Transparency in reporting of phase 3 cancer clinical trial results.
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ABSTRACT:
SUBMITTER: Patel RR
PROVIDER: S-EPMC7951952 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Transparency in reporting of phase 3 cancer clinical trial results.
Patel Roshal R RR Verma Vivek V Fuller Clifton D CD McCaw Zachary R ZR Ludmir Ethan B EB
Acta oncologica (Stockholm, Sweden) 20201213 2
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Project description: Not available
| S-EPMC10413165 | biostudies-literature
Project description:ObjectiveTo annotate a corpus of randomized controlled trial (RCT) publications with the checklist items of CONSORT reporting guidelines and using the corpus to develop text mining methods for RCT appraisal.MethodsWe annotated a corpus of 50 RCT articles at the sentence level using 37 fine-grained CONSORT checklist items. A subset (31 articles) was double-annotated and adjudicated, while 19 were annotated by a single annotator and reconciled by another. We calculated inter-annotator agreement at the article and section level using MASI (Measuring Agreement on Set-Valued Items) and at the CONSORT item level using Krippendorff's α. We experimented with two rule-based methods (phrase-based and section header-based) and two supervised learning approaches (support vector machine and BioBERT-based neural network classifiers), for recognizing 17 methodology-related items in the RCT Methods sections.ResultsWe created CONSORT-TM consisting of 10,709 sentences, 4,845 (45%) of which were annotated with 5,246 labels. A median of 28 CONSORT items (out of possible 37) were annotated per article. Agreement was moderate at the article and section levels (average MASI: 0.60 and 0.64, respectively). Agreement varied considerably among individual checklist items (Krippendorff's α= 0.06-0.96). The model based on BioBERT performed best overall for recognizing methodology-related items (micro-precision: 0.82, micro-recall: 0.63, micro-F1: 0.71). Combining models using majority vote and label aggregation further improved precision and recall, respectively.ConclusionOur annotated corpus, CONSORT-TM, contains more fine-grained information than earlier RCT corpora. Low frequency of some CONSORT items made it difficult to train effective text mining models to recognize them. For the items commonly reported, CONSORT-TM can serve as a testbed for text mining methods that assess RCT transparency, rigor, and reliability, and support methods for peer review and authoring assistance. Minor modifications to the annotation scheme and a larger corpus could facilitate improved text mining models. CONSORT-TM is publicly available at https://github.com/kilicogluh/CONSORT-TM.
| S-EPMC8112250 | biostudies-literature
Project description:ObjectiveTo evaluate the accuracy of a 2015 cross-sectional analysis published in the BMJ Open which reported that pharmaceutical industry compliance with clinical trial registration and results reporting requirements under US law was suboptimal and varied widely among companies.DesignWe performed a reassessment of the data reported in Miller et al to evaluate whether statutory compliance analyses and conclusions were valid.Data sourcesInformation from the Dryad Digital Repository, ClinicalTrials.gov, Drugs@FDA and direct communications with sponsors.Main outcome measuresCompliance with the clinical trial registration and results reporting requirements under the Food and Drug Administration Amendments Act (FDAAA).ResultsIndustry compliance with FDAAA disclosure requirements was notably higher than reported by Miller et al. Among trials subject to FDAAA, Miller et al reported that, per drug, a median of 67% (middle 50% range: 0%-100%) of trials fully complied with registration and results reporting requirements. On reanalysis of the data, we found that a median of 100% (middle 50% range: 93%-100%) of clinical trials for a particular drug fully complied with the law. When looking at overall compliance at the trial level, our reassessment yields 94% timely registration and 90% timely results reporting among the 49 eligible trials, and an overall FDAAA compliance rate of 86%.ConclusionsThe claim by Miller et al that industry compliance is below legal standards is based on an analysis that relies on an incomplete dataset and an interpretation of FDAAA that requires disclosure of study results for drugs that have not yet been approved for any indication. On reanalysis using a different interpretation of FDAAA that focuses on whether results were disclosed within 30 days of drug approval, we found that industry compliance with US statutory disclosure requirements for the 15 reviewed drugs was consistently high.
