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1.  Meeting Report from the Second “Minimum Information for Biological and Biomedical Investigations” (MIBBI) workshop 
Standards in Genomic Sciences  2010;3(3):259-266.
This report summarizes the proceedings of the second workshop of the ‘Minimum Information for Biological and Biomedical Investigations’ (MIBBI) consortium held on Dec 1-2, 2010 in Rüdesheim, Germany through the sponsorship of the Beilstein-Institute. MIBBI is an umbrella organization uniting communities developing Minimum Information (MI) checklists to standardize the description of data sets, the workflows by which they were generated and the scientific context for the work. This workshop brought together representatives of more than twenty communities to present the status of their MI checklists and plans for future development. Shared challenges and solutions were identified and the role of MIBBI in MI checklist development was discussed. The meeting featured some thirty presentations, wide-ranging discussions and breakout groups. The top outcomes of the two-day workshop as defined by the participants were: 1) the chance to share best practices and to identify areas of synergy; 2) defining a series of tasks for updating the MIBBI Portal; 3) reemphasizing the need to maintain independent MI checklists for various communities while leveraging common terms and workflow elements contained in multiple checklists; and 4) revision of the concept of the MIBBI Foundry to focus on the creation of a core set of MIBBI modules intended for reuse by individual MI checklist projects while maintaining the integrity of each MI project. Further information about MIBBI and its range of activities can be found at http://mibbi.org/.
doi:10.4056/sigs.147362
PMCID: PMC3035314  PMID: 21304730
2.  Minimum Information about a Genotyping Experiment (MIGEN) 
Standards in Genomic Sciences  2011;5(2):224-229.
Genotyping experiments are widely used in clinical and basic research laboratories to identify associations between genetic variations and normal/abnormal phenotypes. Genotyping assay techniques vary from single genomic regions that are interrogated using PCR reactions to high throughput assays examining genome-wide sequence and structural variation. The resulting genotype data may include millions of markers of thousands of individuals, requiring various statistical, modeling or other data analysis methodologies to interpret the results. To date, there are no standards for reporting genotyping experiments. Here we present the Minimum Information about a Genotyping Experiment (MIGen) standard, defining the minimum information required for reporting genotyping experiments. MIGen standard covers experimental design, subject description, genotyping procedure, quality control and data analysis. MIGen is a registered project under MIBBI (Minimum Information for Biological and Biomedical Investigations) and is being developed by an interdisciplinary group of experts in basic biomedical science, clinical science, biostatistics and bioinformatics. To accommodate the wide variety of techniques and methodologies applied in current and future genotyping experiment, MIGen leverages foundational concepts from the Ontology for Biomedical Investigations (OBI) for the description of the various types of planned processes and implements a hierarchical document structure. The adoption of MIGen by the research community will facilitate consistent genotyping data interpretation and independent data validation. MIGen can also serve as a framework for the development of data models for capturing and storing genotyping results and experiment metadata in a structured way, to facilitate the exchange of metadata.
doi:10.4056/sigs.1994602
PMCID: PMC3235517  PMID: 22180825
3.  Standardized Metadata for Human Pathogen/Vector Genomic Sequences 
PLoS ONE  2014;9(6):e99979.
High throughput sequencing has accelerated the determination of genome sequences for thousands of human infectious disease pathogens and dozens of their vectors. The scale and scope of these data are enabling genotype-phenotype association studies to identify genetic determinants of pathogen virulence and drug/insecticide resistance, and phylogenetic studies to track the origin and spread of disease outbreaks. To maximize the utility of genomic sequences for these purposes, it is essential that metadata about the pathogen/vector isolate characteristics be collected and made available in organized, clear, and consistent formats. Here we report the development of the GSCID/BRC Project and Sample Application Standard, developed by representatives of the Genome Sequencing Centers for Infectious Diseases (GSCIDs), the Bioinformatics Resource Centers (BRCs) for Infectious Diseases, and the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), informed by interactions with numerous collaborating scientists. It includes mapping to terms from other data standards initiatives, including the Genomic Standards Consortium’s minimal information (MIxS) and NCBI’s BioSample/BioProjects checklists and the Ontology for Biomedical Investigations (OBI). The standard includes data fields about characteristics of the organism or environmental source of the specimen, spatial-temporal information about the specimen isolation event, phenotypic characteristics of the pathogen/vector isolated, and project leadership and support. By modeling metadata fields into an ontology-based semantic framework and reusing existing ontologies and minimum information checklists, the application standard can be extended to support additional project-specific data fields and integrated with other data represented with comparable standards. The use of this metadata standard by all ongoing and future GSCID sequencing projects will provide a consistent representation of these data in the BRC resources and other repositories that leverage these data, allowing investigators to identify relevant genomic sequences and perform comparative genomics analyses that are both statistically meaningful and biologically relevant.
doi:10.1371/journal.pone.0099979
PMCID: PMC4061050  PMID: 24936976
4.  Eurocan plus report: feasibility study for coordination of national cancer research activities 
Summary
The EUROCAN+PLUS Project, called for by the European Parliament, was launched in October 2005 as a feasibility study for coordination of national cancer research activities in Europe. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people, the largest Europe–wide consultation ever conducted in the field of cancer research.
Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
It is essential to include the patients’ voice in the establishment of priority areas in cancer research at the present time. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community is evident. A top priority should be the development of translational research (in its widest form), leading to the development of effective and innovative cancer treatments and preventive strategies. Translational research ranges from bench–to–bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
The EUROCAN+PLUS Project recommends the creation of a small, permanent and independent European Cancer Initiative (ECI). This should be a model structure and was widely supported at both General Assemblies of the project. The ECI should assume responsibility for stimulating innovative cancer research and facilitating processes, becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ organizations, European institutions, Member States, industry and small and medium enterprises (SMEs), putting into practice solutions aimed at alleviating barriers to collaboration and coordination of cancer research activities in the European Union, and dealing with legal and regulatory issues. The development of an effective ECI will require time, but this entity should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co–operation between comprehensive cancer centres and basic research laboratories throughout Europe and (3) networking between funding bodies at the European level.
The European Parliament and its instruments have had a major influence in cancer control in Europe, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
Executive Summary
Cancer is one of the biggest public health crises facing Europe in the 21st century—one for which Europe is currently not prepared nor preparing itself. Cancer is a major cause of death in Europe with two million casualties and three million new cases diagnosed annually, and the situation is set to worsen as the population ages.
These facts led the European Parliament, through the Research Directorate-General of the European Commission, to call for initiatives for better coordination of cancer research efforts in the European Union. The EUROCAN+PLUS Project was launched in October 2005 as a feasibility study for coordination of national cancer research activities. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people. In this respect, the Project became the largest Europe-wide consultation ever conducted in the field of cancer research, implicating researchers, cancer centres and hospitals, administrators, healthcare professionals, funding agencies, industry, patients’ organizations and patients.
The Project first identified barriers impeding research and collaboration in research in Europe. Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain the formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
In addition, there is a shortage of leadership, a multiplicity of institutions each focusing on its own agenda, sub–optimal contact with industry, inadequate training, non–existent career paths, low personnel mobility in research especially among clinicians and inefficient funding—all conspiring against efficient collaboration in cancer care and research. European cancer research today does not have a functional translational research continuum, that is the process that exploits biomedical research innovations and converts them into prevention methods, diagnostic tools and therapies. Moreover, epidemiological research is not integrated with other types of cancer research, and the implementation of the European Directives on Clinical Trials 1 and on Personal Data Protection 2 has further slowed the innovation process in Europe. Furthermore, large inequalities in health and research exist between the EU–15 and the New Member States.
The picture is not entirely bleak, however, as the European cancer research scene presents several strengths, such as excellent basic research and clinical research and innovative etiological research that should be better exploited.
When considering recommendations, several priority dimensions had to be retained. It is essential that proposals include actions and recommendations that can benefit all Member States of the European Union and not just States with the elite centres. It is also essential to have a broader patient orientation to help provide the knowledge to establish cancer control possibilities when we exhaust what can be achieved by the implementation of current knowledge. It is vital that the actions proposed can contribute to the Lisbon Strategy to make Europe more innovative and competitive in (cancer) research.
The Project participants identified six areas for which consensus solutions should be implemented in order to obtain better coordination of cancer research activities. The required solutions are as follows. The proactive management of innovation, detection, facilitation of collaborations and maintenance of healthy competition within the European cancer research community.The establishment of an exchange portal of information for health professionals, patients and policy makers.The provision of guidance for translational and clinical research including the establishment of a translational research platform involving comprehensive cancer centres and cancer research centres.The coordination of calls and financial management of cancer research projects.The construction of a ‘one–stop shop’ as a contact interface between the industry, small and medium enterprises, scientists and other stakeholders.The support of greater involvement of healthcare professionals in translational research and multidisciplinary training.
In the course of the EUROCAN+PLUS consultative process, several key collaborative projects emerged between the various groups and institutes engaged in the consultation. There was a collaboration network established with Europe’s leading Comprehensive Cancer Centres; funding was awarded for a closer collaboration of Owners of Cancer Registries in Europe (EUROCOURSE); there was funding received from FP7 for an extensive network of leading Biological Resource Centres in Europe (BBMRI); a Working Group identified the special needs of Central, Eastern and South–eastern Europe and proposed a remedy (‘Warsaw Declaration’), and the concept of developing a one–stop shop for dealing with academia and industry including the Innovative Medicines Initiative (IMI) was discussed in detail.
