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Osteoarthritis and Cartilage May 2015The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or... (Review)
Review
The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After the members voted we calculated the median score among the nine members of the working group who completed the score. The document includes 25 recommendations regarding randomization, blocking and stratification, blinding, enhancing accuracy of patient-reported outcomes (PRO), selecting a study population and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA.
Topics: Clinical Trials as Topic; Disease Management; Humans; Osteoarthritis, Knee; Practice Guidelines as Topic
PubMed: 25952346
DOI: 10.1016/j.joca.2015.03.005 -
Global Heart Sep 2019Hypertrophic cardiomyopathy (HCM) is a genetic disorder with a very large global burden for which more therapeutic management regimens are required. (Review)
Review
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is a genetic disorder with a very large global burden for which more therapeutic management regimens are required.
OBJECTIVES
In this study, the authors explore HCM-related clinical trials, determine the shortcomings leading to the lack of development of new HCM therapies, and attempt to shed light on potential areas for improvement.
METHODS
In January 2019, the authors completed a search on ClinicalTrials.gov for all therapeutic and interventional clinical trials involving HCM, without any limits for location or date. Information on trial characteristics such as phase, start and end dates, sample size, experimental intervention, publications, study design, selection criteria, and results were collected and analyzed.
RESULTS
Sixty-three trials met the selection criteria. The average trial duration across phases was around 3 years. Around one-half of the trials were conducted in North America (United States and Canada) and 44% of the trials were in their early phases (I and II). Approximately one-third of the trials were completed. Only 14 publications were produced from all the clinical trials studied.
CONCLUSIONS
The study revealed a low number of trials, lack of geographic diversity, and scarcity of published results concerning HCM clinical trials. Proper management of HCM trials is of vast importance to achieve effective therapies.
Topics: Cardiomyopathy, Hypertrophic; Clinical Trials as Topic; Global Health; Humans; Publications; Sample Size
PubMed: 31451240
DOI: 10.1016/j.gheart.2019.07.005 -
International Orthopaedics Sep 2014Skeletal injuries requiring bone augmentation techniques are increasing in the context of avoiding or treating difficult cases with bone defects, bone healing problems,... (Review)
Review
Skeletal injuries requiring bone augmentation techniques are increasing in the context of avoiding or treating difficult cases with bone defects, bone healing problems, and bone regeneration limitations. Musculoskeletal severe trauma, osteoporosis-related fractures, and conditions where bone defect, bone collapse or insufficient bone regeneration occur are prone to disability and serious complications. Bone cell therapy has emerged as a promising technique to augment and promote bone regeneration. Interest in the orthopaedic community is considerable, although many aspects related to the research of this technique in specific indications may be insufficiently recognised by many orthopaedic surgeons. Clinical trials are the ultimate research in real patients that may confirm or refute the value of this new therapy. However, before launching the required trials in bone cell therapy towards bone regeneration, preclinical data is needed with the cell product to be implanted in patients to ensure safety and efficacy. These preclinical studies support the end-points that need to be evaluated in clinical trials. Orthopaedic surgeons are the ultimate players that, through their research, would confirm in clinical trials the benefit of bone cell therapies. To further foster this research, the pathway to eventually obtain authorisation from the National Competent Authorities and Research Ethics Committees under the European regulation is reviewed, and the experience of the REBORNE European project offers information and important clues about the current Voluntary Harmonization Procedure and other opportunities that need to be considered by surgeons and researchers on the topic.
Topics: Bone Diseases; Bone Regeneration; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Europe; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Orthopedics
PubMed: 24728347
DOI: 10.1007/s00264-014-2332-z -
Challenges and Lessons Learned From COVID-19 Trials: Should We Be Doing Clinical Trials Differently?The Canadian Journal of Cardiology Sep 2021The COVID-19 crisis led to a flurry of clinical trials activity. The COVID-evidence database shows 2814 COVID-19 randomized trials registered as of February 16, 2021.... (Review)
Review
The COVID-19 crisis led to a flurry of clinical trials activity. The COVID-evidence database shows 2814 COVID-19 randomized trials registered as of February 16, 2021. Most were small (only 18% have a planned sample size > 500) and the rare completed ones have not provided published results promptly (only 283 trial publications as of February 2021). Small randomized trials and observational, nonrandomized analyses have not had a successful track record and have generated misleading expectations. Different large trials on the same intervention have generally been far more efficient in producing timely and consistent evidence. The rapid generation of evidence and accelerated dissemination of results have led to new challenges for systematic reviews and meta-analyses (eg, rapid, living, and scoping reviews). Pressure to regulatory agencies has also mounted with massive emergency authorizations, but some of them have had to be revoked. Pandemic circumstances have disrupted the way trials are conducted; therefore, new methods have been developed and adopted more widely to facilitate recruitment, consent, and overall trial conduct. On the basis of the COVID-19 experience and its challenges, planning of several large, efficient trials, and wider use of adaptive designs might change the future of clinical research. Pragmatism, integration in clinical care, efficient administration, promotion of collaborative structures, and enhanced integration of existing data and facilities might be several of the legacies of COVID-19 on future randomized trials.