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Project description:BackgroundPancreatic cancer (PC) is a highly malignant tumor of the digestive system. As clinical trials involving PC are increasingly being conducted, the transparency of the generated data has become an important issue of concern. In other areas of medicine, clinical trial transparency presents a worrying state of affairs. However, at present, there has been no study examining the transparency of data derived from PC clinical trials.MethodsA comprehensive search was conducted in the ClinicalTrial.gov database for clinical trials investigating pancreatic cancer as of June 2022. We examined the availability of clinical trial results and recorded the characteristics of the trials.ResultsA total of 856 trials were included in this study, of which 668 were completed and 188 were terminated or suspended. The results of 626 trials (73.13%) were available, of these 230 trials (26.87%) did not disclose any information on the trial data in any form. The publication rate for trials with available results was 86.10%, but the report rate on ClinicalTrial.gov was only 39.78%.ConclusionAlthough approximately 90% of clinical trial investigating interventions on patients with PC have published study results, 30% of trials did not report any findings, and the disclosure of trial results from ClinicalTrial.gov was unsatisfactory. In general, there is still room for improvement in the transparency of PC clinical trials.
| S-EPMC9853913 | biostudies-literature
Project description:We evaluated the efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC). Additionally, chemotherapy-induced changes in the tumor microenvironment and biomarkers of response were evaluated. In this single-arm phase II trial, eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction; then, adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab was given for 3 cycles and maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA-sequencing, reverse phase protein array analyses were performed on pre- and post-chemotherapy samples. Thirty-one eligible patients were enrolled. Median PFS was 14.88 months overall (95% CI 12.40 – 23.00). Among those with PD-L1 Combined Positive Score (CPS), the median PFS and OS were not reached compared to those with CPS<10 (10.50 and 30.90 months, respectively). All patients who initiated chemotherapy with pembrolizumab therapy completed their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling. In conclusion, pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS≥10 may benefit more from this regimen and future studies should investigate this potential biomarker. Funding for this investigator-initiated trial was provided by Merck. Clinicaltrials.gov: NCT02520154.
2025-01-22 | GSE271757 | GEO
Project description:Phase I Safety, Pharmacokinetic and Pharmacogenomic Trial of ES-285, a Novel Marine Cytotoxic Agent Administered as an Infusion over 24 h Every 21 Days in Patients with Solid Tumors Purpose: A dose-escalation, phase I study evaluated the safety, pharmacokinetics, pharmacogenomics and efficacy of ES-285, a novel agent isolated from a marine mollusc, in adult cancer patients. Experimental design: Patients received a 24-hour i.v. infusion of ES-285 once every 3 weeks until disease progression or unacceptable toxicity. The starting dose was 4mg/m2. Dose escalation proceeded according to the worst toxicity observed in the previous cohort. Results: 28 patients were treated with 72 courses of ES-285 across 8 dose levels. No doselimiting toxicities (DLTs) were seen between 4mg/m2 and 128mg/m2. Two out of 4 patients treated at 256mg/m2 had dose-limiting reversible grade 3 transaminitis; one patient at 256mg/m2 also had transient grade 3 central neurotoxicity. One of 3 patients subsequently treated at 200mg/m2 died following drug-related central neurotoxicity. Pharmacokinetic studies indicated dose-proportionality with high volume of distribution (median Vss at 256mg/m2 was 2389L, range 1615-4051L) and long elimination half life (median t1/2 at 256mg/m2 was 29h, range 21-32h). The 3 patients with DLT had the highest drug exposure. Pharmacogenomic studies of paired surrogate tissue samples identified changes in gene expression following treatment that correlated with increasing dose. Pre-treatment 59- and 49-gene sets were identified in blood and skin respectively, that may predict DLT. Disease stabilisation for 6 to 18 weeks was recorded in 9 patients. Conclusion: Using this schedule, 128 mg/m2 was considered safe and feasible. At this dose, pharmacologically relevant concentrations of drug were safely achieved with pharmacogenomic studies indicating changes in the expression of genes of potential biological relevance. Keywords: dose response
