50 research outputs found
The development of a set of key points to aid clinicians and researchers in designing and conducting n-of-1 trials
Get PDFIntroduction
n-of-1 trials are undertaken to optimise the evaluation of health technologies in individual patients. They involve a single patient receiving treatments, both interventional and control, consecutively over set periods of time, the order of which is decided at random. Although n-of-1 trials are undertaken in medical research it could be argued they have the utility to be undertaken more frequently. We undertook the National Institute for Health Research (NIHR) commissioned DIAMOND (Development of generalisable methodology for n-of-1 trials delivery for very low volume treatments) project to develop key points to assist clinicians and researchers in designing and conducting n-of-1 trials.
Methods
The key points were developed by undertaking a stakeholder workshop, followed by a discussion within the study team and then a stakeholder dissemination and feedback event. The stakeholder workshop sought to gain the perspectives of a variety of stakeholders (including clinicians, researchers and patient representatives) on the design and use of n-of-1 trials. A discussion between the study team was held to reflect on the workshop and draft the key points. Lastly, the stakeholders from the workshop were invited to a dissemination and feedback session where the proposed key points were presented and their feedback gained.
Results
A set of 22 key points were developed based on the insights from the workshop and subsequent discussions. They provide guidance on when an n-of-1 trial might be a viable or appropriate study design and discuss key decisions involved in the design of n-of-1 trials, including determining an appropriate number of treatment periods and cycles, the choice of comparator, recommended approaches to randomisation and blinding, the use of washout periods and approaches to analysis.
Conclusions
The key points developed in the project will support clinical researchers to understand key considerations when designing n-of-1 trials. It is hoped they will support the wider implementation of the study design
A methodological review of randomised n-of-1 trials
Get PDFBackground: n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of 12 years, including how the n-of-1 design has been employed to study both rare and non-rare conditions.Methods: databases and clinical trials registries were searched for articles including “n-of-1” in the title between 2011 and 2023. The reference lists of reviews identified by the searches were searched for any additional eligible articles. Randomised n-of-1 trials were selected for inclusion and data were extracted on a range of design, population, and analysis characteristics. Descriptive statistics were produced for all variables.Results: we identified 74 studies meeting our eligibility criteria, 13 of which (17.6%) were conducted in rare condi- tions. They were conducted in a range of clinical areas with the most common being neurological conditions (n = 16, 21.6%). The median (Q1, Q3) number of participants randomised was 9 (4, 20) and 12 trials (16.2%) involved a single patient only. Forty-six (62.2%) trials evaluated pharmaceutical interventions and 49 (66.2%) trials were placebo con- trolled. Trials had a median (Q1, Q3) of six (4, 8) periods and 61 (82.4%) compared two health technologies. Fifty-seven (77.0%) trials incorporated blinding and 32 (43.2%) had a washout period. Forty-nine trials (66.2%) used patient- reported outcome measures (PROMs) to assess the primary outcome. Trials used a range of approaches to analysis and 48 (64.9%) combined data from multiple patients. The characteristics of the n-of-1 trials conducted in rare condi- tions were generally consistent with those in non-rare conditions.Conclusions: n-of-1 trials are still underused and the application of the n-of-1 design for the evaluation of health technologies for rare diseases has been particularly limited. We have summarised the characteristics of randomised n-of-1 trials in rare and non-rare conditions. We hope that it can inform researchers in the design of future n-of-1 stud- ies. Further work is required to provide guidance on specific design considerations, implementation, and statistical analysis of these studies.Trial registration: not applicable.<br/
Induced Endometrial Trauma (endometrial scratch) in the mid-luteal menstrual cycle phase preceding first cycle IVF/ICSI versus usual IVF/ICSI therapy: study protocol for a randomised controlled trial
Get PDFEndometrial trauma commonly known as endometrial scratch (ES) has been shown to improve pregnancy rates in women with a history of repeated implantation failure undergoing in vitro fertilisation (IVF), with or without intracytoplasmic sperm injection (ICSI). However, the procedure has not yet been fully explored in women having IVF/ICSI for the first time. This study aims to examine the effect of performing an ES in the mid-luteal phase prior to a first-time IVF/ICSI cycle on the chances of achieving a clinical pregnancy and live birth. If ES can influence this success rate, there would be a significant cost saving to the National Health Service through decreasing the number of IVF/ICSI cycles necessary to achieve a pregnancy, increase the practice of single embryo transfer and consequently have a large impact on risks and costs associated with multiple pregnancies. This 30-month, UK, multicentre, parallel group, randomised controlled trial includes a 9-month internal pilot and health economic analysis recruiting 1044 women from 16 fertility units. It will follow up participants to identify if IVF/ICSI has been successful and live birth has occurred up to 6 weeks post partum. Primary analysis will be on an intention-to-treat basis. A substudy of endometrial samples obtained during the ES will assess the role of immune factors in embryo implantation. Main trial recruitment commenced on January 2017 and is ongoing.Participants randomised to the intervention group will receive the ES procedure in the mid-luteal phase of the preceding cycle prior to first-time IVF/ICSI treatment versus usual IVF/ICSI treatment in the control group, with 1:1 randomisation. The primary outcome is live birth rate after completed 24 weeks gestation. South Central-Berkshire Research Ethics Committee approved the protocol. Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences. ISRCTN23800982; Pre-results
