Major Clinical Trial Registries Research Articles

Effects of transition programmes to adulthood for adolescents and young adults with CHD: a systematic review with meta-analysis.

The increased survival rate among individuals with CHD has sparked interest in their transition to adult healthcare. Although there is a general agreement on the importance of transition interventions, the empirical evidence supporting them is insufficient. Therefore, this study aimed to conduct a systematic review and meta-analysis of transition interventions for adult healthcare in adolescents and young adults. A literature search was conducted for studies comparing the quantitative effects of transition interventions with control groups, published up to March 15, 2023, in major databases (CENTRAL, Embase, PubMed, Web of Science, CINAHL, KISS, and KMbase), major clinical trial registries, academic journal sites related to the topic, and grey literature databases. Ten studies involving a total of 1,297 participants were identified. Transition interventions proved effective in enhancing disease-related knowledge (Hedge's g = 0.89, 95% CI = 0.29-1.48) and self-management (Hedge's g = 0.67, 95% CI = 0.38-0.95), as well as reducing loss to follow-up (OR = 0.41, 95% CI = 0.22-0.77). The certainty of evidence for the estimated values of each major outcome was low or very low. This study supports the implementation of transition interventions by demonstrating that they can improve patients' disease knowledge and self-management, while also promoting treatment continuity. However, since the available data on transition interventions for adolescents and young adults with CHD remain limited, the widespread adoption of structured transition interventions in the future may alter the conclusions of this study. URL: https://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42023399026.

A Controversial Old Topic Revisited: Should Diagnostic Hysteroscopy Be Routinely Performed prior to the First IVF Cycle? A Systematic Review and Updated Meta-analysis

This systematic review and meta-analysis aimed to analyze the impact of performing diagnostic hysteroscopy before the first in vitro fertilization (IVF) cycle on the clinical pregnancy rate and live birth. PubMed-MEDLINE, Embase, Web of Science, The Cochrane Library, Gynecology and Fertility Specialized Register of Controlled Trials, and Google Scholar were consulted from inception to June 2022 using combinations of the relevant Medical Subject Headings terms and keywords. The search included major clinical trial registries such as ClinicalTrials.gov and the European EudraCT registry without language restrictions. In addition, manual cross-reference searches were also performed. All randomized and controlled clinical trials, prospective and retrospective cohort studies, and case-control studies comparing the probability of pregnancy and live birth among patients who underwent diagnostic hysteroscopy with possible treatment of any abnormal findings before the IVF cycle and patients who underwent the IVF cycle directly have been considered for inclusion. Studies with insufficient information on the results of interest or without the necessary information to perform the pooled analysis, those without a control group or with end points considered different than those of interest, were excluded. The review protocol was registered in PROSPERO (CRD42022354764). A total of 12 studies were included in the quantitative synthesis, reporting the reproductive outcomes of 5056 patients undergoing ART treatment for the first time. Selected studies included 6 randomized controlled trials, 1 prospective cohort study, 3 retrospective cohort studies, and 2 case-control studies. The likelihood of clinical pregnancy of patients undergoing hysteroscopy before IVF was significantly higher than those without hysteroscopy (odds ratio [OR], 1.49; 95% confidence CI 1.16-1.91; I2 = 69%). (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.22-1.88; I2 59%). Eight studies included live birth rate; no statistically significant differences were found between the 2 groups for this outcome (OR,1.24; 95% CI, 0.94-1.64; I2 = 62%). Subsequently, a sensitivity analysis was performed, including only randomized clinical trials. Clinical pregnancy OR of patients undergoing hysteroscopy before starting the IVF cycle remained significantly higher than the control group (OR,1.62, 95% CI, 1.15-2.29; I2 = 62%). Risk of bias assessment was performed using the Grading of Recommendations Assessment, Development, and Evaluation. The available scientific evidence suggests that performing routine hysteroscopy before the first IVF attempt improves the clinical pregnancy rate; however, the live birth rate is unaffected.

Lay titles for clinical trials: Is industry achieving the balance?

