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Medscape Journal of Medicine Apr 2008
Topics: Bariatric Surgery; Clinical Trials as Topic; Diabetes Mellitus; Humans; Postoperative Complications; Quality of Life; Risk Assessment; Treatment Outcome; United States
PubMed: 18504499
DOI: No ID Found -
Journal of the American College of... Jun 2014Management of patients with in-stent restenosis (ISR) remains an important clinical problem. Although drug-eluting stents (DES) have drastically reduced the incidence of... (Review)
Review
Management of patients with in-stent restenosis (ISR) remains an important clinical problem. Although drug-eluting stents (DES) have drastically reduced the incidence of ISR, treatment of DES-ISR is particularly challenging. ISR mainly results from aggressive neointimal proliferation, but recent data also suggest that neoatherosclerosis may play an important pathophysiological role. Intracoronary imaging provides unique insights to unravel the underlying substrate of ISR and may be used to guide repeated interventions. In this paper, we systematically reviewed clinical trial data with currently available therapeutic modalities, including DES and drug-coated balloons, in patients presenting with ISR within bare-metal stents or DES.
Topics: Animals; Clinical Trials as Topic; Coronary Restenosis; Drug-Eluting Stents; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24632282
DOI: 10.1016/j.jacc.2014.02.545 -
Nature Reviews. Neurology Apr 2016Each of the thousands of rare neurological diseases requires a widely distributed network of centres, investigators and patients, so as to foster multidisciplinary... (Review)
Review
Each of the thousands of rare neurological diseases requires a widely distributed network of centres, investigators and patients, so as to foster multidisciplinary investigations and involve sufficient numbers of patients in the discovery of disease pathogenesis and novel treatment. In this Review, we highlight the value of this collaborative approach in patient-oriented research into rare neurological channelopathies. Two networks, the Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) and the Clinical Research Consortium for Studies of Cerebellar Ataxias (CRC-SCA), provide a link between patients with rare channelopathies and investigators who are studying disease pathogenesis and developing novel treatments. Interactions between patients, researchers and advocacy groups promote shared agendas that benefit patient education and recruitment, research collaboration and funding, and training and mentoring of junior investigators who are attracted to the study of the diseases that provide the focus for the two networks. Here, we discuss how linkage of national and international centres has enabled recruitment of study participants, provided opportunities for novel studies of pathogenesis, and facilitated successful clinical trials.
Topics: Biomedical Research; Channelopathies; Clinical Trials as Topic; Humans; Multicenter Studies as Topic; Patient Selection; Treatment Outcome
PubMed: 26943780
DOI: 10.1038/nrneurol.2016.18 -
Journal of the National Cancer Institute Sep 2010Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building... (Review)
Review
Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan-Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation.
Topics: Biomarkers, Tumor; Cancer Vaccines; Clinical Trials as Topic; Humans; Immunity, Cellular; Immunotherapy; Kaplan-Meier Estimate; Models, Statistical; Multicenter Studies as Topic; Neoplasms; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 20826737
DOI: 10.1093/jnci/djq310 -
Journal of the National Cancer Institute Mar 2020Historically, the gold standard for evaluation of cancer therapeutics, including medical devices, has been the randomized clinical trial. Although high-quality clinical... (Review)
Review
Historically, the gold standard for evaluation of cancer therapeutics, including medical devices, has been the randomized clinical trial. Although high-quality clinical data are essential for safe and judicious use of therapeutic oncology devices, class II devices require only preclinical data for US Food and Drug Administration approval and are often not rigorously evaluated prior to widespread uptake. Herein, we review master protocol design in medical oncology and its application to therapeutic oncology devices, using examples from radiation oncology. Unique challenges of clinical testing of radiation oncology devices (RODs) include patient and treatment heterogeneity, lack of funding for trials by industry and health-care payers, and operator dependence. To address these challenges, we propose the use of master protocols to optimize regulatory, financial, administrative, quality assurance, and statistical efficiency of trials evaluating RODs. These device-specific master protocols can be extrapolated to other devices and encompass multiple substudies with the same design, statistical considerations, logistics, and infrastructure. As a practical example, we outline our phase I and II master protocol trial of stereotactic magnetic resonance imaging-guided adaptive radiotherapy, which to the best of our knowledge is the first master protocol trial to test a ROD. Development of more efficient clinical trials is needed to promote thorough evaluation of therapeutic oncology devices, including RODs, in a resource-limited environment, allowing more practical and rapid identification of the most valuable advances in our field.
