48 CFR 5.206 - Notices of subcontracting opportunities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... subcontracts, to increase participation by qualified HUBZone small business, small, small disadvantaged, women-owned small business, veteran-owned small business and service-disabled veteran-owned small business.... (b) The notices must describe— (1) The business opportunity; (2) Any prequalification requirements...

48 CFR 5.206 - Notices of subcontracting opportunities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... subcontracts, to increase participation by qualified HUBZone small business, small, small disadvantaged, women-owned small business, veteran-owned small business and service-disabled veteran-owned small business.... (b) The notices must describe— (1) The business opportunity; (2) Any prequalification requirements...

An Analysis of Bid Evaluation Procedures of Contemporary Models for Procurement in Pakistan

DTIC Science & Technology

2016-12-01

21  E.  COMPONENTS FOR BID EVALUATION .........................................21  1.  Market Intelligence...PROCUREMENT SYSTEM ...............................................23  1.  Basic Principles ...43  1.  Principles of Procurement and Prequalification .......................43  2.  Contract Types

Development of field performance evaluation tools and program for pavement marking materials : technical report

DOT National Transportation Integrated Search

2011-03-01

Historically the prequalification or selection of pavement marking materials (PMMs) is mainly based on : product specifications and lab testing, which do not correlate well with the field performance of the products. : On the other hand, there is no ...

Optimal Contractor Selection in Construction Industry: The Fuzzy Way

NASA Astrophysics Data System (ADS)

Krishna Rao, M. V.; Kumar, V. S. S.; Rathish Kumar, P.

2018-02-01

A purely price-based approach to contractor selection has been identified as the root cause for many serious project delivery problems. Therefore, the capability of the contractor to execute the project should be evaluated using a multiple set of selection criteria including reputation, past performance, performance potential, financial soundness and other project specific criteria. An industry-wide questionnaire survey was conducted with the objective of identifying the important criteria for adoption in the selection process. In this work, a fuzzy set based model was developed for contractor prequalification/evaluation, by using effective criteria obtained from the percept of construction professionals, taking subjective judgments of decision makers also into consideration. A case study consisting of four alternatives (contractors in the present case) solicited from a public works department of Pondicherry in India, is used to illustrate the effectiveness of the proposed approach. The final selection of contractor is made based on the integrated score or Overall Evaluation Score of the decision alternative in prequalification as well as bid evaluation stages.

Peer mentoring: Enhancing the transition from student to professional.

PubMed

Fisher, Margaret; Stanyer, Rachel

2018-05-01

to share the experience of a model of peer mentoring in a pre-qualification midwifery programme DESIGN: description of the framework and benefits of the model SETTING: University and practice PARTICIPANTS: third year midwifery students INTERVENTIONS: practical activities meeting regulatory body requirements in a pre-qualification mentorship module MEASUREMENTS AND FINDINGS: informal evaluations by students of key activities undertaken during peer mentoring demonstrated a range of positive outcomes. These included enhanced confidence, self-awareness, interpersonal and teaching skills, team-working and leadership - factors also associated with emotional intelligence. Students developed an appreciation of the accountability of the mentor including making practice assessment decisions. They stated that the learning achieved had aided their professional development and enhanced employability. this module equips students with skills for their future role in facilitating learners and contributes to development of a 'professional persona', enhancing their transition to qualified midwives. The Peer Mentoring Model would be easily adapted to other programmes and professional contexts. Copyright © 2018 Elsevier Ltd. All rights reserved.

48 CFR 52.250-4 - SAFETY Act Pre-qualification Designation Notice.

Code of Federal Regulations, 2013 CFR

2013-10-01

... (including information technology) or any combination of the foregoing. Design services, consulting services... information, including— (i) A detailed description of and specification for the technology covered by the... Act certification of a technology class that the Department of Homeland Security (DHS) has determined...

48 CFR 52.250-4 - SAFETY Act Pre-qualification Designation Notice.

Code of Federal Regulations, 2014 CFR

2014-10-01

... (including information technology) or any combination of the foregoing. Design services, consulting services... information, including— (i) A detailed description of and specification for the technology covered by the... Act certification of a technology class that the Department of Homeland Security (DHS) has determined...

48 CFR 52.250-4 - SAFETY Act Pre-qualification Designation Notice.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (including information technology) or any combination of the foregoing. Design services, consulting services... information, including— (i) A detailed description of and specification for the technology covered by the... Act certification of a technology class that the Department of Homeland Security (DHS) has determined...

48 CFR 52.250-4 - SAFETY Act Pre-qualification Designation Notice.

Code of Federal Regulations, 2012 CFR

2012-10-01

... (including information technology) or any combination of the foregoing. Design services, consulting services... information, including— (i) A detailed description of and specification for the technology covered by the... Act certification of a technology class that the Department of Homeland Security (DHS) has determined...

48 CFR 52.250-4 - SAFETY Act Pre-qualification Designation Notice.

Code of Federal Regulations, 2010 CFR

2010-10-01

... attempts to use instrumentalities, weapons or other methods designed or intended to cause mass destruction... Technology (QATT) means any technology designed, developed, modified, procured, or sold for the purpose of... (including information technology) or any combination of the foregoing. Design services, consulting services...

The Computerization of the National Library in Paris.

ERIC Educational Resources Information Center

Lerin, Christian; Bernard, Annick

1986-01-01

Describes the organization and automation plan of the Bibliotheque Nationale (Paris, France) that was begun in 1981. Highlights include the method of moving toward computerization; technical choices; the choosing procedure (pre-qualification, bench-mark test); short term and pilot operations; and preparation for the implementation of the…

Working for Learning: Teaching Assistants Developing Mathematics for Teaching

ERIC Educational Resources Information Center

Drake, Pat

2009-01-01

This article derives from a case study of 10 secondary school teaching assistants (TAs) who did not have conventional pre-qualifications in mathematics but who undertook an honours degree in mathematics education studies at a Higher Education Institution in England whilst continuing to work as TAs in school. Work-based learning was thus undertaken…

48 CFR 50.205-3 - Authorization of offers contingent upon SAFETY Act designation or certification before contract...

Code of Federal Regulations, 2011 CFR

2011-10-01

...— (i) For offers contingent upon SAFETY Act designation, a pre-qualification designation notice or a block designation; or (ii) For offers contingent upon SAFETY Act certification, a block certification... contingent upon SAFETY Act designation or certification before contract award. 50.205-3 Section 50.205-3...

Clinical Observed Performance Evaluation: A Prospective Study in Final Year Students of Surgery

ERIC Educational Resources Information Center

Markey, G. C.; Browne, K.; Hunter, K.; Hill, A. D.

2011-01-01

We report a prospective study of clinical observed performance evaluation (COPE) for 197 medical students in the pre-qualification year of clinical education. Psychometric quality was the main endpoint. Students were assessed in groups of 5 in 40-min patient encounters, with each student the focus of evaluation for 8 min. Each student had a series…

Fatigue behaviour analysis for the durability prequalification of strengthening mortars

NASA Astrophysics Data System (ADS)

Bocca, P.; Grazzini, A.; Masera, D.

2011-07-01

An innovative laboratory procedure used as a preliminary design stage for the pre-qualification of strengthening mortars applied to historical masonry buildings is described. In the analysis of the behaviour of masonry structures and their constituent materials, increasing importance has been assumed by the study of the long-term evolution of deformation and mechanical characteristics, which may be affected by both loading and environmental conditions. Through static and fatigue tests on mixed specimens historical brick-reinforced mortar it has been possible to investigate the durability of strengthening materials, in order to select, from a range of alternatives, the most suitable for the historical masonry. Cyclic fatigue stress has been applied to accelerate the static creep and to forecast the corresponding creep behaviour of the historical brick-strengthening mortar system under static long-time loading. This methodology has proved useful in avoiding the errors associated with materials that are not mechanically compatible and guarantees the durability of strengthening work. The experimental procedure has been used effectively in the biggest restoration building site in Europe, the Royal Palace of Venaria, and it is in progress of carrying out at the Special Natural Reserve of the Sacro Monte di Varallo, in Piedmont (Italy).

Experiences with Use of Various Pedagogical Methods Utilizing a Student Response System -- Motivation and Learning Outcome

ERIC Educational Resources Information Center

Arnesen, Ketil; Korpas, Guri Sivertsen; Hennissen, Jon Eirik; Stav, John Birger

2013-01-01

This paper describes use of an online Student Response System (SRS) in a pre-qualification course for engineering studies in Norway. The SRS in use, where students answer quizzes using handheld mobile devices like Smartphones, PADs, iPods etc., has been developed at Sor-Trondelag University College. The development of the SRS was co-funded by the …

Regulatory Pathways That Facilitated Timely Registration of a New Group A Meningococcal Conjugate Vaccine for Africa's Meningitis Belt Countries.

PubMed

Dellepiane, Nora; Akanmori, Bartholomew Dicky; Gairola, Sunil; Jadhav, Suresh S; Parker, Cathy; Rodriguez, Carmen; Srivastava, Swati

2015-11-15

Through its normative and public health leadership roles, the World Health Organization (WHO) plays a key role in the availability of vaccine products in low-and middle-income countries. The recent introduction of a new group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), in Africa exemplifies this process. WHO requires that any new vaccine to be introduced in countries for public health reasons and supplied through United Nations centralized mechanisms be licensed by the national regulatory agency (NRA) in the producing country, then prequalified and given a marketing authorization in the user countries. PsA-TT was manufactured by the Serum Institute of India, Ltd (SIIL), which submitted a license application in April 2009 to the Drug Controller General of India (DCGI), the Indian NRA responsible for licensing vaccines. WHO encouraged the DCGI to establish a collaboration with Health Canada's Centre for Vaccine Evaluation for the review. Through this collaborative effort, registration was facilitated and in December 2009 an export license was granted to SIIL, which subsequently submitted an application for WHO prequalification. Given the importance of the vaccine, WHO "fast tracked" the prequalification review, and after a detailed review and site visit, WHO prequalification was granted to PsA-TT in June 2010. Country use of the new vaccine could not occur until the vaccine was a registered product in each country seeking its use. WHO facilitated country reviews by conducting regulatory training exercises (in French and English) for country NRA staff, which used the PsA-TT registration as a case study. PsA-TT was gradually registered in African countries as vaccine introduction proceeded. The regulatory pathway for this new group A meningococcal conjugate vaccine proved to be a useful training opportunity both in India and Africa, because the availability of the vaccine was a high African public health priority, as well as for WHO as a case study to facilitate registration of vaccines based on reliance on other regulatory bodies. © 2015 World Health Organization; licensee Oxford Journals.

An Analysis of Viable Financial Negotiations Processes and Related Internal Controls for Procurement in Pakistan

DTIC Science & Technology

2016-06-01

regulations are in accordance with UNCITRAL Model Law and are based on principles of “ accountability , transparency, fairness, efficiency and value for... account certain factors about the firm(s) for pre-qualification. These factors include past performance and experience; financial health; managerial...internal control components, along with associated principles , were discussed in detail to develop a suitable internal control system for the financial

From school to work: promoting the application of pre-qualification interprofessional education in the clinical workplace.

PubMed

Murray-Davis, Beth; Marshall, Michelle; Gordon, Frances

2012-09-01

The rationale for Interprofessional Education (IPE) is based on the assumption it will improve practice. Despite evidence that it may modify attitudes and provide knowledge and skills for collaboration, there is little evidence about whether these skills can be transferred to practice. The aim of this research was to explore how midwifery students apply pre-qualification IPE learning to practice and to understand the factors in the clinical workplace that facilitate or hinder this application. A purposive sample of students, educators, Heads of Midwifery and new midwives from four universities throughout the United Kingdom participated in semi-structured interviews and focus groups. Emerging themes were developed using the principles of Grounded Theory. Participants articulated ways in which the clinical environment either promoted or prevented IPE in practice. The extent to which the clinical institution promoted IPE was made visible through the support for students during placements; the support for new midwives; and the evolution of professional roles. Buy-in for the IPE agenda in the workplace influences the ability of new midwives to apply IPE competencies to professional practice. The benefits of a theoretical foundation in interprofessional skills may be lost if students and new midwives find themselves working in contexts that do not make collaboration a priority. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lessons learnt from 12 oral cholera vaccine campaigns in resource-poor settings.

PubMed

Hsiao, Amber; Desai, Sachin N; Mogasale, Vittal; Excler, Jean-Louis; Digilio, Laura

2017-04-01

Improving water and sanitation is the preferred choice for cholera control in the long-term. Nevertheless, vaccination is an available tool that has been shown to be a cost-effective option for cholera prevention in endemic countries or during outbreaks. In 2011 the first low-cost oral cholera vaccine for international use was given prequalification by the World Health Organization (WHO). To increase and prioritize use of the vaccine, WHO created a global stockpile in 2013 from which countries may request oral cholera vaccine for reactive campaigns. WHO has issued specific guidelines for applying for the vaccine, which was previously in short supply (despite prequalification for a second oral vaccine in 2015). The addition of a third WHO-prequalified oral cholera vaccine in 2016 is expected to increase the global stockpile considerably and alleviate supply issues. However, prioritization and best use of the vaccine (e.g. how, when and where to use) will remain challenges. We describe 12 past oral cholera vaccine campaigns, conducted in settings with varying burdens of cholera. These case studies illustrate three key challenges faced in the use of the oral cholera vaccines: regulatory hurdles, cold chain logistics and vaccine coverage and uptake. To pave the way for the introduction of current and future oral cholera vaccines, we discuss operational challenges and make recommendations for future research with respect to each of these challenges.

Lessons learnt from 12 oral cholera vaccine campaigns in resource-poor settings

PubMed Central

Desai, Sachin N; Mogasale, Vittal; Excler, Jean-Louis; Digilio, Laura

2017-01-01

Abstract Improving water and sanitation is the preferred choice for cholera control in the long-term. Nevertheless, vaccination is an available tool that has been shown to be a cost-effective option for cholera prevention in endemic countries or during outbreaks. In 2011 the first low-cost oral cholera vaccine for international use was given prequalification by the World Health Organization (WHO). To increase and prioritize use of the vaccine, WHO created a global stockpile in 2013 from which countries may request oral cholera vaccine for reactive campaigns. WHO has issued specific guidelines for applying for the vaccine, which was previously in short supply (despite prequalification for a second oral vaccine in 2015). The addition of a third WHO-prequalified oral cholera vaccine in 2016 is expected to increase the global stockpile considerably and alleviate supply issues. However, prioritization and best use of the vaccine (e.g. how, when and where to use) will remain challenges. We describe 12 past oral cholera vaccine campaigns, conducted in settings with varying burdens of cholera. These case studies illustrate three key challenges faced in the use of the oral cholera vaccines: regulatory hurdles, cold chain logistics and vaccine coverage and uptake. To pave the way for the introduction of current and future oral cholera vaccines, we discuss operational challenges and make recommendations for future research with respect to each of these challenges. PMID:28479625

A qualitative assessment of the challenges of WHO prequalification for anti-malarial drugs in China.

PubMed

Huang, Yangmu; Pan, Ke; Peng, Danlu; Stergachis, Andy

2018-04-03

While China is a major manufacturer of artemisinin and its derivatives, it lags as a global leader in terms of the total export value of anti-malarial drugs as finished pharmaceutical products ready for marketing and use by patients. This may be due to the limited number of World Health Organization (WHO) prequalified anti-malarial drugs from China. Understanding the reasons for the slow progress of WHO prequalification (PQ) in China can help improve the current situation and may lead to greater efforts in malaria eradication by Chinese manufacturers. In-depth interviews were conducted in China between November 2014 and December 2016. A total of 26 key informants from central government agencies, pharmaceutical companies, universities, and research institutes were interviewed, all of which had current or previous experience overseeing or implementing anti-malarial research and development in China. Chinese anti-malarial drugs that lack WHO PQ are mainly exported for use in the African private market. High upfront costs with unpredictable benefits, as well as limited information and limited technical support on WHO PQ, were reported as the main barriers to obtain WHO PQ for anti-malarial drugs by respondents from Chinese pharmaceutical companies. Potential incentives identified by respondents included tax relief, human resource training and consultation, as well as other incentives related to drug approval, such as China's Fast Track Channel. Government support, as well as innovative incentives and collaboration mechanisms are needed for further adoption of WHO PQ for anti-malarial drugs in China.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2009-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new standards and guidelines were adopted and recommended for use: the current list of available International Chemical Reference Substances and International Infrared Reference Spectra; guidelines on stability testing of active pharmaceutical ingredients and finished pharmaceutical products; procedure for prequalification of pharmaceutical products; and the procedure for assessing the acceptability, in principle, of active pharmaceutical ingredients for use in pharmaceutical products.

WHO expert committee on specifications for pharmaceutical preparations.

PubMed

2013-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: Release procedure for International Chemical Reference Substances; WHO guidelines on quality risk management; WHO guidelines on variations to a prequalified product; and the Collaborative procedure between the World Health Organization Prequalification of Medicines Programme and national medicines regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products.

A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions.

PubMed

Mogasale, Vittal; Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

2017-09-02

A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.

A critical appraisal of instruments to measure outcomes of interprofessional education.

PubMed

Oates, Matthew; Davidson, Megan

2015-04-01

Interprofessional education (IPE) is believed to prepare health professional graduates for successful collaborative practice. A range of instruments have been developed to measure the outcomes of IPE. An understanding of the psychometric properties of these instruments is important if they are to be used to measure the effectiveness of IPE. This review set out to identify instruments available to measure outcomes of IPE and collaborative practice in pre-qualification health professional students and to critically appraise the psychometric properties of validity, responsiveness and reliability against contemporary standards for instrument design. Instruments were selected from a pool of extant instruments and subjected to critical appraisal to determine whether they satisfied inclusion criteria. The qualitative and psychometric attributes of the included instruments were appraised using a checklist developed for this review. Nine instruments were critically appraised, including the widely adopted Readiness for Interprofessional Learning Scale (RIPLS) and the Interdisciplinary Education Perception Scale (IEPS). Validity evidence for instruments was predominantly based on test content and internal structure. Ceiling effects and lack of scale width contribute to the inability of some instruments to detect change in variables of interest. Limited reliability data were reported for two instruments. Scale development and scoring protocols were generally reported by instrument developers, but the inconsistent application of scoring protocols for some instruments was apparent. A number of instruments have been developed to measure outcomes of IPE in pre-qualification health professional students. Based on reported validity evidence and reliability data, the psychometric integrity of these instruments is limited. The theoretical test construction paradigm on which instruments have been developed may be contributing to the failure of some instruments to detect change in variables of interest following an IPE intervention. These limitations should be considered in any future research on instrument design. © 2015 John Wiley & Sons Ltd.

A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions

PubMed Central

Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

2017-01-01

ABSTRACT A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy. PMID:28604164

Correlation of Hollow Cathode Assembly and Plasma Contactor Data from Ground Testing and In-Space Operation on the International Space Station

NASA Technical Reports Server (NTRS)

Kovalkeski, Scott D.; Patterson, Michael J.; Soulas, George C.

2001-01-01

Charge control on the International Space Station (ISS) is currently being provided by two plasma contactor units (PCUs). The plasma contactor includes a hollow cathode assembly (HCA), power processing unit and Xe gas feed system. The hollow cathode assemblies in use in the ISS plasma contactors were designed and fabricated at the NASA Glenn Research Center. Prequalification testing of development HCAs as well as acceptance testing of the flight HCAs is presented. Integration of the HCAs into the Boeing North America built PCU and acceptance testing of the PCU are summarized in this paper. Finally, data from the two on-orbit PCUs is presented.

