Dataset Information

A systematic review of methods used to conduct decentralised clinical trials.

ABSTRACT:

Aims

To evaluate, using quantitative and qualitative approaches, published data on the design and conduct of decentralised clinical trials (DCTs).

Methods

We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, ProQuest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and Google Scholar for publications reporting, discussing, or evaluating decentralised clinical research methods. Reports of randomised clinical trials using decentralised methods were included in a focused quantitative analysis with a primary outcome of number of randomised participants. All publications discussing or evaluating DCTs were included in a wider qualitative analysis to identify advantages, disadvantages, facilitators, barriers and stakeholder opinions of decentralised clinical trials. Quantitative data were summarised using descriptive statistics, and qualitative data analysed using a thematic approach.

Results

Initial searches identified 19 704 articles. After removal of duplicates, 18 553 were screened, resulting in 237 eligible for full-text assessment. Forty-five trials were included in the quantitative analysis; 117 documents were included in the qualitative analysis. Trials were widely heterogeneous in design and reporting, precluding meta-analysis of the effect of DCT methods on the primary recruitment outcome. Qualitative analysis formulated 4 broad themes: value, burden, safety and equity. Participant and stakeholder experiences of DCTs were incompletely represented.

Conclusion

DCTs are developing rapidly. However, there is insufficient evidence to confirm which methods are most effective in trial recruitment, retention, or overall cost. The identified advantages, disadvantages, facilitators and barriers should inform the development of DCT methods. We recommend further research on how DCTs are experienced and perceived by participants and stakeholders to maximise potential benefits.

SUBMITTER: Rogers A

PROVIDER: S-EPMC9306873 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

A systematic review of methods used to conduct decentralised clinical trials.

Rogers Amy A De Paoli Giorgia G Subbarayan Selvarani S Copland Rachel R Harwood Kate K Coyle Joanne J Mitchell Lyn L MacDonald Thomas M TM Mackenzie Isla S IS

British journal of clinical pharmacology 20220127 6

<h4>Aims</h4>To evaluate, using quantitative and qualitative approaches, published data on the design and conduct of decentralised clinical trials (DCTs).<h4>Methods</h4>We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, ProQuest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and Google Scholar for publications reporting, discussing, or evaluating decentralised clinical research methods. Reports of randomised clinical trials using decentralised methods were included in a focused quantitativ ...[more]

PMID: 34961991

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Project description:BackgroundThe COVID-19 pandemic significantly impacted the conduct of clinical trials through delay, interruption or cancellation. Decentralised methods in clinical trials could help to continue trials during a pandemic. This paper presents the results of an exploratory study conducted early in the pandemic to gain insight into and describe the experiences of organisations involved in clinical trials, with regard to the impact of COVID-19 on the conduct of trials, and the adoption of decentralised methods prior to, and as mitigation for the impact, of COVID-19.MethodsA survey with 11 open-ended and four multiple choice questions was conducted in June 2020 among member organisations of the public-private "Trials@Home" consortium. The survey investigated (1) the impact and challenges of COVID-19 on the continuation of ongoing clinical trials, (2) the adoption of decentralised methods in clinical trials prior to and as a mitigation strategy for COVID-19, (3) the challenges of conducting clinical trials during COVID-19, (4) the expected permanency of COVID-19-driven changes to the adoption of decentralised methods in clinical trials, and (5) lessons learned from conducting clinical trials during the COVID-19 pandemic. A thematic, inductive analysis of open survey questions was performed, complemented with descriptive statistics (frequencies and distributions).ResultsThe survey had a response rate of 81%. All organisations included in the analysis (n = 18) implemented (some) decentralised methods in their clinical trials prior to COVID-19, and 15 (83%) implemented decentralised methods as mitigation for COVID-19. Decentralised methods for IMP supply, patient-health care provider interaction and communication, clinic visits and source document verification were used more often as mitigation strategies than they were used prior to COVID-19. Many respondents expect to maintain those decentralised methods they implemented during COVID-19 in ongoing trials, as well as implement them in future trials.ConclusionsDecentralised methods are a widely implemented mitigation strategy for trial conduct in the face of the COVID-19 pandemic. The results of this survey show that there is an interest to continue the use of decentralised methods in future trials, but important points of attention have been identified that need solutions to help guide the transition from the traditional trial model to a more decentralised trial model.