Topics: COVID-19; Clinical Trials as Topic; Drug Repositioning; Humans; Pandemics; Randomized Controlled Trials as Topic; Research Design; SARS-CoV-2
PubMed: 34077789
DOI: 10.1016/j.cjca.2021.05.009 -
Statistics in Medicine Nov 2012Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in... (Review)
Review
Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More Bayesian trials should be designed and conducted to refine the approach and demonstrate their real benefit in action.
Topics: Bayes Theorem; Clinical Trials as Topic; Likelihood Functions; Research Design; Software
PubMed: 22711340
DOI: 10.1002/sim.5404 -
Neurology May 2019The impetus for this consensus discussion was to recommend clinical trial designs that can deliver high-quality data for effective therapies for pediatric patients, in a...
OBJECTIVE
The impetus for this consensus discussion was to recommend clinical trial designs that can deliver high-quality data for effective therapies for pediatric patients, in a reasonable timeframe, with a key focus on short- and long-term safety.
METHODS
The International Pediatric Multiple Sclerosis Study Group convened a meeting of experts to review the advances in the understanding of pediatric-onset multiple sclerosis (MS) and the advent of clinical trials for this population.
RESULTS
In the last few years, convincing evidence has emerged that the biological processes involved in MS are largely shared across the age span. As such, treatments proven efficacious for the care of adults with MS have a biological rationale for use in pediatric MS given the relapsing-remitting course at onset and high relapse frequency. There are also ethical considerations on conducting clinical trials in this age group including the use of placebo owing to highly active disease. It is imperative to reconsider study design and implementation based on what information is needed. Are studies needed for efficacy or should safety be the primary goal? Further, there have been major recruitment challenges in recently completed and ongoing pediatric MS trials. Phase 3 trials for every newly approved therapy for adult MS in the pediatric MS population are simply not feasible.
CONCLUSIONS
A primary goal is to ensure high-quality evidence-based treatment for children and adolescents with MS, which will improve our understanding of the safety of these agents and remove regulatory or insurance-based limitations in access to treatment.
Topics: Adolescent; Child; Clinical Trials as Topic; Evidence-Based Medicine; Humans; Multiple Sclerosis, Relapsing-Remitting
PubMed: 31043474
DOI: 10.1212/WNL.0000000000007572 -
BMC Palliative Care Jan 2017Over the past decades there has been a significant increase in the number of published clinical trials in palliative care. However, empirical evidence suggests that... (Review)
Review
BACKGROUND
Over the past decades there has been a significant increase in the number of published clinical trials in palliative care. However, empirical evidence suggests that there are methodological problems in the design and conduct of studies, which raises questions about the validity and generalisability of the results and of the strength of the available evidence. We sought to evaluate the methodological characteristics and assess the quality of reporting of clinical trials in palliative care.
METHODS
We performed a systematic review of published clinical trials assessing therapeutic interventions in palliative care. Trials were identified using MEDLINE (from its inception to February 2015). We assessed methodological characteristics and describe the quality of reporting using the Cochrane Risk of Bias tool.
RESULTS
We retrieved 107 studies. The most common medical field studied was oncology, and 43.9% of trials evaluated pharmacological interventions. Symptom control and physical dimensions (e.g. intervention on pain, breathlessness, nausea) were the palliative care-specific issues most studied. We found under-reporting of key information in particular on random sequence generation, allocation concealment, and blinding.
CONCLUSIONS
While the number of clinical trials in palliative care has increased over time, methodological quality remains suboptimal. This compromises the quality of studies. Therefore, a greater effort is needed to enable the appropriate performance of future studies and increase the robustness of evidence-based medicine in this important field.
