The BACH project protocol: an international multicentre total Bile Acid Comparison and Harmonisation project and sub-study of the TURRIFIC randomised trial

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Corey Markus ◽  
Suzette Coat ◽  
Hanns-Ulrich Marschall ◽  
Catherine Williamson ◽  
Peter Dixon ◽  
...  
Keyword(s):  
Bile Acid ◽  
Large Scale ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Laboratory Data ◽  
Total Bile Acid ◽  
Laboratory Results ◽  
Randomised Controlled ◽  
Cholestasis Of Pregnancy ◽  
Acid Comparison

Abstract Objectives Multicentre international trials relying on diagnoses derived from biochemical results may overlook the importance of assay standardisation from the participating laboratories. Here we describe a study protocol aimed at harmonising results from total bile acid determinations within the context of an international randomised controlled Trial of two treatments, URsodeoxycholic acid and RIFampicin, for women with severe early onset Intrahepatic Cholestasis of pregnancy (TURRIFIC), referred to as the Bile Acid Comparison and Harmonisation (BACH) study, with the aims of reducing inter-laboratory heterogeneity in total bile acid assays. Methods We have simulated laboratory data to determine the feasibility of total bile acid recalibration using a reference set of patient samples with a consensus value approach and subsequently used regression-based techniques to transform the data. Results From these simulations, we have demonstrated that mathematical recalibration of total bile acid results is plausible, with a high probability of successfully harmonising results across participating laboratories. Conclusions Standardisation of bile acid results facilitates the commutability of laboratory results and collation for statistical analysis. It may provide the momentum for broader application of the described techniques in the setting of large-scale multinational clinical trials dependent on results from non-standardised assays.

scholarly journals Telephone-supported computerised cognitive–behavioural therapy: REEACT-2 large-scale pragmatic randomised controlled trial

2017 ◽  
Vol 210 (5) ◽  
pp. 362-367 ◽  
Author(s):  
Simon Gilbody ◽  
Sally Brabyn ◽  
Karina Lovell ◽  
David Kessler ◽  
Thomas Devlin ◽  
...  
Keyword(s):  
Cognitive Behavioural Therapy ◽  
Large Scale ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Behavioural Therapy ◽  
Telephone Support ◽  
Cognitive Behavioural ◽  
Patient Health ◽  
Randomised Controlled ◽  
Pragmatic Randomised Controlled Trial

BackgroundComputerised cognitive–behavioural therapy (cCBT) for depression has the potential to be efficient therapy but engagement is poor in primary care trials.AimsWe tested the benefits of adding telephone support to cCBT.MethodWe compared telephone-facilitated cCBT (MoodGYM) (n = 187) to minimally supported cCBT (MoodGYM) (n = 182) in a pragmatic randomised trial (trial registration: ISRCTN55310481). Outcomes were depression severity (Patient Health Questionnaire (PHQ)-9), anxiety (Generalized Anxiety Disorder Questionnaire (GAD)-7) and somatoform complaints (PHQ-15) at 4 and 12 months.ResultsUse of cCBT increased by a factor of between 1.5 and 2 with telephone facilitation. At 4 months PHQ-9 scores were 1.9 points lower (95% CI 0.5–3.3) for telephone-supported cCBT. At 12 months, the results were no longer statistically significant (0.9 PHQ-9 points, 95% CI −0.5 to 2.3). There was improvement in anxiety scores and for somatic complaints.ConclusionsTelephone facilitation of cCBT improves engagement and expedites depression improvement. The effect was small to moderate and comparable with other low-intensity psychological interventions.

scholarly journals Research paramedics’ observations regarding the challenges and strategies employed in the implementation of a large-scale out-of-hospital randomised trial

2020 ◽  
Vol 5 (1) ◽  
pp. 26-31
Author(s):  
Jonathan Green ◽  
Maria Robinson ◽  
Richard Pilbery ◽  
Gregory Whitley ◽  
Helen Hall ◽  
...  
Keyword(s):  
Large Scale ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Feasibility Studies ◽  
Cluster Randomised Controlled Trial ◽  
Airway Device ◽  
Lead Author ◽  
Supraglottic Airway ◽  
Cluster Randomised ◽  
Randomised Controlled