Several other dimensions currently lacking were identified. There is an absolute necessity to include the patients’ voice in the establishment of priority areas in cancer research at the present time. It was a salutary lesson when it was recognized that all that is known about the quality of life of the cancer patient comes from the experience of a tiny proportion of cancer patients included in a few clinical trials. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community was evident. A top priority should be the development of translational research (in its widest form) and the development of effective and innovative cancer treatments and preventative strategies in the European Union. Translational research ranges from bench-to-bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
Having taken note of the barriers and the solutions and having examined relevant examples of existing European organizations in the field, it was agreed during the General Assembly of 19 November 2007 that the EUROCAN+PLUS Project had to recommend the creation of a small, permanent and neutral ECI. This should be a model structure and was widely supported at both General Assemblies of the project. The proposal is based on the successful model of the European Molecular Biology Organisation (EMBO), and its principal aims include providing a forum where researchers from all backgrounds and from all countries can meet with members of other specialities including patients, nurses, clinicians, funders and scientific administrators to develop priority programmes to make Europe more competitive in research and more focused on the cancer patient.
The ECI should assume responsibility for: stimulating innovative cancer research and facilitating processes;becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ and organizations;European institutions, Member States, industry and small and medium enterprises;putting into practice the aforementioned solutions aimed at alleviating barriers and coordinating cancer research activities in the EU;dealing with legal and regulatory issues.
Solutions implemented through the ECI will lead to better coordination and collaboration throughout Europe, more efficient use of resources, an increase in Europe’s attractiveness to the biomedical industry and better quality of cancer research and education of health professionals.
The Project considered that European legal instruments currently available were inadequate for addressing many aspects of the barriers identified and for the implementation of effective, lasting solutions. Therefore, the legal environment that could shelter an idea like the ECI remains to be defined but should be done so as a priority. In this context, the initiative of the European Commission for a new legal entity for research infrastructure might be a step in this direction. The development of an effective ECI will require time, but this should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass: (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co-operation between comprehensive cancer centres and basic research laboratories throughout Europe; (3) networking between funding bodies at the European level. Another topic deserving immediate attention is the creation of a European database on cancer research projects and cancer research facilities.
Despite enormous progress in cancer control in Europe during the past two decades, there was an increase of 300,000 in the number of new cases of cancer diagnosed between 2004 and 2006. The European Parliament and its instruments have had a major influence in cancer control, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
doi:10.3332/ecancer.2011.84
PMCID: PMC3234055  PMID: 22274749
5.  MOPED enables discoveries through consistently processed proteomics data 
Journal of proteome research  2013;13(1):107-113.
The Model Organism Protein Expression Database (MOPED, http://moped.proteinspire.org), is an expanding proteomics resource to enable biological and biomedical discoveries. MOPED aggregates simple, standardized and consistently processed summaries of protein expression and metadata from proteomics (mass spectrometry) experiments from human and model organisms (mouse, worm and yeast). The latest version of MOPED adds new estimates of protein abundance and concentration, as well as relative (differential) expression data. MOPED provides a new updated query interface that allows users to explore information by organism, tissue, localization, condition, experiment, or keyword. MOPED supports the Human Proteome Project’s efforts to generate chromosome and diseases specific proteomes by providing links from proteins to chromosome and disease information, as well as many complementary resources. MOPED supports a new omics metadata checklist in order to harmonize data integration, analysis and use. MOPED’s development is driven by the user community, which spans 90 countries guiding future development that will transform MOPED into a multi-omics resource. MOPED encourages users to submit data in a simple format. They can use the metadata a checklist generate a data publication for this submission. As a result, MOPED will provide even greater insights into complex biological processes and systems and enable deeper and more comprehensive biological and biomedical discoveries.
doi:10.1021/pr400884c
PMCID: PMC4039175  PMID: 24350770
6.  Guidelines for information about therapy experiments: a proposal on best practice for recording experimental data on cancer therapy 
BMC Research Notes  2012;5:10.
Background
Biology, biomedicine and healthcare have become data-driven enterprises, where scientists and clinicians need to generate, access, validate, interpret and integrate different kinds of experimental and patient-related data. Thus, recording and reporting of data in a systematic and unambiguous fashion is crucial to allow aggregation and re-use of data. This paper reviews the benefits of existing biomedical data standards and focuses on key elements to record experiments for therapy development. Specifically, we describe the experiments performed in molecular, cellular, animal and clinical models. We also provide an example set of elements for a therapy tested in a phase I clinical trial.
Findings
We introduce the Guidelines for Information About Therapy Experiments (GIATE), a minimum information checklist creating a consistent framework to transparently report the purpose, methods and results of the therapeutic experiments. A discussion on the scope, design and structure of the guidelines is presented, together with a description of the intended audience. We also present complementary resources such as a classification scheme, and two alternative ways of creating GIATE information: an electronic lab notebook and a simple spreadsheet-based format. Finally, we use GIATE to record the details of the phase I clinical trial of CHT-25 for patients with refractory lymphomas. The benefits of using GIATE for this experiment are discussed.
Conclusions
While data standards are being developed to facilitate data sharing and integration in various aspects of experimental medicine, such as genomics and clinical data, no previous work focused on therapy development. We propose a checklist for therapy experiments and demonstrate its use in the 131Iodine labeled CHT-25 chimeric antibody cancer therapy. As future work, we will expand the set of GIATE tools to continue to encourage its use by cancer researchers, and we will engineer an ontology to annotate GIATE elements and facilitate unambiguous interpretation and data integration.
doi:10.1186/1756-0500-5-10
PMCID: PMC3285520  PMID: 22226027
7.  A checklist for identifying determinants of practice: A systematic review and synthesis of frameworks and taxonomies of factors that prevent or enable improvements in healthcare professional practice 
Background
Determinants of practice are factors that might prevent or enable improvements. Several checklists, frameworks, taxonomies, and classifications of determinants of healthcare professional practice have been published. In this paper, we describe the development of a comprehensive, integrated checklist of determinants of practice (the TICD checklist).
Methods
We performed a systematic review of frameworks of determinants of practice followed by a consensus process. We searched electronic databases and screened the reference lists of key background documents. Two authors independently assessed titles and abstracts, and potentially relevant full text articles. We compiled a list of attributes that a checklist should have: comprehensiveness, relevance, applicability, simplicity, logic, clarity, usability, suitability, and usefulness. We assessed included articles using these criteria and collected information about the theory, model, or logic underlying how the factors (determinants) were selected, described, and grouped, the strengths and weaknesses of the checklist, and the determinants and the domains in each checklist. We drafted a preliminary checklist based on an aggregated list of determinants from the included checklists, and finalized the checklist by a consensus process among implementation researchers.
Results
We screened 5,778 titles and abstracts and retrieved 87 potentially relevant papers in full text. Several of these papers had references to papers that we also retrieved in full text. We also checked potentially relevant papers we had on file that were not retrieved by the searches. We included 12 checklists. None of these were completely comprehensive when compared to the aggregated list of determinants and domains. We developed a checklist with 57 potential determinants of practice grouped in seven domains: guideline factors, individual health professional factors, patient factors, professional interactions, incentives and resources, capacity for organisational change, and social, political, and legal factors. We also developed five worksheets to facilitate the use of the checklist.
Conclusions
Based on a systematic review and a consensus process we developed a checklist that aims to be comprehensive and to build on the strengths of each of the 12 included checklists. The checklist is accompanied with five worksheets to facilitate its use in implementation research and quality improvement projects.
doi:10.1186/1748-5908-8-35
PMCID: PMC3617095  PMID: 23522377
8.  CONSORT for Reporting Randomized Controlled Trials in Journal and Conference Abstracts: Explanation and Elaboration 
PLoS Medicine  2008;5(1):e20.
Background
Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract.
Methods and Findings
We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item.
Conclusions
CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results.
The authors extend the CONSORT Statement to develop a minimum list of essential items to consider when reporting the results of a randomized trial in any journal or conference abstract.
doi:10.1371/journal.pmed.0050020
PMCID: PMC2211558  PMID: 18215107
9.  A Model for the Roll-Out of Comprehensive Adult Male Circumcision Services in African Low-Income Settings of High HIV Incidence: The ANRS 12126 Bophelo Pele Project 
PLoS Medicine  2010;7(7):e1000309.
Bertrand Auvert and colleagues describe the large-scale roll-out of adult male circumcision through a program in South Africa.
Background
World Health Organization (WHO)/Joint United Nations Programme on AIDS (UNAIDS) has recommended adult male circumcision (AMC) for the prevention of heterosexually acquired HIV infection in men from communities where HIV is hyperendemic and AMC prevalence is low. The objective of this study was to investigate the feasibility of the roll-out of medicalized AMC according to UNAIDS/WHO operational guidelines in a targeted African setting.
Methods and Findings
The ANRS 12126 “Bophelo Pele” project was implemented in 2008 in the township of Orange Farm (South Africa). It became functional in 5 mo once local and ethical authorizations were obtained. Project activities involved community mobilization and outreach, as well as communication approaches aimed at both men and women incorporating broader HIV prevention strategies and promoting sexual health. Free medicalized AMC was offered to male residents aged 15 y and over at the project's main center, which had been designed for low-income settings. Through the establishment of an innovative surgical organization, up to 150 AMCs under local anesthesia, with sterilized circumcision disposable kits and electrocautery, could be performed per day by three task-sharing teams of one medical circumciser and five nurses. Community support for the project was high. As of November 2009, 14,011 men had been circumcised, averaging 740 per month in the past 12 mo, and 27.5% of project participants agreed to be tested for HIV. The rate of adverse events, none of which resulted in permanent damage or death, was 1.8%. Most of the men surveyed (92%) rated the services provided positively. An estimated 39.1% of adult uncircumcised male residents have undergone surgery and uptake is steadily increasing.