Interventions to combat or prevent drug counterfeiting: a systematic review.

PubMed

El-Jardali, Fadi; Akl, Elie A; Fadlallah, Racha; Oliver, Sandy; Saleh, Nadine; El-Bawab, Lamya; Rizk, Rana; Farha, Aida; Hamra, Rasha

2015-03-18

Drug counterfeiting has serious public health and safety implications. The objective of this study was to systematically review the evidence on the effectiveness of interventions to combat or prevent drug counterfeiting. We searched multiple electronic databases and the grey literature up to March 2014. Two reviewers completed, in duplicate and independently, the study selection, data abstraction and risk of bias assessment. We included randomised trials, non-randomised studies, and case studies examining any intervention at the health system-level to combat or prevent drug counterfeiting. Outcomes of interest included changes in failure rates of tested drugs and changes in prevalence of counterfeit medicines. We excluded studies that focused exclusively on substandard, degraded or expired drugs, or that focused on medication errors. We assessed the risk of bias in each included study. We reported the results narratively and, where applicable, we conducted meta-analyses. We included 21 studies representing 25 units of analysis. Overall, we found low quality evidence suggesting positive effects of drug registration (OR=0.23; 95% CI 0.08 to 0.67), and WHO-prequalification of drugs (OR=0.06; 95% CI 0.01 to 0.35) in reducing the prevalence of counterfeit and substandard drugs. Low quality evidence suggests that licensing of drug outlets is probably ineffective (OR=0.66; 95% CI 0.41 to 1.05). For multifaceted interventions (including a mix of regulations, training of inspectors, public-private collaborations and legal actions), low quality evidence suggest they may be effective. The single RCT provided moderate quality evidence of no effect of 'two extra inspections' in improving drug quality. Policymakers and stakeholders would benefit from registration and WHO-prequalification of drugs and may also consider multifaceted interventions. Future effectiveness studies should address the methodological limitations of the available evidence. PROSPERO CRD42014009269. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2012-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: Development of monographs for The International Pharmacopoeia; WHO good manufacturing practices: water for pharmaceutical use; Pharmaceutical development of multisource (generic) pharmaceutical products--points to consider; Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product for the WHO Prequalification of Medicines Programme: quality part; Development of paediatric medicines: points to consider in formulation; Recommendations for quality requirements for artemisinin as a starting material in the production of antimalarial active pharmaceutical ingredients.

A 30% bandwidth tunerless SIS mixer of quantum-limited sensitivity for Herschel / HIFI Band 1

NASA Astrophysics Data System (ADS)

Salez, Morvan; Delorme, Yan; Peron, I.; Lecomte, Benoit; Dauplay, Frederic; Boussaha, Faouzi; Spatazza, J.; Feret, A.; Krieg, J. M.; Schuster, Karl-Friedrich

2003-02-01

We report on the status of the development of a 30% bandwidth tunerless SIS double-sideband mixer for the "Band 1" (480 GHz-630 GHz) channel of the heterodyne instrument (HIFI) of ESA"s Herschel Space Observatory, scheduled for launch in 2007. After exposing the main features of our mixer design, we present the performance achieved by the demonstration mixer, measured via Fourier Transform Spectroscopy and heterodyne Y factor calibrations. We infer from a preliminary mixer analysis that the mixer has very low, quantum-limited noise and low conversion loss. We also report on some pre-qualification tests, as we currently start to manufacture the qualification models and design the last iteration of masks for SIS junction production.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2014-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use, in addition to 20 monographs and general texts for inclusion in The International Pharmacopoeia and 11 new International Chemical Reference Substances. The International Pharmacopoeia--updating mechanism for the section on radiopharmaceuticals; WHO good manufacturing practices for pharmaceutical products: main principles; Model quality assurance system for procurement agencies; Assessment tool based on the model quality assurance system for procurement agencies: aide-memoire for inspection; Guidelines on submission of documentation for prequalification of finished pharmaceutical products approved by stringent regulatory authorities; and Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product: quality part.

A new star (sensor) is born

NASA Astrophysics Data System (ADS)

Leijtens, Johan; Vliegenthart, Willem; Lampridis, Dimitris; Vacanti, Giuseppe; Monna, Bert; Bechthum, Elbert; Hagenaars, Koen; van der Heide, Erik; Kruijff, Michiel; van Breukelen, Eddie; LeMair, Anita

2017-11-01

In the frame of the Dutch Prequalification for ESA Programs(PEP), as part of the efforts to design an integrated optical attitude control subsytem (IOPACS), a consortium of TNO and several SME's in the Netherlands have been working on a novel type of startracker called MABS (Multiple Aperture Baffled Startracker). The system comprises a single cast metal housing with four reflective optical telescopes which use only structural internal baffling. Inherent to the design are a very high stability and excellent co-alignment between the apertures, a significant decrease in system size and low recurring production cost. The concept is a radical change from more common multiple startracker setups. The presentation will concentrate on the validity of the concept, the predicted performance and benefits for space applications, the produced breadboard and measured performances as well as the costing aspects.

Chinese vaccine products go global: vaccine development and quality control.

PubMed

Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

2015-05-01

Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

Hepatitis E virus: Current epidemiology and vaccine.

PubMed

Wu, Xing; Chen, Pan; Lin, Huijuan; Hao, Xiaotian; Liang, Zhenglun

2016-10-02

Hepatitis E virus infections have been continuously reported in Indian subcontinent, Africa, southeast and central Asia, posing great health threats to the public, especially to pregnant women. Hecolin® is the only licensed HEV vaccine developed by Xiamen Innovax Biotech Co., Ltd. Extensive characterizations on antigenicity, physicochemical properties, efficacy in clinical trials, and manufacturing capability have made Hecolin® a promising vaccine for HEV control. However, there are many obstacles in large scale application of Hecolin®. Efforts are needed to further evaluate safety and efficacy in HEV risk populations, and to complement HEV standards for quality control. Passing World Health Organization prequalification and licensing outside China are priorities as these are also hindering Hecolin® promotion. Multilateral cooperation among Chinese vaccine manufacturers, Chinese National Regulatory Authorization (NRA) and WHO will expedite the entrance of Hecolin® into international market, so that Hecolin® could play its due role in global hepatitis E control.

Limiting Exposure to Medical Malpractice Claims and Defamatory Cyber Postings via Patient Contracts

PubMed Central

Segal, Jeffrey J.

2008-01-01

The documents patients sign on admission to a medical practice can constitute a legal contract. Medical practices around the country are attempting to use these documents as a prospective defense against medical malpractice claims. Protective contractual provisions are often attacked on grounds that they are legally void as a result of unconscionability. Widespread use of arbitration clauses have been met with mixed success. Arbitration clauses that limit damages available in medical negligence cases have been stricken in some states as having provisions that impose excessive entry costs on a patient starting the arbitration process. Other provisions relating to prequalification requirements for expert witnesses are now being used with increasing frequency. Clauses have even been placed in patient contracts that address cyber postings of adverse claims against physicians. Prospective patient contracts may be an effective means to limit exposure to medical malpractice lawsuits and to minimize defamatory cyber postings. PMID:19057975

Testing a model of research intention among U.K. clinical psychologists: a logistic regression analysis.

PubMed

Eke, Gemma; Holttum, Sue; Hayward, Mark

2012-03-01

Previous research highlights barriers to clinical psychologists conducting research, but has rarely examined U.K. clinical psychologists. The study investigated U.K. clinical psychologists' self-reported research output and tested part of a theoretical model of factors influencing their intention to conduct research. Questionnaires were mailed to 1,300 U.K. clinical psychologists. Three hundred and seventy-four questionnaires were returned (29% response-rate). This study replicated in a U.K. sample the finding that the modal number of publications was zero, highlighted in a number of U.K. and U.S. studies. Research intention was bimodally distributed, and logistic regression classified 78% of cases successfully. Outcome expectations, perceived behavioral control and normative beliefs mediated between research training environment and intention. Further research should explore how research is negotiated in clinical roles, and this issue should be incorporated into prequalification training. © 2012 Wiley Periodicals, Inc.

Achievements and challenges for the use of killed oral cholera vaccines in the global stockpile era.

PubMed

Desai, Sachin N; Pezzoli, Lorenzo; Alberti, Kathryn P; Martin, Stephen; Costa, Alejandro; Perea, William; Legros, Dominique

2017-03-04

Cholera remains an important but neglected public health threat, affecting the health of the poorest populations and imposing substantial costs on public health systems. Cholera can be eliminated where access to clean water, sanitation, and satisfactory hygiene practices are sustained, but major improvements in infrastructure continue to be a distant goal. New developments and trends of cholera disease burden, the creation of affordable oral cholera vaccines (OCVs) for use in developing countries, as well as recent evidence of vaccination impact has created an increased demand for cholera vaccines. The global OCV stockpile was established in 2013 and with support from Gavi, has assisted in achieving rapid access to vaccine in emergencies. Recent WHO prequalification of a second affordable OCV supports the stockpile goals of increased availability and distribution to affected populations. It serves as an essential step toward an integrated cholera control and prevention strategy in emergency and endemic settings.

Limiting exposure to medical malpractice claims and defamatory cyber postings via patient contracts.

PubMed

Sacopulos, Michael; Segal, Jeffrey J

2009-02-01

The documents patients sign on admission to a medical practice can constitute a legal contract. Medical practices around the country are attempting to use these documents as a prospective defense against medical malpractice claims. Protective contractual provisions are often attacked on grounds that they are legally void as a result of unconscionability. Widespread use of arbitration clauses have been met with mixed success. Arbitration clauses that limit damages available in medical negligence cases have been stricken in some states as having provisions that impose excessive entry costs on a patient starting the arbitration process. Other provisions relating to prequalification requirements for expert witnesses are now being used with increasing frequency. Clauses have even been placed in patient contracts that address cyber postings of adverse claims against physicians. Prospective patient contracts may be an effective means to limit exposure to medical malpractice lawsuits and to minimize defamatory cyber postings.

Speeding Access to Vaccines and Medicines in Low- and Middle-Income Countries: A Case for Change and a Framework for Optimized Product Market Authorization

PubMed Central

Ahonkhai, Vincent; Portet, Alexandre; Hartman, Dan

2016-01-01

Background The United Nations Millennium Development Goals galvanized global efforts to alleviate suffering of the world’s poorest people through unprecedented public-private partnerships. Donor aid agencies have demonstrably saved millions of lives that might otherwise have been lost to disease through increased access to quality-assured vaccines and medicines. Yet, the introduction of these health interventions in low- and middle-income countries (LMICs) continues to face a time lag due to factors which remain poorly understood. Methods and Findings A recurring theme from our partnership engagements was that an optimized regulatory process would contribute to improved access to quality health products. Therefore, we investigated the current system for medicine and vaccine registration in LMICs as part of our comprehensive regulatory strategy. Here, we report a fact base of the registration timelines for vaccines and drugs used to treat certain communicable diseases in LMICs. We worked with a broad set of stakeholders, including the World Health Organization’s prequalification team, national regulatory authorities, manufacturers, procurers, and other experts, and collected data on the timelines between first submission and last approval of applications for product registration sub-Saharan Africa. We focused on countries with the highest burden of communicable disease and the greatest need for the products studied. The data showed a typical lag of 4 to 7 years between the first regulatory submission which was usually to a regulatory agency in a high-income country, and the final approval in Sub-Saharan Africa. Two of the three typical registration steps which products undergo before delivery in the countries involve lengthy timelines. Failure to leverage or rely on the findings from reviews already performed by competent regulatory authorities, disparate requirements for product approval by the countries, and lengthy timelines by manufacturers to respond to regulatory queries were key underlying factors for the delays. Conclusions We propose a series of measures which we developed in close collaboration with key stakeholders that could be taken to reduce registration time and to make safe, effective medicines more quickly available in countries where they are most needed. Many of these recommendations are being implemented by the responsible stakeholders, including the WHO prequalification team and the national regulatory authorities in Sub-Saharan Africa. Those efforts will be the focus of subsequent publications by the pertinent groups. PMID:27851831

Speeding Access to Vaccines and Medicines in Low- and Middle-Income Countries: A Case for Change and a Framework for Optimized Product Market Authorization.

PubMed

Ahonkhai, Vincent; Martins, Samuel F; Portet, Alexandre; Lumpkin, Murray; Hartman, Dan

2016-01-01

The United Nations Millennium Development Goals galvanized global efforts to alleviate suffering of the world's poorest people through unprecedented public-private partnerships. Donor aid agencies have demonstrably saved millions of lives that might otherwise have been lost to disease through increased access to quality-assured vaccines and medicines. Yet, the introduction of these health interventions in low- and middle-income countries (LMICs) continues to face a time lag due to factors which remain poorly understood. A recurring theme from our partnership engagements was that an optimized regulatory process would contribute to improved access to quality health products. Therefore, we investigated the current system for medicine and vaccine registration in LMICs as part of our comprehensive regulatory strategy. Here, we report a fact base of the registration timelines for vaccines and drugs used to treat certain communicable diseases in LMICs. We worked with a broad set of stakeholders, including the World Health Organization's prequalification team, national regulatory authorities, manufacturers, procurers, and other experts, and collected data on the timelines between first submission and last approval of applications for product registration sub-Saharan Africa. We focused on countries with the highest burden of communicable disease and the greatest need for the products studied. The data showed a typical lag of 4 to 7 years between the first regulatory submission which was usually to a regulatory agency in a high-income country, and the final approval in Sub-Saharan Africa. Two of the three typical registration steps which products undergo before delivery in the countries involve lengthy timelines. Failure to leverage or rely on the findings from reviews already performed by competent regulatory authorities, disparate requirements for product approval by the countries, and lengthy timelines by manufacturers to respond to regulatory queries were key underlying factors for the delays. We propose a series of measures which we developed in close collaboration with key stakeholders that could be taken to reduce registration time and to make safe, effective medicines more quickly available in countries where they are most needed. Many of these recommendations are being implemented by the responsible stakeholders, including the WHO prequalification team and the national regulatory authorities in Sub-Saharan Africa. Those efforts will be the focus of subsequent publications by the pertinent groups.

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Fiftieth report.

PubMed

2016-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use. Good pharmacopoeial practices; FIP-WHO technical guidelines: points to consider in the provision by health-care professionals of children-specific preparations that are not available as authorized products; Guidance on good manufacturing practices for biological products; Guidance on good manufacturing practices: inspection report, including Appendix 1: Model inspection report; Guidance on good data and record management practices; Good trade and distribution practices for starting materials; Guidelines on the conduct of surveys of the quality of medicines; Collaborative procedure between the World Health Organization (WHO) prequalification team and national regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products and vaccines; Guidance for organizations performing in vivo bioequivalence studies; and World Health Organization (WHO) general guidance on variations to multisource pharmaceutical products.

WHO expert committee on specifications for pharmaceutical preparations. Fortieth report.

PubMed

2006-01-01

This report presents the recommendations of an international group of experts convened by the World Health Organization to consider matters concerning the quality assurance of pharmaceuticals and specifications for drug substances and dosage forms. The report is complemented by a number of annexes. These include: a list of available International Chemical Reference Substances and International Infrared Spectra; supplementary guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms; updated supplementary guidelines on good manufacturing practices for the manufacture of herbal medicines; supplementary guidelines on good manufacturing practices for validation; good distribution practices for pharmaceutical products; a model quality assurance system for procurement agencies (recommendations for quality assurance systems focusing on prequalification of products and manufacturers, purchasing, storage and distribution of pharmaceutical products); multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability; a proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms; and additional guidance for organizations performing in vivo bioequivalence studies.

Achievements and challenges for the use of killed oral cholera vaccines in the global stockpile era

PubMed Central

Desai, Sachin N.; Pezzoli, Lorenzo; Alberti, Kathryn P.; Martin, Stephen; Costa, Alejandro; Perea, William; Legros, Dominique

2017-01-01

ABSTRACT Cholera remains an important but neglected public health threat, affecting the health of the poorest populations and imposing substantial costs on public health systems. Cholera can be eliminated where access to clean water, sanitation, and satisfactory hygiene practices are sustained, but major improvements in infrastructure continue to be a distant goal. New developments and trends of cholera disease burden, the creation of affordable oral cholera vaccines (OCVs) for use in developing countries, as well as recent evidence of vaccination impact has created an increased demand for cholera vaccines. The global OCV stockpile was established in 2013 and with support from Gavi, has assisted in achieving rapid access to vaccine in emergencies. Recent WHO prequalification of a second affordable OCV supports the stockpile goals of increased availability and distribution to affected populations. It serves as an essential step toward an integrated cholera control and prevention strategy in emergency and endemic settings. PMID:27813703

Current status of final design and R&D for ITER blanket shield blocks in Korea

NASA Astrophysics Data System (ADS)

Ha, M. S.; Kim, S. W.; Jung, H. C.; Hwang, H. S.; Heo, Y. G.; Kim, D. H.; Ahn, H. J.; Lee, H. G.; Jung, K. J.

2015-07-01

The main function of the ITER blanket shield block (SB) is to provide nuclear shielding and support the first wall (FW) panel. It needs to accommodate all the components located on the vacuum vessel (in particular the in-vessel coils, blanket manifolds and the diagnostics). The conceptual, preliminary and final design reviews have been completed in the framework of the Blanket Integrated Product Team. The Korean Domestic Agency has successfully completed not only the final design activities, including thermo-hydraulic and thermo-mechanical analyses for SBs #2, #6, #8 and #16, but also the SB full scale prototype (FSP) pre-qualification program prior to issuing of the procurement agreement. SBs #2 and #6 are located at the in-board region of the tokamak. The pressure drop was less than 0.3 MPa and fully satisfied the design criteria. The thermo-mechanical stresses were also allowable even though the peak stresses occurred at nearby radial slit end holes, and their fatigue lives were evaluated over many more than 30 000 cycles. SB #8 is one of the most difficult modules to design, since this module will endure severe thermal loading not only from nuclear heating but also from plasma heat flux at uncovered regions by the FW. In order to resolve this design issue, the neutral beam shine-through module concept was applied to the FW uncovered region and it has been successfully verified as a possible design solution. SB #16 is located at the out-board central region of the tokamak. This module is under much higher nuclear loading than other modules and is covered by an enhanced heat flux FW panel. In the early design stage, many cooling headers on the front region were inserted to mitigate peak stresses near the access hole and radial slit end hole. However, the cooling headers on the front region needed to be removed in order to reduce the risk from cover welding during manufacturing. A few cooling headers now remain after efforts through several iterations to remove them and to optimize the cooling channels. The SB #8 FSP was manufactured and tested in accordance with the pre-qualification program based on the preliminary design, and related R&D activities were implemented to resolve the fabrication issues. This paper provides the current status of the final design and relevant R&D activities of the blanket SB.

Interprofessional education and practice guide No. 5: Interprofessional teaching for prequalification students in clinical settings.

