Randomised controlled trials evaluating endometrial scratching: assessment of methodological issues

2019 ◽  
Vol 34 (12) ◽  
pp. 2372-2380 ◽  
Author(s):  
Wentao Li ◽  
Sophie Suke ◽  
Dagmar Wertaschnigg ◽  
Sarah Lensen ◽  
Rui Wang ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Statistical Methods ◽  
Null Hypothesis ◽  
Randomised Controlled Trials ◽  
Trial Registration ◽  
Controlled Trials ◽  
Methodological Issues ◽  
Endometrial Scratching ◽  
Baseline Characteristics ◽  
Randomised Controlled

Abstract STUDY QUESTION Do randomised controlled trials (RCTs) evaluating endometrial scratching suffer from methodological issues including insufficient trial registration, statistical errors or irreproducibility, randomisation errors or miscellaneous issues? SUMMARY ANSWER The majority of RCTs investigating endometrial scratching have methodological issues. WHAT IS KNOWN ALREADY A large number of small RCTs investigating the effectiveness of endometrial scratching prior to in vitro fertilisation (IVF) and intrauterine insemination (IUI)/intercourse have reported favourable findings. Subsequently, systematic reviews incorporating these RCTs yielded meta-analyses in favour of endometrial scratching. Endometrial scratching has been widely adopted by infertility specialists around the world. Recently, an international RCT including 1364 women reported no benefit from endometrial scratching before IVF. STUDY DESIGN, SIZE, DURATION We evaluated several methodological issues of RCTs investigating the effectiveness of endometrial scratching prior to IVF and IUI/intercourse. We identified 25 RCTs for IVF and 12 RCTs for IUI/intercourse with full-text publication. PARTICIPANTS/MATERIALS, SETTING, METHODS We assessed the RCTs on the following criteria: adequacy of trial registration, statistical issues (description of statistical methods and reproducibility of univariable statistical analysis), excessive similarity or difference in baseline characteristics that is not compatible with chance (Monte Carlo simulations and Kolmogorov–Smirnov test) and miscellaneous methodological issues. MAIN RESULTS AND THE ROLE OF CHANCE Of 25 RCTs evaluating endometrial scratching prior to IVF, only eight (32%) had adequate trial registration. In total, 10 (40%) RCTs had issues regarding statistical methods. Nine (69%, 13 applicable) RCTs had at least one inconsistency between reported and reproduced univariable statistical analysis for categorical baseline/intermediate characteristics. Statistical results of at least one outcome were not reproducible in 14 (74%, 19 applicable) RCTs. Only two (8%) RCTs had none of the above issues. Suggested by the simulations, these RCTs did not significantly violate the null hypothesis that the baseline characteristics were the results of a properly conducted randomisation process (P = 0.4395). Of 12 IUI/intercourse RCTs, only 2 (17%) had adequate trial registration. In total, five (42%) studies had issues of statistical methods. Inconsistency between reported and reproduced univariable analysis for baseline/intermediate categorical variable(s) was found in four (57%, 7 applicable) RCTs. Statistical analysis was not reproducible for at least one outcome in eight (80%, 10 applicable) studies. All RCTs had at least one of the above issues. These RCTs were inconsistent with the null hypothesis that their baseline characteristics were the results of proper randomised allocation (P = 1.659*10−7). LIMITATIONS, REASONS FOR CAUTION We were unable to assess RCTs which were not published as full-text papers. We could not analyse individual participant data to investigate possible reasons for statistical inconsistencies. The method to infer the likelihood of proper random sampling rests on assumptions including independent baseline characteristics, simple randomisation and no publication bias. WIDER IMPLICATIONS OF THE FINDINGS The methodological issues common to RCTs evaluating endometrial scratching may have biased the results of the trials. Further development and validation of these novel methods may be helpful for the critical appraisal of RCTs. STUDY FUNDING/COMPETING INTEREST(S) No external funding was sought to support this work. B.W.M. is supported by a National Health Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck and Guerbet. D.W. is supported by a grant from the Paracelsus Medical University Salzburg, Austria (PMU Research Fund—PMU FFF Number: L-18/02/006-WET) and by Drs Haackert Foundation, Germany. S.L. is an author of a trial included in this study, an author of an included systematic review and a Cochrane editor. All other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A

scholarly journals Statistical methods for the analysis of adverse event data in randomised controlled trials: a scoping review and taxonomy