Introduction: AIRWAYS-2 was a cluster randomised controlled trial (RCT) comparing the clinical and cost effectiveness of the i-gel supraglottic airway device with tracheal intubation in the initial airway management of out-of-hospital cardiac arrest (OHCA). In order to successfully conduct this clinical trial, it was necessary for research paramedics to overcome multiple challenges, many of which will be relevant to future emergency medical service (EMS) research. This article aims to describe a number of the challenges that were encountered during the out-of-hospital phase of the AIRWAYS-2 trial and how these were overcome.Methods: The research paramedics responsible for conducting the pre-hospital phase of the trial were asked to reflect on their experience of facilitating the AIRWAYS-2 trial. Responses were then collated by the lead author. A process of iterative revision and review was undertaken by the research paramedics to produce a consensus of opinion.Results: The main challenges identified by the trial research paramedics related to the recruitment and training of paramedics, screening of eligible patients and investigation of protocol deviations / reporting errors. Even though a feasibility study was conducted prior to the commencement of AIRWAYS-2, the scale of these challenges was underestimated.Conclusion: Large-scale pragmatic cluster randomised trials are being successfully undertaken in out-of-hospital care. However, they require intensive engagement with EMS clinicians and local research paramedics, particularly when the intervention is contentious. Feasibility studies are an important part of research but may fail to identify all potential challenges. Therefore, flexibility is required to manage unforeseen difficulties.

scholarly journals Web-based early intervention for children with motor difficulties aged 3–8 years old using multimodal rehabilitation (WECARE): protocol of a patient-centred pragmatic randomised trial of paediatric telerehabilitation to support families

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e046561
Author(s):  
Chantal Camden ◽  
Jill G Zwicker ◽  
Melanie Morin ◽  
Tibor Schuster ◽  
Melanie Couture ◽  
...  
Keyword(s):  
Early Intervention ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Parental Knowledge ◽  
Performance Measure ◽  
Performance Goals ◽  
Web Based ◽  
Study Results ◽  
Motor Difficulties ◽  
Randomised Controlled

IntroductionMild motor difficulties in children are underdiagnosed despite being highly prevalent, leaving such children often underserved and at higher risk for secondary consequences such as cardiovascular disease and anxiety. Evidence suggests that early patient-oriented interventions, coaching parents and providing children with early stimulation should be provided, even in the absence of a diagnosis. Such interventions may be effectively delivered via telerehabilitation.Methods and analysisA family-centred, pragmatic randomised controlled trial will be carried out to evaluate the real-world effectiveness of a Web-based Early intervention for Children using multimodAl REhabilitation (WECARE). Families of children with motor difficulties, 3–8 years of age, living in Quebec, Canada, and receiving no public rehabilitation services (n=118) will be asked to determine up to 12 performance goals, evaluated using the Canadian Occupational Performance Measure (COPM, the primary outcome). Families will be randomised to receive either usual care or the WECARE intervention. The WECARE intervention will be delivered for 1 year via a web-based platform. Families will have access to videoconferences with an assigned rehabilitation therapist using a collaborative coaching approach, a private chat function, a forum open to all intervention arm participants and online resources pertaining to child development. Participants will be asked to re-evaluate the child’s COPM performance goals every 3 months up to 1 year post allocation. The COPM results will be analysed using a mixed Poisson regression model. Secondary outcomes include measures of the child’s functional ability, parental knowledge and skills and health-related quality of life, as well as qualitative outcomes pertaining to parental satisfaction and service delivery trajectories. Investigators and quantitative data analysts will be blinded to group allocation.Ethics and disseminationThe CIUSSS de l’Estrie—CHUS ethics committee approved this trial (2020-3429). Study results will be communicated via peer-reviewed journal publications, conference presentations and stakeholder-specific knowledge transfer activities.Trial registration numberNCT04254302.

scholarly journals Can we rely on non-randomised studies? Findings from a meta-epidemiological review

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
J C Rejon-Parrilla ◽  
M Salcher-Konrad ◽  
M Nguyen ◽  
K Davis ◽  
P Jonsson ◽  
...  
Keyword(s):  
Health Economic ◽  
Analytical Methods ◽  
Large Scale ◽  
Treatment Effects ◽  
Controlled Trial ◽  
Health Economic Evaluation ◽  
Risk Of Bias ◽  
Economic Decision Making ◽  
Wide Range ◽  
Randomised Controlled

