13,580 research outputs found

    Clinical trial metadata:Defining and extracting metadata on the design, conduct, results and costs of 125 randomised clinical trials funded by the National Institute for Health Research Health Technology Assessment programme

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    Background:  By 2011, the Health Technology Assessment (HTA) programme had published the results of over 100 trials with another 220 in progress. The aim of the project was to develop and pilot ‘metadata’ on clinical trials funded by the HTA programme.   Objectives: The aim of the project was to develop and pilot questions describing clinical trials funded by the HTA programme in terms of it meeting the needs of the NHS with scientifically robust studies. The objectives were to develop relevant classification systems and definitions for use in answering relevant questions and to assess their utility.   Data sources: Published monographs and internal HTA documents.   Review methods: A database was developed, ‘populated’ using retrospective data and used to answer questions under six prespecified themes. Questions were screened for feasibility in terms of data availability and/or ease of extraction. Answers were assessed by the authors in terms of completeness, success of the classification system used and resources required. Each question was scored to be retained, amended or dropped.    Results: One hundred and twenty-five randomised trials were included in the database from 109 monographs. Neither the International Standard Randomised Controlled Trial Number nor the term ‘randomised trial’ in the title proved a reliable way of identifying randomised trials. Only limited data were available on how the trials aimed to meet the needs of the NHS. Most trials were shown to follow their protocols but updates were often necessary as hardly any trials recruited as planned. Details were often lacking on planned statistical analyses, but we did not have access to the relevant statistical plans. Almost all the trials reported on cost-effectiveness, often in terms of both the primary outcome and quality-adjusted life-years. The cost of trials was shown to depend on the number of centres and the duration of the trial. Of the 78 questions explored, 61 were well answered, 33 fully with 28 requiring amendment were the analysis updated. The other 17 could not be answered with readily available data.   Limitations: The study was limited by being confined to 125 randomised trials by one funder.   Conclusions: Metadata on randomised controlled trials can be expanded to include aspects of design, performance, results and costs. The HTA programme should continue and extend the work reported here

    Selecting Subjects for Participation in Clinical Research: An Empirical Inquiry and Ethical Analysis

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    Procedures for the selection of subjects for participation in randomized clinical trials--usually formalized as eligibility criteria in the study protocol--have both scientific and ethical implications. In this thesis, I undertake an examination of eligibility criteria at three stages in the genesis and dissemination of medical knowledge: clinical trial protocol, interpretation by investigators, and reporting of study results. In the first chapter, ethical issues in subject selection are reviewed and the main study questions are presented. In the second chapter, the results of an examination of eligibility criteria in two sets of clinical trials, one sponsored by the NSABP, the other sponsored by POG, covering a twenty-year time span are presented. The POG trials had far fewer eligibility criteria than the NSABP studies, suggesting that large numbers of criteria may not be necessary for high quality research. In the third chapter, the impact of subjective eligibility criteria on enrollment and investigator uncertainty is explored. Subjective criteria were associated with more variable enrollment decisions and greater uncertainty. Such criteria represent a threat to the validity, conduct and interpretation of trials and, therefore, should only be included when carefully justified. The fourth chapter examines the accuracy of the reporting of eligibility criteria in sets of corresponding study protocol, methods paper, journal article, and Clinical Alert. Important information is lost at each step in the dissemination of study results. Unnecessary criteria ought to be dropped at a trial\u27s inception; all other criteria must be reported faithfully. The fifth chapter attempts to provide a comprehensive philosophical account of just selection procedures for clinical research using the political philosophy of Michael Walzer. The sixth, and last, chapter, discusses explanatory and pragmatic approaches to clinical trial design, overlapping scientific and ethical concerns related to eligibility criteria, and questions for further study