PubMed

Lie, Désirée A; Forest, Christopher P; Kysh, Lynn; Sinclair, Lynne

2016-05-01

The importance of interprofessional education in health professions training is increasingly recognised through new accreditation guidelines. Clinician teachers from different professions may find themselves being asked to teach or supervise learners from multiple health professions, focusing on interprofessional dynamics, interprofessional communication, role understanding, and the values and ethics of collaboration. Clinician teachers often feel prepared to teach learners from their own profession but may feel ill prepared to teach learners from other professions. In this guide, we draw upon the collective experience from two countries: an institution from the United States with experience in guiding faculty to teach in a student-run interprofessional clinic and an institution from Canada that offers interprofessional experiences to students in community and hospital settings. This guide offers teaching advice to clinician educators in all health professions who plan to or already teach in an interprofessional clinical setting. We anticipate that clinician teachers can learn to fully engage learners from different professions, precept effectively, recognise common pitfalls, increase their confidence, reflect, and become role models to deliver effective teaching in interprofessional settings.

Project safety as a sustainable competitive advantage.

PubMed

Rechenthin, David

2004-01-01

To be consistently profitable, a construction company must complete projects in scope, on schedule, and on budget. At the same time, the nature of the often high-risk work performed by construction companies can result in high accident rates. Clients and other stakeholders are placing increasing pressure on companies to decrease those accident rates. Clients routinely demand copies of safety plans and evidence of past results at the "pre-qualification" or "request for proposal" stages of the procurement process. Are high accident rates and the associated costs just a part of business? Companies that deliver on scope, schedule, and budget have a competitive advantage. Is it possible for projects with low accident rates to use it as a competitive advantage? Is the value added by safety just a temporary or parity issue, or does a successful safety program offer significant advantage to the company and the client? This article concludes that in the case of a high-risk industry, such as the construction industry, an organization with a successful safety program can promote safety performance as a sustainable competitive advantage. It is a choice the company can make.

Partners to invite bids for Qatari plant

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

Alperowicz, N.

Qasenco, a joint venture planning to build a methanol plant at Umm Said, Qatar, will issue prequalification documents to contractors in early July. Partnership agreements to form the joint venture are expected to be concluded at the beginning of June. Qatar General Petroleum Corp. (Doha) will hold 50%. The remaining share will be split between Petronas (Kuala Lumpur) and Penspen (London). Other shareholders may also join. Market studies for the 2,500-m.t./day plant were based on ICI`s technology, but the partners want to look at other available processes-including Mitsubishi Gas Chemical`s-before committing to the $400-million venture. Schroder Wagg (London) has beenmore » appointed as the project`s financial adviser. About 30% of the financing is expected to come from equity and the rest as longterm credit. Petronas, the Malaysian state-owned energy company, already owns a 2,000-m.t./day methanol plant at Labuan but needs more product for its customers in the Far East. The company is interested in taking at least 50% of the output from the Umm Said plant.« less

Consolidated Development Objectives Document (CDOD) For MB-60

NASA Technical Reports Server (NTRS)

Greene, William D.

2013-01-01

This document defines the objectives related to liquid rocket engine system development to be undertaken by JAXA in support of the Space Launch System (SLS) Program managed out of the NASA Marshall Space Flight Center (MSFC). These objectives include furnishing the necessary management, labor, facilities, tools, equipment, and materials required to execute the specified activities. 1.1 Project Scope: The scope of this effort is to develop a rocket engine and associated products per the objectives and technical requirements established in this document. This engine, minus the engine controller, designated here as MB ]60, is to be developed through to a prequalification point of maturity. It is assumed that should JCNE ]1 development proceed beyond this maturity point towards actual flight qualification, the engine controller will be supplied and integrated by NASA. 1.2 Document Structure: The structure of this Consolidated Development Objectives Document (CDOD) includes a traditional description of objectives in a SOO, plus the associated Data Products Document (DPD) in an attached appendix, and then Engine Requirements Document (ERD) as another attached appendix. It is the intent that this document, in conjunction with the cited applicable documents, should constitute a complete programmatic and technical description of the development effort to be pursued.

Sofosbuvir as treatment against dengue?

PubMed

Gan, Chye Sheng; Lim, See Khai; Chee, Chin Fei; Yusof, Rohana; Heh, Choon Han

2018-02-01

Dengvaxia ® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC 90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue. © 2017 John Wiley & Sons A/S.

SCALE UP OF CERAMIC WASTE FORMS FOR THE EBR-II SPENT FUEL TREATMENT PROCESS

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

Matthew C. Morrison; Kenneth J. Bateman; Michael F. Simpson

2010-11-01

ABSTRACT SCALE UP OF CERAMIC WASTE FORMS FOR THE EBR-II SPENT FUEL TREATMENT PROCESS Matthew C. Morrison, Kenneth J. Bateman, Michael F. Simpson Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415 The ceramic waste process is the intended method for disposing of waste salt electrolyte, which contains fission products from the fuel-processing electrorefiners (ER) at the INL. When mixed and processed with other materials, the waste salt can be stored in a durable ceramic waste form (CWF). The development of the CWF has recently progressed from small-scale testing and characterization to full-scale implementation and experimentation using surrogate materialsmore » in lieu of the ER electrolyte. Two full-scale (378 kg and 383 kg) CWF test runs have been successfully completed with final densities of 2.2 g/cm3 and 2.1 g/cm3, respectively. The purpose of the first CWF was to establish material preparation parameters. The emphasis of the second pre-qualification test run was to evaluate a preliminary multi-section CWF container design. Other considerations were to finalize material preparation parameters, measure the material height as it consolidates in the furnace, and identify when cracking occurs during the CWF cooldown process.« less

An empirical review of antimalarial quality field surveys: the importance of characterising outcomes.

PubMed

Grech, James; Robertson, James; Thomas, Jackson; Cooper, Gabrielle; Naunton, Mark; Kelly, Tamsin

2018-01-05

For decades, thousands of people have been dying from malaria infections because of poor-quality medicines (PQMs). While numerous efforts have been initiated to reduce their presence, PQMs are still risking the lives of those seeking treatment. This review addresses the importance of characterising results of antimalarial medicine field surveys based upon the agreement of clearly defined definitions. Medicines found to be of poor quality can be falsified or counterfeit, substandard or degraded. The distinction between these categories is important as each category requires a different countermeasure. To observe the current trends in the reporting of field surveys, a systematic literature search of six academic databases resulted in the quantitative analysis of 61 full-text journal articles. Information including sample size, sampling method, geographical regions, analytical techniques, and characterisation conclusions was observed for each. The lack of an accepted uniform reporting system has resulted in varying, incomplete reports, which may not include important information that helps form effective countermeasures. The programmes influencing medicine quality such as prequalification, procurement services, awareness and education can be supported with the information derived from characterised results. The implementation of checklists such as the Medicine Quality Assessment Reporting Guidelines will further strengthen the battle against poor-quality antimalarials. Copyright © 2017 Elsevier B.V. All rights reserved.

Challenges and priorities in the management of HIV/HBV and HIV/HCV coinfection in resource-limited settings.

PubMed

Easterbrook, Philippa; Sands, Anita; Harmanci, Hande

2012-05-01

Liver disease due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is now emerging as an increasing cause of morbidity and mortality in human immunodeficiency virus- (HIV-) infected persons in resource-limited settings (RLS). Existing management guidelines have generally focused on care in tertiary level facilities in developed countries. Less than half of low-income countries have guidance, and in those that do, there are important omissions or disparities in recommendations. There are multiple challenges to delivery of effective hepatitis care in RLS, but the most important remains the limited access to antiviral drugs and diagnostic tests. In 2010, the World Health Assembly adopted a resolution calling for a comprehensive approach for the prevention, control, and management of viral hepatitis. We describe activities at the World Health Organization (WHO) in three key areas: the establishment of a global hepatitis Program and interim strategy; steps toward the development of global guidance on management of coinfection for RLS; and the WHO prequalification program of HBV and HCV diagnostic assays. We highlight key research gaps and the importance of applying the lessons learned from the public health scale-up of ART to hepatitis care. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Scaling up HIV self-testing in sub-Saharan Africa: a review of technology, policy and evidence.

PubMed

Indravudh, Pitchaya P; Choko, Augustine T; Corbett, Elizabeth L

2018-02-01

HIV self-testing (HIVST) can provide complementary coverage to existing HIV testing services and improve knowledge of status among HIV-infected individuals. This review summarizes the current technology, policy and evidence landscape in sub-Saharan Africa and priorities within a rapidly evolving field. HIVST is moving towards scaled implementation, with the release of WHO guidelines, WHO prequalification of the first HIVST product, price reductions of HIVST products and a growing product pipeline. Multicountry evidence from southern and eastern Africa confirms high feasibility, acceptability and accuracy across many delivery models and populations, with minimal harms. Evidence on the effectiveness of HIVST on increased testing coverage is strong, while evidence on demand generation for follow-on HIV prevention and treatment services and cost-effective delivery is emerging. Despite these developments, HIVST delivery remains limited outside of pilot implementation. Important technology gaps include increasing availability of more sensitive HIVST products in low and middle-income countries. Regulatory and postmarket surveillance systems for HIVST also require further development. Randomized trials evaluating the effectiveness and cost-effectiveness under multiple distribution models, including unrestricted delivery and with a focus on linkage to HIV prevention and treatment, remain priorities. Diversification of studies from west and central Africa and around blood-based products should be addressed.

Innovations in cold chain equipment for immunization supply chains.

PubMed

Robertson, Joanie; Franzel, Lauren; Maire, Denis

2017-04-19

Since 2010, numerous new technologies have entered the immunization cold chain equipment market. The World Health Organization (WHO) Immunization Devices Programme-Performance, Quality and Safety (PQS)-has played a key role in bringing these to market. In this article, the authors explore the emergence of new cold chain equipment technologies from 2004 to 2016 and the role of PQS in this evolution. This review focuses on three major vaccine cold chain technology innovations-solar direct-drive refrigerators, long-term passive cold boxes, and equipment with user-independent freeze prevention. For the review, we used online data from WHO PQS, a literature search, and unpublished research reports. Timelines with key milestones in the emergence of the three focus technologies show delays of between one and three years between earliest field trials and publication of WHO specifications; procurement builds after the WHO prequalification of initial devices. The timelines show the role of PQS as both gatekeeper and enabler for cold chain equipment technologies. The use of target product profiles by PQS has increased its ability to signal preferred attributes and to engage with manufacturers during the product-development stage. Procurement data show how demand for solar direct-drive refrigerators increased over time. Gavi, the Vaccine Alliance, is employing demand-generation strategies to try to drive procurement of technologies with favorable technical attributes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Enhancing student communication during end-of-life care: A pilot study.

PubMed

Bloomfield, Jacqueline G; O'Neill, Bernadette; Gillett, Karen

2015-12-01

Quality end-of-life care requires effective communication skills, yet medical and nursing students report limited opportunities to develop these skills, and that they lack confidence and the related competence. Our purpose was to design, implement, and evaluate an educational intervention employing simulated patient actors to enhance students' abilities to communicate with dying patients and their families. A study employing a mixed-methods design was conducted with prequalification nursing and medical students recruited from a London university. The first phase involved focus groups with students, which informed the development of an educational intervention involving simulated patient actors. Questionnaires measuring students' perceptions of confidence and competence levels when communicating with dying patients and their families were administered before and after the intervention. The themes from focus groups related to responding to grief and anger, difficulties dealing with emotions, knowing the "right thing" to say, and a lack of experience. A significant increase (p < 0.5) in competence and confidence from baseline levels followed participation in the simulated scenarios. Simulation was found to be an effective means of preparing students to communicate with dying patients and their families. The opportunity to develop communication skills was valued. Integration of educational interventions employing simulated patient actors into nursing and medical curricula may assist in improving the care provided to patients at the end of life.

Effectiveness of Oral Cholera Vaccine in Haiti: 37-Month Follow-Up.

PubMed

Sévère, Karine; Rouzier, Vanessa; Anglade, Stravinsky Benedict; Bertil, Claudin; Joseph, Patrice; Deroncelay, Alexandra; Mabou, Marie Marcelle; Wright, Peter F; Guillaume, Florence Duperval; Pape, Jean William

2016-05-04

The first oral cholera vaccine (OCV) campaign, since its prequalification by the World Health Organization, in response to an ongoing cholera epidemic (reactive vaccination) was successfully conducted in a poor urban slum of approximately 70,000 inhabitants in Port-au-Prince, Haiti, in 2012. Vaccine coverage was 75% of the target population. This report documents the impact of OCV in reducing the number of culture-confirmed cases of cholera admitted to the Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) cholera treatment center from that community in the 37 months postvaccination (April 2012-April 30, 2015). Of 1,788 patients with culture-confirmed cholera, 1,770 (99%) were either from outside the vaccine area (1,400 cases) or from the vaccinated community who had not received OCV (370 cases). Of the 388 people from the catchment area who developed culture-confirmed cholera, 370 occurred among the 17,643 people who had not been vaccinated (2.1%) and the remaining 18 occurred among the 52,357 people (0.034%) who had been vaccinated (P < 0.001), for an efficacy that approximates 97.5%. Despite not being designed as a randomized control trial, the very high efficacy is a strong evidence for the effectiveness of OCV as part of an integrated package for the control of cholera in outbreak settings. © The American Society of Tropical Medicine and Hygiene.

Vaccines today, vaccines tomorrow: a perspective.

PubMed

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

A randomized, non-inferiority trial comparing two bivalent killed, whole cell, oral cholera vaccines (Euvichol vs Shanchol) in the Philippines.

PubMed

Baik, Yeong Ok; Choi, Seuk Keun; Olveda, Remigio M; Espos, Roberto A; Ligsay, Antonio D; Montellano, May B; Yeam, Jong Sun; Yang, Jae Seung; Park, Ju Yeon; Kim, Deok Ryun; Desai, Sachin N; Singh, Ajit Pal; Kim, Ick Young; Kim, Chan Wha; Park, Sue-nie

2015-11-17

Currently, there are two oral cholera vaccines (OCV) that are prequalified by the World Health Organization. Both (Dukoral and Shanchol) have been proven to be safe, immunogenic, and effective. As the global supply of OCV remains limited, we assessed the safety and immunogenicity of a new low cost, killed, bivalent OCV (Euvichol) in the Philippines. The randomized controlled trial was carried out in healthy Filipino adults and children. Two doses of either the current WHO prequalified OCV (Shanchol) or the same composition OCV being considered for WHO prequalification (Euvichol) were administered to participants. The pivotal study was conducted in total of 1263 healthy participants (777 adults and 486 children). No serious adverse reactions were elicited in either vaccine groups. Vibriocidal antibody responses to V. cholerae O1 Inaba following administration of two doses of Euvichol were non-inferior to those of Shanchol in adults (82% vs 76%) and children (87% vs 89%). Similar findings were observed for O1 Ogawa in adults (80% vs 74%) and children (91% vs 88%). A two dose schedule with Euvichol induces a strong vibriocidal response comparable to those elicited by the currently WHO prequalified OCV, Shanchol. Euvichol will be an oral cholera vaccine suitable for use in lower income countries, where cholera still has a significant economic and public health impact. Copyright © 2015 Elsevier Ltd. All rights reserved.

Scaling up HIV self-testing in sub-Saharan Africa: a review of technology, policy and evidence

PubMed Central

Indravudh, Pitchaya P.; Choko, Augustine T.; Corbett, Elizabeth L.

2018-01-01

Purpose of review HIV self-testing (HIVST) can provide complementary coverage to existing HIV testing services and improve knowledge of status among HIV-infected individuals. This review summarizes the current technology, policy and evidence landscape in sub-Saharan Africa and priorities within a rapidly evolving field. Recent findings HIVST is moving towards scaled implementation, with the release of WHO guidelines, WHO prequalification of the first HIVST product, price reductions of HIVST products and a growing product pipeline. Multicountry evidence from southern and eastern Africa confirms high feasibility, acceptability and accuracy across many delivery models and populations, with minimal harms. Evidence on the effectiveness of HIVST on increased testing coverage is strong, while evidence on demand generation for follow-on HIV prevention and treatment services and cost-effective delivery is emerging. Despite these developments, HIVST delivery remains limited outside of pilot implementation. Summary Important technology gaps include increasing availability of more sensitive HIVST products in low and middle-income countries. Regulatory and postmarket surveillance systems for HIVST also require further development. Randomized trials evaluating the effectiveness and cost-effectiveness under multiple distribution models, including unrestricted delivery and with a focus on linkage to HIV prevention and treatment, remain priorities. Diversification of studies from west and central Africa and around blood-based products should be addressed. PMID:29232277

Cross-national research on contractor evaluation procedures in public works procurement

NASA Astrophysics Data System (ADS)

Kinoshita, Seiya; Sato, Naoyoshi; Matsumoto, Naoya

Contractor evaluation methods in Japan's public works procurement, beginning with construction business licensure, going through biennial preliminary firm rating, up to project-by-project prequalification and comprehensive point rating, were developed during the period when public works were mostly procured through designated competitive bidding. It is essential to focus attention on contractor evaluation methods for introducing different types of procurement procedures which enhance the use of technological capabilities held by private businesses. An overall review of contractor evaluation procedures should be conducted in view of the present situation, where the open competitive bidding has become mainly used in combination with comprehensive evaluation, as well as to allow for further diversification of procurement methods. In Western countries, improvements have been made for the past several years in contractor evaluation procedures with more emphasis on "Value for Money." Advanced efforts made by these countries will be useful as a reference for overhauling Japan's contractor evaluation system. This study conducts a comparative review of contractor evaluation procedures for public procurement in Western countries such as the United States, the United Kingdom and France by identifying similarities and differences between those of Japan and the above mentioned countries. This reveals that a contractor's technical or professional ability is looked at separately from its economic and financial standing in those countries studied, and there is no case like Japan in which those two factors are integrated into one for evaluation.

[Lack of bioavailability of generic lopinavir/ritonavir not prequalified by WHO marketed in Africa (Congo Brazzaville)].

PubMed

Camara, S; Zucman, D; Vasse, M; Goudjo, A; Guillard, E; Peytavin, G

2015-02-01

Although second-line generic antiretroviral drugs are of great value in developing countries there are concerns regarding their quality and safety. This study is a case report and pharmacological study in healthy volunteers. A French subject of sub-saharan origin who visited Republic of Congo received a post-exposure treatment with AZT+3TC and LPV/r (200/50 mg, Arga-L®, India) following unprotected sexual intercourse. Two days later, in France, tests showed that plasma concentrations of lopinavir and ritonavir were undetectable. The WHO prequalification list showed Arga-L® was not prequalified. A pharmacological study in healthy volunteers evaluated oral bioavailability: plasma concentrations of generic LPV/r Arga-L® and LPV/r Kaletra® (400/100 mg) were measured after one single dose at 7 days apart in four healthy volunteers. Concentrations of Arga-L® at 12 h after intake were considerably lower than those of Kaletra®, revealing very low oral bioavailability of generic lopinavir and ritonavir (<10%) compared to the brand-name drug. We found that Arga-L®, despite having adequate qualitative and quantitative drug contents, had very poor bio availability compared to Kaletra®. In order to avoid the selection and the spread of drug-resistant HIV strains, rigorous pharmacological monitoring of generic antiretroviral drugs that are not pre-qualified by WHO, but are marketed in Africa, must be a priority for health authorities.

The complexity and cost of vaccine manufacturing - An overview.

