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2.
Drug Saf ; 42(11): 1297-1309, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31452075

RESUMO

Research that makes secondary use of administrative and clinical healthcare databases is increasingly influential for regulatory, reimbursement, and other healthcare decision-making. Consequently, there are numerous guidance documents on reporting for studies that use 'real-world' data captured in administrative claims and electronic health record (EHR) databases. These guidance documents are intended to improve transparency, reproducibility, and the ability to evaluate validity and relevance of design and analysis decisions. However, existing guidance does not differentiate between structured and unstructured information contained in EHRs, registries, or other healthcare data sources. While unstructured text is convenient and readily interpretable in clinical practice, it can be difficult to use for investigation of causal questions, e.g., comparative effectiveness and safety, until data have been cleaned and algorithms applied to extract relevant information to structured fields for analysis. The goal of this paper is to increase transparency for healthcare decision makers and causal inference researchers by providing general recommendations for reporting on steps taken to make unstructured text-based data usable for comparative effectiveness and safety research. These recommendations are designed to be used as an adjunct for existing reporting guidance. They are intended to provide sufficient context and supporting information for causal inference studies involving use of natural language processing- or machine learning-derived data fields, so that researchers, reviewers, and decision makers can be confident in their ability to evaluate the validity and relevance of derived measures for exposures, inclusion/exclusion criteria, covariates, and outcomes for the causal question of interest.

3.
Front Med (Lausanne) ; 6: 73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31134200

RESUMO

Aims: To facilitate regulatory learning, we evaluated similarities and differences in evidence requirements between regulatory and health technology assessment (HTA) bodies of Alzheimer's disease (AD) approved products. Methods: The European marketing authorisation application dossiers and European public assessment reports (EPARs) of the licensed AD drugs were screened to identify the phase III randomised controlled trials (RCTs) and outcomes used. We also screened the assessment reports of the National Institute of Health and Care Excellence (NICE, England) and the National Health Care Institute (ZiN, the Netherlands) to identify the studies and outcomes used in HTA assessments. Results: The application dossiers of donepezil, galantamine, rivastigmine, and memantine contained 16 phase III RCTs in total. These trials were also included in HTA assessments except that NICE excluded studies that were not published (n = 2) or trials that included patients with other types of dementia (n = 3). In the regulatory assessments the focus was on cognitive and global outcomes, and to some extent on function. In the HTA assessments of clinical effectiveness other domains were also covered including: function, behaviour and mood, and, occasionally, quality of life. In the economic analyses of NICE the domains cognition, function, and quality of life were included. Conclusion: There was a large overlap in inclusion of trials in regulatory and HTA assessments, although the focus on specific outcomes slightly differed. Understanding the methods and perceptions of both authorities can stimulate regulatory and HTA cross-talk and further alignment, and therefore more rapid patient access to new treatments.

4.
Br J Clin Pharmacol ; 85(7): 1427-1433, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30849187

RESUMO

In 2016, the European Medicines Agency published the conclusions of its pilot on adaptive pathways, with products in early stages of development still building up to their marketing authorisation. Adaptive pathways rests on three principles: iterative development; gathering evidence through real-life use to supplement clinical trial data; and early engagement of patients, payers and health technology assessment bodies in discussions on a medicine's development. While the pilot has now finished, the practical system-wide implications of employing the adaptive pathways approach are not known and further consideration of these three principles is required. In this paper we used the three principles that underpin adaptive pathways to discuss main scientific and European policy developments likely to determine progress on further implementing adaptive pathways in the European setting.

5.
J Alzheimers Dis ; 67(2): 495-501, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30584137

RESUMO

ROADMAP is a public-private advisory partnership to evaluate the usability of multiple data sources, including real-world evidence, in the decision-making process for new treatments in Alzheimer's disease, and to advance key concepts in disease and pharmacoeconomic modeling. ROADMAP identified key disease and patient outcomes for stakeholders to make informed funding and treatment decisions, provided advice on data integration methods and standards, and developed conceptual cost-effectiveness and disease models designed in part to assess whether early treatment provides long-term benefit.