Conclusion
This study demonstrates that a quality AMC roll-out adapted to African low-income settings is feasible and can be implemented quickly and safely according to international guidelines. The project can be a model for the scale-up of comprehensive AMC services, which could be tailored for other rural and urban communities of high HIV prevalence and low AMC rates in Eastern and Southern Africa.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed about 25 million people since 1981, and more than 30 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV infection is extremely important. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having one or a few partners, and by always using a male or female condom. In addition, three trials in sub-Saharan Africa recently reported that medicalized adult male circumcision (AMC)—the surgical removal of the foreskin, a loose fold of skin that covers the head of the penis—can reduce HIV transmission rates in men by more than a half. Thus, AMC delivered as a catch-up campaign—in the long-term, circumcision of male infants is likely to be a more sustainable strategy—has the potential to reduce the prevalence of HIV (the proportion of the population infected with HIV) in sub-Saharan Africa.
Why Was This Study Done?
The World Health Organization (WHO) and the Joint United Nations Programme on AIDS (UNAIDS) now recommend that AMC programs should be rolled-out wherever there is a generalized HIV epidemic and few men are circumcised. Accordingly, these organizations have defined a minimum package of AMC services and have issued guidelines and tools designed to engage communities in the roll-out and to ensure that appropriate AMC counseling and surgical facilities are available. But is rapid AMC roll-out feasible in real-life settings? Here, the researchers try to find out by studying the “Bophelo Pele” (Health First) project. This project, which follows the WHO/UNAIDS guidelines for AMC, aims to offer free, safe AMC services to all men aged 15 years or more living in the Orange Farm township in South Africa as part of a community-based intervention against HIV. Orange Farm is in a low-income region of South Africa where HIV prevalence is 15.2% and AMC prevalence is about 25%.
What Did the Researchers Do and Find?
Before the Bophelo Pele project started in January 2008, the researchers consulted the community about the implementation of AMC, helped to create a community advisory board, organized community workshops to discuss the project, and surveyed people's knowledge about AMC and willingness to undergo AMC. These activities indicated a high level of community support for the project and a high level of willingness among men to undergo AMC. Once the project started, the researchers used multiple communication channels to tell the Orange Farm residents about AMC and broader HIV prevention strategies and provided eligible men with counseling about AMC and with voluntary HIV counseling and testing during the recruitment process. Three days after recruitment, eligible men were circumcised free-of-charge at the project's main center, where three teams of one medical circumciser and five nurses were able to complete up to 150 AMCs per day. By November 2009, 14,011 men had been circumcised (more than a third of the eligible men in the township), and AMC uptake was still increasing steadily. Nearly all the men circumcised over one 2-month period rated the AMC services positively in a survey and adverse effects (all mild) occurred after fewer than 1 in 50 circumcisions.
What Do These Findings Mean?
These findings suggest that the rapid roll-out of high-quality, free AMC as an intervention against HIV has been successful in the Orange Farm township. However, other findings highlight some of the challenges that face AMC roll-out. For example, only a quarter of the participants agreed to voluntary HIV counseling and testing, which is worrying because newly circumcised HIV-positive men have an increased risk of transmitting HIV if they resume sexual activity too soon after the operation. Similarly, only two-thirds of the participants returned for a check-up after circumcision; this proportion needs to be increased to ensure the safety and efficacy of AMC programs. Nevertheless, these findings and those from similar intervention programs in Kenya and Uganda indicate that AMC scale-up should be feasible, at least in the short term, as an HIV prevention strategy in low-income communities where there is a high HIV prevalence and a low AMC rate.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000309.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, and on circumcision and HIV (in English and Spanish)
More information about male circumcision is available from WHO and from the Clearinghouse on Male Circumcision, including a June 2010 report from WHO/UNAIDS entitled Progress in male circumcision scale-up: country implementation and research update
More information about the Bophelo Pele project is available
doi:10.1371/journal.pmed.1000309
PMCID: PMC2907271  PMID: 20652013
10.  Guidelines, Editors, Pharma And The Biological Paradigm Shift 
Mens Sana Monographs  2007;5(1):27-30.
Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both.
There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.
Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin) and the marketing maneuvers of Eli Lilly's Xigris (rhAPC). Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour.
A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.
Clinical practice guidelines (CPG) are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a relatively recent survey of 2002, it was found that about 60% of 192 authors of clinical practice guidelines reported they had financial connections with the companies whose drugs were under consideration. There is a strong case for making CPGs based not just on effectivity but cost effectivity. The various ramifications of this need to be spelt out. Work of bodies like the Appraisal of Guidelines Research and Evaluation (AGREE) Collaboration and Guidelines Advisory Committee (GAC) are also worth a close look.
Even the actions of Foundations that work for disease amelioration have come under scrutiny. The process of setting up ‘Best Practices’ Guidelines for interactions between the pharmaceutical industry and clinicians has already begun and can have important consequences for patient care. Similarly, Good Publication Practice (GPP) for pharmaceutical companies have also been set up aimed at improving the behaviour of drug companies while reporting drug trials
The rapidly increasing trend toward influence and control by industry has become a concern for many. It is of such importance that the Association of American Medical Colleges has issued two relatively new documents - one, in 2001, on how to deal with individual conflicts of interest; and the other, in 2002, on how to deal with institutional conflicts of interest in the conduct of clinical research. Academic Medical Centers (AMCs), as also medical education and research institutions at other places, have to adopt means that minimize their conflicts of interest.
Both medical associations and research journal editors are getting concerned with individual and institutional conflicts of interest in the conduct of clinical research and documents are now available which address these issues. The 2001 ICMJE revision calls for full disclosure of the sponsor's role in research, as well as assurance that the investigators are independent of the sponsor, are fully accountable for the design and conduct of the trial, have independent access to all trial data and control all editorial and publication decisions. However the findings of a 2002 study suggest that academic institutions routinely participate in clinical research that does not adhere to ICMJE standards of accountability, access to data and control of publication.
There is an inevitable slant to produce not necessarily useful but marketable products which ensure the profitability of industry and research grants outflow to academia. Industry supports new, not traditional, therapies, irrespective of what is effective. Whatever traditional therapy is supported is most probably because the company concerned has a product with a big stake there, which has remained a ‘gold standard’ or which that player thinks has still some ‘juice’ left.
Industry sponsorship is mainly for potential medications, not for trying to determine whether there may be non-pharmacological interventions that may be equally good, if not better. In the paradigm shift towards biological psychiatry, the role of industry sponsorship is not overt but probably more pervasive than many have realised, or the right thinking may consider good, for the health of the branch in the long run.
An issue of major concern is protection of the interests of research subjects. Patients agree to become research subjects not only for personal medical benefit but, as an extension, to benefit the rest of the patient population and also advance medical research.
We all accept that industry profits have to be made, and investment in research and development by the pharma industry is massive. However, we must also accept there is a fundamental difference between marketing strategies for other entities and those for drugs.
The ultimate barometer is patient welfare and no drug that compromises it can stand the test of time. So, how does it make even commercial sense in the long term to market substandard products? The greatest mistake long-term players in industry may make is try to adopt the shady techniques of the upstart new entrant. Secrecy of marketing/sales tactics, of the process of manufacture, of other strategies and plans of business expansion, of strategies to tackle competition are fine business tactics. But it is critical that secrecy as a tactic not extend to reporting of research findings, especially those contrary to one's product.
Pharma has no option but to make a quality product, do comprehensive adverse reaction profiles, and market it only if it passes both tests.
Why does pharma adopt questionable tactics? The reasons are essentially two:
What with all the constraints, a drug comes to the pharmacy after huge investments. There are crippling overheads and infrastructure costs to be recovered. And there are massive profit margins to be maintained. If these were to be dependent only on genuine drug discoveries, that would be taking too great a risk.Industry players have to strike the right balance between profit making and credibility. In profit making, the marketing champions play their role. In credibility ratings, researchers and paid spokes-persons play their role. All is hunky dory till marketing is based on credibility. When there is nothing available to make for credibility, something is projected as one and marketing carried out, in the calculated hope that profits can accrue, since profit making must continue endlessly. That is what makes pharma adopt even questionable means to make profits.
Essentially, there are four types of drugs. First, drugs that work and have minimal side-effects; second, drugs which work but have serious side-effects; third, drugs that do not work and have minimal side-effects; and fourth, drugs which work minimally but have serious side-effects. It is the second and fourth types that create major hassles for industry. Often, industry may try to project the fourth type as the second to escape censure.
The major cat and mouse game being played by conscientious researchers is in exposing the third and fourth for what they are and not allowing industry to palm them off as the first and second type respectively. The other major game is in preventing the second type from being projected as the first. The third type are essentially harmless, so they attract censure all right and some merriment at the antics to market them. But they escape anything more than a light rap on the knuckles, except when they are projected as the first type.
What is necessary for industry captains and long-term players is to realise:
Their major propelling force can only be producing the first type. 2. They accept the second type only till they can lay their hands on the first. 3. The third type can be occasionally played around with to shore up profits, but never by projecting them as the first type. 4. The fourth type are the laggards, real threat to credibility and therefore do not deserve any market hype or promotion.
In finding out why most pharma indulges in questionable tactics, we are lead to some interesting solutions to prevent such tactics with the least amount of hassles for all concerned, even as both profits and credibility are kept intact.
doi:10.4103/0973-1229.32176
PMCID: PMC3192391  PMID: 22058616
Academia; Pharmaceutical Industry; Clinical Practice Guidelines; Best Practice Guidelines; Academic Medical Centers; Medical Associations; Research Journals; Clinical Research; Public Welfare; Pharma Image; Corporate Welfare; Biological Psychiatry; Law Suits Against Industry
11.  Psychometric Properties of Self-Report Concussion Scales and Checklists 
Journal of Athletic Training  2012;47(2):221-223.
Reference/Citation:
Alla S, Sullivan SJ, Hale L, McCrory P. Self-report scales/checklists for the measurement of concussion symptoms: a systematic review. Br J Sports Med. 2009;43 (suppl 1):i3–i12.
Clinical Question:
Which self-report symptom scales or checklists are psychometrically sound for clinical use to assess sport-related concussion?