2020 ◽  
Author(s):  
Rachel Phillips ◽  
Odile Sauzet ◽  
Victoria Cornelius
Keyword(s):  
Statistical Methods ◽  
Scoping Review ◽  
Randomised Controlled Trials ◽  
Effective Means ◽  
Estimation Methods ◽  
Controlled Trials ◽  
Event Data ◽  
Group Sequential ◽  
Group Sequential Methods ◽  
Randomised Controlled

Abstract BackgroundStatistical methods for the analysis of harm outcomes in randomised controlled trials (RCTs) are rarely used, and there is a reliance on simple approaches to display information such as in frequency tables. We aimed to identify whether any statistical methods had been specifically developed to analyse prespecified secondary harm outcomes and non-specific emerging adverse events (AEs).MethodsA scoping review was undertaken to identify articles that proposed original methods or the original application of existing methods for the analysis of AEs that aimed to detect potential adverse drug reactions (ADRs) in phase II-IV parallel controlled group trials. Methods where harm outcomes were the (co)-primary outcome were excluded.Information was extracted on methodological characteristics such as: whether the method required the event to be prespecified or could be used to screen emerging events; and whether it was applied to individual events or the overall AE profile. Each statistical method was appraised and a taxonomy was developed for classification.ResultsForty-four eligible articles proposing 73 individual methods were included. A taxonomy was developed and articles were categorised as: visual summary methods (8 articles proposing 20 methods); hypothesis testing methods (11 articles proposing 16 methods); estimation methods (15 articles proposing 24 methods); or methods that provide decision-making probabilities (10 articles proposing 13 methods). Methods were further classified according to whether they required a prespecified event (9 articles proposing 12 methods), or could be applied to emerging events (35 articles proposing 61 methods); and if they were (group) sequential methods (10 articles proposing 12 methods) or methods to perform final/one analyses (34 articles proposing 61 methods). ConclusionsThis review highlighted that a broad range of methods exist for AE analysis. Immediate implementation of some of these could lead to improved inference for AE data in RCTs. For example, a well-designed graphic can be an effective means to communicate complex AE data and methods appropriate for counts, time-to-event data and that avoid dichotomising continuous outcomes can improve efficiencies in analysis. Previous research has shown that adoption of such methods in the scientific press is limited and that strategies to support change are needed.

scholarly journals Statistical methods for the analysis of adverse event data in randomised controlled trials: a comprehensive review and taxonomy

2020 ◽  
Author(s):  
Rachel Phillips ◽  
Odile Sauzet ◽  
Victoria Cornelius
Keyword(s):  
Statistical Methods ◽  
Randomised Controlled Trials ◽  
Effective Means ◽  
Estimation Methods ◽  
Controlled Trials ◽  
Event Data ◽  
Group Sequential ◽  
Group Sequential Methods ◽  
Original Application ◽  
Randomised Controlled

Abstract Background Statistical methods for the analysis of harm outcomes in randomised controlled trials (RCTs) are rarely used, and there is a reliance on simple approaches to display information such as in frequency tables. We aimed to identify whether any statistical methods had been specifically developed to analyse prespecified secondary harm outcomes and non-specific emerging adverse events (AEs). Methods A scoping review was undertaken to identify articles that proposed original methods or the original application of existing methods for the analysis of AEs that aimed to detect potential adverse drug reactions (ADRs) in phase II-IV parallel controlled group trials. Methods where harm outcomes were the (co)-primary outcome were excluded. Information was extracted on methodological characteristics such as: whether the method required the event to be prespecified or could be used to screen emerging events; and whether it was applied to individual events or aggregate events. Each statistical method was appraised and a taxonomy was developed for classification.Results Forty-four eligible articles proposing 73 individual methods were included. A taxonomy was developed and articles were categorised as: visual summary methods (8 articles proposing 20 methods); hypothesis testing methods (11 articles proposing 16 methods); estimation methods (15 articles proposing 24 methods); or methods that provide decision-making probabilities (10 articles proposing 13 methods). Methods were further classified according to whether they required a prespecified event (9 articles proposing 12 methods), or could be applied to emerging events (35 articles proposing 61 methods); and if they were (group) sequential methods (10 articles proposing 12 methods) or methods to perform final/one analyses (34 articles proposing 61 methods). Conclusions This review highlighted that a broad range of methods exist for AE analysis. Immediate implementation of some of these could lead to improved inference for AE data in RCTs. For example, a well-designed graphic can be an effective means to communicate complex AE data and methods appropriate for counts, time-to-event data and that avoid dichotomising continuous outcomes can improve efficiencies in analysis. Previous research has shown that adoption of such methods in the scientific press is limited and that strategies to support change are needed.

