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Circulation Jul 2019Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary... (Review)
Review
Home-Based Cardiac Rehabilitation: A Scientific Statement From the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology.
Cardiac rehabilitation (CR) is an evidence-based intervention that uses patient education, health behavior modification, and exercise training to improve secondary prevention outcomes in patients with cardiovascular disease. CR programs reduce morbidity and mortality rates in adults with ischemic heart disease, heart failure, or cardiac surgery but are significantly underused, with only a minority of eligible patients participating in CR in the United States. New delivery strategies are urgently needed to improve participation. One potential strategy is home-based CR (HBCR). In contrast to center-based CR services, which are provided in a medically supervised facility, HBCR relies on remote coaching with indirect exercise supervision and is provided mostly or entirely outside of the traditional center-based setting. Although HBCR has been successfully deployed in the United Kingdom, Canada, and other countries, most US healthcare organizations have little to no experience with such programs. The purpose of this scientific statement is to identify the core components, efficacy, strengths, limitations, evidence gaps, and research necessary to guide the future delivery of HBCR in the United States. Previous randomized trials have generated low- to moderate-strength evidence that HBCR and center-based CR can achieve similar improvements in 3- to 12-month clinical outcomes. Although HBCR appears to hold promise in expanding the use of CR to eligible patients, additional research and demonstration projects are needed to clarify, strengthen, and extend the HBCR evidence base for key subgroups, including older adults, women, underrepresented minority groups, and other higher-risk and understudied groups. In the interim, we conclude that HBCR may be a reasonable option for selected clinically stable low- to moderate-risk patients who are eligible for CR but cannot attend a traditional center-based CR program.
Topics: American Heart Association; Cardiac Rehabilitation; Cardiology; Cardiovascular Diseases; Clinical Trials as Topic; Exercise Therapy; Home Care Services; Humans; Lung Diseases; United States
PubMed: 31082266
DOI: 10.1161/CIR.0000000000000663 -
Current Treatment Options in Oncology Jul 2021Clinical trials play a critical role in discovering new treatments, but the path to regulatory approval can be cumbersome and time consuming. Efforts to increase the... (Review)
Review
Clinical trials play a critical role in discovering new treatments, but the path to regulatory approval can be cumbersome and time consuming. Efforts to increase the efficiency and interpretability of clinical trials within the neuro-oncology community have focused on standardization of response assessment, development of consensus guidelines for clinical trial conduct, decentralization of clinical trials, removal of barriers to clinical trial accrual, and re-examination of patient eligibility criteria.
Topics: Clinical Trials as Topic; Humans; Medical Oncology; Nervous System Neoplasms; Outcome Assessment, Health Care; Practice Guidelines as Topic; Research Design
PubMed: 34213625
DOI: 10.1007/s11864-021-00875-8 -
The Journal of Invasive Cardiology Apr 2020The results of the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approach) trial were presented at the American Heart...
The results of the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approach) trial were presented at the American Heart Association Scientific Sessions in November, 2019 in Philadelphia, Pennsylvania, and recently published on March 30, 2020 in the New England Journal of Medicine. After an average follow-up of 3.5 years, invasive therapy did not reduce the major adverse cardiac event (MACE) rate compared with optimal medical therapy (OMT) in patients with stable ischemic heart disease. However, the ISCHEMIA trial results might stem from the revascularization of inappropriate vessels and from the lack of a lesion-specific ischemia detection algorithm to guide revascularization instead of conventional stress testing. The utilization of an initial computed tomography (CT) angiogram with or without fractional flow reserve CT could have produced better revascularization results.
Topics: Clinical Trials as Topic; Coronary Angiography; Coronary Artery Disease; Exercise Test; Fractional Flow Reserve, Myocardial; Humans; Ischemia; Myocardial Ischemia; Tomography, X-Ray Computed; Treatment Failure
PubMed: 32234969
DOI: No ID Found -
Neurotherapeutics : the Journal of the... Jul 2021
Topics: Anticonvulsants; Clinical Trials as Topic; Epilepsy; Genetic Testing; Humans; Precision Medicine
PubMed: 34704188
DOI: 10.1007/s13311-021-01147-x -
The Journal of Pain 2020Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial direct current stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment.
OBJECTIVE
To systematically review the most up-to-date literature and perform a meta-analysis of the effects of tDCS on pain intensity in fibromyalgia.
METHODS
The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane Library, and Web of Science. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and nonrandomized. Crossover and parallel-group design studies were included. Risk of bias was assessed for all included studies. Meta-analysis was conducted on studies investigating pain intensity after tDCS in participants with fibromyalgia and analyzed using standardized mean difference and 95% confidence intervals.
RESULTS
Fourteen clinical studies were included. Ten were controlled trials and 4 were within-subjects crossover studies. Meta-analysis of data from 8 controlled trials provides tentative evidence of pain reduction when active tDCS is delivered compared to sham. However, substantial statistical heterogeneity and high risk of bias of primary studies prevent more conclusive recommendations being made.
CONCLUSIONS
tDCS is a safe intervention with the potential to lower pain intensity in fibromyalgia. However, there is a need for more empirical research of the neural target sites and optimum stimulation parameters to achieve the greatest effects before conducting further clinical studies.
PERSPECTIVE
This systematic review and meta-analysis synthesizes current evidence for the clinical effectiveness of tDCS in the treatment of fibromyalgia pain. There is only tentative evidence of pain reduction when active tDCS is compared to sham. High heterogeneity and risk of bias across studies suggest a need for further empirical research.