    Implementing the EffTox dose-finding design in the Matchpoint trial

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    Background: The Matchpoint trial aims to identify the optimal dose of ponatinib to give with conventional chemotherapy consisting of fludarabine, cytarabine and idarubicin to chronic myeloid leukaemia patients in blastic transformation phase. The dose should be both tolerable and efficacious. This paper describes our experience implementing EffTox in the Matchpoint trial. Methods: EffTox is a Bayesian adaptive dose-finding trial design that jointly scrutinises binary efficacy and toxicity outcomes. We describe a nomenclature for succinctly describing outcomes in phase I/II dose-finding trials. We use dose-transition pathways, where doses are calculated for each feasible set of outcomes in future cohorts. We introduce the phenomenon of dose ambivalence, where EffTox can recommend different doses after observing the same outcomes. We also describe our experiences with outcome ambiguity, where the categorical evaluation of some primary outcomes is temporarily delayed. Results: We arrived at an EffTox parameterisation that is simulated to perform well over a range of scenarios. In scenarios where dose ambivalence manifested, we were guided by the dose-transition pathways. This technique facilitates planning, and also helped us overcome short-term outcome ambiguity. Conclusions: EffTox is an efficient and powerful design, but not without its challenges. Joint phase I/II clinical trial designs will likely become increasingly important in coming years as we further investigate non-cytotoxic treatments and streamline the drug approval process. We hope this account of the problems we faced and the solutions we used will help others implement this dose-finding clinical trial design. Trial registration: Matchpoint was added to the European Clinical Trials Database (2012-005629-65) on 2013-12-30

    Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

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    Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

    Barriers to Accrual and Enrollment in Brain Tumor Trials

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    Many factors contribute to the poor survival of malignant brain tumor patients, some of which are not easily remedied. However, one contributor to the lack of progress that may be modifiable is poor clinical trial accrual. Surveys of brain tumor patients and neuro-oncology providers suggest that clinicians do a poor job of discussing clinical trials with patients and referring patients for clinical trials. Yet, data from the Cancer Action Network of the American Cancer Society suggest that most eligible oncology patients asked to enroll on a clinical trial will agree to do so. To this end, the Society for Neuro-Oncology (SNO) in collaboration with the Response Assessment in Neuro-Oncology (RANO) Working Group, patient advocacy groups, clinical trial cooperative groups including the Adult Brain Tumor Consortium (ABTC), and other partners are working together with the intent to double clinical trial accrual over the next five years. Here we describe the factors contributing to poor clinical trial accrual in neuro-oncology and offer possible solutions

    Lived experiences of informal caregivers of people with chronic musculoskeletal pain: a systematic review and meta-ethnography

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    BACKGROUND: People with chronic pain often seek support from friends and family for everyday tasks. These individuals are termed informal caregivers. There remains uncertainty regarding the lived experiences of these people who care for individuals with chronic musculoskeletal pain. The aim of this paper is to synthase the evidence on the lived experiences of informal caregivers providing care to people with chronic musculoskeletal pain. METHODS: A systematic literature review was undertaken of published and unpublished literature databases including: EMBASE, MEDLINE, CINAHL, PubMed, the WHO International Clinical Trial Registry and ClinicalTrials.gov registry (to September 2019). Qualitative studies exploring the lived experiences of informal caregivers of people with chronic musculoskeletal pain were included. Data were synthesised using a meta-ethnography approach. Evidence was evaluated using the Critical Appraisal Skills Programme (CASP) qualitative appraisal tool. RESULTS: From 534 citations, 10 studies were eligible (360 participants: 171 informal caregivers of 189 care recipients). The evidence was moderate quality. Seven themes arose: the relationship of caregivers to healthcare professionals, role reversal with care recipients; acting the confidant to the care recipient; a constant burden in caregiving; legitimising care recipient’s condition; knowledge and skills to provide caregiving; and the perception of other family members and wider-society to the caregiver/care recipient dyad. CONCLUSIONS: The lived experiences of caregivers of people with chronic musculoskeletal pain is complex and dynamic. There is an inter-connected relationship between caregivers, care recipients and healthcare professionals. Exploring how these experiences can be modified to improve a caregiving dyad’s lived experience is now warranted

    Active Surveillance for Favorable-Risk Prostate Cancer: A Short Review

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    Active surveillance is becoming a more widely accepted management strategy in men with low-risk localized prostate cancer. This is in recognition of the knowledge that most men with such cancer are likely to die from other causes. The obvious benefits of active surveillance are reduced morbidity by delaying or avoiding radical gland therapy. These advantages should be balanced against appropriate selection criteria and triggers for moving to radical therapy while on active surveillance. The optimal method by which to identify the small number of men who will progress by use of clinical, biopsy, and imaging data is yet to be defined. Nevertheless, active surveillance is an appealing management option in selected men with prostate cancer and represents a solution to the significant problem of the overdiagnosis of clinically insignificant disease that accompanies prostate-specific antigen (PSA) screening

