practices in Prevention: A Curriculum on Alcohol, Tobacco and Other Drugs, and Violence. Grades 6 and 7. Life Skills Component. Project Oz.

ERIC Educational Resources Information Center

Bilyk-Glancy, Joanne; Caison, Shelia; Campbell, Melissa; Carlton, Chris; Dobbins, Mike; Menkhaus, Lisa; Nappi, Beth; Payne, Sue; Rankaitis, Peter; Sutton, Arthur; Wisted, Nancy

Project Oz is a not-for-profit special services agency providing drug education and crisis intervention services. Project Oz curricula provide compact and well-researched information for teachers, supplemented by student learning activities that reinforce the lecture portions of the topic. These activities are grade-appropriate and incorporate…

Best Practices in Prevention: A Curriculum on Alcohol, Tobacco and Other Drugs, and Violence. Grades 6 and 7. Violence Prevention Component. Project Oz.

ERIC Educational Resources Information Center

Bilyk-Glancy, Joanne; Caison, Shelia; Campbell, Melissa; Carlton, Chris; Dobbins, Mike; Menkhaus, Lisa; Nappi, Beth; Payne, Sue; Rankaitis, Peter; Sutton, Arthur; Wisted, Nancy

Project Oz is a not-for-profit special services agency providing drug education and crisis intervention services. Project Oz curricula provide compact and well-researched information for teachers, supplemented by student learning activities that reinforce the lecture portions of the topic. These activities are grade-appropriate and incorporate…

Best Practices in Prevention: A Curriculum on Alcohol, Tobacco and Other Drugs, and Violence. Grades 4 and 5. Violence Component. Project Oz.

ERIC Educational Resources Information Center

Bilyk-Glancy, Joanne; Carlton, Chris; Dobbins, E. Mike; Fisher, Barbara; Menkhaus, Lisa

Project Oz is a not-for-profit special services agency providing drug education and crisis intervention services. Project Oz curricula provide compact and well-researched information for teachers, supplemented by student learning activities that reinforce the lecture portions of the topic. These activities are grade-appropriate and incorporate…

Templates of patient brochures for the preparation, administration and safe-handling of oral chemotherapy.

PubMed

Siden, Rivka; Kem, Ravie; Ostrenga, Andrew; Nicksy, Darcy; Bernhardt, Brooke; Bartholomew, Joy

2014-06-01

The increased use of oral chemotherapy for the treatment of cancer introduces new challenges for patients and caregivers. Among them are the ability to swallow oral solid dosage forms, the proper administration of the agents and the safe-handling of chemotherapeutic drugs in the home. Since these drugs are hazardous, proper preparation, administration, and disposition introduces a variety of safety issues. The increased toxicity of these drugs coupled with complicated dosing regimens and the occasional need to dilute the drug or measure a liquid dosage form require careful instruction of the patient and/or caregivers. The purpose of this project was to create templates for writing patient instruction brochures. A group of clinicians specializing in oncology from several institutions in the United States and Canada met through a series of conference calls. The group included pharmacists with a specialty in pediatric oncology, investigational drug pharmacists, and an oncology nurse practitioner. National guidelines and practices at each institution were used for the creation of templates to be used in developing templates for medication and formulation-specific instruction brochures. The group developed six templates. The templates ranged in scope from instructions on the administration of intact tablets or capsules to directions on opening capsules or crushing tablets and mixing the content with foods or liquids. Thirty-three drug-specific brochures were developed using the templates. Templates of patient brochures and drug-specific brochures on the safe handling of chemotherapy in the home can be created using a collaborative, multi-institutional approach.

Computer-aided drug design at Boehringer Ingelheim

NASA Astrophysics Data System (ADS)

Muegge, Ingo; Bergner, Andreas; Kriegl, Jan M.

2017-03-01

Computer-Aided Drug Design (CADD) is an integral part of the drug discovery endeavor at Boehringer Ingelheim (BI). CADD contributes to the evaluation of new therapeutic concepts, identifies small molecule starting points for drug discovery, and develops strategies for optimizing hit and lead compounds. The CADD scientists at BI benefit from the global use and development of both software platforms and computational services. A number of computational techniques developed in-house have significantly changed the way early drug discovery is carried out at BI. In particular, virtual screening in vast chemical spaces, which can be accessed by combinatorial chemistry, has added a new option for the identification of hits in many projects. Recently, a new framework has been implemented allowing fast, interactive predictions of relevant on and off target endpoints and other optimization parameters. In addition to the introduction of this new framework at BI, CADD has been focusing on the enablement of medicinal chemists to independently perform an increasing amount of molecular modeling and design work. This is made possible through the deployment of MOE as a global modeling platform, allowing computational and medicinal chemists to freely share ideas and modeling results. Furthermore, a central communication layer called the computational chemistry framework provides broad access to predictive models and other computational services.

Learning from the past for TB drug discovery in the future

PubMed Central

Mikušová, Katarína; Ekins, Sean

2016-01-01

Tuberculosis drug discovery has shifted in recent years from a primarily target-based approach to one that uses phenotypic high-throughput screens. As examples of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis was target-based and our more-recent More Medicines for Tuberculosis project predominantly used phenotypic screening. From these projects we have examples of success (DprE1) and failure (PimA) going from drug to target and from target to drug, respectively. It is clear that we still have much to learn about the drug targets and the complex effects of the drugs on Mycobacterium tuberculosis. We propose a more integrated approach that learns from earlier drug discovery efforts that could help to move drug discovery forward. PMID:27717850

Qualitative research with a Kenyan flavour.

PubMed

Mburu, J; Cogswell, L; Crane, E; Todreas, I L

1991-01-01

The Essential Drugs Program in Kenya's Ministry of Health included a qualitative research phase of focus group discussions (FGDs) to assess the communication needs in educating the public about responsible essential drug use. This article discusses the general parameters of FGDs, and specific outcomes of essential drug FGDs and the evaluation of the health education tools generated in the FGDs. The purpose of the pilot project was to develop effective materials on the correct use of drug regimens and promoting authorized drug providers. FGDs were used as a quick and relatively inexpensive means of gauging a target audience's beliefs and practices. The facilitator of the group directed discussion and probed for participants views on the community's needs, and forms of expression. (Drawing on positive social customs within a culture helps bridge the difference between local perceptions and knowledge.) Pretesting of draft materials in FGDs assured the ability to reach the target audience. These 2 methods contributed to the project's success by involving the target group as experts in providing useful information, fostering a sense of ownership and commitment, and building a relationship between the staff and target group that renewed dedication and willingness to cooperate. Program staff conducted 19 FGDs with 171 clients and 9 FGDs with 63 providers, and also interviewed 36 providers and observed in 4 locations client/provider exchanges. The results showed that client were unaware of the importance of strict compliance with a drug regimen, and consequences of ineffectiveness. Clients were uneasy about side effects, and purchased drugs from unauthorized dealers. The 3 messages to be promoted were 1) return to the clinic or hospital if drug problems arise, 2) use only authorized providers, and 3) follow directions carefully and completely. It was also decided that posters and audio cassette were the communication modes. A description of the materials developed is described. 24 health centers in 3 districts received the materials. A 3 month evaluation was conducted, after which time quantitative information was analyzed. Behavioral changes were observed in the returns to the clinic for more information, and closing of some unauthorized clinics and loss of business, and fewer complaints of lingering illness. Communication, trust, and good health care resulted.

Nanopharmaceuticals (part 1): products on the market.

PubMed

Weissig, Volkmar; Pettinger, Tracy K; Murdock, Nicole

2014-01-01

In 2000, the National Institute of Health launched the National Nanotechnology Initiative to support, coordinate, and advance research and development of nanoscale projects. The impact of this new program on health-science related research and development became quickly visible. Broad governmental financial support advanced the start of new, and the deepening of already existing, interdisciplinary research. The anticipated merger of nanoscience with medicine quickly instigated the conceptualization of nanomedicine. The adoption of nanoscience terminology by pharmaceutical scientists resulted in the advent of nanopharmaceuticals. The term "nano" became tantamount to "cutting-edge" and was quickly embraced by the pharmaceutical science community. Colloidal drug delivery systems reemerged as nanodrug delivery systems; colloidal gold became a suspension of nano gold particles. In this review, we first review nanoscience related definitions applied to pharmaceuticals, we then discuss all 43 currently approved drug formulations which are publicized as nanopharmaceuticals, and finally we analyze clinical aspects of selected drug formulations.

Nanopharmaceuticals (part 1): products on the market

PubMed Central

Weissig, Volkmar; Pettinger, Tracy K; Murdock, Nicole

2014-01-01

In 2000, the National Institute of Health launched the National Nanotechnology Initiative to support, coordinate, and advance research and development of nanoscale projects. The impact of this new program on health-science related research and development became quickly visible. Broad governmental financial support advanced the start of new, and the deepening of already existing, interdisciplinary research. The anticipated merger of nanoscience with medicine quickly instigated the conceptualization of nanomedicine. The adoption of nanoscience terminology by pharmaceutical scientists resulted in the advent of nanopharmaceuticals. The term “nano” became tantamount to “cutting-edge” and was quickly embraced by the pharmaceutical science community. Colloidal drug delivery systems reemerged as nanodrug delivery systems; colloidal gold became a suspension of nano gold particles. In this review, we first review nanoscience related definitions applied to pharmaceuticals, we then discuss all 43 currently approved drug formulations which are publicized as nanopharmaceuticals, and finally we analyze clinical aspects of selected drug formulations. PMID:25258527

Specialty pharmaceuticals: policy initiatives to improve assessment, pricing, prescription, and use.

PubMed

Robinson, James C; Howell, Scott

2014-10-01

The value of "specialty pharmaceuticals" for cancer and other complex conditions depends not merely on their molecular structures but also on the manner in which the drugs are assessed, insured, priced, prescribed, and used. This article analyzes the five principal stages through which a specialty drug must pass on its journey from the laboratory to the bedside. These include regulatory approval by the Food and Drug Administration for market access, insurance coverage, pricing and payment, physician prescription, and patient engagement. If structured appropriately, each stage improves performance and supports continued research and development. If structured inappropriately, however, each stage adds to administrative burdens, distorts clinical decision making, and weakens incentives for innovation. Cautious optimism is in order, but neither the continued development of breakthrough products nor their use according to evidence-based guidelines can be taken for granted. Project HOPE—The People-to-People Health Foundation, Inc.

A Liver-centric Multiscale Modeling Framework for Xenobiotics ...

EPA Pesticide Factsheets

We describe a multi-scale framework for modeling acetaminophen-induced liver toxicity. Acetaminophen is a widely used analgesic. Overdose of acetaminophen can result in liver injury via its biotransformation into toxic product, which further induce massive necrosis. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. To validate the model, we estimated our model parameters by fi?tting serum concentrations of acetaminophen and its glucuronide and sulfate metabolites to experiments, and carried out sensitivity analysis on 35 parameters selected from three modules. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. This multiscale model bridges the CompuCell3D tool used by the Virtual Tissue project with the httk tool developed by the Rapid Exposure and Dosimetry project.

Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes.

PubMed

Chen, Yang; Gao, Zhen; Wang, Bingcheng; Xu, Rong

2016-08-22

Glioblastoma (GBM) is the most common and aggressive brain tumors. It has poor prognosis even with optimal radio- and chemo-therapies. Since GBM is highly heterogeneous, drugs that target on specific molecular profiles of individual tumors may achieve maximized efficacy. Currently, the Cancer Genome Atlas (TCGA) projects have identified hundreds of GBM-associated genes. We develop a drug repositioning approach combining disease genomics and mouse phenotype data towards predicting targeted therapies for GBM. We first identified disease specific mouse phenotypes using the most recently discovered GBM genes. Then we systematically searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM. We evaluated the ranks for approved and novel GBM drugs, and compared with an existing approach, which also use the mouse phenotype data but not the disease genomics data. We achieved significantly higher ranks for the approved and novel GBM drugs than the earlier approach. For all positive examples of GBM drugs, we achieved a median rank of 9.2 45.6 of the top predictions have been demonstrated effective in inhibiting the growth of human GBM cells. We developed a computational drug repositioning approach based on both genomic and phenotypic data. Our approach prioritized existing GBM drugs and outperformed a recent approach. Overall, our approach shows potential in discovering new targeted therapies for GBM.

Knowledge Integration and Use-Case Analysis for a Customized Drug-Drug Interaction CDS Service

NASA Astrophysics Data System (ADS)

Kam, Hye Jin; Park, Man Young; Kim, Woojae; Yoon, Duk Yong; Ahn, Eun Kyoung; Park, Rae Woong

Clinical decision support systems (CDSSs) are thought to reduce adverse drug events (ADEs) by monitoring drug-drug interactions(DDIs). However, clinically improper or excessive alerts can result in high alert overrides. A tailored CDS service, which is appropriate for clinicians and their ordering situations, is required to increase alert acceptance. In this study, we conducted a 12-week pilot project adopting a tailed CDSS at an emergency department. The new CDSS was conducted via a stepwise integration of additional new rules. The alert status with changes in acceptance rate was analyzed. The most frequent DDI alerts were related to prescriptions of anti-inflammatory drugs. The percentages of alert overrides for each stage were 98.0%, 96.0%, 96.9%, and 98.1%, respectively. 91.5% of overridden alerts were related to discharge medications. To reduce the potential hazards of ADEs, the development of an effective customized DDI CDSS is required, via in-depth analysis on alert patterns and overridden reasons.

Chemistry challenges in lead optimization: silicon isosteres in drug discovery.

PubMed

Showell, Graham A; Mills, John S

2003-06-15

During the lead optimization phase of drug discovery projects, the factors contributing to subsequent failure might include poor portfolio decision-making and a sub-optimal intellectual property (IP) position. The pharmaceutical industry has an ongoing need for new, safe medicines with a genuine biomedical benefit, a clean IP position and commercial viability. Inherent drug-like properties and chemical tractability are also essential for the smooth development of such agents. The introduction of bioisosteres, to improve the properties of a molecule and obtain new classes of compounds without prior art in the patent literature, is a key strategy used by medicinal chemists during the lead optimization process. Sila-substitution (C/Si exchange) of existing drugs is an approach to search for new drug-like candidates that have beneficial biological properties and a clear IP position. Some of the fundamental differences between carbon and silicon can lead to marked alterations in the physicochemical and biological properties of the silicon-containing analogues and the resulting benefits can be exploited in the drug design process.

Core competencies for pharmaceutical physicians and drug development scientists

PubMed Central

Silva, Honorio; Stonier, Peter; Buhler, Fritz; Deslypere, Jean-Paul; Criscuolo, Domenico; Nell, Gerfried; Massud, Joao; Geary, Stewart; Schenk, Johanna; Kerpel-Fronius, Sandor; Koski, Greg; Clemens, Norbert; Klingmann, Ingrid; Kesselring, Gustavo; van Olden, Rudolf; Dubois, Dominique

2013-01-01

Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide. PMID:23986704

The drug effectiveness review project: an important step forward.

PubMed

Gibson, Mark; Santa, John

2006-01-01

Peter Neumann's paper on the Drug Effectiveness Review Project (DERP) is a constructive if incomplete point of departure for discussing the work done by the project and the use of that work by decision-makers in states and elsewhere. This Perspective attempts to establish the proper context for judging the DERP by comparing its product and processes with those commonly produced and used by industry and other parties. It also provides a direct response to the criticisms of the project noted by Neumann.

The Queensland experience of participation in a national drug use evaluation project, Community-acquired pneumonia – towards improving outcomes nationally (CAPTION)

PubMed Central

Pulver, Lisa K; Tett, Susan E; Coombes, Judith

2009-01-01

Background Multicentre drug use evaluations are described in the literature infrequently and usually publish only the results. The purpose of this paper is to describe the experience of Queensland hospitals participating in the Community-Acquired Pneumonia Towards Improving Outcomes Nationally (CAPTION) project, specifically evaluating the implementation of this project, detailing benefits and drawbacks of involvement in a national drug use evaluation program. Methods Emergency departments from nine hospitals in Queensland, Australia, participated in CAPTION, a national quality improvement project, conducted in 37 Australian hospitals. CAPTION was aimed at optimising prescribing in the management of Community-Acquired Pneumonia according to the recommendations of the Australian Therapeutic Guidelines: Antibiotic 12th edition. The project involved data collection, and evaluation, feedback of results and a suite of targeted educational interventions including audit and feedback, group presentations and academic detailing. A baseline audit and two drug use evaluation cycles were conducted during the 2-year project. The implementation of the project was evaluated using feedback forms after each phase of the project (audit or intervention). At completion a group meeting with the hospital coordinators identified positive and negative elements of the project. Results Evaluation by hospitals of their participation in CAPTION demonstrated both benefits and drawbacks. The benefits were grouped into the impact on the hospital dynamic such as; improved interdisciplinary working relationships (e.g. between pharmacist and doctor), recognition of the educational/academic role of the pharmacist, creation of ED Pharmacist positions and enhanced involvement with the National Prescribing Service, and personal benefits. Personal benefits included academic detailing training for participants, improved communication skills and opportunities to present at conferences. The principal drawback of participation was the extra burden on already busy staff members. Conclusion A national multicentre drug use evaluation project such as CAPTION allows hospitals which would otherwise not undertake such projects the opportunity to participate. The Queensland arm of CAPTION demonstrated benefits to both the individual participants and their hospitals, highlighting the additional value of participating in a multicentre project of this type. PMID:19646287

Knowledge Translation to Advance Evidence-Based Health Policy in Thailand

ERIC Educational Resources Information Center

Ti, Lianlian; Hayashi, Kanna; Ti, Lianping; Kaplan, Karyn; Suwannawong, Paisan; Kerr, Thomas

2017-01-01

Significant gaps between scientific evidence and policy have resulted in growing interest in the role that knowledge translation (KT) can play in informing evidence-based policy. The Mitsampan Community Research Project, in consultation with the local community of people who inject drugs, developed a comprehensive KT strategy that aimed to…

Evaluation of Project Chrysalis: A School-based Intervention To Reduce Negative Consequences of Abuse.

ERIC Educational Resources Information Center

Brown, Kelly J.; Block, Audrey J.

2001-01-01

Evaluated a school-based program that served female adolescents with histories of physical, sexual, or emotional abuse. Found that participation produced healthier beliefs and attitudes about alcohol and other drug use and reduced initiation of tobacco and marijuana use. Findings support enrolling younger girls before they develop negative…

Postmarketing surveillance in developing countries.

PubMed

Meirik, O

1988-01-01

Authorities in developing countries need to monitor the possible adverse consequences of the increasing use of drugs in their countries. Definite differences exist in the risk-benefit ratios for developed and developing countries, particularly with fertility-regulating drugs. Some physicians believe that the increased risk of thrombosis associated with oral contraceptives (OCs) should not be considered as important in developing countries due to the fact that the background level of venous thrombosis is so low in developing countries that even a 50- or 100-fold increase in relative risk would neither be detectable nor important compared to the risk of unwanted pregnancy. In addition, evidence exists of geographically linked factors in the etiology of some adverse drug reactions (ADRs). Authorities in Brazil, India, Indonesia, Pakistan, the Philippines, Thailand, and Venezuela have established voluntary ADR reporting systems. Several developing countries also actively follow the World Health Organization's International Drug Monitoring Program and have access to its data base. A number of other methodological approaches to postmarketing surveillance are in use in addition to voluntary ADR reporting systems. These include cross-sectional surveys, studies of temporal and geographic correlations of diseases and drug use, and case-control and cohort studies. Each of these approaches offers specific advantages. Postmarketing surveillance should begin at the time new drugs, including contraceptive methods are introduced. Surveillance needs to be an integral part of plans for the introduction of new contraceptive methods in settings where the infrastructure to carry out such surveillance is in place. 3 major public sector agencies, Family Health International, the Population Council, and the World Health Organization, developed a plan to obtain funding for the postmarketing surveillance of a contraceptive implant, Norplant-R. A controlled cohort study will be conducted in 6-10 developing countries. The pilot phase of the surveillance began in 1987. The project objective is to detect possible adverse effects of Norplant-R as well as any health benefits of the method. It also will assess the feasibility of the cohort methodology for postmarketing surveillance in developing countries.

A large-scale initiative to disseminate an evidence-based drug abuse prevention program in Italy: Lessons learned for practitioners and researchers.

PubMed

Velasco, Veronica; Griffin, Kenneth W; Antichi, Mariella; Celata, Corrado

2015-10-01

Across developed countries, experimentation with alcohol, tobacco, and other drugs often begins in the early adolescent years. Several evidence-based programs have been developed to prevent adolescent substance use. Many of the most rigorously tested and empirically supported prevention programs were initially developed and tested in the United States. Increasingly, these interventions are being adopted for use in Europe and throughout the world. This paper reports on a large-scale comprehensive initiative designed to select, adapt, implement, and sustain an evidence-based drug abuse prevention program in Italy. As part of a large-scale regionally funded collaboration in the Lombardy region of Italy, we report on processes through which a team of stakeholders selected, translated and culturally adapted, planned, implemented and evaluated the Life Skills Training (LST) school-based drug abuse prevention program, an evidence-based intervention developed in the United States. We discuss several challenges and lessons learned and implications for prevention practitioners and researchers attempting to undertake similar international dissemination projects. We review several published conceptual models designed to promote the replication and widespread dissemination of effective programs, and discuss their strengths and limitations in the context of planning and implementing a complex, large-scale real-world dissemination effort. Copyright © 2015 Elsevier Ltd. All rights reserved.

Accurate Binding Free Energy Predictions in Fragment Optimization.

PubMed

Steinbrecher, Thomas B; Dahlgren, Markus; Cappel, Daniel; Lin, Teng; Wang, Lingle; Krilov, Goran; Abel, Robert; Friesner, Richard; Sherman, Woody

2015-11-23

Predicting protein-ligand binding free energies is a central aim of computational structure-based drug design (SBDD)--improved accuracy in binding free energy predictions could significantly reduce costs and accelerate project timelines in lead discovery and optimization. The recent development and validation of advanced free energy calculation methods represents a major step toward this goal. Accurately predicting the relative binding free energy changes of modifications to ligands is especially valuable in the field of fragment-based drug design, since fragment screens tend to deliver initial hits of low binding affinity that require multiple rounds of synthesis to gain the requisite potency for a project. In this study, we show that a free energy perturbation protocol, FEP+, which was previously validated on drug-like lead compounds, is suitable for the calculation of relative binding strengths of fragment-sized compounds as well. We study several pharmaceutically relevant targets with a total of more than 90 fragments and find that the FEP+ methodology, which uses explicit solvent molecular dynamics and physics-based scoring with no parameters adjusted, can accurately predict relative fragment binding affinities. The calculations afford R(2)-values on average greater than 0.5 compared to experimental data and RMS errors of ca. 1.1 kcal/mol overall, demonstrating significant improvements over the docking and MM-GBSA methods tested in this work and indicating that FEP+ has the requisite predictive power to impact fragment-based affinity optimization projects.

Tools, techniques, organisation and culture of the CADD group at Sygnature Discovery.

PubMed

St-Gallay, Steve A; Sambrook-Smith, Colin P

2017-03-01

Computer-aided drug design encompasses a wide variety of tools and techniques, and can be implemented with a range of organisational structures and focus in different organisations. Here we outline the computational chemistry skills within Sygnature Discovery, along with the software and hardware at our disposal, and briefly discuss the methods that are not employed and why. The goal of the group is to provide support for design and analysis in order to improve the quality of compounds synthesised and reduce the timelines of drug discovery projects, and we reveal how this is achieved at Sygnature. Impact on medicinal chemistry is vital to demonstrating the value of computational chemistry, and we discuss the approaches taken to influence the list of compounds for synthesis, and how we recognise success. Finally we touch on some of the areas being developed within the team in order to provide further value to the projects and clients.

Tools, techniques, organisation and culture of the CADD group at Sygnature Discovery

NASA Astrophysics Data System (ADS)

St-Gallay, Steve A.; Sambrook-Smith, Colin P.

2017-03-01

Computer-aided drug design encompasses a wide variety of tools and techniques, and can be implemented with a range of organisational structures and focus in different organisations. Here we outline the computational chemistry skills within Sygnature Discovery, along with the software and hardware at our disposal, and briefly discuss the methods that are not employed and why. The goal of the group is to provide support for design and analysis in order to improve the quality of compounds synthesised and reduce the timelines of drug discovery projects, and we reveal how this is achieved at Sygnature. Impact on medicinal chemistry is vital to demonstrating the value of computational chemistry, and we discuss the approaches taken to influence the list of compounds for synthesis, and how we recognise success. Finally we touch on some of the areas being developed within the team in order to provide further value to the projects and clients.

Making drugs accessible.

PubMed

1999-01-01

Making drugs accessible for common HIV-associated illnesses in West Africa is discussed. HIV-positive people in Ouagadougou, Burkina Faso, could not afford drugs for treating their illnesses; thus, volunteers from La Bergerie-FUC, a Christian organization, have established a day care center for HIV-positive people. A French church supplies the drugs; oral rehydration salts are provided through the Ministry of Health. Since the organization did not have enough drugs to meet the needs of all its patients, two strategies were developed to improve its drug supply. The first strategy was to raise money to buy drugs through the support of a local NGO, the Initiative Privee et Communautaire de lutte contre le SIDA (IPC). IPC initially refused to support them, but, eventually agreed to fund drug purchasing as a pilot project. The second strategy was to look at ways of reducing the cost of drugs, which resulted in a list of essential drugs for HIV-associated infections. The list was approved by Care and Support Committee of the national AIDS program for use by other organizations. The organizations have created a national network to improve the delivery of community-based care and support services in Burkina Faso. Recently, the national AIDS program has asked this network to help them change the national essential drugs list to include essential drugs for treating common HIV-associated infections.

The QDREC web server: determining dose-response characteristics of complex macroparasites in phenotypic drug screens.

PubMed

Asarnow, Daniel; Rojo-Arreola, Liliana; Suzuki, Brian M; Caffrey, Conor R; Singh, Rahul

2015-05-01

Neglected tropical diseases (NTDs) caused by helminths constitute some of the most common infections of the world's poorest people. The etiological agents are complex and recalcitrant to standard techniques of molecular biology. Drug screening against helminths has often been phenotypic and typically involves manual description of drug effect and efficacy. A key challenge is to develop automated, quantitative approaches to drug screening against helminth diseases. The quantal dose-response calculator (QDREC) constitutes a significant step in this direction. It can be used to automatically determine quantitative dose-response characteristics and half-maximal effective concentration (EC50) values using image-based readouts from phenotypic screens, thereby allowing rigorous comparisons of the efficacies of drug compounds. QDREC has been developed and validated in the context of drug screening for schistosomiasis, one of the most important NTDs. However, it is equally applicable to general phenotypic screening involving helminths and other complex parasites. QDREC is publically available at: http://haddock4.sfsu.edu/qdrec2/. Source code and datasets are at: http://tintin.sfsu.edu/projects/phenotypicAssays.html. rahul@sfsu.edu. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Drug testing in Europe: monitoring results of the Trans European Drug Information (TEDI) project.

PubMed

Brunt, Tibor M; Nagy, Constanze; Bücheli, Alexander; Martins, Daniel; Ugarte, Miren; Beduwe, Cécile; Ventura Vilamala, Mireia

2017-02-01

Drug testing is a harm reduction strategy that has been adopted by certain countries in Europe. Drug users are able to hand in their drugs voluntarily for chemical analysis of composition and dose. Drug users will be alerted about dangerous test results by the drug testing systems directly and through warning campaigns. An international collaborative effort was launched to combine data of drug testing systems, called the Trans European Drug Information (TEDI) project. Drug testing systems of Spain, Switzerland, Belgium, Austria, Portugal, and the Netherlands participated in this project. This study presents results of some of the main illicit drugs encountered: cocaine, ecstasy and amphetamine and also comments on new psychoactive substances (NPS) detected between 2008 and 2013. A total of 45 859 different drug samples were analyzed by TEDI. The drug markets of the distinct European areas showed similarities, but also some interesting differences. For instance, purity of cocaine and amphetamine powders was generally low in Austria, whilst high in Spain and the Netherlands. And the market for ecstasy showed a contrast: whereas in the Netherlands and Switzerland there was predominantly a market for ecstasy tablets, in Portugal and Spain MDMA (3,4-methylenedioxymethamphetamine) crystals were much more prevalent. Also, some NPS appearing in ecstasy seemed more specific for one country than another. In general, prevalence of NPS clearly increased between 2008 and 2013. Drug testing can be used to generate a global picture of drug markets and provides information about the pharmacological contents of drugs for the population at risk. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The EURITRACK project: development of a tagged neutron inspection system for cargo containers

NASA Astrophysics Data System (ADS)

Perot, Bertrand; Perret, Gregory; Mariani, Alain; Ma, Jean-Luc; Szabo, Jean-Louis; Mercier, Emmanuel; Sannie, Guillaume; Viesti, Giuseppe; Nebbia, Giancarlo; Pesente, Silvia; Lunardon, Marcello; Formisano, Paola; Moretto, Sandra; Fabris, Daniela; Zenoni, Aldo; Bonomi, Germano; Donzella, Antonietta; Fontana, Andrea; Boghen, Gaia; Valkovic, Vladivoj; Sudac, Darovin; Moszynski, Marek; Batsch, Tadeusz; Gierlik, Michal; Wolski, Dariusz; Klamra, Wlodzimierz; Isaksson, Patrick; Le Tourneur, Philippe; Lhuissier, Miguel; Colonna, Annamaria; Tintori, Carlo; Peerani, Paolo; Sequeira, Vitor; Salvato, Martino

2006-05-01

The EURopean Illicit TRAfficing Countermeasures Kit project is part of the 6th European Union Framework Program, and aims at developing a neutron inspection system for detecting threat materials (explosives, drugs, etc.) in cargo containers. Neutron interaction in the container produces specific gamma-rays used to determine the chemical composition of the inspected material. An associated particle sealed tube neutron generator is developed to allow precise location of the interaction point by direction and time-of-flight measurements of the neutrons tagged by alpha-particles. The EURITRACK project consists in developing: a transportable deuterium-tritium neutron generator including a position sensitive alpha detector (8×8 matrix of YAP:Ce crystals coupled to a multi-anode photomultiplier), fast neutron and gamma-ray detectors, front-end electronics to perform coincidence and spectroscopic measurements, and an integrated software which manages neutron generator and detectors positioning, data acquisition and analysis. Hardware components have been developed and tested by the consortium partners. Current status of this work and provisional performances of the system assessed by Monte Carlo calculations are presented.

