scholarly journals Modern achievements in pharmacotherapy of osteoarthritis based on endo- and phenotyping

2021 ◽  
Vol 14 (3) ◽  
pp. 379-406
Author(s):  
I. V. Sarvilina ◽  
O. A. Shavlovskaya ◽  
O. A. Gromova ◽  
A. V. Naumov ◽  
M. N. Sharov ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Medical Literature ◽  
Diagnosis And Treatment ◽  
Alternative Methods ◽  
Controlled Trials ◽  
Disease Phenotypes ◽  
Randomized Controlled ◽  
Methodological Approaches

The review of medical literature is devoted to modern data in the field of diagnosis and treatment of osteoarthritis using endo- and phenotyping. It includes the latest data on the epidemiology of osteoarthritis of different localizations, modern definitions and classifications of osteoarthritis endotypes and phenotypes, pathobiochemical patterns and pathomorphological parallels of disease phenotypes, new methodological approaches to the phenotyping of osteoarthritis (prognostic, prescriptive phenotyping, alternative methods), as well as modern advances in pharmacotherapy of the disease based on data from selected randomized controlled trials and meta-analyzes.

scholarly journals Improving Power and Accuracy in Randomized Controlled Trials of Pain Treatments by Accounting for Concurrent Analgesic Use: Statistical Simulations and Analyses of Randomized Controlled Trial Data

2021 ◽  
Author(s):  
Pradeep Suri ◽  
Patrick J Heagerty ◽  
Anna Korpak ◽  
Mark P Jensen ◽  
Laura S Gold ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Pain Intensity ◽  
Rating Scale ◽  
Controlled Trial ◽  
Simulated Data ◽  
Alternative Methods ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Analytic Methods ◽  
Analgesic Use

The 0 to 10 numeric rating scale (NRS) of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between 'observed' pain intensity (the NRS, irrespective of concurrent analgesic use), and 'underlying' pain intensity (what the NRS would be had concurrent analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections (LESI). The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to observed pain intensity for those who were taking an analgesic (the QPAC1.5) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC1.5 as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs.

scholarly journals The randomised controlled trial in medical research: using bibliometric methods to identify core journals

2006 ◽  
Vol 1 (1) ◽  
pp. 104
Author(s):  
John Loy
Keyword(s):  
Growth Rate ◽  
Drug Therapy ◽  
Randomized Controlled Trials ◽  
Detailed Analysis ◽  
Medical Literature ◽  
Controlled Trial ◽  
The United States ◽  
Growth Patterns ◽  
Controlled Trials ◽  
Randomized Controlled

A review of: Tsay, Migh-yueh, and Yen-hsu Yang. “Bibliometric Analysis of the Literature of Randomized Controlled Trials.” Journal of the Medical Library Association 93.4 (October 2005): 450-58. Objective – To explore the characteristics and distribution of randomized controlled trials (RCTs) in the medical literature. The study aims to identify the growth patterns of the RCT, key subject matter, country and language of publication, and determine a list of core journals which contain a substantial proportion of the RCT literature. Design – Retrospective analysis of RCTs. Setting – Medical journal literature. Subjects – A total of 160,213 articles published between 1965-2001. Detailed analysis of a subset numbering 114,850 articles published from 1990-2001. Methods – The study seeks to identify all RCTs in MEDLINE from 1965-2001, and examines the growth rate of the RCT. The authors then do a more detailed analysis on a subset of data from 1990-2001, using Access database and Excel spreadsheet software, and PERL programming language. The references were analyzed by five fields within MEDLINE; publication type, source, language, country of publication, and descriptor (subject index). Main results – An exponential growth rate for the RCT is demonstrated, suggesting that in the medical literature development has not yet matured and that research using this method continues to grow. A growth rate for the RCT of 11.2% per annum is identified. The most common form of publication is the journal article, making up approximately 98% of the RCT literature. Approximately 75% of the RCTs are multicentre trials indicating that this is the design of choice adopted by researchers. The United States proves to be the greatest source of RCT literature, with 39.9% of journals and 50.6% of articles originating there. After the USA, the most productive countries are England (15.8% of journals and 21.7% articles) and Germany (6.5% journals and 6.1% articles). As might be expected, English is the predominant language providing 92.9% of the total publications. Of the remaining 7%, German is the most common language accounting for 2.2%. The top three areas being researched are: 1. Drug therapy for hypertension - 2291 citations 2. Anticancer drug combinations - 2140 citations 3. Drug therapy and asthma - 1397 citations Bradford’s law of scattering is successfully applied, identifying four zones of journals which each publish approximately 26,000 articles. Conclusion – The results indicate that bibliometric methods can be applied to the medical literature, and highlight those disciplines in which RCTs more often occur. A core list of 42 journal titles is presented, providing busy practitioners with invaluable guidance as to which journals are most likely to publish the greater number of RCTs.

