SO063POOR REPORTING AND CONDUCT OF CLUSTER AND CROSSOVER RANDOMISED TRIALS IN THE HAEMODIALYSIS POPULATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Prachi Kaushal ◽  
Daniel March ◽  
Helen Eborall ◽  
Laura Gray ◽  
James Burton
Keyword(s):  
Sample Size ◽  
Cluster Size ◽  
Primary Outcome ◽  
Statistical Significance ◽  
Attrition Rate ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomised Trials ◽  
Stepped Wedge ◽  
Crossover Trials

Abstract Background and Aims There are fewer trials conducted in nephrology than any other speciality. Many trials fail to recruit to target and are therefore underpowered, resulting in unclear evidence and unlikely to be implemented into clinical practice. Carefully designed trials could improve the treatment options for haemodialysis patients. These could include designs other than individually randomised parallel group designs. We have reviewed cluster, stepped wedge and crossover randomised trials carried out in prevalent haemodialysis patients. Method A search for randomised controlled trials (RCTs) in haemodialysis patients was conducted across five databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) in October 2019. The first publication of a stepped wedge trial in haemodialysis was in 2013, so we searched from 2013-2019. Inclusion criteria were RCTs including adults receiving at least 3 months of haemodialysis. Once eligible studies were identified, we compared the sample size sections to the CONSORT requirements and extracted data on these parameters and assessed recruitment targets, attrition rates and primary outcome result. Results We identified 911 RCTs of which 13 (1.4%) cluster randomised trials, including one stepped wedge, and 145 (15.9%) crossover trials were identified. Data were extracted for 10 randomly selected crossover trials. The total sample size required was not reported in 46% (n=6) cluster trials and 60% (n=6) crossover trials, with only 37.5% (n=3) of cluster trials and 50% (n=4) of crossover trials providing a justification for their sample size. In cluster trials, 13% (n=1) stated number of clusters required and 25% (n=2) gave the average cluster size, none of these stated the anticipated variance in cluster size and only 12.5% (n=1) stated the intracluster correlation (ICC) used to calculate the sample size, with none taking into account uncertainty in ICC. In 31% (n=4) of the cluster trials, the dialysis centre was the cluster and in the other 69% (n=9), the dialysis shift was the cluster. For crossover trials, within participant variability was only accounted for in 12.5% (n=1) of trials. A CONSORT flow diagram was reported in 70% of the trials assessed, with 39% recruiting to target. There were also some differences seen between crossover and cluster designs. The average number of participants at the start of a cluster trial was 470, compared to 26 in crossover trials. Where able to assess, cluster trials had an average attrition rate of 25% this was lower in crossover trials, where the average attrition rate was 14%. Eighty five percent (n=11) of cluster trials had a primary outcome reaching statistical significance, however only 20% (n=2) of crossover trials reached statistical significance. Conclusion Cluster and crossover randomised trials are poorly reported. There was insufficient information provided for sample size calculations to be replicated in majority of trials. The average attrition rate was low in crossover trials, however a large proportion of these trials did not have a primary outcome reaching statistical significance, suggesting these trials could have been underpowered. Improvements in the design, conduct and reporting of cluster and crossover trials in the haemodialysis population is urgently required.

Hydroxyurea for β-Thalassemia Major: A Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4894-4894 ◽  
Author(s):  
Ali H. Algiraigri ◽  
Nicola A. Wright ◽  
Aliya Kassam
Keyword(s):  
Sample Size ◽  
Clinical Efficacy ◽  
Observational Studies ◽  
Response Rate ◽  
Meta Analysis ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Controlled Trials ◽  
Cochrane Central Register