Topics: Chronic Pain; Clinical Trials as Topic; Fibromyalgia; Humans; Pain Management; Transcranial Direct Current Stimulation; Treatment Outcome
PubMed: 31982685
DOI: 10.1016/j.jpain.2020.01.003 -
Neurology May 2021Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3... (Review)
Review
Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success. Here, we discuss exploratory clinical trials in neurodegenerative dementias. These are generally phase 1b or phase 2a trials that are designed to assess pharmacologic effects and rely on biomarker outcomes, with shorter treatment durations and fewer patients than traditional phase 2 studies. Exploratory trials can establish go/no-go decision points, support proof of concept and dose selection, and terminate drugs that fail to show target engagement with suitable exposure and acceptable safety profiles. Early failure saves valuable resources including opportunity costs. This is especially important for programs in academia and small biotechnology companies but may be applied to high-risk projects in large pharmaceutical companies to achieve proof of concept more rapidly at lower costs than traditional approaches. Exploratory studies in a staged clinical development program may provide promising data to warrant the substantial resources needed to advance compounds through late-stage development. To optimize the design and application of exploratory trials, the Alzheimer's Drug Discovery Foundation and the Association for Frontotemporal Degeneration convened an advisory panel to provide recommendations on outcome measures and statistical considerations for these types of studies and study designs that can improve efficiency in clinical development.
Topics: Alzheimer Disease; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dementia; Drug Development; Frontotemporal Dementia; Humans; Neurodegenerative Diseases; Outcome Assessment, Health Care; Proof of Concept Study; Research Design; Treatment Failure; Treatment Outcome
PubMed: 33674360
DOI: 10.1212/WNL.0000000000011774 -
Osteoarthritis and Cartilage Mar 2021
Topics: Cognitive Behavioral Therapy; Humans; Low Back Pain; Mediation Analysis; Patient Satisfaction; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33429055
DOI: 10.1016/j.joca.2020.12.011 -
Annals of Clinical and Translational... Jul 2021The spinocerebellar ataxias (SCAs) are a group of dominantly inherited diseases that share the defining feature of progressive cerebellar ataxia. The disease process,... (Review)
Review
The spinocerebellar ataxias (SCAs) are a group of dominantly inherited diseases that share the defining feature of progressive cerebellar ataxia. The disease process, however, is not confined to the cerebellum; other areas of the brain, in particular, the brainstem, are also affected, resulting in a high burden of morbidity and mortality. Currently, there are no disease-modifying treatments for the SCAs, but preclinical research has led to the development of therapeutic agents ripe for testing in patients. Unfortunately, due to the rarity of these diseases and their slow and variable progression, there are substantial hurdles to overcome in conducting clinical trials. While the epidemiological features of the SCAs are immutable, the feasibility of conducting clinical trials is being addressed through a combination of strategies. These include improvements in clinical outcome measures, the identification of imaging and fluid biomarkers, and innovations in clinical trial design. In this review, we highlight current challenges in initiating clinical trials for the SCAs and also discuss pathways for researchers and clinicians to mitigate these challenges and harness opportunities for clinical trial development.
Topics: Biomarkers; Clinical Trials as Topic; Humans; Neuroimaging; Prevalence; Spinocerebellar Ataxias
PubMed: 34019331
DOI: 10.1002/acn3.51370 -
British Journal of Cancer Oct 2019International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing... (Review)
Review
International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing treatments in diverse populations and facilitating the study of rare tumours or specific molecular subtypes. However, a number of challenges continue to hinder the efficient and productive conduct of both commercial and non-commercial international clinical trials. These challenges include complex and burdensome regulatory requirements, the high cost of conducting trials, and logistical challenges associated with ethics review, drug supply and biospecimen collection and management. We propose solutions to promote oncology trial collaboration, such as regulatory reform, harmonisation of trial initiation and management processes and greater recognition and funding of academic (non-commercial) clinical trials. It is only through coordinated effort and leadership from researchers, regulators and those responsible for health systems that the full potential of international trial collaboration can be realised.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Government Regulation; Humans; Information Dissemination; International Cooperation; Medical Oncology; Multicenter Studies as Topic; Neoplasms; Research Support as Topic; Specimen Handling
PubMed: 31378784
DOI: 10.1038/s41416-019-0532-4 -
Contemporary Clinical Trials Jun 2024Since the 1950s, randomized clinical trials (RCTs) have served as the gold standard for confirming the benefits of a new drug. Accordingly, phase 3 trials, the last... (Review)
Review
BACKGROUND
Since the 1950s, randomized clinical trials (RCTs) have served as the gold standard for confirming the benefits of a new drug. Accordingly, phase 3 trials, the last steps in the evaluation process for a new drug, have been recommended to all be RCTs. Nevertheless, single-arm phase 3 trials still appear to be in use.
METHODS
We performed a PubMed search to identify the use of a single-arm design in phase 3 trials, excluding only non-English articles. Three categories were distinguished: past use of an RCT, of any other trial design, or no previous trial; and according to diagnosis (oncology, infection, others).
RESULTS
A total of 176 single-arm phase 3 trials (19 oncology, 43 infections and 114 others) were identified by the search, with exponential growth since 1994, in parallel with that of RCTs. Among them, 64 (36%) were preceded by an RCT, 58 (33%) by a non-randomized trial, and 54 (31%) had no previous trial, with no main influence of the diagnosis setting. Justification of the design was reported in 30 (18%) of those trials, with ethical concerns comprising one-third of those justifications. This was similar in the 14 single-arm phase 2-3 trials, with about one-third in each group, and 17% justification of a non-comparative design.
CONCLUSION
The use of a single-arm phase 3 trial is heterogeneous, ranging from first trials up to confirmatory trials after a previously conducted RCT. Justification for these single-arm designs as confirmatory evidence should be more clearly reported, along with potential sources of bias.
Topics: Humans; Research Design; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic; Non-Randomized Controlled Trials as Topic
PubMed: 38508234
DOI: 10.1016/j.cct.2024.107506