scholarly journals Risks of using pre-event time scale and ordinal scale measurements in COVID-19 clinical trials

2021 ◽  
pp. 32-37
Author(s):  
M.V. Yashchenko
Keyword(s):  
Clinical Trials ◽  
Clinical Outcome ◽  
Oxygen Therapy ◽  
Resource Dependence ◽  
Hospital Admissions ◽  
Outcome Data ◽  
Phase Iii ◽  
Ordinal Scale ◽  
Time To Event ◽  
Ordinal Scales

BACKGROUND. The article shows the results of literature search and analysis of endpoints of interventional clinical trials of phase III-IV of the treatment of hospitalized patients with coronavirus disease (COVID-19) and of its prevention. MATERIALS AND METHODS. Among 102 trials found, ordinal scales were used in 60 trials, time-to-event outcome measures were used in 54 trials, both scales – in 49 trials. Time-to-event endpoints were related to hospitalization/intensive care unit term, discontinuation of oxygen therapy, and clinical improvement standardized on ordinal scales. At the same time, the early discontinuation of oxygen therapy and the early discharge create risks to the biometric measurement. RESULTS AND DISCUSSION. Statistical calculations showed the association of the number of new COVID-19 hospital admissions per day with the percentage of free beds, but not only with the number of new coronavirus infection cases in general, the number of deaths and the number of people recovering from COVID-19 per day in different regions of Ukraine. These results may indicate that resource-dependence and organizational aspects affect the hospitalization of patients with COVID-19. CONCLUSIONS. Therefore, to ensure that the discharge or discontinuation of oxygen therapy was due solely to a positive clinical outcome, data on changes of number of beds, access to oxygen supplies as well as data relevant to determination of the desired clinical outcome (body temperature, oxygen saturation, severity of symptoms, etc.) should be collected. It is recommended to collect biomarker data after discharge, if possible.

scholarly journals Bayesian Joint Models for Longitudinal and Multi-state Survival Data

2019 ◽  
Vol 8 (2) ◽  
pp. 34
Author(s):  
Josua Mwanyekange ◽  
Samuel Musili Mwalili ◽  
Oscar Ngesa
Keyword(s):  
Clinical Trials ◽  
Survival Data ◽  
Phase Iii ◽  
Dependence Structure ◽  
Linear Mixed Effect Model ◽  
Time To Event ◽  
Joint Models ◽  
Mixed Effect ◽  
State Process ◽  
Proportional Intensity

Joint models for longitudinal and time to event data are frequently used in many observational studies such as clinical trials with the aim of investigating how biomarkers which are recorded repeatedly in time are associated with time to an event of interest. In most cases, these joint models only consider a univariate time to event process. However, many clinical trials of patients with cancer, involve multiple recurrences of a single event together with a single terminal event experienced by patients over time. Therefore, this article proposes joint modelling approachs for longitudinal and multi-state data. The approach considers two sub-models that are linked by a common latent random variable. The first sub-model is linear mixed effect model that defines the longitudinal process and the second sub-model is a proportional intensity function for the multi-state process. Furthermore, on the proportional intensity model, two different formulations are used to define dependence structure between longitudinal and multi-state processes. In this article, a semi-Markov process that consider the time spent in the current state is defined for the transitions between states. Moreover, the time spent in each transient state is assumed to have Gompertz distribution. A Bayesian method using Markov Chain Monte Carlo (MCMC) is developed for parameter estimation and inferences. The deviance information criterion (DIC) is also derived for Bayesian model selection and comparison. Finally, our proposed joint modeling approach is evaluated through a simulation study and is applied to real datasets (colorectal and colorectal.Longi) which present a random selection of 150 patients from a multi-center randomized phase III clinical trial FFCD 2000-05 of patients diagnosed with metastatic colorectal cancer.

scholarly journals A Web-based Tool for Automatically linking Clinical Trials to their Publications

2021 ◽  
Author(s):  
Neil R. Smalheiser ◽  
Arthur W. Holt
Keyword(s):  
Clinical Trials ◽  
Clinical Outcome ◽  
Evidence Synthesis ◽  
Outcome Data ◽  
Uncertain Process ◽  
Multiple Features ◽  
Web Based ◽  
Policy Makers ◽  
Objective Evidence ◽  
Ranked List