6.
CNS Drugs ; 32(12): 1085-1090, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30467744

RESUMO

Although there are a growing number of well-reported, late-stage clinical trial failures in Alzheimer's disease, the introduction of a disease-modifying therapy within the next 5 years may be anticipated. These treatments are likely to target Alzheimer's disease in the earlier disease stages, unlike drugs that are currently available that treat symptoms of moderate-to-severe dementia. Therefore, there is a need to establish a consensus on regulatory and health technology assessment requirements for Alzheimer's disease, as a new drug will need to undergo regulatory and health technology assessments before it becomes available to patients. This article reports the discussions and activities of the regulatory and health technology assessment expert advisory group of the 2-year ROADMAP (real-world outcomes across the Alzheimer's disease spectrum: a multimodal data access platform) project. The expert advisory group discussions identified a lack of consensus on validated outcomes in the earliest Alzheimer's disease stages, the need for filling gaps between outcomes used across clinical trials and real-world settings, and the role that real-world evidence might have in characterising the impact of a possible disease-modifying therapy on caregivers, resource use and long-term outcomes.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/uso terapêutico , Avaliação da Tecnologia Biomédica , Resultado do Tratamento , Progressão da Doença , Feminino , Humanos , Masculino , Modelos Econométricos
7.
Int J Technol Assess Health Care ; 34(2): 163-171, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29633673

RESUMO

OBJECTIVES: Value assessment frameworks have gained prominence recently in the context of U.S. healthcare. Such frameworks set out a series of factors that are considered in funding decisions. The UK's National Institute of Health and Care Excellence (NICE) is an established health technology assessment (HTA) agency. We present a novel application of text analysis that characterizes NICE's Technology Appraisals in the context of the newer assessment frameworks and present the results in a visual way. METHODS: A total of 243 documents of NICE's medicines guidance from 2007 to 2016 were analyzed. Text analysis was used to identify a hierarchical set of decision factors considered in the assessments. The frequency of decision factors stated in the documents was determined and their association with terms related to uncertainty. The results were incorporated into visual representations of hierarchical factors. RESULTS: We identified 125 decision factors, and hierarchically grouped these into eight domains: Clinical Effectiveness, Cost Effectiveness, Condition, Current Practice, Clinical Need, New Treatment, Studies, and Other Factors. Textual analysis showed all domains appeared consistently in the guidance documents. Many factors were commonly associated with terms relating to uncertainty. A series of visual representations was created. CONCLUSIONS: This study reveals the complexity and consistency of NICE's decision-making processes and demonstrates that cost effectiveness is not the only decision-criteria. The study highlights the importance of processes and methodology that can take both quantitative and qualitative information into account. Visualizations can help effectively communicate this complex information during the decision-making process and subsequently to stakeholders.


Assuntos
Tomada de Decisões , Medicina Estatal/organização & administração , Avaliação da Tecnologia Biomédica/organização & administração , Análise Custo-Benefício , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Incerteza , Reino Unido
8.
BMJ Open ; 8(3): e019777, 2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29523564

RESUMO

BACKGROUND: The National Institute for Health and Care Excellence (NICE) was established in 1999 and provides national guidance and advice to improve health and social care. Several steps in the research cycle have been identified that can support the reduction of waste that occurs in biomedical research. The first step in the process is ensuring appropriate research priority setting occurs so only the questions that are needed to fill existing gaps in the evidence are funded. This paper summarises the research priority setting processes at NICE. METHODS: NICE uses its guidance production processes to identify and prioritise research questions through systematic reviews, economic analyses and stakeholder consultations and then highlights those priorities by engagement with the research community. NICE also highlights its methodological areas for research to ensure the appropriate development and growth of the evidence landscape. RESULTS: NICE has prioritised research questions through its guidance production and methodological work and has successfully had several research products funded through the National Institute for Health Research and Medical Research Council. This paper summarises those activities and results. CONCLUSIONS: This activity of NICE therefore reduces research waste by ensuring that the research it recommends has been systematically prioritised through evidence reviews and stakeholder input.


Assuntos
Medicina Baseada em Evidências/economia , Pesquisa sobre Serviços de Saúde/economia , Análise Custo-Benefício , Inglaterra , Prioridades em Saúde , Humanos
9.
Pharmacoeconomics ; 36(3): 359-368, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29214389

