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"Clinical Studies as Topic - methods"
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Can an early phase clinical pharmacology study replace a thorough QT study? Experience with a novel H3-receptor antagonist/inverse agonist
Objective
The objective of the present study was to compare the effects of pitolisant on QTcF interval in a single ascending dose (SAD) study and a thorough QT (TQT) study.
Methods
The SAD study at three dose levels of pitolisant enrolled 24 males and the TQT study at two dose levels 25 males. Both studies intensively monitored ECGs and pitolisant exposure. Effect on QTcF interval was analysed by Intersection Union Test (IUT) and by exposure–response (ER) analysis. Results from the two studies were compared.
Results
In both studies, moxifloxacin effect established assay sensitivity. IUT analysis revealed comparable pitolisant-induced maximum mean (90 % confidence interval (CI)) placebo-corrected increase from baseline (ΔΔQTcF) in both the studies, being 13.3 (8.1; 18.5) ms at 200-mg and 9.9 (4.7; 15.1) ms at 240-mg doses in SAD study and 5.27 (2.35; 8.20) ms at 120-mg dose in TQT study. ER analysis revealed that ER slopes in SAD and TQT studies were comparable and significantly positive (0.031 vs 0.027 ms/ng/mL, respectively). At geometric mean concentrations, bootstrap predicted ΔΔQTcF (90 % CI) were 9.23 (4.68; 14.4) ms at 279 ng/mL (240-mg dose) in the SAD study and 4.97 (3.42; 8.19) ms at 156 ng/mL (120-mg dose) in the TQT study.
Conclusion
Pitolisant lacked an effect of regulatory concern on QTc interval in both the studies, however analysed, suggesting that the results from the SAD study could have mitigated the need for a TQT study. Our findings add to the growing evidence that intensive ECG monitoring in early phase clinical studies can replace a TQT study.
Journal Article
Standardized Methods for Enhanced Quality and Comparability of Tuberculous Meningitis Studies
Tuberculous meningitis (TBM) remains a major cause of death and disability in tuberculosis-endemic areas, especially in young children and immunocompromised adults. Research aimed at improving outcomes is hampered by poor standardization, which limits study comparison and the generalizability of results. We propose standardized methods for the conduct of TBM clinical research that were drafted at an international tuberculous meningitis research meeting organized by the Oxford University Clinical Research Unit in Vietnam. We propose a core dataset including demographic and clinical information to be collected at study enrollment, important aspects related to patient management and monitoring, and standardized reporting of patient outcomes. The criteria proposed for the conduct of observational and intervention TBM studies should improve the quality of future research outputs, can facilitate multicenter studies and meta-analyses of pooled data, and could provide the foundation for a global TBM data repository.
Journal Article
Bridging the Gap Between Research and Practice: Implementation Science
Purpose: This article introduces implementation science, which focuses on research methods that promote the systematic application of research findings to practice. Method: The narrative defines implementation science and highlights the importance of moving research along the pipeline from basic science to practice as one way to facilitate evidence-based service delivery. This review identifies challenges in developing and testing interventions in order to achieve widespread adoption in practice settings. A framework for conceptualizing implementation research is provided, including an example to illustrate the application of principles in speech-language pathology. Last, the authors reflect on the status of implementation research in the discipline of communication sciences and disorders. Conclusions: The extant literature highlights the value of implementation science for reducing the gap between research and practice in our discipline. While having unique principles guiding implementation research, many of the challenges and questions are similar to those facing any investigators who are attempting to design valid and reliable studies. This article is intended to invigorate interest in the uniqueness of implementation science among those pursuing both basic and applied research. In this way, it should help ensure the discipline's knowledge base is realized in practice and policy that affects the lives of individuals with communication disorders.
Journal Article
Evaluating biosimilars: safety, efficacy, and regulatory considerations in clinical studies
Biosimilars are a rapidly growing area of clinical research, yet they encounter significant challenges, especially in emerging markets where regulatory and clinical hurdles differ markedly from those in established regions like Europe and the US. This commentary addresses these unique challenges and offers new perspectives on the global adoption of biosimilars. It emphasizes the crucial role of real world evidence in supporting biosimilar approvals, an aspect often underrepresented in current literature. The commentary also provides a comparative analysis of the regulatory frameworks in China and Europe, highlighting how these differences shape biosimilar development and market approval processes. By focusing on the issues of indication extrapolation and immunogenicity, this commentary highlights the necessity of continuous real-world data collection to ensure the safety and efficacy of biosimilars across multiple indications. Our analysis enhances the understanding of biosimilar research and supports their broader adoption as safe, effective, and accessible healthcare solutions globally.
Journal Article
Methodological Tutorial Series for Epidemiological Studies: When and How to Split the Follow-up Time in the Analysis of Epidemiological or Clinical Studies With Follow-ups
In epidemiological or clinical studies with follow-ups, data tables generated and processed for statistical analysis are often of the “wide-format” type, consisting of one row per individual. However, depending on the situation and purpose of the study, they may need to be transformed into the “long-format” type, which allows for multiple rows per individual. This tutorial clarifies the typical situations wherein researchers are recommended to split follow-up times to generate long-format data tables. In such applications, the major analytical aims consist of (i) estimating the outcome incidence rates or their ratios between ≥2 groups, according to specific follow-up time periods; (ii) examining the interaction between the exposure status and follow-up time to assess the proportional hazards assumption in Cox models; (iii) dealing with time-varying exposures for descriptive or predictive purposes; (iv) estimating the causal effects of time-varying exposures while adjusting for time-varying confounders that may be affected by past exposures; and (v) comparing different time periods within the same individual in self-controlled case-series analyses. This tutorial also discusses how to split follow-up times according to their purposes in practical settings, providing example codes in Stata, R, and SAS.