[Drug, food, alcohol abuse and smoking in young workers. Methodology of a survey aimed at developing preventive interventions targeted to different type of workers: the Valentino Study].

PubMed

Manzoli, L; Mensorio, M; Di Virgilio, M; Rosetti, A; Angeli, G; Panell, M; Cicchetti, A; Di Stanislao, F; Siliquini, Roberta

2007-01-01

Current epidemiological data suggest that the number of preventive interventions aimed at controlling alcohol, drug, food abuse and smoking achieved only partial success, especially in young individuals. In order to improve preventive action efficacy, the literature suggests the adoption of contents and communication instruments specifically targeted to different groups of individuals. The Valentino Project is a comprehensive survey on the characteristics of abuse of a representative sample of 3000 young workers (aged 18-35 years)from the Abruzzo Region of Italy. This paper describes its main methodological issues and the complete version of the questionnaire HW-80 (Healthy-Worker 80), that will be administered. HW-80 questionnaire includes 80 items on demographic characteristics, self-reported health, job-related stress, work organization, pattern of abuse, physical activity and others, and several of these items have been taken or derived from repeatedly validated questionnaires (SF-12, CAGE, Job-Strain, Effort-Reward, EU-DAP, etc.). The aims of the Valentino Project are to quantify the prevalence of obesity, alcohol use, smoking and drug addiction in diverse typologies of workers, and to describe their pattern of use. The ultimate purpose is to provide the necessary knowledge for the development of preventive strategies targeted to different professions, in order to maximize their efficacy.

Models of antimicrobial pressure on intestinal bacteria of the treated host populations.

PubMed

Volkova, V V; Cazer, C L; Gröhn, Y T

2017-07-01

Antimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria.

Translational Partnership Development Lead | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION The Frederick National Laboratory for Cancer Research (FNLCR) is a Federally Funded Research and Development Center operated by Leidos Biomedical Research, Inc on behalf of the National Cancer Institute (NCI). The staff of FNLCR support the NCI’s mission in the fight against cancer and HIV/AIDS. Currently we are seeking a Translational Partnership Development Lead (TPDL) who will work closely with the Office of Translational Resources (OTR) within the Office of the Director (OD) of NCI’s Center for Cancer Research (CCR) to facilitate the successful translation of CCR’s basic and preclinical research advances into new therapeutics and diagnostics. The TPDL with be strategically aligned within FNLCR’s Partnership Development Office (PDO), to maximally leverage the critical mass of expertise available within the PDO. CCR comprises the basic and clinical components of the NCI’s Intramural Research Program (IRP) and consists of ~230 basic and clinical Investigators located at either the NIH main campus in Bethesda or the NCI-Frederick campus. CCR Investigators are focused primarily on cancer and HIV/AIDS, with special emphasis on the most challenging and important high-risk/high-reward problems driving the fields. (See https://ccr.cancer.gov for a full delineation of CCR Investigators and their research activities.) The process of developing research findings into new clinical applications is high risk, complex, variable, and requires multiple areas of expertise seldom available within the confines of a single Investigator’s laboratory. To accelerate this process, OTR serves as a unifying force within CCR for all aspects of translational activities required to achieve success and maintain timely progress. A key aspect of OTR’s function is to develop and strengthen essential communications and collaborations within NIH, with extramural partners and with industry to bring together experts in chemistry, human subjects research, intellectual property, mouse study design, pharmacokinetics (PK), drug screening, industrial project management and other areas needed to facilitate rapid translation. Currently, FNLCR is seeking an expert who can work across organizational boundaries to catalyze these interactions with the primary objective to develop and enable strategies that will facilitate the identification of partners who can collaborate with CCR Investigators. The TPDL will work with the partners and NCI to facilitate the swift and effective translation of pre-clinical discoveries with high potential toward clinical application. A critical part of the TPDL function will be to strengthen interactions among groups with strong translational interests located at NCI-Frederick, including the Molecular Targets Laboratory (MTL), and the NIH main campus, including the National Center for Advancing Translational Science (NCATS). KEY ROLES/RESPONSIBILITIES Advise Principal Investigators and senior leadership on project-based and organizational/translational strategies for discoveries. Enable partnerships and strengthen communications/collaborations within and outside of NIH with biotech industry and groups with strong translational interests/expertise. This includes continuing and strengthening the close collaboration with the Molecular Targets Laboratory (MTL) in Frederick as well as increasing interactions with groups that can facilitate drug development and translational work such as those at NCATS, the NCI’s Division of Cancer Treatment and Diagnosis (DCTD) and with current and potential industry partners. Facilitate outreach to biotech/pharma to develop partnerships furthering translational research projects that may lead to licensing or other agreements. Create outreach opportunities aimed at engaging PIs with potential drug development projects and provide guidance through the translational pipeline. Identify strategic improvements in CCR's technology and drug development process and infrastructure.

Development of a chemotherapy regimen interaction database for the mobile internet: detecting interactions with psychotropics through OncoRx-MI.

PubMed

Yap, Kevin Yi-Lwern; Chui, Wai Keung; Chan, Alexandre

2011-09-01

Cancer patients are at high risks of drug-drug interactions (DDIs). Clinicians need to know the magnitude of DDIs so as to better manage their patients' drug therapies. We have previously created a novel interaction database for oncology prescriptions (OncoRx). In this project, we leverage on 3G networks to further develop this database into an iPhone-specific application for the mobile internet (OncoRx-MI). Data on anticancer drugs (ACDs), chemotherapy regimens (CRegs) and DDIs with psychotropics were compiled from various hardcopy and online resources, and published articles from PubMed, Scopus and Science Direct. The database and iPhone web documents were designed using Adobe Dreamweaver CS4 and associated with a combination of open-source programming scripts. OncoRx-MI currently detects over 5000 DDIs (69.3% pharmacokinetic, 30.7% pharmacodynamic) between 256 single-agent and combination CRegs with 51 psychotropic drugs. OncoRx-MI fits the iPhone screen configuration, and displays information regarding the regimen, pharmacokinetics of the drugs and detected DDIs in tabular format for improved usability. OncoRx-MI is the first mobile DDI application of its kind which detects interactions for combination CRegs. Future versions will include DDIs with other drug categories. Usability studies on its impact in clinical practice will also be carried out.

Balancing novelty with confined chemical space in modern drug discovery.

PubMed

Medina-Franco, José L; Martinez-Mayorga, Karina; Meurice, Nathalie

2014-02-01

The concept of chemical space has broad applications in drug discovery. In response to the needs of drug discovery campaigns, different approaches are followed to efficiently populate, mine and select relevant chemical spaces that overlap with biologically relevant chemical spaces. This paper reviews major trends in current drug discovery and their impact on the mining and population of chemical space. We also survey different approaches to develop screening libraries with confined chemical spaces balancing physicochemical properties. In this context, the confinement is guided by criteria that can be divided in two broad categories: i) library design focused on a relevant therapeutic target or disease and ii) library design focused on the chemistry or a desired molecular function. The design and development of chemical libraries should be associated with the specific purpose of the library and the project goals. The high complexity of drug discovery and the inherent imperfection of individual experimental and computational technologies prompt the integration of complementary library design and screening approaches to expedite the identification of new and better drugs. Library design approaches including diversity-oriented synthesis, biological-oriented synthesis or combinatorial library design, to name a few, and the design of focused libraries driven by target/disease, chemical structure or molecular function are more efficient if they are guided by multi-parameter optimization. In this context, consideration of pharmaceutically relevant properties is essential for balancing novelty with chemical space in drug discovery.

Biopharmaceuticals: From peptide to drug

NASA Astrophysics Data System (ADS)

Hannappel, Margarete

2017-08-01

Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells. They are highly specific molecules and play a crucial role as therapeutics for the treatment of severe and chronic diseases (e.g. cancer, rheumatoid arthritis, diabetes, autoimmune disorders). The development of new biologics and biologics-based drugs gains more and more importance in the fight against various diseases. A short overview on biotherapeutical drug development is given. Cone snails are a large group of poisonous, predatory sea snails with more than 700 species. They use a very powerful venom which rapidly inactivates and paralyzes their prey. Most bioactive venom components are small peptides (conotoxins, conopeptides) which are precisely directed towards a specific target (e.g. ion channel, receptors). Due to their small size, their precision and speed of action, naturally occurring cone snail venom peptides represent an attractive source for the identification and design of novel biological drug entities. The Jagna cone snail project is an encouraging initiative to map the ecological variety of cone snails around the island of Bohol (Philippines) and to conserve the biological information for potential future application.

Recent development in software and automation tools for high-throughput discovery bioanalysis.

PubMed

Shou, Wilson Z; Zhang, Jun

2012-05-01

Bioanalysis with LC-MS/MS has been established as the method of choice for quantitative determination of drug candidates in biological matrices in drug discovery and development. The LC-MS/MS bioanalytical support for drug discovery, especially for early discovery, often requires high-throughput (HT) analysis of large numbers of samples (hundreds to thousands per day) generated from many structurally diverse compounds (tens to hundreds per day) with a very quick turnaround time, in order to provide important activity and liability data to move discovery projects forward. Another important consideration for discovery bioanalysis is its fit-for-purpose quality requirement depending on the particular experiments being conducted at this stage, and it is usually not as stringent as those required in bioanalysis supporting drug development. These aforementioned attributes of HT discovery bioanalysis made it an ideal candidate for using software and automation tools to eliminate manual steps, remove bottlenecks, improve efficiency and reduce turnaround time while maintaining adequate quality. In this article we will review various recent developments that facilitate automation of individual bioanalytical procedures, such as sample preparation, MS/MS method development, sample analysis and data review, as well as fully integrated software tools that manage the entire bioanalytical workflow in HT discovery bioanalysis. In addition, software tools supporting the emerging high-resolution accurate MS bioanalytical approach are also discussed.

Biosensor technology for the detection of illegal drugs II: antibody development and detection techniques

NASA Astrophysics Data System (ADS)

Hilpert, Reinhold; Bauer, Christian; Binder, Florian; Grol, Michael; Hallermayer, Klaus; Josel, Hans-Peter; Klein, Christian; Maier, Josef; Makower, Alexander; Oberpriller, Helmut; Ritter, Josef

1994-10-01

In a joint project of Deutsche Aerospace, Boehringer Mannheim and the University of Potsdam portable devices for the detection of illegal drugs, based on biosensor technology, are being developed. The concept enrichment of the drug from the gas phase and detection by immunological means. This publication covers the development of specific antibodies and various detection procedures. Antibodies with a high affinity for cocaine have been developed with the aid of specially synthesized immunogens. A competitive detection procedure with biosensors based on optical grating couplers and applying particulate labels has been established, showing a lower detection limit of 10-10 mol/l for cocaine. Additionally, a combination of a displacement-immunoreactor and an enzymatically amplified electrode was investigated, which at present still suffers from insufficient sensitivity of the immunoreactor. An alternative, fleece-matrix based test procedure, where enrichment and detection steps are integrated in a single unit, is promising in terms of simplicity and sensitivity. A simple swab-test for the detection of cocaine at surfaces has been developed, which has a lower detection limit of about 10 ng and which can be performed within one minute.

Open-source chemogenomic data-driven algorithms for predicting drug-target interactions.

PubMed

Hao, Ming; Bryant, Stephen H; Wang, Yanli

2018-02-06

While novel technologies such as high-throughput screening have advanced together with significant investment by pharmaceutical companies during the past decades, the success rate for drug development has not yet been improved prompting researchers looking for new strategies of drug discovery. Drug repositioning is a potential approach to solve this dilemma. However, experimental identification and validation of potential drug targets encoded by the human genome is both costly and time-consuming. Therefore, effective computational approaches have been proposed to facilitate drug repositioning, which have proved to be successful in drug discovery. Doubtlessly, the availability of open-accessible data from basic chemical biology research and the success of human genome sequencing are crucial to develop effective in silico drug repositioning methods allowing the identification of potential targets for existing drugs. In this work, we review several chemogenomic data-driven computational algorithms with source codes publicly accessible for predicting drug-target interactions (DTIs). We organize these algorithms by model properties and model evolutionary relationships. We re-implemented five representative algorithms in R programming language, and compared these algorithms by means of mean percentile ranking, a new recall-based evaluation metric in the DTI prediction research field. We anticipate that this review will be objective and helpful to researchers who would like to further improve existing algorithms or need to choose appropriate algorithms to infer potential DTIs in the projects. The source codes for DTI predictions are available at: https://github.com/minghao2016/chemogenomicAlg4DTIpred. Published by Oxford University Press 2018. This work is written by US Government employees and is in the public domain in the US.

Capacity building in anthelmintic drug discovery.

PubMed

Kron, Michael; Yousif, Fouad; Ramirez, Bernadette

2007-10-01

International collaboration in anthelmintic drug discovery holds special challenges compared with local or national discovery projects, and at the same time presents the opportunity to build capacity, forge long lasting inter-institutional relationships and strengthen infrastructure in multinational priority areas. This chapter discusses important issues that should be considered in the context of anthelmintic screening centre development and will give examples (Philippines and Egypt) of the productivity of developing country based screening centres. The positive outcomes of infrastructure building is realised in greater capacities for anthelmintic screening at institutions in the countries where the parasitic diseases are endemic and allows for optimum use of specialised resources for public health priority diseases that may be different from those in Western countries. Support for developing country based screening centres also can help countries optimise product development procedures and policies and can facilitate diffusion of desirable technology in corresponding global regions around the world.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the pathways program.

PubMed

Sakuma, Kari-Lyn K; Riggs, Nathaniel R; Pentz, Mary Ann

2012-04-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the Pathways program

PubMed Central

Sakuma, Kari-Lyn K.; Riggs, Nathaniel R.; Pentz, Mary Ann

2012-01-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided. PMID:21987475

Roadside drug testing: An evaluation of the Alere DDS® 2 mobile test system.

PubMed

Rohrig, Timothy P; Moore, Christine M; Stephens, Kimberly; Cooper, Kelsey; Coulter, Cynthia; Baird, Tyson; Garnier, Margaux; Miller, Samuel; Tuyay, James; Osawa, Kei; Chou, Joshua; Nuss, Carson; Collier, Jeff; Wittman, Karen Cudlin

2018-04-01

The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action. Copyright © 2017 John Wiley & Sons, Ltd.

The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery.

PubMed

Thomas, Craig E; Will, Yvonne

2012-02-01

Attrition in the drug industry due to safety findings remains high and requires a shift in the current safety testing paradigm. Many companies are now positioning safety assessment at each stage of the drug development process, including discovery, where an early perspective on potential safety issues is sought, often at chemical scaffold level, using a variety of emerging technologies. Given the lengthy development time frames of drugs in the pharmaceutical industry, the authors believe that the impact of new technologies on attrition is best measured as a function of the quality and timeliness of candidate compounds entering development. The authors provide an overview of in silico and in vitro models, as well as more complex approaches such as 'omics,' and where they are best positioned within the drug discovery process. It is important to take away that not all technologies should be applied to all projects. Technologies vary widely in their validation state, throughput and cost. A thoughtful combination of validated and emerging technologies is crucial in identifying the most promising candidates to move to proof-of-concept testing in humans. In spite of the challenges inherent in applying new technologies to drug discovery, the successes and recognition that we cannot continue to rely on safety assessment practices used for decades have led to rather dramatic strategy shifts and fostered partnerships across government agencies and industry. We are optimistic that these efforts will ultimately benefit patients by delivering effective and safe medications in a timely fashion.

Guidelines for research on drugged driving

PubMed Central

Walsh, J. Michael; Verstraete, Alain G.; Huestis, Marilyn A.; Mørland, Jørg

2009-01-01

Aim A major problem in assessing the true public health impact of drug-use on driving and overall traffic safety is that the variables being measured across studies vary significantly. In studies reported in a growing global literature, basic parameters assessed, analytical techniques and drugs tested are simply not comparable due to lack of standardization in the field. These shortcomings severely limit the value of this research to add knowledge to the field. A set of standards to harmonize research findings is sorely needed. This project was initiated by several international organizations to develop guidelines for research on drugged driving. Methods A September 2006 meeting of international experts discussed the harmonization of protocols for future research on drugged driving. The principal objective of the meeting was to develop a consensus report setting guidelines, standards, core data variables and other controls that would form the basis for future international research. A modified Delphi method was utilized to develop draft guidelines. Subsequently, these draft guidelines were posted on the internet for global review, and comments received were integrated into the final document. Results The Guidelines Document is divided into three major sections, each focusing upon different aspects of drugged driving research (e.g. roadside surveys, prevalence studies, hospital studies, fatality and crash investigations, etc.) within the critical issue areas of ‘behavior’, ‘epidemiology’ and ‘toxicology’. The behavioral section contains 32 specific recommendations; (2) epidemiology 40 recommendations; and (3) toxicology 64 recommendations. Conclusions It is anticipated that these guidelines will improve significantly the overall quality of drugged driving research and facilitate future cross-study comparisons nationally and globally. PMID:18855814

Exploring Post-Treatment Reversion of Antimicrobial Resistance in Enteric Bacteria of Food Animals as a Resistance Mitigation Strategy.

PubMed

Volkova, Victoriya V; KuKanich, Butch; Riviere, Jim E

2016-11-01

Antimicrobial drug use in food animals is associated with an elevation in relative abundance of bacteria resistant to the drug among the animal enteric bacteria. Some of these bacteria are potential foodborne pathogens. Evidence suggests that at least in the enteric nontype-specific Escherichia coli, after treatment the resistance abundance reverts to the background pre-treatment levels, without further interventions. We hypothesize that it is possible to define the distribution of the time period after treatment within which resistance to the administered drug, and possibly other drugs in case of coselection, in fecal bacteria of the treated animals returns to the background pre-treatment levels. Furthermore, it is possible that a novel resistance mitigation strategy for microbiological food safety could be developed based on this resistance reversion phenomenon. The strategy would be conceptually similar to existing antimicrobial drug withdrawal periods, which is a well-established and accepted mitigation strategy for avoiding violative drug residues in the edible products from the treated animals. For developing resistance-relevant withdrawals, a mathematical framework can be used to join the necessary pharmacological, microbiological, and animal production components to project the distributions of the post-treatment resistance reversion periods in the production animal populations for major antimicrobial drug classes in use. The framework can also help guide design of empirical studies into the resistance-relevant withdrawal periods and development of mitigation approaches to reduce the treatment-associated elevation of resistance in animal enteric bacteria. We outline this framework, schematically and through exemplar equations, and how its components could be formulated.

Composite multi-parameter ranking of real and virtual compounds for design of MC4R agonists: renaissance of the Free-Wilson methodology.

PubMed

Nilsson, Ingemar; Polla, Magnus O

2012-10-01

Drug design is a multi-parameter task present in the analysis of experimental data for synthesized compounds and in the prediction of new compounds with desired properties. This article describes the implementation of a binned scoring and composite ranking scheme for 11 experimental parameters that were identified as key drivers in the MC4R project. The composite ranking scheme was implemented in an AstraZeneca tool for analysis of project data, thereby providing an immediate re-ranking as new experimental data was added. The automated ranking also highlighted compounds overlooked by the project team. The successful implementation of a composite ranking on experimental data led to the development of an equivalent virtual score, which was based on Free-Wilson models of the parameters from the experimental ranking. The individual Free-Wilson models showed good to high predictive power with a correlation coefficient between 0.45 and 0.97 based on the external test set. The virtual ranking adds value to the selection of compounds for synthesis but error propagation must be controlled. The experimental ranking approach adds significant value, is parameter independent and can be tuned and applied to any drug discovery project.

Folate receptor-specific, redox-responsive mesoporous silica nanoparticles for the simultaneous delivery of cisplatin and gemcitabine to treat cancer

NASA Astrophysics Data System (ADS)

Fink, Eric Douglas

Nanoparticles are an innovative platform for cancer treatment that reduces systemic toxicity and allows for active targeting of tumor sites to enhance the therapeutic efficacy. Mesoporous silica nanoparticles (MSNs) have emerged as an attractive drug delivery system due to their high surface area, vast functionalization potential, and biocompatibility. The main goal of this project is to develop a target-specific stimuli-responsive MSN based drug delivery system for the simultaneous delivery of cisplatin and gemcitabine. Both drugs were chemically attached to the MSNs via stimuli-responsive linkers that respond to the high reducing environment and low pH characteristic of cancer cells. The MSN materials fabricated in this work were successfully synthesized and characterized with a wide variety of spectroscopic and microscopic techniques. The loading of cisplatin and gemcitabine and their release profile under high reducing conditions were determined using atomic absorption (AA) and UV-vis spectroscopy, respectively. In vitro toxicity studies were performed on human cervical cancer (HeLa) cells in the presence of different ratios of cisplatin/gemcitabine drugs to determine the best ratio to kill HeLa cells. Based on this data, MSN materials carrying individual drugs and the corresponding combinatorial nanoparticles were fabricated and their in vitro cytotoxicity evaluated in HeLa and pancreatic cancer cells (AsPC1 and BxPC-3). The next step in this project was to further modify with folic acid to enhance its targeting ability toward cancer cells overexpressing folate receptors.

Partnership, knowledge translation, and substance abuse prevention with a First Nations community.

PubMed

Baydala, Lola; Fletcher, Fay; Worrell, Stephanie; Kajner, Tania; Letendre, Sherry; Letendre, Liz; Rasmussen, Carmen

2014-01-01

Having identified substance abuse as an issue of concern in their community, the Alexis Nakota Sioux Nation invited University of Alberta researchers to partner on the cultural adaptation, delivery, and evaluation of a school-based drug and alcohol abuse prevention program. Researchers conducted a literature review of available drug and alcohol prevention programs for children and youth, identifying the Life Skills Training (LST) program as a viable model for cultural adaptation. Four program objectives were developed: (1) Review and cultural adaptation of the elementary and junior high LST programs, (2) delivery of the adapted programs, (3) measurement of changes in students' knowledge of the negative effects of drug and alcohol use, attitudes toward drugs and alcohol, drug and alcohol refusal and life skills, and changes in self-esteem/self-concept, and (4) documentation of the community's experience of the project. Using the principles of community-based participatory research (CBPR), we employed both qualitative and quantitative methods to evaluate the impact of the project. Qualitative evaluation of the program adaptation and implementation were both positive. Qualitative measures of program impact on students revealed a positive effect, whereas results of the quantitative measures were mixed. Culturally adapted, evidence-based programs can have a positive effect on Aboriginal youth and their communities. Strategies to expand knowledge translation (KT) when working with Aboriginal communities include working to create an "ethical space" that draws on the strengths of both Western and Indigenous worldviews.

Molecular Mechanics

PubMed Central

Vanommeslaeghe, Kenno; Guvench, Olgun; MacKerell, Alexander D.

2014-01-01

Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This section introduces the reader to the fundamentals of MM, with a special emphasis on how the target data used in the parametrization of force fields determine their strengths and weaknesses. Variations and recent developments such as polarizable force fields are discussed. The section ends with a brief overview of common force fields in CSBDD. PMID:23947650

Designing an intuitive web application for drug discovery scientists.

PubMed

Karamanis, Nikiforos; Pignatelli, Miguel; Carvalho-Silva, Denise; Rowland, Francis; Cham, Jennifer A; Dunham, Ian

2018-06-01

We discuss how we designed the Open Targets Platform (www.targetvalidation.org), an intuitive application for bench scientists working in early drug discovery. To meet the needs of our users, we applied lean user experience (UX) design methods: we started engaging with users very early and carried out research, design and evaluation activities within an iterative development process. We also emphasize the collaborative nature of applying lean UX design, which we believe is a foundation for success in this and many other scientific projects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

LABONFOIL: investigations regarding microfluidic skin patches for drug detection using flexible OLEDs

NASA Astrophysics Data System (ADS)

Scholles, M.; Kroker, L.; Vogel, U.; Krüger, J.; Walczak, R.; Ruano-Lopez, J.

2010-02-01

This contribution describes first results concerning the overall and especially optical system design of microfluidic skin patches for drug detection based on fluorescence analysis of sweat samples. This work has been carried out within the European project LABONFOIL which aims to develop low-cost lab-on-chip systems for four different applications, one of them for the detection of cocaine abuse by professional drivers. To date work has focused on the integrated design of the skin patch itself including methods for sweat collection as well as studies concerning the feasibility of OLEDs for optical excitation of the fluorescence signal.

Projections for antiinfective drug shortages and time to actual resolution.

PubMed

McLaughlin, Milena M; Pentoney, Zachary; Skoglund, Erik; Scheetz, Marc H

2014-12-01

The results of a national study of projected versus actual times to resolution of temporary U.S. shortages of antiinfective drugs are presented. Descriptive data on antiinfective drug shortages, including differences between manufacturer-estimated and actual times to shortage resolution, were collected over a one-year period via regular monitoring of the websites of ASHP and the Food and Drug Administration. Inventory data from one large hospital in the Midwest were collected in order to characterize realized shortages (i.e., those for which mitigation was required). During the study period, there were 47 transient shortages of antiinfective medications involving 381 unique products or formulations, of which 40% (n = 19) were emergent shortages. Generic-only and brand-only medications accounted for 53% (n = 25) and 21% (n = 10) of the evaluated shortages, respectively; the median shortage duration was 40 days (interquartile range [IQR], 22-91 days). The reasons for shortages most frequently cited by manufacturers were product or formulation discontinuation (21%), increased demand (12%), and raw material shortfalls (8%). Some shortages were resolved sooner than originally projected, but overall, actual shortage durations exceeded manufacturer-projected durations by a median of 17 days (IQR, 0-52.5 days). Ten realized shortages occurred at the hospital study site, compelling the antimicrobial stewardship team to recommend alternative therapies or restrict the use of drugs in short supply. The actual durations of evaluated antiinfective drug shortages during the study period were longer than the manufacturer-projected durations by a median of 17 days. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

New Business Models to Accelerate Innovation in Pediatric Oncology Therapeutics: A Review.

PubMed

Das, Sonya; Rousseau, Raphaël; Adamson, Peter C; Lo, Andrew W

2018-06-02

Few patient populations are as helpless and in need of advocacy as children with cancer. Pharmaceutical companies have historically faced significant financial disincentives to pursue pediatric oncology therapeutics, including low incidence, high costs of conducting pediatric trials, and a lack of funding for early-stage research. Review of published studies of pediatric oncology research and the cost of drug development, as well as clinical trials of pediatric oncology therapeutics at ClinicalTrials.gov, identified 77 potential drug development projects to be included in a hypothetical portfolio. The returns of this portfolio were simulated so as to compute the financial returns and risk. Simulated business strategies include combining projects at different clinical phases of development, obtaining partial funding from philanthropic grants, and obtaining government guarantees to reduce risk. The purely private-sector portfolio exhibited expected returns ranging from -24.2% to 10.2%, depending on the model variables assumed. This finding suggests significant financial disincentives for pursuing pediatric oncology therapeutics and implies that financial support from the public and philanthropic sectors is essential. Phase diversification increases the likelihood of a successful drug and yielded expected returns of -5.3% to 50.1%. Standard philanthropic grants had a marginal association with expected returns, and government guarantees had a greater association by reducing downside exposure. An assessment of a proposed venture philanthropy fund demonstrated stronger performance than the purely private-sector-funded portfolio or those with traditional amounts of philanthropic support. A combination of financial and business strategies has the potential to maximize expected return while eliminating some downside risk-in certain cases enabling expected returns as high as 50.1%-that can overcome current financial disincentives and accelerate the development of pediatric oncology therapeutics.

Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure.

PubMed

Bender, Andreas; Scheiber, Josef; Glick, Meir; Davies, John W; Azzaoui, Kamal; Hamon, Jacques; Urban, Laszlo; Whitebread, Steven; Jenkins, Jeremy L

2007-06-01

Preclinical Safety Pharmacology (PSP) attempts to anticipate adverse drug reactions (ADRs) during early phases of drug discovery by testing compounds in simple, in vitro binding assays (that is, preclinical profiling). The selection of PSP targets is based largely on circumstantial evidence of their contribution to known clinical ADRs, inferred from findings in clinical trials, animal experiments, and molecular studies going back more than forty years. In this work we explore PSP chemical space and its relevance for the prediction of adverse drug reactions. Firstly, in silico (computational) Bayesian models for 70 PSP-related targets were built, which are able to detect 93% of the ligands binding at IC(50) < or = 10 microM at an overall correct classification rate of about 94%. Secondly, employing the World Drug Index (WDI), a model for adverse drug reactions was built directly based on normalized side-effect annotations in the WDI, which does not require any underlying functional knowledge. This is, to our knowledge, the first attempt to predict adverse drug reactions across hundreds of categories from chemical structure alone. On average 90% of the adverse drug reactions observed with known, clinically used compounds were detected, an overall correct classification rate of 92%. Drugs withdrawn from the market (Rapacuronium, Suprofen) were tested in the model and their predicted ADRs align well with known ADRs. The analysis was repeated for acetylsalicylic acid and Benperidol which are still on the market. Importantly, features of the models are interpretable and back-projectable to chemical structure, raising the possibility of rationally engineering out adverse effects. By combining PSP and ADR models new hypotheses linking targets and adverse effects can be proposed and examples for the opioid mu and the muscarinic M2 receptors, as well as for cyclooxygenase-1 are presented. It is hoped that the generation of predictive models for adverse drug reactions is able to help support early SAR to accelerate drug discovery and decrease late stage attrition in drug discovery projects. In addition, models such as the ones presented here can be used for compound profiling in all development stages.