Ethics of RCTs

2020 ◽  
pp. 280-292
Author(s):  
Michel Abramowicz ◽  
Ariane Szafarz
Keyword(s):  
Social Sciences ◽  
Randomized Controlled Trials ◽  
Development Economics ◽  
Medical Literature ◽  
Control Group ◽  
Controlled Trials ◽  
Clinical Investigator ◽  
Randomized Controlled ◽  
Ex Ante

Equipoise is defined by Freedman (1987: 141) as a “state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial.” This principle is grounded in the ethical motivation that any ex-ante preference for a given option would undermine the interests of those who are offered another. Randomized controlled trials (RCTs) in development economics disregard the equipoise requirement by typically disadvantaging the control group. This chapter investigates how the equipoise principle is formalized in the medical literature and discusses whether and how it should be taken into consideration by economists. It argues that equipoise is especially relevant when double (or even single) blindness is excluded and when the control group includes already vulnerable individuals. More generally, this chapter advocates for developing a vibrant ethics conversation on the design and fairness of RCTs in social sciences.

Empirical power comparison of statistical tests in contemporary phase III randomized controlled trials with time-to-event outcomes in oncology

2020 ◽  
Vol 17 (6) ◽  
pp. 597-606
Author(s):  
Miki Horiguchi ◽  
Michael J Hassett ◽  
Hajime Uno
Keyword(s):  
Randomized Controlled Trials ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Alternative Methods ◽  
Rank Test ◽  
Controlled Trials ◽  
Empirical Power ◽  
Randomized Controlled ◽  
Log Rank Test

Background: More than 95% of recent cancer randomized controlled trials used the log-rank test to detect a treatment difference making it the predominant tool for comparing two survival functions. As with other tests, the log-rank test has both advantages and disadvantages. One advantage is that it offers the highest power against proportional hazards differences, which may be a major reason why alternative methods have rarely been employed in practice. The performance of statistical tests has traditionally been investigated both theoretically and numerically for several patterns of difference between two survival functions. However, to the best of our knowledge, there has been no attempt to compare the performance of various statistical tests using empirical data from past oncology randomized controlled trials. So, it is unknown whether the log-rank test offers a meaningful power advantage over alternative testing methods in contemporary cancer randomized controlled trials. Focusing on recently reported phase III cancer randomized controlled trials, we assessed whether the log-rank test gave meaningfully greater power when compared with five alternative testing methods: generalized Wilcoxon, test based on maximum of test statistics from multiple weighted log-rank tests, difference in t-year event rate, and difference in restricted mean survival time with fixed and adaptive [Formula: see text]. Methods: Using manuscripts from cancer randomized controlled trials recently published in high-tier clinical journals, we reconstructed patient-level data for overall survival (69 trials) and progression-free survival (54 trials). For each trial endpoint, we estimated the empirical power of each test. Empirical power was measured as the proportion of trials for which a test would have identified a significant result ( p value < .05). Results: For overall survival, t-year event rate offered the lowest (30.4%) empirical power and restricted mean survival time with fixed [Formula: see text] offered the highest (43.5%). The empirical power of the other types of tests was almost identical (36.2%–37.7%). For progression-free survival, the tests we investigated offered numerically equivalent empirical power (55.6%–61.1%). No single test consistently outperformed any other test. Conclusion: The empirical power assessment with the past cancer randomized controlled trials provided new insights on the performance of statistical tests. Although the log-rank test has been used in almost all trials, our study suggests that the log-rank test is not the only option from an empirical power perspective. Near universal use of the log-rank test is not supported by a meaningful difference in empirical power. Clinical trial investigators could consider alternative methods, beyond the log-rank test, for their primary analysis when designing a cancer randomized controlled trial. Factors other than power (e.g. interpretability of the estimated treatment effect) should garner greater consideration when selecting statistical tests for cancer randomized controlled trials.