scholarly journals A survey of instructions to authors in surgical journals on reporting by CONSORT and PRISMA

2012 ◽  
Vol 94 (7) ◽  
pp. 468-471 ◽  
Author(s):  
S Shantikumar ◽  
J Wigley ◽  
W Hameed ◽  
A Handa
Keyword(s):  
Systematic Reviews ◽  
Randomised Controlled Trials ◽  
Trial Registration ◽  
Controlled Trials ◽  
Clinical Trial Registration ◽  
Journal Citation Reports ◽  
Randomised Controlled ◽  
The Uk ◽  
Meta Analyses ◽  
Surgical Journals

INTRODUCTION Guidance has been published on how best to report randomised controlled trials (Consolidated Standards of Reporting Trials – CONSORT) and systematic reviews (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – PRISMA). The aim of this study was to establish to what extent surgical journals formally endorse CONSORT and PRISMA in the respective reporting of randomised controlled trials and systematic reviews. METHODS Overall, 136 surgical journals indexed in Journal Citation Reports® were studied. Author guidelines were scrutinised for the following guidance: conflict of interests (COI), the Uniform Requirements for Manuscripts (URM), clinical trial registration, CONSORT and PRISMA. RESULTS The frequency of guidance endorsement was found to be as follows: COI 82%, URM 62%, trial registration 32%, CONSORT 29% and PRISMA 10%. Journals with a higher impact were more likely to adopt trial registration, CONSORT and PRISMA. Journals with editorial offices in the UK were more likely to insist on disclosure of COI and to endorse CONSORT. CONCLUSIONS Guidelines produced to improve publication practice have not been implemented widely by surgical journals. This may contribute to an overall poorer quality of published research. Editors of surgical journals should uniformly endorse reporting guidance and update their instructions to authors to reflect this.

scholarly journals Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in Patients with Ultra-Acute Stroke: Study Protocol for the “Rapid Intervention with GTN in Hypertensive Stroke Trial” (RIGHT, ISRCTN66434824)

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Sandeep Ankolekar ◽  
Gillian Sare ◽  
Chamila Geeganage ◽  
Michael Fuller ◽  
Lynn Stokes ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Functional Outcomes ◽  
Randomised Controlled Trials ◽  
Controlled Trial ◽  
Trial Registration ◽  
Controlled Trials ◽  
Stroke Study ◽  
Registration Number ◽  
Randomised Controlled ◽  
The Uk

Background. Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments. No completed randomised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK, and the practicalities of recruiting, consenting, and treating patients are unknown.Methods. RIGHT is an ambulance based, single-blind, randomised controlled trial with blinded-outcome assessment. The trial will assess feasibility of using ambulance services to deliver ultra-acute stroke treatments; a secondary aim is to assess the effect of glyceryl trinitrate (GTN) on haemodynamic variables and functional outcomes. Initial consent, randomisation, and treatment are performed by paramedics prior to hospitalisation. Patients with ultra-acute stroke (≤4 hours of onset) are randomised to transdermal GTN (5 mg/24 hours) or gauze dressing daily for 7 days. The primary outcome is systolic blood pressure at 2 hours. Secondary outcomes include feasibility, haemodynamics, dependency, and other functional outcomes. A nested qualitative study is included.Trial Status. The trial has all relevant ethics and regulatory approvals and recruitment started on February 15, 2010. The trial stopped recruitment in December 2011 after 41 patients were recruited.Trial Registration. The trial registration number is ISRCTN66434824 and EudraCT number is 2007-004766-40.

scholarly journals O32: TRANSPARENCY IN SURGICAL RANDOMISED CONTROLLED TRIALS: CROSS-SECTIONAL, OBSERVATIONAL STUDY

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
JA Helliwell ◽  
B Shelton ◽  
H Mahmood ◽  
R Blanco-Colino ◽  
JE Fitzgerald ◽  
...  
Keyword(s):  
Data Sharing ◽  
Randomised Controlled Trials ◽  
Conflicts Of Interest ◽  
Trial Registration ◽  
Controlled Trials ◽  
Cross Sectional ◽  
Research Waste ◽  
Funding Sources ◽  
Randomised Controlled ◽  
Personal Conflicts Of Interest