Promoting Adoption of the 3Rs through Regulatory Qualification.

PubMed

Walker, Elizabeth Gribble; Baker, Amanda F; Sauer, John-Michael

2016-12-01

One mechanism to advance the application of novel safety assessment methodologies in drug development, including in silico or in vitro approaches that reduce the use of animals in toxicology studies, is regulatory qualification. Regulatory qualification, a formal process defined at the the U. S. Food and Drug Administration and the European Medicines Agency, hinges on a central concept of stating an appropriate "context of use" for a novel drug development tool (DDT) that precisely defines how that DDT can be used to support decision making in a regulated drug development setting. When accumulating the data to support a particular "context-of-use," the concept of "fit-for-purpose" often guides assay validation, as well as the type and amount of data or evidence required to evaluate the tool. This paper will review pathways for regulatory acceptance of novel DDTs and discuss examples of safety projects considered for regulatory qualification. Key concepts to be considered when defining the evidence required to formally adopt and potentially replace animal-intensive traditional safety assessment methods using qualified DDTs are proposed. Presently, the use of qualified translational kidney safety biomarkers can refine and reduce the total numbers of animals used in drug development. We propose that the same conceptual regulatory framework will be appropriate to assess readiness of new technologies that may eventually replace whole animal models. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Characterization of 12 GnRH peptide agonists – a kinetic perspective

PubMed Central

Nederpelt, Indira; Georgi, Victoria; Schiele, Felix; Nowak‐Reppel, Katrin; Fernández‐Montalván, Amaury E.; IJzerman, Adriaan P.

2015-01-01

Background and Purpose Drug‐target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin‐releasing hormone (GnRH) receptor for the treatment of hormone‐dependent diseases. Surprisingly, the kinetic receptor‐binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor‐binding kinetics of 12 GnRH peptide agonists, including many marketed drugs. Experimental Approach A novel radioligand‐binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [125I]‐triptorelin. In addition to radioligand‐binding studies, a homogeneous time‐resolved FRET Tag‐lite™ method was developed as an alternative assay for the same purpose. Key Results Two novel competition association assays were successfully developed and applied to determine the kinetic receptor‐binding characteristics of 12 high‐affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin). Conclusions and Implications Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor. PMID:26398856

Grants4Targets - an innovative approach to translate ideas from basic research into novel drugs.

PubMed

Lessl, Monika; Schoepe, Stefanie; Sommer, Anette; Schneider, Martin; Asadullah, Khusru

2011-04-01

Collaborations between industry and academia are steadily gaining importance. To combine expertises Bayer Healthcare has set up a novel open innovation approach called Grants4Targets. Ideas on novel drug targets can easily be submitted to http://www.grants4targets.com. After a review process, grants are provided to perform focused experiments to further validate the proposed targets. In addition to financial support specific know-how on target validation and drug discovery is provided. Experienced scientists are nominated as project partners and, depending on the project, tools or specific models are provided. Around 280 applications have been received and 41 projects granted. According to our experience, this type of bridging fund combined with joint efforts provides a valuable tool to foster drug discovery collaborations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Kamikazes: youth serving youth in a dangerous climate. Algeria.

PubMed

Gataa, R

1995-01-01

The Algerian Family Planning Association (FPA) launched its youth project in July 1993 in Oran. The first project of its kind in the Arab world, members call themselves Kamikazes in recognition of the hostile climate they face. The project's goal was to deal with social, cultural, and health problems. They also designed the project's logo, a cartoon booklet on the dangers of AIDS, and a T-shirt for members to wear. They based their activities in the local government-run information center. Between 15 and 25 years old, from a wide variety of social backgrounds, the young people drew up a list of common problems: drugs, alcohol, smoking, relationships with the opposite sex, abortion, contraception, sex education, AIDS, homosexuality, unemployment, the lack of clubs for young people, delinquency, lack of communication between parents and children, the repression of women, the lack of popular entertainment for young people, and the shortage of books. This project now is to be extended to Algiers and other cities. Over an 8-month period, the committee received instruction in contraception and combatting drug addition, participated in a workshop on empowerment and self esteem, and were trained in role-playing techniques. In their first 18 months of existence, the Kamikazes in Oran have succeeded in involving over 1000 of their peers. They have had particular success in reaching teenagers in secondary schools. One of the most valuable aspects of the project has been the sessions held with gynecologists and psychologists on sexual development, relationships between the sexes, and the avoidance of unwanted pregnancies, abortion, and sexually transmitted diseases. The success of the Oran Kamikaze project bodes well for the extension of the project to other parts of Algeria and indeed to some other countries of the Arab world.

[Hospital pharmacist has a rule for best practice use and French hospital activity tariffs. Example of a pharmaceutical quality control for drugs reimbursed in addition of DRGs].

PubMed

Hedoux, S; Dode, X; Pivot, C; Couray-Targe, S; Aulagner, G

2012-07-01

The best practice contract has given a new objective to the hospital pharmacists for the reimbursement in addition to Diagnosis Related Groups' (DRGs) tariffs. We built our pharmaceutical quality control for the administration traceability follow-up regarding the DRGs and the cost of care, for two reasons: the nominal drugs dispensation in link with the prescription made by pharmacist and the important expenditure of these drugs. Our organization depends on the development level of the informatized drugs circuit and minimizes the risk of financial shortfalls or wrong benefits, possible causes of economic penalties for our hospital. On the basis of this follow-up, we highlighted our activity and identified problems of management and drugs circuit organization. The quality of the administration traceability impacts directly on the quality of the medical records and the reimbursements of the expensive drugs. A better knowledge of prescription software is also required for a better quality and security of the medical data used in the medical informatic systems. The drugs management and the personal treatment in and between the care units need to be improved too. We have to continue and improve our organization with the future financial model for ATU drugs and the FIDES project. The health personnel awareness and the development of best informatic tools are also required. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Application Instructions | Division of Cancer Prevention

Cancer.gov

This is NOT a grant application - if successful, funds will not be transferred to your institution to support your project. Rather, this is an application to access the scientific capabilities and resources of the NCI with the goal of moving promising cancer chemopreventive agents into clinical testing. If successful, you will partner with the NCI in developing a drug

Developing and Implementing a Multispecialty Graduate Medical Education Curriculum on Screening, Brief Intervention, and Referral to Treatment (SBIRT)

ERIC Educational Resources Information Center

Tetrault, Jeanette M.; Green, Michael L.; Martino, Steve; Thung, Stephen F.; Degutis, Linda C.; Ryan, Sheryl A.; Martel, Shara; Pantalon, Michael V.; Bernstein, Steven L.; O'Connor, Patrick G.; Fiellin, David A.; D'Onofrio, Gail

2012-01-01

The authors sought to evaluate the feasibility and acceptability of initiating a Screening, Brief Intervention, and Referral to Treatment (SBIRT) for alcohol and other drug use curriculum across multiple residency programs. SBIRT project faculty in the internal medicine (traditional, primary care internal medicine, medicine/pediatrics),…

Modifying pro-drug risk factors in adolescents: results from project ALERT.

PubMed

Ghosh-Dastidar, Bonnie; Longshore, Douglas L; Ellickson, Phyllis L; McCaffrey, Daniel F

2004-06-01

The objective of this study was to evaluate the impact of a revised state-of-the-art drug prevention program, Project ALERT, on risk factors for drug use in mostly rural midwestern schools and communities. Fifty-five middle schools from South Dakota were randomly assigned to treatment or control conditions. Treatment-group students received 11 lessons in Grade 7 and 3 more in Grade 8. Effects for 4276 eighth graders were assessed 18 months after baseline. Results indicate that Project ALERT had statistically significant effects on all the targeted risk factors associated with cigarette and marijuana use and more modest gains with the pro-alcohol risk factors. The program helped adolescents at low, moderate, and high risk for future use, with the effect sizes typically stronger for the low- and moderate-risk groups. Thus, school-based drug prevention programs can lower risk factors that correlate with drug use, help low- to high-risk adolescents, and be effective in diverse school environments.

42 CFR 423.910 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Special Rules for States-Eligibility Determinations... to defray a portion of the Medicare drug expenditures for individuals whose projected Medicaid drug... capita Medicaid expenditures for prescription drugs for 2003 for full-benefit dual eligibles not...

Opportunities and Challenges for Drug Development: Public-Private Partnerships, Adaptive Designs and Big Data.

PubMed

Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C

2016-01-01

Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development.

Opportunities and Challenges for Drug Development: Public–Private Partnerships, Adaptive Designs and Big Data

PubMed Central

Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C.

2016-01-01

Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public–private partnerships, adaptive designs and big data. Public–private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development. PMID:27999543

A physiome interoperability roadmap for personalized drug development

PubMed Central

2016-01-01

The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have multiple causes at various scales, ranging from gross anatomical differences to differences in genome sequence. Relevant data for many of these aspects, particularly related to molecular assays (known as ‘-omics’), are available in online resources, but identification and assignment to appropriate model variables and parameters is a significant bottleneck in the model development process. Through its efforts to standardize annotation with consequent increase in data usability, the human physiome project has a vital role in improving productivity in model development and, thus, the development of personalized therapy regimes. Here, we review the current status of personalized medicine in clinical practice, outline some of the challenges that must be overcome in order to expand its applicability, and discuss the relevance of personalized medicine to the more widespread challenges being faced in drug discovery and development. We then review some of (i) the key data resources available for use in model development and (ii) the potential areas where advances made within the physiome modelling community could contribute to physiologically based pharmacokinetic and physiologically based pharmacokinetic/pharmacodynamic modelling in support of personalized drug development. We conclude by proposing a roadmap to further guide the physiome community in its on-going efforts to improve data usability, and integration with modelling efforts in the support of personalized medicine development. PMID:27051513

Drugs of Abuse and Addiction: An integrated approach to teaching.

PubMed

Miller, Lindsey N; Mercer, Susan L

2017-05-01

To describe the design, implementation, and student perceptions of a Drugs of Abuse and Addiction elective course utilizing an integrated teaching model. Third-year pharmacy students enrolled in the two credit hour elective. Teaching methodology included didactic lecture, journal club, simulated addiction assignment with reflection, debates, external speakers, site visit to a residential drug court program and research paper with presentation. A course objective survey was administered upon course completion. All students strongly agreed that having science- and clinical-based faculty members develop and deliver course content was beneficial. Additionally, all students agree to strongly agree that their research project helped them integrate and comprehend the science and practice surrounding drugs of abuse and addiction. Students enjoyed an integrated teaching approach and multiple teaching methodologies leading to increased engagement and enhancement of student learning. Course enrollment was beneficial for personalized learning, but limited student perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

A community effort to assess and improve drug sensitivity prediction algorithms

PubMed Central

Costello, James C; Heiser, Laura M; Georgii, Elisabeth; Gönen, Mehmet; Menden, Michael P; Wang, Nicholas J; Bansal, Mukesh; Ammad-ud-din, Muhammad; Hintsanen, Petteri; Khan, Suleiman A; Mpindi, John-Patrick; Kallioniemi, Olli; Honkela, Antti; Aittokallio, Tero; Wennerberg, Krister; Collins, James J; Gallahan, Dan; Singer, Dinah; Saez-Rodriguez, Julio; Kaski, Samuel; Gray, Joe W; Stolovitzky, Gustavo

2015-01-01

Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms. The top-performing approaches modeled nonlinear relationships and incorporated biological pathway information. We found that gene expression microarrays consistently provided the best predictive power of the individual profiling data sets; however, performance was increased by including multiple, independent data sets. We discuss the innovations underlying the top-performing methodology, Bayesian multitask MKL, and we provide detailed descriptions of all methods. This study establishes benchmarks for drug sensitivity prediction and identifies approaches that can be leveraged for the development of new methods. PMID:24880487

A community effort to assess and improve drug sensitivity prediction algorithms.

PubMed

Costello, James C; Heiser, Laura M; Georgii, Elisabeth; Gönen, Mehmet; Menden, Michael P; Wang, Nicholas J; Bansal, Mukesh; Ammad-ud-din, Muhammad; Hintsanen, Petteri; Khan, Suleiman A; Mpindi, John-Patrick; Kallioniemi, Olli; Honkela, Antti; Aittokallio, Tero; Wennerberg, Krister; Collins, James J; Gallahan, Dan; Singer, Dinah; Saez-Rodriguez, Julio; Kaski, Samuel; Gray, Joe W; Stolovitzky, Gustavo

2014-12-01

Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms. The top-performing approaches modeled nonlinear relationships and incorporated biological pathway information. We found that gene expression microarrays consistently provided the best predictive power of the individual profiling data sets; however, performance was increased by including multiple, independent data sets. We discuss the innovations underlying the top-performing methodology, Bayesian multitask MKL, and we provide detailed descriptions of all methods. This study establishes benchmarks for drug sensitivity prediction and identifies approaches that can be leveraged for the development of new methods.

Evolving BioAssay Ontology (BAO): modularization, integration and applications

PubMed Central

2014-01-01

The lack of established standards to describe and annotate biological assays and screening outcomes in the domain of drug and chemical probe discovery is a severe limitation to utilize public and proprietary drug screening data to their maximum potential. We have created the BioAssay Ontology (BAO) project (http://bioassayontology.org) to develop common reference metadata terms and definitions required for describing relevant information of low-and high-throughput drug and probe screening assays and results. The main objectives of BAO are to enable effective integration, aggregation, retrieval, and analyses of drug screening data. Since we first released BAO on the BioPortal in 2010 we have considerably expanded and enhanced BAO and we have applied the ontology in several internal and external collaborative projects, for example the BioAssay Research Database (BARD). We describe the evolution of BAO with a design that enables modeling complex assays including profile and panel assays such as those in the Library of Integrated Network-based Cellular Signatures (LINCS). One of the critical questions in evolving BAO is the following: how can we provide a way to efficiently reuse and share among various research projects specific parts of our ontologies without violating the integrity of the ontology and without creating redundancies. This paper provides a comprehensive answer to this question with a description of a methodology for ontology modularization using a layered architecture. Our modularization approach defines several distinct BAO components and separates internal from external modules and domain-level from structural components. This approach facilitates the generation/extraction of derived ontologies (or perspectives) that can suit particular use cases or software applications. We describe the evolution of BAO related to its formal structures, engineering approaches, and content to enable modeling of complex assays and integration with other ontologies and datasets. PMID:25093074

Evolving BioAssay Ontology (BAO): modularization, integration and applications.

PubMed

Abeyruwan, Saminda; Vempati, Uma D; Küçük-McGinty, Hande; Visser, Ubbo; Koleti, Amar; Mir, Ahsan; Sakurai, Kunie; Chung, Caty; Bittker, Joshua A; Clemons, Paul A; Brudz, Steve; Siripala, Anosha; Morales, Arturo J; Romacker, Martin; Twomey, David; Bureeva, Svetlana; Lemmon, Vance; Schürer, Stephan C

2014-01-01

The lack of established standards to describe and annotate biological assays and screening outcomes in the domain of drug and chemical probe discovery is a severe limitation to utilize public and proprietary drug screening data to their maximum potential. We have created the BioAssay Ontology (BAO) project (http://bioassayontology.org) to develop common reference metadata terms and definitions required for describing relevant information of low-and high-throughput drug and probe screening assays and results. The main objectives of BAO are to enable effective integration, aggregation, retrieval, and analyses of drug screening data. Since we first released BAO on the BioPortal in 2010 we have considerably expanded and enhanced BAO and we have applied the ontology in several internal and external collaborative projects, for example the BioAssay Research Database (BARD). We describe the evolution of BAO with a design that enables modeling complex assays including profile and panel assays such as those in the Library of Integrated Network-based Cellular Signatures (LINCS). One of the critical questions in evolving BAO is the following: how can we provide a way to efficiently reuse and share among various research projects specific parts of our ontologies without violating the integrity of the ontology and without creating redundancies. This paper provides a comprehensive answer to this question with a description of a methodology for ontology modularization using a layered architecture. Our modularization approach defines several distinct BAO components and separates internal from external modules and domain-level from structural components. This approach facilitates the generation/extraction of derived ontologies (or perspectives) that can suit particular use cases or software applications. We describe the evolution of BAO related to its formal structures, engineering approaches, and content to enable modeling of complex assays and integration with other ontologies and datasets.

Promoting innovation and excellence to face the rapid diffusion of novel psychoactive substances in the EU: the outcomes of the ReDNet project.

PubMed

Corazza, Ornella; Assi, Sulaf; Simonato, Pierluigi; Corkery, John; Bersani, Francesco Saverio; Demetrovics, Zsolt; Stair, Jacqueline; Fergus, Suzanne; Pezzolesi, Cinzia; Pasinetti, Manuela; Deluca, Paolo; Drummond, Colin; Davey, Zoe; Blaszko, Ursula; Moskalewicz, Jacek; Mervo, Barbara; Furia, Lucia Di; Farre, Maggi; Flesland, Liv; Pisarska, Agnieszka; Shapiro, Harry; Siemann, Holger; Skutle, Arvid; Sferrazza, Elias; Torrens, Marta; Sambola, F; van der Kreeft, Peer; Scherbaum, Norbert; Schifano, Fabrizio

2013-07-01

The recent emergence of new psychoactive compounds (novel psychoactive substances (NPS)) has raised prominent challenges in the fields of drug policy, substance use research, public health and service provision. The Recreational Drugs European Network project, funded by the European Commission, was implemented to improve the information stream to young people and professionals about effects/risks of NPS by identifying online products and disseminating relevant information through technological tools. Regular multilingual qualitative assessments of websites, drugs fora and other online resources were carried out using the Google search engine in eight languages from collaborating countries. These included the following: the UK, Norway, Belgium, Germany, Hungary, Poland, Italy and Spain. Products were tested and prevention messages were developed and disseminated via technological tools such as interactive websites, SMS alert, social networking (Facebook, Twitter), Multimedia (You Tube), Smartphone applications (iPhone) and virtual learning environments (Second Life). The Recreational Drugs European Network project established itself as the first Europe-wide prevention programme designed for NPS based on the efficacy of novel information and communication technology-based forms of intervention. More than 650 NPS products and combinations were identified; relevant information was disseminated to target population and advice was given to both European Union/international agencies and national policy makers. Web-monitoring activities are essential for mapping the diffusion of NPS and the use of technological tools can be successfully incorporated in specific prevention programmes. Furthermore, the involvement of multi-disciplinary international partnerships was and continues to be fundamental for responding to such a prominent challenge. Copyright © 2013 John Wiley & Sons, Ltd.

Meta-analyses of seven of the National Institute on Drug Abuse's principles of drug addiction treatment.

PubMed

Pearson, Frank S; Prendergast, Michael L; Podus, Deborah; Vazan, Peter; Greenwell, Lisa; Hamilton, Zachary

2012-07-01

Of the 13 principles of drug addiction treatment disseminated by the National Institute on Drug Abuse (NIDA), 7 were meta-analyzed as part of the Evidence-based Principles of Treatment (EPT) project. By averaging outcomes over the diverse programs included in the EPT, we found that 5 of the NIDA principles examined are supported: matching treatment to the client's needs, attending to the multiple needs of clients, behavioral counseling interventions, treatment plan reassessment, and counseling to reduce risk of HIV. Two of the NIDA principles are not supported: remaining in treatment for an adequate period and frequency of testing for drug use. These weak effects could be the result of the principles being stated too generally to apply to the diverse interventions and programs that exist or unmeasured moderator variables being confounded with the moderators that measured the principles. Meta-analysis should be a standard tool for developing principles of effective treatment for substance use disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Intravital Microscopy Imaging Approaches for Image-Guided Drug Delivery Systems

PubMed Central

Kirui, Dickson K.; Ferrari, Mauro

2016-01-01

Rapid technical advances in the field of non-linear microscopy have made intravital microscopy a vital pre-clinical tool for research and development of imaging-guided drug delivery systems. The ability to dynamically monitor the fate of macromolecules in live animals provides invaluable information regarding properties of drug carriers (size, charge, and surface coating), physiological, and pathological processes that exist between point-of-injection and the projected of site of delivery, all of which influence delivery and effectiveness of drug delivery systems. In this Review, we highlight how integrating intravital microscopy imaging with experimental designs (in vitro analyses and mathematical modeling) can provide unique information critical in the design of novel disease-relevant drug delivery platforms with improved diagnostic and therapeutic indexes. The Review will provide the reader an overview of the various applications for which intravital microscopy has been used to monitor the delivery of diagnostic and therapeutic agents and discuss some of their potential clinical applications. PMID:25901526

3D-Lab: a collaborative web-based platform for molecular modeling.

PubMed

Grebner, Christoph; Norrby, Magnus; Enström, Jonatan; Nilsson, Ingemar; Hogner, Anders; Henriksson, Jonas; Westin, Johan; Faramarzi, Farzad; Werner, Philip; Boström, Jonas

2016-09-01

The use of 3D information has shown impact in numerous applications in drug design. However, it is often under-utilized and traditionally limited to specialists. We want to change that, and present an approach making 3D information and molecular modeling accessible and easy-to-use 'for the people'. A user-friendly and collaborative web-based platform (3D-Lab) for 3D modeling, including a blazingly fast virtual screening capability, was developed. 3D-Lab provides an interface to automatic molecular modeling, like conformer generation, ligand alignments, molecular dockings and simple quantum chemistry protocols. 3D-Lab is designed to be modular, and to facilitate sharing of 3D-information to promote interactions between drug designers. Recent enhancements to our open-source virtual reality tool Molecular Rift are described. The integrated drug-design platform allows drug designers to instantaneously access 3D information and readily apply advanced and automated 3D molecular modeling tasks, with the aim to improve decision-making in drug design projects.

Consensus Statement on Research Definitions for Drug-Resistant Tuberculosis in Children.

PubMed

Seddon, James A; Perez-Velez, Carlos M; Schaaf, H Simon; Furin, Jennifer J; Marais, Ben J; Tebruegge, Marc; Detjen, Anne; Hesseling, Anneke C; Shah, Sarita; Adams, Lisa V; Starke, Jeffrey R; Swaminathan, Soumya; Becerra, Mercedes C

2013-06-01

Few children with drug-resistant (DR) tuberculosis (TB) are identified, diagnosed, and given an appropriate treatment. The few studies that have described this vulnerable population have used inconsistent definitions. The World Health Organization (WHO) definitions used for adults with DR-TB and for children with drug-susceptible TB are not always appropriate for children with DR-TB. The Sentinel Project on Pediatric Drug-Resistant Tuberculosis was formed in 2011 as a network of experts and stakeholders in childhood DR-TB. An early priority was to establish standardized definitions for key parameters in order to facilitate study comparisons and the development of an evidence base to guide future clinical management. This consensus statement proposes standardized definitions to be used in research. In particular, it suggests consistent terminology, as well as definitions for measures of exposure, drug resistance testing, previous episodes and treatment, certainty of diagnosis, site and severity of disease, adverse events, and treatment outcome. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society.

The affordability of antiretroviral therapy in developing countries: what policymakers need to know.

PubMed

Forsythe, S S

1998-01-01

The objective of this paper is to assist policymakers in developing countries and international donors by providing an outline of economic information needed to make a decision regarding the purchase of drugs to provide highly active antiretroviral therapy (HAART). The following paper: (i) reviews existing experiences of policymakers in developing countries regarding the purchase of drugs needed for HAART, (ii) identifies issues that would need to be addressed and data that would be required to make more informed decisions regarding this issue, (iii) develops a cost-benefit model that could be utilized in designing an economic research project evaluating the economic costs and benefits of HAART, and (iv) performs a preliminary test of this model with data from Costa Rica. A review of experiences with this issue reveals that there are growing political, legal and budgetary pressures for countries to make tenable decisions regarding the purchase of drugs for HAART. An economic model describing the costs and benefits of HAART is proposed, although much of the required data for using such a model is currently neither available or in the process of being collected. It is imperative that economic data be collected to better inform policymakers in developing countries about their decision regarding the purchase of these drugs. It is recommended that such economic data be collected as organizations such as the United Nations Joint Programme on HIV/ AIDS (UNAIDS) initiate their medical assessments of HAART in developing countries.

GPCR ontology: development and application of a G protein-coupled receptor pharmacology knowledge framework.

PubMed

Przydzial, Magdalena J; Bhhatarai, Barun; Koleti, Amar; Vempati, Uma; Schürer, Stephan C

2013-12-15

Novel tools need to be developed to help scientists analyze large amounts of available screening data with the goal to identify entry points for the development of novel chemical probes and drugs. As the largest class of drug targets, G protein-coupled receptors (GPCRs) remain of particular interest and are pursued by numerous academic and industrial research projects. We report the first GPCR ontology to facilitate integration and aggregation of GPCR-targeting drugs and demonstrate its application to classify and analyze a large subset of the PubChem database. The GPCR ontology, based on previously reported BioAssay Ontology, depicts available pharmacological, biochemical and physiological profiles of GPCRs and their ligands. The novelty of the GPCR ontology lies in the use of diverse experimental datasets linked by a model to formally define these concepts. Using a reasoning system, GPCR ontology offers potential for knowledge-based classification of individuals (such as small molecules) as a function of the data. The GPCR ontology is available at http://www.bioassayontology.org/bao_gpcr and the National Center for Biomedical Ontologies Web site.

The Cedar Project WelTel mHealth intervention for HIV prevention in young Indigenous people who use illicit drugs: study protocol for a randomized controlled trial.

PubMed

Jongbloed, Kate; Friedman, Anton J; Pearce, Margo E; Van Der Kop, Mia L; Thomas, Vicky; Demerais, Lou; Pooyak, Sherri; Schechter, Martin T; Lester, Richard T; Spittal, Patricia M

2016-03-09

Despite successes in preventing and treating HIV, Indigenous people in Canada continue to face disproportionately high rates of HIV infection. Programs that support healing from lifetime trauma, support connection to culture, and reduce drug-related harms are critical to preventing HIV among young Indigenous people who use drugs. The Cedar Project WelTel mHealth intervention proposed here is a structured mobile-phone initiative to connect young Indigenous people who use drugs with Cedar Case Managers in a community-based setting. The intervention consists of a package of supports, including a mobile phone and cellular plan, weekly two-way text messaging, and support from Cedar Case Managers. The Cedar Project WelTel mHealth study is a multi-site Zelen pre-randomized trial to measure the effect of a two-way supportive text-message intervention to reduce HIV vulnerability among young Indigenous people who use illicit drugs in two Canadian cities. The trial is nested within the Cedar Project, an ongoing cohort study addressing HIV and hepatitis C vulnerability among young Indigenous people who use drugs in Vancouver and Prince George, British Columbia. The Cedar Project Partnership, an independent body of Indigenous Elders, leaders, and health/social service experts, governs all aspects of the study. Two hundred participants will be followed over a 16-month period, with HIV propensity score at 6 months as the primary outcome. Secondary outcomes include HIV propensity at 1 year, HIV risk, resilience, psychological distress, access to drug-related services, and connection to culture measured at 6 months and 1 year. Primary analysis is by intention to treat. Culturally safe interventions that address barriers to HIV prevention while supporting the strength of young Indigenous people who use drugs are urgently needed. Despite presenting a tremendous opportunity to connect young, highly transient Indigenous people who use drugs to prevention services, supportive two-way mHealth programs have yet to be tested for HIV prevention in a community-based setting with this population. ClinicalTrials.gov NCT02437123 https://clinicaltrials.gov/show/NCT02437123 (registered 4 May 2015). Protocol version: 24 July 2015.

75 FR 33268 - Technology Innovation Program (TIP) Notice of Availability of Funds; Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

... military/ weaponry applications (e.g. warhead manufacture, chemical/biological warfare materials production.... production of biofuels or small molecule drugs); Projects that primarily focus on drug discovery or design of... design that are not a part of the manufacturing of engineered tissues; and Projects that do not have a...

Project SMART: A Social Approach to Drug Abuse Prevention. Teacher's Guide.

ERIC Educational Resources Information Center

Johnson, C. Anderson; And Others

This document presents the teacher's guide for an experimental research and demonstration project which focuses on the prevention of drug abuse among youth through self-management and resistance training. The major purpose of the curriculum described in this document is to prevent and reduce the incidence of habitual cigarette smoking and of…

"US": Primary Prevention, Para-Counseling, Research Project.

ERIC Educational Resources Information Center

Lynch, Mallory B.

This report provides both a focal (part) and a subsidiary (whole) description of the process and results of a primary prevention, paracounseling, research project, funded for two years by the National Institute on Drug Abuse to create and research a "model" program which could be used nation-wide to help prevent drug abuse. Adolescents,…

77 FR 46764 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0011] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01) AGENCY: Food... orphan products. Orphan products are drugs, biologics, medical devices, and medical foods that are...

Reaction and Aggregation Dynamics of Cell Surface Receptors

NASA Astrophysics Data System (ADS)

Wang, Michelle Dong

This dissertation is composed of both theoretical and experimental studies of cell surface receptor reaction and aggregation. Project I studies the reaction rate enhancement due to surface diffusion of a bulk dissolved ligand with its membrane embedded target, using numerical calculations. The results show that the reaction rate enhancement is determined by ligand surface adsorption and desorption kinetic rates, surface and bulk diffusion coefficients, and geometry. In particular, we demonstrate that the ligand surface adsorption and desorption kinetic rates, rather than their ratio (the equilibrium constant), are important in rate enhancement. The second and third projects are studies of acetylcholine receptor clusters on cultured rat myotubes using fluorescence techniques after labeling the receptors with tetramethylrhodamine -alpha-bungarotoxin. The second project studies when and where the clusters form by making time-lapse movies. The movies are made from overlay of the pseudocolored total internal reflection fluorescence (TIRF) images of the cluster, and the schlieren images of the cell cultures. These movies are the first movies made using TIRF, and they clearly show the cluster formation from the myoblast fusion, the first appearance of clusters, and the eventual disappearance of clusters. The third project studies the fine structural features of individual clusters observed under TIRF. The features were characterized with six parameters by developing a novel fluorescence technique: spatial fluorescence autocorrelation. These parameters were then used to study the feature variations with age, and with treatments of drugs (oligomycin and carbachol). The results show little variation with age. However, drug treatment induced significant changes in some parameters. These changes were different for oligomycin and carbachol, which indicates that the two drugs may eliminate clusters through different mechanisms.