2009-04-01 | GSE12062 | GEO
Project description:Cytomegalovirus (CMV) is one of the most significant viral pathogens during pregnancy and in immunocompromised patients. Antiviral prophylactic strategies are limited by toxicities, drug-drug interactions and development of antiviral resistance. A safe and protective vaccine against CMV is highly desirable in view of the potential positive impact on CMV-associated morbidity and mortality as well as healthcare costs. Unfortunately, this demand could not be met in the past four decades although development of a CMV vaccine has been ranked at the highest priority by the US Institute of Medicine. Multiple different vaccine candidates have been developed and evaluated in phase I clinical trials and few succeeded to phase II trials. Nevertheless, two different vaccines showed recently promising results in trials that studied healthy adults and immunocompromised solid-organ and bone-marrow transplant recipients, respectively. The gB/MF59 vaccine exhibited a vaccine efficacy of 50% in healthy, postpartum females. In transplant patients, gB/MF59 and the DNA vaccine TransVax both limited the periods of viraemia and consequently the need for antiviral treatment. The success of these trials is encouraging and will probably give new impetus to the development of an effective CMV vaccine. Sterilizing immunity may not be attainable in the near future and may not be necessary for a CMV vaccine to have a significant impact on health care as discussed in the present review.
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Project description:Randomized controlled trials (RCTs) can produce valid estimates of the benefits and harms of therapeutic interventions. However, incomplete reporting can undermine the validity of their conclusions. Reporting guidelines, such as SPIRIT for protocols and CONSORT for results, have been developed to improve transparency in RCT publications. In this study, we report a corpus of 200 RCT publications, named SPIRIT-CONSORT-TM, annotated for transparency. We used a comprehensive data model that includes 83 items from SPIRIT and CONSORT checklists for annotation. Inter-annotator agreement was calculated for 30 pairs. The dataset includes 26,613 sentences annotated with checklist items and 4,231 terms. We also trained natural language processing (NLP) models that automatically identify these items in publications. The sentence classification model achieved 0.742 micro-F1 score (0.865 at the article level). The term extraction model yielded 0.545 and 0.663 micro-F1 score in strict and lenient evaluation, respectively. The corpus serves as a benchmark to train models that assist stakeholders of clinical research in maintaining high reporting standards and synthesizing information on study rigor and conduct.
| S-EPMC11871027 | biostudies-literature
Project description:Randomized controlled trials (RCTs) can produce valid estimates of the benefits and harms of therapeutic interventions. However, incomplete reporting can undermine the validity of their conclusions. Reporting guidelines, such as SPIRIT for protocols and CONSORT for results, have been developed to improve transparency in RCT publications. In this study, we report a corpus of 200 RCT publications, named SPIRIT-CONSORT-TM, annotated for transparency. We used a comprehensive data model that includes 83 items from SPIRIT and CONSORT checklists for annotation. Inter-annotator agreement was calculated for 30 pairs. The dataset includes 26,613 sentences annotated with checklist items and 4,231 terms. We also trained natural language processing (NLP) models that automatically identify these items in publications. The sentence classification model achieved 0.742 micro-F1 score (0.865 at the article level). The term extraction model yielded 0.545 and 0.663 micro-F1 score in strict and lenient evaluation, respectively. The corpus serves as a benchmark to train models that assist stakeholders of clinical research in maintaining high reporting standards and synthesizing information on study rigor and conduct.
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Project description:More than one published paper are often derived from analyzing the same cohort of individuals to make full use of the collected information. Preplanned study outcomes are generally mentioned in open databases while exhaustive information on methodological aspects are provided in submitted articles.
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