PubMed

Plotkin, Stanley; Robinson, James M; Cunningham, Gerard; Iqbal, Robyn; Larsen, Shannon

2017-07-24

As companies, countries, and governments consider investments in vaccine production for routine immunization and outbreak response, understanding the complexity and cost drivers associated with vaccine production will help to inform business decisions. Leading multinational corporations have good understanding of the complex manufacturing processes, high technological and R&D barriers to entry, and the costs associated with vaccine production. However, decision makers in developing countries, donors and investors may not be aware of the factors that continue to limit the number of new manufacturers and have caused attrition and consolidation among existing manufacturers. This paper describes the processes and cost drivers in acquiring and maintaining licensure of childhood vaccines. In addition, when export is the goal, we describe the requirements to supply those vaccines at affordable prices to low-resource markets, including the process of World Health Organization (WHO) prequalification and supporting policy recommendation. By providing a generalized and consolidated view of these requirements we seek to build awareness in the global community of the benefits and costs associated with vaccine manufacturing and the challenges associated with maintaining consistent supply. We show that while vaccine manufacture may prima facie seem an economic growth opportunity, the complexity and high fixed costs of vaccine manufacturing limit potential profit. Further, for most lower and middle income countries a large majority of the equipment, personnel and consumables will need to be imported for years, further limiting benefits to the local economy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analyzing FTIR spectra using high sensitivity compare function of FTIR software for 2-pack epoxy paints

NASA Astrophysics Data System (ADS)

Saaid, Farish Irfal; Chan, Chin Han; Ong, Max Chong Hup; Winie, Tan; Harun, Mohamad Kamal

2015-08-01

The existing problem of oil and gas companies faced for on-site jobs of polymeric coatings on steel pipelines is that the quality of polymeric coatings varies from job to job for the same product brand from the same supplier or paint manufacturer. This can be due to the inherent problem of the reformulation of polymeric coatings or in other words adulterated polymeric coatings are supplied, where the quality of the coatings deviates from the submitted specifications for prequalification and tender purpose. Major oil and gas companies in Malaysia are calling for Coating Fingerprinting Certificate for the supply of polymeric coatings from local paint manufactures as quality assurance requirement of the coatings supplied. This will reduce the possibility of failures of the polymeric coatings, which lead to the corrosion of steel pipelines resulting in leakage of crude oil and gas to the environment. In this case, Fourier-transform infrared (FTIR) is a simple and reliable tool for coating fingerprinting. In this study, we conclude that, revelation of possible components of the 2-pack epoxy paints by carrying out extensive FTIR libraries search on FTIR spectra seems to be extremely challenging. Estimation of correlation of the sample spectrum to that of the reference spectrum using Compare function from one FTIR manufacturer, even the FTIR spectra are collected by different FTIR spectrometers from different FTIR manufacturers, can be made. The results of the correlation are reproducible.

Changing dietary behaviour: the role and development of practitioner communication.

PubMed

Whitehead, Kirsten

2015-05-01

The need to support people to change diet-related behaviour is widely advocated and how to do this effectively in practice is an expanding area of research. Important factors to consider are how healthcare practitioners communicate with their patients and how that communication may affect diet-related behaviour change and subsequent outcomes. The aim of the present paper is to discuss communication skills for behaviour change (CSBC), focusing predominantly on registered dietitians who are required to communicate effectively and have an important role in supporting patients to change diet-related behaviour. The views of dietitians in relation to CSBC have been investigated and respondents have consistently reported that they perceive these skills to be of vital importance in practice. Patient views have reiterated the importance of good CSBC in one-to-one consultations. However, pre-qualification training of dietitians is thought to deliver practitioners who are competent at a minimum level. The need for ongoing continuous professional development (CPD) in relation to CSBC has been recognised but currently most CPD focuses on updating knowledge rather than improving these essential skills. Measuring CSBC in a consistent and objective manner is difficult and an assessment tool, DIET-COMMS, has been developed and validated for this purpose. DIET-COMMS can be used to support CSBC development, but concerns about logistical challenges and acceptability of implementing this in practice have been raised. Although a suitable assessment tool now exists there is a need to develop ways to facilitate assessment of CSBC in practice.

Interprofessional education: a review of context, learning and the research agenda.

PubMed

Thistlethwaite, Jill

2012-01-01

Interprofessional education (IPE) is not a recent phenomenon and has been the subject of several World Health Organization reports. Its focus is on health professionals and students learning with, from and about one another to improve collaboration and the quality of patient care. The drivers for IPE include new models of health care delivery in the context of an ageing population and the increasing prevalence of long-term chronic disease, in addition to the patient safety agenda. The delivery of complex health care requires a team-based and collaborative approach, although teamwork and collaborative practice are not necessarily synonymous. The rationale for IPE is that learning together enhances future working together. Systematic reviews of IPE have shown some evidence that IPE fosters positive interaction among different professions and variable evidence that it improves attitudes towards other professionals. Generalisation across published papers is difficult because IPE initiatives are diverse and good evaluation methodology and data are lacking. In terms of constructive alignment from an education viewpoint, there is a need for educators to define learning outcomes and match these with learning activities to ensure that IPE demonstrates added value over uniprofessional learning. Assessment is difficult as pre-qualification professional education focuses on the individual and professional accreditation organisations mandate only for their own professions. Interprofessional education draws from a number of education, sociology and psychology theories, and these are briefly discussed. The most pressing research questions for the IPE community are defined and the challenges for IPE explored. © Blackwell Publishing Ltd 2012.

Advancing a vaccine to prevent human schistosomiasis.

PubMed

Merrifield, Maureen; Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

2016-06-03

Several candidate human schistosomiasis vaccines are in different stages of preclinical and clinical development. The major targets are Schistosoma haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis) that account for 99% of the world's 252 million cases, with 90% of these cases in Africa. Two recombinant S. mansoni vaccines - Sm-TSP-2 and Sm-14 are in Phase 1 trials, while Smp80 (calpain) is undergoing testing in non-human primates. Sh28GST, also known as Bilhvax is in advanced clinical development for S. haematobium infection. The possibility remains that some of these vaccines may cross-react to target both schistosome species. These vaccines were selected on the basis of their protective immunity in preclinical challenge models, through human immune-epidemiological studies or both. They are being advanced through a combination of academic research institutions, non-profit vaccine product development partnerships, biotechnology companies, and developing country vaccine manufacturers. In addition, new schistosome candidate vaccines are being identified through bioinformatics, OMICs approaches, and moderate throughput screening, although the full potential of reverse vaccinology for schistosomiasis has not yet been realized. The target product profiles of these vaccines vary but many focus on vaccinating children, in some cases following mass treatment with praziquantel, also known as vaccine-linked chemotherapy. Several regulatory pathways have been proposed, some of which rely on World Health Organization prequalification. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Reflectometric measurement of n-hexane adsorption on ZnO2 nanohybrid film modified by hydrophobic gold nanoparticles

NASA Astrophysics Data System (ADS)

Sebők, Dániel; Csapó, Edit; Ábrahám, Nóra; Dékány, Imre

2015-04-01

Zinc-peroxide/poly(styrenesulfonate) nanohybrid thin films (containing 20 bilayers: [ZnO2/PSS]20, d ∼ 500 nm) were prepared using layer-by-layer (LbL) method. The thin film surface was functionalized by different surface modifying agents (silanes, alkylthiols and hydrophobized nanoparticles). Based on the experimental results of quartz crystal microbalance (QCM) and contact angle measurements (as prequalifications) the octanethiol covered gold nanoparticles (OT-AuNPs) were selected for further vapour adsorption studies. Reflectometric interference spectroscopy (RIfS) was used to measure n-hexane vapour adsorption on the original and modified nanohybrid films in a gas flow platform. The thin film provides only the principle of the measurement (by interference phenomenon), the selectivity and hydrophobicity is controlled and enhanced by surface functionalization (by dispersion interaction between the alkyl chains). The interference pattern shift (Δλ) caused by the increase of the optical thickness of the thin film due to vapour adsorption was investigated. It was found that due to the surface functionalization by hydrophobic nanoparticles the effect of water vapour adsorption decreased significantly, while for n-hexane opposite tendency was observed (the effective refractive index and thus the interference pattern shift increased drastically). The correlation between QCM technique and optical method (RIfS) was specified: linear specific adsorbed amount vs. wavelength shift calibration curves were determined in the pr = 0-0.4 relative vapour pressure range. The thin film is suitable for sensorial application (e.g. volatile organic compound/VOC sensor).

Geotechnical characterization of mined clay from Appalachian Ohio: challenges and implications for the clay mining industry.

PubMed

Moran, Anthony R; Hettiarachchi, Hiroshan

2011-07-01

Clayey soil found in coal mines in Appalachian Ohio is often sold to landfills for constructing Recompacted Soil Liners (RSL) in landfills. Since clayey soils possess low hydraulic conductivity, the suitability of mined clay for RSL in Ohio is first assessed by determining its clay content. When soil samples are tested in a laboratory, the same engineering properties are typically expected for the soils originated from the same source, provided that the testing techniques applied are standard, but mined clay from Appalachian Ohio has shown drastic differences in particle size distribution depending on the sampling and/or laboratory processing methods. Sometimes more than a 10 percent decrease in the clay content is observed in the samples collected at the stockpiles, compared to those collected through reverse circulation drilling. This discrepancy poses a challenge to geotechnical engineers who work on the prequalification process of RSL material as it can result in misleading estimates of the hydraulic conductivity of the samples. This paper describes a laboratory investigation conducted on mined clay from Appalachian Ohio to determine how and why the standard sampling and/or processing methods can affect the grain-size distributions. The variation in the clay content was determined to be due to heavy concentrations of shale fragments in the clayey soils. It was also concluded that, in order to obtain reliable grain size distributions from the samples collected at a stockpile of mined clay, the material needs to be processed using a soil grinder. Otherwise, the samples should be collected through drilling.

Chemistry, manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers.

PubMed

Wahid, Rahnuma; Holt, Renee; Hjorth, Richard; Berlanda Scorza, Francesco

2016-10-26

With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs. Copyright © 2016 Elsevier Ltd. All rights reserved.

WHO consultation on clinical evaluation of vaccines, 17-18 July 2014, WHO Headquarters, Geneva, Switzerland.

PubMed

Knezevic, Ivana; Moorthy, Vasee; Sheets, Rebecca

2015-04-21

A World Health Organization (WHO) consultation on guidelines for National Regulatory Authorities (NRAs) and vaccine manufacturers on clinical evaluation of vaccines was held from 17 to 18 July 2014, to review key scientific challenges that regulators have been facing since the establishment of the WHO Guidelines on Clinical Evaluation of Vaccines. The guidelines, adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2001, have served as the basis for setting or updating national requirements for the evaluation and licensing of a broad range of vaccines as well as for WHO vaccine prequalification. Regulators from Australia, Brazil, China, Canada, Germany, India, Republic of Korea, South Africa, United States of America and the United Kingdom were represented. The International Federation for Pharmaceutical Manufacturers' Association (IFPMA) and the Developing Country Vaccine Manufacturers' Network (DCVMN) provided industry representation. The consultation concluded that the guidelines should be revised to address issues that were raised in the context of vaccines that were the subject of clinical development in the past decade. Although the current guidelines have served well over time, it was recognized that an update would further increase their utility and would help regulators, manufacturers, vaccine developers and academia to respond to the challenging questions regarding the safety, immunogenicity, efficacy and effectiveness of vaccines intended for global use. A summary of the main outcomes of the consultation and proposals for the next steps regarding the guidelines and beyond are provided in this report. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluating the abuse potential of opioids and abuse-deterrent -opioid formulations: A review of clinical study methodology.

PubMed

Setnik, Beatrice; Schoedel, Kerri A; Levy-Cooperman, Naama; Shram, Megan; Pixton, Glenn C; Roland, Carl L

With the development of opioid abuse-deterrent formulations (ADFs), there is a need to conduct well-designed human abuse potential studies to evaluate the effectiveness of their deterrent properties. Although these types of studies have been conducted for many years, largely to evaluate inherent abuse potential of a molecule and inform drug scheduling, methodological approaches have varied across studies. The focus of this review is to describe current "best practices" and methodological adaptations required to assess abuse-deterrent opioid formulations for regulatory submissions. A literature search was conducted in PubMed® to review methodological approaches (study conduct and analysis) used in opioid human abuse potential studies. Search terms included a combination of "opioid," "opiate," "abuse potential," "abuse liability," "liking," AND "pharmacodynamic," and only studies that evaluated single doses of opioids in healthy, nondependent individuals with or without prior opioid experience were included. Seventy-one human abuse potential studies meeting the prespecified criteria were identified, of which 21 studies evaluated a purported opioid ADF. Based on these studies, key methodological considerations were reviewed and summarized according to participant demographics, study prequalification, comparator and dose selection, route of administration and drug manipulation, study blinding, outcome measures and training, safety, and statistical analyses. The authors recommend careful consideration of key elements (eg, a standardized definition of a "nondependent recreational user"), as applicable, and offer key principles and "best practices" when conducting human abuse potential studies for opioid ADFs. Careful selection of appropriate study conditions is dependent on the type of ADF technology being evaluated.

'It teaches you what to expect in future . . . ': interprofessional learning on a training ward for medical, nursing, occupational therapy and physiotherapy students.

PubMed

Reeves, Scott; Freeth, Della; McCrorie, Peter; Perry, David

2002-04-01

This paper presents findings from a multimethod evaluation of an interprofessional training ward placement for medical, nursing, occupational therapy and physiotherapy students. Unique in the UK, and following the pioneering work at Linköping, the training ward allowed senior pre-qualification students, under the supervision of practitioners, to plan and deliver interprofessional care for a group of orthopaedic and rheumatology patients. This responsibility enabled students to develop profession-specific skills and competencies in dealing with patients. It also allowed them to enhance their teamworking skills in an interprofessional environment. Student teams were supported by facilitators who ensured medical care was optimal, led reflective sessions and facilitated students' problem solving. Data were collected from all groups of participants involved in the ward: students, facilitators and patients. Methods included questionnaires, interviews and observations. Findings are presented from each participating group, with a particular emphasis placed on the perspective of medicine. The study found that students valued highly the experiential learning they received on the ward and felt the ward prepared them more effectively for future practice. However, many encountered difficulties adopting an autonomous learning style during their placement. Despite enjoying their work on the ward, facilitators were concerned that the demands of their role could result in 'burn-out'. Patients enjoyed their ward experience and scored higher on a range of satisfaction indicators than a comparative group of patients. Participants were generally positive about the training ward. All considered that it was a worthwhile experience and felt the ward should recommence in the near future.

The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration to Accelerate Diagnosis and Treatment of Traumatic Brain Injury.

PubMed

Manley, Geoffrey T; MacDonald, Christine L; Markowitz, Amy; Stephenson, Diane; Robbins, Ann; Gardner, Raquel C; Winkler, Ethan A; Bodien, Yelena; Taylor, Sabrina; Yue, John K; Kannan, Lakshmi; Kumar, Allison; McCrea, Michael; Wang, Kevin K W

2017-03-31

The Traumatic Brain Injury Endpoints Development (TED) Initiative is a 5-year, Department of Defense (DoD) funded project that is working toward the ultimate goal of developing better designed clinical trials, leading to more precise diagnosis, and effective treatments for traumatic brain injury (TBI). TED is comprised of leading academic clinician-scientists, along with innovative industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropists, working collaboratively with regulatory authorities, specifically the US Food and Drug Administration (FDA). The goals of the TED Initiative are to gain consensus and validation of TBI clinical outcome assessment measures and biomarkers for endorsement by global regulatory agencies for use in drug and device development processes. This manuscript summarizes the Initiative's Stage 1 progress over the first 18 months, including intensive engagement with a number of FDA divisions responsible for review and validation of biomarkers and clinical outcome assessments, progression into the prequalification phase of FDA's Medical Device Development Tool program for a candidate set of neuroimaging biomarkers, and receipt of FDA's Recognition of Research Importance Letter regarding TBI. Other signal achievements relate to the creation of the TED Metadataset, harmonizing study measures across eight major TBI studies, and the leadership role played by TED investigators in the conversion of the NINDS TBI Common Data Elements (CDEs) to Clinical Data Interchange Standards Consortium (CDISC) standards. This paper frames both the near-term expectations and the Initiative's long-term vision to accelerate approval of treatments for patients affected by TBI in urgent need of effective therapies.

[Medical habilitation in German-speaking countries : Quantitative assessment of content and elaboration of habilitation guidelines].

PubMed

Weineck, S B; Koelblinger, D; Kiesslich, T

2015-04-01

Habilitation defines the qualification to conduct self-contained university teaching and is the key for access to a professorship at German, Austrian and Swiss universities. Despite all changes implemented in the European higher education systems during the Bologna process, it is the highest qualification level issued through the process of an university examination and remains the core concept of scientific careers in these countries. In the field of medicine, this applies not only to scientific staff at the universities but also to those medical doctors aiming at a clinical career track. To provide a quantitative analysis of the scientific, didactic, and procedural criteria for medical habilitation in German-speaking countries. Based on the guidelines of all 43 medical academic institutions, the criteria which candidates are required to fulfil prior to habilitation as well as formal requirements related to the habilitation procedure itself have been acquired and quantitatively analyzed. Having evaluated all habilitation guidelines by means of 87 items, the quantitative analysis revealed significant differences in terms of number, kind and scale of criteria stated therein. Most habilitation guidelines scarcely define the capabilities applicants have to prove: concerning the scientific qualifications on types of publications for instance, no item was mentioned in more than half of all habilitation guidelines. Based on this data analysis, the authors discuss the related literature and describe five main distinguishing areas of habilitation guidelines in terms of the set of the formal and procedural framework as well as the prequalification and postqualification criteria imposed on habilitation candidates. There are therefore substantial differences in the organization of the habilitation for medicine.

Geotechnical Characterization of Mined Clay from Appalachian Ohio: Challenges and Implications for the Clay Mining Industry

PubMed Central

Moran, Anthony R.; Hettiarachchi, Hiroshan

2011-01-01

Clayey soil found in coal mines in Appalachian Ohio is often sold to landfills for constructing Recompacted Soil Liners (RSL) in landfills. Since clayey soils possess low hydraulic conductivity, the suitability of mined clay for RSL in Ohio is first assessed by determining its clay content. When soil samples are tested in a laboratory, the same engineering properties are typically expected for the soils originated from the same source, provided that the testing techniques applied are standard, but mined clay from Appalachian Ohio has shown drastic differences in particle size distribution depending on the sampling and/or laboratory processing methods. Sometimes more than a 10 percent decrease in the clay content is observed in the samples collected at the stockpiles, compared to those collected through reverse circulation drilling. This discrepancy poses a challenge to geotechnical engineers who work on the prequalification process of RSL material as it can result in misleading estimates of the hydraulic conductivity of the samples. This paper describes a laboratory investigation conducted on mined clay from Appalachian Ohio to determine how and why the standard sampling and/or processing methods can affect the grain-size distributions. The variation in the clay content was determined to be due to heavy concentrations of shale fragments in the clayey soils. It was also concluded that, in order to obtain reliable grain size distributions from the samples collected at a stockpile of mined clay, the material needs to be processed using a soil grinder. Otherwise, the samples should be collected through drilling. PMID:21845150

A strategic management model for evaluation of health, safety and environmental performance.