Objective. Evidence synthesis teams, physicians, policy makers, and patients and their families all have an interest in following the outcomes of clinical trials and would benefit from being able to evaluate both the results posted in trial registries and in the publications that arise from them. Manual searching for publications arising from a given trial is a laborious and uncertain process. We sought to create a statistical model to automatically identify PubMed articles likely to report clinical outcome results from each registered trial in ClinicalTrials.gov. Materials and Methods. A machine learning-based model was trained on pairs (publications linked to specific registered trials). Multiple features were constructed based on the degree of matching between the PubMed article metadata and specific fields of the trial registry, as well as matching with the set of publications already known to be linked to that trial. Results. Evaluation of the model using NCT-linked articles as gold standard showed that they tend to be top ranked (median best rank = 1.0), and 91% of them are ranked in the top ten. Discussion. Based on this model, we have created a free, public web based tool at http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/TrialPubLinking/trial_pub_link_start.cgithat, given any registered trial in ClinicalTrials.gov, presents a ranked list of the PubMed articles in order of estimated probability that they report clinical outcome data from that trial. The tool should greatly facilitate studies of trial outcome results and their relation to the original trial designs.

Abstract WMP103: Comparative Impact of Extent of Lobar Intracerebral Hemorrhage Removal on Outcome in the MISTIE III and STICH II Trials

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sean P Polster ◽  
Julian Carrion-Penagos ◽  
Barbara A Gregson ◽  
Ying Cao ◽  
Richard E Thompson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Outcome ◽  
Minimally Invasive ◽  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Phase Iii ◽  
Surgical Interventions ◽  
Hematoma Evacuation ◽  
Functional Benefit ◽  
End Of Treatment

Introduction: The Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation Phase III trial (MISTIE III) concluded that the extent of hematoma reduction confers a mortality and functional benefit. It is unclear if a minimum extent of evacuation is needed for mortality and functional outcome benefit in lobar cases with MISTIE and with open surgical interventions. Objective: We analyzed the effect of extent of lobar ICH evacuation on clinical outcome at 180 days after undergoing the MISTIE procedure and open craniotomy, in the context of the MISTIE III and STICH II clinical trials, respectively. Methods: Patients randomized to the surgical arm with lobar ICH, who underwent the procedure in the MISTIE III trial (n=84) and the STICH II trial (n=266) were analyzed, excluding cases crossing over to surgery. We assessed end of treatment ICH volume on post procedure CT scans and % hematoma evacuation, in relation to survival and likelihood of mRS 0-3. Cubic spline modeling with dichotomized outcome was used to compare the extent of hematoma evacuation on clinical outcome. Results: End of treatment volume of < 28 mL in lobar ICH MISTIE III patients and < 30 mL in STICH II trial patients showed a significantly increased probability of achieving an mRS of 0-3 at 180 days (p<0.03, p<0.006, respectively). This threshold was achieved in 83.1% of lobar cases undergoing MISTIE and in 92.1% of surgical cases in STICH II. Achieving survival benefit at 180 days trended towards improved probability with further hematoma volume reduction without a threshold value in MISTIE III, and was significant per mL reduction in STICH II (p<0.001). Analysis by percent of hematoma evacuation trended toward better probabilities of survival and improved functional outcome but were not significant. Conclusion: This analysis confirms that extent of hematoma evacuation is important in attaining the benefits of both minimally invasive and open surgical interventions in non-herniating lobar ICH patients randomized in clinical trials. Extent of ICH evacuation must be considered in the analysis of comparative effectiveness of various techniques and in the design of future trials.

Physical and Biological Basis of Proton and of Carbon Ion Radiation Therapy and Clinical Outcome Data

2009 ◽  
Vol 02 (01) ◽  
pp. 1-15 ◽  
Author(s):  
Herman Suit ◽  
Thomas F. Delaney ◽  
Alexei Trofimov
Keyword(s):  
Clinical Trials ◽  
Radiation Therapy ◽  
Dose Distribution ◽  
Particle Beam ◽  
Initial Energy ◽  
Outcome Data ◽  
Ion Beams ◽  
Phase Iii ◽  
Dose Fractionation ◽  
Carbon Ion

There is a clear basis in physics for the clinical use of proton and carbon beams in radiation therapy, namely, the finite range of the particle beam. The range is dependent on the beam initial energy, density and atomic composition of tissues along the beam path. Beams can be designed that penetrate to the required depth and deliver a uniform biologically effective dose across the depth of interest. The yield is a superior dose distribution relative to photon beams. There is a potential clinical advantage from the high linear energy transfer (LET) characteristics of carbon beams. This is based on a lower oxygen enhancement ratio (OER) and a flatter age response function. However, due to uncertainties relating OER with relative biological effectiveness (RBE), there is no clinical evidence to date that carbon ion beams have an advantage over proton beams. We strongly support performance Phase III clinical trials of protons vs carbon ion beams designed to feature a single variable, LET. Dose fractionation would be identical in both arms and dose distribution would be similar for the sites to be tested. For sites for which the carbon beam has a demonstrated important advantage in comparative treatment planning due to the narrower penumbra would not be selected for the clinical trials.