Topics: Clinical Trials as Topic; Equipment and Supplies; Humans; Magnetic Resonance Imaging; Neoplasms; Radiation Oncology; Radiotherapy, Image-Guided; Randomized Controlled Trials as Topic; Stereotaxic Techniques; United States; United States Food and Drug Administration
PubMed: 31504680
DOI: 10.1093/jnci/djz167 -
European Spine Journal : Official... Jun 2010Transforaminal endoscopic techniques have become increasingly popular in surgery of patients with lumbar stenosis. The literature has not yet been systematically... (Meta-Analysis)
Meta-Analysis Review
Transforaminal endoscopic techniques have become increasingly popular in surgery of patients with lumbar stenosis. The literature has not yet been systematically reviewed. A comprehensive systematic literature review up to November 2009 to assess the effectiveness of transforaminal endoscopic surgery in patients with symptomatic lumbar stenosis was made. Two reviewers independently checked all retrieved titles and abstracts and relevant full text articles for inclusion criteria. Included articles were assessed for quality, and relevant data, including outcomes, were extracted by two reviewers independently. No randomized controlled trials were identified, but seven observational studies. The studies were of poor methodological quality and heterogeneous regarding patient selection, indications, operation techniques, follow-up period and outcome measures. Overall, 69-83% reported the outcome as satisfactory and a complication rate of 0-8.3%. The reported re-operation rate varied from 0 to 20%. At present, there is no valid evidence from randomized controlled trials on the effectiveness of transforaminal endoscopic surgery for lumbar stenosis. Randomized controlled trials comparing transforaminal endoscopic surgery with other surgical techniques are direly needed.
Topics: Clinical Trials as Topic; Endoscopy; Humans; Lumbar Vertebrae; Outcome Assessment, Health Care; Radiography; Spinal Canal; Spinal Stenosis; Treatment Outcome
PubMed: 20087610
DOI: 10.1007/s00586-009-1272-6 -
Pediatrics Jun 2014Despite overall improvement in survival, morbidity, and quality of life of US patients with cancer, this progress is less prevalent in the population of adolescent and... (Review)
Review
Despite overall improvement in survival, morbidity, and quality of life of US patients with cancer, this progress is less prevalent in the population of adolescent and young adult patients with cancer, including those between the ages of 15 and 19 years. Evidence suggests that participation in clinical trials is associated with better survival outcomes among children and adolescents with cancer; however, adolescents have lower clinical trial participation rates compared with younger age cohorts. To better understand the unique concerns among adolescent patients with cancer, the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention convened a workgroup of researchers and health care providers in the field of adolescent and young adult oncology and cancer survivorship to examine the barriers and challenges limiting the participation of adolescents in clinical trials and to define ways to improve upon these concerns. This article summarizes the activities of the workgroup and their suggestions for enhanced accrual.
Topics: Adolescent; Clinical Trials as Topic; Education; Humans; Neoplasms; Patient Selection; Referral and Consultation
PubMed: 24918214
DOI: 10.1542/peds.2014-0122D -
Pediatrics Jun 2014Adolescents (aged 15-19 years) have not experienced the same survival gains as children and older adults diagnosed with cancer. Poor clinical trial enrollment and... (Review)
Review
Adolescents (aged 15-19 years) have not experienced the same survival gains as children and older adults diagnosed with cancer. Poor clinical trial enrollment and adherence rates among adolescents may account for some of this disparity. Although biological, regulatory, systemic, and practice-related challenges to clinical trial enrollment and adherence have been examined, studies of psychosocial factors, which can serve as barriers or facilitators to enrollment and adherence, are limited. To bring attention to these psychological factors, we reviewed existing literature on psychosocial barriers and facilitators that can affect an adolescent's decision to enroll and adhere to a clinical trial. We also provide potential strategies to address psychosocial factors affecting clinical trial accrual and adherence.
Topics: Adolescent; Clinical Trials as Topic; Health Knowledge, Attitudes, Practice; Humans; Neoplasms; Patient Compliance; Patient Selection; Psychology
PubMed: 24918211
DOI: 10.1542/peds.2014-0122I -
Epilepsy & Behavior : E&B Oct 2020On May 22-24, 2019, the 15th Antiepileptic Drug and Device (AEDD) Trials Conference was held, which focused on current issues related to AEDD development from... (Review)
Review
On May 22-24, 2019, the 15th Antiepileptic Drug and Device (AEDD) Trials Conference was held, which focused on current issues related to AEDD development from preclinical models to clinical prognostication. The conference featured regulatory agencies, academic laboratories, and healthcare companies involved in emerging epilepsy therapies and research. The program included discussions around funding and support for investigations in epilepsy and neurologic research, clinical trial design and integrated outcome measures for people with epilepsy, and drug development and upcoming disease-modifying therapies. Finally, the conference included updates from the preclinical, clinical, and device pipeline. Summaries of the talks are provided in this paper, with the various pipeline therapeutics in the listed tables to be outlined in a subsequent publication.
Topics: Animals; Anticonvulsants; Clinical Trials as Topic; Congresses as Topic; Device Approval; Drug Development; Epilepsy; Florida; Genetic Testing; Humans; Mass Screening; National Institute of Neurological Disorders and Stroke (U.S.); United States
PubMed: 32563052
DOI: 10.1016/j.yebeh.2020.107189 -
The British Journal of Ophthalmology May 2015Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical... (Review)
Review
Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies.
Topics: Antihypertensive Agents; Biomarkers; Clinical Trials as Topic; Diagnostic Imaging; Endpoint Determination; Glaucoma; Humans; Intraocular Pressure; Optic Disk; Tonometry, Ocular; Visual Fields
PubMed: 25034049
DOI: 10.1136/bjophthalmol-2014-305550