PubMed

Abbaspour, Majid; Toutounchian, Solmaz; Roayaei, Emad; Nassiri, Parvin

2012-05-01

Strategic health, safety, and environmental management system (HSE-MS) involves systematic and cooperative planning in each phase of the lifecycle of a project to ensure that interaction among the industry group, client, contractor, stakeholder, and host community exists with the highest level of health, safety, and environmental standard performances. Therefore, it seems necessary to assess the HSE-MS performance of contractor(s) by a comparative strategic management model with the aim of continuous improvement. The present Strategic Management Model (SMM) has been illustrated by a case study and the results show that the model is a suitable management tool for decision making in a contract environment, especially in oil and gas fields and based on accepted international standards within the framework of management deming cycle. To develop this model, a data bank has been created, which includes the statistical data calculated by converting the HSE performance qualitative data into quantitative values. Based on this fact, the structure of the model has been formed by defining HSE performance indicators according to the HSE-MS model. Therefore, 178 indicators have been selected which have been grouped into four attributes. Model output provides quantitative measures of HSE-MS performance as a percentage of an ideal level with maximum possible score for each attribute. Defining the strengths and weaknesses of the contractor(s) is another capability of this model. On the other hand, this model provides a ranking that could be used as the basis for decision making at the contractors' pre-qualification phase or during the execution of the project.

The effectiveness of case-based learning in health professional education. A BEME systematic review: BEME Guide No. 23.

PubMed

Thistlethwaite, Jill Elizabeth; Davies, David; Ekeocha, Samilia; Kidd, Jane M; MacDougall, Colin; Matthews, Paul; Purkis, Judith; Clay, Diane

2012-01-01

Case-based learning (CBL) is a long established pedagogical method, which is defined in a number of ways depending on the discipline and type of 'case' employed. In health professional education, learning activities are commonly based on patient cases. Basic, social and clinical sciences are studied in relation to the case, are integrated with clinical presentations and conditions (including health and ill-health) and student learning is, therefore, associated with real-life situations. Although many claims are made for CBL as an effective learning and teaching method, very little evidence is quoted or generated to support these claims. We frame this review from the perspective of CBL as a type of inquiry-based learning. To explore, analyse and synthesise the evidence relating to the effectiveness of CBL as a means of achieving defined learning outcomes in health professional prequalification training programmes. We focused the review on CBL for prequalification health professional programmes including medicine, dentistry, veterinary science, nursing and midwifery, social care and the allied health professions (physiotherapy, occupational therapy, etc.). Papers were required to have outcome data on effectiveness. The search covered the period from 1965 to week 4 September 2010 and the following databases: ASSIA, CINAHL, EMBASE, Education Research, Medline and Web of Knowledge (WoK). Two members of the topic review group (TRG) independently reviewed the 173 abstracts retrieved from Medline and compared findings. As there was good agreement on inclusion, one went onto review the WoK and ASSIA EndNote databases and the other the Embase, CINAHL and Education Research databases to decide on papers to submit for coding. Coding and data analysis: The TRG modified the standard best evidence medical education coding sheet to fit our research questions and assessed each paper for quality. After a preliminary reliability exercise, each full paper was read and graded by one reviewer with the papers scoring 3-5 (of 5) for strength of findings being read by a second reviewer. A summary of each completed coding form was entered into an Excel spread sheet. The type of data in the papers was not amenable to traditional meta-analysis because of the variability in interventions, information given, student numbers (and lack of) and timings. We, therefore, adopted a narrative synthesis method to compare, contrast, synthesise and interpret the data, working within a framework of inquiry-based learning. The final number of coded papers for inclusion was 104. The TRG agreed that 23 papers would be classified as of higher quality and significance (22%). There was a wide diversity in the type, timing, number and length of exposure to cases and how cases were defined. Medicine was the most commonly included profession. Numbers of students taking part in CBL varied from below 50 to over 1000. The shortest interventions were two hours, and one case, whereas the longest was CBL through a whole year. Group sizes ranged from students working alone to over 30, with the majority between 2 and 15 students per group. The majority of studies involved single cohorts of students (61%), with 29% comparing multiple groups, 8% involving different year groups and 2% with historical controls. The outcomes evaluation was either carried out postintervention only (78 papers; 75%), preintervention and postintervention (23 papers; 22%) or during and postintervention (3 papers; <3%). Our analysis provided the basis for discussion of definitions of CBL, methods used and advocated, topics and learning outcomes and whether CBL is effective based on the evaluation data. Overwhelmingly, students enjoy CBL and think that it enhances their learning. The empirical data taken as a whole are inconclusive as to the effects on learning compared with other types of activity. Teachers enjoy CBL, partly because it engages, and is perceived to motivate, students. CBL seems to foster learning in small groups though whether this is the case delivery or the group learning effect is unclear.

Teaching and learning communication skills in physiotherapy: what is done and how should it be done?

PubMed

Parry, Ruth H; Brown, Kay

2009-12-01

To survey practice and opinion regarding school-based teaching of communication skills, to summarise relevant research evidence from physiotherapy and beyond, to reflect on practice in light of evidence, and to propose associated recommendations. Survey using customised questionnaires. Basic descriptive statistical analysis and thematic content analysis were used. The results were compared with evidence from systematic reviews to derive recommendations. SURVEY PARTICIPANTS AND SETTING: Educators in all UK centres delivering physiotherapy qualifying programmes in 2006. A response rate of 69% was achieved. The majority of respondents reported delivering communication-specific modules. Lecturing was common, and more experiential methods were also used. Assessment was mainly by written work. Educators commented on challenges and strategies involved in student engagement, provision of authentic experiences, availability of teaching time and expertise, and physiotherapy-specific teaching resources. Evidence from allied health profession, medical and nursing education research emphasises the importance of experiential teaching, formative feedback, observational assessment and a substantial evidence base on which to ground course content. In physiotherapy, the latter is emerging but incomplete. There are also gaps in direct evidence about advantages or otherwise of stand-alone modules and benefits of pre-qualification communication training. Evidence suggests that effective training requires substantial teaching time, expertise and a body of empirical research on specific communication practices and their effects. Curriculum designers and educators should endeavour to maximise the degree to which training in this area is experiential, provide training when students have already had some contact with patients, and assess students by observation if at all possible. Due to gaps in the evidence, some important questions about optimal practice remain unanswered.

Vaccines, inspiring innovation in health.

PubMed

Pagliusi, Sonia; Dennehy, Maureen; Kim, Hun

2018-05-19

This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers' Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of vaccine supply in developing countries. Copyright © 2018. Published by Elsevier Ltd.

Cost benefit of investment on quality in pharmaceutical manufacturing: WHO GMP pre- and post-certification of a Nigerian pharmaceutical manufacturer.

PubMed

Anyakora, Chimezie; Ekwunife, Obinna; Alozie, Faith; Esuga, Mopa; Ukwuru, Jonathan; Onya, Steve; Nwokike, Jude

2017-09-18

Pharmaceutical companies in Africa need to invest in both facilities and quality management systems to achieve good manufacturing practice (GMP) compliance. Compliance to international GMP standards is important to the attainment of World Health Organization (WHO) prequalification. However, most of the local pharmaceutical manufacturing companies may be deterred from investing in quality because of many reasons, ranging from financial constraints to technical capacity. This paper primarily evaluates benefits against the cost of investing in GMP, using a Nigerian pharmaceutical company, Chi Pharmaceuticals Limited, as a case study. This paper also discusses how to drive more local manufacturers to invest in quality to attain GMP compliance; and proffers practical recommendations for local manufacturers who would want to invest in quality to meet ethical and regulatory obligations. The cost benefit of improving the quality of Chi Pharmaceuticals Limited's facilities and system to attain WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was calculated by dividing the annual benefits derived from quality improvement interventions by the annual costs of implementing quality improvement interventions, referred to as a benefit-cost ratio (BCR). Cost benefit of obtaining WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was 5.3 (95% confidence interval of 5.0-5.5). Investment in quality improvement intervention is cost-beneficial for local manufacturing companies. Governments and regulators in African countries should support pharmaceutical companies striving to invest in quality. Collaboration of local manufacturing companies with global companies will further improve quality. Local pharmaceutical companies should be encouraged to key into development opportunities available for pharmaceutical companies in Africa.

The insulin dilemma in resource-limited countries. A way forward?

PubMed

Gill, G V; Yudkin, J S; Keen, H; Beran, D

2011-01-01

The International Insulin Foundation (IIF) has developed and validated a needs-assessment instrument called the Rapid Assessment Protocol for Insulin Access (RAPIA) which has been used in seven countries in four continents to analyse the constraints to delivering effective continuing care for people with diabetes. One major contributor to the difficulties in availability of insulin is a failure to use the least costly sources and types of insulin and other effective drugs for diabetes. The purchase of insulins can consume as much as 10% of government expenditure on drugs, this being highly sensitive to the selection of newer analogue insulins as first-choice options, which cost between three and 13 times more than biosynthetic human insulin. Insulin cartridges for use with injection pens further add to costs. Similar considerations apply to most of the newer treatments for people with type 2 diabetes, which may cost up to 40 times more than metformin and sulfonylureas, still considered first-line drugs by European and US guidelines. Both biosynthetic human insulin and the first-line oral hypoglycaemic drugs are available from generic manufacturers. With the present price differentials, there is thus a growing need for countries involved in tendering for sourcing insulin to be provided with the guarantees of Good Manufacturing Practice, quality and bioequivalence, which would come from a WHO Pre-Qualification Scheme as currently exists for a variety of drugs for chronic diseases, both communicable and non-communicable. The IIF has developed a position statement on the provision and choice of diabetes treatments in resource-limited settings which should be applicable wherever consideration of resources is a component of therapeutic decision making.

An open source business model for malaria.

PubMed

Årdal, Christine; Røttingen, John-Arne

2015-01-01

Greater investment is required in developing new drugs and vaccines against malaria in order to eradicate malaria. These precious funds must be carefully managed to achieve the greatest impact. We evaluate existing efforts to discover and develop new drugs and vaccines for malaria to determine how best malaria R&D can benefit from an enhanced open source approach and how such a business model may operate. We assess research articles, patents, clinical trials and conducted a smaller survey among malaria researchers. Our results demonstrate that the public and philanthropic sectors are financing and performing the majority of malaria drug/vaccine discovery and development, but are then restricting access through patents, 'closed' publications and hidden away physical specimens. This makes little sense since it is also the public and philanthropic sector that purchases the drugs and vaccines. We recommend that a more "open source" approach is taken by making the entire value chain more efficient through greater transparency which may lead to more extensive collaborations. This can, for example, be achieved by empowering an existing organization like the Medicines for Malaria Venture (MMV) to act as a clearing house for malaria-related data. The malaria researchers that we surveyed indicated that they would utilize such registry data to increase collaboration. Finally, we question the utility of publicly or philanthropically funded patents for malaria medicines, where little to no profits are available. Malaria R&D benefits from a publicly and philanthropically funded architecture, which starts with academic research institutions, product development partnerships, commercialization assistance through UNITAID and finally procurement through mechanisms like The Global Fund to Fight AIDS, Tuberculosis and Malaria and the U.S.' President's Malaria Initiative. We believe that a fresh look should be taken at the cost/benefit of patents particularly related to new malaria medicines and consider alternative incentives, like WHO prequalification.

Developing a comprehensive response for treatment of children under 6 years of age with schistosomiasis: research and development of a pediatric formulation of praziquantel.

PubMed

Reinhard-Rupp, Jutta; Klohe, Katharina

2017-08-03

Schistosomiasis is a parasitic disease caused by blood flukes. The disease is caused by an inflammatory reaction to parasite eggs retained in the liver, bladder and reproductive organs. According to 2017 World Health Organization (WHO) estimates 220 million people are potentially infected, from which probably 10% are children under 6 years of age. The regular treatment approach of a single, oral dose of 40 mg/kg body weight with praziquantel however, is difficult for children under the age of 6, leaving them without a treatment option. In order to address this important gap in treatment target populations, an international public-private partnership that works on a not-for-profit basis in the field of drug research and development for schistosomiasis was established in 2012. This is called the Pediatric Praziquantel Consortium. Its mission was and continues to be to develop, register and provide access to a suitable pediatric praziquantel formulation for treating schistosomiasis in preschool-age children (3-6 months up to 6 years). The Target Product Profile for the pediatric formulation of praziquantel that would be suitable to treat children as young as 3-6 months was then defined by a group of experts, including members from the Pediatric Praziquantel Consortium partner organizations as well as experts from WHO (as observer) and schistosomiasis endemic countries. The development of the drug is ongoing and the Pediatric Praziquantel Consortium aims to submit the regulatory dossier for marketing approval in endemic countries and WHO prequalification in 2018/19 with approval and product launch for schistosomiasis pediatric case management in key endemic countries in 2019. Ultimately, the goal is for the product to be considered for a large-scale mass distribution program by 2022.

Interprofessional education in the care of people diagnosed with dementia and their carers: a systematic review

PubMed Central

Jackson, Marcus; Pelone, Ferruccio; Reeves, Scott; Hassenkamp, Anne Marie; Emery, Claire; Titmarsh, Kumud; Greenwood, Nan

2016-01-01

Objectives This systematic review is linked to the multifaceted social, economic and personal challenges of dementia and the international recognition of the value of interprofessional education (IPE) and its influence on health and social care outcomes. This review therefore aimed to identify, describe and evaluate the impact of IPE interventions on health and social care practitioners (prequalification and postqualification) understanding of dementia, the quality of care for people with dementia and support for their carers. Methods Following PRISMA guidelines, 9 databases were searched (MEDLINE, EMBASE, The Cochrane Library, PsycINFO, CINAHL Plus, Applied Social Sciences Index and Abstracts, Healthcare Management Information Consortium, ERIC and British Education Index). Narrative analysis of the findings was undertaken. Design Systematic review. Results 6 studies meeting the inclusion criteria were identified. The majority of studies were conducted in North America. Participants in 4 studies were health and social care practitioners caring for people with dementia, whereas the remaining studies focused on training graduate or undergraduate students. Diverse IPE activities with varying content, delivery mode and duration were reported. Although some studies reported more positive attitudes to interprofessional working as a result of the interventions, none reported benefits to patients or carers. The quality of the included studies varied. Overall, the evidence for the reported outcomes was considered weak. Conclusions This review identified 6 studies describing IPE interventions intended to improve collaborative knowledge, skills, interprofessional practice and organisational awareness of dementia and dementia care. The small number of studies, their varied nature, scope and settings combined with poor quality of evidence limits our understanding of the effectiveness of IPE on the care and support of people with dementia and their carers. Further research is required to develop the evidence base and provide robust studies to inform IPE development. Trial registration number CRD42014015075. PMID:27531724

Interprofessional education in the care of people diagnosed with dementia and their carers: a systematic review.

PubMed

Jackson, Marcus; Pelone, Ferruccio; Reeves, Scott; Hassenkamp, Anne Marie; Emery, Claire; Titmarsh, Kumud; Greenwood, Nan

2016-08-16

This systematic review is linked to the multifaceted social, economic and personal challenges of dementia and the international recognition of the value of interprofessional education (IPE) and its influence on health and social care outcomes. This review therefore aimed to identify, describe and evaluate the impact of IPE interventions on health and social care practitioners (prequalification and postqualification) understanding of dementia, the quality of care for people with dementia and support for their carers. Following PRISMA guidelines, 9 databases were searched (MEDLINE, EMBASE, The Cochrane Library, PsycINFO, CINAHL Plus, Applied Social Sciences Index and Abstracts, Healthcare Management Information Consortium, ERIC and British Education Index). Narrative analysis of the findings was undertaken. Systematic review. 6 studies meeting the inclusion criteria were identified. The majority of studies were conducted in North America. Participants in 4 studies were health and social care practitioners caring for people with dementia, whereas the remaining studies focused on training graduate or undergraduate students. Diverse IPE activities with varying content, delivery mode and duration were reported. Although some studies reported more positive attitudes to interprofessional working as a result of the interventions, none reported benefits to patients or carers. The quality of the included studies varied. Overall, the evidence for the reported outcomes was considered weak. This review identified 6 studies describing IPE interventions intended to improve collaborative knowledge, skills, interprofessional practice and organisational awareness of dementia and dementia care. The small number of studies, their varied nature, scope and settings combined with poor quality of evidence limits our understanding of the effectiveness of IPE on the care and support of people with dementia and their carers. Further research is required to develop the evidence base and provide robust studies to inform IPE development. CRD42014015075. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

An Open Source Business Model for Malaria

PubMed Central

Årdal, Christine; Røttingen, John-Arne

2015-01-01

Greater investment is required in developing new drugs and vaccines against malaria in order to eradicate malaria. These precious funds must be carefully managed to achieve the greatest impact. We evaluate existing efforts to discover and develop new drugs and vaccines for malaria to determine how best malaria R&D can benefit from an enhanced open source approach and how such a business model may operate. We assess research articles, patents, clinical trials and conducted a smaller survey among malaria researchers. Our results demonstrate that the public and philanthropic sectors are financing and performing the majority of malaria drug/vaccine discovery and development, but are then restricting access through patents, ‘closed’ publications and hidden away physical specimens. This makes little sense since it is also the public and philanthropic sector that purchases the drugs and vaccines. We recommend that a more “open source” approach is taken by making the entire value chain more efficient through greater transparency which may lead to more extensive collaborations. This can, for example, be achieved by empowering an existing organization like the Medicines for Malaria Venture (MMV) to act as a clearing house for malaria-related data. The malaria researchers that we surveyed indicated that they would utilize such registry data to increase collaboration. Finally, we question the utility of publicly or philanthropically funded patents for malaria medicines, where little to no profits are available. Malaria R&D benefits from a publicly and philanthropically funded architecture, which starts with academic research institutions, product development partnerships, commercialization assistance through UNITAID and finally procurement through mechanisms like The Global Fund to Fight AIDS, Tuberculosis and Malaria and the U.S.’ President’s Malaria Initiative. We believe that a fresh look should be taken at the cost/benefit of patents particularly related to new malaria medicines and consider alternative incentives, like WHO prequalification. PMID:25658590

The effect of computer-assisted learning versus conventional teaching methods on the acquisition and retention of handwashing theory and skills in pre-qualification nursing students: a randomised controlled trial.

PubMed

Bloomfield, Jacqueline; Roberts, Julia; While, Alison

2010-03-01

High quality health care demands a nursing workforce with sound clinical skills. However, the clinical competency of newly qualified nurses continues to stimulate debate about the adequacy of current methods of clinical skills education and emphasises the need for innovative teaching strategies. Despite the increasing use of e-learning within nurse education, evidence to support its use for clinical skills teaching is limited and inconclusive. This study tested whether nursing students could learn and retain the theory and skill of handwashing more effectively when taught using computer-assisted learning compared with conventional face-to-face methods. The study employed a two group randomised controlled design. The intervention group used an interactive, multimedia, self-directed computer-assisted learning module. The control group was taught by an experienced lecturer in a clinical skills room. Data were collected over a 5-month period between October 2004 and February 2005. Knowledge was tested at four time points and handwashing skills were assessed twice. Two-hundred and forty-two first year nursing students of mixed gender; age; educational background and first language studying at one British university were recruited to the study. Participant attrition increased during the study. Knowledge scores increased significantly from baseline in both groups and no significant differences were detected between the scores of the two groups. Skill performance scores were similar in both groups at the 2-week follow-up with significant differences emerging at the 8-week follow-up in favour of the intervention group, however, this finding must be interpreted with caution in light of sample size and attrition rates. The computer-assisted learning module was an effective strategy for teaching both the theory and practice of handwashing to nursing students and in this study was found to be at least as effective as conventional face-to-face teaching methods. Copyright 2009 Elsevier Ltd. All rights reserved.