Abstract Introduction Randomised controlled trials (RCT) often provide the scientific basis on which commissioning and treatment decisions are made. It is essential that their results and methods are reported transparently. The aim of this study was to explore transparency with respect to trial registration, disclosure of funding sources, conflicts of interest (COI), and data sharing. Method This was a cross-sectional review of surgical RCTs. Data were extracted from RCTs in ten high-impact journals published in the years 2009, 2012, 2015, and 2018. Outcomes of interest were the incidence of reported trial registration, disclosure of funding sources, disclosure of investigator COI, and presence of a statement of data sharing plans. Result A total of 475 were eligible for analysis. Trial registration was present in 73 (67%) studies in 2009, 137 (84%) in 2012, 111 (89%) in 2015 and 110 (93%) in 2018. Funding statements were provided in 55%, 65%, 69.4%, and 75.4% of manuscripts, respectively. Conflicts of interest statements were provided in 49.5%, 89.1%, 94.6%, and 98.3% of manuscripts, respectively. Data sharing statements were present in only 15 (3.2%) RCTs. Eleven of these were in studies published most recently in 2018. Conclusion Trial registration, presence of funding statements, and disclosure of personal conflicts of interest in surgical RCTs have improved rapidly over the last 10 years. In contrast, disclosure of data sharing plans is exceptionally low. This may contribute to research waste and represents an essential target for improvement. Take-home message Trial registration, presence of funding statements, and disclosure of personal conflicts of interest in surgical RCTs have improved rapidly over the last 10 years. In contrast, disclosure of data sharing plans is exceptionally low. This may contribute to research waste and represents an essential target for improvement.

scholarly journals Feasibility of Comparative Health Research Outcome of Novel Surgery in prostate cancer (IP4-CHRONOS): statistical analysis plan for the randomised feasibility phase of the CHRONOS study

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Emily Day ◽  
A. Toby Prevost ◽  
Matthew R. Sydes ◽  
Deepika Reddy ◽  
Taimur T. Shah ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Statistical Analysis ◽  
Health Research ◽  
Randomised Controlled Trials ◽  
Statistical Analysis Plan ◽  
Controlled Trials ◽  
Main Stage ◽  
Multi Centre Study ◽  
Randomised Controlled ◽  
Comparative Health Research

Abstract Background Randomised controlled trials (RCTs) for surgical interventions have often proven difficult with calls for innovative approaches. The Imperial Prostate (IP4) Comparative Health Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS) study aims to deliver level 1 evidence on outcomes following focal therapy which involves treating just the tumour rather than whole-gland surgery or radiotherapy. Our aim is to test the feasibility of two parallel RCTs within an overarching strategy that fits with existing patient and physician equipoise and maximises the chances of success and potential benefit to patients and healthcare services. Methods and design IP4-CHRONOS is a randomised, unblinded multi-centre study, including two parallel randomised controlled trials targeting the same patient population: IP4-CHRONOS-A and IP4-CHRONOS-B. IP4-CHRONOS-A is a 1:1 RCT and the other is a multi-arm, multi-stage (MAMS) RCT starting with three arms and a 1:1:1 randomisation. The two linked RCTs are discussed with patients at the time of consent and the choice of A or B is dependent on physician and patient equipoise. The primary outcome is the feasibility of recruitment, acceptance of randomisation and compliance to allocated arm. Results This paper describes the statistical analysis plan (SAP) for the feasibility study within IP4-CHRONOS given its innovative approach. Version 1.0 of the SAP has been reviewed by the Trial Steering Committee (TSC), Chief Investigator (CI), Senior Statistician and Trial Statistician and signed off. The study is ongoing and recruiting. Recruitment is scheduled to finish later in 2021. The SAP documents approved methods and analyses that will be conducted. Since this is written in advance of the analysis, we avoid bias arising from prior knowledge of the study data and findings. Discussion Our feasibility analysis will demonstrate if IP4-CHRONOS is feasible in terms of recruitment, randomisation and compliance, and whether to continue both A and B or just one to the main stage. Trial registration ISRCTN ISRCTN17796995. Registered on 08 October 2019

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