Project ATHENA Creates Surrogate Human Organ Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacQueen, Luke; Knospel, Fanny; Sherrod, Stacy

2015-06-15

The development of miniature surrogate human organs, coupled with highly sensitive mass spectrometry technologies, could one day revolutionize the way new drugs and toxic agents are studied. “By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs,” said Rashi Iyer, a senior scientist at Los Alamos National Laboratory. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is nearing the full integration of four human organ constructs — liver, heart, lung andmore » kidney — each organ component is about the size of a smartphone screen, and the whole ATHENA “body” of interconnected organs will fit neatly on a desk. A new video available on the Los Alamos National Laboratory YouTube channel updates the ATHENA project as it begins to integrate the various organ systems into a single system. Some 40 percent of pharmaceuticals fail their clinical trials and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success. ATHENA is funded by the Defense Threat Reduction Agency (DTRA) and is a collaboration of Los Alamos National Laboratory, Harvard University, Vanderbilt University, Charité Universitätsmedizin, Berlin, Germany, CFD Research Corporation, and the University of California San Francisco.« less

Decision support in addiction: The development of an e-health tool to assess and prevent risk of fatal overdose. The ORION Project.

PubMed

Baldacchino, A; Crocamo, C; Humphris, G; Neufeind, J; Frisher, M; Scherbaum, N; Carrà, G

2016-09-01

The application of e-health technology to the field of substance use disorders is at a relatively early stage, and methodological quality is still variable. Few have explored the extent of utilization of communication technology in exploring risk perception by patients enrolled in substance abuse services. The Overdose RIsk InfOrmatioN (ORION) project is a European Commission funded programme, aimed to develop and pilot an e-health psycho-educational tool to provide information to drug using individuals about the risks of suffering a drug overdose. In this article, we report on phase 1 (risk estimation), phase 2 (design), and phase 3 (feasibility) of the ORION project. The development of ORION e-health tool underlined the importance of an evidence-based intervention aimed in obtaining reliable evaluation of risk. The ORION tool supported a decision making process aimed at influencing the substance users' self-efficacy and the degree to which the substance users' understand risk factors. Therefore, its innovative power consisted in translating risks combination into a clear estimation for the user who will then appear more likely to be interested in his/her risk perception. Exploratory field testing and validation confirmed the next stage of evaluation, namely, collection of routine patient samples in study clinics. The associations between risk perception of overdose, engagement with the ORION tool and willingness to alter overdose risk factors, in a clinical setting across various EU member states will further confirm the ORION tool's generalisability and effectiveness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An Outreach Program in Drug Education; Teaching a Rational Approach to Drug Use

ERIC Educational Resources Information Center

Sorensen, James L.; Joffe, Stephen J.

1975-01-01

Aimed at encouraging rational decision making about drug use, a peer oriented drug education program was conducted in a community youth project. Youth and leaders shared feelings and knowledge about drugs. Compared with four program dropouts, six participants exhibited more positive attitudes toward the drug group, its leaders and themselves.…

Toward preclinical predictive drug testing for metabolism and hepatotoxicity by using in vitro models derived from human embryonic stem cells and human cell lines - a report on the Vitrocellomics EU-project.

PubMed

Mandenius, Carl-Fredrik; Andersson, Tommy B; Alves, Paula M; Batzl-Hartmann, Christine; Björquist, Petter; Carrondo, Manuel J T; Chesne, Christophe; Coecke, Sandra; Edsbagge, Josefina; Fredriksson, J Magnus; Gerlach, Jörg C; Heinzle, Elmar; Ingelman-Sundberg, Magnus; Johansson, Inger; Küppers-Munther, Barbara; Müller-Vieira, Ursula; Noor, Fozia; Zeilinger, Katrin

2011-05-01

Drug-induced liver injury is a common reason for drug attrition in late clinical phases, and even for post-launch withdrawals. As a consequence, there is a broad consensus in the pharmaceutical industry, and within regulatory authorities, that a significant improvement of the current in vitro test methodologies for accurate assessment and prediction of such adverse effects is needed. For this purpose, appropriate in vivo-like hepatic in vitro models are necessary, in addition to novel sources of human hepatocytes. In this report, we describe recent and ongoing research toward the use of human embryonic stem cell (hESC)-derived hepatic cells, in conjunction with new and improved test methods, for evaluating drug metabolism and hepatotoxicity. Recent progress on the directed differentiation of human embryonic stem cells to the functional hepatic phenotype is reported, as well as the development and adaptation of bioreactors and toxicity assay technologies for the testing of hepatic cells. The aim of achieving a testing platform for metabolism and hepatotoxicity assessment, based on hESC-derived hepatic cells, has advanced markedly in the last 2-3 years. However, great challenges still remain, before such new test systems could be routinely used by the industry. In particular, we give an overview of results from the Vitrocellomics project (EU Framework 6) and discuss these in relation to the current state-of-the-art and the remaining difficulties, with suggestions on how to proceed before such in vitro systems can be implemented in industrial discovery and development settings and in regulatory acceptance. 2011 FRAME.

A Framework for Incorporating Patient Preferences Regarding Benefits and Risks into Regulatory Assessment of Medical Technologies.

PubMed

Ho, Martin; Saha, Anindita; McCleary, K Kimberly; Levitan, Bennett; Christopher, Stephanie; Zandlo, Kristen; Braithwaite, R Scott; Hauber, A Brett

In response to 2012 guidance in which the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) stated the importance of patient-centric measures in regulatory benefit-risk assessments, the Medical Device Innovation Consortium (MDIC) initiated a project. The project was used to develop a framework to help the Food and Drug Administration (FDA) and industry sponsors understand how patient preferences regarding benefit and risk might be integrated into the review of innovative medical devices. A public-private partnership of experts from medical device industry, government, academia and non-profits collaborated on development of the MDIC patient centered benefit-risk framework. The MDIC Framework examines what patient preference information is and the potential use and value of patient preference information in the regulatory process and across the product development life cycle. The MDIC Framework also includes a catalog of patient preference assessment methods and an agenda for future research to advance the field. This article discusses key concepts in patient preference assessment of particular importance for regulators and researchers that are addressed in the MDIC Framework for patient centered benefit-risk assessment as well as the unique public-private collaboration that led its development. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity

PubMed Central

Rayan, Anwar; Raiyn, Jamal

2017-01-01

Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab. PMID:29121120

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

PubMed

Rayan, Anwar; Raiyn, Jamal; Falah, Mizied

2017-01-01

Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

How effective is drug abuse resistance education? A meta-analysis of Project DARE outcome evaluations.

PubMed Central

Ennett, S T; Tobler, N S; Ringwalt, C L; Flewelling, R L

1994-01-01

OBJECTIVES. Project DARE (Drug Abuse Resistance Education) is the most widely used school-based drug use prevention program in the United States, but the findings of rigorous evaluations of its effectiveness have not been considered collectively. METHODS. We used meta-analytic techniques to review eight methodologically rigorous DARE evaluations. Weighted effect size means for several short-term outcomes also were compared with means reported for other drug use prevention programs. RESULTS. The DARE effect size for drug use behavior ranged from .00 to .11 across the eight studies; the weighted mean for drug use across studies was .06. For all outcomes considered, the DARE effect size means were substantially smaller than those of programs emphasizing social and general competencies and using interactive teaching strategies. CONCLUSIONS. DARE's short-term effectiveness for reducing or preventing drug use behavior is small and is less than for interactive prevention programs. PMID:8092361

Formulation Predictive Dissolution (fPD) Testing to Advance Oral Drug Product Development: an Introduction to the US FDA Funded '21st Century BA/BE' Project.

PubMed

Hens, Bart; Sinko, Patrick; Job, Nicholas; Dean, Meagan; Al-Gousous, Jozef; Salehi, Niloufar; Ziff, Robert M; Tsume, Yasuhiro; Bermejo, Marival; Paixão, Paulo; Brasseur, James G; Yu, Alex; Talattof, Arjang; Benninghoff, Gail; Langguth, Peter; Lennernäs, Hans; Hasler, William L; Marciani, Luca; Dickens, Joseph; Shedden, Kerby; Sun, Duxin; Amidon, Gregory E; Amidon, Gordon L

2018-06-23

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions. Copyright © 2018. Published by Elsevier B.V.

Drug target ontology to classify and integrate drug discovery data.

PubMed

Lin, Yu; Mehta, Saurabh; Küçük-McGinty, Hande; Turner, John Paul; Vidovic, Dusica; Forlin, Michele; Koleti, Amar; Nguyen, Dac-Trung; Jensen, Lars Juhl; Guha, Rajarshi; Mathias, Stephen L; Ursu, Oleg; Stathias, Vasileios; Duan, Jianbin; Nabizadeh, Nooshin; Chung, Caty; Mader, Christopher; Visser, Ubbo; Yang, Jeremy J; Bologa, Cristian G; Oprea, Tudor I; Schürer, Stephan C

2017-11-09

One of the most successful approaches to develop new small molecule therapeutics has been to start from a validated druggable protein target. However, only a small subset of potentially druggable targets has attracted significant research and development resources. The Illuminating the Druggable Genome (IDG) project develops resources to catalyze the development of likely targetable, yet currently understudied prospective drug targets. A central component of the IDG program is a comprehensive knowledge resource of the druggable genome. As part of that effort, we have developed a framework to integrate, navigate, and analyze drug discovery data based on formalized and standardized classifications and annotations of druggable protein targets, the Drug Target Ontology (DTO). DTO was constructed by extensive curation and consolidation of various resources. DTO classifies the four major drug target protein families, GPCRs, kinases, ion channels and nuclear receptors, based on phylogenecity, function, target development level, disease association, tissue expression, chemical ligand and substrate characteristics, and target-family specific characteristics. The formal ontology was built using a new software tool to auto-generate most axioms from a database while supporting manual knowledge acquisition. A modular, hierarchical implementation facilitate ontology development and maintenance and makes use of various external ontologies, thus integrating the DTO into the ecosystem of biomedical ontologies. As a formal OWL-DL ontology, DTO contains asserted and inferred axioms. Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target characteristics. DTO has been implemented in the IDG user interface Portal, Pharos and the TIN-X explorer of protein target disease relationships. DTO was built based on the need for a formal semantic model for druggable targets including various related information such as protein, gene, protein domain, protein structure, binding site, small molecule drug, mechanism of action, protein tissue localization, disease association, and many other types of information. DTO will further facilitate the otherwise challenging integration and formal linking to biological assays, phenotypes, disease models, drug poly-pharmacology, binding kinetics and many other processes, functions and qualities that are at the core of drug discovery. The first version of DTO is publically available via the website http://drugtargetontology.org/ , Github ( http://github.com/DrugTargetOntology/DTO ), and the NCBO Bioportal ( http://bioportal.bioontology.org/ontologies/DTO ). The long-term goal of DTO is to provide such an integrative framework and to populate the ontology with this information as a community resource.

Contribution of NIH funding to new drug approvals 2010–2016

PubMed Central

Beierlein, Jennifer M.; Khanuja, Navleen Surjit; McNamee, Laura M.; Ledley, Fred D.

2018-01-01

This work examines the contribution of NIH funding to published research associated with 210 new molecular entities (NMEs) approved by the Food and Drug Administration from 2010–2016. We identified >2 million publications in PubMed related to the 210 NMEs (n = 131,092) or their 151 known biological targets (n = 1,966,281). Of these, >600,000 (29%) were associated with NIH-funded projects in RePORTER. This funding included >200,000 fiscal years of NIH project support (1985–2016) and project costs >$100 billion (2000–2016), representing ∼20% of the NIH budget over this period. NIH funding contributed to every one of the NMEs approved from 2010–2016 and was focused primarily on the drug targets rather than on the NMEs themselves. There were 84 first-in-class products approved in this interval, associated with >$64 billion of NIH-funded projects. The percentage of fiscal years of project funding identified through target searches, but not drug searches, was greater for NMEs discovered through targeted screening than through phenotypic methods (95% versus 82%). For targeted NMEs, funding related to targets preceded funding related to the NMEs, consistent with the expectation that basic research provides validated targets for targeted screening. This analysis, which captures basic research on biological targets as well as applied research on NMEs, suggests that the NIH contribution to research associated with new drug approvals is greater than previously appreciated and highlights the risk of reducing federal funding for basic biomedical research. PMID:29440428

Decline in economic returns from new drugs raises questions about sustaining innovations.

PubMed

Berndt, Ernst R; Nass, Deanna; Kleinrock, Michael; Aitken, Murray

2015-02-01

The sales and financial returns realized by pharmaceutical companies are a frequent topic of discussion and debate. In this study we analyzed the economic returns for four cohorts of new prescription drugs launched in the United States (in 1991-94, 1995-99, 2000-04, and 2005-09) and compared fluctuations in revenues with changing average research and development (R&D) and other costs to determine patterns in rewards for pharmaceutical innovation. We found that the average present values of lifetime net economic returns were positive and reached a peak with the 1995-99 and 2000-04 new drug cohorts. However, returns have fallen sharply since then, with those for the 2005-09 cohort being very slightly negative and, on average, failing to recoup research and development and other costs. If this level of diminished returns persists, we believe that the rewards for innovation will not be sufficient for pharmaceutical manufacturers to maintain the historical rates of investments needed to sustain biomedical innovation. Project HOPE—The People-to-People Health Foundation, Inc.

Public health the leading force of the Indonesian response to the HIV/AIDS crisis among people who inject drugs

PubMed Central

Mesquita, Fabio; Winarso, Inang; Atmosukarto, Ingrid I; Eka, Bambang; Nevendorff, Laura; Rahmah, Amala; Handoyo, Patri; Anastasia, Priscillia; Angela, Rosi

2007-01-01

Issue Indonesia has an explosive HIV/AIDS epidemic starting from the beginning of this century, and it is in process to build its response. Reported AIDS cases doubled from 2003 – 2004, and approximately 54% of these cases are in people who inject drugs. Setting Indonesia is the 4th largest country in population in the world, a predominantly Muslim country with strong views on drug users and people living with HIV/AIDS. Globally speaking, Indonesia has one of the most explosive epidemics in recent years. The project IHPCP (Indonesia HIV/AIDS Prevention and Care Project) is a joint support project (primarily AusAID-based) that works in partnership with the Government of Indonesia. IHPCP has been a key player of in the country's response, particularly pioneering NSP; stimulating and supporting methadone programs, and being key in promoting ARV for people who currently inject drugs. The project works via both the public health system and NGOs. Outcomes It is still early to measure the impact of current interventions; however, this paper describes the current status of Indonesia's response to the HIV/AIDS crisis among people who inject drugs, and analyses future challenges of the epidemic in Indonesia. PMID:17306033

Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection.

PubMed

Dong, Zuoli; Zhang, Naiqian; Li, Chun; Wang, Haiyun; Fang, Yun; Wang, Jun; Zheng, Xiaoqi

2015-06-30

An enduring challenge in personalized medicine is to select right drug for individual patients. Testing drugs on patients in large clinical trials is one way to assess their efficacy and toxicity, but it is impractical to test hundreds of drugs currently under development. Therefore the preclinical prediction model is highly expected as it enables prediction of drug response to hundreds of cell lines in parallel. Recently, two large-scale pharmacogenomic studies screened multiple anticancer drugs on over 1000 cell lines in an effort to elucidate the response mechanism of anticancer drugs. To this aim, we here used gene expression features and drug sensitivity data in Cancer Cell Line Encyclopedia (CCLE) to build a predictor based on Support Vector Machine (SVM) and a recursive feature selection tool. Robustness of our model was validated by cross-validation and an independent dataset, the Cancer Genome Project (CGP). Our model achieved good cross validation performance for most drugs in the Cancer Cell Line Encyclopedia (≥80% accuracy for 10 drugs, ≥75% accuracy for 19 drugs). Independent tests on eleven common drugs between CCLE and CGP achieved satisfactory performance for three of them, i.e., AZD6244, Erlotinib and PD-0325901, using expression levels of only twelve, six and seven genes, respectively. These results suggest that drug response could be effectively predicted from genomic features. Our model could be applied to predict drug response for some certain drugs and potentially play a complementary role in personalized medicine.

Anesthesia and the role of short-term service delivery in developing countries.

PubMed

Froese, Alison

2007-11-01

To clarify the ongoing need for involvement of anesthesiologists in short-term surgical projects in developing countries, and provide information to guide the selection of, application for, and preparation for these rewarding experiences. The lack of safe anesthesia services severely limits the performance of needed surgical procedures in developing countries around the world. Even in countries where well-trained anesthesiologists are available in major urban centres, resources are often absent or limited for large numbers of people in rural or remote areas. Anesthesiologists are highly sought members of surgical teams. Internet sites provide extensive project information. Projects occur in Central and South America, Africa, Asia and Eastern Europe. Projects can bring specialized surgical expertise to an otherwise well-serviced urban area, or work in remote areas that have surgical services only when a team comes. Available equipment, drugs, housing, food and transportation vary markedly with project site. Flexibility, adaptability and problem-solving skills are essential. Translators provide language assistance. Anesthesiologists who have experience providing anesthetics in settings with less technological support can assist other anesthesiologists in adapting to less sophisticated settings. Severe shortages of trained health professionals plague developing countries, reflecting complex economic and political problems that will require decades for resolution. Until such time as surgical services are widely available and affordable in remote as well as urban areas of developing countries, anesthesiologists will continue to provide a valuable and personally rewarding contribution through short-term assistance.

What will the crowd fund? Preferences of prospective donors for drug development fundraising campaigns.

PubMed

Dragojlovic, Nick; Lynd, Larry D

2016-12-01

Biomedical researchers are increasingly turning to project-based online fundraising (i.e., crowdfunding) as a complementary source of research funding. To help inform the fundraising strategies adopted by researchers who take this approach, we conducted an online survey of prospective donors in North America. Respondents indicated not only an overwhelming preference for donating to projects conducted by nonprofit research organizations, but also an openness to donating to companies that have a 'for-benefit' corporate structure. They also showed a strong preference for projects that have alternate sources of funding, that have the potential to yield a curative therapy, and that focus on common and pediatric diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharmacovigilance in Space: Stability Payload Compliance Procedures

NASA Technical Reports Server (NTRS)

Daniels, Vernie R.; Putcha, Lakshmi

2007-01-01

Pharmacovigilance is the science of, and activities relating to the detection, assessment, understanding, and prevention of drug-related problems. Over the lase decade, pharmacovigilance activities have contributed to the development of numerous technological and conventional advances focused on medication safety and regulatory intervention. The topics discussed include: 1) Proactive Pharmacovigilance; 2) A New Frontier; 3) Research Activities; 4) Project Purpose; 5) Methods; 6) Flight Stability Kit Components; 7) Experimental Conditions; 8) Research Project Logistics; 9) Research Plan; 10) Pharmaceutical Stability Research Project Pharmacovigilance Aspects; 11) Security / Control; 12) Packaging/Containment Actions; 13) Shelf-Life Assessments; 14) Stability Assessment Parameters; 15) Chemical Content Analysis; 16) Preliminary Results; 17) Temperature/Humidity; 18) Changes in PHysical and Chemical Assessment Parameters; 19) Observations; and 20) Conclusions.

Zebrafish-Based Discovery of Antiseizure Compounds from the Red Sea: Pseurotin A2 and Azaspirofuran A.

PubMed

Copmans, Daniëlle; Rateb, Mostafa; Tabudravu, Jioji N; Pérez-Bonilla, Mercedes; Dirkx, Nina; Vallorani, Riccardo; Diaz, Caridad; Pérez Del Palacio, José; Smith, Alan J; Ebel, Rainer; Reyes, Fernando; Jaspars, Marcel; de Witte, Peter A M

2018-04-19

In search for novel antiseizure drugs (ASDs), the European FP7-funded PharmaSea project used zebrafish embryos and larvae as a drug discovery platform to screen marine natural products to identify promising antiseizure hits in vivo for further development. Within the framework of this project, seven known heterospirocyclic γ-lactams, namely, pseurotin A, pseurotin A 2 , pseurotin F1, 11- O-methylpseurotin A, pseurotin D, azaspirofuran A, and azaspirofuran B, were isolated from the bioactive marine fungus Aspergillus fumigatus, and their antiseizure activity was evaluated in the larval zebrafish pentylenetetrazole (PTZ) seizure model. Pseurotin A 2 and azaspirofuran A were identified as antiseizure hits, while their close chemical analogues were inactive. Besides, electrophysiological analysis from the zebrafish midbrain demonstrated that pseurotin A 2 and azaspirofuran A also ameliorate PTZ-induced epileptiform discharges. Next, to determine whether these findings translate to mammalians, both compounds were analyzed in the mouse 6 Hz (44 mA) psychomotor seizure model. They lowered the seizure duration dose-dependently, thereby confirming their antiseizure properties and suggesting activity against drug-resistant seizures. Finally, in a thorough ADMET assessment, pseurotin A 2 and azaspirofuran A were found to be drug-like. Based on the prominent antiseizure activity in both species and the drug-likeness, we propose pseurotin A 2 and azaspirofuran A as lead compounds that are worth further investigation for the treatment of epileptic seizures. This study not only provides the first evidence of antiseizure activity of pseurotins and azaspirofurans, but also demonstrates the value of the zebrafish model in (marine) natural product drug discovery in general, and for ASD discovery in particular.

Project Towards No Drug Abuse (TND): Needs Assessment of a Social Service Referral Telephone Program for High Risk Youth

PubMed Central

SUSSMAN, STEVE; SKARA, SILVANA; PUMPUANG, PATCHAREEYA

2011-01-01

The purpose of this study was to conduct a needs assessment of a potential social service resource telephone program component among high risk youth who received the Project Towards No Drug Abuse (TND) classroom-based program (approximately 1 year earlier). Results supported youths’ overwhelming receptiveness of a social service referral program. The vast majority of respondents indicated a strong desire for resource and referral information on vocational, educational, recreational, transportation, and mental health and drug counseling. Further research is needed to investigate the effectiveness of the provision of social service resource information on drug use among emerging adults. PMID:18720266

21 CFR 201.129 - Drugs; exemption for radioactive drugs for research use.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to human research subjects during the course of a research project intended to obtain basic research... labeled drug or regarding human physiology, pathophysiology, or biochemistry (but not intended for...

'Government Patent Use': A Legal Approach To Reducing Drug Spending.

PubMed

Kapczynski, Amy; Kesselheim, Aaron S

2016-05-01

The high cost of patent-protected brand-name drugs can strain budgets and curb the widespread use of new medicines. An example is the case of direct-acting antiviral drugs for the treatment of hepatitis C. While prices for these drugs have come down in recent months, they still create barriers to treatment. Additionally, prescribing restrictions imposed by insurers put patients at increased risk of medical complications and contribute to transmission of the hepatitis C virus. We propose that the federal government invoke its power under an existing "government patent use" law to reduce excessive prices for important patent-protected medicines. Using this law would permit the government to procure generic versions of patented drugs and in exchange pay the patent-holding companies reasonable royalties to compensate them for research and development. This would allow patients in federal programs, and perhaps beyond, to be treated with inexpensive generic medicines according to clinical need-meaning that many more patients could be reached for no more, and perhaps far less, money than is currently spent. Another benefit would be a reduction in the opportunity for companies to extract monopoly profits that far exceed their risk-adjusted costs of research and development. Project HOPE—The People-to-People Health Foundation, Inc.

Hepatic transporter drug-drug interactions: an evaluation of approaches and methodologies.

PubMed

Williamson, Beth; Riley, Robert J

2017-12-01

Drug-drug interactions (DDIs) continue to account for 5% of hospital admissions and therefore remain a major regulatory concern. Effective, quantitative prediction of DDIs will reduce unexpected clinical findings and encourage projects to frontload DDI investigations rather than concentrating on risk management ('manage the baggage') later in drug development. A key challenge in DDI prediction is the discrepancies between reported models. Areas covered: The current synopsis focuses on four recent influential publications on hepatic drug transporter DDIs using static models that tackle interactions with individual transporters and in combination with other drug transporters and metabolising enzymes. These models vary in their assumptions (including input parameters), transparency, reproducibility and complexity. In this review, these facets are compared and contrasted with recommendations made as to their application. Expert opinion: Over the past decade, static models have evolved from simple [I]/k i models to incorporate victim and perpetrator disposition mechanisms including the absorption rate constant, the fraction of the drug metabolised/eliminated and/or clearance concepts. Nonetheless, models that comprise additional parameters and complexity do not necessarily out-perform simpler models with fewer inputs. Further, consideration of the property space to exploit some drug target classes has also highlighted the fine balance required between frontloading and back-loading studies to design out or 'manage the baggage'.

Interaction Patterns among Drug Dealers. Drug Abuse Information Research Project.

ERIC Educational Resources Information Center

Atkyns, Robert L.; Hanneman, Gerhard J.

Drug dealers are often popularly stereotyped as "pushers" who actively engage in enticing young people into the drug habit, but there have been no scientific studies of their behavior or their attitudes on drug abuse or public health. In an attempt to gain information about behavior characteristics and communication patterns of middle…

A Residential School's Outdoor Education Program for Emotionally Handicapped Adolescents. Final Project Report of the Rhinecliff Union Free School District, Holy Cross Campus.

ERIC Educational Resources Information Center

Rigothi, Anthony, Ed.

Concept definition and activity description constituted the major focus of implementation proceedings of this outdoor education program designed for a residential school serving secondary students with emotional and drug related problems. Major program objectives were the development of greater academic growth and more positive self-concept for…

Development of a New Class of Drugs To Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers

DTIC Science & Technology

2016-10-01

crystals and may represent a new crystal form. Key outcome 2: We have carried out followup crystallization screening operations with the ARdbd protein...related projects. 1. Tam, K., Dalal, K., Hsing, M., Cheng, C.W., Chiang , Y.T., Sharma, A., Peacock, J.W., Wang, W., Cherkasov, A., Rennie, P.S

76 FR 3913 - National Institute on Drug Abuse; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-21

... evaluation of individual intramural programs and projects conducted by the National Institute on Drug Abuse... individual investigators. Place: Intramural Research Program, National Institute on Drug Abuse, NIH, Johns... Psychologist, Clinical Pharmacology Branch, Intramural Research Program, National Institute on Drug Abuse...

Drug resistant Mycobacterium tuberculosis in Mexico.

PubMed

Zazueta-Beltran, Jorge; León-Sicairos, Claudia; Canizalez-Roman, Adrián

2009-04-30

Tuberculosis (TB) remains a serious public health problem, worsened by an increased frequency of multidrug-resistant (MDR) Mycobacterium tuberculosis strains. The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) launched the Global Project on Anti-Tuberculosis Drug Resistance Surveillance to measure the prevalence of drug resistance. Data from the global reports on resistance to anti-tuberculosis (anti-TB) drugs have shown that drug resistance still presents worldwide and that MDR-TB is present in almost all the world. Though the Global Project (WHO) has been operating since 1994, very few countries and states have reported new information. Data from repeated surveys employing comparable methodologies over several years are essential to determine with any certainty in which direction the prevalence of drug resistance is moving. Drug-resistant tuberculosis and MDR-TB have been identified in Mexico, even with the existence of a National Tuberculosis Program based on Directly Observed Treatment, Short-course (DOTS). This review discusses available surveillance data on drug susceptibility data for TB in different states of Mexico.

Drug Information in Space Medicine

NASA Technical Reports Server (NTRS)

Bayuse, Tina M.

2009-01-01

Published drug information is widely available for terrestrial conditions. However, information on dosing, administration, drug interactions, stability, and side effects is scant as it relates to use in Space Medicine. Multinational crews on board the International Space Station present additional challenges for drug information because medication nomenclature, information available for the drug as well as the intended use for the drug is not standard across countries. This presentation will look at unique needs for drug information and how the information is managed in Space Medicine. A review was conducted of the drug information requests submitted to the Johnson Space Center Pharmacy by Space Medicine practitioners, astronaut crewmembers and researchers. The information requested was defined and cataloged. A list of references used was maintained. The wide range of information was identified. Due to the information needs for the medications in the on-board medical kits, the Drug Monograph Project was created. A standard method for answering specific drug information questions was generated and maintained by the Johnson Space Center Pharmacy. The Drug Monograph Project will be presented. Topic-centered requests, including multinational drug information, drug-induced adverse reactions, and medication events due to the environment will be highlighted. Information management of the drug information will be explained. Future considerations for drug information needs will be outlined.

The view of the pharmaceutical industry.

PubMed

Roche, G; Helenport, J P

1994-06-01

Rhône-Poulenc Rorer has committed itself to the development of artemether because we believe the drug will be of considerable benefit to sufferers from severe falciparum malaria, and because it is a stable, effective and economical compound that can be given by intramuscular injection. The quality of the pharmaceutical product meets international regulatory standards. Artemether is unlikely to yield big profits, but we believe that major pharmaceutical companies have a responsibility to develop such much-needed products. To develop this project further, we will need the assistance of academic institutions, research organizations and international bodies.

Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving.

PubMed

Li, Xuan; Witonsky, Kailyn R; Lofaro, Olivia M; Surjono, Felicia; Zhang, Jianjun; Bossert, Jennifer M; Shaham, Yavin

2018-02-28

Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R-glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L→DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L→DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT→DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L→DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L→DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L→DMS glutamatergic projections in incubation of drug craving and drug seeking. SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of methamphetamine craving. We previously found that D1R-mediated dopamine transmission in the dorsomedial striatum plays a critical role in this incubation phenomenon. Here, we used neuroanatomical and neuropharmacological methods in rats to demonstrate that an interaction between the glutamatergic projection from the lateral anterior intralaminar nuclei of the thalamus to the dorsomedial striatum and local dopamine D1 receptors plays a critical role in relapse to methamphetamine seeking after prolonged withdrawal. Our study identified a novel motivation-related thalamostriatal projection critical to relapse to drug seeking. Copyright © 2018 the authors 0270-6474/18/382270-13$15.00/0.