Project description:ObjectivesTo identify published closed-loop Bayesian mixed treatment comparisons (MTCs) and to summarise characteristics regarding their conduct and reporting.DesignSystematic review.MethodsWe searched multiple bibliographic databases (January 2006-31 July 2011) for full-text, English language publications of Bayesian MTCs comparing the effectiveness or safety of ≥3 interventions based on randomised controlled trials and having at least one closed loop. Methodological and reporting characteristics of MTCs were extracted in duplicate and summarised descriptively.ResultsWe identified 34 Bayesian MTCs spanning 13 clinical areas. Publication of MTCs increased over the 5-year period; with 76.5% published during or after 2009. MTCs included a mean (±SD) of 35.9±30.1 trials (n=33 459±71 233 participants) and 8.5±4.3 interventions (85.7% pharmacological). Non-informative and informative prior distributions were reported to be used in 44.1% and 8.8% of MTCs, respectively, with the remainder failing to specify the prior used. A random-effects model was used to analyse the networks of trials in 58.5% of MTCs, all using WinBUGS; however, code was infrequently provided (20.6%). More than two-thirds of MTCs (76.5%) also conducted traditional meta-analysis. Methods used to evaluate convergence, heterogeneity and inconsistency were infrequently reported, but from those providing detail, methods appeared varied. MTCs most often used a binary effect measure (85.3%) and ranking of interventions based on probability was common (61.8%), although rarely displayed in a figure (8.8% of MTCs). MTCs were published in 24 different journals with a mean impact factor of 9.20±8.71. While 70.8% of journals imposed limits on word counts and 45.8% limits on the number of tables/figures, online supplements/appendices were allowed in 79.2% of journals. Publication of closed-loop Bayesian MTCs is increasing in frequency, but details regarding their methodology are often poorly described. Efforts in clarifying the appropriate methods and reporting of Bayesian MTCs should be of priority.

Project description:ObjectiveTo systematically review the conduct and reporting of formula trials.DesignSystematic review.Data sourcesMedline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 1 January 2006 to 31 December 2020.Review methodsIntervention trials comparing at least two formula products in children less than three years of age were included, but not trials of human breast milk or fortifiers of breast milk. Data were extracted in duplicate and primary outcome data were synthesised for meta-analysis with a random effects model weighted by the inverse variance method. Risk of bias was evaluated with Cochrane risk of bias version 2.0, and risk of undermining breastfeeding was evaluated according to published consensus guidance. Primary outcomes of the trials included in the systematic review were identified from clinical trial registries, protocols, or trial publications.Results22 201 titles were screened and 307 trials were identified that were published between 2006 and 2020, of which 73 (24%) trials in 13 197 children were prospectively registered. Another 111 unpublished but registered trials in 17 411 children were identified. Detailed analysis was undertaken for 125 trials (23 757 children) published since 2015. Seventeen (14%) of these recently published trials were conducted independently of formula companies, 26 (21%) were prospectively registered with a clear aim and primary outcome, and authors or sponsors shared prospective protocols for 11 (9%) trials. Risk of bias was low in five (4%) and high in 100 (80%) recently published trials, mainly because of inappropriate exclusions from analysis and selective reporting. For 68 recently published superiority trials, a pooled standardised mean difference of 0.51 (range -0.43 to 3.29) was calculated with an asymmetrical funnel plot (Egger's test P<0.001), which reduced to 0.19 after correction for asymmetry. Primary outcomes were reported by authors as favourable in 86 (69%) trials, and 115 (92%) abstract conclusions were favourable. One of 38 (3%) trials in partially breastfed infants reported adequate support for breastfeeding and 14 of 87 (16%) trials in non-breastfed infants confirmed the decision not to breastfeed was firmly established before enrolment in the trial.ConclusionsThe results show that formula trials lack independence or transparency, and published outcomes are biased by selective reporting.Systematic review registrationPROSPERO 2018 CRD42018091928.