Data Sources:
Articles available in full text, published from the establishment of each database through December 2008, were identified from PubMed, Medline, CINAHL, Scopus, Web of Science, SPORTDiscus, PsycINFO, and AMED. Search terms included brain concussion, signs or symptoms, and athletic injuries, in combination with the AND Boolean operator, and were limited to studies published in English. The authors also hand searched the reference lists of retrieved articles. Additional searches of books, conference proceedings, theses, and Web sites of commercial scales were done to provide additional information about the psychometric properties and development for those scales when needed in articles meeting the inclusion criteria.
Study Selection:
Articles were included if they identified all the items on the scale and the article was either an original research report describing the use of scales in the evaluation of concussion symptoms or a review article that discussed the use or development of concussion symptom scales. Only articles published in English and available in full text were included.
Data Extraction:
From each study, the following information was extracted by the primary author using a standardized protocol: study design, publication year, participant characteristics, reliability of the scale, and details of the scale or checklist, including name, number of items, time of measurement, format, mode of report, data analysis, scoring, and psychometric properties. A quality assessment of included studies was done using 16 items from the Downs and Black checklist1 and assessed reporting, internal validity, and external validity.
Main Results:
The initial database search identified 421 articles. After 131 duplicate articles were removed, 290 articles remained and were added to 17 articles found during the hand search, for a total of 307 articles; of those, 295 were available in full text. Sixty articles met the inclusion criteria and were used in the systematic review. The quality of the included studies ranged from 9 to 15 points out of a maximum quality score of 17. The included articles were published between 1995 and 2008 and included a collective total of 5864 concussed athletes and 5032 nonconcussed controls, most of whom participated in American football. The majority of the studies were descriptive studies monitoring the resolution of concussive self-report symptoms compared with either a preseason baseline or healthy control group, with a smaller number of studies (n = 8) investigating the development of a scale.
The authors initially identified 20 scales that were used among the 60 included articles. Further review revealed that 14 scales were variations of the Pittsburgh Steelers postconcussion scale (the Post-Concussion Scale, Post-Concussion Scale: Revised, Post-Concussion Scale: ImPACT, Post-Concussion Symptom Scale: Vienna, Graded Symptom Checklist [GSC], Head Injury Scale, McGill ACE Post-Concussion Symptoms Scale, and CogState Sport Symptom Checklist), narrowing down to 6 core scales, which the authors discussed further. The 6 core scales were the Pittsburgh Steelers Post-Concussion Scale (17 items), Post-Concussion Symptom Assessment Questionnaire (10 items), Concussion Resolution Index postconcussion questionnaire (15 items), Signs and Symptoms Checklist (34 items), Sport Concussion Assessment Tool (SCAT) postconcussion symptom scale (25 items), and Concussion Symptom Inventory (12 items). Each of the 6 core scales includes symptoms associated with sport-related concussion; however, the number of items on each scale varied. A 7-point Likert scale was used on most scales, with a smaller number using a dichotomous (yes/no) classification.
Only 7 of the 20 scales had published psychometric properties, and only 1 scale, the Concussion Symptom Inventory, was empirically driven (Rasch analysis), with development of the scale occurring before its clinical use. Internal consistency (Cronbach α) was reported for the Post-Concussion Scale (.87), Post-Concussion Scale: ImPACT 22-item (.88–.94), Head Injury Scale 9-item (.78), and Head Injury Scale 16-item (.84). Test-retest reliability has been reported only for the Post-Concussion Scale (Spearman r = .55) and the Post-Concussion Scale: ImPACT 21-item (Pearson r = .65). With respect to validity, the SCAT postconcussion scale has demonstrated face and content validity, the Post-Concussion Scale: ImPACT 22-item and Head Injury Scale 9-item have reported construct validity, and the Head Injury Scale 9-item and 16-item have published factorial validity.
Sensitivity and specificity have been reported only with the GSC (0.89 and 1.0, respectively) and the Post-Concussion Scale: ImPACT 21-item when combined with the neurocognitive component of ImPACT (0.819 and 0.849, respectively). Meaningful change scores were reported for the Post-Concussion Scale (14.8 points), Post-Concussion Scale: ImPACT 22-item (6.8 points), and Post-Concussion Scale: ImPACT 21-item (standard error of the difference = 7.17; 80% confidence interval = 9.18).
Conclusions:
Numerous scales exist for measuring the number and severity of concussion-related symptoms, with most evolving from the neuropsychology literature pertaining to head-injured populations. However, very few of these were created in a systematic manner that follows scale development processes and have published psychometric properties. Clinicians need to understand these limitations when choosing and using a symptom scale for inclusion in a concussion assessment battery. Future authors should assess the underlying constructs and measurement properties of currently available scales and use the ever-increasing prospective data pools of concussed athlete information to develop scales following appropriate, systematic processes.
PMCID: PMC3418135  PMID: 22488289
mild traumatic brain injuries; evaluation; reliability; validity; sensitivity; specificity
12.  Enhancing the reporting and transparency of rheumatology research: a guide to reporting guidelines 
Manuscripts and abstracts from biomedical journals frequently do not contain proper information for meeting required standards and serving the multiple needs of their end users. Reporting guidelines and checklists help researchers to meet those standards by providing rules or principles for specific research areas. Rheumatology research includes a broad range of heterogeneous research areas, each with its own requirements, producing several distinct categories of articles. Our objectives with this article are to raise awareness of the existence and importance of reporting guidelines, to present a structured overview of reporting guidelines that rheumatology journals could apply, and to encourage their use by journal authors, editors, and reviewers, including those of Arthritis Research & Therapy. Internationally recognized reporting guidelines exist for a diversity of research areas. We encourage colleagues to consult the 'Enhancing the QUAlity and Transparency Of health Research' (EQUATOR) network when writing scientific papers. EQUATOR is an international initiative that seeks to improve the reliability and value of biomedical research literature by promoting transparent and accurate reporting of studies. We propose specific reporting guidelines for a number of study designs: animal research, randomized trials, reliability and agreement studies, systematic reviews with and without meta-analyses, diagnostic test accuracy studies, and also observational research including cross-sectional, cohort, and case-control studies. We encourage authors, editors, and reviewers to adhere to and enforce the use of the appropriate guidelines when writing, reading, and reviewing scientific papers.
doi:10.1186/ar4145
PMCID: PMC3672749  PMID: 23448311
13.  Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this analysis was to conduct an evidence-based assessment of home telehealth technologies for patients with chronic obstructive pulmonary disease (COPD) in order to inform recommendations regarding the access and provision of these services in Ontario. This analysis was one of several analyses undertaken to evaluate interventions for COPD. The perspective of this assessment was that of the Ontario Ministry of Health and Long-Term Care, a provincial payer of medically necessary health care services.
Clinical Need: Condition and Target Population
Canada is facing an increase in chronic respiratory diseases due in part to its aging demographic. The projected increase in COPD will put a strain on health care payers and providers. There is therefore an increasing demand for telehealth services that improve access to health care services while maintaining or improving quality and equality of care. Many telehealth technologies however are in the early stages of development or diffusion and thus require study to define their application and potential harms or benefits. The Medical Advisory Secretariat (MAS) therefore sought to evaluate telehealth technologies for COPD.
Technology
Telemedicine (or telehealth) refers to using advanced information and communication technologies and electronic medical devices to support the delivery of clinical care, professional education, and health-related administrative services.
Generally there are 4 broad functions of home telehealth interventions for COPD:
to monitor vital signs or biological health data (e.g., oxygen saturation),
to monitor symptoms, medication, or other non-biologic endpoints (e.g., exercise adherence),
to provide information (education) and/or other support services (such as reminders to exercise or positive reinforcement), and
to establish a communication link between patient and provider.
These functions often require distinct technologies, although some devices can perform a number of these diverse functions. For the purposes of this review, MAS focused on home telemonitoring and telephone only support technologies.
Telemonitoring (or remote monitoring) refers to the use of medical devices to remotely collect a patient’s vital signs and/or other biologic health data and the transmission of those data to a monitoring station for interpretation by a health care provider.
Telephone only support refers to disease/disorder management support provided by a health care provider to a patient who is at home via telephone or videoconferencing technology in the absence of transmission of patient biologic data.
Research Questions
What is the effectiveness, cost-effectiveness, and safety of home telemonitoring compared with usual care for patients with COPD?
What is the effectiveness, cost-effectiveness, and safety of telephone only support programs compared with usual care for patients with COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on November 3, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2000 until November 3, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low, or very low according to GRADE methodology.
Inclusion Criteria – Question #1
frequent transmission of a patient’s physiological data collected at home and without a health care professional physically present to health care professionals for routine monitoring through the use of a communication technology;
monitoring combined with a coordinated management and feedback system based on transmitted data;
telemonitoring as a key component of the intervention (subjective determination);
usual care as provided by the usual care provider for the control group;
randomized controlled trials (RCTs), controlled clinical trials (CCTs), systematic reviews, and/or meta-analyses;
published between January 1, 2000 and November 3, 2010.
Inclusion Criteria – Question #2
scheduled or frequent contact between patient and a health care professional via telephone or videoconferencing technology in the absence of transmission of patient physiological data;
monitoring combined with a coordinated management and feedback system based on transmitted data;
telephone support as a key component of the intervention (subjective determination);
usual care as provided by the usual care provider for the control group;
RCTs, CCTs, systematic reviews, and/or meta-analyses;
published between January 1, 2000 and November 3, 2010.
Exclusion Criteria
published in a language other than English;
intervention group (and not control) receiving some form of home visits by a medical professional, typically a nurse (i.e., telenursing) beyond initial technology set-up and education, to collect physiological data, or to somehow manage or treat the patient;
not recording patient or health system outcomes (e.g., technical reports testing accuracy, reliability or other development-related outcomes of a device, acceptability/feasibility studies, etc.);
not using an independent control group that received usual care (e.g., studies employing historical or periodic controls).
