Topic
Trial Phase
About: Trial Phase is a research topic. Over the lifetime, 19 publications have been published within this topic receiving 339 citations.
Papers
TL;DR: Over half of clinical trials initiated for rare diseases were either discontinued or not published 4 years after completion, resulting in large numbers of patients with rare diseases exposed to interventions that did not lead to informative findings.
Abstract: Background Rare diseases affect as many as 60 million people in the United States and Europe. However, most rare diseases lack effective therapies and are in critical need of clinical research. Our objective was to determine the frequency of noncompletion and nonpublication of trials studying rare diseases. Methods and findings We conducted a cross-sectional analysis of randomized clinical trials studying rare diseases as defined by the Genetic and Rare Disease Information Center database that were registered in ClinicalTrials.gov between January 1, 2010, and December 31, 2012, and completed or discontinued by December 31, 2014. Our main outcome measures were the frequency of trial noncompletion and, among completed studies, frequency of trial nonpublication at 2 and 4 years following trial completion. Reasons for discontinuation were extracted from the registry, and trial sponsors were contacted for additional information, as needed. Two independent investigators performed publication searches for each trial in PubMed, EMBASE, and GoogleScholar, allowing for a minimum of 45 months between trial completion and publication. When a publication could not be identified, trial sponsors were contacted to confirm publication status. The impact of funding source on trial noncompletion was assessed with multivariable logistic regression, and the effect on time to publication was examined with Cox proportional hazards regression. Control variables included intervention type, trial phase, masking, enrollment, and study population. We analyzed 659 rare disease trials accounting for 70,305 enrolled patients. Industry was the primary funder for 327 trials (49.6%) and academic institutions for 184 trials (27.9%). There were 79 trials (12.0%) focused on pediatric populations. A total of 199 trials (30.2%) were discontinued. Lack of patient accrual (n = 64, 32.1%) and informative termination (n = 41, 20.6%) were the most common reasons for trial noncompletion. Among completed trials, 306 (66.5%) remained unpublished at 2 years and 142 (31.5%) at 4 years. In multivariable analyses, industry-funded trials were less likely to be discontinued than trials funded by healthcare centers (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.34–4.39, P = 0.003). We found no significant association between funding source and time to publication. A total of 18,148 patients were enrolled in trials that were discontinued or unpublished 4 years after completion. A potential limitation of our study is that certain interventional trials for rare diseases may not have been registered in ClinicalTrials.gov, in particular Phase 0 and Phase I trials, which are not required to be registered. Conclusions In this study, over half of clinical trials initiated for rare diseases were either discontinued or not published 4 years after completion, resulting in large numbers of patients with rare diseases exposed to interventions that did not lead to informative findings. Concerted efforts are needed to ensure that participation of patients in rare disease trials advances scientific knowledge and treatments for rare diseases.
79 citations
TL;DR: Using a whole of service stepped care model of treatment for personality disorder significantly reduced demand on hospital services.
Abstract: Background and objectives People with personality disorders are prevalent in emergency and inpatient mental health services. We examined whether implementing a stepped care model of psychological therapy reduces demand on hospital units by people with personality disorder, in a cluster randomized controlled trial. Method A total of 642 inpatients (average age 36.8, 50.5% female) with a primary ICD-10 personality disorder were recruited during 18 months baseline, then monitored during an 18 month active trial phase. In the active trial phase two equivalent sites were randomised to either treatment as usual (TAU), or a whole of service intervention that diverted people away from hospital and into stepped care psychological therapy clinics. The study design was cost neutral, with no additional staff or resources deployed between sites. A linear mixed models analysis evaluated outcomes. Results As predicted, demand on hospital services reduced significantly in the intervention compared to TAU site. The intervention site evidenced shorter bed days, from an average of 13.46 days at baseline to 4.28 days per admission, and patients were 1.3 times less likely to re-present to the emergency department compared to TAU. Direct cost savings for implementing the approach was estimated at USD$2,720 per patient per year. Limitations included not directly comparing individual symptom changes. Conclusions Using a whole of service stepped care model of treatment for personality disorder significantly reduced demand on hospital services.