Summary of Outcome Data for Youth Alcohol and Other Drug Abuse Programs.

ERIC Educational Resources Information Center

Buck, Connie

The purpose of this report is to summarize steps taken in evaluating outcomes for the prevention of youth alcohol and other drug abuse (AODA) for selected AODA prevention programs and projects as reported to Wisconsin's Department of Health and Family Services by grantees. A study by Wisconsin's Legislative Audit Bureau evaluated 6 projects, which…

Collaboration for rare disease drug discovery research.

PubMed

Litterman, Nadia K; Rhee, Michele; Swinney, David C; Ekins, Sean

2014-01-01

Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives.

Collaboration for rare disease drug discovery research

PubMed Central

Litterman, Nadia K.; Rhee, Michele; Swinney, David C.; Ekins, Sean

2014-01-01

Rare disease research has reached a tipping point, with the confluence of scientific and technologic developments that if appropriately harnessed, could lead to key breakthroughs and treatments for this set of devastating disorders. Industry-wide trends have revealed that the traditional drug discovery research and development (R&D) model is no longer viable, and drug companies are evolving their approach. Rather than only pursue blockbuster therapeutics for heterogeneous, common diseases, drug companies have increasingly begun to shift their focus to rare diseases. In academia, advances in genetics analyses and disease mechanisms have allowed scientific understanding to mature, but the lack of funding and translational capability severely limits the rare disease research that leads to clinical trials. Simultaneously, there is a movement towards increased research collaboration, more data sharing, and heightened engagement and active involvement by patients, advocates, and foundations. The growth in networks and social networking tools presents an opportunity to help reach other patients but also find researchers and build collaborations. The growth of collaborative software that can enable researchers to share their data could also enable rare disease patients and foundations to manage their portfolio of funded projects for developing new therapeutics and suggest drug repurposing opportunities. Still there are many thousands of diseases without treatments and with only fragmented research efforts. We will describe some recent progress in several rare diseases used as examples and propose how collaborations could be facilitated. We propose that the development of a center of excellence that integrates and shares informatics resources for rare diseases sponsored by all of the stakeholders would help foster these initiatives. PMID:25685324

Creating a Tiny Human Body on a Chip

ScienceCinema

Hunsberger, Maren; Soscia, Dave; Moya, Monica

2018-06-21

LLNL science communicator Maren Hunsberger takes us "Inside the Lab" to learn about the iChip (In-vitro Chip-based Human Investigational Platform) project at Lawrence Livermore National Laboratory. "One application of the iChip system would be to develop new pharmaceutical drugs," explains Dave Soscia, LLNL postdoc. "When you test in a mouse for example, it's not as close to the human system as you can get. If we can take human cells and put them on devices and actually mimic the structure and function of the organ systems in the human, we can actually replace animal testing and even make a better system for testing pharmaceutical drugs."

What is good governance in the context of drug policy?

PubMed

Singleton, Nicola; Rubin, Jennifer

2014-09-01

The concept of governance is applied in a wide range of contexts, but this paper focuses on governance in relation to public administration, i.e. states and how they take action, and specifically governance of particular policy areas. In the current context of financial austerity and an era of globalisation, policy-makers face pressures and challenges from a growing range of interests and local, national and supranational actors. Drug policy is an example of a particularly contentious and polarised area in which governance-related challenges abound. In response to these challenges, interest has grown in developing agreed policy governance standards and processes and articulating policy-making guidelines, including the use of available evidence to inform policy-making. Attempts have been made to identify 'policy fundamentals' - factors or aspects of policy-making apparently associated with successful policy development and implementation (Hallsworth & Rutter, 2011; Laughrin, 2011) and, in the drug policy field, Hughes et al. (2010) reflecting on the co-ordination of Australian drug policy highlighted some of what they considered principles of good governance. But how useful is the concept of 'good governance'; how well can it be defined, and to what purpose? As part of a wider project considering the governance of drug policy, RAND Europe and the UK Drug Policy Commission undertook a targeted review of other research and sought expert views, from within and beyond drug policy, on principles, processes, structures and stakeholders associated with good drug policy governance. From this emerged some perceived characteristics of good governance that were then used by the UK Drug Policy Commission to assess the extent to which drug policy making in the UK fits with these perceived good governance characteristics, and to suggest possible improvements. Particular consideration was given to the range of interests at stake, the overarching aims of drug policy and the development and inclusion of an evidence base where possible. This paper draws on findings of the study to highlight challenges associated with defining good governance, provides an example of a framework for assessing drug policy governance and discusses the feasibility, transferability and potential benefits of such an undertaking. Copyright © 2014 Elsevier B.V. All rights reserved.

78 FR 25282 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... Project: Mandatory Guidelines for Federal Workplace Drug Testing Programs (OMB No. 0930-0158)--Revision SAMHSA's Mandatory Guidelines for Federal Workplace Drug Testing Programs will request OMB approval for the Federal Drug Testing Custody and Control Form for federal agency and federally regulated drug...

76 FR 65517 - National Institute on Drug Abuse Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

... individual intramural programs and projects conducted by the National Institute on Drug Abuse, including.... Place: Intramural Research Program, National Institute on Drug Abuse, NIH, Johns Hopkins Bayview Campus..., Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, 251 Bayview Boulevard, Baltimore...

78 FR 55265 - National Institute on Drug Abuse; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... individual intramural programs and projects conducted by the National Institute on Drug Abuse, including.... Place: Intramural Research Program, National Institute on Drug Abuse, NIH, Johns Hopkins Bayview Campus..., Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, 251 Bayview Boulevard, Baltimore...

Early Life Stress and Sleep Restriction as Risk Factors in PTSD: An Integrative Pre-Clinical Approach

DTIC Science & Technology

2014-04-01

potential risk factors, with high relevance to soldiers. The primary aims of the project are thus. 1) To establish an effective animal model of PTSD that...develop the model as a platform for pharmacological testing of novel targets for drug development 5) As an additional aim – once an effective animal model...thus: 1) To establish an effective animal model of PTSD that would take into consideration the contribution of risk factors to the induction of the

Design and implementation of a laboratory-based drug design and synthesis advanced pharmacy practice experience.

PubMed

Philip, Ashok; Stephens, Mark; Mitchell, Sheila L; Watkins, E Blake

2015-04-25

To provide students with an opportunity to participate in medicinal chemistry research within the doctor of pharmacy (PharmD) curriculum. We designed and implemented a 3-course sequence in drug design or drug synthesis for pharmacy students consisting of a 1-month advanced elective followed by two 1-month research advanced pharmacy practice experiences (APPEs). To maximize student involvement, this 3-course sequence was offered to third-year and fourth-year students twice per calendar year. Students were evaluated based on their commitment to the project's success, productivity, and professionalism. Students also evaluated the course sequence using a 14-item course evaluation rubric. Student feedback was overwhelmingly positive. Students found the experience to be a valuable component of their pharmacy curriculum. We successfully designed and implemented a 3-course research sequence that allows PharmD students in the traditional 4-year program to participate in drug design and synthesis research. Students report the sequence enhanced their critical-thinking and problem-solving skills and helped them develop as independent learners. Based on the success achieved with this sequence, efforts are underway to develop research APPEs in other areas of the pharmaceutical sciences.

A novel, bottom-up approach to promote evidence-based HIV prevention for people who inject drugs in Ukraine: protocol for the MICT (‘Bridge’) HIV prevention exchange project

PubMed Central

2014-01-01

Background Ukraine has one of the most severe HIV epidemics in Eastern Europe, with an estimated 1.6% of the adult population living with the virus. Injection drug use accounts for 36% of new HIV cases. Nongovernmental organizations in Ukraine have little experience with effective, theory-based behavioral risk reduction interventions necessary to reduce the scope of the HIV epidemic among Ukrainians who inject drugs. This study seeks to promote the use of evidence-based HIV prevention strategies among Ukrainian organizations working with drug users. Methods/design This study combines qualitative and quantitative methods to explore a model of HIV prevention intervention development and implementation that disseminates common factors of effective behavioral risk reduction interventions and enables service providers to develop programs that reflect their specific organizational contexts. Eight agencies, located in regions of Ukraine with the highest HIV and drug use rates and selected to represent key organizational context criteria (e.g., agency size, target population, experience with HIV prevention), will be taught common factors as the basis for intervention development. We will use qualitative methods, including interviews and observations, to document the process of intervention development and implementation at each agency. Using risk assessments with intervention participants, we will also assess intervention effectiveness. The primary outcome analyses will determine the extent to which agencies develop and implement an intervention for drug users that incorporates common factors of effective behavioral interventions. Effectiveness analyses will be conducted, and effect size of each intervention will be compared to that of published HIV prevention interventions for drug users with demonstrated effectiveness. This study will explore the role of organizational context on intervention development and implementation, including resource allocation decisions, problem-solving around intervention development, and barriers and facilitators to inclusion of common factors and delivery of a high quality intervention. Discussion This innovative approach to HIV prevention science dissemination and intervention development draws on providers’ ability to quickly develop innovative programs and reach populations in greatest need of services. It has the potential to enhance providers’ ability to use HIV prevention science to develop sustainable interventions in response to a rapidly changing epidemic. PMID:24491185

The Search for Drug Abuse Information. Drug Abuse Information Research Project (Revised).

ERIC Educational Resources Information Center

Hanneman, Gerhard J.; Pet, Marilyn L.

A large proportion of those who seek drug abuse information from a telephone hotline service have immediate drug information needs, either for themselves or to assist others. Requests for general or pharmacological information are less frequent. Content analysis was applied in a study of telephone calls to a Hartford, Connecticut, "drug abuse…

Expanded HIV Screening Projected to Decrease Spread of the Virus

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs Over-the- ...

Contribution of NIH funding to new drug approvals 2010-2016.

PubMed

Galkina Cleary, Ekaterina; Beierlein, Jennifer M; Khanuja, Navleen Surjit; McNamee, Laura M; Ledley, Fred D

2018-03-06

This work examines the contribution of NIH funding to published research associated with 210 new molecular entities (NMEs) approved by the Food and Drug Administration from 2010-2016. We identified >2 million publications in PubMed related to the 210 NMEs ( n = 131,092) or their 151 known biological targets ( n = 1,966,281). Of these, >600,000 (29%) were associated with NIH-funded projects in RePORTER. This funding included >200,000 fiscal years of NIH project support (1985-2016) and project costs >$100 billion (2000-2016), representing ∼20% of the NIH budget over this period. NIH funding contributed to every one of the NMEs approved from 2010-2016 and was focused primarily on the drug targets rather than on the NMEs themselves. There were 84 first-in-class products approved in this interval, associated with >$64 billion of NIH-funded projects. The percentage of fiscal years of project funding identified through target searches, but not drug searches, was greater for NMEs discovered through targeted screening than through phenotypic methods (95% versus 82%). For targeted NMEs, funding related to targets preceded funding related to the NMEs, consistent with the expectation that basic research provides validated targets for targeted screening. This analysis, which captures basic research on biological targets as well as applied research on NMEs, suggests that the NIH contribution to research associated with new drug approvals is greater than previously appreciated and highlights the risk of reducing federal funding for basic biomedical research. Copyright © 2018 the Author(s). Published by PNAS.

Pharmacological classification of herbal extracts by means of comparison to spectral EEG signatures induced by synthetic drugs in the freely moving rat.

PubMed

Dimpfel, Wilfried

2013-09-16

Herbal extracts targeting at the brain remain a continuous challenge to pharmacology. Usually, a number of different animal tests have to be performed in order to find a potential clinical use. Due to manifold possibly active ingredients biochemical approaches are difficult. A more holistic approach using a neurophysiological technique has been developed earlier in order to characterise synthetic drugs. Stereotactic implantation of four semi-microelectrodes into frontal cortex, hippocampus, striatum and reticular formation of rats allowed continuous wireless monitoring of field potentials (EEG) before and after drug intake. After frequency analysis (Fast Fourier Transformation) electric power was calculated for 6 ranges (delta, theta, alpha1, alpha2, beta1 and beta2). Data from 14 synthetic drugs - tested earlier and representative for different clinical indications - were taken for construction of discriminant functions showing the projection of the frequency patterns in a six-dimensional graph. Quantitative analysis of the EEG frequency pattern from the depth of the brain succeeded in discrimination of drug effects according to their known clinical indication (Dimpfel and Schober, 2003). Extracts from Valerian root, Ginkgo leaves, Paullinia seed, Hop strobile, Rhodiola rosea root and Sideritis scardica herb were tested now under identical conditions. Classification of these extracts based on the matrix from synthetic drugs revealed that Valerian root and hop induced a pattern reminiscent of physiological sleep. Ginkgo and Paullinia appeared in close neighbourhood of stimulatory drugs like caffeine or to an analgesic profile (tramadol). Rhodiola and Sideritis developed similar frequency patterns comparable to a psychostimulant drug (methylphenidate) as well to an antidepressive drug (paroxetine). © 2013 The Author. Published by Elsevier Ireland Ltd. All rights reserved.

75 FR 41488 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

.... Project: Mandatory Guidelines for Federal Workplace Drug Testing Programs (OMB No. 0930-0158)--Revision SAMHSA's Mandatory Guidelines for Federal Workplace Drug Testing Programs will request OMB approval for the Federal Drug Testing Custody and Control Form for Federal agency and federally regulated drug...

76 FR 22715 - National Institute on Drug Abuse; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

... personal privacy. Name of Committee: National Institute on Drug Abuse Special Emphasis Panel; NIDA Blending..., Training and Special Projects Review Branch, Office of Extramural Affairs, National Institute on Drug Abuse... Assistance Program Nos.: 93.279, Drug Abuse and Addiction Research Programs, National Institutes of Health...

The Napa Project: 02 Year Annual Drug Survey.

ERIC Educational Resources Information Center

Moskowitz, Joel M.; And Others

The results of a survey administered to junior and senior high students in the Napa Valley (CA) Unified School District in 1980 are summarized. The questionnaire administered was the Drug and Alcohol Survey, a group administered, self-report instrument. The questionnaire assesses: (1) drug knowledge; (2) general drug attitudes; (3) perceived…

Drugged Driving in Wisconsin: Oral Fluid Versus Blood.

PubMed

Edwards, Lorrine D; Smith, Katherine L; Savage, Theodore

2017-07-01

A pilot project was conducted in Dane County, Wisconsin, to evaluate the frequency of individuals driving under the influence of drugs (DUID). Evidentiary blood specimens, collected from subjects arrested for Operating While Intoxicated (OWI), were compared to oral fluid (OF) results obtained with the Alere DDS2®, a handheld screening device. The project objectives were to evaluate (i) the Alere DDS2® for use by police officers in the field, (ii) the frequency of individuals DUID and drugs combined with alcohol among OWI cases, (iii) the differences between detecting drugs in OF and in blood, and (iv) the effect of the laboratory drug testing cancellation policy (LCP) when the blood alcohol concentration (BAC) exceeds 0.100 g/100 mL. Following the arrest and collection of blood, subjects were asked to voluntarily participate in the project and provide an OF specimen. The OF was presumptively screened with the Alere DDS2® for six drug categories including (ng/mL) amphetamine (50), benzodiazepines (temazepam, 20), cocaine (benzoylecgonine, 30), methamphetamine (50), opioids (morphine, 40) and THC (delta-9-THC, 25). Results obtained with the OF screening instrument were not confirmed. A total of 104 subjects (22 female, 82 male), ages 18-72, were included in the project. Blood specimens were tested by gas chromatography-headspace (GCHS-FID) for volatiles, enzyme immunoassay (Siemens Viva-E Drug Testing System), and an alkaline basic drug screen with gas chromatography-mass spectrometry (GCMS) analysis. To compensate for differences between the EIA and the Alere DDS2® drug categories, results from the enzyme immunoassay and the alkaline basic drug screen were combined for purposes of comparing OF to blood. Seventy-six of 104 (73%) subjects arrested for OWI were driving under the influence of alcohol; 71 of the 76 had a BAC exceeding 0.10 g/100 mL. Subjects with a BAC exceeding the LCP, screened positive for drugs in both OF (n = 29) and blood (n = 28). Overall, one or more positive drug screening result was observed in 57 (55%) and 50 (48%) subjects for OF and blood specimens, respectively. THC was the most frequently detected drug category in both OF (n = 46) and whole blood (n = 44). Drug Recognition Expert (DRE) evaluations were performed on 18 subjects. In general, the Alere DDS2® results were consistent with the combined screening results observed in evidentiary blood specimens. This project was limited in scope as a second OF specimen was not collected for confirmation of drugs, however it did demonstrate that nearly 40% of the subjects with concentrations of alcohol exceeding 0.10 g/100 mL, screened positive for one or more drug categories in both OF and blood. The Alere DDS2® portable OF screening instrument may be useful in assisting law enforcement with identifying individuals driving under the influence of drugs and establishing probable cause at roadside for making DUID arrests. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Repositioning of drugs using open-access data portal DTome: A test case with probenecid (Review).

PubMed

Ahmed, Mohammad U; Bennett, Dylan J; Hsieh, Tze-Chen; Doonan, Barbara B; Ahmed, Saba; Wu, Joseph M

2016-01-01

The one gene-one enzyme hypothesis, first introduced by Beadle and Tatum in the 1940s and based on their genetic analysis and observation of phenotype changes in Neurospora crassa challenged by various experimental conditions, has witnessed significant advances in recent decades. Much of our understanding of the association between genes and their phenotype expression has benefited from the completion of the human genome project, and has shown continual transformation guided by the effort directed at the annotation and characterization of human genes. Similarly, the idea of one drug‑one primary disease indication that traditionally has been the benchmark for the labeling and usage of drugs has also undergone evident progressive refinements; in recent years the science and practice of pharmaceutical development has notable success in the strategy of drug repurposing. Drug repurposing is an innovative approach where, instead of de novo synthesis and discovery of new drugs with novel indications, drug candidates with the desired usage are identified by a process of re‑profiling using an open‑source database or knowledge of known or failed drugs already in existence. In the present study, the repurposing drug strategy employing open‑access data portal drug‑target interactome (DTome) is applied to the uncovering of new clinical usage for probenecid.

The World Health Organization and the Pharmaceutical Industry. Common areas of interest and differing views.

PubMed

Hardwicke, Caroline J

2002-01-01

No article published in the scientific press in the last 10 years reviews the various areas of interest common to the World Health Organization (WHO) and the pharmaceutical industry. Despite a vast amount of information in the public domain, the policies expound the views only of the bodies they represent rather than comparing differing views. An understanding of the factors which affect the interaction between these organisations as well as the organisational structures and the actual areas of intersecting interest, may help to find ways for the industry to assist the WHO in its endeavours in developing countries. Modern drug development is performed initially in and for western society, leaving the areas of infectious or tropical diseases with relatively less industry investment than cancer and cardiovascular disorders. Aspects of the development of an ethical drug, regardless of its therapeutic class (selection of drug name, intellectual property rights, drug safety, marketing and pricing, quality assurance and counterfeiting, generic use, emerging drug donations) are influenced to varying degrees by the triad of money, politics and medical need and the perspectives (each defensible) placed thereon by the WHO and industry. Instead of simply defending their positions combining the best of these strategies to optimise drug development for the needs of developing countries appears logical. Similarly, via its philanthropic initiatives, industry will have donated over $US1 billion in drug and research aid in the period 1995 to 2005. These charitable projects should yield useful information for planning and organising future aid efforts. Global warming, only recently given serious governmental consideration, is an area not yet addressed in drug development policy although along with geographical effects, it is likely to have an impact on the epidemiology of diseases e.g. malaria returning to the Mediterranean, worldwide. With changing disease patterns (and particularly if the western world is affected directly), a shift in emphasis on future medical needs and drug development can be anticipated. Furthermore, given the increased modern interest in herbal medicines and the fact that poorer countries rely heavily on traditional medicines, archiving of botanicals under threat would preserve plants for future medicinal testing or use. Coupled with the environmental and poverty issues that the WHO already attempts to address in developing countries, it is timely for both bodies to work towards certain agreed mutual aims. To work effectively, it is realistic that both bodies must benefit and also make concessions in this interactive process.

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

Responsible Management and Use of a Personal Take-Home Naloxone Supply: A Pilot Project

ERIC Educational Resources Information Center

McAuley, Andrew; Lindsay, George; Woods, Maureen; Louttit, Derek

2010-01-01

Aims: To assess if Scottish drug users, their family and friends could be trained in critical incident management and the safe and effective administration of naloxone. The project also sought to monitor whether drug users can manage their own personal take-home naloxone (THN) supply and use it appropriately in an emergency opiate overdose…

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Contents of application; research projects in which drugs will be administered. 2a.5 Section 2a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PROTECTION OF IDENTITY-RESEARCH SUBJECTS § 2a.5 Contents of...

Fragment-based screening by protein crystallography: successes and pitfalls.

PubMed

Chilingaryan, Zorik; Yin, Zhou; Oakley, Aaron J

2012-10-08

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.

Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls

PubMed Central

Chilingaryan, Zorik; Yin, Zhou; Oakley, Aaron J.

2012-01-01

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality. PMID:23202926

Modeling & Informatics at Vertex Pharmaceuticals Incorporated: our philosophy for sustained impact

NASA Astrophysics Data System (ADS)

McGaughey, Georgia; Patrick Walters, W.

2017-03-01

Molecular modelers and informaticians have the unique opportunity to integrate cross-functional data using a myriad of tools, methods and visuals to generate information. Using their drug discovery expertise, information is transformed to knowledge that impacts drug discovery. These insights are often times formulated locally and then applied more broadly, which influence the discovery of new medicines. This is particularly true in an organization where the members are exposed to projects throughout an organization, such as in the case of the global Modeling & Informatics group at Vertex Pharmaceuticals. From its inception, Vertex has been a leader in the development and use of computational methods for drug discovery. In this paper, we describe the Modeling & Informatics group at Vertex and the underlying philosophy, which has driven this team to sustain impact on the discovery of first-in-class transformative medicines.

Health Promotion Efforts in an Isolated Hispanic Community: The Mora Substance Abuse Prevention Project.

ERIC Educational Resources Information Center

Duryea, Elias J.; And Others

An alcohol and drug use education program was developed by teachers and administrators in Mora, a small, isolated Hispanic community in northern New Mexico, in cooperation with the town's public health nurses and a University of New Mexico research team. Pre- and posttests were given to 150 students in grades 7-9 in the Mora Public Schools to…

[Structured medication management in primary care - a tool to promote medication safety].

PubMed

Mahler, Cornelia; Freund, Tobias; Baldauf, Annika; Jank, Susanne; Ludt, Sabine; Peters-Klimm, Frank; Haefeli, Walter Emil; Szecsenyi, Joachim

2014-01-01

Patients with chronic disease usually need to take multiple medications. Drug-related interactions, adverse events, suboptimal adherence, and self-medication are components that can affect medication safety and lead to serious consequences for the patient. At present, regular medication reviews to check what medicines have been prescribed and what medicines are actually taken by the patient or the structured evaluation of drug-related problems rarely take place in Germany. The process of "medication reconciliation" or "medication review" as developed in the USA and the UK aim at increasing medication safety and therefore represent an instrument of quality assurance. Within the HeiCare(®) project a structured medication management was developed for general practice, with medical assistants playing a major role in the implementation of the process. Both the structured medication management and the tools developed for the medication check and medication counselling will be outlined in this article; also, findings on feasibility and acceptance in various projects and experiences from a total of 200 general practices (56 HeiCare(®), 29 HiCMan,115 PraCMan) will be described. The results were obtained from questionnaires and focus group discussions. The implementation of a structured medication management intervention into daily routine was seen as a challenge. Due to the high relevance of medication reconciliation for daily clinical practice, however, the checklists - once implemented successfully - have been applied even after the end of the project. They have led to the regular review and reconciliation of the physicians' documentation of the medicines prescribed (medication chart) with the medicines actually taken by the patient. Copyright © 2013. Published by Elsevier GmbH.

Project ATHENA Creates Surrogate Human Organ Systems

ScienceCinema

MacQueen, Luke; Knospel, Fanny; Sherrod, Stacy; Iy

2018-06-06

The development of miniature surrogate human organs, coupled with highly sensitive mass spectrometry technologies, could one day revolutionize the way new drugs and toxic agents are studied. “By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs,” said Rashi Iyer, a senior scientist at Los Alamos National Laboratory. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is nearing the full integration of four human organ constructs — liver, heart, lung and kidney — each organ component is about the size of a smartphone screen, and the whole ATHENA “body” of interconnected organs will fit neatly on a desk. A new video available on the Los Alamos National Laboratory YouTube channel updates the ATHENA project as it begins to integrate the various organ systems into a single system. Some 40 percent of pharmaceuticals fail their clinical trials and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success. ATHENA is funded by the Defense Threat Reduction Agency (DTRA) and is a collaboration of Los Alamos National Laboratory, Harvard University, Vanderbilt University, Charité Universitätsmedizin, Berlin, Germany, CFD Research Corporation, and the University of California San Francisco.

Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description.

PubMed

Spyrakis, Francesca; Cavasotto, Claudio N

2015-10-01

Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Copyright © 2015 Elsevier Inc. All rights reserved.

Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks.

PubMed

Haque, Azizul; Hober, Didier; Blondiaux, Joel

2015-10-01

Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Using medication list--problem list mismatches as markers of potential error.

PubMed Central

Carpenter, James D.; Gorman, Paul N.

2002-01-01

The goal of this project was to specify and develop an algorithm that will check for drug and problem list mismatches in an electronic medical record (EMR). The algorithm is based on the premise that a patient's problem list and medication list should agree, and a mismatch may indicate medication error. Successful development of this algorithm could mean detection of some errors, such as medication orders entered into a wrong patient record, or drug therapy omissions, that are not otherwise detected via automated means. Additionally, mismatches may identify opportunities to improve problem list integrity. To assess the concept's feasibility, this study compared medications listed in a pharmacy information system with findings in an online nursing adult admission assessment, serving as a proxy for the problem list. Where drug and problem list mismatches were discovered, examination of the patient record confirmed the mismatch, and identified any potential causes. Evaluation of the algorithm in diabetes treatment indicates that it successfully detects both potential medication error and opportunities to improve problem list completeness. This algorithm, once fully developed and deployed, could prove a valuable way to improve the patient problem list, and could decrease the risk of medication error. PMID:12463796

Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks

PubMed Central

Hober, Didier; Blondiaux, Joel

2015-01-01

Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. PMID:26248374

Improved in vitro models for preclinical drug and formulation screening focusing on 2D and 3D skin and cornea constructs.

PubMed

Beißner, Nicole; Bolea Albero, Antonio; Füller, Jendrik; Kellner, Thomas; Lauterboeck, Lothar; Liang, Jinghu; Böl, Markus; Glasmacher, Birgit; Müller-Goymann, Christel C; Reichl, Stephan

2018-05-01

The present overview deals with current approaches for the improvement of in vitro models for preclinical drug and formulation screening which were elaborated in a joint project at the Center of Pharmaceutical Engineering of the TU Braunschweig. Within this project a special focus was laid on the enhancement of skin and cornea models. For this reason, first, a computation-based approach for in silico modeling of dermal cell proliferation and differentiation was developed. The simulation should for example enhance the understanding of the performed 2D in vitro tests on the antiproliferative effect of hyperforin. A second approach aimed at establishing in vivo-like dynamic conditions in in vitro drug absorption studies in contrast to the commonly used static conditions. The reported Dynamic Micro Tissue Engineering System (DynaMiTES) combines the advantages of in vitro cell culture models and microfluidic systems for the emulation of dynamic drug absorption at different physiological barriers and, later, for the investigation of dynamic culture conditions. Finally, cryopreserved shipping was investigated for a human hemicornea construct. As the implementation of a tissue-engineering laboratory is time-consuming and cost-intensive, commercial availability of advanced 3D human tissue is preferred from a variety of companies. However, for shipping purposes cryopreservation is a challenge to maintain the same quality and performance of the tissue in the laboratory of both, the provider and the customer. Copyright © 2017 Elsevier B.V. All rights reserved.

Meta-Analyses of Seven of NIDA’s Principles of Drug Addiction Treatment

PubMed Central

Pearson, Frank S.; Prendergast, Michael L.; Podus, Deborah; Vazan, Peter; Greenwell, Lisa; Hamilton, Zachary

2011-01-01

Seven of the 13 Principles of Drug Addiction Treatment disseminated by the National Institute on Drug Abuse (NIDA) were meta-analyzed as part of the Evidence-based Principles of Treatment (EPT) project. By averaging outcomes over the diverse programs included in EPT, we found that five of the NIDA principles examined are supported: matching treatment to the client’s needs; attending to the multiple needs of clients; behavioral counseling interventions; treatment plan reassessment; and counseling to reduce risk of HIV. Two of the NIDA principles are not supported: remaining in treatment for an adequate period of time and frequency of testing for drug use. These weak effects could be the result of the principles being stated too generally to apply to the diverse interventions and programs that exist or of unmeasured moderator variables being confounded with the moderators that measured the principles. Meta-analysis should be a standard tool for developing principles of effective treatment for substance use disorders. PMID:22119178

Do Medicare Beneficiaries Living With HIV/AIDS Choose Prescription Drug Plans That Minimize Their Total Spending?