RESUMO

BACKGROUND: Reimbursement decisions are conventionally based on evidence from randomised controlled trials (RCTs), which often have high internal validity but low external validity. Real-world data (RWD) may provide complimentary evidence for relative effectiveness assessments (REAs) and cost-effectiveness assessments (CEAs). This study examines whether RWD is incorporated in health technology assessment (HTA) of melanoma drugs by European HTA agencies, as well as differences in RWD use between agencies and across time. METHODS: HTA reports published between 1 January 2011 and 31 December 2016 were retrieved from websites of agencies representing five jurisdictions: England [National Institute for Health and Care Excellence (NICE)], Scotland [Scottish Medicines Consortium (SMC)], France [Haute Autorité de santé (HAS)], Germany [Institute for Quality and Efficacy in Healthcare (IQWiG)] and The Netherlands [Zorginstituut Nederland (ZIN)]. A standardized data extraction form was used to extract information on RWD inclusion for both REAs and CEAs. RESULTS: Overall, 52 reports were retrieved, all of which contained REAs; CEAs were present in 25 of the reports. RWD was included in 28 of the 52 REAs (54%), mainly to estimate melanoma prevalence, and in 22 of the 25 (88%) CEAs, mainly to extrapolate long-term effectiveness and/or identify drug-related costs. Differences emerged between agencies regarding RWD use in REAs; the ZIN and IQWiG cited RWD for evidence on prevalence, whereas the NICE, SMC and HAS additionally cited RWD use for drug effectiveness. No visible trend for RWD use in REAs and CEAs over time was observed. CONCLUSION: In general, RWD inclusion was higher in CEAs than REAs, and was mostly used to estimate melanoma prevalence in REAs or to predict long-term effectiveness in CEAs. Differences emerged between agencies' use of RWD; however, no visible trends for RWD use over time were observed.


Assuntos
Análise Custo-Benefício/métodos , Análise de Dados , Avaliação da Tecnologia Biomédica/métodos , Europa (Continente) , Humanos
10.
J Comp Eff Res ; 6(6): 485-490, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28857631

RESUMO

In light of increasing attention towards the use of real-world evidence (RWE) in decision making in recent years, this commentary aims to reflect on the experiences gained in accessing and using RWE for comparative effectiveness research as a part of the Innovative Medicines Initiative GetReal Consortium and discuss their implications for RWE use in decision-making.


Assuntos
Tomada de Decisão Clínica , Pesquisa Comparativa da Efetividade , Coleta de Dados , Medicina Baseada em Evidências , Humanos , Avaliação da Tecnologia Biomédica
11.
Prim Health Care Res Dev ; 15(1): 111-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23714273

RESUMO

The quality and quantity of primary care prescribing represents a fundamental determinant of the clinical and cost-effectiveness of the UK NHS. The aim of this study was to determine the 'supply' factors that affect primary care prescribing, controlling for 'demand' factors and consider the implications for clinical commissioning groups (CCGs). A detailed regression analysis was undertaken of prescribing in six therapeutic areas to determine differences in prescribing across primary care trusts (PCTs) in England. Results indicate that there are large unexplained variations in primary care prescribing. With the disbanding of the PCTs, and budgets moving to general practitioners (GPs), the role of efficiently and effectively managing prescribing will fall to GP commissioners. Therefore, mechanisms need to be put in place now to ensure that GPs are able to monitor their prescribing and reduce unnecessary drug usage, and further research into the reasons for variations in prescribing needs to be conducted at the CCG level.


Assuntos
Padrões de Prática Médica/tendências , Atenção Primária à Saúde/organização & administração , Medicina Estatal/organização & administração , Análise Custo-Benefício , Revisão de Uso de Medicamentos , Inglaterra , Necessidades e Demandas de Serviços de Saúde , Humanos , Padrões de Prática Médica/economia , Padrões de Prática Médica/normas , Atenção Primária à Saúde/economia , Atenção Primária à Saúde/normas , Análise de Regressão , Medicina Estatal/economia
13.
Clin Child Psychol Psychiatry ; 14(3): 437-54, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19515758

RESUMO

In order for us to begin to understand the effect of abusive experiences in childhood on young people's personality development and symptomatology, we have to draw upon a number of theories. The most important of these relate to attachment, mentalization, dissociation, trauma, and how abusive experiences affect the development of the individual and their developing brain. In this article I will share with you my attempts to understand the young people that come to stay on our intensive care unit and consider how these theories inform our understanding of them and the treatment approach that we try to provide.


Assuntos
Cuidados Críticos/psicologia , Apego ao Objeto , Desenvolvimento da Personalidade , Comportamento Autodestrutivo/psicologia , Tentativa de Suicídio/psicologia , Adolescente , Adoção/psicologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Consumo de Bebidas Alcoólicas/psicologia , Nível de Alerta , Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/terapia , Abuso Sexual na Infância/psicologia , Abuso Sexual na Infância/terapia , Terapia Combinada , Transtornos Dissociativos/psicologia , Transtornos Dissociativos/terapia , Feminino , Humanos , Rememoração Mental , Comportamento Autodestrutivo/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Tentativa de Suicídio/prevenção & controle , Violência/prevenção & controle , Violência/psicologia
14.
Bioinformatics ; 22(18): 2291-7, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16844706