Outcomes of Interest
hospitalizations (primary outcome)
mortality
emergency department visits
length of stay
quality of life
other […]
Subgroup Analyses (a priori)
length of intervention (primary)
severity of COPD (primary)
Quality of Evidence
The quality of evidence assigned to individual studies was determined using a modified CONSORT Statement Checklist for Randomized Controlled Trials. (1) The CONSORT Statement was adapted to include 3 additional quality measures: the adequacy of control group description, significant differential loss to follow-up between groups, and greater than or equal to 30% study attrition. Individual study quality was defined based on total scores according to the CONSORT Statement checklist: very low (0 to < 40%), low (≥ 40 to < 60%), moderate (≥ 60 to < 80%), and high (≥ 80 to 100%).
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Six publications, representing 5 independent trials, met the eligibility criteria for Research Question #1. Three trials were RCTs reported across 4 publications, whereby patients were randomized to home telemonitoring or usual care, and 2 trials were CCTs, whereby patients or health care centers were nonrandomly assigned to intervention or usual care.
A total of 310 participants were studied across the 5 included trials. The mean age of study participants in the included trials ranged from 61.2 to 74.5 years for the intervention group and 61.1 to 74.5 years for the usual care group. The percentage of men ranged from 40% to 64% in the intervention group and 46% to 72% in the control group.
All 5 trials were performed in a moderate to severe COPD patient population. Three trials initiated the intervention following discharge from hospital. One trial initiated the intervention following a pulmonary rehabilitation program. The final trial initiated the intervention during management of patients at an outpatient clinic.
Four of the 5 trials included oxygen saturation (i.e., pulse oximetry) as one of the biological patient parameters being monitored. Additional parameters monitored included forced expiratory volume in one second, peak expiratory flow, and temperature.
There was considerable clinical heterogeneity between trials in study design, methods, and intervention/control. In relation to the telemonitoring intervention, 3 of the 5 included studies used an electronic health hub that performed multiple functions beyond the monitoring of biological parameters. One study used only a pulse oximeter device alone with modem capabilities. Finally, in 1 study, patients measured and then forwarded biological data to a nurse during a televideo consultation. Usual care varied considerably between studies.
Only one trial met the eligibility criteria for Research Question #2. The included trial was an RCT that randomized 60 patients to nurse telephone follow-up or usual care (no telephone follow-up). Participants were recruited from the medical department of an acute-care hospital in Hong Kong and began receiving follow-up after discharge from the hospital with a diagnosis of COPD (no severity restriction). The intervention itself consisted of only two 10-to 20-minute telephone calls, once between days 3 to 7 and once between days 14 to 20, involving a structured, individualized educational and supportive programme led by a nurse that focused on 3 components: assessment, management options, and evaluation.
Regarding Research Question #1:
Low to very low quality evidence (according to GRADE) finds non-significant effects or conflicting effects (of significant or non-significant benefit) for all outcomes examined when comparing home telemonitoring to usual care.
There is a trend towards significant increase in time free of hospitalization and use of other health care services with home telemonitoring, but these findings need to be confirmed further in randomized trials of high quality.
There is severe clinical heterogeneity between studies that limits summary conclusions.
The economic impact of home telemonitoring is uncertain and requires further study.
Home telemonitoring is largely dependent on local information technologies, infrastructure, and personnel, and thus the generalizability of external findings may be low. Jurisdictions wishing to replicate home telemonitoring interventions should likely test those interventions within their jurisdictional framework before adoption, or should focus on home-grown interventions that are subjected to appropriate evaluation and proven effective.
Regarding Research Question #2:
Low quality evidence finds significant benefit in favour of telephone-only support for self-efficacy and emergency department visits when compared to usual care, but non-significant results for hospitalizations and hospital length of stay.
There are very serious issues with the generalizability of the evidence and thus additional research is required.
PMCID: PMC3384362  PMID: 23074421
14.  The Toxic Effects of Cigarette Additives. Philip Morris' Project Mix Reconsidered: An Analysis of Documents Released through Litigation 
PLoS Medicine  2011;8(12):e1001145.
Stanton Glantz and colleagues analyzed previously secret tobacco industry documents and peer-reviewed published results of Philip Morris' Project MIX about research on cigarette additives, and show that this research on the use of cigarette additives cannot be taken at face value.
Background
In 2009, the promulgation of US Food and Drug Administration (FDA) tobacco regulation focused attention on cigarette flavor additives. The tobacco industry had prepared for this eventuality by initiating a research program focusing on additive toxicity. The objective of this study was to analyze Philip Morris' Project MIX as a case study of tobacco industry scientific research being positioned strategically to prevent anticipated tobacco control regulations.
Methods and Findings
We analyzed previously secret tobacco industry documents to identify internal strategies for research on cigarette additives and reanalyzed tobacco industry peer-reviewed published results of this research. We focused on the key group of studies conducted by Phillip Morris in a coordinated effort known as “Project MIX.” Documents showed that Project MIX subsumed the study of various combinations of 333 cigarette additives. In addition to multiple internal reports, this work also led to four peer-reviewed publications (published in 2001). These papers concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied. Internal documents revealed post hoc changes in analytical protocols after initial statistical findings indicated an additive-associated increase in cigarette toxicity as well as increased total particulate matter (TPM) concentrations in additive-modified cigarette smoke. By expressing the data adjusted by TPM concentration, the published papers obscured this underlying toxicity and particulate increase. The animal toxicology results were based on a small number of rats in each experiment, raising the possibility that the failure to detect statistically significant changes in the end points was due to underpowering the experiments rather than lack of a real effect.
Conclusion
The case study of Project MIX shows tobacco industry scientific research on the use of cigarette additives cannot be taken at face value. The results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes, including the level of TPM. In particular, regulatory authorities, including the FDA and similar agencies elsewhere, could use the Project MIX data to eliminate the use of these 333 additives (including menthol) from cigarettes.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The tobacco industry in the United States has recognized that regulation of its products was inevitable as early as 1963 and devoted increasing attention to the likelihood of regulation by the US Food and Drug Administration in the mid-1990s, which finally became law in 2009. In addition, the World Health Organization (WHO) Framework Convention on Tobacco Control (WHO FCTC), which came into force in June 2003, includes provisions addressing the regulation of the contents of tobacco products and the regulation of tobacco product disclosures. Although these steps represent progress in tobacco control, the events of the past few decades show the determination of the tobacco industry to avoid regulation, including the regulation of additives. In the United States, executives of the tobacco company Philip Morris (PM) recognized the inevitability of regulation and responded by initiating efforts to shape legislation and regulation by reorganizing its internal scientific activities and conducting scientific research that could be used to shape any proposed regulations. For example, the company conducted “Project MIX,” a study of chemical constituents in and toxicity of smoke produced by burning cigarettes containing three different combinations of 333 cigarette additives that “were constructed to resemble typical commercial blended cigarettes.” The resulting four papers published in Food and Chemical Toxicology in January 2002 concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied.
Why Was This Study Done?
The use of cigarette additives is an important concern of the WHO, FDA, and similar national regulatory bodies around the world. Philip Morris has used the published Project MIX papers to assert the safety of individual additives and other cigarette companies have done similar studies that reached similar conclusions. In this study, the researchers used documents made public as a result of litigation against the tobacco industry to investigate the origins and design of Project MIX and to conduct their own analyses of the results to assess the reliability of the conclusions in the papers published in Food and Chemical Toxicology.
What Did the Researchers Do and Find?
The researchers systematically examined tobacco industry documents in the University of California San Francisco Legacy Tobacco Documents Library (then about 60 million pages made publicly available as a result of litigation) and used an iterative process of searching, analyzing, and refining to identify and review in detail 500 relevant documents.
The researchers found that in the original Project MIX analysis, the published papers obscured findings of toxicity by adjusting the data by total particulate matter (TPM) concentration. When the researchers conducted their own analysis by studying additives per cigarette (as was specified in the original Project MIX protocol), they found that 15 carcinogenic chemicals increased by 20%. The researchers also reported that, for unexplained reasons, Philip Morris deemphasized 19 of the 51 chemicals tested in the presentation of results, including nine that were substantially increased in smoke on a per cigarette basis of additive-added cigarettes, compared to smoke of control cigarettes.
The researchers explored the possibility that the failure of Project MIX to detect statistically significant changes in the toxicity of the smoke from cigarettes containing the additives was due to underpowered experiments rather than lack of a real effect by conducting their own statistical analysis. This analysis suggests that a better powered study would have detected a much broader range of biological effects associated with the additives than was identified in Philip Morris' published paper, suggesting that it substantially underestimated the toxic potential of cigarette smoke and additives.
The researchers also found that Food and Chemical Toxicology, the journal in which the four Project MIX papers were published, had an editor and 11 of its International Editorial Board with documented links to the tobacco industry. The scientist and leader of Project MIX Edward Carmines described the process of publication as “an inside job.”
What Do These Findings Mean?
These findings show that the tobacco industry scientific research on the use of cigarette additives cannot be taken at face value: the results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes. In addition, better powered studies would probably have detected a much broader range of adverse biological effects associated with the additives than identified to those identified in PM's published papers suggesting that the published papers substantially underestimate the toxic potential combination of cigarette smoke and additives.
Regulatory authorities, including the FDA and similar agencies elsewhere who are implementing WHO FCTC, should conduct their own independent analysis of Project MIX data, which, analyzed correctly, could provide a strong evidence base for the elimination of the use of the studied additives (including menthol) in cigarettes on public health grounds.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001145.