    Increasing Lung Cancer Screening Referrals in Patients with Tobacco Use Disorder

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    Lung cancer in the United States is a substantial cause of mortality. According to the American College of Radiology’s Lung Cancer Screening Registry, only 1.9% of eligible patients were screened for lung cancer in 2016. The National Comprehensive Cancer Network and U.S. Preventative Services Task Force (USPSTF) guidelines recommend lung cancer screening (LCS) in high-risk patients. The USPSTF recommends screening current and former smokers aged 55-80 years who have smoked for 20 or more pack-years, and for former smokers, those that have quit within 15 years

    Patient preferences of genomic testing in precision cancer medicine

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    Aims: The aim of this thesis was to identify and rate themed patient preference attributes of genomic testing in precision cancer medicine (PCM). The effect of clinical treatment intent and time since completing treatment was examined as a novel hypothesis that these factors influence identified preference attribute themes and/or ratings. This thesis then benchmarked the identified preference attributes against the ATLANTIS clinical trial design, in order to assess how a current clinical trial incorporates patient preferences. Methods: A narrative review of current cancer treatment paradigms was undertaken alongside systematic review of the literature assessing patient preferences of genomic testing in PCM. In addition, mixed methods research, using Nominal Group Technique (NGT), identified and rated preference attribute themes of genomic testing amongst cancer patients. These preference attributes were then benchmarked against genomic testing undertaken within the ATLANTIS clinical trial, to determine how a novel PCM study design incorporated the attributes. Results: Patient preferences of genomic testing in PCM are influenced by clinical treatment intent and time since completing treatment. Patients undergoing cancer treatment with radical intent demonstrated higher preference ratings for test sensitivity (true positive) and specificity (true negative). Invasiveness of testing and test turnaround time were higher rated preference attributes amongst patients undergoing treatment with palliative intent. Ten preference attribute themes of genomic testing were identified: regulatory/NHS approval, test turnaround time, invasiveness of testing, physician approval, test sensitivity (true positive), test specificity (true negative), prevalence of variant, distance to travel, implications for family and family endorsement for testing. The novel adaptive design of the ATLANTIS trial incorporated many of the preference attribute themes of genomic testing demonstrated in this thesis. Conclusions: Patient preferences of genomic testing in PCM are influenced by clinical treatment intent. This thesis identified and rated preference attribute themes of genomic testing for patients, as well as benchmarking these against a current UK PCM clinical trial. The adaptive design of the ATLANTIS trial incorporated many of the preference attributes, but does not allow for assessment of interaction between multiple inter-related attributes. The results of this thesis augment novel clinical trial design for studies incorporating genomic testing in order they retain patient-centred values at their core

    Understanding Elements Involved in Active Racial and Ethnic Minority Recruitment Practices for Biopharmaceutical-Sponsored Clinical Trials: A Socio-Ecological Qualitative Inquiry

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    Inequitable participation in clinical trials continues to be a problem, and trial populations do not always reflect the demographics of the population that the investigational product will ultimately be treating. Because genetic differences between racial and ethnic groups affect the safety and efficacy of new treatments, it is important that standard of care decisions are made based on a representative population. The purpose of this study is to understand the socio-ecological elements that are involved in the active implementation of racial and ethnic minority recruitment practices for biopharmaceutical-funded trials in the United States. This general qualitative study was both descriptive and exploratory in nature and utilized semi-structured, in-depth interviews for data collection. The socio-ecological model was utilized as the conceptual framework guiding this study (McLeroy, Bibeau, Stecker, & Glanz, 1988). The interview guide was designed to explore the perceptions, practices and experiences of 15 clinical research site professionals related to recruiting racially and ethnically diverse trial participants. Data analysis utilized a coding process in which data were coded inductively. Codes were classified according to the socio-ecological model. Following data analysis, 20 themes emerged from information pertaining to the actual implementation of minority recruitment practices. These 20 themes represent each level of the socio-ecological model and provide explanations for intrapersonal, interpersonal, organizational, community and policy components. A holistic view that facilitates a comprehensive understanding of effective minority recruitment practices is offered after considering the interaction of the components at all levels of the socio-ecological model. These multi-faceted findings reveal that an ecological perspective offers insight into improving access to clinical trials by focusing on environmental change initiatives, rather than individual change on a patient level. This study’s findings offer practical guidance for the implementation of change initiatives in minority recruitment practices at research sites. The results of this study demonstrate that environmental change can provide a premise for improving access to clinical trials among minority populations
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