Titles of clinical trials may directly influence whether patients, caretakers, or healthcare professionals will want to obtain more information about the trial. Major clinical trial registries require lay titles (referred to as “brief” or “public” titles) that are understandable to the public. However, devising adequate lay titles is challenging. In this study, we assessed the quality of lay titles from Phase II/III and III clinical trials registered in ClinicalTrials.gov in 2021. Assessments included the presence of recommended elements, use of technical terms, an expert assessment of adequacy and informativeness, title length, and the use of acronyms. A large proportion (72%) of lay titles did not include all recommended elements, contained technical terms (73%), and were not adequate according to experts (51%). Often, brevity was given precedence over content and understandability. Generally, lay titles with acronyms had better ratings in all assessed categories. These results suggest that industry sponsors can do more to create lay titles that better inform patients and healthcare providers.

OP218 Searching Preprint Repositories For COVID-19 Therapeutics Using A Semi-Automated Text-Mining Tool

IntroductionThe COVID-19 pandemic led to a significant surge in clinical research activities in the search for effective and safe treatments. Attempting to disseminate early findings from clinical trials in a bid to accelerate patient access to promising treatments, a rise in the use of preprint repositories was observed. In the UK, NIHR Innovation Observatory (NIHRIO) provided primary horizon-scanning intelligence on global trials to a multi-agency initiative on COVID-19 therapeutics. This intelligence included signals from preliminary results to support the selection, prioritisation and access to promising medicines.MethodsA semi-automated text mining tool in Python3 used trial IDs (identifiers) of ongoing and completed studies selected from major clinical trial registries according to pre-determined criteria. Two sources, BioRxiv and MedRxiv are searched using the IDs as search criteria. Weekly, the tool automatically searches, de-duplicates, excludes reviews, and extracts title, authors, publication date, URL and DOI. The output produced is verified by two reviewers that manually screen and exclude studies that do not report results.ResultsA total of 36,771 publications were uploaded to BioRxiv and MedRxiv between March 3 and November 9 2020. Approximately 20–30 COVID-19 preprints per week were pre-selected by the tool. After manual screening and selection, a total of 123 preprints reporting clinical trial preliminary results were included. Additionally, 50 preprints that presented results of other study types on new vaccines and repurposed medicines for COVID-19 were also reported.ConclusionsUsing text mining for identification of clinical trial preliminary results proved an efficient approach to deal with the great volume of information. Semi-automation of searching increased efficiency allowing the reviewers to focus on relevant papers. More consistency in reporting of trial IDs would support automation. A comparison of accuracy of the tool on screening titles/abstract or full papers may help to support further refinement and increase efficiency gains.This project is funded by the NIHR [(HSRIC-2016-10009)/Innovation Observatory]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

The Alzheimer\u2019s disease drug development landscape

BackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disease leading to dementia. The field has made significant progress over the last 15 years. AD diagnosis has shifted from syndromal, based on signs and symptoms, to a biomarker construct based on the pathological hallmarks of the disease: amyloid β deposition, pathologic tau, and neurodegeneration. Numerous genetic risk factors for sporadic AD have been identified, providing further insight into the molecular underpinnings of the disease. For the last two decades, however, drug development for AD has been proven to be particularly challenging. Here, we provide a unique overview of the drug development landscape for AD. By comparing preclinical and clinical drug development pipelines, we aim to describe trends and differences regarding target classes and therapeutic modalities in preclinical and clinical development.MethodsWe analyzed proprietary and public databases and company websites for drugs in preclinical development for AD by the pharmaceutical industry and major clinical trial registries for drugs in clinical development for AD. Drugs were categorized by target class and treatment modality.ResultsWe found a higher proportion of preclinical interventions targeting molecular pathways associated with sporadic AD genetic risk variants, compared to clinical stage interventions. These include apolipoprotein E (ApoE) and lipids, lysosomal/endosomal targets, and proteostasis. Further, we observed a trend suggesting that more traditional therapeutic modalities are developed for these novel targets, while more novel treatment modalities such as gene therapies and enzyme treatments are in development for more traditional targets such as amyloid β and tau. Interestingly, the percentage of amyloid β targeting therapies in preclinical development (19.2%) is even higher than the percentage in clinical development (10.7%), indicating that diversification away from interventions targeting amyloid-beta has not materialized. Inflammation is the second most popular target class in both preclinical and clinical development.ConclusionsOur observations show that the AD drug development pipeline is diversifying in terms of targets and treatment modalities, while amyloid-targeting therapies remain a prominent avenue of development as well. To further advance AD drug development, novel companion diagnostics are needed that are directed at disease mechanisms related to genetic risk factors of AD, both for patient stratification and assessment of therapeutic efficacy in clinical trials.