Journal Article
Improving site selection in clinical studies: a standardised, objective, multistep method and first experience results
IntroductionA considerable number of clinical studies experience delays, which result in increased duration and costs. In multicentre studies, patient recruitment is among the leading causes of delays. Poor site selection can result in low recruitment and bad data quality. Site selection is therefore crucial for study quality and completion, but currently no specific guidelines are available.Material and methodsSelection of sites adequate to participate in a prospective multicentre cohort study was performed through an open call using a newly developed objective multistep approach. The method is based on use of a network, definition of objective criteria and a systematic screening process.Illustrative example of the method at workOut of 266 interested sites, 24 were shortlisted and finally 12 sites were selected to participate in the study. The steps in the process included an open call through a network, use of selection questionnaires tailored to the study, evaluation of responses using objective criteria and scripted telephone interviews. At each step, the number of candidate sites was quickly reduced leaving only the most promising candidates. Recruitment and quality of data went according to expectations in spite of the contracting problems faced with some sites.ConclusionThe results of our first experience with a standardised and objective method of site selection are encouraging. The site selection method described here can serve as a guideline for other researchers performing multicentre studies.Trial registration numberClinicalTrials.gov: NCT02297581.
Journal Article
Implementation Science: Buzzword or Game Changer?
Purpose: The purpose of this supplement article is to provide a resource of pertinent information concerning implementation science for immediate research application in communication sciences and disorders. Method: Key terminology related to implementation science is reviewed. Practical suggestions for the application of implementation science theories and methodologies are provided, including an overview of hybrid research designs that simultaneously investigate clinical effectiveness and implementation as well as an introduction to approaches for engaging stakeholders in the research process. A detailed example from education is shared to show how implementation science was utilized to move an intervention program for autism into routine practice in the public school system. In particular, the example highlights the value of strong partnership among researchers, policy makers, and frontline practitioners in implementing and sustaining new evidence-based practices. Conclusions: Implementation science is not just a buzzword. This is a new field of study that can make a substantive contribution in communication sciences and disorders by informing research agendas, reducing health and education disparities, improving accountability and quality control, increasing clinician satisfaction and competence, and improving client outcomes.
Journal Article
Deferred consent for delivery room studies: the providers’ perspective
ObjectiveTo gain insight into neonatal care providers’ perceptions of deferred consent for delivery room (DR) studies in actual scenarios.MethodsWe conducted semistructured interviews with 46 neonatal intensive care unit (NICU) staff members of the Leiden University Medical Center (the Netherlands) and the Hospital of the University of Pennsylvania (USA). At the time interviews were conducted, both NICUs conducted the same DR studies, but differed in their consent approaches. Interviews were audio-recorded, transcribed and analysed using the qualitative data analysis software Atlas.ti V.7.0.ResultsAlthough providers reported to regard the prospective consent approach as the most preferable consent approach, they acknowledged that a deferred consent approach is needed for high-quality DR management. However, providers reported concerns about parental autonomy, approaching parents for consent and ethical review of study protocols that include a deferred consent approach. Providers furthermore differed in perceived appropriateness of a deferred consent approach for the studies that were being conducted at their NICUs. Providers with first-hand experience with deferred consent reported positive experiences that they attributed to appropriate communication and timing of approaching parents for consent.ConclusionInsight into providers’ perceptions of deferred consent for DR studies in actual scenarios suggests that a deferred consent approach is considered acceptable, but that actual usage of the approach for DR studies can be improved on.
Journal Article
The Use of Allograft Bone in the Lateral Approach of Sinus Floor Elevation: A Systematic Review of Clinical Studies
Background and Objectives: The aim of this systematic review was to assess the efficiency of using allografts for sinus lift. Materials and Methods: This systematic review was written under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendation of the Cochrane Handbook for Systematic Reviews of Interventions. Three electronic databases were screened until October 2023. The risk of bias was assessed according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines. Statistical analysis was performed for median bone volume and implant survival rate. Results: From 321 articles retrieved, 7 articles were included in this review. A comparison between freeze-dried bone allograft (FDBA) and deproteinized bovine bone (DBB) for mean bone volume indicated a weighted mean difference (WMD) of −0.17 [−0.69, 0.36] (95% confidence interval (CI)), p = 0.53. For implant survival rate, a comparison was made between FDBA and autogenous bone indicating a risk ratio (RR) of 1.00 [0.96, 1.05] (95% CI), p = 1.00. Conclusions: The available evidence suggested that allograft bone can be used in sinus lift procedures. The results obtained are insufficient to compare with other types of bone graft, requiring a longer follow-up time. Future clinical trials are needed in order to evaluate the advantages of using allograft bone.
Journal Article