PubMed

Desmond, Katherine A; Rice, Thomas H; Leibowitz, Arleen A

2017-01-01

This article examines whether California Medicare beneficiaries with HIV/AIDS choose Part D prescription drug plans that minimize their expenses. Among beneficiaries without low-income supplementation, we estimate the excess cost, and the insurance policy and beneficiary characteristics responsible, when the lowest cost plan is not chosen. We use a cost calculator developed for this study, and 2010 drug use data on 1453 California Medicare beneficiaries with HIV who were taking antiretroviral medications. Excess spending is defined as the difference between projected total spending (premium and cost sharing) for the beneficiary's current drug regimen in own plan vs spending for the lowest cost alternative plan. Regression analyses related this excess spending to individual and plan characteristics. We find that beneficiaries pay more for Medicare Part D plans with gap coverage and no deductible. Higher premiums for more extensive coverage exceeded savings in deductible and copayment/coinsurance costs. We conclude that many beneficiaries pay for plan features whose costs exceed their benefits.

Evaluation of a peer-led drug abuse risk reduction project for runaway/homeless youths.

PubMed

Fors, S W; Jarvis, S

1995-01-01

The purpose of this study was to evaluate the Drug Prevention in Youth risk reduction program that was implemented in shelters for runaway/homeless youths in the Southeastern United States. The program focuses on knowledge, attitudes and skills that can help this group of high risk young people minimize the serious negative consequences of drug abuse. An evaluation strategy was developed so comparisons could be made between peer-led, adult-led and non-intervention groups. Dependent samples t tests and least squares ANCOVAS were used to measure pretest-posttest differences both within and between groups. Results indicate that the peer-led groups were more successful than the other two groups, and that program effects were the most powerful with the youngest group of shelter clients. Process evaluation revealed important factors related to group leader training and group management. It is concluded that well-trained and motivated peer/near peer leaders have particularly valuable contributions to make with regard to drug abuse risk reduction for shelter clients.

Do Medicare Beneficiaries Living With HIV/AIDS Choose Prescription Drug Plans That Minimize Their Total Spending?

PubMed Central

Desmond, Katherine A.; Rice, Thomas H.; Leibowitz, Arleen A.

2017-01-01

This article examines whether California Medicare beneficiaries with HIV/AIDS choose Part D prescription drug plans that minimize their expenses. Among beneficiaries without low-income supplementation, we estimate the excess cost, and the insurance policy and beneficiary characteristics responsible, when the lowest cost plan is not chosen. We use a cost calculator developed for this study, and 2010 drug use data on 1453 California Medicare beneficiaries with HIV who were taking antiretroviral medications. Excess spending is defined as the difference between projected total spending (premium and cost sharing) for the beneficiary’s current drug regimen in own plan vs spending for the lowest cost alternative plan. Regression analyses related this excess spending to individual and plan characteristics. We find that beneficiaries pay more for Medicare Part D plans with gap coverage and no deductible. Higher premiums for more extensive coverage exceeded savings in deductible and copayment/coinsurance costs. We conclude that many beneficiaries pay for plan features whose costs exceed their benefits. PMID:28990452

Effects of Academic Service Learning in Drug Misuse and Addiction on Students’ Learning Preferences and Attitudes Toward Harm Reduction

PubMed Central

Kabli, Noufissa; Liu, Ben; Seifert, Tricia

2013-01-01

Objective. To examine academic service-learning pedagogy on student learning and perceptions of drug misuse and addiction. Design. Third- and fourth-year pharmacology students were exposed to an academic service-learning pedagogy that integrated a community service experience with lectures, in-class discussions and debates, group projects, a final paper, and an examination. Reflective writing assignments throughout the course required students to assimilate and apply what they had learned in the classroom to what they learned in their community placement. Assessment. Changes in students’ responses on pre- and post-course survey instruments reflected shifts toward higher-order thinking. Also, subjective student-learning modalities shifted toward learning by writing. Students’ perspectives and attitudes allowed improved context of issues associated with drug misuse and harm reduction models. Conclusion. Academic service-learning pedagogy contributes to developing adaptable, well-rounded, engaged learners who become more compassionate and pragmatic in addressing scientific and social questions relating to drug addiction. PMID:23610481

YouTube, "Drug Videos" and Drugs Education

ERIC Educational Resources Information Center

Manning, Paul

2013-01-01

Aims: This article reports on findings to emerge from a project examining YouTube "drug videos" in the light of an emerging literature on the relationship between YouTube and health education. The aim of this article is to describe the variety of discourses circulated by the "drug videos" available on YouTube and to consider…

In Vivo Measurement of Drug Efficacy in Breast Cancer

DTIC Science & Technology

2015-10-01

treatment. 15. SUBJECT TERMS Breast Cancer, Intravital Imaging , Nanoparticles, Pharmacokinetics/ Pharmacodynamics, Chemotherapy, Drug Distribution 16...drug testing in year 2 of the project. 2. KEYWORDS Breast Cancer, Intravital Imaging , Nanoparticles, Pharmacokinetics/ Pharmacodynamics, Chemotherapy...left side of the diagram displays the overall proposed algorithm for analyzing intravital images and determining drug concentration. This algorithm is

An Alternative to the Physiological Psychology Laboratory: Identification of an Unknown Drug Through Behavioral Testing.

ERIC Educational Resources Information Center

Schumacher, Susan J.

1982-01-01

A laboratory project introduced physiological psychology students to research by requiring them to identify an unknown drug given to laboratory animals. Students read material about drugs and animal drug studies, designed behavioral tests, constructed the testing apparatus, conducted the tests, and wrote progress reports. (SR)

The ACTwatch project: methods to describe anti-malarial markets in seven countries.

PubMed

Shewchuk, Tanya; O'Connell, Kathryn A; Goodman, Catherine; Hanson, Kara; Chapman, Steven; Chavasse, Desmond

2011-10-31

Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012.ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision-making. ACTwatch is a unique multi-country research project that threads together anti-malarial supply and consumer behaviour to provide an evidence base to policy makers that can help determine where interventions may positively impact access to and use of quality-assured ACT and RDTs. Because of its ability to detect change over time, it is well suited to monitor the effects of policy or intervention developments in a country.

The ACTwatch project: methods to describe anti-malarial markets in seven countries

PubMed Central

2011-01-01

Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision-making. Conclusions ACTwatch is a unique multi-country research project that threads together anti-malarial supply and consumer behaviour to provide an evidence base to policy makers that can help determine where interventions may positively impact access to and use of quality-assured ACT and RDTs. Because of its ability to detect change over time, it is well suited to monitor the effects of policy or intervention developments in a country. PMID:22039780

A Network Approach to Rare Disease Modeling

NASA Astrophysics Data System (ADS)

Ghiassian, Susan; Rabello, Sabrina; Sharma, Amitabh; Wiest, Olaf; Barabasi, Albert-Laszlo

2011-03-01

Network approaches have been widely used to better understand different areas of natural and social sciences. Network Science had a particularly great impact on the study of biological systems. In this project, using biological networks, candidate drugs as a potential treatment of rare diseases were identified. Developing new drugs for more than 2000 rare diseases (as defined by ORPHANET) is too expensive and beyond expectation. Disease proteins do not function in isolation but in cooperation with other interacting proteins. Research on FDA approved drugs have shown that most of the drugs do not target the disease protein but a protein which is 2 or 3 steps away from the disease protein in the Protein-Protein Interaction (PPI) network. We identified the already known drug targets in the disease gene's PPI subnetwork (up to the 3rd neighborhood) and among them those in the same sub cellular compartment and higher coexpression coefficient with the disease gene are expected to be stronger candidates. Out of 2177 rare diseases, 1092 were found not to have any drug target. Using the above method, we have found the strongest candidates among the rest in order to further experimental validations.

Illicit drug policy in Spain: the opinion of health and legal professionals.

PubMed

Rossi, Paola; Blay, Ester; Costela, Víctor; Torrens, Marta

2018-01-01

The high frequency of criminal behaviour and related legal problems associated with substance addiction generates a field of interaction between legal and healthcare systems. This study was developed as a multicentre project to investigate the opinions of professionals from legal and healthcare systems about policies on illegal drugs and their implementation in practice. A multiple choice questionnaire designed ad hoc was administered to a sample of 230 professionals from legal and healthcare fields working in the cities of Barcelona, Granada and Bilbao. The questionnaire included sociodemographic and work-related data, and assessed interviewees' information about the response to drug-related crime and opinion on drug policy issues. This article presents the results from Spain. The main results showed that both groups of professionals value alternative measures to imprisonment (AMI) as useful tools to prevent offenses related to drug use and claim a broader application of AMI. They also evaluated positively the regulations on cannabis use in effect. Though the attitude of healthcare professionals towards the application of AMI is more permissive, both groups favour restricting these sanctions in cases of recidivism. Both groups show mild satisfaction with the current addiction healthcare system and express dissatisfaction with actual drug policies in Spain.

[Discussion on efficacy evaluation thought and method for innovation medicine of Chinese herbal compound formula based on clinical application characteristics].

PubMed

Sun, Jian-Ning; Sun, Wen-Yan; Dong, Shi-Fen

2017-03-01

The Chinese herbal compound formula preparation was made based on theory of Chinese medicine, which was confirmed by long period clinical application, and with multi-compound and multi-target characteristics. During the exploitation process of innovation medicine of Chinese herbal compound formula, selecting and speeding up the research development of drugs with clinical value shall be paid more attention, and as request of rules involved in new drug research and development, the whole process management should be carried out, including project evaluation, manufacturing process determination, establishment of quality control standards, evaluation for pharmacological and toxic effect, as well as new drug application process. This reviews was aimed to give some proposals for pharmacodynamics research methods involved in exploration of Chinese herbal compound formula preparation, including： ①the endpoint criteria should meet the clinical attribution of new drugs; ②the pre-clinical pharmacodynamics evaluation should be carried on appropriate animal models according to the characteristics of diagnosis and therapy of Chinese medicine and observation indexes; ③during the innovation of drug for infants and children, information on drug action conforming to physiological characteristics of infants and children should be supplied, and the pharmacodynamics and toxicology research shall be conducted in immature rats according to the body weight of children. In a summary, the clinical application characteristics are the important criteria for evaluation of pharmacological effect of innovation medicine of Chinese herbal compound formula. Copyright© by the Chinese Pharmaceutical Association.

Human genetics: international projects and personalized medicine.

PubMed

Apellaniz-Ruiz, Maria; Gallego, Cristina; Ruiz-Pinto, Sara; Carracedo, Angel; Rodríguez-Antona, Cristina

2016-03-01

In this article, we present the progress driven by the recent technological advances and new revolutionary massive sequencing technologies in the field of human genetics. We discuss this knowledge in relation with drug response prediction, from the germline genetic variation compiled in the 1000 Genomes Project or in the Genotype-Tissue Expression project, to the phenome-genome archives, the international cancer projects, such as The Cancer Genome Atlas or the International Cancer Genome Consortium, and the epigenetic variation and its influence in gene expression, including the regulation of drug metabolism. This review is based on the lectures presented by the speakers of the Symposium "Human Genetics: International Projects & New Technologies" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held on the 20th and 21st of April 2015.

An empirical approach to estimate near-infra-red photon propagation and optically induced drug release in brain tissues

NASA Astrophysics Data System (ADS)

Prabhu Verleker, Akshay; Fang, Qianqian; Choi, Mi-Ran; Clare, Susan; Stantz, Keith M.

2015-03-01

The purpose of this study is to develop an alternate empirical approach to estimate near-infra-red (NIR) photon propagation and quantify optically induced drug release in brain metastasis, without relying on computationally expensive Monte Carlo techniques (gold standard). Targeted drug delivery with optically induced drug release is a noninvasive means to treat cancers and metastasis. This study is part of a larger project to treat brain metastasis by delivering lapatinib-drug-nanocomplexes and activating NIR-induced drug release. The empirical model was developed using a weighted approach to estimate photon scattering in tissues and calibrated using a GPU based 3D Monte Carlo. The empirical model was developed and tested against Monte Carlo in optical brain phantoms for pencil beams (width 1mm) and broad beams (width 10mm). The empirical algorithm was tested against the Monte Carlo for different albedos along with diffusion equation and in simulated brain phantoms resembling white-matter (μs'=8.25mm-1, μa=0.005mm-1) and gray-matter (μs'=2.45mm-1, μa=0.035mm-1) at wavelength 800nm. The goodness of fit between the two models was determined using coefficient of determination (R-squared analysis). Preliminary results show the Empirical algorithm matches Monte Carlo simulated fluence over a wide range of albedo (0.7 to 0.99), while the diffusion equation fails for lower albedo. The photon fluence generated by empirical code matched the Monte Carlo in homogeneous phantoms (R2=0.99). While GPU based Monte Carlo achieved 300X acceleration compared to earlier CPU based models, the empirical code is 700X faster than the Monte Carlo for a typical super-Gaussian laser beam.

Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

PubMed

Gough, Albert H; Chen, Ning; Shun, Tong Ying; Lezon, Timothy R; Boltz, Robert C; Reese, Celeste E; Wagner, Jacob; Vernetti, Lawrence A; Grandis, Jennifer R; Lee, Adrian V; Stern, Andrew M; Schurdak, Mark E; Taylor, D Lansing

2014-01-01

One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.

Impact of data base structure in a successful in vitro-in vivo correlation for pharmaceutical products.

PubMed

Roudier, B; Davit, B; Schütz, H; Cardot, J-M

2015-01-01

The in vitro-in vivo correlation (IVIVC) (Food and Drug Administration 1997) aims to predict performances in vivo of a pharmaceutical formulation based on its in vitro characteristics. It is a complex process that (i) incorporates in a gradual and incremental way a large amount of information and (ii) requires information from different properties (formulation, analytical, clinical) and associated dedicated treatments (statistics, modeling, simulation). These results in many studies that are initiated and integrated into the specifications (quality target product profile, QTPP). This latter defines the appropriate experimental designs (quality by design, QbD) (Food and Drug Administration 2011, 2012) whose main objectives are determination (i) of key factors of development and manufacturing (critical process parameters, CPPs) and (ii) of critical points of physicochemical nature relating to active ingredients (API) and critical quality attribute (CQA) which may have implications in terms of efficiency, safety, and inoffensiveness for the patient, due to their non-inclusion. These processes generate a very large amount of data that is necessary to structure. In this context, the storage of information in a database (DB) and the management of this database (database management system, DBMS) become an important issue for the management of projects and IVIVC and more generally for development of new pharmaceutical forms. This article describes the implementation of a prototype object-oriented database (OODB) considered as a tool, which is helpful for decision taking, responding in a structured and consistent way to the issues of project management of IVIVC (including bioequivalence and bioavailability) (Food and Drug Administration 2003) necessary for the implementation of QTPP.

China's role as a global health donor in Africa: what can we learn from studying under reported resource flows?

PubMed

Grépin, Karen A; Fan, Victoria Y; Shen, Gordon C; Chen, Lucy

2014-12-30

There is a growing recognition of China's role as a global health donor, in particular in Africa, but there have been few systematic studies of the level, destination, trends, or composition of these development finance flows or a comparison of China's engagement as a donor with that of more traditional global health donors. Using newly released data from AidData on China's development finance activities in Africa, developed to track under reported resource flows, we identified 255 health, population, water, and sanitation (HPWS) projects from 2000-2012, which we descriptively analyze by activity sector, recipient country, project type, and planned activity. We compare China's activities to projects from traditional donors using data from the OECD's Development Assistance Committee (DAC) Creditor Reporting System. Since 2000, China increased the number of HPWS projects it supported in Africa and health has increased as a development priority for China. China's contributions are large, ranking it among the top 10 bilateral global health donors to Africa. Over 50% of the HPWS projects target infrastructure, 40% target human resource development, and the provision of equipment and drugs is also common. Malaria is an important disease priority but HIV is not. We find little evidence that China targets health aid preferentially to natural resource rich countries. China is an important global health donor to Africa but contrasts with traditional DAC donors through China's focus on health system inputs and on malaria. Although better data are needed, particularly through more transparent aid data reporting across ministries and agencies, China's approach to South-South cooperation represents an important and distinct source of financial assistance for health in Africa.

Fragment-Based Drug Discovery in the Bromodomain and Extra-Terminal Domain Family.

PubMed

Radwan, Mostafa; Serya, Rabah

2017-08-01

Bromodomain and extra-terminal domain (BET) inhibition has emerged recently as a potential therapeutic target for the treatment of many human disorders such as atherosclerosis, inflammatory disorders, chronic obstructive pulmonary disease (COPD), some viral infections, and cancer. Since the discovery of the two potent inhibitors, I-BET762 and JQ1, different research groups have used different techniques to develop novel potent and selective inhibitors. In this review, we will be concerned with the trials that used fragment-based drug discovery (FBDD) approaches to discover or optimize BET inhibitors, also showing fragments that can be further optimized in future projects to reach novel potent BET inhibitors. © 2017 Deutsche Pharmazeutische Gesellschaft.

Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus

PubMed Central

Sweeney, Noreena L.; Lipker, Lauren; Hanson, Alicia M.; Bohl, Chris J.; Engel, Katie E.; Kalous, Kelsey S.; Stemper, Mary E.; Sem, Daniel S.; Schwan, William R.

2017-01-01

The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Staphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the Mycobacterium tuberculosis thioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability against S. aureus strains, including drug-resistant clinical isolates. The findings support continued development of the pyrazolone compounds as potential anti-S. aureus antibiotics. PMID:28134858

Creating a Tiny Human Body on a Chip

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunsberger, Maren; Soscia, Dave; Moya, Monica

LLNL science communicator Maren Hunsberger takes us "Inside the Lab" to learn about the iChip (In-vitro Chip-based Human Investigational Platform) project at Lawrence Livermore National Laboratory. "One application of the iChip system would be to develop new pharmaceutical drugs," explains Dave Soscia, LLNL postdoc. "When you test in a mouse for example, it's not as close to the human system as you can get. If we can take human cells and put them on devices and actually mimic the structure and function of the organ systems in the human, we can actually replace animal testing and even make a bettermore » system for testing pharmaceutical drugs."« less

FAF-Drugs3: a web server for compound property calculation and chemical library design

PubMed Central

Lagorce, David; Sperandio, Olivier; Baell, Jonathan B.; Miteva, Maria A.; Villoutreix, Bruno O.

2015-01-01

Drug attrition late in preclinical or clinical development is a serious economic problem in the field of drug discovery. These problems can be linked, in part, to the quality of the compound collections used during the hit generation stage and to the selection of compounds undergoing optimization. Here, we present FAF-Drugs3, a web server that can be used for drug discovery and chemical biology projects to help in preparing compound libraries and to assist decision-making during the hit selection/lead optimization phase. Since it was first described in 2006, FAF-Drugs has been significantly modified. The tool now applies an enhanced structure curation procedure, can filter or analyze molecules with user-defined or eight predefined physicochemical filters as well as with several simple ADMET (absorption, distribution, metabolism, excretion and toxicity) rules. In addition, compounds can be filtered using an updated list of 154 hand-curated structural alerts while Pan Assay Interference compounds (PAINS) and other, generally unwanted groups are also investigated. FAF-Drugs3 offers access to user-friendly html result pages and the possibility to download all computed data. The server requires as input an SDF file of the compounds; it is open to all users and can be accessed without registration at http://fafdrugs3.mti.univ-paris-diderot.fr. PMID:25883137

Innovation strategies for generic drug companies: moving into supergenerics.

PubMed

Ross, Malcolm S F

2010-04-01

Pharmaceutical companies that market generic products generally are not regarded as innovators, but rather as companies that produce copies of originator products to be launched at patent expiration. However, many generics companies have developed excellent scientific innovative skills in an effort to circumvent the defense patents of originator companies. More patents per product, in terms of both drug substances (process patents and polymorph patents) and formulations, are issued to generics companies than to companies that are traditionally considered to be 'innovators'. This quantity of issued patents highlights the technical knowledge and skill sets that are available in generics companies. In order to adopt a completely innovative model (ie, the development of NCEs), a generics company would require a completely new set of skills in several fields, including a sufficient knowledge base, project and risk management experience, and capability for clinical data evaluation. However, with relatively little investment, generics companies should be able to progress into the so-called 'supergeneric' drug space - an area of innovation that reflects the existing competencies of both innovative and generics companies.

Prospects for new antibacterials: can we do better?

PubMed

Georgopapadakou, Nafsika H

2014-02-01

Bacterial resistance to antibacterial drugs has been increasing relentlessly over the past two decades. This includes common residents of the human body: Staphylococcus aureus (methicillin resistant or MRSA) Enteroccus faecalis and E. faecium (vancomycin resistant or VRE): Enterobacteriaceae (multiresistant, carbapenems included or CRE). It also includes environmental, opportunistic, but intrinsically multiresistant species: Pseudomonas aeruginosa and Acinetobacter baumannii. Financial considerations have curtailed R&D activity in the antibacterial field in all, but a couple of large pharmaceutical companies and small biotech companies have largely been unable to fill the drug discovery gap. Antibacterials currently under development have targeted, almost exclusively, Gram-positive bacteria; hence, greater effort must be directed against Gram-negative bacteria, particularly enterobacteria. There also has to be more transparency and care in clinical development. To get ahead of the problem of resistance, we must look for first-in-class antibacterials and new targets. The need to innovate is best addressed through partnerships between drug-makers and public institutions. Such partnerships would provide a long-term view and stability to projects, but also balance the interests of corporate and public stakeholders.

PeptideNavigator: An interactive tool for exploring large and complex data sets generated during peptide-based drug design projects.

PubMed

Diller, Kyle I; Bayden, Alexander S; Audie, Joseph; Diller, David J

2018-01-01

There is growing interest in peptide-based drug design and discovery. Due to their relatively large size, polymeric nature, and chemical complexity, the design of peptide-based drugs presents an interesting "big data" challenge. Here, we describe an interactive computational environment, PeptideNavigator, for naturally exploring the tremendous amount of information generated during a peptide drug design project. The purpose of PeptideNavigator is the presentation of large and complex experimental and computational data sets, particularly 3D data, so as to enable multidisciplinary scientists to make optimal decisions during a peptide drug discovery project. PeptideNavigator provides users with numerous viewing options, such as scatter plots, sequence views, and sequence frequency diagrams. These views allow for the collective visualization and exploration of many peptides and their properties, ultimately enabling the user to focus on a small number of peptides of interest. To drill down into the details of individual peptides, PeptideNavigator provides users with a Ramachandran plot viewer and a fully featured 3D visualization tool. Each view is linked, allowing the user to seamlessly navigate from collective views of large peptide data sets to the details of individual peptides with promising property profiles. Two case studies, based on MHC-1A activating peptides and MDM2 scaffold design, are presented to demonstrate the utility of PeptideNavigator in the context of disparate peptide-design projects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control of Ebola hemorrhagic fever: vaccine development and our Ebola project in Sierra Leone.

PubMed

Watanabe, Tokiko; Kawaoka, Yoshihiro

2016-01-01

Since December 2013, West Africa has experienced the worst Ebola virus outbreak in recorded history. Of the 28,639 cases reported to the World Health Organization as of March 2016, nearly half (14,124) occurred in Sierra Leone. With a case fatality rate of approximately 40%, this outbreak has claimed the lives of 11,316 individuals. No FDA-approved vaccines or drugs are available to prevent or treat Ebola virus infection. Experimental vaccines and therapies are being developed; however, their safety and efficacy are still being evaluated. Therefore, there is an urgent need to develop control measures to prevent or limit future Ebola virus outbreaks.Previously, we developed a replication-defective Ebola virus that lacks the coding region for the essential viral transcription activator VP30 (Ebola ΔVP30 virus). Here, we evaluated the vaccine efficacy of Ebola ΔVP30 virus in a non-human primate model and describe our collaborative Ebola project in Sierra Leone.

Ayurgenomics for stratified medicine: TRISUTRA consortium initiative across ethnically and geographically diverse Indian populations.

PubMed

Prasher, Bhavana; Varma, Binuja; Kumar, Arvind; Khuntia, Bharat Krushna; Pandey, Rajesh; Narang, Ankita; Tiwari, Pradeep; Kutum, Rintu; Guin, Debleena; Kukreti, Ritushree; Dash, Debasis; Mukerji, Mitali

2017-02-02

Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-individual variability "Prakriti" in development and administration of drug in an individualized manner. Prakriti of an individual largely determines responsiveness to external environment including drugs as well as susceptibility to diseases. Prakriti has also been shown to have molecular and genomic correlates. We highlight how integration of Prakriti concepts can augment the efficiency of drug discovery and development programs through a unique initiative of Ayurgenomics TRISUTRA consortium. Five aspects that have been carried out are (1) analysis of variability in FDA approved pharmacogenomics genes/SNPs in exomes of 72 healthy individuals including predominant Prakriti types and matched controls from a North Indian Indo-European cohort (2) establishment of a consortium network and development of five genetically homogeneous cohorts from diverse ethnic and geo-climatic background (3) identification of parameters and development of uniform standard protocols for objective assessment of Prakriti types (4) development of protocols for Prakriti evaluation and its application in more than 7500 individuals in the five cohorts (5) Development of data and sample repository and integrative omics pipelines for identification of genomic correlates. Highlight of the study are (1) Exome sequencing revealed significant differences between Prakriti types in 28 SNPs of 11 FDA approved genes of pharmacogenomics relevance viz. CYP2C19, CYP2B6, ESR1, F2, PGR, HLA-B, HLA-DQA1, HLA-DRB1, LDLR, CFTR, CPS1. These variations are polymorphic in diverse Indian and world populations included in 1000 genomes project. (2) Based on the phenotypic attributes of Prakriti we identified anthropometry for anatomical features, biophysical parameters for skin types, HRV for autonomic function tests, spirometry for vital capacity and gustometry for taste thresholds as objective parameters. (3) Comparison of Prakriti phenotypes across different ethnic, age and gender groups led to identification of invariant features as well as some that require weighted considerations across the cohorts. Considering the molecular and genomics differences underlying Prakriti and relevance in disease pharmacogenomics studies, this novel integrative platform would help in identification of differently susceptible and drug responsive population. Additionally, integrated analysis of phenomic and genomic variations would not only allow identification of clinical and genomic markers of Prakriti for application in personalized medicine but also its integration in drug discovery and development programs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Tentative Drug Use Scale: A Quick and Relatively Problem Free Outcome Measure for Drug Abuse Prevention Projects

ERIC Educational Resources Information Center

Horan, John J.; Williams, John M.

1975-01-01

Difficulties involved with the evaluation of drug abuse prevention programs are numerous. Tentative Drug Use Scale (TDUS) was designed in response to a number of specific problems associated with obtaining behavioral data. Advantages of this scale over others are discussed. Reliability and validity information are provided. (Author)

Bringing the Evidence Base to the Alcohol and Other Drugs Sector

ERIC Educational Resources Information Center

Shelling, Jane

2009-01-01

The National Drug Sector Information Service is committed to supporting those who work to prevent or reduce the harm to individuals, families, communities and the nation caused by alcohol and other drugs. This paper describes a project to assist particular members of the alcohol and other drugs sector to improve quality and the transfer of…

Health for All. Project WHERE (World Health Education Resources Exchange). Field Tested and Revised. Teenage Health Teaching Modules.

ERIC Educational Resources Information Center

American Association for World Health, Washington, DC.

Every two seconds somewhere in the world a child dies from a preventable disease. Millions lack access to safe drinking water. Smoking, alcoholism, and drug abuse are on the increase in developing nations. In the United States, experts estimate that one out of every ten people, a majority of them women and children, go to bed hungry, and the…

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2011-08-01

induced RSR breast cell model, in which cyclin E can be conditionally induced to trigger RSR in normal breast cells. Using this model, we demonstrated...which makes these defects effective targets for both breast cancer prevention and breast cancer treatment. This project is to use cutting-edge...defective RSR; identify drugs that target these defects; and develop RSR-defect-targeting nanoparticles for diagnostic imaging, prevention, and

Drug Development and Conservation of Biodiversity in West and Central Africa.

DTIC Science & Technology

1998-10-01

identifications. A topography map has been created for the first 25-ha. Many researhers within the project have traveled to collaborate on plot work, data entry...over 50 papers on tropical forest dynamics, diversity, stand distribution, canopy biology , reproductive biology , conservation, and management. The...Climate Change", followed by a reception. The panel was co-sponsored by Smithsonian’s Institute of Conservation Biology and CTFS. The panelist

SOCIAL PSYCHOLOGICAL DYNAMICS OF ENHANCED HIV RISK REDUCTION AMONG PEER INTERVENTIONISTS

PubMed Central

Dickson-Gomez, Julia; Weeks, Margaret R.; Convey, Mark; Li, Jianghong

2014-01-01

The authors present a model of interactive social psychological and relational feedback processes leading to human immunodeficiency virus (HIV) risk reduction behavior change among active drug users trained as Peer Health Advocates (PHAs). The model is supported by data from qualitative interviews with PHAs and members of their drug-using networks in the Risk Avoidance Partnership (RAP) project. Results suggest three mutually reinforcing social psychological processes that motivate PHAs to provide HIV prevention intervention to their peers and to reduce their own risk behaviors: development of a prosocial identity, positive social reinforcement from drug users and community members, and cognitive dissonance associated with continued risk behavior while engaging in health advocacy. These processes directly influence peer interventionists’ motivation and efficacy to continue giving intervention to their peers, and to reduce their HIV risk behaviors. The authors discuss implications of the model for continued research on effective HIV prevention in high-risk groups. PMID:25414528

Controlled Release System for Localized and Sustained Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Rodriguez, Lidia Betsabe

Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is possible to prepare biodegradable microparticles with a uniform size distribution and high drug loading efficiency. However, this could only be achieved with a hybrid system consisting of chitosan matrix interior and then exterior coating of PLGA or PLA. A two layer coating of PLGA 50:50 was shown to be optimal with sustainable controlled drug release for almost 5 days and with 91% of degradation (weight loss) in 8 weeks.

Updates on drug-target network; facilitating polypharmacology and data integration by growth of DrugBank database.