For PLoS Medicine's own policy on publishing papers sponsored by the tobacco industry see http://www.plosmedicine.org/static/policies.action#funders
The World Health Organization (WHO) provides information on the Framework Convention on Tobacco Control (FCTC)
The documents that the researchers reviewed in this paper can be found at the Legacy Tobacco Documents Library
doi:10.1371/journal.pmed.1001145
PMCID: PMC3243707  PMID: 22205885
15.  Why Do Women Not Use Antenatal Services in Low- and Middle-Income Countries? A Meta-Synthesis of Qualitative Studies 
PLoS Medicine  2013;10(1):e1001373.
In a synthesis of 21 qualitative studies representing the views of more than 1,230 women from 15 countries, Kenneth Finlayson and Soo Downe examine the reasons why many women in low- and middle-income countries do not receive adequate antenatal care.
Background
Almost 50% of women in low- and middle-income countries (LMICs) don't receive adequate antenatal care. Women's views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies.
Methods and Findings
Using a predetermined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMICs who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line-of-argument synthesis. We derived policy-relevant hypotheses from the findings. We included 21 papers representing the views of more than 1,230 women from 15 countries. Three key themes were identified: “pregnancy as socially risky and physiologically healthy”, “resource use and survival in conditions of extreme poverty”, and “not getting it right the first time”. The line-of-argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralised, risk-focused antenatal care programmes may be at odds with the resources, beliefs, and experiences of pregnant women who underuse antenatal services.
Conclusions
Our findings suggest that there may be a misalignment between current antenatal care provision and the social and cultural context of some women in LMICs. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences is likely to be underused, especially when attendance generates increased personal risks of lost family resources or physical danger during travel, when the promised care is not delivered because of resource constraints, and when women experience covert or overt abuse in care settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Although maternal deaths worldwide have almost halved since 1990, according to the latest figures, every day roughly 800 women and adolescent girls still die from the complications of pregnancy or childbirth: in 2010, 287,000 women died during or following pregnancy and childbirth, with almost all of these deaths (99%) occurring in low-resource settings. Most maternal deaths are avoidable, as the interventions to prevent or manage the most common complications (severe bleeding, infections, high blood pressure during pregnancy, and unsafe abortion) are well known. Furthermore, many of these complications can be prevented, detected, or treated during antenatal care visits with trained health workers.
Why Was This Study Done?
The World Health Organization (WHO) recommends a minimum of four antenatal visits per pregnancy, but according to WHO figures, between 2005 and 2010 only 53% of pregnant women worldwide attended the recommended four antenatal visits; in low-income countries, this figure was a disappointing 36%. Unfortunately, despite huge international efforts to promote and provide antenatal care, there has been little improvement in these statistics over the past decade. It is therefore important to investigate the reasons for poor antenatal attendance and to seek the views of users of antenatal care. In this study, the researchers combined studies from low- and middle-income countries (LMICs) that included women's views on antenatal care in a meta-synthesis of qualitative studies (qualitative research uses techniques, such as structured interviews, to gather an in-depth understanding of human behaviour, and a meta-synthesis combines and interprets information across studies, contexts, and populations).
What Did the Researchers Do and Find?
The researchers searched several medical, sociological, and psychological databases to find appropriate qualitative studies published between January 1980 and February 2012 that explored the antenatal care experiences, attitudes, and beliefs of women from LMICs who had chosen to access antenatal care late (after 12 weeks' gestation), infrequently (less than four times), or not at all. The researchers included 21 studies (out of the 2,997 initially identified) in their synthesis, representing the views of 1,239 women from 15 countries (Bangladesh, Benin, Cambodia, Gambia, India, Indonesia, Kenya, Lebanon, Mexico, Mozambique, Nepal, Pakistan, South Africa, Tanzania, and Uganda) who were either interviewed directly or gave their opinion as part of a focus group.
The researchers identified three main themes. The first theme reflects women's views that pregnancy is a healthy state and so saw little reason to visit health professionals when they perceived no risk to their well-being—the researchers called this theme, “pregnancy as socially contingent and physiologically healthy.” The second theme relates to women's limited financial resources, so that even when antenatal care was offered free of charge, the cost of transport to get there, the loss of earnings associated with the visit, and the possibility of having to pay for medicines meant that women were unable to attend—the researchers called this theme “resource use and survival in conditions of extreme poverty.” The third theme the researchers identified related to women's views that the antenatal services were inadequate and that the benefits of attending did not outweigh any potential harms. For example, pregnant women who initially recognized the benefits of antenatal care were often disappointed by the lack of resources they found when they got there and, consequently, decided not to return. The researchers called this theme “not getting it right the first time.”
What Do These Findings Mean?
These findings suggest that there may be a misalignment between the principles that underpin the provision of antenatal care and the beliefs and socio-economic contexts of pregnant women in LMICs, meaning that even high-quality antenatal care may not be used by some pregnant women unless their views and concerns are addressed. The themes identified in this meta-synthesis could provide the basis for a new approach to the design and delivery of antenatal care that takes local beliefs and values and resource availability into account. Such programs might help ensure that antenatal care meets pregnant women's expectations and treats them appropriately so that they want to regularly attend antenatal care.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001373.
Wikipedia describes antenatal care (note that Wikipedia is a free online encyclopedia that anyone can edit)
The World Health Organization has a wealth of information relating to pregnancy, including antenatal care
The UK National Institute for Health and Clinical Excellence has evidence-based guidelines on antenatal care
The White Ribbon Alliance for Safe Motherhood has a series of web pages and links relating to respectful maternity care in LMICs
International Federation of Gynecology and Obstetrics is an international organization with connections to various maternity initiatives in LMICs
International Confederation of Midwives has details of the Millennium Development Goals relating to maternity care
doi:10.1371/journal.pmed.1001373
PMCID: PMC3551970  PMID: 23349622
16.  Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise 
Background:
Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item.
Methods:
We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added.
Results:
We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items.
Interpretation:
The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date.
doi:10.1503/cmaj.131237
PMCID: PMC3928232  PMID: 24344144
17.  Guidelines for Reporting Case Studies on Extracorporeal Treatments in Poisonings: Methodology 
Seminars in Dialysis  2014;27(4):407-414.
A literature review performed by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup highlighted deficiencies in the existing literature, especially the reporting of case studies. Although general reporting guidelines exist for case studies, there are none in the specific field of extracorporeal treatments in toxicology. Our goal was to construct and propose a checklist that systematically outlines the minimum essential items to be reported in a case study of poisoned patients undergoing extracorporeal treatments. Through a modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP workgroup) were asked to vote on the pertinence of a set of items to identify those considered minimally essential for reporting complete and accurate case reports. Furthermore, independent raters validated the clarity of each selected items between each round of voting. All case reports containing data on extracorporeal treatments in poisoning published in Medline in 2011 were reviewed during the external validation rounds. Twenty-one panelists (20 from the EXTRIP workgroup and an invited expert on pharmacology reporting guidelines) participated in the modified Delphi technique. This group included journal editors and experts in nephrology, clinical toxicology, critical care medicine, emergency medicine, and clinical pharmacology. Three independent raters participated in the validation rounds. Panelists voted on a total of 144 items in the first round and 137 items in the second round, with response rates of 96.3% and 98.3%, respectively. Twenty case reports were evaluated at each validation round and the independent raters' response rate was 99.6% and 98.8% per validation round. The final checklist consists of 114 items considered essential for case study reporting. This methodology of alternate voting and external validation rounds was useful in developing the first reporting guideline for case studies in the field of extracorporeal treatments in poisoning. We believe that this guideline will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports may provide early signals of effectiveness and/or harm, thereby improving healthcare decision-making.
doi:10.1111/sdi.12251
PMCID: PMC4282789  PMID: 24890576
18.  Improving the use of research evidence in guideline development: 16. Evaluation 
Background
The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the last of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this.
Objectives
We reviewed the literature on evaluating guidelines and recommendations, including their quality, whether they are likely to be up-to-date, and their implementation. We also considered the role of guideline developers in undertaking evaluations that are needed to inform recommendations.
Methods
We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments.
Key questions and answers
Our answers to these questions were informed by a review of instruments for evaluating guidelines, several studies of the need for updating guidelines, discussions of the pros and cons of different research designs for evaluating the implementation of guidelines, and consideration of the use of uncertainties identified in systematic reviews to set research priorities.
How should the quality of guidelines or recommendations be appraised?
• WHO should put into place processes to ensure that both internal and external review of guidelines is undertaken routinely.
• A checklist, such as the AGREE instrument, should be used.
• The checklist should be adapted and tested to ensure that it is suitable to the broad range of recommendations that WHO produces, including public health and health policy recommendations, and that it includes questions about equity and other items that are particularly important for WHO guidelines.
When should guidelines or recommendations be updated?
• Processes should be put into place to ensure that guidelines are monitored routinely to determine if they are in need of updating.
• People who are familiar with the topic, such as Cochrane review groups, should do focused, routine searches for new research that would require revision of the guideline.
• Periodic review of guidelines by experts not involved in developing the guidelines should also be considered.
• Consideration should be given to establishing guideline panels that are ongoing, to facilitate routine updating, with members serving fixed periods with a rotating membership.
How should the impact of guidelines or recommendations be evaluated?
• WHO headquarters and regional offices should support member states and those responsible for policy decisions and implementation to evaluate the impact of their decisions and actions by providing advice regarding impact assessment, practical support and coordination of efforts.
• Before-after evaluations should be used cautiously and when there are important uncertainties regarding the effects of a policy or its implementation, randomised evaluations should be used when possible.
What responsibility should WHO take for ensuring that important uncertainties are addressed by future research when the evidence needed to inform recommendations is lacking?
• Guideline panels should routinely identify important uncertainties and research priorities. This source of potential priorities for research should be used systematically to inform priority-setting processes for global research.
doi:10.1186/1478-4505-4-28
PMCID: PMC1702533  PMID: 17156460
19.  The BioLexicon: a large-scale terminological resource for biomedical text mining 
BMC Bioinformatics  2011;12:397.