Project description:There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus.Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded.Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used.Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments.The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

Project description:BackgroundIn non-inferiority trials with non-adherence to interventions (or non-compliance), intention-to-treat and per-protocol analyses are often performed; however, non-random non-adherence generally biases these estimates of efficacy.ObjectiveTo identify statistical methods that adjust for the impact of non-adherence and thus estimate the causal effects of experimental interventions in non-inferiority trials.DesignA systematic review was conducted by searching the Ovid MEDLINE database (31 December 2020) to identify (1) randomised trials with a primary analysis for non-inferiority that applied (or planned to apply) statistical methods to account for the impact of non-adherence to interventions, and (2) methodology papers that described such statistical methods and included a non-inferiority trial application.OutcomesThe statistical methods identified, their impacts on non-inferiority conclusions, and their advantages/disadvantages.ResultsA total of 24 papers were included (4 protocols, 13 results papers and 7 methodology papers) reporting relevant methods on 26 occasions. The most common were instrumental variable approaches (n=9), including observed adherence as a covariate within a regression model (n=3), and modelling adherence as a time-varying covariate in a time-to-event analysis (n=3). Other methods included rank preserving structural failure time models and inverse-probability-of-treatment weighting. The methods identified in protocols and results papers were more commonly specified as sensitivity analyses (n=13) than primary analyses (n=3). Twelve results papers included an alternative analysis of the same outcome; conclusions regarding non-inferiority were in agreement on six occasions and could not be compared on six occasions (different measures of effect or results not provided in full).ConclusionsAvailable statistical methods which attempt to account for the impact of non-adherence to interventions were used infrequently. Therefore, firm inferences about their influence on non-inferiority conclusions could not be drawn. Since intention-to-treat and per-protocol analyses do not guarantee unbiased conclusions regarding non-inferiority, the methods identified should be considered for use in sensitivity analyses.Prospero registration numberCRD42020177458.

Project description:Rationale & objectiveAdaptive design methods are intended to improve the efficiency of clinical trials and are relevant to evaluating interventions in dialysis populations. We sought to determine the use of adaptive designs in dialysis clinical trials and quantify trends in their use over time.Study designWe completed a novel full-text systematic review that used a machine learning classifier (RobotSearch) for filtering randomized controlled trials and adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines.Setting & study populationsWe searched MEDLINE (PubMed) and ClinicalTrials.gov using sensitive dialysis search terms.Selection criteria for studiesWe included all randomized clinical trials with patients receiving dialysis or clinical trials with dialysis as a primary or secondary outcome. There was no restriction of disease type or intervention type.Data extraction & analytical approachWe performed a detailed data extraction of trial characteristics and a completed a narrative synthesis of the data.Results57 studies, available as 68 articles and 7 ClinicalTrials.gov summaries, were included after full-text review (initial search, 209,033 PubMed abstracts and 6,002 ClinicalTrials.gov summaries). 31 studies were conducted in a dialysis population and 26 studies included dialysis as a primary or secondary outcome. Although the absolute number of adaptive design methods is increasing over time, the relative use of adaptive design methods in dialysis trials is decreasing over time (6.12% in 2009 to 0.43% in 2019, with a mean of 1.82%). Group sequential designs were the most common type of adaptive design method used. Adaptive design methods affected the conduct of 50.9% of trials, most commonly resulting in stopping early for futility (41.2%) and early stopping for safety (23.5%). Acute kidney injury was studied in 32 trials (56.1%), kidney failure requiring dialysis was studied in 24 trials (42.1%), and chronic kidney disease was studied in 1 trial (1.75%). 27 studies (47.4%) were supported by public funding. 44 studies (77.2%) did not report their adaptive design method in the title or abstract and would not be detected by a standard systematic review.LimitationsWe limited our search to 2 databases (PubMed and ClinicalTrials.gov) due to the scale of studies sourced (209,033 and 6,002 results, respectively).ConclusionsAdaptive design methods are used in dialysis trials but there has been a decline in their relative use over time.

Project description:BackgroundConduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders. There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals. The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems.MethodsStandard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006. Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies.Results57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes.ConclusionParenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.

Dataset Information

A systematic review of methods used to conduct decentralised clinical trials.

Aims

Methods

Results

Conclusion

Publications

A systematic review of methods used to conduct decentralised clinical trials.

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