Abstract Background β-thalassemia major (β-TM) is one of the most common inherited diseases worldwide, characterized by a reduced ability to produce hemoglobin resulting in life-long transfusion-dependent anemia. Chronic transfusions carry significant risks such as infection, and result in iron overload that can cause significant multisystem organ damage. Hydroxyurea, an oral chemotherapeutic drug, is anticipated to decrease the need for transfusions, either completely or partially by raising hemoglobin levels and thus decreasing the short and long term complications of chronic transfusions. Objectives To evaluate the clinical efficacy and safety of hydroxyurea in β-thalassemia major (β-TM) patients of any age. Search strategy We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ongoing trials registers, and major preceding conferences. Hand searches were also conducted using reference lists from primary studies. All searches were updated to June 5, 2014. Selection criteria Randomized controlled trials (RCTs) and observational studies (sample size ≥ 5) assessing the clinical efficacy of hydroxyurea alone for three months or longer, for the treatment of patients with β-TM were included. Data collection and analysis Two authors acted as reviewers and independently assessed study quality and extracted data from the included studies. Authors of included studies were contacted if further information was required. β-TM includes the classical β-TM as well as severe hemoglobin E/β thalassemia, both of which are characterized by lifelong transfusion needs. The effect size was estimated as a proportion (those showing response to treatment over the total number treated) and reported as overall response rate (ORR) or complete response rate (CRR). ORR was defined as ≥ 50% reduction in transfusion need and CRR was defined as complete cessation of regular transfusion. All data was analyzed using Stata, Version 13.0. Results A total of 10 observational studies involving 620 patients were included. Hydroxyurea was associated with a statistically significant decrease in transfusion need with CRR of 36% (95% CI, 23-50%) and ORR of 66% (95% CI, 52-79%). All of the studies had several limitations, such as small sample size, lack of comparison group, under-reporting of data and methods, and being observational studies. Adverse events (AEs) were transient and improved with temporary cessation of the drug and/or adjustment of the dose. No long-term AEs, including cancer or end organ damage were reported. Authors’ conclusion Hydroxyurea appears to be effective in the management of β-TM by decreasing the need for chronic blood transfusions completely or partially in a significant number of patients. It appears to be well tolerated and associated with mild and transient AEs. Patients with β-TM may benefit from a trial of hydroxyurea, though large RCTs assessing efficacy should be done to confirm the findings of this meta-analysis. Disclosures Off Label Use: Hydroxyurea for β-Thalassemia.

scholarly journals Ridge Preservation Procedures after Tooth Extractions: A Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Gabriella Balli ◽  
Andreas Ioannou ◽  
Charles A. Powell ◽  
Nikola Angelov ◽  
Georgios E. Romanos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Data Analysis ◽  
Bone Resorption ◽  
Sample Size ◽  
Controlled Trials ◽  
Ridge Preservation ◽  
Cochrane Central Register ◽  
Bovine Bone ◽  
Exclusion Criteria ◽  
Randomized Controlled

Background. The purpose of this systematic review was to accurately assess the procedural success of ridge preservation technique through the application of strict inclusion and exclusion criteria. Data Sources. A methodical search of PubMed of the US National Library of Medicine and the Cochrane Central Register of Controlled Trials was conducted for applicable articles. Only randomized controlled trials comparing ridge preservation treatment with a nongrafting control, ten-subject minimum sample size, and three or more months of follow-up were included in our study. Types of Studies Reviewed. In a screening between January 1980 and September 2017, articles meeting predetermined criteria were further examined in a qualitative data analysis. A thorough search of the databases provided 1876 articles. Of these records, 174 were assessed for eligibility through the systematic employment of inclusion and exclusion criteria. Results. Two records were appropriate for further data analysis. One study used a mixture of a deproteinized cancellous bovine bone and porcine collagen fibers in a block form (DBB/CF), while the other study used leukocyte-platelet-rich fibrin (L-PRF). The use of DBB/CF reduced the magnitude of vertical bone resorption, yet the study showed high risk of bias. The use of L-PRF reduced the magnitude of both the horizontal and vertical crestal bone resorption; however, the low sample size created wide standard deviations between the test and control groups. Inherent weaknesses were present in both studies. Through methodical analysis of both records, the dissimilarities prevented the conduction of a meta-analysis. Implications of Key Findings. Within the limitations of this systematic review, L-PRF reduced the magnitude of vertical and horizontal bone resorption, which places L-PRF as a potential material of choice for ridge preservation procedures. Conclusions. Within the limitations and weaknesses of both studies, the use of DBB/CF prevented the vertical crestal bone resorption while the L-PRF prevented both the horizontal and vertical crestal bone resorption. More randomized controlled clinical trials are needed to eliminate all the confounding factors, which bias the outcome of ridge preservation techniques.

scholarly journals Hydroxyurea for Non-Transfusion-Dependent β-Thalassemias: A Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4897-4897
Author(s):  
Ali H. Algiraigri ◽  
Nicola A. Wright ◽  
Aliya Kassam
Keyword(s):  
Sample Size ◽  
Clinical Efficacy ◽  
Observational Studies ◽  
Response Rate ◽  
Meta Analysis ◽  
Small Sample ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Hemoglobin E ◽  
Transfusion Requirements