Code choice and code-switching in Swiss-German internet relay chat rooms
No full textIn the German-speaking regions of Switzerland, dialect is spoken by all social groups in most communicative situations, Standard German being used only when prescribed. Swiss dialects rarely appeared in written form before the 1980s, apart from the genre of dialect literature. Due to the growing acceptance of informal writing styles in many European languages, dialect is increasingly employed for written personal communication, in particular in computer-mediated communication (CMC). In Swiss Internet Relay Chat (IRC) rooms, varieties of German are used side by side as all chatters have a command of both standard and dialectal varieties. Depending on the channel, the proportion of dialectal contributions can be as high as 90 percent. The choice of a particular variety depends on both individual preference and on the predominant variety used within a specific thread. In this paper I take a quantitative approach to language variation in IRC and demonstrate how such an approach can help embed qualitative research on code-switching in CMC
Outpatient paracentesis for the management of ovarian hyperstimulation syndrome: study protocol for the STOP-OHSS randomised controlled trial
Get PDFIntroduction Ovarian hyperstimulation syndrome (OHSS) is the most significant short-term complication of pharmacological ovarian stimulation. Symptoms range from mild abdominal discomfort to rare complications such as renal failure, thromboembolism and respiratory distress syndrome. Currently, clinical practice typically involves monitoring the patient until the condition becomes severe, at which point they are admitted to hospital, where drainage of ascitic fluid (paracentesis) may take place. Preliminary studies have indicated that earlier outpatient paracentesis may reduce the progression of OHSS and prevent hospitalisation in women. Methods and analysis This UK, multicentre, pragmatic, two-arm, parallel-group, adaptive (group sequential with one interim analysis), open-label, superiority, confirmatory, group sequential, individually randomised controlled trial, with internal pilot will assess the clinical and cost-effectiveness and safety of outpatient paracentesis versus conservative management (usual care) for moderate or severe OHSS. 224 women from 20 National Health Service and private fertility units will be randomised (1:1) and followed up for up to 13.5 months. The primary outcome is the rate of OHSS related hospital admission of at least 24 hours within 28 days postrandomisation. The primary analysis will be an intention to treat with difference in hospitalisation rates as measure of treatment effect. Secondary outcomes include time to resolution of symptoms, patient satisfaction, adverse events and cost-effectiveness. A qualitative substudy will facilitate the feasibility of recruitment. Participant recruitment commenced in June 2022. Ethics and dissemination London - Southeast Research Ethics Committee approved the protocol (reference: 22/LO/0015). Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences, as well as being disseminated to trial participants and patient groups. Trial registration number ISRCTN71978064.</p
Endometrial scratch to increase live birth rates in women undergoing first-time in vitro fertilisation : RCT and systematic review
Get PDFBackground
In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure is an in vitro fertilisation ‘add-on’ that is sometimes provided prior to the first in vitro fertilisation cycle, but there is a lack of evidence to support its use.
Objectives
(1) To assess the clinical effectiveness, safety and cost-effectiveness of endometrial scratch compared with treatment as usual in women undergoing their first in vitro fertilisation cycle (the ‘Endometrial Scratch Trial’) and (2) to undertake a systematic review to combine the results of the Endometrial Scratch Trial with those of previous trials in which endometrial scratch was provided prior to the first in vitro fertilisation cycle.
Design
A pragmatic, multicentre, superiority, open-label, parallel-group, individually randomised controlled trial. Participants were randomised (1 : 1) via a web-based system to receive endometrial scratch or treatment as usual using stratified block randomisation. The systematic review involved searching electronic databases (undertaken in January 2020) and clinicaltrials.gov (undertaken in September 2020) for relevant trials.
Setting
Sixteen UK fertility units.
Participants
Women aged 18–37 years, inclusive, undergoing their first in vitro fertilisation cycle. The exclusion criteria included severe endometriosis, body mass index ≥ 35 kg/m2 and previous trauma to the endometrium.
Interventions
Endometrial scratch was undertaken in the mid-luteal phase of the menstrual cycle prior to in vitro fertilisation, and involved inserting a pipelle into the cavity of the uterus and rotating and withdrawing it three or four times. The endometrial scratch group then received usual in vitro fertilisation treatment. The treatment-as-usual group received usual in vitro fertilisation only.