Rome I versus Rome II; Overlap in patients enrolled in tegaserod phase III clinical trials for irritable bowel syndrome (IBS)

2001 ◽  
Vol 120 (5) ◽  
pp. A284-A284
Author(s):  
B NAULT ◽  
S SUE ◽  
J HEGGLAND ◽  
S GOHARI ◽  
G LIGOZIO ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Irritable Bowel ◽  
Rome I

Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials

2001 ◽  
Vol 28 (6) ◽  
pp. 620-625 ◽  
Author(s):  
Pierre Falardeau ◽  
Pierre Champagne ◽  
Patrick Poyet ◽  
Claude Hariton ◽  
[Eacute]ric Dupont
Keyword(s):  
Clinical Trials ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Naturally Occurring ◽  
Antiangiogenic Drug

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

A Multivariate Approach to Analyze Ordinal Data Collected in Clinical Trials of Analgesic Agents

1979 ◽  
Vol 18 (03) ◽  
pp. 175-179
Author(s):  
E. Mabubini ◽  
M. Rainisio ◽  
V. Mandelli
Keyword(s):  
Clinical Trials ◽  
Multivariate Analysis ◽  
Analgesic Effect ◽  
Ordinal Data ◽  
Ordinal Scale ◽  
Multivariate Approach ◽  
Controlled Clinical Trials ◽  
Second Stage ◽  
Analgesic Agents ◽  
Relevant Factors

After pointing out the drawbacks of the approach commonly used to analyze the data collected in controlled clinical trials carried out to evaluate the analgesic effect of potential agents, the authors suggest a procedure suitable for analyzing data coded according to an ordinal scale. In the first stage a multivariate analysis is carried out on the codec! data and the projection of each result in the space of the most relevant factors is obtained. In the second stage the whole set of these values is processed by distribution-free tests. The procedure has been applied to data previously published by VENTAITBIDDA et al. [18].

Stroke Prevention in Non-Valvular Atrial Fibrillation

1997 ◽  
Vol 17 (03) ◽  
pp. 166-169
Author(s):  
Judith O’Brien ◽  
Wendy Klittich ◽  
J. Jaime Caro
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Care Home ◽  
Relevant Literature ◽  
Clinical Trial Data ◽  
Outcome Data ◽  
Sensitivity Analyses ◽  
Bleeding Events ◽  
Discharge Data ◽  
The Cost

SummaryDespite evidence from 6 major clinical trials that warfarin effectively prevents strokes in atrial fibrillation, clinicians and health care managers may remain reluctant to support anticoagulant prophylaxis because of its perceived costs. Yet, doing nothing also has a price. To assess this, we carried out a pharmacoe-conomic analysis of warfarin use in atrial fibrillation. The course of the disease, including the occurrence of cerebral and systemic emboli, intracranial and other major bleeding events, was modeled and a meta-analysis of the clinical trials and other relevant literature was carried out to estimate the required probabilities with and without warfarin use. The cost of managing each event, including acute and subsequent care, home care equipment and MD costs, was derived by estimating the cost per resource unit, the proportion consuming each resource and the volume of use. Unit costs and volumes of use were determined from established US government databases, all charges were adjusted using cost-to-charge ratios, and a 3% discount rate was applied to costs incurred beyond the first year. The proportions of patients consuming each resource were estimated by fitting a joint distribution to the clinical trial data, stroke outcome data from a recent Swedish study and aggregate ICD-9 specific, Massachusetts discharge data. If nothing is done, 3.2% more patients will suffer serious emboli annually and the expected annual cost of managing a patient will increase by DM 2,544 (1996 German Marks), from DM 4,366 to DM 6,910. Extensive multiway sensitivity analyses revealed that the higher price of doing nothing persists except for very extreme combinations of inputs unsupported by literature or clinical standards. The price of doing nothing is thus so high, both in health and economic terms, that cost-consciousness as well as clinical considerations mandate warfarin prophylaxis in atrial fibrillation.

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