PubMed

Barneh, Farnaz; Jafari, Mohieddin; Mirzaie, Mehdi

2016-11-01

Network pharmacology elucidates the relationship between drugs and targets. As the identified targets for each drug increases, the corresponding drug-target network (DTN) evolves from solely reflection of the pharmaceutical industry trend to a portrait of polypharmacology. The aim of this study was to evaluate the potentials of DrugBank database in advancing systems pharmacology. We constructed and analyzed DTN from drugs and targets associations in the DrugBank 4.0 database. Our results showed that in bipartite DTN, increased ratio of identified targets for drugs augmented density and connectivity of drugs and targets and decreased modular structure. To clear up the details in the network structure, the DTNs were projected into two networks namely, drug similarity network (DSN) and target similarity network (TSN). In DSN, various classes of Food and Drug Administration-approved drugs with distinct therapeutic categories were linked together based on shared targets. Projected TSN also showed complexity because of promiscuity of the drugs. By including investigational drugs that are currently being tested in clinical trials, the networks manifested more connectivity and pictured the upcoming pharmacological space in the future years. Diverse biological processes and protein-protein interactions were manipulated by new drugs, which can extend possible target combinations. We conclude that network-based organization of DrugBank 4.0 data not only reveals the potential for repurposing of existing drugs, also allows generating novel predictions about drugs off-targets, drug-drug interactions and their side effects. Our results also encourage further effort for high-throughput identification of targets to build networks that can be integrated into disease networks. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Developmental considerations for substance use interventions from middle school through college.

PubMed

D'Amico, Elizabeth J; Ellickson, Phyllis L; Wagner, Eric F; Turrisi, Rob; Fromme, Kim; Ghosh-Dastidar, Bonnie; Longshore, Douglas L; McCaffrey, Daniel F; Montgomery, Marilyn J; Schonlau, Matthias; Wright, Dale

2005-03-01

This article summarizes a symposium organized by Dr. Elizabeth D'Amico and presented at the 2004 Annual Meeting of the Research Society on Alcoholism in Vancouver, Canada. The four presentations illustrate the importance of creating substance use interventions that are developmentally appropriate for youth. They represent innovative approaches to working with preteens, teenagers, and young adults. Dr. D'Amico's paper describes her research on the development of a voluntary brief intervention targeting alcohol use among middle school students. Findings indicated that by using school and community input, she was able to obtain a diverse a sample of youth across grades, sex, ethnicity, and substance use status. Dr. Ellickson's paper describes her research on Project ALERT, a school-based prevention program for middle school youth. Her findings indicate that Project ALERT worked for students at all levels of risk (low, moderate, and high) and for all students combined. Dr. Wagner's Teen Intervention Project was a randomized clinical trial to test the efficacy of a standardized Student Assistance Program for treating middle and high school students with alcohol and other drug problems. The study provided a unique opportunity to begin to examine how development may impact response to an alcohol or other drug intervention. Dr. Turrisi's paper examined processes underlying the nature of the effects of a parent intervention on college student drinking tendencies. Findings suggested that the parent intervention seems to have its impact on student drinking by reducing the influence of negative communications and decreasing the susceptibility of influences from closest friends. Dr. Kim Fromme provided concluding remarks.

[Salvia divinorum--representation of a new drug in the Internet].

PubMed

Siemann, H; Specka, M; Schifano, F; Deluca, P; Scherbaum, N

2006-05-01

The German pages of the Internet were searched for the presence of the hallucinogenic herbal drug Salvia divinorum, which is not dealt with in current addiction medicine or psychiatric text books. The investigation is part of the EU sponsored project "Psychonaut" as preparatory work for the development of an Internet-based early warning system. The first 100 websites of the search using "Salvia divinorum" were compared with the search results for "cannabis" and "LSD". The following aspects of the sites were especially analyzed: the originator, marketing of drugs, and the attitude towards drug use. Salvia was offered for sale on approximately a third of the sites (29%); cannabis and LSD were not marketed on any sites. Official websites such as those from governmental organizations or universities were seldom found when searching for "Salvia divinorum", and then only under the last hits. The percentage of institutional sites (e. g. public organizations) were 12% with Salvia, 21% with cannabis, and 38% with LSD. A drug-friendly attitude was found at 64 % of the sites with regard to Salvia, 58% for cannabis, and 24% for LSD. The drug help system must be aware of that the Internet is a source of drug-related information, and of drug trade. As this investigation shows, sites often have a drug-friendly attitude. The low availability of official information on Salvia divinorum (also outside the Internet) relative to the presence of drug-friendly or drug trading sites is an indication that new trends of drug consumption can be tracked in the Internet before they will be found in official literature.

Modern approaches to accelerate discovery of new antischistosomal drugs.

PubMed

Neves, Bruno Junior; Muratov, Eugene; Machado, Renato Beilner; Andrade, Carolina Horta; Cravo, Pedro Vitor Lemos

2016-06-01

The almost exclusive use of only praziquantel for the treatment of schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes. Consequently, there is an urgent need for new antischistosomal drugs. The identification of leads and the generation of high quality data are crucial steps in the early stages of schistosome drug discovery projects. Herein, the authors focus on the current developments in antischistosomal lead discovery, specifically referring to the use of automated in vitro target-based and whole-organism screens and virtual screening of chemical databases. They highlight the strengths and pitfalls of each of the above-mentioned approaches, and suggest possible roadmaps towards the integration of several strategies, which may contribute for optimizing research outputs and led to more successful and cost-effective drug discovery endeavors. Increasing partnerships and access to funding for drug discovery have strengthened the battle against schistosomiasis in recent years. However, the authors believe this battle also includes innovative strategies to overcome scientific challenges. In this context, significant advances of in vitro screening as well as computer-aided drug discovery have contributed to increase the success rate and reduce the costs of drug discovery campaigns. Although some of these approaches were already used in current antischistosomal lead discovery pipelines, the integration of these strategies in a solid workflow should allow the production of new treatments for schistosomiasis in the near future.

Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data.

PubMed

Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

2016-07-05

Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification problem, however, models based on pathway level data performed significantly better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development.

Deep learning applications for predicting pharmacological properties of drugs and drug repurposing using transcriptomic data

PubMed Central

Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

2016-01-01

Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF‐7 and PC‐3 cell lines from the LINCS project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled dataset of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both gene and pathway level classification, DNN convincingly outperformed support vector machine (SVM) model on every multiclass classification problem, however, models based on a pathway level classification perform better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development. PMID:27200455

Project-focused activity and knowledge tracker: a unified data analysis, collaboration, and workflow tool for medicinal chemistry project teams.

PubMed

Brodney, Marian D; Brosius, Arthur D; Gregory, Tracy; Heck, Steven D; Klug-McLeod, Jacquelyn L; Poss, Christopher S

2009-12-01

Advances in the field of drug discovery have brought an explosion in the quantity of data available to medicinal chemists and other project team members. New strategies and systems are needed to help these scientists to efficiently gather, organize, analyze, annotate, and share data about potential new drug molecules of interest to their project teams. Herein we describe a suite of integrated services and end-user applications that facilitate these activities throughout the medicinal chemistry design cycle. The Automated Data Presentation (ADP) and Virtual Compound Profiler (VCP) processes automate the gathering, organization, and storage of real and virtual molecules, respectively, and associated data. The Project-Focused Activity and Knowledge Tracker (PFAKT) provides a unified data analysis and collaboration environment, enhancing decision-making, improving team communication, and increasing efficiency.

Substance abuse treatment management information systems: balancing federal, state, and service provider needs.

PubMed

Camp, J M; Krakow, M; McCarty, D; Argeriou, M

1992-01-01

There is increased interest in documenting the characteristics and treatment outcomes of clients served with Alcohol, Drug Abuse, and Mental Health Block Grant funds. The evolution of federal client-based management systems for substance abuse treatment services demonstrates that data collection systems are important but require continued support. A review of the Massachusetts substance abuse management information system illustrates the utility of a client-based data set. The development and implementation of a comprehensive information system require overcoming organizational barriers and project delays, fostering collaborative efforts among staff from diverse agencies, and employing considerable resources. In addition, the need to develop mechanisms for increasing the reliability of the data and ongoing training for the users is presented. Finally, three applications of the management information system's role in shaping policy are reviewed: developing services for special populations (communities of color, women, and pregnant substance abusers, and injection drug users), utilizing MIS data for evaluation purposes, and determining funding allocations.

21 CFR 886.1810 - Tangent screen (campimeter).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tangent screen (campimeter). 886.1810 Section 886.1810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... a patient's visual field. This generic type of device includes projection tangent screens, target...

Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd

PubMed Central

Wang, Zichen; Monteiro, Caroline D.; Jagodnik, Kathleen M.; Fernandez, Nicolas F.; Gundersen, Gregory W.; Rouillard, Andrew D.; Jenkins, Sherry L.; Feldmann, Axel S.; Hu, Kevin S.; McDermott, Michael G.; Duan, Qiaonan; Clark, Neil R.; Jones, Matthew R.; Kou, Yan; Goff, Troy; Woodland, Holly; Amaral, Fabio M R.; Szeto, Gregory L.; Fuchs, Oliver; Schüssler-Fiorenza Rose, Sophia M.; Sharma, Shvetank; Schwartz, Uwe; Bausela, Xabier Bengoetxea; Szymkiewicz, Maciej; Maroulis, Vasileios; Salykin, Anton; Barra, Carolina M.; Kruth, Candice D.; Bongio, Nicholas J.; Mathur, Vaibhav; Todoric, Radmila D; Rubin, Udi E.; Malatras, Apostolos; Fulp, Carl T.; Galindo, John A.; Motiejunaite, Ruta; Jüschke, Christoph; Dishuck, Philip C.; Lahl, Katharina; Jafari, Mohieddin; Aibar, Sara; Zaravinos, Apostolos; Steenhuizen, Linda H.; Allison, Lindsey R.; Gamallo, Pablo; de Andres Segura, Fernando; Dae Devlin, Tyler; Pérez-García, Vicente; Ma'ayan, Avi

2016-01-01

Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization. PMID:27667448

Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd.

PubMed

Wang, Zichen; Monteiro, Caroline D; Jagodnik, Kathleen M; Fernandez, Nicolas F; Gundersen, Gregory W; Rouillard, Andrew D; Jenkins, Sherry L; Feldmann, Axel S; Hu, Kevin S; McDermott, Michael G; Duan, Qiaonan; Clark, Neil R; Jones, Matthew R; Kou, Yan; Goff, Troy; Woodland, Holly; Amaral, Fabio M R; Szeto, Gregory L; Fuchs, Oliver; Schüssler-Fiorenza Rose, Sophia M; Sharma, Shvetank; Schwartz, Uwe; Bausela, Xabier Bengoetxea; Szymkiewicz, Maciej; Maroulis, Vasileios; Salykin, Anton; Barra, Carolina M; Kruth, Candice D; Bongio, Nicholas J; Mathur, Vaibhav; Todoric, Radmila D; Rubin, Udi E; Malatras, Apostolos; Fulp, Carl T; Galindo, John A; Motiejunaite, Ruta; Jüschke, Christoph; Dishuck, Philip C; Lahl, Katharina; Jafari, Mohieddin; Aibar, Sara; Zaravinos, Apostolos; Steenhuizen, Linda H; Allison, Lindsey R; Gamallo, Pablo; de Andres Segura, Fernando; Dae Devlin, Tyler; Pérez-García, Vicente; Ma'ayan, Avi

2016-09-26

Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.

Trichothecene resistance in wheat: Development of molecular markers for PDR-type ABC transporter genes.

PubMed

Mitterbauer, R; Heinrich, M; Rauscher, R; Lemmens, M; Bürstmayr, H; Adam, G

2003-03-01

Infection withFusarium graminearum andF. culmorum not only causes severe yield and quality losses, the most relevant concern is the contamination of cereal foods and feeds with trichothecenes (e.g. deoxynivalenol, DON). The ability to synthesize trichothecenes has been shown to be a virulence factor ofF. graminearum on wheat and, on the other hand, toxin resistance is most likely an important component of field resistance. Our hypothesis is that pleiotropic drug resistance mediated by PDR-type ABC transporter proteins (acting as membrane located drug efflux pumps) is a relevant mechanism of DON resistance not only in yeast but also in wheat. Goal of this project is the development of molecular markers for this gene family for use in marker-assisted plant breeding programs. The technical difficulties caused by the large size of the PDR-family are discussed.

Multisite cost analysis of a school-based voluntary alcohol and drug prevention program.

PubMed

Kilmer, Beau; Burgdorf, James R; D'Amico, Elizabeth J; Miles, Jeremy; Tucker, Joan

2011-09-01

This article estimates the societal costs of Project CHOICE, a voluntary after-school alcohol and other drug prevention program for adolescents. To our knowledge, this is the first cost analysis of an after-school program specifically focused on reducing alcohol and other drug use. The article uses microcosting methods based on the societal perspective and includes a number of sensitivity analyses to assess how the results change with alternative assumptions. Cost data were obtained from surveys of participants, facilitators, and school administrators; insights from program staff members; program expenditures; school budgets; the Bureau of Labor Statistics; and the National Center for Education Statistics. From the societal perspective, the cost of implementing Project CHOICE in eight California schools ranged from $121 to $305 per participant (Mdn = $238). The major cost drivers included labor costs associated with facilitating Project CHOICE, opportunity costs of displaced class time (because of in-class promotions for Project CHOICE and consent obtainment), and other efforts to increase participation. Substituting nationally representative cost information for wages and space reduced the range to $100-$206 (Mdn = $182), which is lower than the Substance Abuse and Mental Health Services Administration's estimate of $262 per pupil for the "average effective school-based program in 2002." Denominating national Project CHOICE costs by enrolled students instead of participants generates a median per-pupil cost of $21 (range: $14-$28). Estimating the societal costs of school-based prevention programs is crucial for efficiently allocating resources to reduce alcohol and other drug use. The large variation in Project CHOICE costs across schools highlights the importance of collecting program cost information from multiple sites.

Multisite Cost Analysis of a School-Based Voluntary Alcohol and Drug Prevention Program*

PubMed Central

Kilmer, Beau; Burgdorf, James R.; D'amico, Elizabeth J.; Miles, Jeremy; Tucker, Joan

2011-01-01

Objective: This article estimates the societal costs of Project CHOICE, a voluntary after-school alcohol and other drug prevention program for adolescents. To our knowledge, this is the first cost analysis of an after-school program specifically focused on reducing alcohol and other drug use. Method: The article uses microcosting methods based on the societal perspective and includes a number of sensitivity analyses to assess how the results change with alternative assumptions. Cost data were obtained from surveys of participants, facilitators, and school administrators; insights from program staff members; program expenditures; school budgets; the Bureau of Labor Statistics; and the National Center for Education Statistics. Results: From the societal perspective, the cost of implementing Project CHOICE in eight California schools ranged from $121 to $305 per participant (Mdn = $238). The major cost drivers included labor costs associated with facilitating Project CHOICE, opportunity costs of displaced class time (because of in-class promotions for Project CHOICE and consent obtainment), and other efforts to increase participation. Substituting nationally representative cost information for wages and space reduced the range to $100–$206 (Mdn = $182), which is lower than the Substance Abuse and Mental Health Services Administration's estimate of $262 per pupil for the "average effective school-based program in 2002." Denominating national Project CHOICE costs by enrolled students instead of participants generates a median per-pupil cost of $21 (range: $14—$28). Conclusions: Estimating the societal costs of school-based prevention programs is crucial for efficiently allocating resources to reduce alcohol and other drug use. The large variation in Project CHOICE costs across schools highlights the importance of collecting program cost information from multiple sites. PMID:21906509

Rejuvenating harm reduction projects for injection drug users: Ukraine's nationwide introduction of peer-driven interventions.

PubMed

Smyrnov, Pavlo; Broadhead, Robert S; Datsenko, Oleksandra; Matiyash, Oksana

2012-03-01

A peer-driven intervention (PDI) for injecting drug users (IDUs) was implemented in five Ukrainian city-sites to test-pilot its effectiveness in rejuvenating harm reduction (HR) projects that had become moribund. A PDI relies on drug users in a unique way to educate their peers in the community and recruit them for HIV prevention services. The goal of the PDI was to recruit in six month 500 IDUs who had never been respondents before to each of the five HR projects, especially stimulant- and women-injectors, and IDUs<25 years of age. We standardized the PDI's structure and operations across all five sites. All five PDIs were started in May 2007 using a carefully selected handful of "seed" IDU-recruiters who were trained to educate three peers who had never received HR services. We also accessed the database of all five projects and analysed the new respondents they recruited six-months prior to the start-up of the PDIs with the new recruits generated by the PDIs. Whilst the HR projects in the five city-sites recruited 72 new respondents on average during the six months prior to the PDIs' start-up, the PDIs recruited 455 new respondents on average in each city during their six months of operation, indicating that the PDI was 6.3 times more powerful as a recruitment mechanism. Compared to traditional outreach the PDIs resulted in significant increases in the recruitment of women- and young-injectors, and IDUs who injected a more diverse variety of drugs. The PDI can have a rejuvenating effect when added to HR projects that had become stagnate over time, resulting in an increase in the number and diversity of new IDU-respondents. Copyright © 2012 Elsevier B.V. All rights reserved.

Embarking on large-scale qualitative research: reaping the benefits of mixed methods in studying youth, clubs and drugs

PubMed Central

Hunt, Geoffrey; Moloney, Molly; Fazio, Adam

2012-01-01

Qualitative research is often conceptualized as inherently small-scale research, primarily conducted by a lone researcher enmeshed in extensive and long-term fieldwork or involving in-depth interviews with a small sample of 20 to 30 participants. In the study of illicit drugs, traditionally this has often been in the form of ethnographies of drug-using subcultures. Such small-scale projects have produced important interpretive scholarship that focuses on the culture and meaning of drug use in situated, embodied contexts. Larger-scale projects are often assumed to be solely the domain of quantitative researchers, using formalistic survey methods and descriptive or explanatory models. In this paper, however, we will discuss qualitative research done on a comparatively larger scale—with in-depth qualitative interviews with hundreds of young drug users. Although this work incorporates some quantitative elements into the design, data collection, and analysis, the qualitative dimension and approach has nevertheless remained central. Larger-scale qualitative research shares some of the challenges and promises of smaller-scale qualitative work including understanding drug consumption from an emic perspective, locating hard-to-reach populations, developing rapport with respondents, generating thick descriptions and a rich analysis, and examining the wider socio-cultural context as a central feature. However, there are additional challenges specific to the scale of qualitative research, which include data management, data overload and problems of handling large-scale data sets, time constraints in coding and analyzing data, and personnel issues including training, organizing and mentoring large research teams. Yet large samples can prove to be essential for enabling researchers to conduct comparative research, whether that be cross-national research within a wider European perspective undertaken by different teams or cross-cultural research looking at internal divisions and differences within diverse communities and cultures. PMID:22308079

Addiction research centres and the nurturing of creativity: the Department of Alcohol, Drugs and Addiction at the National Institute for Health and Welfare in Finland: diverse problems, diverse perspectives.

PubMed

Hakkarainen, Pekka; Kiianmaa, Kalervo; Kuoppasalmi, Kimmo; Tigerstedt, Christoffer

2012-10-01

The Department of Alcohol, Drugs and Addiction started operations on 1 January 2009, when the National Institute of Public Health (KTL) and the National Research and Development Centre for Welfare and Health (STAKES) were merged. The newly formed institute, called the National Institute for Health and Welfare (THL), operates under the Finnish Ministry of Social Affairs and Health. The scope of the research and preventive work conducted in the Department covers alcohol, drugs, tobacco and gambling issues. The two main tasks of the Department are (i) to research, produce and disseminate information on alcohol and drugs, substance use, addictions and their social and health-related effects and (ii) to develop prevention and good practices with a view to counteracting the onset and development of alcohol and drug problems and the damaging effects of smoking and other addictions. The number of staff hovers at approximately 60 people. The Department is organized into three units, one specialized in social sciences (the Alcohol and Drug Research Unit), another in laboratory analytics (the Alcohol and Drug Analytics Unit) and the third primarily in preventive work (the Addiction Prevention Unit). These units incorporate a rich variety and long traditions of both research and preventive work. The mixture of different disciplines creates good opportunities for interdisciplinary research projects and collaboration within the Department. Also, the fact that in the same administrative context there are both researchers and people specialized in preventive work opens up interesting possibilities for combining efforts from these two branches. Nationally, the Department is a key player in all its fields of interest. It engages in a great deal of cooperation both nationally and internationally, and among its strengths are the high-quality, regularly collected long-term data sets. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Using RxNorm and NDF-RT to classify medication data extracted from electronic health records: experiences from the Rochester Epidemiology Project.

PubMed

Pathak, Jyotishman; Murphy, Sean P; Willaert, Brian N; Kremers, Hilal M; Yawn, Barbara P; Rocca, Walter A; Chute, Christopher G

2011-01-01

RxNorm and NDF-RT published by the National Library of Medicine (NLM) and Veterans Affairs (VA), respectively, are two publicly available federal medication terminologies. In this study, we evaluate the applicability of RxNorm and National Drug File-Reference Terminology (NDF-RT) for extraction and classification of medication data retrieved using structured querying and natural language processing techniques from electronic health records at two different medical centers within the Rochester Epidemiology Project (REP). Specifically, we explore how mappings between RxNorm concept codes and NDF-RT drug classes can be leveraged for hierarchical organization and grouping of REP medication data, identify gaps and coverage issues, and analyze the recently released NLM's NDF-RT Web service API. Our study concludes that RxNorm and NDF-RT can be applied together for classification of medication extracted from multiple EHR systems, although several issues and challenges remain to be addressed. We further conclude that the Web service APIs developed by the NLM provide useful functionalities for such activities.

The Brisbane Longitudinal Twin Study Pathways to Cannabis Use, Abuse and Dependence Project: Current status, preliminary results and future directions

PubMed Central

Gillespie, NA; Henders, AK; Davenport, TA; Hermens, DF; Wright, MJ; Martin, NG; Hickie, IB

2013-01-01

We describe the data being collected from the Brisbane Longitudinal Twin Study (BLTS) in Australia as part of the US National Institute on Drug Abuse (NIDA) funded project Pathways to Cannabis Use, Abuse and Dependence. The history, recruitment, assessment and retention of twin families in this project are described in detail along with preliminary findings and plans for future research. The goal of this NIDA project is to make a significant contribution to the discovery of quantitative trait loci (QTL) influencing cannabis use disorders. Although the focus is cannabis use, abuse and dependence in young adults, measures of comorbid illicit drug use disorders are also being collected. In addition, a variety of internalizing and externalizing disorders are being assessed, funded by support from the Australian National Health and Medical Research Council. Because these same twins have participated in numerous twin studies since 1992, future plans will include linking different phenotypes to investigate relationships between drug use, psychiatric disorders and psychological phenotypes within cross-sectional and longitudinal or developmental frameworks. PMID:23187020

The Brisbane Longitudinal Twin Study: Pathways to Cannabis Use, Abuse, and Dependence project-current status, preliminary results, and future directions.

PubMed

Gillespie, Nathan A; Henders, Anjali K; Davenport, Tracy A; Hermens, Daniel F; Wright, Margie J; Martin, Nicholas G; Hickie, Ian B

2013-02-01

We describe the data being collected from the Brisbane Longitudinal Twin Study in Australia as part of the US National Institute on Drug Abuse (NIDA)-funded project, Pathways to Cannabis Use, Abuse and Dependence. The history, recruitment, assessment, and retention of twin families in this project are described in detail, along with preliminary findings and plans for future research. The goal of this NIDA project is to make a significant contribution to the discovery of quantitative trait loci influencing cannabis use disorders. Although the focus is cannabis use, abuse, and dependence in young adults, measures of comorbid illicit drug use disorders are also being collected. In addition, a variety of internalizing and externalizing disorders are being assessed, funded by support from the Australian National Health and Medical Research Council. Because these same twins have participated in numerous twin studies since 1992, future plans will include linking different phenotypes to investigate relationships between drug use, psychiatric disorders, and psychological phenotypes within cross-sectional and longitudinal or developmental frameworks.

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 7.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of recent drug abuse literature, derived from scanning the major publications media in the area. This includes scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports.…

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 8.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of recent drug abuse literature, derived from scanning the major publications media in the area. This includes scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports.…

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 6.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of the recent drug abuse literature, derived from scanning the major publications media in the area, including scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports. The…

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 2.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of the recent drug abuse literature, derived from scanning the major publications media in the area, including scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports. The…

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 1.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of the recent drug abuse literature, derived from scanning the major publications media in the area, including scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports. The…

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 9.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of the recent drug abuse literature, derived from scanning the major publications media in the area, including scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports. The…

Drug Abuse Awareness System (DACAS), Volume 1 Number 5.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of the recent drug abuse literature, derived from scanning the major publications media in the area, including scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports. The…

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 4.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of the recent drug abuse literature, derived from scanning the major publications media in the area, including scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports. The…

Drug Abuse Current Awareness System (DACAS), Volume 1 Number 3.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

The Drug Abuse Current Awareness System (DACAS) is a comprehensive biweekly listing of citations of the recent drug abuse literature derived from scanning the major publications media in the area, including scientific and technical journals, popular magazines, underground newspapers, books, legal journals, and government project reports. The…

Experimental design-based strategy for the simulation of complex gaseous mixture spectra to detect drug precursors

NASA Astrophysics Data System (ADS)

Calderisi, Marco; Ulrici, Alessandro; Pigani, Laura; Secchi, Alberto; Seeber, Renato

2012-09-01

The EU FP7 project CUSTOM (Drugs and Precursor Sensing by Complementing Low Cost Multiple Techniques) aims at developing a new sensing system for the detection of drug precursors in gaseous samples, which includes an External Cavity-Quantum Cascade Laser Photo-Acoustic Sensor (EC-QCLPAS) that is in the final step of realisation. Thus, a simulation based on FT-IR literature spectra has been accomplished, where the development of a proper strategy for the design of the composition of the environment, as much as possible realistic and representative of different scenarios, is of key importance. To this aim, an approach based on the combination of signal processing and experimental design techniques has been developed. The gaseous mixtures were built by adding the considered 4 drug precursor (target) species to the gases typically found in atmosphere, taking also into account possible interfering species. These last chemicals were selected considering custom environments (20 interfering chemical species), whose concentrations have been inferred from literature data. The spectra were first denoised by means of a Fast Wavelet Transform-based algorithm; then, a procedure based on a sigmoidal transfer function was developed to multiply the pure components spectra by the respective concentration values, in a way to correctly preserve background intensity and shape, and to operate only on the absorption bands. The noise structure of the EC-QCLPAS was studied using sample spectra measured with a prototype instrument, and added to the simulated mixtures. Finally a matrix containing 5000 simulated spectra of gaseous mixtures was built up.

Sports medicine and drug control programs of the U.S. Olympic Committee.

PubMed

Clarke, K S

1984-05-01

The Amateur Sports Act of 1978 reconstituted the U.S. Olympic Committee ( USOC ), giving it new responsibilities and opportunities as a unifying force in amateur sports, including sports medicine. Sports medicine is the sum of attentions that promote and protect the health of the active person. Olympic sports medicine includes attention to the needs of both the elite athlete and the developing athlete. In some instances the attentions are the same; in others they are not. Those in Olympic sports medicine must thereby reduce the increasing array of general concepts and issues to the applicable specifics of the respective occasion, sport, and individual. The USOC Sports Medicine Program is guided by a 15-person volunteer Sports Medicine Council and implemented by a core Sports Medicine Division staff. Services are provided at the Olympic training centers in Colorado Springs and Lake Placid and extended through a budding network of colleagues in the field to clusters of athletes across the nations. Organizationally , the Division is composed of departments of biomechanics, sports physiology, clinical services, and educational services. Special projects are developed as warranted to provide focal attention to sports psychology, nutrition, chronobiology, vision enhancement, and drug control. The USOC Drug Control Program was born at the 1983 Pan American Games in Caracas after a long gestation period. Drug education in sports has been a frequent activity for the past 20 yr. sometimes focusing on illicit drugs (e.g., marijuana and cocaine) and sometimes on sports performance drugs (e.g., amphetamines and anabolic steroids).(ABSTRACT TRUNCATED AT 250 WORDS)

The Association between Parent Early Adult Drug Use Disorder and Later Observed Parenting Practices and Child Behavior Problems: Testing Alternate Models

PubMed Central

Bailey, Jennifer A.; Hill, Karl G.; Guttmannova, Katarina; Oesterle, Sabrina; Hawkins, J. David; Catalano, Richard F.; McMahon, Robert J.

2012-01-01

This study tested the association between parent illicit drug use disorder (DUD) in early adulthood and observed parenting practices at ages 27 – 28 and examined the following three, theoretically-derived models explaining this link: a) a disrupted parent adult functioning model, b) a pre-existing parent personality factor model, c) a disrupted adolescent family process model. Associations between study variables and child externalizing problems also were examined. Longitudinal data linking two generations were drawn from the Seattle Social Development Project (SSDP) and The SSDP Intergenerational Project (TIP), and included 167 parents and their 2- to 8-year-old child. Path modeling revealed that parent DUD in early adulthood predicted later observed low-skilled parenting, which was related to child externalizing problems. The pre-existing parent personality factor model was supported. Parent negative emotionality accounted for the association between parent early adult DUD and later parenting practices. Parent negative emotionality also was related directly to child externalizing behavior. Limited support for the disrupted transition to adulthood model was found. The disrupted adolescent family process model was not supported. Results suggest that problem drug use that occurs early in adulthood may affect later parenting skills, independent of subsequent parent drug use. Findings highlight the importance of parent negative emotionality in influencing their own problem behavior, their interactions with their child, and their child’s problem behavior. Prevention and treatment programs targeting young adult substance use, poor parenting practices, and child behavior problems should address parent personality factors that may contribute to these behaviors. PMID:22799581

The association between parent early adult drug use disorder and later observed parenting practices and child behavior problems: testing alternate models.