Validation of a new ELISA method for in vitro potency testing of hepatitis A vaccines.

PubMed

Morgeaux, S; Variot, P; Daas, A; Costanzo, A

2013-01-01

The goal of the project was to standardise a new in vitro method in replacement of the existing standard method for the determination of hepatitis A virus antigen content in hepatitis A vaccines (HAV) marketed in Europe. This became necessary due to issues with the method used previously, requiring the use of commercial test kits. The selected candidate method, not based on commercial kits, had already been used for many years by an Official Medicines Control Laboratory (OMCL) for routine testing and batch release of HAV. After a pre-qualification phase (Phase 1) that showed the suitability of the commercially available critical ELISA reagents for the determination of antigen content in marketed HAV present on the European market, an international collaborative study (Phase 2) was carried out in order to fully validate the method. Eleven laboratories took part in the collaborative study. They performed assays with the candidate standard method and, in parallel, for comparison purposes, with their own in-house validated methods where these were available. The study demonstrated that the new assay provides a more reliable and reproducible method when compared to the existing standard method. A good correlation of the candidate standard method with the in vivo immunogenicity assay in mice was shown previously for both potent and sub-potent (stressed) vaccines. Thus, the new standard method validated during the collaborative study may be implemented readily by manufacturers and OMCLs for routine batch release but also for in-process control or consistency testing. The new method was approved in October 2012 by Group of Experts 15 of the European Pharmacopoeia (Ph. Eur.) as the standard method for in vitro potency testing of HAV. The relevant texts will be revised accordingly. Critical reagents such as coating reagent and detection antibodies have been adopted by the Ph. Eur. Commission and are available from the EDQM as Ph. Eur. Biological Reference Reagents (BRRs).

Analysis of Criteria Influencing Contractor Selection Using TOPSIS Method

NASA Astrophysics Data System (ADS)

Alptekin, Orkun; Alptekin, Nesrin

2017-10-01

Selection of the most suitable contractor is an important process in public construction projects. This process is a major decision which may influence the progress and success of a construction project. Improper selection of contractors may lead to problems such as bad quality of work and delay in project duration. Especially in the construction projects of public buildings, the proper choice of contractor is beneficial to the public institution. Public procurement processes have different characteristics in respect to dissimilarities in political, social and economic features of every country. In Turkey, Turkish Public Procurement Law PPL 4734 is the main regulatory law for the procurement of the public buildings. According to the PPL 4734, public construction administrators have to contract with the lowest bidder who has the minimum requirements according to the criteria in prequalification process. Public administrators are not sufficient for selection of the proper contractor because of the restrictive provisions of the PPL 4734. The lowest bid method does not enable public construction administrators to select the most qualified contractor and they have realised the fact that the selection of a contractor based on lowest bid alone is inadequate and may lead to the failure of the project in terms of time delay Eand poor quality standards. In order to evaluate the overall efficiency of a project, it is necessary to identify selection criteria. This study aims to focus on identify importance of other criteria besides lowest bid criterion in contractor selection process of PPL 4734. In this study, a survey was conducted to staff of Department of Construction Works of Eskisehir Osmangazi University. According to TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution) for analysis results, termination of construction work in previous tenders is the most important criterion of 12 determined criteria. The lowest bid criterion is ranked in rank 5.

MMV in partnership: the Eurartesim® experience

PubMed Central

2013-01-01

Background This case study describes how a public-private partnership between Medicines for Malaria Venture (MMV) and Sigma-Tau Industrie Farmaceutiche Riunite SpA achieved international regulatory approval for use of the fixed-dose artemisinin-based combination therapy dihydroartemisinin-piperaquine (Eurartesim®) for the treatment of malaria, enabling more widespread access to the medicine in malaria-endemic countries. Case description The combination of dihydroartemisinin and piperaquine demonstrated success in clinical trials for the treatment of malaria in Asia and Africa in the 2000s. However, as it had not been developed to international regulatory standards it was out of the reach of the majority of patients in disease-endemic countries, particularly those reliant on public healthcare systems supported by international donor funding. To overcome this, as of 2004 MMV worked in partnership with Sigma-Tau, Holleykin, Oxford University, the Institute of Tropical Medicine Antwerp, and the National Institute of Malaria Research India to develop the dihydroartemisinin-piperaquine combination to international standards. In 2011, the European Commission granted full marketing authorization to Sigma-Tau for Eurartesim. Discussion and evaluation The partnership between MMV, Sigma-Tau, and numerous other academic and industrial partners across the world, led to the successful development to EMA regulatory standards of a high-quality and highly efficacious anti-malarial treatment that otherwise would not have been possible. The dossier has also been submitted to the WHO for prequalification, and a safety statement to guide correct use of Eurartesim has been produced. In July 2012, the first delivery to a disease-endemic country was made to Cambodia, where the medicine is being used to treat patients and help counter the emergence of artemisinin resistance in the area. A paediatric dispersible formulation of Eurartesim is being developed, with the objective to submit the dossier to the EMA by the end of 2014. Conclusions The development of Eurartesim to international regulatory standards exemplifies the strengths of the product development partnership model in utilising the individual skills and expertise of partners with differing objectives to achieve a common goal. Successful uptake of Eurartesim by public health systems in malaria-endemic countries poses new challenges, which may require additional partnerships as we move forward. PMID:23782869

The use of paediatric artemisinin combinations in sub-Saharan Africa: a snapshot questionnaire survey of health care personnel

PubMed Central

2011-01-01

Background Paediatric drug formulations for artemisinin combination therapy (P-ACT) have been developed over the past few years and have been shown to improve the therapeutic management of young children with uncomplicated falciparum malaria. This process was however not equally paralleled by a timely adoption of P-ACT in national and international treatment recommendations. National malaria programmes in sub-Saharan Africa have not yet widely embraced this new therapeutic tool. To which extent P-ACT is used in the field in sub-Saharan Africa is not known to date. Methods This snapshot questionnaire survey aimed to provide an overview on the current routine practices for the availability and use of P-ACT as anti-malarial treatment for young children in sub-Saharan Africa. Health care personnel in seven countries in West-, Central, and East-Africa were invited to answer a structured questionnaire assessing use and availability of P-ACT. Results A total of 71 respondents including doctors, nurses and pharmacy personnel responsible for the anti-malarial treatment of young children were interviewed. P-ACT was used by 83% (95% confidence interval: 73-90%; n = 59) as first-line treatment for young children. Use of 15 different P-ACT products was reported among which only two have received WHO prequalification status and approval by a stringent registration authority. Use of a specific P-ACT product was not linked to consumer prices or availability of supporting clinical trial data, but may depend more on the marketing capacity of the manufacturer. Major differences in frequency and dosing of anti-malarial regimens with identical anti-malarial compounds and the marketing of loose combinations were recorded. Conclusion Paediatric ACT is widely used for the treatment of uncomplicated malaria in young children. However, the majority of P-ACT formulations in use do not meet highest international quality standards evoking concerns for patients' safety and the induction of drug resistance. Improving the quality of currently marketed P-ACT should constitute a public health priority besides their adoption into official treatment recommendations. PMID:22168234

Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience

PubMed Central

2011-01-01

Background This case study describes how a public-private partnership initiated to develop a new anti-malarial combination, ASAQ Winthrop, has evolved over time to address issues posed by its effective deployment in the field. Case description In 2002, DNDi created the FACT project to develop two fixed-dose combinations, artesunate-amodiaquine and artesunate-mefloquine, to meet the WHO anti-malarial treatment recommendations and international regulatory agencies approval standards. In 2002, Sanofi-aventis had started a development programme for a fixed-dose combination of artesunate and amodiaquine, to replace its co-blister combination. DNDi and sanofi-aventis joined forces in 2004, with the objective of developing within the shortest possible time frame a non-patented, affordable and easy to use fixed-dose combination of artesunate and amodiaquine adapted to the needs of patients, in particular, those of children. The partners developed Coarsucam®/Artesunate Amodiaquine Winthrop® ("ASAQ Winthrop") which was prequalified by the WHO in 2008. Additional partnerships have since been established by DNDi and sanofi-aventis to ensure: 1) the adoption of this new medicine by malaria-endemic countries, 2) its appropriate usage through a broad range of information tools, and 3) the monitoring of its safety and efficacy in the field through an innovative Risk Management Plan. Discussion and evaluation The partnership between DNDi and sanofi-aventis has enabled the development and pre-qualification of ASAQ Winthrop in a short timeframe. As a result of the multiple collaborations established by the two partners, as of late 2010, ASAQ Winthrop was registered in 30 sub-Saharan African countries and in India, with over 80 million treatments distributed in 21 countries. To date, 10 clinical studies, involving 3432 patients with ASAQ Winthrop were completed to document efficacy and safety issues identified in the Risk Management Plan. Conclusions The speed at which ASAQ Winthrop was adopted in the field shows that this drug fits the needs of patients and health authorities. It also demonstrates the power of partnerships that combine different sets of strengths and skills, and that evolve to include additional actors to meet new global health challenges for poverty-related diseases. PMID:21605364

Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience.

PubMed

Bompart, François; Kiechel, Jean-René; Sebbag, Robert; Pecoul, Bernard

2011-05-23

This case study describes how a public-private partnership initiated to develop a new anti-malarial combination, ASAQ Winthrop, has evolved over time to address issues posed by its effective deployment in the field. In 2002, DNDi created the FACT project to develop two fixed-dose combinations, artesunate-amodiaquine and artesunate-mefloquine, to meet the WHO anti-malarial treatment recommendations and international regulatory agencies approval standards. In 2002, Sanofi-Aventis had started a development programme for a fixed-dose combination of artesunate and amodiaquine, to replace its co-blister combination. DNDi and Sanofi-Aventis joined forces in 2004, with the objective of developing within the shortest possible time frame a non-patented, affordable and easy to use fixed-dose combination of artesunate and amodiaquine adapted to the needs of patients, in particular, those of children. The partners developed Coarsucam®/Artesunate Amodiaquine Winthrop® ("ASAQ Winthrop") which was prequalified by the WHO in 2008. Additional partnerships have since been established by DNDi and Sanofi-Aventis to ensure: 1) the adoption of this new medicine by malaria-endemic countries, 2) its appropriate usage through a broad range of information tools, and 3) the monitoring of its safety and efficacy in the field through an innovative Risk Management Plan. The partnership between DNDi and Sanofi-Aventis has enabled the development and pre-qualification of ASAQ Winthrop in a short timeframe. As a result of the multiple collaborations established by the two partners, as of late 2010, ASAQ Winthrop was registered in 30 sub-Saharan African countries and in India, with over 80 million treatments distributed in 21 countries. To date, 10 clinical studies, involving 3432 patients with ASAQ Winthrop were completed to document efficacy and safety issues identified in the Risk Management Plan. The speed at which ASAQ Winthrop was adopted in the field shows that this drug fits the needs of patients and health authorities. It also demonstrates the power of partnerships that combine different sets of strengths and skills, and that evolve to include additional actors to meet new global health challenges for poverty-related diseases.

First Outbreak Response Using an Oral Cholera Vaccine in Africa: Vaccine Coverage, Acceptability and Surveillance of Adverse Events, Guinea, 2012

PubMed Central

Luquero, Francisco J.; Grout, Lise; Ciglenecki, Iza; Sakoba, Keita; Traore, Bala; Heile, Melat; Dialo, Alpha Amadou; Itama, Christian; Serafini, Micaela; Legros, Dominique; Grais, Rebecca F.

2013-01-01

Background Despite World Health Organization (WHO) prequalification of two safe and effective oral cholera vaccines (OCV), concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol) as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. Methodology/Principal Findings We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea). Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4–91.8%] and 87.7% [95%CI:84.2–90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6–83.4%] and 82.9% [95%CI:76.6–87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting) was 75.8% [95%CI: 71.2–75.9%] in Boffa and 75.9% [95%CI: 69.8–80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. Conclusions/Significance The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they should be integrated as an additional tool into the response. PMID:24147164

Health professionals' perceptions of the barriers and facilitators to providing smoking cessation advice to women in pregnancy and during the post-partum period: a systematic review of qualitative research.

PubMed

Flemming, Kate; Graham, Hilary; McCaughan, Dorothy; Angus, Kathryn; Sinclair, Lesley; Bauld, Linda

2016-03-31

Reducing smoking in pregnancy is a policy priority in many countries and as a result there has been a rise in the development of services to help pregnant women to quit. A wide range of professionals are involved in providing these services, with midwives playing a particularly pivotal role. Understanding professionals' experiences of providing smoking cessation support in pregnancy can help to inform the design of interventions as well as to improve routine care. A synthesis of qualitative research of health professionals' perceptions of the barriers and facilitators to providing smoking cessation advice to women in pregnancy and the post-partum period was conducted using meta-ethnography. Searches were undertaken from 1990 to January 2015 using terms for maternity health professionals and smoking cessation advisors, pregnancy, post-partum, smoking, and qualitative in seven electronic databases. The review was reported in accordance with the 'Enhancing transparency in reporting the synthesis of qualitative research' (ENTREQ) statement. Eight studies reported in nine papers were included, reporting on the views of 190 health professionals/key informants, including 85 midwives and health visitors. The synthesis identified that both the professional role of participants and the organisational context in which they worked could act as either barriers or facilitators to an individual's ability to provide smoking cessation support to pregnant or post-partum women. Underpinning these factors was an acknowledgment that the association between maternal smoking and social disadvantage was a considerable barrier to addressing and supporting smoking cessation The review identifies a role for professional education, both pre-qualification and in continuing professional development that will enable individuals to provide smoking cessation support to pregnant women. Key to the success of this education is recognising the centrality of the professional-client/patient relationship in any interaction. The review also highlights a widespread professional perception of the barriers associated with helping women give up smoking in pregnancy, particularly for those in disadvantaged circumstances. Improving the quality and accessibility of evidence on effective healthcare interventions, including evidence on 'what works' to support smoking cessation in disadvantaged groups, should therefore be a priority. PROSPERO 2013: CRD42013004170.

The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership.

PubMed

Lacaze, Catherine; Kauss, Tina; Kiechel, Jean-René; Caminiti, Antonella; Fawaz, Fawaz; Terrassin, Laurent; Cuart, Sylvie; Grislain, Luc; Navaratnam, Visweswaran; Ghezzoul, Bellabes; Gaudin, Karen; White, Nick J; Olliaro, Piero L; Millet, Pascal

2011-05-23

Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation tablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of both industrialized and low income countries. Pharmaceutical development was performed by a research laboratory at the University Bordeaux Segalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further transferred to a company specialized in pharmaceutical development, and then provided to another company for clinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal) within a larger Public Private partnership (the FACT project), set up by WHO/TDR, Médecins Sans Frontières and the Drugs for Neglected Disease initiative (DNDi). The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles while preventing artesunate degradation under tropical conditions. Several options were attempted and failed to provide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH regulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in controlled conditions. However, long-term stability could be achieved, in experimental batches under GMP conditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu blisters. Conduction of the workplan was monitored by DNDi. Collaborations between research and industrial groups greatly accelerated the process of development of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the development process, and no intellectual property right was claimed. This approach resulted in a rapid technology transfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO pre-qualification of the fixed-dose co-formulation together with DNDi. The bi-layered tablet is made available under the names of Coarsucam® and Artesunate amodiaquine Winthrop®, Sanofi-Aventis. The issue related to the difficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of applied research is discussed.

The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership

PubMed Central

2011-01-01

Background Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation tablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of both industrialized and low income countries. Methods Pharmaceutical development was performed by a research laboratory at the University Bordeaux Segalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further transferred to a company specialized in pharmaceutical development, and then provided to another company for clinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal) within a larger Public Private partnership (the FACT project), set up by WHO/TDR, Médecins Sans Frontières and the Drugs for Neglected Disease initiative (DNDi). Results The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles while preventing artesunate degradation under tropical conditions. Several options were attempted and failed to provide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH regulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in controlled conditions. However, long-term stability could be achieved, in experimental batches under GMP conditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu blisters. Conduction of the workplan was monitored by DNDi. Conclusions Collaborations between research and industrial groups greatly accelerated the process of development of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the development process, and no intellectual property right was claimed. This approach resulted in a rapid technology transfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO pre-qualification of the fixed-dose co-formulation together with DNDi. The bi-layered tablet is made available under the names of Coarsucam® and Artesunate amodiaquine Winthrop®, Sanofi-Aventis. The issue related to the difficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of applied research is discussed. PMID:21605361

The global pediatric antiretroviral market: analyses of product availability and utilization reveal challenges for development of pediatric formulations and HIV/AIDS treatment in children.

PubMed

Waning, Brenda; Diedrichsen, Ellen; Jambert, Elodie; Bärnighausen, Till; Li, Yun; Pouw, Mieke; Moon, Suerie

2010-10-17

Important advances in the development and production of quality-certified pediatric antiretroviral (ARV) formulations have recently been made despite significant market disincentives for manufacturers. This progress resulted from lobbying and innovative interventions from HIV/AIDS activists, civil society organizations, and international organizations. Research on uptake and dispersion of these improved products across countries and international organizations has not been conducted but is needed to inform next steps towards improving child health. We used information from the World Health Organization Prequalification Programme and the United States Food and Drug Administration to describe trends in quality-certification of pediatric formulations and used 7,989 donor-funded, pediatric ARV purchase transactions from 2002-2009 to measure uptake and dispersion of new pediatric ARV formulations across countries and programs. Prices for new pediatric ARV formulations were compared to alternative dosage forms. Fewer ARV options exist for HIV/AIDS treatment in children than adults. Before 2005, most pediatric ARVs were produced by innovator companies in single-component solid and liquid forms. Five 2-in1 and four 3-in-1 generic pediatric fixed-dose combinations (FDCs) in solid and dispersible forms have been quality-certified since 2005. Most (67%) of these were produced by one quality-certified manufacturer. Uptake of new pediatric FDCs outside of UNITAID is low. UNITAID accounted for 97-100% of 2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible FDC purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID. Only three Global Fund country recipients reported purchase of these FDCs in 2008. Prices for pediatric FDCs were considerably lower than liquids but typically higher than half of an adult FDC. Pediatric ARV markets are more fragile than adult markets. Ensuring a long-term supply of quality, well-adapted ARVs for children requires ongoing monitoring and improved understanding of global pediatric markets, including country-based research to explain and address low uptake of new, improved formulations. Continued innovation in pediatric ARV development may be threatened by outdated procurement practices failing to connect clinicians making prescribing decisions, supply chain staff dealing with logistics, donors, international organizations, and pharmaceutical manufacturers. Perceptions of global demand must be better informed by accurate estimates of actual country-level demand.