Glaucoma Clinical Research: Trends in Treatment Strategies and Drug Development.

Purpose: To investigate the trends and progresses in glaucoma research by searching two major clinical trial registries; clinicaltrials.gov, and Australianclinicaltrials.gov.au.Methods: All clinical trials with glaucoma covered by Clinicaltrials.gov, and Australianclinicaltrials.gov.au starting the study before 1 January 2021 were included. Trials evaluating glaucoma treatment were separated from non-treatment trials and divided into three major categories: “laser treatment,” “surgical treatment,” and “medical treatment.” In the category of “medical treatment,” new compounds and their individual targets were identified and subcategorized according to treatment strategy; intraocular pressure (IOP)-lowering, neuroprotective or vascular. The phase transition success rates were calculated.Results: One-thousand five hundred and thirty-seven trials were identified. Sixty-three percent (n = 971) evaluated glaucoma treatment, of which medical treatment accounted for the largest proportion (53%). The majority of medical trials evaluated IOP-lowering compounds, while trials with neuroprotective or vascular compounds accounted for only 5 and 3%, respectively. Eighty-eight new compounds were identified. Phase I, II, and III transition success rates were 63, 26, and 47%, respectively.Conclusion: The number of clinical trials in glaucoma research has increased significantly over the last 30 years. Among the most recently evaluated compounds, all three main treatment strategies were represented, but clinical trials in neuroprotection and vascular modalities are still sparse. In addition to traditional medicines, dietary supplements and growth factors are assessed for a potential anti-glaucomatous effect. Phase II and III success rates were below previously reported success rates for all diseases and ophthalmology in general. A stricter phenotyping of patients can improve the success rates in glaucoma and ophthalmological research and gain a better understanding of responders and non-responders.

Scarce quality assurance documentation in major clinical trial registries for approved medicines used in post-marketing clinical trials

BackgroundThis research reviewed major Clinical Trial Registries (CTRs) and assessed the availability of fields on quality assurance for approved medicines used as Investigational Medicinal Products (IMPs) in phase IV clinical trials.MethodsTwo reviewers independently assessed CTRs of the International Committee of Medical Journal Editors (ICJME) and of World Health Organization (WHO) platforms. Each CTR was checked by two reviewers on availability of fields on brand name, manufacturer’s name, approval status, approving authority, compliance with Good Manufacturing Practices, and quality testing. In case of discrepancy, consensus was sought between the two reviewers.ResultsOf 19 identified CTRs, 8 and 6 belonged to WHO and ICMJE, respectively, while 5 were equally part of both platforms. All CTRs had an ‘intervention’ field where data on IMPs and IMP comparators are captured. The Canadian CTR used ‘drug name’ rather than ‘intervention’. The EU, Peruvian, and UK CTRs had fields for ‘brand name’. However, only the EU CTR had fields for ‘manufacturer’s name’, ‘approval status’, and ‘approving authority’. None of the CTRs had fields on ‘compliance with Good Manufacturing Practices’ or ‘quality testing’.ConclusionThis study demonstrates that none of the CTRs of ICMJE and WHO platforms has adequate fields to establish that the source of post-marketing IMPs is of assured quality. This is astonishing given the lengthy requirements in WHO and ICMJE guidelines. Considering the relation between IMP quality and safety of clinical trial participants, the gap of quality assurance fields should be bridged at CTRs concurrently to adjustments of WHO and ICMJE guidelines on CTRs. Specifically, IMP quality testing addressing issues on IMP appearance, impurities, microbial contamination, and dosing should be conducted and reported before, during, and after clinical trial conduct. Until adoption of these measures, the EU CTR should be preferred for registration of phase IV clinical trials conducted in countries lacking stringent regulatory capacities.