PubMed

Bailey, Jennifer A; Hill, Karl G; Guttmannova, Katarina; Oesterle, Sabrina; Hawkins, J David; Catalano, Richard F; McMahon, Robert J

2013-05-01

This study tested the association between parent illicit drug use disorder (DUD) in early adulthood and observed parenting practices at ages 27-28 and examined the following 3 theoretically derived models explaining this link: (a) a disrupted parent adult functioning model,(b) a preexisting parent personality factor model, and (c) a disrupted adolescent family process model. Associations between study variables and child externalizing problems also were examined. Longitudinal data linking 2 generations were drawn from the Seattle Social Development Project (SSDP) and The SSDP Intergenerational Project (TIP), and included 167 parents and their 2- to 8-year-old child. Path modeling revealed that parent DUD in early adulthood predicted later observed low-skilled parenting, which was related to child externalizing problems. The preexisting parent personality factor model was supported. Parent negative emotionality accounted for the association between parent early adult DUD and later parenting practices. Parent negative emotionality also was related directly to child externalizing behavior. Limited support for the disrupted transition to adulthood model was found. The disrupted adolescent family process model was not supported. Results suggest that problem drug use that occurs early in adulthood may affect later parenting skills, independent of subsequent parent drug use. Findings highlight the importance of parent negative emotionality in influencing his or her own problem behavior, interactions with his or her child, and his or her child's problem behavior. Prevention and treatment programs targeting young adult substance use, poor parenting practices, and child behavior problems should address parent personality factors that may contribute to these behaviors.

Planned and ongoing projects (pop) database: development and results.

PubMed

Wild, Claudia; Erdös, Judit; Warmuth, Marisa; Hinterreiter, Gerda; Krämer, Peter; Chalon, Patrice

2014-11-01

The aim of this study was to present the development, structure and results of a database on planned and ongoing health technology assessment (HTA) projects (POP Database) in Europe. The POP Database (POP DB) was set up in an iterative process from a basic Excel sheet to a multifunctional electronic online database. The functionalities, such as the search terminology, the procedures to fill and update the database, the access rules to enter the database, as well as the maintenance roles, were defined in a multistep participatory feedback loop with EUnetHTA Partners. The POP Database has become an online database that hosts not only the titles and MeSH categorizations, but also some basic information on status and contact details about the listed projects of EUnetHTA Partners. Currently, it stores more than 1,200 planned, ongoing or recently published projects of forty-three EUnetHTA Partners from twenty-four countries. Because the POP Database aims to facilitate collaboration, it also provides a matching system to assist in identifying similar projects. Overall, more than 10 percent of the projects in the database are identical both in terms of pathology (indication or disease) and technology (drug, medical device, intervention). In addition, approximately 30 percent of the projects are similar, meaning that they have at least some overlap in content. Although the POP DB is successful concerning regular updates of most national HTA agencies within EUnetHTA, little is known about its actual effects on collaborations in Europe. Moreover, many non-nationally nominated HTA producing agencies neither have access to the POP DB nor can share their projects.

Genome Science and Personalized Cancer Treatment

ScienceCinema

Gray, Joe

2017-12-09

August 4, 2009 Berkeley Lab lecture: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks — particularly with regard to breast cancer.

Molecular Innovations Towards Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2013-09-01

14. ABSTRACT: In this project, we propose to develop a new drug delivery vehicle based on dendrimer nanotechnology for personalized medicine. This new...PI’s lab will make dendrimers bearing functional handles to conjugate with chelating agents provided by the Initiating PI’s lab for PET imaging and...has designed and synthesized the proposed bifunctional chelator scaffold system, CB-TE2A(tBu)2-N3 for the further construction of dendrimer -based

Systematic review on what works, what does not work and why of implementation of mobile health (mHealth) projects in Africa.

PubMed

Aranda-Jan, Clara B; Mohutsiwa-Dibe, Neo; Loukanova, Svetla

2014-02-21

Access to mobile phone technology has rapidly expanded in developing countries. In Africa, mHealth is a relatively new concept and questions arise regarding reliability of the technology used for health outcomes. This review documents strengths, weaknesses, opportunities, and threats (SWOT) of mHealth projects in Africa. A systematic review of peer-reviewed literature on mHealth projects in Africa, between 2003 and 2013, was carried out using PubMed and OvidSP. Data was synthesized using a SWOT analysis methodology. Results were grouped to assess specific aspects of project implementation in terms of sustainability and mid/long-term results, integration to the health system, management process, scale-up and replication, and legal issues, regulations and standards. Forty-four studies on mHealth projects in Africa were included and classified as: "patient follow-up and medication adherence" (n = 19), "staff training, support and motivation" (n = 2), "staff evaluation, monitoring and guidelines compliance" (n = 4), "drug supply-chain and stock management" (n = 2), "patient education and awareness" (n = 1), "disease surveillance and intervention monitoring" (n = 4), "data collection/transfer and reporting" (n = 10) and "overview of mHealth projects" (n = 2). In general, mHealth projects demonstrate positive health-related outcomes and their success is based on the accessibility, acceptance and low-cost of the technology, effective adaptation to local contexts, strong stakeholder collaboration, and government involvement. Threats such as dependency on funding, unclear healthcare system responsibilities, unreliable infrastructure and lack of evidence on cost-effectiveness challenge their implementation. mHealth projects can potentially be scaled-up to help tackle problems faced by healthcare systems like poor management of drug stocks, weak surveillance and reporting systems or lack of resources. mHealth in Africa is an innovative approach to delivering health services. In this fast-growing technological field, research opportunities include assessing implications of scaling-up mHealth projects, evaluating cost-effectiveness and impacts on the overall health system.

Diverse ways of perturbing the human arachidonic acid metabolic network to control inflammation.

PubMed

Meng, Hu; Liu, Ying; Lai, Luhua

2015-08-18

Inflammation and other common disorders including diabetes, cardiovascular disease, and cancer are often the result of several molecular abnormalities and are not likely to be resolved by a traditional single-target drug discovery approach. Though inflammation is a normal bodily reaction, uncontrolled and misdirected inflammation can cause inflammatory diseases such as rheumatoid arthritis and asthma. Nonsteroidal anti-inflammatory drugs including aspirin, ibuprofen, naproxen, or celecoxib are commonly used to relieve aches and pains, but often these drugs have undesirable and sometimes even fatal side effects. To facilitate safer and more effective anti-inflammatory drug discovery, a balanced treatment strategy should be developed at the biological network level. In this Account, we focus on our recent progress in modeling the inflammation-related arachidonic acid (AA) metabolic network and subsequent multiple drug design. We first constructed a mathematical model of inflammation based on experimental data and then applied the model to simulate the effects of commonly used anti-inflammatory drugs. Our results indicated that the model correctly reproduced the established bleeding and cardiovascular side effects. Multitarget optimal intervention (MTOI), a Monte Carlo simulated annealing based computational scheme, was then developed to identify key targets and optimal solutions for controlling inflammation. A number of optimal multitarget strategies were discovered that were both effective and safe and had minimal associated side effects. Experimental studies were performed to evaluate these multitarget control solutions further using different combinations of inhibitors to perturb the network. Consequently, simultaneous control of cyclooxygenase-1 and -2 and leukotriene A4 hydrolase, as well as 5-lipoxygenase and prostaglandin E2 synthase were found to be among the best solutions. A single compound that can bind multiple targets presents advantages including low risk of drug-drug interactions and robustness regarding concentration fluctuations. Thus, we developed strategies for multiple-target drug design and successfully discovered several series of multiple-target inhibitors. Optimal solutions for a disease network often involve mild but simultaneous interventions of multiple targets, which is in accord with the philosophy of traditional Chinese medicine (TCM). To this end, our AA network model can aptly explain TCM anti-inflammatory herbs and formulas at the molecular level. We also aimed to identify activators for several enzymes that appeared to have increased activity based on MTOI outcomes. Strategies were then developed to predict potential allosteric sites and to discover enzyme activators based on our hypothesis that combined treatment with the projected activators and inhibitors could balance different AA network pathways, control inflammation, and reduce associated adverse effects. Our work demonstrates that the integration of network modeling and drug discovery can provide novel solutions for disease control, which also calls for new developments in drug design concepts and methodologies. With the rapid accumulation of quantitative data and knowledge of the molecular networks of disease, we can expect an increase in the development and use of quantitative disease models to facilitate efficient and safe drug discovery.

Sharing adverse drug event data using business intelligence technology.

PubMed

Horvath, Monica M; Cozart, Heidi; Ahmad, Asif; Langman, Matthew K; Ferranti, Jeffrey

2009-03-01

Duke University Health System uses computerized adverse drug event surveillance as an integral part of medication safety at 2 community hospitals and an academic medical center. This information must be swiftly communicated to organizational patient safety stakeholders to find opportunities to improve patient care; however, this process is encumbered by highly manual methods of preparing the data. Following the examples of other industries, we deployed a business intelligence tool to provide dynamic safety reports on adverse drug events. Once data were migrated into the health system data warehouse, we developed census-adjusted reports with user-driven prompts. Drill down functionality enables navigation from aggregate trends to event details by clicking report graphics. Reports can be accessed by patient safety leadership either through an existing safety reporting portal or the health system performance improvement Web site. Elaborate prompt screens allow many varieties of reports to be created quickly by patient safety personnel without consultation with the research analyst. The reduction in research analyst workload because of business intelligence implementation made this individual available to additional patient safety projects thereby leveraging their talents more effectively. Dedicated liaisons are essential to ensure clear communication between clinical and technical staff throughout the development life cycle. Design and development of the business intelligence model for adverse drug event data must reflect the eccentricities of the operational system, especially as new areas of emphasis evolve. Future usability studies examining the data presentation and access model are needed.

A rapid approach for characterization of thiol-conjugated antibody-drug conjugates and calculation of drug-antibody ratio by liquid chromatography mass spectrometry.

PubMed

Firth, David; Bell, Leonard; Squires, Martin; Estdale, Sian; McKee, Colin

2015-09-15

We present the demonstration of a rapid "middle-up" liquid chromatography mass spectrometry (LC-MS)-based workflow for use in the characterization of thiol-conjugated maleimidocaproyl-monomethyl auristatin F (mcMMAF) and valine-citrulline-monomethyl auristatin E (vcMMAE) antibody-drug conjugates. Deconvoluted spectra were generated following a combination of deglycosylation, IdeS (immunoglobulin-degrading enzyme from Streptococcus pyogenes) digestion, and reduction steps that provide a visual representation of the product for rapid lot-to-lot comparison-a means to quickly assess the integrity of the antibody structure and the applied conjugation chemistry by mass. The relative abundance of the detected ions also offer information regarding differences in drug conjugation levels between samples, and the average drug-antibody ratio can be calculated. The approach requires little material (<100 μg) and, thus, is amenable to small-scale process development testing or as an early component of a complete characterization project facilitating informed decision making regarding which aspects of a molecule might need to be examined in more detail by orthogonal methodologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Estimating equivalent cutoff thresholds for drugs in blood and oral fluid using prevalence regression: a study of tetrahydrocannabinol and amphetamine.

PubMed

Gjerde, Hallvard; Verstraete, Alain G

2011-10-10

To validate a method for determining equivalent drug cutoff concentrations for tetrahydrocannabinol and amphetamine in blood and oral fluid, which ensures that the drug prevalence in samples of blood and oral fluid taken simultaneously is equal. A method using regression analysis of drug concentrations for defined percentiles in blood and oral fluid was developed. The accuracy and precision of this technique was investigated. As study populations, 311 cannabis users and 197 amphetamine users from the Rosita-2 Project were used. A total of 80 paired oral fluid and blood concentrations were needed to determine accurate regression formulae. When using the formulae to calculate drug cutoff concentrations in oral fluid corresponding to 2.0, 4.0, 6.0, 8.0 and 10.0 ng/ml tetrahydrocannabinol in blood and 200, 400, 600, 800 and 1000 ng/ml amphetamine in blood, the accuracy was better than 100 ± 20% compared to actual prevalence in blood with precision better than ± 20%. Prevalence regression may be a useful tool in estimating equivalent cutoff concentrations in blood and oral fluid. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Stabilization of protein-protein interactions in drug discovery.

PubMed

Andrei, Sebastian A; Sijbesma, Eline; Hann, Michael; Davis, Jeremy; O'Mahony, Gavin; Perry, Matthew W D; Karawajczyk, Anna; Eickhoff, Jan; Brunsveld, Luc; Doveston, Richard G; Milroy, Lech-Gustav; Ottmann, Christian

2017-09-01

PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.

Dissonance-Based Interventions for Substance Using Alternative High-School Youth

PubMed Central

Steiker, Lori Holleran; Powell, Tara

2011-01-01

This article describes an innovative new intervention tailored to older youth who are already abusing drugs, but who are not diagnostically ready for treatment. The basic tenet of this intervention is to utilize adolescents engaged in drug use as “experts” in the prevention curriculum adaptation activity. This activity then serves as a mechanism for their dissonance-based change. This process is designed to intervene with drug abusing youth prior to their development of substance dependence. The community-based design grew from a United States federally funded NIDA project (National Institute of Drug Abuse Mentored Research Scientist Award) which found that the youth who conduct program adaptations were effectively engaged, animatedly discussing the payoffs and downsides of drug and alcohol abuse. It is maintained through this research that dissonance between their role of “Preventionist” and their own substance abuse behaviors lead to shifts in attitudes and behaviors. Dissonance-based interventions (DBIs) have been successfully utilized for positive behavioral change with a variety of disorders, but have not yet been implemented with substance abusing youth. Findings of pilot research are shared along with implications for future research and interventions. PMID:22611306

Washington State CARE Project: downstream cost changes associated with the provision of cognitive services by pharmacists.

PubMed

Smith, D H; Fassett, W E; Christensen, D B

1999-01-01

To determine the changes in drug costs associated with drug therapy changes resulting from pharmacists' cognitive services (CS) provided to Medicaid recipients during a 1-year period following the documented CS. A study-control group analysis of documented pharmacists' CS interventions linked to Medicaid prescription claims. Each CS resulting in a drug therapy change was linked to an index prescription claim and all refills for the same drug within 365 days. The drug cost change associated with the CS was calculated as the difference between the estimated cost of the prescription as originally written less the actual cost to Medicaid for the stream of refills dispensed. Pharmacies serving ambulatory Medicaid patients in the state of Washington, excluding staff-model health maintenance organization pharmacies and pharmacies predominantly serving long-term care residents. Approximately 200 community pharmacies participating in the Washington State Cognitive Activities and Reimbursement Effectiveness (CARE) Project. Pharmacies were randomly assigned to a group that was paid a fee for each CS provided or a group that was not paid. Payment for CS. Downstream drug costs associated with CS resulting in a drug therapy change. CS resulting in drug therapy changes accounted for 5,417 out of 20,240 (27%) documented CS in the CARE Project. Of the 2,002 CS records analyzed in this study, 76% indicated a change in the prescribed drug or drug regimen, 9% indicated that a drug was added, 5% indicated that a current drug was discontinued, and 10% indicated that an originally prescribed drug was never dispensed. Only 9% involved generic substitution; all other changes would have necessitated prior prescriber approval. Overall, CS resulting in a drug therapy change generated a mean drug cost savings of $13.05 per CS intervention. There were no significant differences in average savings per intervention between the paid and nonpaid groups. For all result categories except "add drug therapy," the extrapolated cost savings in the paid group exceeded the savings estimated from the nonpaid group, sometimes by a considerable amount. At the payment rate used in this study, paying for CS that result in a drug therapy change (except add drug therapy) is estimated to save an additional $10 per 1,000 prescriptions dispensed. Those CS that result in addition of drug therapy are estimated to add an incremental cost of about $13 per 1,000 prescriptions. A sensitivity analysis revealed that a higher intervention rate would lead to a higher potential savings. This finding suggests that efforts to encourage CS interventions may lead to greater savings.

Identification of Granulocyte Colony-Stimulating Factor and Interleukin-6 as Candidate Biomarkers of CBLB502 Efficacy as a Medical Radiation Countermeasure

PubMed Central

Krivokrysenko, Vadim I.; Shakhov, Alexander N.; Singh, Vijay K.; Bone, Frederick; Kononov, Yevgeniy; Shyshynova, Inna; Cheney, Alec; Maitra, Ratan K.; Purmal, Andrei; Whitnall, Mark H.; Feinstein, Elena

2012-01-01

Given an ever-increasing risk of nuclear and radiological emergencies, there is a critical need for development of medical radiation countermeasures (MRCs) that are safe, easily administered, and effective in preventing and/or mitigating the potentially lethal tissue damage caused by acute high-dose radiation exposure. Because the efficacy of MRCs for this indication cannot be ethically tested in humans, development of such drugs is guided by the Food and Drug Administration's Animal Efficacy Rule. According to this rule, human efficacious doses can be projected from experimentally established animal efficacious doses based on the equivalence of the drug's effects on efficacy biomarkers in the respective species. Therefore, identification of efficacy biomarkers is critically important for drug development under the Animal Efficacy Rule. CBLB502 is a truncated derivative of the Salmonella flagellin protein that acts by triggering Toll-like receptor 5 (TLR5) signaling and is currently under development as a MRC. Here, we report identification of two cytokines, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), as candidate biomarkers of CBLB502's radioprotective/mitigative efficacy. Induction of both G-CSF and IL-6 by CBLB502 1) is strictly TLR5-dependent, 2) occurs in a CBLB502 dose-dependent manner within its efficacious dose range in both nonirradiated and irradiated mammals, including nonhuman primates, and 3) is critically important for the ability of CBLB502 to rescue irradiated animals from death. After evaluation of CBLB502 effects on G-CSF and IL-6 levels in humans, these biomarkers will be useful for accurate prediction of human efficacious CBLB502 doses, a key step in the development of this prospective radiation countermeasure. PMID:22837010

Médicarte software developed for the Quebec microprocessor health card project.

PubMed

Lavoie, G; Tremblay, L; Durant, P; Papillon, M J; Bérubé, J; Fortin, J P

1995-01-01

The Quebec Patient Smart Card Project is a Provincial Government initiative under the responsibility of the Rgie de l'assurance-maladie du Québec (Quebec Health Insurance Board). Development, implementation, and assessment duties were assigned to a team from Université Laval, which in turn joined a group from the Direction de la santé publique du Bas-St-Laurent in Rimouski, where the experiment is taking place. The pilot project seeks to evaluate the use and acceptance of a microprocessor card as a way to improve the exchange of clinical information between card users and various health professionals. The card can be best described as a résumé containing information pertinent to an individual's health history. It is not a complete medical file; rather, it is a summary to be used as a starting point for a discussion between health professionals and patients. The target population is composed of persons 60 years and over, pregnant women, infants under 18 months, and the residents of a small town located in the target area, St-Fabien, regardless of age. The health professionals involved are general practitioners, specialists, pharmacists, nurses, and ambulance personnel. Participation in the project is on a voluntary basis. Each health care provider participating in the project has a personal identification number (PIN) and must use both an access card and a user card to access information. This prevents unauthorized access to a patient's card and allows the staff to sign and date information entered onto the patient card. To test the microprocessor card, we developed software based on a problem-oriented approach integrating diagnosis, investigations, treatments, and referrals. This software is not an expert system that constrains the clinician to a particular decisional algorithm. Instead, the software supports the physician in decision making. The software was developed with a graphical interface (Windows 3.1) to maximize its user friendliness. A version of the software was developed for each of the four groups of health care providers involved. In addition we designed an application to interface with existing pharmaceutical software. For practical reasons and to make it possible to differentiate between the different access profiles, the information stored on the card is divided in several blocks: Identification, Emergency, History (personal and family), Screening Tests, Vaccinations, Drug Profile, General follow-up, and some Specific follow-ups (Pregnancy, Ophthalmology, Kidney failure, Cardiology, Pediatrics, Diabetes, Pneumology, Specific parameters). Over 14,000 diagnoses and symptoms are classified with four levels of precision, the codification being based on the ICPC (International Classification for Primary Care). The software contains different applications to assist the clinician in decision making. A "Drug Advisor" helps the prescriber by detecting possible interactions between drugs, giving indications (doses) and contraindications, cautions, potential side-effects and therapeutic alternatives. There is also a prevention module providing recommendations for vaccination and periodic examinations based on the patient's age and sex. The pharmaceutical, vaccination, and screening tests data banks are updated every six months. These sections of the software are accessible to access card holders at any times, even without a patient card, and constitute in themselves an interesting clinical tool. We developed a software server (SCAM) allowing the different applications to access the data in a memory card regardless of the type of memory card used. Using a single high level command language, this server provides a standardized utilization of memory cards from various manufacturers. It ensures the compatibility of the applications using the card as a storage medium. (abstract truncated)

Structure-based discovery and binding site analysis of histamine receptor ligands.

PubMed

Kiss, Róbert; Keserű, György M

2016-12-01

The application of structure-based drug discovery in histamine receptor projects was previously hampered by the lack of experimental structures. The publication of the first X-ray structure of the histamine H1 receptor has been followed by several successful virtual screens and binding site analysis studies of H1-antihistamines. This structure together with several other recently solved aminergic G-protein coupled receptors (GPCRs) enabled the development of more realistic homology models for H2, H3 and H4 receptors. Areas covered: In this paper, the authors review the development of histamine receptor models and their application in drug discovery. Expert opinion: In the authors' opinion, the application of atomistic histamine receptor models has played a significant role in understanding key ligand-receptor interactions as well as in the discovery of novel chemical starting points. The recently solved H1 receptor structure is a major milestone in structure-based drug discovery; however, our analysis also demonstrates that for building H3 and H4 receptor homology models, other GPCRs may be more suitable as templates. For these receptors, the authors envisage that the development of higher quality homology models will significantly contribute to the discovery and optimization of novel H3 and H4 ligands.

Automation of 3D cell culture using chemically defined hydrogels.

PubMed

Rimann, Markus; Angres, Brigitte; Patocchi-Tenzer, Isabel; Braum, Susanne; Graf-Hausner, Ursula

2014-04-01

Drug development relies on high-throughput screening involving cell-based assays. Most of the assays are still based on cells grown in monolayer rather than in three-dimensional (3D) formats, although cells behave more in vivo-like in 3D. To exemplify the adoption of 3D techniques in drug development, this project investigated the automation of a hydrogel-based 3D cell culture system using a liquid-handling robot. The hydrogel technology used offers high flexibility of gel design due to a modular composition of a polymer network and bioactive components. The cell inert degradation of the gel at the end of the culture period guaranteed the harmless isolation of live cells for further downstream processing. Human colon carcinoma cells HCT-116 were encapsulated and grown in these dextran-based hydrogels, thereby forming 3D multicellular spheroids. Viability and DNA content of the cells were shown to be similar in automated and manually produced hydrogels. Furthermore, cell treatment with toxic Taxol concentrations (100 nM) had the same effect on HCT-116 cell viability in manually and automated hydrogel preparations. Finally, a fully automated dose-response curve with the reference compound Taxol showed the potential of this hydrogel-based 3D cell culture system in advanced drug development.

Key Issues in Education: Drug-Free Schools. 1990-91 Program Evaluation of Federally Funded Drug-Free Schools Programs.

ERIC Educational Resources Information Center

Smyer, Roxane

The Austin (Texas) Independent School District (AISD) received monies to combat drug and alcohol abuse on its campuses through the Drug-Free Schools and Communities (DFSC) Act of 1986. Each year, programs funded and services purchased with these funds have changed. In 1990-91 most of the DFSC monies were used for these projects: the Secondary…

Design and Evaluation of an Alcohol and Other Drug Abuse Prevention Program for High Risk Families with Preschool Children.

ERIC Educational Resources Information Center

Powers, Stephen; And Others

In fall, 1991, La Frontera Center, the Tucson Council for Alcohol and Drug Dependence, and the Community Organization for Drug Abuse Control were funded to carry out an educational program to reduce alcohol and other drug abuse in the Tucson, Arizona area. The resulting project, Pasos Adelante (Steps Forward), is an early intervention…

Current European data collection on emergency department presentations with acute recreational drug toxicity: gaps and national variations.

PubMed

Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Yates, Christopher; Dines, Alison M; Sedefov, Roumen; Wood, David M; Dargan, Paul I

2014-12-01

The number of new (novel) psychoactive substances (NPS) available in the illegal market is increasing; however, current monitoring of the drug situation in Europe focuses mainly on classical drugs of abuse, with limited emphasis on clinical presentation in the emergency department (ED). The European Drug Emergencies Network (Euro-DEN) is a European Commission-funded project that aims to improve the knowledge of acute drug toxicity of both classical recreational drugs and NPS. As a baseline for this project, we performed a study to establish which data are currently being collected and reported in Europe on ED presentations with acute toxicity related to NPS and classical drugs of abuse. We used a three-pronged approach to identify any systematic collection of data on NPS toxicity in Europe by i) performing a literature search, ii) utilising an online survey of the European Monitoring Centre for Drugs and Drug Addiction Re seau Europe en d'Information sur les Drogues et les Toxicomanies national focal points and iii) exploiting the knowledge and resources of the Euro-DEN network members. The literature search revealed 21 papers appropriate for assessment, but only one described a systematic collection of clinical data on NPS. Twenty-seven of thirty countries responded to the online survey. More than half of all the countries (52%) did not perform any registration at all of such data, 37% collected systematic clinical data on NPS at a national level, while 44% collected data on classical drugs. A few examples for good practice of systematic collection of clinical data on ED presentations due to acute toxicity were identified. The systematic collection of data on ED presentation of toxicity related to NPS and classical drugs in Europe is scarce; the existing collection is limited to single centres, single countries, groups of patients or not focused on novel drugs; the collection of data is highly variable between the different countries. Euro-DEN, a European Commission funded project, aims at closing some of these gaps.

"Academic drug-detailing": from project to practice in a Swedish urban area.

PubMed

Lundborg, C S; Hensjö, L O; Gustafsson, L L

1997-01-01

To develop and test the long-term feasibility of an interdisciplinary independent drug information service providing both written and oral drug information to physicians in an urban area of Sweden (> 400,000 inhabitants). A drug information service was developed encouraging a cooperative approach between a department of clinical pharmacology, general practitioners (GPs), pharmacists, and Drug and Therapeutic Committees. Scientifically-based drug information was condensed and interpreted by a team and presented in both written and oral form. In one part of the area, both oral and written information was provided, while in another part of the area, only written information was distributed. Questionnaires and one prescription survey were performed to elucidate the knowledge and attitudes of the GPs regarding drug treatment of one condition (urinary tract infection, UTI, and norfloxacin were used as examples), as well as their opinion of our services. Over a period of 10 years, 75 issues of a drug bulletin (2000 copies) were distributed. Oral producer-independent drug information, provided jointly by a GP and a pharmacist, was given on 16 occasions in each of 30 health centres (150 GPs). Around 80% of the GPs participated in the meetings. Of these GPs, 75% found the service important for their daily work. A majority of the GPs had prescribed the test drug, norfloxacin, not a first-line drug according to local recommendations, 1 year after approval. A significantly lower proportion of prescribers were observed in the area where the GPs had been provided with both written and oral information regarding recommended treatment (including first-line drugs) for uncomplicated cystitis. The approximate cost for this service in 1995 was SEK 0.685 million (USD 0.1 million); the prescribing costs of the 150 GPs were estimated at SEK 255 million per year. This means that the cost of the service per GP is only around 0.3% of normal prescribing costs. Over a period of 10 years the information/education method described here has proven sustainable and feasible in terms of providing the information, regarding participation of the target group GPs in the oral sessions, and regarding integration of the service into the existing health care system.

Thomas checks the condition of the MIS-B middeck locker experiment

NASA Image and Video Library

1995-07-28

STS070-329-022 (13-22 JULY 1995)--- Astronaut Donald A. Thomas, mission specialist, prepares to activate the Microcapsules in Space (MIS-B) experiment on the space shuttle Discovery?s middeck. MIS-B is an Army project to improve the understanding of microencapsulated drug technology and demonstrate the feasibility of producing pharmaceutical microcapsules in the weightlessness of space. This is the second flight of the experiment, which originally flew on STS-53 in 1992. Microcapsules are tiny spheres about 50 to 100 micrometers in diameter (about the thickness of a strand of human hair). They are used to develop high-performance chemical products and innovative pharmaceuticals such as time-release prescriptions. The drug used in the MIS experiments was ampicillin.

Reducing the Complexity of an Agent-Based Local Heroin Market Model

PubMed Central

Heard, Daniel; Bobashev, Georgiy V.; Morris, Robert J.

2014-01-01

This project explores techniques for reducing the complexity of an agent-based model (ABM). The analysis involved a model developed from the ethnographic research of Dr. Lee Hoffer in the Larimer area heroin market, which involved drug users, drug sellers, homeless individuals and police. The authors used statistical techniques to create a reduced version of the original model which maintained simulation fidelity while reducing computational complexity. This involved identifying key summary quantities of individual customer behavior as well as overall market activity and replacing some agents with probability distributions and regressions. The model was then extended to allow external market interventions in the form of police busts. Extensions of this research perspective, as well as its strengths and limitations, are discussed. PMID:25025132

[Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

PubMed

Benninger-Döring, G; Boos, J

2006-07-01

Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed.

The “Translators”: Engaging Former Drug Users as Key Research Staff to Design and Implement a Risk Reduction Program for Rural Cocaine Users

PubMed Central

Stewart, Katharine E.; Wright, Patricia B.; Sims, Desi; Tyner, Kathy Russell; Montgomery, Brooke E. E.

2013-01-01

This manuscript describes lessons learned in the development and implementation of a clinical behavioral trial to reduce sexual risk among African-American cocaine users in rural Arkansas, from the perspectives of a multidisciplinary investigative team and community staff members with a history as local drug users who served as “translators.” Recommendations for investigators doing community-based research with active substance users are provided in the following domains: (a) engaging the community during formative research, (b) establishing bidirectional trust, (c) ensuring community voices are heard, and (d) managing conflict. The “translator’s” role is critical to the success of such projects. PMID:22428822