Abstract Background Non-transfusion-dependent (NTD) β-thalassemia syndromes consist of β-thalassemia intermedia and moderate Hemoglobin E/ β thalassemias. They are characterized by varying degrees of chronic anemia and a wide spectrum of complications due to ineffective erythropoiesis and iron overload from chronic transfusions. Hydroxyurea, an oral chemotherapeutic drug, is anticipated to decrease disease severity by raising hemoglobin (Hb) levels and reducing transfusion requirements. Objectives To examine the evidence for clinical efficacy and safety of hydroxyurea in NTD β-thalassemia patients of any age. Search strategy We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ongoing trials registers, and major preceding conferences. Hand searches were also conducted using reference lists from primary studies. All searches were updated to June 5, 2014. Selection criteria Randomized controlled trials (RCTs) and observational studies (sample size ≥ 5) assessing the clinical efficacy of hydroxyurea alone for three months or longer, for the treatment of patients with NTD β-thalassemia were included. Data collection and analysis Two authors acted as reviewers and independently assessed study quality and extracted data from the included studies. Authors of included studies were contacted if further information was required. NTD β-thalassemia was sub-classified into two groups; mild (no or < 4 transfusion per year) and severe (≥4 transfusions per year). The effect size was estimated as a proportion (responders over sample size). For Mild-NTD-β-thalassemia, response rate (RR) was identified as a ≥10g/dL increase in Hb. In Severe-NTD-β-thalassemia, overall response rate (ORR) was defined as ≥ 50% reduction in transfusion need and complete response rate (CRR) was defined as complete cessation of regular transfusion. All data was analyzed using Stata, Version 13.0. Results For Mild-NTD β-thalassemia, a total of 14 studies (1 RCT and 13 observational studies) involving 344 patients met inclusion criteria. Hydroxyurea therapy was effective in raising Hb by 10g/dL from baseline in 56% (95% CI, 46-67%). In Severe-NTD-β-thalassemia, 8 studies (1 RCT and 7 observational studies) involving 305 patients were included. Hydroxyurea was associated with a statistically significant decrease in transfusion need with CRR of 53% (95% CI, 37-70%) and ORR of 79% (95% CI, 68-91%). All of the studies had several limitations, such as small sample size, lack of comparison group, under-reporting of data and methods, and the majority having been observational studies. Adverse events (AEs) were transient and improved with temporary cessation of the drug and/or adjustment of the dose. Author’s conclusion Hydroxyurea appears to be effective in the management of NTD β-thalassemia (both mild and severe forms) by raising the Hb by at least 10g/dL and decreasing the need for chronic blood transfusions completely or partially, respectively, in the majority of patients. It appears to be well tolerated and associated with mild and transient AEs. Patients with NTD β-thalassemia may benefit from a trial of hydroxyurea, though large RCTs assessing efficacy should be done to confirm the findings of this meta-analysis. Disclosures Off Label Use: Hydroxyurea for β-Thalassemia.

scholarly journals Exercise for premenstrual syndrome: a systematic review and meta-analysis of randomised controlled trials

BJGP Open ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. bjgpopen20X101032 ◽  
Author(s):  
Emma Pearce ◽  
Kate Jolly ◽  
Laura L Jones ◽  
Gemma Matthewman ◽  
Mandana Zanganeh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Premenstrual Syndrome ◽  
Randomised Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Current Evidence ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Exercise Interventions ◽  
Randomised Controlled

BackgroundExercise is recommended as a treatment for premenstrual syndrome (PMS) in clinical guidelines, but this is currently based on poor-quality trial evidence.AimTo systematically review the evidence for the effectiveness of exercise as a treatment for PMS.Design & settingThis systematic review searched eight major databases, including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), and two trial registries from inception until April 2019.MethodRandomised controlled trials (RCTs) comparing exercise interventions of a minimum of 8-weeks duration with non-exercise comparator groups in women with PMS were included. Mean change scores for any continuous PMS outcome measure were extracted from eligible trials and standardised mean differences (SMDs) were calculated where possible. Random-effects meta-analysis of the effect of exercise on global PMS symptoms was the primary outcome. Secondary analyses examined the effects of exercise on predetermined clusters of psychological, physical, and behavioural symptoms.ResultsA total of 436 non-duplicate returns were screened, with 15 RCTs eligible for inclusion (n = 717). Seven trials contributed data to the primary outcome meta-analysis (n = 265); participants randomised to an exercise intervention reported reduced global PMS symptom scores (SMD = -1.08; 95% confidence interval [CI] = -1.88 to -0.29) versus comparator, but with substantial heterogeneity (I2 = 87%). Secondary results for psychological (SMD = -1.67; 95% CI = -2.38 to -0.96), physical (SMD = -1.62; 95% CI = -2.41 to -0.83) and behavioural (SMD = -1.94; 95% CI = -2.45 to -1.44) symptom groupings displayed similar findings. Most trials (87%) were considered at high risk of bias.ConclusionBased on current evidence, exercise may be an effective treatment for PMS, but some uncertainty remains.