Effectiveness of triple antibiotic paste as an intra-canal medication for the root canal treatment of non-vital teeth with apical periodontitis: A systematic review

Background: This is a systematic review to assess and provide a pooled effect estimate, if possible, for the effects of triple antibiotic paste as an intra-canal medication for root canal treatment of mature permanent non-vital teeth with apical periodontitis. This review will assess post-operative pain, flare-up incidence, and clinical and radiographic healing. Methods: Nine electronic databases (Pubmed, CENTRAL, VHL, Scopus, EBSCOhost, Web of Science, Trip, OpenGrey, Proquest) were searched along with two major clinical trial registries. Conference proceedings, reference lists and citations of the included studies were also searched. A total of 537 records were identified and 392 were obtained after duplicate removal. Six records were identified after screening and three studies were included after full text eligibility assessment. Results: Three comparators were reported in the included studies: calcium hydroxide paste, 2% chlorhexidine gel and ledermix paste. There was no statistically significant difference between triple antibiotic paste and calcium hydroxide regarding postoperative pain, and clinical and radiographic healing of periapical lesions. There was no difference between triple antibiotic paste and chlorhexidine regarding flare-up incidence. However, triple antibiotic paste reduced the level of post-operative pain more than ledermix, which was statistically significant. Conclusions: The evidence is still insufficient surrounding the use of triple antibiotic paste; therefore more clinical investigations with high levels of evidence and rigorous methodologies are needed.

Effect of carboplatin on pathologic complete remission rate and hematotoxicity incidence in neoadjuvant treatment of triple-negative breast cancer: A meta-analysis.

e12638Background: To evaluate the efficacy and safety of carboplatin-based neoadjuvant chemotherapy in triple-negative breast cancer patients (TNBC). Methods: PubMed, EMBASE, the Web of Science, th...

Efficacy of carboplatin-based preoperative chemotherapy for triple-negative breast cancer. A meta-analysis of randomized controlled trials.

Objectives:To evaluate the efficacy and safety of carboplatin-based preoperative chemotherapy in triple-negative breast cancer patients (TNBC).Methods:PubMed, EMBASE, the Web of Science, the Cochrane Library, major clinical trial registries, and abstract collections from major international meetings were systematically searched for relevant randomized controlled trials. Endpoints included rates of pathologic complete response (pCR), overall response (ORR), breast-conserving surgery (BCS) and toxicity. Pooled relative risk (RR) was calculated for each endpoint using a fixed- or random-effect model depending on the heterogeneity among included studies.Results:A total of 5 randomized controlled trials involving 1007 patients were included in the meta-analysis. Carboplatin-based chemotherapy was associated with a pooled pCR rate of 53.3%, which was significantly higher than the rate associated with non-carboplatin therapy (37.8%, RR: 1.41, 95% confidence interval [CI]: 1.23 to 1.62, p<0.00001). Compared with non-carboplatin therapy (48.1%), carboplatin-based chemotherapy increased BCS rate (59.7%, RR: 1.24, 95% CI: 1.06 to 1.46, p=0.007). Carboplatin-based chemotherapy was associated with similar ORR as non-carboplatin therapy. Carboplatin-based chemotherapy was associated with higher incidence of grade 3 or 4 anemia, neutropenia, febrile neutropenia, and thrombocytopenia than non-carboplatin therapy, while the 2 regimens were associated with similar incidence of fatigue, leucopenia, and nausea/vomiting.Conclusion:The available evidence suggests that carboplatin-based preoperative chemotherapy is associated with significantly better pCR and BCS rates than non-carboplatin-based therapy in TNBC patients.