Intervening in global markets to improve access to HIV/AIDS treatment: an analysis of international policies and the dynamics of global antiretroviral medicines markets

PubMed Central

2010-01-01

Background Universal access to antiretroviral therapy (ART) in low- and middle-income countries faces numerous challenges: increasing numbers of people needing ART, new guidelines recommending more expensive antiretroviral (ARV) medicines, limited financing, and few fixed-dose combination (FDC) products. Global initiatives aim to promote efficient global ARV markets, yet little is known about market dynamics and the impact of global policy interventions. Methods We utilize several data sources, including 12,958 donor-funded, adult first-line ARV purchase transactions, to describe the market from 2002-2008. We examine relationships between market trends and: World Health Organization (WHO) HIV/AIDS treatment guidelines; WHO Prequalification Programme (WHO Prequal) and United States (US) Food and Drug Administration (FDA) approvals; and procurement policies of the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), US President's Emergency Plan for AIDS Relief (PEPFAR) and UNITAID. Results WHO recommended 7, 4, 24, and 6 first-line regimens in 2002, 2003, 2006 and 2009 guidelines, respectively. 2009 guidelines replaced a stavudine-based regimen ($88/person/year) with more expensive zidovudine- ($154-260/person/year) or tenofovir-based ($244-465/person/year) regimens. Purchase volumes for ARVs newly-recommended in 2006 (emtricitabine, tenofovir) increased >15-fold from 2006 to 2008. Twenty-four generic FDCs were quality-approved for older regimens but only four for newer regimens. Generic FDCs were available to GFATM recipients in 2004 but to PEPFAR recipients only after FDA approval in 2006. Price trends for single-component generic medicines mirrored generic FDC prices. Two large-scale purchasers, PEPFAR and UNITAID, together accounted for 53%, 84%, and 77% of market volume for abacavir, emtricitabine, and tenofovir, respectively, in 2008. PEPFAR and UNITAID purchases were often split across two manufacturers. Conclusions Global initiatives facilitated the creation of fairly efficient markets for older ARVs, but markets for newer ARVs are less competitive and slower to evolve. WHO guidelines shape demand, and their complexity may help or hinder achievement of economies of scale in pharmaceutical manufacturing. Certification programs assure ARV quality but can delay uptake of new formulations. Large-scale procurement policies may decrease the numbers of buyers and sellers, rendering the market less competitive in the longer-term. Global policies must be developed with consideration for their short- and long-term impact on market dynamics. PMID:20500827

The global pediatric antiretroviral market: analyses of product availability and utilization reveal challenges for development of pediatric formulations and HIV/AIDS treatment in children

PubMed Central

2010-01-01

Background Important advances in the development and production of quality-certified pediatric antiretroviral (ARV) formulations have recently been made despite significant market disincentives for manufacturers. This progress resulted from lobbying and innovative interventions from HIV/AIDS activists, civil society organizations, and international organizations. Research on uptake and dispersion of these improved products across countries and international organizations has not been conducted but is needed to inform next steps towards improving child health. Methods We used information from the World Health Organization Prequalification Programme and the United States Food and Drug Administration to describe trends in quality-certification of pediatric formulations and used 7,989 donor-funded, pediatric ARV purchase transactions from 2002-2009 to measure uptake and dispersion of new pediatric ARV formulations across countries and programs. Prices for new pediatric ARV formulations were compared to alternative dosage forms. Results Fewer ARV options exist for HIV/AIDS treatment in children than adults. Before 2005, most pediatric ARVs were produced by innovator companies in single-component solid and liquid forms. Five 2-in1 and four 3-in-1 generic pediatric fixed-dose combinations (FDCs) in solid and dispersible forms have been quality-certified since 2005. Most (67%) of these were produced by one quality-certified manufacturer. Uptake of new pediatric FDCs outside of UNITAID is low. UNITAID accounted for 97-100% of 2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible FDC purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID. Only three Global Fund country recipients reported purchase of these FDCs in 2008. Prices for pediatric FDCs were considerably lower than liquids but typically higher than half of an adult FDC. Conclusion Pediatric ARV markets are more fragile than adult markets. Ensuring a long-term supply of quality, well-adapted ARVs for children requires ongoing monitoring and improved understanding of global pediatric markets, including country-based research to explain and address low uptake of new, improved formulations. Continued innovation in pediatric ARV development may be threatened by outdated procurement practices failing to connect clinicians making prescribing decisions, supply chain staff dealing with logistics, donors, international organizations, and pharmaceutical manufacturers. Perceptions of global demand must be better informed by accurate estimates of actual country-level demand. PMID:20950492

Introducing quality improvement to pre-qualification nursing students: evaluation of an experiential programme.

PubMed

Kyrkjebø, J M; Hanssen, T A; Haugland, B Ø

2001-12-01

To evaluate a programme introducing quality improvement (QI) in nursing education. Betanien College of Nursing and clinical practices at hospitals in Bergen. 52 nursing students from a second year class working in 16 groups undertaking hospital based practical studies. Second year nursing students were assigned to follow a patient during a day's work and to record the processes of care from the patient's perspective. Data collected included waiting times, patient information, people in contact with the patient, investigations, and procedures performed. Students also identified aspects of practice that could be improved. They then attended a 2 day theoretical introductory course in QI and each group produced flow charts, cause/effect diagrams, and outlines of quality goals using structure, process, and results criteria to describe potential improvements. Each group produced a report of their findings. Main measures-A two-part questionnaire completed by the students before and after the intervention was used to assess the development of their understanding of QI. Evidence that students could apply a range of QI tools and techniques in the specific setting of a hospital ward was assessed from the final reports of their clinical attachments. The students had a significantly better knowledge of QI after the introductory course and group work than before it, and most students indicated that they considered the topic highly relevant for their later career. They reported that it was quite useful to observe one patient throughout one shift and, to some extent, they learned something new. Students found the introductory course and working in groups useful, and most thought the programme should be included in the curriculum for other nursing students. They considered it important for nurses in general to have knowledge about QI, indicating a high perceived relevance of the course. All 16 groups delivered reports of their group work which were approved by the tutors. Through the reports, all the groups demonstrated knowledge and ability to apply tools and techniques in their practical studies in a hospital setting. The introduction of a short experience-based programme into the practical studies of second year nursing students enabled them to learn about the concepts, tools, and techniques of continuous QI in a way that should provide them with the skills to undertake it as part of routine practice.

Minimizing Project Cost by Integrating Subcontractor Selection Decisions with Scheduling

NASA Astrophysics Data System (ADS)

Biruk, Sławomir; Jaśkowski, Piotr; Czarnigowska, Agata

2017-10-01

Subcontracting has been a worldwide practice in the construction industry. It enables the construction enterprises to focus on their core competences and, at the same time, it makes complex project possible to be delivered. Since general contractors bear full responsibility for the works carried out by their subcontractors, it is their task and their risk to select a right subcontractor for a particular work. Although subcontractor management has been admitted to significantly affect the construction project’s performance, current practices and past research deal with subcontractor management and scheduling separately. The proposed model aims to support subcontracting decisions by integrating subcontractor selection with scheduling to enable the general contractor to select the optimal combination of subcontractors and own crews for all work packages of the project. The model allows for the interactions between the subcontractors and their impacts on the overall project performance in terms of cost and, indirectly, time and quality. The model is intended to be used at the general contractor’s bid preparation stage. The authors claim that the subcontracting decisions should be taken in a two-stage process. The first stage is a prequalification - provision of a short list of capable and reliable subcontractors; this stage is not the focus of the paper. The resulting pool of available resources is divided into two subsets: subcontractors, and general contractor’s in-house crews. Once it has been defined, the next stage is to assign them to the work packages that, bound by fixed precedence constraints, form the project’s network diagram. Each package is possible to be delivered by the general contractor’s crew or some of the potential subcontractors, at a specific time and cost. Particular crews and subcontractors can be contracted more than one package, but not at the same time. Other constraints include the predefined project completion date (the project is not allowed to take longer) and maximum total value of subcontracted work. The problem is modelled as a mixed binary linear program that minimizes project cost. It can be solved using universal solvers (e.g. LINGO, AIMMS, CPLEX, MATLAB and Optimization Toolbox, etc.). However, developing a dedicated decision-support tool would facilitate practical applications. To illustrate the idea of the model, the authors present a numerical example to find the optimal set of resources allocated to a project.

An assessment of the supply, programmatic use, and regulatory issues of single low-dose primaquine as a Plasmodium falciparum gametocytocide for sub-Saharan Africa.

PubMed

Chen, Ingrid; Poirot, Eugenie; Newman, Mark; Kandula, Deepika; Shah, Renee; Hwang, Jimee; Cohen, Justin M; Gosling, Roly; Rooney, Luke

2015-05-15

Global ambitions to eliminate malaria are intensifying, underscoring a critical need for transmission blocking tools. In 2012, the WHO recommended the use of 0.25 mg/kg of single low-dose (SLD) primaquine to stop Plasmodium falciparum transmission. To ensure the availability of SLD primaquine to countries in need of this tool, more information on the supply, programmatic, and regulatory barriers to the rollout of SLD primaquine is required. Challenges to the rollout of SLD primaquine in sub-Saharan Africa were established through semi-structured qualitative interviews with three primaquine manufacturers, 43 key informants from Ethiopia, Senegal, Swaziland, Zambia, and Tanzania, and 16 malaria research experts. Sanofi and Remedica are the only two sources of SRA-approved primaquine suitable for procurement by international donors. Neither manufacturer produces primaquine tablet strengths suitable for the transmission blocking indication. In-country key informants revealed that the WHO weight-based recommendation to use SLD primaquine is challenging to implement in actual field settings. Malaria programmes expressed safety concerns of SLD primaquine use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as well as potential interactions between primaquine and co-morbidities, and drug-drug interactions with HIV and/or tuberculosis treatments. Regulatory processes are a major barrier to the rollout of SLD primaquine, requiring multiple steps at both the country and global level. Despite these barriers, demand for SLD primaquine is growing, and malaria researchers are interested in primaquine deployment through mass screen and treat and/or mass drug administration campaigns. Demand for primaquine as a transmission blocking agent is growing rapidly yet multiple barriers to SLD primaquine use exist. Research is needed to define the therapeutic dose range, which will guide dosing regimens in the field, inform the development of new, lower strength primaquine tablets and/or formulation(s), and allay programmatic safety concerns in individuals with G6PD deficiency. Potential interactions between primaquine and co-morbidities and treatments should be explored. To minimize regulatory delays, countries need to prepare for product registration at an early stage, WHO prequalification for suitable primaquine tablet strengths and/or new formulations should be sought, and in the meanwhile only Stringent Regulatory Authority (SRA)-approved primaquine should be used.

A dense Black Carbon network in the region of Paris, France: Implementation, objectives, and first results

NASA Astrophysics Data System (ADS)

Sciare, Jean; Petit, Jean-Eudes; Sarda-Esteve, Roland; Bonnaire, Nicolas; Gros, Valérie; Pernot, Pierre; Ghersi, Véronique; Ampe, Christophe; Songeur, Charlotte; Brugge, Benjamin; Debert, Christophe; Favez, Olivier; Le Priol, Tiphaine; Mocnik, Grisa

2013-04-01

Motivations. Road traffic and domestic wood burning emissions are two major contributors of particulate pollution in our cities. These two sources emit ultra-fine, soot containing, particles in the atmosphere, affecting health adversely, increasing morbidity and mortality from cardiovascular and respiratory conditions and casing lung cancer. A better characterization of soot containing aerosol sources in our major cities provides useful information for policy makers for assessment, implementation and monitoring of strategies to tackle air pollution issues affecting human health with additional benefits for climate change. Objectives. This study on local sources of primary Particulate Matter (PM) in the megacity of Paris is a follow-up of several programs (incl. EU-FP7-MEGAPOLI) that have shown that fine PM - in the Paris background atmosphere - is mostly secondary and imported. A network of 14 stations of Black Carbon has been implemented in the larger region of Paris to provide highly spatially resolved long term survey of local combustion aerosols. To our best knowledge, this is the first time that such densely BC network is operating over a large urban area, providing novel information on the spatial/temporal distribution of combustion aerosols within a post-industrialized megacity. Experimental. As part of the PRIMEQUAL "PREQUALIF" project, a dense Black Carbon network (of 14 stations) has been installed over the city of Paris beginning of 2012 in order to produce spatially resolved Equivalent Black Carbon (EBC) concentration maps with high time resolution through modeling and data assimilation. This network is composed of various real-time instruments (Multi-Angle Absorption Photometer, MAAP by THERMO; Multi-wavelength Aethalometers by MAGEE Scientific) implemented in contrasted sites (rural background, urban background, traffic) complementing the regulated measurements (PM, NOx) in the local air quality network AIRPARIF (http://www.airparif.asso.fr/). Contribution of imported versus local EBC is calculated using the "Lenschow" methodology (Lenschow et al., 2001), whereas the influence of domestic wood burning EBC (vs traffic) over the region of Paris is evaluated using the Aethalometer model developed by Sandradewi et al. (2008). Results and discussion. First results of this BC network are presented here including the temporal variations of EBC from wood burning (domestic heating) and fossil fuel (traffic) for the various sites (1-year observation for rural background and traffic sites; 4-year observations for urban background). The local versus imported contributions of EBC are also presented and discussed for these 2 sources. References. Lenschow, P., et al., Some ideas about the sources of PM10, Atmospheric Environment 35 Supplement No. 1 (2001) S23-S33 Sandradewi, J., et al., Using aerosol light absorption measurements for the quantitative determination of wood burning and traffic emission contributions to particulate matter, Environ. Sci. Technol., 42, 3316-3323, 2008

Mass Vaccination with a New, Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model

PubMed Central

Kar, Shantanu K.; Sah, Binod; Patnaik, Bikash; Kim, Yang Hee; Kerketta, Anna S.; Shin, Sunheang; Rath, Shyam Bandhu; Ali, Mohammad; Mogasale, Vittal; Khuntia, Hemant K.; Bhattachan, Anuj; You, Young Ae; Puri, Mahesh K.; Lopez, Anna Lena; Maskery, Brian; Nair, Gopinath B.; Clemens, John D.; Wierzba, Thomas F.

2014-01-01

Introduction The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. Methods All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. Results The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person. Discussion This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem. PMID:24516675

Mass vaccination with a new, less expensive oral cholera vaccine using public health infrastructure in India: the Odisha model.

PubMed

Kar, Shantanu K; Sah, Binod; Patnaik, Bikash; Kim, Yang Hee; Kerketta, Anna S; Shin, Sunheang; Rath, Shyam Bandhu; Ali, Mohammad; Mogasale, Vittal; Khuntia, Hemant K; Bhattachan, Anuj; You, Young Ae; Puri, Mahesh K; Lopez, Anna Lena; Maskery, Brian; Nair, Gopinath B; Clemens, John D; Wierzba, Thomas F

2014-02-01

The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6-17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person. This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.

Indian vaccine innovation: the case of Shantha Biotechnics

PubMed Central

2011-01-01

Background Although the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held monopolies on the recombinant Hepatitis B vaccine. At a price as high as USD$23 a dose, most Indians families could not afford vaccination. Shantha Biotechnics, a pioneering Indian biotechnology company founded in 1993, saw an unmet need domestically, and developed novel processes for manufacturing Hepatitis B vaccine to reduce prices to less than $1/dose. Further expansion enabled low-cost mass vaccination globally through organizations such as UNICEF. In 2009, Shantha sold over 120 million doses of vaccines. The company was recently acquired by Sanofi-Aventis at a valuation of USD$784 million. Methods The case study and grounded research method was used to illustrate how the globalization of healthcare R&D is enabling private sector companies such as Shantha to address access to essential medicines. Sources including interviews, literature analysis, and on-site observations were combined to conduct a robust examination of Shantha's evolution as a major provider of vaccines for global health indications. Results Shantha's ability to become a significant global vaccine manufacturer and achieve international valuation and market success appears to have been made possible by focusing first on the local health needs of India. How Shantha achieved this balance can be understood in terms of a framework of four guiding principles. First, Shantha identified a therapeutic area (Hepatitis B) in which cost efficiencies could be achieved for reaching the poor. Second, Shantha persistently sought investments and partnerships from non-traditional and international sources including the Foreign Ministry of Oman and Pfizer. Third, Shantha focused on innovation and quality - investing in innovation from the outset yielded the crucial process innovation that allowed Shantha to make an affordable vaccine. Fourth, Shantha constructed its own cGMP facility, which established credibility for vaccine prequalification by the World Health Organization and generated interest from large pharmaceutical companies in its contract research services. These two sources of revenue allowed Shantha to continue to invest in health innovation relevant to the developing world. Conclusions The Shantha case study underscores the important role the private sector can play in global health and access to medicines. Home-grown companies in the developing world are becoming a source of low-cost, locally relevant healthcare R&D for therapeutics such as vaccines. Such companies may be compelled by market forces to focus on products relevant to diseases endemic in their country. Sanofi-Aventis' acquisition of Shantha reveals that even large pharmaceutical companies based in the developed world have recognized the importance of meeting the health needs of the developing world. Collectively, these processes suggest an ability to tap into private sector investments for global health innovation, and illustrate the globalization of healthcare R&D to the developing world. PMID:21507259

Indian vaccine innovation: the case of Shantha Biotechnics.

PubMed

Chakma, Justin; Masum, Hassan; Perampaladas, Kumar; Heys, Jennifer; Singer, Peter A

2011-04-20

Although the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held monopolies on the recombinant Hepatitis B vaccine. At a price as high as USD$23 a dose, most Indians families could not afford vaccination. Shantha Biotechnics, a pioneering Indian biotechnology company founded in 1993, saw an unmet need domestically, and developed novel processes for manufacturing Hepatitis B vaccine to reduce prices to less than $1/dose. Further expansion enabled low-cost mass vaccination globally through organizations such as UNICEF. In 2009, Shantha sold over 120 million doses of vaccines. The company was recently acquired by Sanofi-Aventis at a valuation of USD$784 million. The case study and grounded research method was used to illustrate how the globalization of healthcare R&D is enabling private sector companies such as Shantha to address access to essential medicines. Sources including interviews, literature analysis, and on-site observations were combined to conduct a robust examination of Shantha's evolution as a major provider of vaccines for global health indications. Shantha's ability to become a significant global vaccine manufacturer and achieve international valuation and market success appears to have been made possible by focusing first on the local health needs of India. How Shantha achieved this balance can be understood in terms of a framework of four guiding principles. First, Shantha identified a therapeutic area (Hepatitis B) in which cost efficiencies could be achieved for reaching the poor. Second, Shantha persistently sought investments and partnerships from non-traditional and international sources including the Foreign Ministry of Oman and Pfizer. Third, Shantha focused on innovation and quality - investing in innovation from the outset yielded the crucial process innovation that allowed Shantha to make an affordable vaccine. Fourth, Shantha constructed its own cGMP facility, which established credibility for vaccine prequalification by the World Health Organization and generated interest from large pharmaceutical companies in its contract research services. These two sources of revenue allowed Shantha to continue to invest in health innovation relevant to the developing world. The Shantha case study underscores the important role the private sector can play in global health and access to medicines. Home-grown companies in the developing world are becoming a source of low-cost, locally relevant healthcare R&D for therapeutics such as vaccines. Such companies may be compelled by market forces to focus on products relevant to diseases endemic in their country. Sanofi-Aventis' acquisition of Shantha reveals that even large pharmaceutical companies based in the developed world have recognized the importance of meeting the health needs of the developing world. Collectively, these processes suggest an ability to tap into private sector investments for global health innovation, and illustrate the globalization of healthcare R&D to the developing world.

The performance of community health workers in the management of multiple childhood infectious diseases in Lira, northern Uganda - a mixed methods cross-sectional study.