Topics: Clinical Trials as Topic; Data Accuracy; Humans; Medicine; Outcome and Process Assessment, Health Care; Palliative Care; Research Design; Sample Size; Surveys and Questionnaires
PubMed: 28122560
DOI: 10.1186/s12904-016-0181-9 -
Experimental Neurology Dec 2014Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that is characterized by progressive degeneration of motor neurons in the cortex,... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that is characterized by progressive degeneration of motor neurons in the cortex, brainstem and spinal cord. This leads to paralysis, respiratory insufficiency and death within an average of 3 to 5 years from disease onset. While the genetics of ALS are becoming more understood in familial cases, the mechanisms underlying disease pathology remain unclear and there are no effective treatment options. Without understanding what causes ALS it is difficult to design treatments. However, in recent years stem cell transplantation has emerged as a potential new therapy for ALS patients. While motor neuron replacement remains a focus of some studies trying to treat ALS with stem cells, there is more rationale for using stem cells as support cells for dying motor neurons as they are already connected to the muscle. This could be through reducing inflammation, releasing growth factors, and other potential less understood mechanisms. Prior to moving into patients, stringent pre-clinical studies are required that have at least some rationale and efficacy in animal models and good safety profiles. However, given our poor understanding of what causes ALS and whether stem cells may ameliorate symptoms, there should be a push to determine cell safety in pre-clinical models and then a quick translation to the clinic where patient trials will show if there is any efficacy. Here, we provide a critical review of current clinical trials using either mesenchymal or neural stem cells to treat ALS patients. Pre-clinical data leading to these trials, as well as those in development are also evaluated in terms of mechanisms of action, validity of conclusions and rationale for advancing stem cell treatment strategies for this devastating disorder.
Topics: Amyotrophic Lateral Sclerosis; Animals; Clinical Trials as Topic; History, 20th Century; History, 21st Century; Humans; Stem Cell Transplantation
PubMed: 24613827
DOI: 10.1016/j.expneurol.2014.02.021 -
Anesthesiology Apr 2020
Topics: Anesthesiology; Clinical Trials as Topic; Humans; Practice Guidelines as Topic
PubMed: 32053562
DOI: 10.1097/ALN.0000000000003162 -
Therapie 2022Clinical research in outpatient healthcare, particularly in general practice, which is the first line of contact with the population, is now a public health issue....
Clinical research in outpatient healthcare, particularly in general practice, which is the first line of contact with the population, is now a public health issue. However, this type of research has specific characteristics that differentiate it from clinical research conducted in a hospital setting and requires an adaptation of its conditions of practice: in terms of organisation, the development of research in outpatient healthcare relies on the appropriation of its fundamentals by the investigators, which implies their presentation, upstream, from the initial cycle, and the participation of practitioners in training modules adapted to research in primary care, such as those already organised by several GIRCI (Groupement Inter régional de la Recherche Clinique et de l'Innovation [French Interregional Clusters for Clinical Research and Innovation]). To compensate for the fragmented nature of their location, on the model of the EMRCs (équipes mobiles de recherche clinique [mobile clinical research teams]) in oncology, mobile research teams should enable general medical practices to participate in clinical trials. This presupposes, on the one hand, the allocation of earmarked funding to ensure the sustainability of a base of dedicated personnel and, on the other hand, the impetus of a national dynamic through the setting up of a multi-organisation thematic institute for "research in primary care" associated, at the operational level, with a national scale investigation network supported by a platform of excellence. The use of digital tools and innovations (telemedicine; data collection via connected tools; e-consent; electronic signature) which make it possible to digitise and relocate all or part of the research procedures for both the participant and the investigation teams. An adaptation of the legal framework in order to bring the place of research closer to the patient and not the other way round, which means moving the equipment and investigations closer to the patient. Taking into account the acceptability of the patient, thus limiting the disruption that may be caused by his or her participation in a research protocol and motivating the practitioner by valuing his or her contribution and providing all the guarantees of scientific relevance and independence of practice. In view of the contextual analysis, positive feedback and the availability of organisational and digital support points facilitating the delocalisation and digitisation of the conduct of research activity as close as possible to the patient and his or her doctor, the round table concluded that opportunities exist today which favour the development of clinical research in general practice. It is important to seize this opportunity and make the most of it without delay.
Topics: Ambulatory Care; Clinical Trials as Topic; Critical Pathways; Female; Hospitals; Humans; Male; Physicians
PubMed: 35090752
DOI: 10.1016/j.therap.2022.01.004