Registry randomised trials: a methodological perspective.
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ABSTRACT:
SUBMITTER: Doherty DA
PROVIDER: S-EPMC9980340 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
Publications
Registry randomised trials: a methodological perspective.
Doherty Dorota A DA Tong Steven Y C SYC Reilly Jennifer J Shrapnel Jane J McDonald Stephen S Ahern Susannah S Harris Ian I Tam Charmaine S CS Brennan Angela L AL Hodgson Carol C Wilcox Leonie L Balagurunathan Anitha A Butcher Belinda E BE Reid Christopher M CM
BMJ open 20230301 3
Registry randomised clinical trials (RRCTs) have the potential to provide pragmatic answers to important clinical questions. RRCTs can be embedded into large population-based registries or smaller single site registries to provide timely answers at a reduced cost compared with traditional randomised controlled trials. RRCTs can take a number of forms in addition to the traditional individual-level randomised trial, including parallel group trials, platform or adaptive trials, cluster randomised ...[more]
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Project description:Backgroundn-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.MethodsDatabases 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.ResultsWe identified 74 studies meeting our eligibility criteria, 13 of which (17.6%) were conducted in rare conditions. 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 controlled. 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 conditions were generally consistent with those in non-rare conditions.Conclusionsn-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 studies. Further work is required to provide guidance on specific design considerations, implementation, and statistical analysis of these studies.Trial registrationNot applicable.
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Project description:IntroductionIt is essential to choose a realistic anticipated intervention effect when calculating a sample size for a randomised clinical trial. Unfortunately, anticipated intervention effects are often inflated, when compared with the 'true' intervention effects. This is documented for mortality in critical care trials. A similar pattern might exist across different medical specialties. This study aims to estimate the range of observed intervention effects for all-cause mortality in trials included in Cochrane Reviews, within each Cochrane Review Group.Methods and analysisWe will include randomised clinical trials assessing all-cause mortality as an outcome. Trials will be identified from Cochrane Reviews published in the Cochrane Database of Systematic Reviews. Cochrane Reviews will be clustered according to the registered Cochrane Review Group (eg, Anaesthesia, Emergency and Critical Care) and the statistical analyses will be conducted for each Cochrane Review Group and overall. The median relative risk and IQR for all-cause mortality and the proportion of trials with a relative all-cause mortality risk within seven different ranges will be reported (relative risk below 0.70, 0.70-0.79, 0.80-0.89, 0.90-1.09, 1.10-1.19, 1.20-1.30 and above 1.30). Subgroup analyses will explore the effects of original design, sample size, risk of bias, disease, intervention type, follow-up length, participating centres, funding type, information size and outcome hierarchy.Ethics and disseminationSince we will use summary data from trials already approved by relevant ethical committees, this study does not require ethical approval. Regardless of our findings, the results will be published in an international peer-reviewed journal.
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Project description:ObjectiveAcupuncture systematic reviewers have increasingly searched Chinese databases and journals to identify eligible randomised clinical trials (RCTs). However, reviewers have infrequently searched for eligible RCTs in Korean databases and journals. This study aimed to identify difficult to locate acupuncture RCTs in Korean databases and journals and to assess the characteristics and quality of the identified RCTs.MethodsEleven electronic databases and seven journals were searched up to December 2012. All RCTs using needle acupuncture were considered for inclusion. Key study characteristics were extracted and risk of bias was assessed using the Cochrane Collaboration tool.ResultsOne hundred and forty-three publications met our inclusion criteria. Acupuncture RCTs in the Korean literature emerged in the mid-1990s and increased in the mid-2000s. Diverse methods of acupuncture were used, including some methods unique to Korea (eg, Saam acupuncture). The largest proportion of trials evaluated acupuncture for musculoskeletal conditions (27.3%). The mean sample size was 44.3±25.3 per trial. Random sequence generation methods were reported in 44.8% of the RCTs, whereas only 11.9% reported methods of allocation concealment. A low proportion of trials reported participant blinding (32.9%) and outcome assessment blinding (18.9%).ConclusionsKorean acupuncture trials, many of which evaluate acupuncture styles unique to Korea, are typically omitted from systematic reviews of acupuncture, resulting in the potential for language bias. The development of this database of difficult to locate Korean trials, which includes English language translations of abstracts, will enable these trials of varying quality to be assessed for inclusion in future acupuncture systematic reviews.
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Project description:This narrative review describes a new approach to navigation in a challenging landscape of clinical drug development in diabetes. Successful outcome studies in recent years have led to new indications and guidelines in type 2 diabetes, yet the number of clinical trials in diabetes is now declining. This is due to many environmental factors acting in concert, including the prioritisation of funding for other diseases, high costs of large randomised clinical trials, increase in regulatory requirements and limited entry of novel candidate drugs. There is a need for novel and cost-effective paradigms of clinical development to meet these and other challenges. The concept of registry-based randomised clinical trials (RRCTs) is an attractive option. In this review we focus on type 2 diabetes and the prevention of cardiovascular and microvascular comorbidities and mortality, using the Swedish SMARTEST trial as an example of an RRCT. We also give some examples from other disease areas. The RRCT concept is a novel, cost-effective and scientifically sound approach for conducting large-scale diabetes trials in a real-world setting.
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Project description: Not available
| S-EPMC10544368 | biostudies-literature
Project description:BackgroundThere is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies.Methods and findingsSearches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93-1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance.ConclusionsEmpirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors' Summary.
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Project description:BackgroundWith rising obesity rates worldwide, clinical trials focused on identifying effective treatments are increasing. While guidelines exist for pharmaceutical drugs targeting obesity, there are none for herbal medicine clinical trials for anti-obesity. Both industries refer to the same guidelines for clinical trials.ObjectivesThis scoping review aimed to gather information from herbal medicine anti-obesity randomised controlled trials (RCTs), analyse the methodologies and assess their alignment with international guidelines.Eligibility criteriaThis review included RCTs of participants of all ages with obesity utilising herbal medicine with any comparators and focusing on various outcome measures.Sources of evidence: Only published journal articles were included.Charting methodsArticles were extracted from MEDLINE, CENTRAL and EMBASE using predetermined keywords. Relevant data, such as the study characteristics, types of herbal interventions and controls, treatment durations, outcome measures and safety monitoring methods were recorded in a table format for comparative analysis.ResultsWe included 99 RCTs that showed participant sample sizes ranging from 8 to 182, ages 18 to 80 years and body mass indexes (BMIs) between 25 and 49.9 kg/m2. Herbal interventions used single herbs (n = 57) and mixtures (n = 42), given for 14 days to 56 weeks. Studies implementing diet modifications include restricted calorie diets (n = 35), food-portion controlled diets (n = 7) and fixed calorie diets (n = 7). Of the 28 studies implementing exercise, most were of moderate intensity (n = 22). All studies collected BMI and weight as primary outcomes. Body fat composition was measured in over 50% of studies using a body analyser (n = 57). Waist, hip and abdominal circumferences were infrequently measured. Radiological tools used include dual-energy X-ray absorptiometry (n = 16), computed tomography scans (n = 10) and ultrasound (n = 2). Safety monitoring methods were reported in most studies (n = 76).ConclusionIn conclusion, almost 50% of the studies adhered to international pharmaceutical clinical trial guidelines, addressing dietary, lifestyle, physical activity and cardiovascular risk factors. Nonetheless, more herbal anti-obesity studies need to consider the assessment of weight maintenance.
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