RESUMO

MOTIVATION: The study of interactomes, or networks of protein-protein interactions, is increasingly providing valuable information on biological systems. Here we report a study of cancer proteins in an extensive human protein-protein interaction network constructed by computational methods. RESULTS: We show that human proteins translated from known cancer genes exhibit a network topology that is different from that of proteins not documented as being mutated in cancer. In particular, cancer proteins show an increase in the number of proteins they interact with. They also appear to participate in central hubs rather than peripheral ones, mirroring their greater centrality and participation in networks that form the backbone of the proteome. Moreover, we show that cancer proteins contain a high ratio of highly promiscuous structural domains, i.e., domains with a high propensity for mediating protein interactions. These observations indicate an underlying evolutionary distinction between the two groups of proteins, reflecting the central roles of proteins, whose mutations lead to cancer. CONTACT: paul.bates@cancer.org.uk SUPPLEMENTARY INFORMATION: The interactome data are available though the PIP (Potential Interactions of Proteins) web server at http://bmm.cancerresearchuk.org/servers/pip. Further additional material is available at http://bmm.cancerresearchuk.org/servers/pip/bioinformatics/


Assuntos
Algoritmos , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Mapeamento de Interação de Proteínas/métodos , Proteoma/metabolismo , Transdução de Sinais , Biomarcadores Tumorais/classificação , Biomarcadores Tumorais/metabolismo , Simulação por Computador , Humanos , Proteínas de Neoplasias/classificação , Proteoma/classificação
15.
BMC Bioinformatics ; 7: 2, 2006 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-16398927

RESUMO

BACKGROUND: Protein-protein interactions have traditionally been studied on a small scale, using classical biochemical methods to investigate the proteins of interest. More recently large-scale methods, such as two-hybrid screens, have been utilised to survey extensive portions of genomes. Current high-throughput approaches have a relatively high rate of errors, whereas in-depth biochemical studies are too expensive and time-consuming to be practical for extensive studies. As a result, there are gaps in our knowledge of many key biological networks, for which computational approaches are particularly suitable. RESULTS: We constructed networks, or 'interactomes', of putative protein-protein interactions in the rat proteome--the rat being an organism extensively used for cancer studies. This was achieved by integrating experimental protein-protein interaction data from many species and translating this data into the reference frame of the rat. The putative rat protein interactions were given confidence scores based on their homology to proteins that have been experimentally observed to interact. The confidence score was furthermore weighted according to the extent of the experimental evidence, giving a higher weight to more frequently observed interactions. The scoring function was subsequently validated and networks constructed around key proteins, identified as being highly up- or down-regulated in rat cell lines of high metastatic potential. Using clustering methods on the networks, we have identified key protein communities involved in cancer metastasis. CONCLUSION: The protein network generation and subsequent network analysis used here, were shown to be useful for highlighting key proteins involved in metastasis. This approach, in conjunction with microarray expression data, can be extended to other species, thereby suggesting possible pathways around proteins of interest.


Assuntos
Biomarcadores Tumorais/metabolismo , Mapeamento Cromossômico/métodos , Perfilação da Expressão Gênica/métodos , Proteínas de Neoplasias/metabolismo , Mapeamento de Interação de Proteínas/métodos , Sarcoma/metabolismo , Sarcoma/secundário , Algoritmos , Animais , Inteligência Artificial , Linhagem Celular Tumoral , Análise por Conglomerados , Diagnóstico por Computador/métodos , Reconhecimento Automatizado de Padrão/métodos , Ratos , Reprodutibilidade dos Testes , Sarcoma/diagnóstico , Sensibilidade e Especificidade , Análise de Sequência de Proteína/métodos , Homologia de Sequência de Aminoácidos , Transdução de Sinais
16.
J Mol Biol ; 333(5): 1045-59, 2003 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-14583198

RESUMO

Intron boundaries were extracted from genomic data and mapped onto single-domain human and murine protein structures taken from the Protein Data Bank. A first analysis of this set of proteins shows that intron boundaries prefer to be in non-regular secondary structure elements, while avoiding alpha-helices and beta-strands. This fact alone suggests an evolutionary model in which introns are constrained by protein structure, particularly by tertiary structure contacts. In addition, in silico recombination experiments of a subset of these proteins together with their homologues, including those in different species, show that introns have a tendency to occur away from artificial crossover hot spots. Altogether, these findings support a model in which genes can preferentially harbour introns in less constrained regions of the protein fold they code for. In the light of these findings, we discuss some implications for protein modelling and design.


Assuntos
Éxons/fisiologia , Engenharia de Proteínas , Estrutura Terciária de Proteína , Animais , Simulação por Computador , Proteínas de Ligação a DNA/metabolismo , Humanos , Camundongos , Modelos Moleculares , Fatores de Regulação Miogênica/metabolismo , Fatores de Transcrição , Tripsina/metabolismo
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