60 citations
1 Nov 2014
TL;DR: This work developed a classifier to identify combination trials and oncology trials through natural language processing techniques and categorized them based on selected characteristics and observed trends present, which may facilitate future trial design and move more preclinical combination studies to the clinical trial stage.
Abstract: Within the past few decades, drug combination therapy has been intensively studied in oncology and other complex disease areas, especially during the early drug discovery stage, as drug combinations have the potential to improve treatment response, minimize development of resistance or minimize adverse events. In the present, designing combination trials relies mainly on clinical and empirical experience. While empirical experience has indeed crafted efficacious combination therapy clinical trials (combination trials), however, garnering experience with patients can take a lifetime. The preliminary step to eliminating this barrier of time, then, is to understand the current state of combination trials. Thus, we present the first large-scale study of clinical trials (2008-2013) from ClinicalTrials.gov to compare combination trials to non-combination trials, with a focus on oncology. In this work, we developed a classifier to identify combination trials and oncology trials through natural language processing techniques. After clustering trials, we categorized them based on selected characteristics and observed trends present. Among the characteristics studied were primary purpose, funding source, endpoint measurement, allocation, and trial phase. We observe a higher prevalence of combination therapy in oncology (25.6% use combination trials) in comparison to other disease trials (6.9%). However, surprisingly the prevalence of combinations does not increase over the years. In addition, the trials supported by the NIH are significantly more likely to use combinations of drugs than those supported by industry. Our preliminary study of current combination trials may facilitate future trial design and move more preclinical combination studies to the clinical trial stage.
56 citations
TL;DR: Much of the information collected in unsuccessful drug trials is inaccessible to the broader research and practice communities and provides an evidence base and rationale for policy reforms aimed at promoting transparency, ethics, and accountability in clinical research.
Abstract: Objective To quantify the proportion of trials for unsuccessfully licensed drugs that are not published. Design A systematic assessment of the availability of published research reports for publicly registered trials testing drugs stalling in clinical development (“stalled drugs”) and drugs receiving regulatory licensure in the same time period (“licensed drugs”). Data sources Searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, and electronic query of contacts in registries to identify trials and assess publication status. Eligibility criteria The cohort of licensed drugs consisted of all disease modifying drugs in cancer, cardiovascular disease, or neurological disorders that received Food and Drug Administration licensure during 2005 to 2009 inclusive. The cohort of stalled drugs included unlicensed drugs in the same disease areas that had at least one completed phase III trial before 2009 and no evidence of any clinical trial activity after 31 December 2009. Inclusion criteria for registered trials advanced into publication searching were an intervention tested in a disease modifying, phase II, III, or IV trial registered on clinicaltrials.gov, with enrolment of at least one patient, that reported primary outcome collection end date between 1 January 2006 and 31 December 2008. Results The unadjusted publication proportion for registered trials of licensed drugs was 75% (72/96) versus 37% (30/81) for stalled drugs. The adjusted hazard ratio for publication was 2.7 (95% confidence interval 1.7 to 4.3) in favour of licensed drug trials. Higher publication rates for licensed drug trials were observed regardless of disease type, sponsorship, trial phase, and geography. The rate of non-publication of stalled drug trials was significantly higher for studies that did not complete enrolment compared with licensed drug trials. A total of 20 135 patients participated in trials of stalled drugs that were never published. Conclusions Much of the information collected in unsuccessful drug trials is inaccessible to the broader research and practice communities. These findings provide an evidence base and rationale for policy reforms aimed at promoting transparency, ethics, and accountability in clinical research.
29 citations
TL;DR: Whether early intervention during the first 2 years of life is effective and cost-effective in preventing childhood overweight and obesity at 3½ and 5 years old is ascertained.
26 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 1 |
| 2020 | 2 |
| 2019 | 2 |
| 2018 | 2 |
| 2017 | 3 |
| 2015 | 2 |