Abstract Background Increasingly, health technology assessment (HTA) agencies must decide whether new medicines should be used routinely in the absence of randomised controlled trial (RCT) data, relying solely on non-randomised studies (NRS), which are at high risk of bias due to confounding. Against the background of increased availability and improved methods to analyse non-randomised data (e.g., propensity score methods and instrumental variables), it is important for decision-makers to have guidance on the analysis and interpretation of NRS to inform health economic evaluation. We therefore aimed to systematically and empirically assess the performance of NRS using different analytical methods as compared to RCTs and develop recommendations on the basis of our findings. Methods We conducted a large-scale meta-epidemiological review to obtain estimates of the discrepancy in treatment effects in matched RCTs and NRS of pharmacologic interventions from published meta-analyses indexed in MEDLINE and the Cochrane Database of Systematic Reviews. We also consulted with HTA bodies, regulators and academics from five European countries to learn from their experience with using non-randomised evidence. Results We compiled the largest dataset of clinical topics with matching RCTs and NRS using various analytical methods to date, covering >100 unique clinical questions. Incorporating information on direction of effect and effect size from >700 unique studies, the dataset can be used to evaluate discrepancies in treatment effects between study designs across a wide range of therapeutic areas. Conclusions An empirically based understanding of the risk of bias in NRS is required in order to promote the adequate use of non-randomised evidence as input for health economic decision-making.

scholarly journals Effects of a workplace prevention programme for problem gambling: study protocol for a cluster randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e015963 ◽  
Author(s):  
Jonas Rafi ◽  
Ekaterina Ivanova ◽  
Alexander Rozental ◽  
Per Carlbring
Keyword(s):  
Problem Gambling ◽  
Large Scale ◽  
Controlled Trial ◽  
Public Health Problem ◽  
Cluster Randomised Controlled Trial ◽  
Severity Index ◽  
The Body ◽  
Prevention Programme ◽  
Open Access Journals ◽  
Randomised Controlled

IntroductionDespite being considered a public health problem, no prevention programme for problem gambling in workplace settings has been scientifically evaluated. This study aims to fill a critical gap in the field of problem gambling by implementing and evaluating a large-scale prevention programme in organisations.Methods and analysisTen organisations, with a total of n=549 managers and n=8572 employees, will be randomised to either receiving a prevention programme or to a waitlist control condition. Measurements will be collected at the baseline and 3, 12 and 24 months after intervention. The primary outcome of interest is the managers’ inclination to act when worried or suspicious about an employee’s problem gambling or other harmful use. Additional outcomes of interest include the Problem Gambling Severity Index and gambling habits in both managers and employees. Furthermore, qualitative analyses of the responses from semistructured interviews with managers will be performed.Ethics and disseminationThis study has been approved by the regional ethics board of Stockholm, Sweden, and it will contribute to the body of knowledge concerning prevention of problem gambling. The findings will be published in peer-reviewed, open-access journals.Trial registration numberNCT02925286; Pre-results.

scholarly journals Methods for delivering the UK's multi-centre prison-based naloxone-on-release pilot randomised trial (N-ALIVE): Europe's largest prison-based randomised controlled trial

2017 ◽  
Vol 37 (4) ◽  
pp. 487-498 ◽  
Author(s):  
Angela Mary Meade ◽  
Sheila Macdonald Bird ◽  
John Strang ◽  
Tracey Pepple ◽  
Laura Lea Nichols ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Randomised Controlled

scholarly journals The comparison of total bile acid concentration and alcohol dehydrogenase activity as markers of intrahepatic cholestasis of pregnancy

2021 ◽  
Author(s):  
Wojciech Jelski ◽  
Joanna Piechota ◽  
Karolina Orywal ◽  
Barbara Mroczko
Keyword(s):  
Bile Acid ◽  
Alcohol Dehydrogenase ◽  
Bile Acids ◽  
Intrahepatic Cholestasis ◽  
Total Bile Acid ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Third Trimester ◽  
Total Bile Acids ◽  
Adh Activity ◽  
Cholestasis Of Pregnancy