scholarly journals Cluster randomised trials with different numbers of measurements at baseline and endline: Sample size and optimal allocation

2019 ◽  
Vol 17 (1) ◽  
pp. 69-76
Author(s):  
Andrew J Copas ◽  
Richard Hooper
Keyword(s):  
Sample Size ◽  
Cluster Size ◽  
Randomised Trial ◽  
Sample Size Calculation ◽  
Baseline Data ◽  
Cluster Randomised Trial ◽  
Randomised Trials ◽  
Cluster Randomised Trials ◽  
Cluster Randomised ◽  
The Impact

Background/Aims: Published methods for sample size calculation for cluster randomised trials with baseline data are inflexible and primarily assume an equal amount of data collected at baseline and endline, that is, before and after the intervention has been implemented in some clusters. We extend these methods to any amount of baseline and endline data. We explain how to explore sample size for a trial if some baseline data from the trial clusters have already been collected as part of a separate study. Where such data aren’t available, we show how to choose the proportion of data collection devoted to the baseline within the trial, when a particular cluster size or range of cluster sizes is proposed. Methods: We provide a design effect given the cluster size and correlation parameters, assuming different participants are assessed at baseline and endline in the same clusters. We show how to produce plots to identify the impact of varying the amount of baseline data accounting for the inevitable uncertainty in the cluster autocorrelation. We illustrate the methodology using an example trial. Results: Baseline data provide more power, or allow a greater reduction in trial size, with greater values of the cluster size, intracluster correlation and cluster autocorrelation. Conclusion: Investigators should think carefully before collecting baseline data in a cluster randomised trial if this is at the expense of endline data. In some scenarios, this will increase the sample size required to achieve given power and precision.

scholarly journals Outcomes of coronavirus 2019 infection in patients with chronic kidney disease: a systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204062232199886
Author(s):  
Yi-Chih Lin ◽  
Tai-Shuan Lai ◽  
Shuei-Liong Lin ◽  
Yung-Ming Chen ◽  
Tzong-Shinn Chu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Case Series ◽  
Pooled Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
All Cause Mortality

Background: Information on coronavirus disease 2019 (COVID-19) infection in patients with chronic kidney disease (CKD) remains limited. To understand the influence of COVID-19 infection in patients with pre-existing CKD, we conducted a systematic review and meta-analysis to evaluate and compare the risks of all-cause mortality, hospitalization, and critical progression between patients with and without CKD. Methods: We selected randomized controlled trials (RCTs), prospective or retrospective observational, case-control, cross-sectional, and case-series studies analyzing outcomes of COVID-19 infection in patients with pre-existing CKD from the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases published on the Internet before 16 July 2020. Results: A total of 27 studies comprising 77,856 patients with COVID-19 infection was identified; 3922 patients with pre-existing CKD were assigned CKD group, and 73,934 patients were assigned to the non-CKD group. The pooled analysis showed that patients with CKD had a significantly higher risk of all-cause mortality and hospitalization than those without CKD [odds ratio (OR) 2.25, 95% confidence interval (CI) 1.91–2.66, p < 0.001; OR 4.29, 95% CI 2.93–6.28, p < 0.001; respectively]. Patients with CKD had a higher risk of critically ill conditions than those without CKD in the pooled analysis of studies with multivariable adjustment (adjusted OR 2.12, 95% CI 0.95–4.77, p = 0.07) and in the analysis of all included studies (OR 1.27, 95% CI 0.71–2.26, p = 0.41), but both analyses did not attain statistical significance. Conclusion: COVID-19 infected patients with CKD had significantly increased risks of all-cause mortality and hospitalization compared with those without CKD.

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