PubMed

Wanduru, Phillip; Tetui, Moses; Tuhebwe, Doreen; Ediau, Michael; Okuga, Monica; Nalwadda, Christine; Ekirapa-Kiracho, Elizabeth; Waiswa, Peter; Rutebemberwa, Elizeus

2016-01-01

Community health workers (CHWs) have the potential to reduce child mortality by improving access to care, especially in remote areas. Uganda has one of the highest child mortality rates globally. Moreover, rural areas bear the highest proportion of this burden. The optimal performance of CHWs is critical. In this study, we assess the performance of CHWs in managing malaria, pneumonia, and diarrhea in the rural district of Lira, in northern Uganda. A cross-sectional mixed methods study was undertaken to investigate the performance of 393 eligible CHWs in the Lira district of Uganda. Case scenarios were conducted with a medical officer observing CHWs in their management of children suspected of having malaria, pneumonia, or diarrhea. Performance data were collected using a pretested questionnaire with a checklist used by the medical officer to score the CHWs. The primary outcome, CHW performance, is defined as the ability to diagnose and treat malaria, diarrhea, and pneumonia appropriately. Participants were described using a three group performance score (good vs. moderate vs. poor). A binary measure of performance (good vs. poor) was used in multivariable logistic regression to show an association between good performance and a range of independent variables. The qualitative component comprised seven key informant interviews with experts who had informed knowledge with regard to the functionality of CHWs in Lira district. Overall, 347 CHWs (88.3%) had poor scores in managing malaria, diarrhea, and pneumonia, 26 (6.6%) had moderate scores, and 20 (5.1%) had good scores. The factors that were positively associated with performance were secondary-level education (adjusted odds ratio [AOR] 2.72; 95% confidence interval [CI] 1.50-4.92) and meeting with supervisors in the previous month (AOR 2.52; 95% CI 1.12-5.70). Those factors negatively associated with CHW performance included: serving 100-200 households (AOR 0.24; 95% CI 0.12-0.50), serving more than 200 households (AOR 0.22; 95% CI 0.10-0.48), and an initial training duration lasting 2-3 days (AOR 0.13; 95% CI 0.04-0.41). The qualitative findings reinforced the quantitative results by indicating that refresher training, workload, and in-kind incentives were important determinants of performance. The performance of CHWs in Lira was inadequate. There is a need to consider pre-qualification testing before CHWs are appointed. Providing ongoing support and supervision, and ensuring that CHWs have at least secondary education can be helpful in improving their performance. Health system managers also need to ensure that the CHWs' workload is moderated as work overload will reduce performance. Finally, although short training programs are beneficial to some degree, they are not sufficient and should be followed up with regular refresher training.

Establishment of replacement batches for heparin low-molecular-mass for calibration CRS, and the International Standard Low Molecular Weight Heparin for Calibration.

PubMed

Mulloy, B; Heath, A; Behr-Gross, M-E

2007-12-01

An international collaborative study involving fourteen laboratories has taken place, organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM) with National Institute for Biological Standards & Control (NIBSC) (in its capacity as a World Health Organisation (WHO) Laboratory for Biological Standardisation) to provide supporting data for the establishment of replacement batches of Heparin Low-Molecular-Mass (LMM) for Calibration Chemical Reference Substance (CRS), and of the International Reference Reagent (IRR) Low Molecular Weight Heparin for Molecular Weight Calibration. A batch of low-molecular-mass heparin was donated to the organisers and candidate preparations of freeze-dried heparin were produced at NIBSC and EDQM. The establishment study was organised in two phases: a prequalification (phase 1, performed in 3 laboratories in 2005) followed by an international collaborative study (phase 2). In phase 2, started in March 2006, molecular mass parameters were determined for seven different LMM heparin samples using the current CRS batch and two batches of candidate replacement material with a defined number average relative molecular mass (Mn) of 3,700, determined in phase 1. The values calculated using the candidates as standard were systematically different from values calculated using the current batch with its assigned number-average molecular mass (Mna) of 3,700. Using raw data supplied by participants, molecular mass parameters were recalculated using the candidates as standard with values for Mna of 3,800 and 3,900. Values for these parameters agreed more closely with those calculated using the current batch supporting the fact that the candidates, though similar to batch 1 in view of the production processes used, differ slightly in terms of molecular mass distribution. Therefore establishment of the candidates was recommended with an assigned Mna value of 3,800 that is both consistent with phase 1 results and guarantees continuity with the current CRS batch. In phase 2, participants also determined molecular weight parameters for the seven different LMM heparin samples using both the 1st IRR (90/686) and its Broad Standard Table and the candidate World Health Organization (WHO) 2nd International Standard (05/112) (2nd IS) using a Broad Standard Table established in phase 1. Mean molecular weights calculated using 2nd IS were slightly higher than with 1st IRR, and participants in the study indicated that this systematic difference precluded establishment of 2nd IS with the table supplied. A replacement Broad Standard Table has been devised on the basis of the central recalculations of raw data supplied by participants; this table gives improved agreement between values derived using the 1st IRR and the candidate 2nd IS. On the basis of this study a recommendation was made for the establishment of 2nd IS and its proposed Broad Standard Table as a replacement for the 1st International Reference Reagent Low Molecular Weight Heparin for Molecular Weight Calibration. Unlike the 1st IRR however, the candidate material 2nd IS is not suitable for use with the method of Nielsen. The candidate materials were established as heparin low-molecular-mass for calibration batches 2 and 3 by the Ph. Eur. Commission in March 2007 and as 2nd IS low-molecular-weight heparin for molecular weight calibration (05/112) by the Expert Committee on Biological Standardization in November 2007.

VERITAS?: A time for VERIQAS™ and a new approach to training, education, and the quality assessment of CD4+ T lymphocyte counting (I).

PubMed

Barnett, David; Whitby, Liam; Wong, John; Louzao, Raul; Reilly, John T; Denny, Thomas N

2012-03-01

The aim of clinical laboratories is to produce accurate and reproducible results to enable effective and reliable clinical practice and patient management. The standard approach is to use both internal quality control (IQC) and external quality assessment (EQA). IQC serves, in many instances, as a "go, no go" tool to provide real time assurance that instruments and reagent or test systems are performing within defined specifications. EQA however, takes a snapshot at a specific point in time of the full testing process, results are compared to other laboratories performing similar testing but inevitably has some built in delay from sample issue to performance data review. In addition, if IQC or EQA identify areas of concern it can be difficult to determine the exact nature of the problem. In an attempt to address this problem, we have developed an instant QA panel that we have termed VERIQAS™, specifically for CD4(+) T lymphocyte counting, and have undertaken a "proof of principle" pilot study to examine how the use of VERIQAS™ could result in improvement of laboratory performance. In addition, we have examined how this approach could be used as a training and education tool (in a domestic/international setting) and potentially be of value in instrument validation/switch studies (a switch study being defined as a laboratory changing from one method/instrument to a new method/instrument with the VERIQAS™ panel being used as an adjunct to their standard switch study protocol). The basic panel consists of 20 stabilized samples, with predefined CD4(+) T lymphocyte counts, that span low clinically relevant to normal counts, including some blinded replicates (singlet up to quadruplicate combinations). The CD4(+) T lymphocyte target values for each specimen is defined as the trimmed mean ± 2 trimmed standard deviations, where the trimmed values are derived from the CD4(+) T lymphocyte counts reported by the participating centers (~780 laboratories) that receive each UK NEQAS for Leucocyte Immunophenotyping send out. Results for the VERIQAS™ panel were returned online, via a specially designed website, and the participant was provided with an immediate assessment (pass or fail). To date, the panel has been preliminary trialed by eight laboratories to (i) assess pre-EQA qualification (two laboratories); (ii) address performance issues (two laboratories); or (iii) validate new instruments or techniques (four laboratories). Interestingly, even in this pilot study, the panel has been instrumental in identifying specific technical problems in laboratories with EQA performance issues as well as confirming that implementation of new techniques or instruments have been successful. We report here a new and novel "proof of principle" pilot study to quality assessment, that we have termed VERIQAS™, designed to provide instant feedback on performance. Participating laboratories receive 20 "blinded" samples that are in singlet up to quadruplicate combinations. Once a centre reports its results via a website, immediate feedback is provided to both the participant and the EQA organizers, enabling, if required, the initiation of targeted remedial action. We have also shown that this approach has the potential to be used as a tool for prequalification, troubleshooting, training and instrument verification. Pilot phase field trials with VERIQAS™ have shown that the panel can highlight laboratory performance problems, such as suboptimal instrument set up, pipetting and gating strategies, in a rapid and efficient manner. VERIQAS™ will now be introduced, where appropriate, as a second phase study within UK NEQAS for Leucocyte Immunophenotyping to assist those laboratories that have performance issues and also made available to laboratories for training and education of staff and instrument validation studies. Copyright © 2011 International Clinical Cytometry Society.

One or two serological assay testing strategy for diagnosis of HBV and HCV infection? The use of predictive modelling.

PubMed

Parry, John V; Easterbrook, Philippa; Sands, Anita R

2017-11-01

Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost. Our objective was to examine the diagnostic outcomes of a one- versus two-assay serological testing strategy. These data were used to inform recommendations in the 2017 WHO Guidelines on hepatitis B and C testing. Few published studies have compared diagnostic outcomes for one-assay versus two-assay serological testing strategies for HBsAg and anti-HCV. Therefore, the principles of Bayesian statistics were used to conduct a modelling exercise to examine the outcomes of a one-assay versus two-assay testing strategy when applied to a hypothetical population of 10,000 individuals. The resulting model examined the diagnostic outcomes (true and false positive diagnoses; true and false negative diagnoses; positive and negative predictive values as a function of prevalence; and total tests required) for both one-assay and two-assay testing strategies. The performance characteristics assumed for assays used within the testing strategies were informed by WHO prequalification assessment findings and systematic reviews for diagnostic accuracy studies. Each of the presumptive testing strategies (one-assay or two-assay) was modelled at varying prevalences of HBsAg (10%, 2% and 0.4%) and of anti-HCV (40%, 10%, 2% and 0.4%), aimed at representing the range of testing populations typically encountered in WHO Member States. When the two-assay testing strategy was considered, the model assumed the independence of the two assays. Modeling demonstrated that applying a single assay (HBsAg or anti-HCV), even with high specificity (99%), may result in considerable numbers of false positive diagnoses and low positive predictive values (PPV), particularly in lower prevalence settings. Even at very low prevalences shifting to a two-assay testing strategy would result in a PPV approaching 1.0. When test sensitivity is high (>99%) false negative reactions are rare at all but the highest prevalences; but a two-test strategy might yield more false negative diagnoses. The order in which the tests are used has no impact on the overall accuracy of a two-assay strategy though it may impact the total number of tests needed to complete the diagnostic strategy, incurring added cost and complexity. HBsAg assays may have a low sensitivity (<90%), and result in large numbers of false negative diagnoses, particularly in high prevalence settings, which would be exacerbated in the two-assay testing strategy. In contrast, most anti-HCV assays have high sensitivity and lead to fewer false negative results, both in the one-assay and two-assay testing strategies. At prevalences ≤2% the number of tests needed using a second assay was nearly always small, at <300 per 10,000 individuals tested, making sustainability of a second assay uncertain in such a setting. A key public health objective of an effective testing strategy is to identify all individuals who would benefit from treatment. Therefore, a strategy that prioritizes a high NPV (minimal false negatives) may be acceptable even if the PPV is suboptimal (some false positives) as the implementation of such a public health programme must also take account of other factors such as costs, feasibility, impact on testing uptake and linkage to care, and consequences of a false-positive test. This rationale informed the development of the WHO Viral Hepatitis Testing Guidelines, with a conditional recommendation for a one-assay serological testing strategy in most testing settings and populations (≥0.4% prevalence in population tested). A one-test strategy results in few failures to diagnose infection and, although it is associated under most assumptions with a sub-optimal PPV, benefits include greater simplicity, easier implementation, lower costs and better feasibility, uptake and linkage to care. Furthermore, prior to antiviral therapy all those diagnosed either HBsAg or anti-HCV positive will require confirmation of viræmia, preventing unnecessary treatment of those who may be false positive on serology. For HBsAg, in low-prevalence settings (≤0.4%), a second recommendation was made to consider a two-assay testing strategy, using a confirmatory neutralization step or a second different HBsAg assay.

Governance arrangements for health systems in low-income countries: an overview of systematic reviews

PubMed Central

Herrera, Cristian A; Lewin, Simon; Paulsen, Elizabeth; Ciapponi, Agustín; Opiyo, Newton; Pantoja, Tomas; Rada, Gabriel; Wiysonge, Charles S; Bastías, Gabriel; Garcia Marti, Sebastian; Okwundu, Charles I; Peñaloza, Blanca; Oxman, Andrew D

2017-01-01

Background Governance arrangements include changes in rules or processes that determine authority and accountability for health policies, organisations, commercial products and health professionals, as well as the involvement of stakeholders in decision-making. Changes in governance arrangements can affect health and related goals in numerous ways, generally through changes in authority, accountability, openness, participation and coherence. A broad overview of the findings of systematic reviews can help policymakers, their technical support staff and other stakeholders to identify strategies for addressing problems and improving the governance of their health systems. Objectives To provide an overview of the available evidence from up-to-date systematic reviews about the effects of governance arrangements for health systems in low-income countries. Secondary objectives include identifying needs and priorities for future evaluations and systematic reviews on governance arrangements and informing refinements of the framework for governance arrangements outlined in the overview. Methods We searched Health Systems Evidence in November 2010 and PDQ Evidence up to 17 December 2016 for systematic reviews. We did not apply any date, language or publication status limitations in the searches. We included well-conducted systematic reviews of studies that assessed the effects of governance arrangements on patient outcomes (health and health behaviours), the quality or utilisation of healthcare services, resource use (health expenditures, healthcare provider costs, out-of-pocket payments, cost-effectiveness), healthcare provider outcomes (such as sick leave), or social outcomes (such as poverty, employment) and that were published after April 2005. We excluded reviews with limitations that were important enough to compromise the reliability of the findings of the review. Two overview authors independently screened reviews, extracted data and assessed the certainty of evidence using GRADE. We prepared SUPPORT Summaries for eligible reviews, including key messages, 'Summary of findings' tables (using GRADE to assess the certainty of the evidence) and assessments of the relevance of findings to low-income countries. Main results We identified 7272 systematic reviews and included 21 of them in this overview (19 primary reviews and 2 supplementary reviews). We focus here on the results of the 19 primary reviews, one of which had important methodological limitations. The other 18 were reliable (with only minor limitations). We grouped the governance arrangements addressed in the reviews into five categories: authority and accountability for health policies (three reviews); authority and accountability for organisations (two reviews); authority and accountability for commercial products (three reviews); authority and accountability for health professionals (seven reviews); and stakeholder involvement (four reviews). Overall, we found desirable effects for the following interventions on at least one outcome, with moderate- or high-certainty evidence and no moderate- or high-certainty evidence of undesirable effects. Decision-making about what is covered by health insurance - Placing restrictions on the medicines reimbursed by health insurance systems probably decreases the use of and spending on these medicines (moderate-certainty evidence). Stakeholder participation in policy and organisational decisions - Participatory learning and action groups for women probably improve newborn survival (moderate-certainty evidence). - Consumer involvement in preparing patient information probably improves the quality of the information and patient knowledge (moderate-certainty evidence). Disclosing performance information to patients and the public - Disclosing performance data on hospital quality to the public probably encourages hospitals to implement quality improvement activities (moderate-certainty evidence). - Disclosing performance data on individual healthcare providers to the public probably leads people to select providers that have better quality ratings (moderate-certainty evidence). Authors' conclusions Investigators have evaluated a wide range of governance arrangements that are relevant for low-income countries using sound systematic review methods. These strategies have been targeted at different levels in health systems, and studies have assessed a range of outcomes. Moderate-certainty evidence shows desirable effects (with no undesirable effects) for some interventions. However, there are important gaps in the availability of systematic reviews and primary studies for the all of the main categories of governance arrangements. Effects of governance arrangements for health systems in low-income countries What is the aim of this overview? The aim of this Cochrane Overview is to provide a broad summary of what is known about the effects of different governance arrangements for health systems in low-income countries. This overview is based on 19 relevant systematic reviews. These systematic reviews searched for studies that evaluated different types of governance arrangements. The reviews included a total of 172 studies. This overview is one of a series of four Cochrane Overviews that evaluate health system arrangements. Main results What are the effects of different ways of organising authority and accountability for health policies? Three reviews were included and the key findings are that: - collaboration between local health agencies and other local government agencies may lead to little or no difference in physical health or quality of life (low-certainty evidence); - placing restrictions on the medicines reimbursed by health insurance systems probably decreases the use of and spending on these medicines (moderate-certainty evidence); - it is uncertain if fraud prevention, detection and response interventions reduce healthcare fraud and related spending (very low-certainty evidence). What are the effects of different ways of organising authority and accountability for organisations? Two reviews were included and the key findings are that: - Contracting non-state, not-for-profit providers to deliver health services may increase access to and use of these services, improve people's health outcomes and reduce household spending on health (low-certainty evidence). No evidence was available on whether contracting out was more effective than using these funds in the state sector. What are the effects of different ways of organising authority and accountability for commercial products such as medicines and technologies? Three reviews were included and the key findings are that: - systems in which the World Health Organization (WHO) certifies medicine manufacturers (prequalification) and medicines registration (in which medicine regulatory authorities assess medicine manufacturers to ensure they meet international standards) may decrease the proportion of medicines that are substandard or counterfeit (low-certainty evidence); - establishing a maximum reimbursement for pharmacies dispensing similar medicines covered by insurance may increase the use of generic medicines and may reduce the use of brand-name medicines (low-certainty evidence), but it is uncertain whether this approach affects the overall amount spent on medicines (very low-certainty evidence); - direct-to-consumer advertising increases people's requests for medicines and the numbers of prescriptions given (high-certainty evidence). What are the effects of different ways of organising authority and accountability for healthcare providers? Seven reviews were included and the key findings are that: - training programmes for district health system managers may increase their knowledge of planning processes and their monitoring and evaluation skills (low-certainty evidence); - reducing immigration restrictions in high-income countries probably increases the migration of nurses from low- and middle-income to these countries (moderate-certainty evidence); - it is uncertain whether inspection by an external body of healthcare organisation adherence to quality standards improves adherence, quality of care or health-acquired infection rates in hospitals (very low-certainty evidence). What are the effects of different ways of organising stakeholder involvement in governing health services? Four reviews were included and the key findings are that: - participatory learning and action groups for women probably improve newborn survival (moderate-certainty evidence) and may improve maternal survival (low-certainty evidence); - disclosing performance data on health insurance scheme quality to the public may lead people to select health plans that have better quality ratings or to avoid those with worse ratings and may lead to slight improvements in clinical outcomes for health insurance schemes (low-certainty evidence); - disclosing performance data on hospital quality to the public may lead to little or no difference in people's selection of hospitals (low-certainty evidence), probably encourages hospitals to implement quality improvement activities (moderate-certainty evidence) and may lead to slight improvements in hospital clinical outcomes (low-certainty evidence); - disclosing performance on individual healthcare providers to the public probably leads people to select providers that have better quality ratings (moderate-certainty evidence). No studies evaluated the effects of stakeholder participation in policy and organisational decisions. How up-to-date is this overview? The overview authors searched for systematic reviews that had been published up to 17 December 2016. PMID:28895125