Background
Due to the rapidly expanding body of biomedical literature, biologists require increasingly sophisticated and efficient systems to help them to search for relevant information. Such systems should account for the multiple written variants used to represent biomedical concepts, and allow the user to search for specific pieces of knowledge (or events) involving these concepts, e.g., protein-protein interactions. Such functionality requires access to detailed information about words used in the biomedical literature. Existing databases and ontologies often have a specific focus and are oriented towards human use. Consequently, biological knowledge is dispersed amongst many resources, which often do not attempt to account for the large and frequently changing set of variants that appear in the literature. Additionally, such resources typically do not provide information about how terms relate to each other in texts to describe events.
Results
This article provides an overview of the design, construction and evaluation of a large-scale lexical and conceptual resource for the biomedical domain, the BioLexicon. The resource can be exploited by text mining tools at several levels, e.g., part-of-speech tagging, recognition of biomedical entities, and the extraction of events in which they are involved. As such, the BioLexicon must account for real usage of words in biomedical texts. In particular, the BioLexicon gathers together different types of terms from several existing data resources into a single, unified repository, and augments them with new term variants automatically extracted from biomedical literature. Extraction of events is facilitated through the inclusion of biologically pertinent verbs (around which events are typically organized) together with information about typical patterns of grammatical and semantic behaviour, which are acquired from domain-specific texts. In order to foster interoperability, the BioLexicon is modelled using the Lexical Markup Framework, an ISO standard.
Conclusions
The BioLexicon contains over 2.2 M lexical entries and over 1.8 M terminological variants, as well as over 3.3 M semantic relations, including over 2 M synonymy relations. Its exploitation can benefit both application developers and users. We demonstrate some such benefits by describing integration of the resource into a number of different tools, and evaluating improvements in performance that this can bring.
doi:10.1186/1471-2105-12-397
PMCID: PMC3228855  PMID: 21992002
20.  Developing a checklist for guideline implementation planning: review and synthesis of guideline development and implementation advice 
Background
Developers, users and others have requested or advocated for guidance on how to plan for, and implement guidelines concurrent to their development given that existing resources are lacking such information. The purpose of this research was to develop a guideline implementation planning checklist.
Methods
Documents that described or evaluated the processes of planning or undertaking implementation were identified in several publications that had systematically identified such resources, and by searching medical literature databases (MEDLINE, EMBASE). Data that described implementation planning; how to develop guideline versions or tools that would support user implementation; and options and mechanisms for disseminating or implementing guidelines were independently extracted from eligible documents by the principal investigator and a trained research assistant. Data were integrated to create a unique list of guideline implementation planning processes and considerations.
Results
Thirty-five documents were eligible. Of these, 16 (45.7%) provided sparse information on implementation planning, 25 (71.4%) mentioned different versions or tools for implementation, and 30 (85.7%) listed options for dissemination or implementation. None provided instructions for operationalizing implementation strategies. Data were integrated into a multi-item Guideline Implementation Planning Checklist including considerations for implementation planning (12), development of implementation tools (8), types of implementation tools (12), and options for dissemination (11) and implementation (12).
Conclusions
Developers or users can apply the Guideline Implementation Planning Checklist to prepare for and/or undertake guideline implementation. Further development of the checklist is warranted to elaborate on all components. In ongoing research, we will consult with the international guideline community to do so. At the same time, guideline implementation is complex, so developers and users would benefit from training, and by including knowledge translation experts and brokers on implementation planning committees.
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-015-0205-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s13012-015-0205-5
PMCID: PMC4329197
Guidelines; Implementation
21.  Quality assessment of phase I dose-finding cancer trials: proposal of a checklist 
Background
Qualitative checklists for phase III trials have been proposed, to improve the reporting of such trials and to assess the validity of their results.
Purpose
Our objective was to develop such a scale for phase I cancer trials.
Methods
From a review of existing guidelines and checklists for phase III clinical trials, a staff team was responsible for the first selection of items and the construction of the questionnaire. The proposed quality assessment measures were rated by the survey respondents comprised of phase I research clinicians and statisticians on a 4-point Likert scale. Selected items from the quantitative analysis of the questionnaires were reviewed by an expert team who was responsible for providing the final items list. This was then applied to 103 recently published cancer phase I trials.
Results
Of the 48 initial items proposed by the staff team, 17 were selected from the quantitative analysis of the 99 participants’ ratings. After qualitative analysis by the expert team, a 15-item checklist was derived, with 5 items related to trial objective, 5 to design, and 5 to analysis. The application to 103 recent journal articles on phase I cancer trials evaluating cytotoxic drugs showed on average the report of 10 items (range: 6–13) with 4 items reported in more than 95% of papers, while 2 were poorly reported.
Limitations
The response rate of participants was 20.7%.
Conclusions
A quality assessment checklist was developed for improved critical appraisal of the reporting of cytotoxic, dose-finding phase I oncology trials. This may be a first step toward a minimum standard of quality measures for all phase I clinical trial reports.
doi:10.1177/1740774508096653
PMCID: PMC2819819  PMID: 18827040
22.  The Biomedical Genomics Core 
Journal of Biomolecular Techniques : JBT  2010;21(3 Suppl):S69-S70.
CF-8
The Biomedical Genomics Core is a shared resource of The Research Institute at Nationwide Children's Hospital. We provide expertise in multiple aspects of genomics analysis, from assistance with appropriate experimental design to the final steps of bioinformatics and data interpretation. Services include consultation and assistance with experimental design, quality control of starting material (DNA or RNA), sample labeling, hybridization, image acquisition, data processing, statistical analysis and interpretation. Currently, investigators are able to choose from a wide array of commercially available catalog arrays from both Agilent Technologies and Affymetrix, or create low-cost custom arrays through Agilent's eArray technology. The diverse range of services provided by the core enables investigators to perform 1) Global transcriptional profiling of both mRNAs and microRNAs, 2) Gene regulation analysis to explore genome functions including mapping transcription factor binding sites and promoter region analysis (ChIP-on-Chip) and DNA methylation analysis, and 3) Whole genome analysis to conduct large-scale linkage analysis, association, and copy number studies. All array data generated by the core undergoes stringent quality control testing, and complete data analysis and statistical interpretation is performed in-house using advanced bioinformatics techniques. Strict sample submission requirements, including a minimum of four biological replicates for any given condition, combined with careful monitoring of sample quality prior to analysis, has significantly enhanced the generation of publication quality data sets. All users of the facility are encouraged to deposit their data into MIAME compliant public repositories, and assistance is provided with data submission into the NCBI Gene Expression Omnibus (GEO) database. The Biomedical Genomics Core has become nationally recognized and was recently awarded official “Certified Service Provider” status by Agilent Technologies, becoming the first and only academic laboratory in the United States to have achieved this status.
PMCID: PMC2918025
23.  Behavioural Interventions for Type 2 Diabetes 
Executive Summary
In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry’s newly released Diabetes Strategy.
After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report.
To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html,
Diabetes Strategy Evidence Platform: Summary of Evidence-Based Analyses
Continuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based Analysis
Behavioural Interventions for Type 2 Diabetes: An Evidence-Based Analysis
Bariatric Surgery for People with Diabetes and Morbid Obesity: An Evidence-Based Summary
Community-Based Care for the Management of Type 2 Diabetes: An Evidence-Based Analysis
Home Telemonitoring for Type 2 Diabetes: An Evidence-Based Analysis
Application of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario
Objective
The objective of this report is to determine whether behavioural interventions1 are effective in improving glycemic control in adults with type 2 diabetes.
Background
Diabetes is a serious chronic condition affecting millions of people worldwide and is the sixth leading cause of death in Canada. In 2005, an estimated 8.8% of Ontario’s population had diabetes, representing more than 816,000 Ontarians. The direct health care cost of diabetes was $1.76 billion in the year 2000 and is projected to rise to a total cost of $3.14 billion by 2016. Much of this cost arises from the serious long-term complications associated with the disease including: coronary heart disease, stroke, adult blindness, limb amputations and kidney disease.
Type 2 diabetes accounts for 90–95% of diabetes and while type 2 diabetes is more prevalent in people aged 40 years and older, prevalence in younger populations is increasing due to a rise in obesity and physical inactivity in children.
Data from the United Kingdom Prospective Diabetes Study (UKPDS) has shown that tight glycemic control can significantly reduce the risk of developing serious complications in type 2 diabetics. Despite physicians’ and patients’ knowledge of the importance of glycemic control, Canadian data has shown that only 38% of patients with diabetes have HbA1C levels in the optimal range of 7% or less. This statistic highlights the complexities involved in the management of diabetes, which is characterized by extensive patient involvement in addition to the support provided by physicians. An enormous demand is, therefore, placed on patients to self-manage the physical, emotional and psychological aspects of living with a chronic illness.
Despite differences in individual needs to cope with diabetes, there is general agreement for the necessity of supportive programs for patient self-management. While traditional programs were didactic models with the goal of improving patients’ knowledge of their disease, current models focus on behavioural approaches aimed at providing patients with the skills and strategies required to promote and change their behaviour.
Several meta-analyses and systematic reviews have demonstrated improved health outcomes with self-management support programs in type 2 diabetics. They have all, however, either looked at a specific component of self-management support programs (i.e. self-management education) or have been conducted in specific populations. Most reviews are also qualitative and do not clearly define the interventions of interest, making findings difficult to interpret. Moreover, heterogeneity in the interventions has led to conflicting evidence on the components of effective programs. There is thus much uncertainty regarding the optimal design and delivery of these programs by policymakers.
Evidence-Based Analysis of Effectiveness
Research Questions
Are behavioural interventions effective in improving glycemic control in adults with type 2 diabetes?
Is the effectiveness of the intervention impacted by intervention characteristics (e.g. delivery of intervention, length of intervention, mode of instruction, interventionist etc.)?