Main outcome measures
The primary outcome was live birth after completion of 24 weeks’ gestation within 10.5 months of egg collection. Secondary outcomes included implantation, pregnancy, ectopic pregnancy, miscarriage, pain and tolerability of the procedure, adverse events and treatment costs.
Results
One thousand and forty-eight (30.3%) women were randomised to treatment as usual (n = 525) or endometrial scratch (n = 523) and were followed up between July 2016 and October 2019 and included in the intention-to-treat analysis. In the endometrial scratch group, 453 (86.6%) women received the endometrial scratch procedure. A total of 494 (94.1%) women in the treatment-as-usual group and 497 (95.0%) women in the endometrial scratch group underwent in vitro fertilisation. The live birth rate was 37.1% (195/525) in the treatment-as-usual group and 38.6% (202/523) in the endometrial scratch group: an unadjusted absolute difference of 1.5% (95% confidence interval –4.4% to 7.4%; p = 0.621). There were no statistically significant differences in secondary outcomes. Safety events were comparable across groups. No neonatal deaths were recorded. The cost per successful live birth was £11.90 per woman (95% confidence interval –£134 to £127). The pooled results of this trial and of eight similar trials found no evidence of a significant effect of endometrial scratch in increasing live birth rate (odds ratio 1.03, 95% confidence interval 0.87 to 1.22).
Limitations
A sham endometrial scratch procedure was not undertaken, but it is unlikely that doing so would have influenced the results, as objective fertility outcomes were used. A total of 9.2% of women randomised to receive endometrial scratch did not undergo the procedure, which may have slightly diluted the treatment effect.
Conclusions
We found no evidence to support the theory that performing endometrial scratch in the mid-luteal phase in women undergoing their first in vitro fertilisation cycle significantly improves live birth rate, although the procedure was well tolerated and safe. We recommend that endometrial scratch is not undertaken in this population.
Trial registration
This trial is registered as ISRCTN23800982
Lifestyle matters randomized controlled trial of a preventive health intervention for older people: Qualitative sub study with participants and intervention facilitators
Get PDFObjective: This qualitative study embedded within a randomized controlled trial was conducted to explore the acceptability, experiences of, and short-term impact of a preventive health intervention (Lifestyle Matters) from the perspectives of those who took part, and to uncover any evidence for the theorised mechanisms of action (improved participation and self efficacy) underpinning the intervention. It was also conducted to help explain the quantitative trial results.
Methods: A purposive sample of 13 trial participants who had been randomized to receive the Lifestyle Matters intervention (approximately 10%) were individually qualitatively interviewed immediately following their involvement. All four intervention facilitators were also individually interviewed.
Results: Evidence of the hypothesized behavioural changes could be identified within the interview data, demonstrating the potential of this intervention. However, lack of adherence to the overall intervention eroded receipt of benefit. This finding complements the quantitative trial results which found that the study had failed to recruit those who considered themselves to be at risk of age-related decline.
Conclusion: This form of preventive health intervention requires proactive identification of those who recognise the need to make lifestyle changes. This is difficult if reactive health and social care systems are the main referral routes. The methodological approaches taken towards the study of complex interventions requires reconsideration if potential benefits are to be accurately assessed.