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is the liver disorder in the second or early third trimester of pregnancy. It is characterized by pruritus with increased serum bile acids concentration and other liver function tests. ICP  is connected with increased risk of fetal mortality, but is unfortunately detected quite late. Therefore, it is important to recognize the disease in its early stages. We aimed to investigate the serum alcohol dehydrogenase (ADH) activity and compare it with the concentration of total bile acid (TBA) in women with ICP. Methods: Serum samples were taken for routine investigation from 80 pregnancies with ICP in the second or third trimester of pregnancy and from 80 healthy pregnant women in the same time of pregnancy. For measurement of class I activity we used the spectrofluorometric methods. The total ADH activitiy was measured by the photometric method. Results: The analysis of results shows a statistically significant increase in the activity of ADH I and ADH total (about 60% and 41.3%, respectively). Activity of ADH I well correlated with aminotransferases (alanine ALT and aspartate AST) and total bile acids (TBA) concentration. The total ADH activity was also positively correlated with ALT, AST and total bile acids. Conclusion: We can state that the activity of class I alcohol dehydrogenase isoenzyme in the sera of patients with ICP is increased and seems to be a good indicator of liver cell destruction during this disease and is comparable with the value of other markers.

scholarly journals Effect of riboflavin supplementation on blood pressure and possible effect modification by the MTHFR C677T polymorphism: a randomised trial in rural Gambia

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1034
Author(s):  
Modou Jobe ◽  
Mary Ward ◽  
Bakary Sonko ◽  
Abdul Khalie Muhammad ◽  
Ebrima Danso ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Large Scale ◽  
Methylenetetrahydrofolate Reductase ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Phenotypic Effect ◽  
Riboflavin Deficiency ◽  
Mthfr C677t Polymorphism

Introduction: Emerging evidence links a functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (rs1801133) with hypertension in adults. This variant reduces the affinity of MTHFR for its cofactor flavin-adenine dinucleotide (FAD) which is derived from riboflavin. Previous work has demonstrated a blood pressure (BP)-lowering effect of riboflavin in Irish adults with the MTHFR 677TT variant. We hypothesize that the almost-universal severe riboflavin deficiency seen in rural Gambia mimics the BP phenotypic effect of the TT variant and exacerbate the effect of the CT variant. We will test this in a randomised, placebo-controlled trial, whether intervention with riboflavin can decrease BP in adults in rural Gambia. Methods: This is a phase 2 recall-by-genotype randomised single-blind placebo-controlled riboflavin supplementation trial. We will use the Keneba biobank to recruit approximately 102 individuals aged between 18-70, previously genotyped for the MTHFR C677T polymorphism and identified as carrying the T allele; these individuals will be age- and sex-matched to a similar number of homozygotes for the C allele. The participants will be randomised to a 16-week supplementation trial of 5 mg/day riboflavin or placebo, supplied every 14 days. The primary outcome, BP, will be measured at baseline and at weeks 8 and 16. Blood samples, collected at baseline and week 16, will be analysed for riboflavin, homocysteine, red cell folate, cobalamin (vitamin B12) and pyridoxine (vitamin B6). Discussion: The study will evaluate the role of riboflavin supplementation in BP control within a population with high levels of riboflavin deficiency and will test a possible gene-nutrient interaction with the MTHFR C677T polymorphism. If improvements in BP are observed in this study, and proven in subsequent large-scale interventions, riboflavin could offer a cost-effective, safe and accessible option for the  prevention and control of hypertension in this population. Trial registration: ClinicalTrials.gov Identifier NCT03151096. Registered on 12 May 2017.

scholarly journals Drooling Reduction Intervention randomised trial (DRI): comparing the efficacy and acceptability of hyoscine patches and glycopyrronium liquid on drooling in children with neurodisability

2017 ◽  
Vol 103 (4) ◽  
pp. 371-376 ◽  
Author(s):  
Jeremy R Parr ◽  
Emma Todhunter ◽  
Lindsay Pennington ◽  
Deborah Stocken ◽  
Jill Cadwgan ◽  
...  
Keyword(s):  
Side Effects ◽  
Controlled Trial ◽  
Symptom Control ◽  
Randomised Trial ◽  
Frequency Scale ◽  
Skin Patch ◽  
Impact Scale ◽  
Significant Difference ◽  
Secondary Outcomes ◽  
Randomised Controlled