Rethinking the Gold Standard With Multi-armed Bandits: Machine Learning Allocation Algorithms for Experiments

2019 ◽  
Vol 24 (1) ◽  
pp. 78-103
Author(s):  
Chris Kaibel ◽  
Torsten Biemann
Keyword(s):  
Machine Learning ◽  
Randomized Controlled Trials ◽  
Machine Learning Algorithms ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Treatment Conditions ◽  
Scientific Disciplines ◽  
New Information ◽  
Methodological Approaches ◽  
Allocation Algorithms

In experiments, researchers commonly allocate subjects randomly and equally to the different treatment conditions before the experiment starts. While this approach is intuitive, it means that new information gathered during the experiment is not utilized until after the experiment has ended. Based on methodological approaches from other scientific disciplines such as computer science and medicine, we suggest machine learning algorithms for subject allocation in experiments. Specifically, we discuss a Bayesian multi-armed bandit algorithm for randomized controlled trials and use Monte Carlo simulations to compare its efficiency with randomized controlled trials that have a fixed and balanced subject allocation. Our findings indicate that a randomized allocation based on Bayesian multi-armed bandits is more efficient and ethical in most settings. We develop recommendations for researchers and discuss the limitations of our approach.

scholarly journals Rivaroxaban versus Aspirin in Prevention of Venous Thromboembolism: A Meta-Analysis of 9 Randomized Controlled Trials comprising 7,656 Patients

2019 ◽  
Vol 119 (09) ◽  
pp. 1517-1526
Author(s):  
Jian Xie ◽  
Mingyang Jiang ◽  
Yunni Lin ◽  
Huachu Deng ◽  
Xiaoyong Xie ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Randomized Controlled Trials ◽  
Medical Literature ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Negative Side Effects ◽  
Preventive Effects ◽  
Risk Ratios

Aim This article evaluates the preventive effects of rivaroxaban versus aspirin on venous thromboembolism (VTE) through meta-analysis of recent randomized controlled trials (RCTs). Methods RCTs were retrieved from medical literature databases. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare the primary and safety endpoints. Results In total, 9 trials (11 trial comparisons) were retrieved which contained 7,656 patients. Among these patients, 4,383 patients (57.2%) received rivaroxaban, whereas 3,273 patients (42.8%) received aspirin. Compared with aspirin, rivaroxaban significantly reduced VTE (1.3% vs. 3.5%) (RR: 0.36, 95% CI, 0.26–0.48, I 2 = 27.9%), but significantly increased nonmajor bleeding (11.5% vs. 7.5%) (RR: 1.28, 95% CI, 1.13–1.44, I 2 = 38.6%). There were no significant differences in the all-cause mortality (0.3% vs. 0.3%) (RR: 0.75, 95% CI, 0.35–1.61, I 2 = 32.0%) and major bleeding (0.3% vs. 0.4%) (RR: 0.81, 95% CI, 0.42–1.55, I 2 = 33.7%) between the two groups. Conclusion This meta-analysis indicated that rivaroxaban can significantly reduce the incidence of VTE when compared with aspirin. The preventive effect of rivaroxaban on VTE was more potent than that of aspirin. However, rivaroxaban had some negative side effects to patients such as nonmajor bleeding compared to aspirin.

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