Clinical Trial Registration: ISRCTN6720915
Psychological and psychosocial interventions for cannabis cessation in adults: a systematic review short report
Get PDFBackground: Cannabis is the most commonly used illicit drug worldwide. Cannabis dependence is a recognised psychiatric diagnosis, often diagnosed via the Diagnostic and Statistical Manual of Mental Disorders criteria and the International Classification of Diseases, 10th Revision. Cannabis use is associated with an increased risk of medical and psychological problems. This systematic review evaluates the use of a wide variety of psychological and psychosocial interventions, such as motivational interviewing (MI), cognitive–behavioural therapy (CBT) and contingency management. Objective: To systematically review the clinical effectiveness of psychological and psychosocial interventions for cannabis cessation in adults who use cannabis regularly. Data sources: Studies were identified via searches of 11 databases [MEDLINE, EMBASE, Cochrane Controlled Trials Register, Health Technology Assessment (HTA) database, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, NHS Economic Evaluation Database, PsycINFO, Web of Science Conference Proceedings Citation Index, ClinicalTrials.gov and metaRegister of Current Controlled Trials] from inception to February 2014, searching of existing reviews and reference tracking. Methods: Randomised controlled trials (RCTs) assessing psychological or psychosocial interventions in a community setting were eligible. Risk of bias was assessed using adapted Cochrane criteria and narrative synthesis was undertaken. Outcomes included change in cannabis use, severity of cannabis dependence, motivation to change and intervention adherence. Results: The review included 33 RCTs conducted in various countries (mostly the USA and Australia). General population studies: 26 studies assessed the general population of cannabis users. Across six studies, CBT (4–14 sessions) significantly improved outcomes (cannabis use, severity of dependence, cannabis problems) compared with wait list post treatment, maintained at 9 months in the one study with later follow-up. Studies of briefer MI or motivational enhancement therapy (MET) (one or two sessions) gave mixed results, with some improvements over wait list, while some comparisons were not significant. Four studies comparing CBT (6–14 sessions) with MI/MET (1–4 sessions) also gave mixed results: longer courses of CBT provided some improvements over MI. In one small study, supportive–expressive dynamic psychotherapy (16 sessions) gave significant improvements over one-session MI. Courses of other types of therapy (social support group, case management) gave similar improvements to CBT based on limited data. Limited data indicated that telephone- or internet-based interventions might be effective. Contingency management (vouchers for abstinence) gave promising results in the short term; however, at later follow-ups, vouchers in combination with CBT gave better results than vouchers or CBT alone. Psychiatric population studies: seven studies assessed psychiatric populations (schizophrenia, psychosis, bipolar disorder or major depression). CBT appeared to have little effect over treatment as usual (TAU) based on four small studies with design limitations (both groups received TAU and patients were referred). Other studies reported no significant difference between types of 10-session therapy. Limitations: Included studies were heterogeneous, covering a wide range of interventions, comparators, populations and outcomes. The majority were considered at high risk of bias. Effect sizes were reported in different formats across studies and outcomes. Conclusions: Based on the available evidence, courses of CBT and (to a lesser extent) one or two sessions of MI improved outcomes in a self-selected population of cannabis users. There was some evidence that contingency management enhanced long-term outcomes in combination with CBT. Results of CBT for cannabis cessation in psychiatric populations were less promising, but may have been affected by provision of TAU in both groups and the referred populations. Future research should focus on the number of CBT/MI sessions required and potential clinical effectiveness and cost-effectiveness of shorter interventions. CBT plus contingency management and mutual aid therapies warrant further study. Studies should consider potential effects of recruitment methods and include inactive control groups and long-term follow-up. TAU arms in psychiatric population studies should aim not to confound the study intervention. Study registration: This study is registered as PROSPERO CRD42014008952. Funding: The National Institute for Health Research HTA programme
SIMMER: Software and Systems Integration Modelling Metrics and Risks (Getting to Level 4)
No full textThis article documents the mid-term progress and provisional conclusions of SIMMER; an ESSI funded Process Improvement Experiment. The overall objective of the experiment is to produce a more effective means of planning and controlling complex software and systems integration projects. In order to remain competitive, ICL (as well as many other companies) needs to continually improve its predictability of costs and schedules for integration projects, to reduce time to market and to reduce costs without detriment to the quality of the products. The developments of our complex software and systems rely more and more on using commodity components and collaborations as a way to meet these business objectives. The ability to accurately predict effort and time scales and the ability to keep within budget is becoming increasingly difficult in such projects. The specific purposes of the experiment are to demonstrate the applicability of the "Cellular Manufacturing Process Model" (CMPM) technology to a business critical, live software and systems development Chapter <Nr> <Title> 2 / 23/11/98/simgot.doc Version <Nr> / <Author-Acronyme>
Endometrial scratch in women undergoing first-time IVF treatment : a systematic review and meta-analysis of randomized controlled trials
Get PDFThe endometrial scratch procedure is an IVF ‘add-on’ sometimes provided prior to the first IVF cycle. A 2019 systematic review concluded that there was insufficient evidence to show whether endometrial scratch has a significant effect on pregnancy outcomes (including live birth rate, LBR) when undertaken prior to the first IVF cycle. Further evidence was published following this review, including the Endometrial Scratch Trial (ISRCTN23800982). The objective of the current review was to synthesize and critically appraise the evidence for the clinical effectiveness and safety of the endometrial scratch procedure in women undergoing their first IVF cycle. Databases searched include MEDLINE, Embase, CINAHL and ClinicalTrials.gov. Eligible randomized controlled trials included women undergoing IVF for the first time that reported the effectiveness and/or safety of the endometrial scratch procedure; 12 studies were included. Meta-analysis showed no evidence of a significant effect of the endometrial scratch on LBR (10 trials, odds ratio [OR] 1.17, 95% confidence interval [CI] 0.76–1.79) or other pregnancy outcomes. This review confirms that there is a lack of evidence that endometrial scratch improves pregnancy outcomes, including LBR, for women undergoing their first IVF cycle. Clinicians are recommended not to perform this procedure in individuals undergoing their first cycle of IVF