Inclusion Criteria
English Language
Published between January 1996 to August 2008
Type 2 diabetic adult population (>18 years)
Randomized controlled trials (RCTs)
Systematic reviews, or meta-analyses
Describing a multi-faceted self-management support intervention as defined by the 2007 Self-Management Mapping Guide (1)
Reporting outcomes of glycemic control (HbA1c) with extractable data
Studies with a minimum of 6-month follow up
Exclusion Criteria
Studies with a control group other than usual care
Studies with a sample size <30
Studies without a clearly defined intervention
Outcomes of Interest
Primary outcome: glycemic control (HbA1c)
Secondary outcomes: systolic blood pressure (SBP) control, lipid control, change in smoking status, weight change, quality of life, knowledge, self-efficacy, managing psychosocial aspects of diabetes, assessing dissatisfaction and readiness to change, and setting and achieving diabetes goals.
Search Strategy
A search was performed in OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), The Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published between January 1996 and August 2008. Abstracts were reviewed by a single author and studies meeting the inclusion criteria outlined above were obtained. Data on population characteristics, glycemic control outcomes, and study design were extracted. Reference lists were also checked for relevant studies. The quality of the evidence was assessed as being either high, moderate, low, or very low according to the GRADE methodology.
Summary of Findings
The search identified 638 citations published between 1996 and August 2008, of which 12 met the inclusion criteria and one was a meta-analysis (Gary et al. 2003). The remaining 11 studies were RCTs (9 were used in the meta-analysis) and only one was defined as small (total sample size N=47).
Summary of Participant Demographics across studies
A total of 2,549 participants were included in the 11 identified studies. The mean age of participants reported was approximately 58 years and the mean duration of diabetes was approximately 6 years. Most studies reported gender with a mean percentage of females of approximately 67%. Of the eleven studies, two focused only on women and four included only Hispanic individuals. All studies evaluated type 2 diabetes patients exclusively.
Study Characteristics
The studies were conducted between 2002 and 2008. Approximately six of 11 studies were carried out within the USA, with the remaining studies conducted in the UK, Sweden, and Israel (sample size ranged from 47 to 824 participants). The quality of the studies ranged from moderate to low with four of the studies being of moderate quality and the remaining seven of low quality (based on the Consort Checklist). Differences in quality were mainly due to methodological issues such as inadequate description of randomization, sample size calculation allocation concealment, blinding and uncertainty of the use of intention-to-treat (ITT) analysis. Patients were recruited from several settings: six studies from primary or general medical practices, three studies from the community (e.g. via advertisements), and two from outpatient diabetes clinics. A usual care control group was reported in nine of 11 of the studies and two studies reported some type of minimal diabetes care in addition to usual care for the control group.
Intervention Characteristics
All of the interventions examined in the studies were mapped to the 2007 Self-management Mapping Guide. The interventions most often focused on problem solving, goal setting and encouraging participants to engage in activities that protect and promote health (e.g. modifying behaviour, change in diet, and increase physical activity). All of the studies examined comprehensive interventions targeted at least two self-care topics (e.g. diet, physical activity, blood glucose monitoring, foot care, etc.). Despite the homogeneity in the aims of the interventions, there was substantial clinical heterogeneity in other intervention characteristics such as duration, intensity, setting, mode of delivery (group vs. individual), interventionist, and outcomes of interest (discussed below).
Duration, Intensity and Mode of Delivery
Intervention durations ranged from 2 days to 1 year, with many falling into the range of 6 to 10 weeks. The rest of the interventions fell into categories of ≤ 2 weeks (2 studies), 6 months (2 studies), or 1 year (3 studies). Intensity of the interventions varied widely from 6 hours over 2 days, to 52 hours over 1 year; however, the majority consisted of interventions of 6 to 15 hours. Both individual and group sessions were used to deliver interventions. Group counselling was used in five studies as a mode of instruction, three studies used both individual and group sessions, and one study used individual sessions as its sole mode of instruction. Three studies also incorporated the use of telephone support as part of the intervention.
Interventionists and Setting
The following interventionists were reported (highest to lowest percentage, categories not mutually exclusive): nurse (36%), dietician (18%), physician (9%), pharmacist (9%), peer leader/community worker (18%), and other (36%). The ‘other’ category included interventionists such as consultants and facilitators with unspecified professional backgrounds. The setting of most interventions was community-based (seven studies), followed by primary care practices (three studies). One study described an intervention conducted in a pharmacy setting.
Outcomes
Duration of follow up of the studies ranged from 6 months to 8 years with a median follow-up duration of 12 months. Nine studies followed up patients at a minimum of two time points. Despite clear reporting of outcomes at follow up time points, there was poor reporting on whether the follow up was measured from participant entry into study or from end of intervention. All studies reported measures of glycemic control, specifically HbA1c levels. BMI was measured in five studies, while body weight was reported in two studies. Cholesterol was examined in three studies and blood pressure reduction in two. Smoking status was only examined in one of the studies. Additional outcomes examined in the trials included patient satisfaction, quality of life, diabetes knowledge, diabetes medication reduction, and behaviour modification (i.e. daily consumption of fruits/vegetables, exercise etc). Meta-analysis of the studies identified a moderate but significant reduction in HbA1c levels -0.44% 95%CI: -0.60, -0.29) for behavioural interventions in comparison to usual care for adults with type 2 diabetes. Subgroup analyses suggested the largest effects in interventions which were of at least duration and interventions in diabetics with higher baseline HbA1c (≥9.0). The quality of the evidence according to GRADE for the overall estimate was moderate and the quality of evidence for the subgroup analyses was identified as low.
Summary of Meta-Analysis of Studies Investigating the Effectiveness of Behavioural Interventions on HbA1c in Patients with Type 2 Diabetes.
Based on one study
Conclusions
Based on moderate quality evidence, behavioural interventions as defined by the 2007 Self-management mapping guide (Government of Victoria, Australia) produce a moderate reduction in HbA1c levels in patients with type 2 diabetes compared with usual care.
Based on low quality evidence, the interventions with the largest effects are those:
- in diabetics with higher baseline HbA1c (≥9.0)
- in which the interventions were of at least 1 year in duration
PMCID: PMC3377516  PMID: 23074526
24.  The CAP cancer protocols – a case study of caCORE based data standards implementation to integrate with the Cancer Biomedical Informatics Grid 
Background
The Cancer Biomedical Informatics Grid (caBIG™) is a network of individuals and institutions, creating a world wide web of cancer research. An important aspect of this informatics effort is the development of consistent practices for data standards development, using a multi-tier approach that facilitates semantic interoperability of systems. The semantic tiers include (1) information models, (2) common data elements, and (3) controlled terminologies and ontologies. The College of American Pathologists (CAP) cancer protocols and checklists are an important reporting standard in pathology, for which no complete electronic data standard is currently available.
Methods
In this manuscript, we provide a case study of Cancer Common Ontologic Representation Environment (caCORE) data standard implementation of the CAP cancer protocols and checklists model – an existing and complex paper based standard. We illustrate the basic principles, goals and methodology for developing caBIG™ models.
Results
Using this example, we describe the process required to develop the model, the technologies and data standards on which the process and models are based, and the results of the modeling effort. We address difficulties we encountered and modifications to caCORE that will address these problems. In addition, we describe four ongoing development projects that will use the emerging CAP data standards to achieve integration of tissue banking and laboratory information systems.
Conclusion
The CAP cancer checklists can be used as the basis for an electronic data standard in pathology using the caBIG™ semantic modeling methodology.
doi:10.1186/1472-6947-6-25
PMCID: PMC1524939  PMID: 16787533
25.  Design and utilization of the colorectal and pancreatic neoplasm virtual biorepository: An early detection research network initiative 
Background:
The Early Detection Research Network (EDRN) colorectal and pancreatic neoplasm virtual biorepository is a bioinformatics-driven system that provides high-quality clinicopathology-rich information for clinical biospecimens. This NCI-sponsored EDRN resource supports translational cancer research. The information model of this biorepository is based on three components: (a) development of common data elements (CDE), (b) a robust data entry tool and (c) comprehensive data query tools.
Methods:
The aim of the EDRN initiative is to develop and sustain a virtual biorepository for support of translational research. High-quality biospecimens were accrued and annotated with pertinent clinical, epidemiologic, molecular and genomic information. A user-friendly annotation tool and query tool was developed for this purpose. The various components of this annotation tool include: CDEs are developed from the College of American Pathologists (CAP) Cancer Checklists and North American Association of Central Cancer Registries (NAACR) standards. The CDEs provides semantic and syntactic interoperability of the data sets by describing them in the form of metadata or data descriptor. The data entry tool is a portable and flexible Oracle-based data entry application, which is an easily mastered, web-based tool. The data query tool facilitates investigators to search deidentified information within the warehouse through a “point and click” interface thus enabling only the selected data elements to be essentially copied into a data mart using a dimensional-modeled structure from the warehouse’s relational structure.
Results:
The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository database contains multimodal datasets that are available to investigators via a web-based query tool. At present, the database holds 2,405 cases and 2,068 tumor accessions. The data disclosure is strictly regulated by user’s authorization. The high-quality and well-characterized biospecimens have been used in different translational science research projects as well as to further various epidemiologic and genomics studies.
Conclusions:
The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository with a tangible translational biomedical informatics infrastructure facilitates translational research. The data query tool acts as a central source and provides a mechanism for researchers to efficiently query clinically annotated datasets and biospecimens that are pertinent to their research areas. The tool ensures patient health information protection by disclosing only deidentified data with Institutional Review Board and Health Insurance Portability and Accountability Act protocols.
doi:10.4103/2153-3539.70831
PMCID: PMC2956178  PMID: 21031013
Colorectal and pancreatic neoplasm; tissue banking informatics

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