ObjectiveInvestigate whether hyoscine patch or glycopyrronium liquid is more effective and acceptable to treat drooling in children with neurodisability.DesignMulticentre, single-blind, randomised controlled trial.SettingRecruitment through neurodisability teams; treatment by parents.ParticipantsNinety children with neurodisability who had never received medication for drooling (55 boys, 35 girls; median age 4 years). Exclusion criteria: medication contraindicated; in a trial that could affect drooling or management.InterventionChildren were randomised to receive a hyoscine skin patch or glycopyrronium liquid. Dose was increased over 4 weeks to achieve optimum symptom control with minimal side-effects; steady dose then continued to 12 weeks.Primary and secondary outcomesPrimary outcome: Drooling Impact Scale (DIS) score at week-4. Secondary outcomes: change in DIS scores over 12 weeks, Drooling Severity and Frequency Scale and Treatment Satisfaction Questionnaire for Medication; adverse events; children’s perception about treatment.ResultsBoth medications yielded clinically and statistically significant reductions in mean DIS at week-4 (25.0 (SD 22.2) for hyoscine and 26.6 (SD 16) for glycopyrronium). There was no significant difference in change in DIS scores between treatment groups. By week-12, 26/47 (55%) children starting treatment were receiving hyoscine compared with 31/38 (82%) on glycopyrronium. There was a 42% increased chance of being on treatment at week-12 for children randomised to glycopyrronium relative to hyoscine (1.42, 95% CI 1.04 to 1.95).ConclusionsHyoscine and glycopyrronium are clinically effective in treating drooling in children with neurodisability. Hyoscine produced more problematic side effects leading to a greater chance of treatment cessation.Trial registration numbersISRCTN75287237; EUDRACT: 2013-000863-94; Medicines and Healthcare Products Regulatory Agency: 17136/0264/001-0003

scholarly journals Effects of injectable progestogen contraception versus the copper intrauterine device on HIV acquisition: sub-study of a pragmatic randomised controlled trial

2017 ◽  
Vol 43 (3) ◽  
pp. 175-180 ◽  
Author(s):  
G Justus Hofmeyr ◽  
Mandisa Singata-Madliki ◽  
Theresa A Lawrie ◽  
Eduardo Bergel ◽  
Marleen Temmerman
Keyword(s):  
Randomised Controlled Trial ◽  
South African ◽  
Pregnancy Termination ◽  
Controlled Trial ◽  
Intrauterine Device ◽  
Randomised Trial ◽  
Contraceptive Device ◽  
Increased Risk ◽  
Hiv Acquisition ◽  
Randomised Controlled

BackgroundEvidence from observational studies suggests an increased risk of HIV acquisition among women using depot medroxyprogesterone acetate (DMPA) contraception.MethodsWithin the context of a South African programme to increase women's access to the intrauterine contraceptive device (IUD), we conducted a pragmatic, open-label, parallel-arm, randomised controlled trial (RCT) of the IUD versus injectable progestogen contraception (IPC) at two South African hospitals. The primary outcome was pregnancy; secondary outcomes included HIV acquisition. Consenting women attending termination of pregnancy services were randomised after pregnancy termination between July 2009 and November 2012. Condoms were promoted for the prevention of sexually transmitted infections. Voluntary HIV testing was offered at baseline and at 12 or more months later. Findings on HIV acquisition are reported in this article.ResultsHIV acquisition data were available for 1290 initially HIV-negative women who underwent a final study interview at a median of 20 months after randomisation to IPC or an IUD. Baseline group characteristics were comparable. In the IPC group, 545/656 (83%) of participants received DMPA, 96 (15%) received injectable norethisterone enanthate, 14 (2%) received the IUD and one received oral contraception. In the IUD group 609 (96%) received the IUD, 20 (3%) received IPC and 5 (1%) had missing data. According to intention-to-treat analysis, HIV acquisition occurred in 20/656 (3.0%) women in the IPC arm and 22/634 (3.5%) women in the IUD arm (IPC vs IUD, risk ratio 0.88; 95% confidence interval 0.48–1.59;p=0.7).ConclusionsThis sub-study was underpowered to rule out moderate differences in HIV risk, but confirms the feasibility of randomised trial methodology to address this question. Larger RCTs are needed to determine the relative risks of various contraceptive methods on HIV acquisition with greater precision.Trial registration numberPan African Clinical Trials Registry number PACTR201409000880157 (04-09-2014).

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