scholarly journals Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

2021 ◽  
pp. ASN.2021070948
Author(s):  
Brendon Neuen ◽  
Hocine Tighiouart ◽  
Hiddo Heerspink ◽  
Edward Vonesh ◽  
Juhi Chaudhari ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Kidney Disease ◽  
Disease Progression ◽  
Acute Treatment ◽  
Treatment Effects ◽  
Randomized Clinical Trials ◽  
Acute Effects ◽  
Long Term Treatment ◽  
The Mean ◽  
Acute Changes

Background Acute changes in glomerular filtration rate (GFR) can occur following initiation of interventions targeting progression of chronic kidney disease (CKD). These acute changes complicate the interpretation of long-term treatment effects. Methods To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression enrolling 56,413 participants with at least one estimated GFR measurement by 6 months following randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable meta-regression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. Results The mean acute effect across all studies was -0.21 mL/min per 1.73m2 (95% confidence interval, -0.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, -2.50 to +2.08 mL/min per 1.73m2). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR. Conclusion The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD.

scholarly journals Estimating and reporting treatment effects in clinical trials for weight management: using estimands to interpret effects of intercurrent events and missing data

2021 ◽  
Author(s):  
Sean Wharton ◽  
Arne Astrup ◽  
Lars Endahl ◽  
Michael E. J. Lean ◽  
Altynai Satylganova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Missing Data ◽  
Weight Management ◽  
Treatment Effect ◽  
Repeated Measures ◽  
Treatment Effects ◽  
Randomized Clinical Trials ◽  
Weight Losses ◽  
The Difference ◽  
Treatment Of Obesity

AbstractIn the approval process for new weight management therapies, regulators typically require estimates of effect size. Usually, as with other drug evaluations, the placebo-adjusted treatment effect (i.e., the difference between weight losses with pharmacotherapy and placebo, when given as an adjunct to lifestyle intervention) is provided from data in randomized clinical trials (RCTs). At first glance, this may seem appropriate and straightforward. However, weight loss is not a simple direct drug effect, but is also mediated by other factors such as changes in diet and physical activity. Interpreting observed differences between treatment arms in weight management RCTs can be challenging; intercurrent events that occur after treatment initiation may affect the interpretation of results at the end of treatment. Utilizing estimands helps to address these uncertainties and improve transparency in clinical trial reporting by better matching the treatment-effect estimates to the scientific and/or clinical questions of interest. Estimands aim to provide an indication of trial outcomes that might be expected in the same patients under different conditions. This article reviews how intercurrent events during weight management trials can influence placebo-adjusted treatment effects, depending on how they are accounted for and how missing data are handled. The most appropriate method for statistical analysis is also discussed, including assessment of the last observation carried forward approach, and more recent methods, such as multiple imputation and mixed models for repeated measures. The use of each of these approaches, and that of estimands, is discussed in the context of the SCALE phase 3a and 3b RCTs evaluating the effect of liraglutide 3.0 mg for the treatment of obesity.

scholarly journals Efficacy of Enamel Derivatives to Improve Keratinized Tissue as Adjunct to Coverage of Gingival Recessions: A Systematic Review and Meta-Analysis

Materials ◽  
2019 ◽  
Vol 12 (17) ◽  
pp. 2790
Author(s):  
Nicola Discepoli ◽  
Raffaele Mirra ◽  
Marco Ferrari
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Enamel Matrix ◽  
Lower Upper ◽  
Coronally Advanced Flap ◽  
Keratinized Tissue ◽  
Enamel Matrix Derivatives ◽  
The Mean ◽  
Matrix Derivatives

Background: The systematic review was designed to answer the following focused question: Are enamel matrix derivatives able to improve the quantity of keratinized tissue (KT) around natural dentition in patients with recessions defects after their treatment with periodontal plastic procedures? Methods: Only Randomized Clinical Trials (RCT) in English language evaluating root coverage procedures in combination with enamel matrix derivatives (commercially known as Emdogain®—EMD), with at least 10 subjects and a minimum duration of six months, were included. The search was applied to PUBMED and SCOPUS and it consists of a combination of MeSH terms and free text words (from January 2000 to June 2019). Risk of bias in individual studies and across studies was also evaluated. Results: After the full text analysis and the exclusion of further 18 articles, 12 articles were finally included. In total 639 recessions were treated (334 tests and 305 control). The recessions defects were classified according to the classification of Miller (Class I, II, III, IV). Only one trial included Miller Class III recessions (7 in total). Enamel matrix derivatives were applied in conjunction with Coronally Advanced Flap (CAF), Coronally Advanced Flap + Sub Epithelial Connective Tissue Graft (CAF + CTG), Semilunar Flap (SF). For the group CAF vs CAF + EMD the mean difference between the keratinized tissue gain in the two procedures was 0.40 mm (95% Confindence Interval Lower/Upper: 0.014–0.81) (p < 0.058); for the comparison CAF + CTG + EMD vs. CAF + CTG the mean difference between the two groups resulted in −0.06 mm (95% Confindence Interval Lower Upper −0.45 to 0.33) (p = 0.7603). Discussion: Randomized clinical trials included medium-low quality evidence. The application of Enamel Matrix Derivatives to surgical procedures aimed to cover gingival recessions does not add robust clinical benefit to conventional plastic procedure alone.

Estimating Treatment Effects in Clinical Trials Subject to Regression to the Mean

Biometrics ◽  
1985 ◽  
Vol 41 (2) ◽  
pp. 555 ◽  
Author(s):  
Stephen J. Senn ◽  
Richard A. Brown ◽  
K. E. James
Keyword(s):  
Clinical Trials ◽  
Treatment Effects ◽  
Regression To The Mean ◽  
The Mean
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