FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2793479504> ?p ?o ?g. }

• W2793479504 endingPage "614" @default.
• W2793479504 startingPage "611" @default.
• W2793479504 abstract "Reports and publications on late phase clinical trials and other medical research are nowadays highly regulated, in particular confirmatory trials aiming to demonstrate the efficacy and safety of health technologies. This does not only affect the actual submission of drug dossiers to health authorities to achieve marketing authorisation. It already starts with the registration of clinical trials in publicly available registers at the time when the study protocols have been finalised and extends to requirements and guidelines for publications in medical journals 1. The key objective of these regulations is to achieve transparency how the research was actually planned, performed and analysed and which decisions had been made to accommodate unplanned situations. Thereby allowing the internal and external validity of the trial results to be judged, so that the interpretations and conclusions are comprehensible for readers. The targeted audience includes reviewers who are to decide whether an intended publication is fit to be presented to the wider scientific community. Thus, convincing the reader of the quality of one's research means convincing the reviewer first. Accordingly, within the EQUATOR network (Enhancing the QUAlity and Transparency Of health Research), a large number of reporting recommendations have been developed. Starting with the CONSORT statement on confirmatory randomised parallel group clinical trials 2, there are now extensions for trials with particular designs (e.g. equivalence trials or N-of-1 trials), but also more general fields like systematic reviews (PRISMA) or diagnostic/prognostic studies. So it seems that most of the medical research has its own reporting guideline. Interestingly, these guidelines do not cover clinical pharmacology studies. There are some extensions that might appear to be closely related, such as the “reporting within-person randomised trials,” or the “reporting randomised pilot and feasibility trials,” but a closer view clarifies that their overlap with clinical pharmacology is rather minor. For example, the “within-person trials” guideline does not cover conventional crossover trials (with sequential treatments), but trials in which two treatments are applied simultaneously to the same person (e.g. to both eyes, to teeth or to different places of the skin). The “pilot and feasibility trial” guideline focuses on the practical development of the trial design and its implementation for a confirmatory trial, rather than on the development of a pharmacological treatment in Phase I-IIa regarding pharmacokinetics, pharmacodynamics and proof of principle with “surrogates” like biomarkers. In a BJCP editorial about 2 years ago 3, it was asked whether clinical pharmacology would benefit from having such guidelines. On one hand, clinical pharmacology trials are very diverse, sometimes not randomised, with quite different objectives, designs, and analysis methods. On the other hand, the editors and reviewers of this journal and of other journals in this field will receive manuscripts of quite heterogeneous quality, and it sometimes takes a number of review cycles to expand a good research to a good publication. So it might be beneficial to have at least some general framework (in addition to the journal specific “author guidelines”). What is the status? A few years ago, some pharmacologists, pharmacometricians and statisticians from both industry and academia had initiated a working group to look into the current reporting quality in clinical pharmacology and to develop recommendations. They started their work based on earlier investigations on the quality of reporting 4, 5, which they have expanded and updated by reviewing a variety of publications to evaluate whether modifications to the main CONSORT 2010 statement for an extension to clinical pharmacology should be proposed. The main conclusion was that specific recommendations should be given to detailing the methodology sections of a clinical pharmacology trial report. The methodological section shall highlight the original plan of the trial, which encompasses in clinical pharmacology trials, e.g. choice of design, starting dose, dose escalation schemes and stopping rules, PK and PD sampling schedules, selection of PK and PD descriptors and how they are derived, other variables to be computed from original assessments as well as intended statistical modelling and evaluation. This is of particular importance in case of integrated protocols, which combine more than one element (e.g. single ascending dose, multiple ascending dose, food effect, absolute/relative bioavailability) in a single clinical trial. In line with the exploratory nature of these trials, changes to the initial trial protocol as well as interim analyses not fully pre-specified may become necessary. Changes and adaptations must be adequately explained, pointing out the reasons for these decisions. Accounting for the scientific considerations leading to changes as well as the ethical and regulatory implications is compulsory. Newly developed biomarkers indicating e.g. target engagement may require extra detail to enable readers to understand why they were applied. Advanced pharmacokinetic evaluations, methods used to establish the dose/concentration-effect relationship or PK/PD modelling usually are quite sophisticated and may well be worth the focus on methodological scientific details. In early phase medicines development, it will yet always be challenging to balance the need for methodological transparency adding to the credibility of trial results versus the requirement for protection of commercially confidential information. The working group felt that the other sections of the CONSORT statement might not need specific adaptations for reporting clinical pharmacology trials, if the trial methodology is adequately described and followed. For example, outcomes that are declared as “primary” in the methodology section should indeed be reported more extensively than other outcomes – yet if the authors feel that the initial focus has changed because e.g. other parameters showed more relevant results, then again this should be accounted for in the methodology section. A poster of the pilot outcomes is available online as Supporting Information to this Editorial (see Data S1). To illustrate our reflections on the methodology presentation in publications of clinical pharmacology trials, we have chosen some well taken examples from the 2016 issues of the BJCP. As a clinical pharmacological study, this trial was designed to address the biomarker cascade associated with the pharmacological behaviour of RCT-18 (drug name) at six escalating levels 6. The present open-label, non-randomized, three-arm phase 1 study was conducted at four sites in the United States between 27 August 2013 (first patient enrolled) and 5 February 2015 (data cut-off) 7. The renally impaired subjects and the healthy volunteers were matched as far as reasonably possible for age, weight and tobacco use, and an attempt was made to have a similar number of males and females within each group 8. To compare salivary and plasma concentrations over a wide range of caffeine concentrations, the paired samples were obtained at varying PMAs (postmenstrual ages) and caffeine doses 9. All subjects were thoroughly trained and familiarized with the psychometric tests within 14 days preceding study start to minimize learning effects during the study. Each baseline or pre-dose assessment was performed twice at the beginning of each occasion. The lack of placebo arm in the older subjects group was handled by using the PD baseline measurements to estimate the scopolamine effects 10. All study investigators were blinded to the trial fluid intervention. Independent hospital pharmacy staff provided the solutions in identical unmarked blinded vials. Treatment allocation was only revealed after data analysis was performed 11. Intravenous cannulas were used for the volunteers participating in the overnight sampling, to limit the disturbance to the normal day–night rhythm 12. The average response was believed to reflect the general effect of the study treatment during the observation period and be superior to the maximum value since the latter may be more prone to a potential placebo effect 6. Due to the long half-life of sonidegib, other PK parameters (e.g. AUCinf [area under curve from time zero to in finity], CL/F [apparent oral clearance], Vz/F [apparent volume of distribution], and t1/2 [elimination half-life]) were not part of the analysis 13. The degree of impairment was determined using the estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease Study, which is the equation recom-mended by the FDA Guidance for Industry for the estimation of creatinine clearance. (Arguably, estimation of GFR based on cystatin C might have provided more accurate results. However, any difference would not have changed the interpretation of the pharmacokinetic analyses 8.) There were no formal statistical hypotheses. All analyses were descriptive 13. The stepwise selection was done in SAS 9.2 using procedure GLMSELECT with default model selection criterion (i.e.Schwarz Bayesian Information criterion) and additional options (i.e. intercept suppressed and AUC(0,2.5 days) forced to be included in the model) 13. To account for multiple comparisons, a reduced two-sided P value of 0.01 was used to indicate statistical significance for post hoc comparisons 13. As the correlation (slope of trend ≠0) between a PK parameter and the renal function was found to be significant (P < 0.05), an analysis of variance (ANOVA) was performed to assess the differences in the PK parameter among the control group and the three groups of subjects with impaired renal function, and the 90% confidence interval of the difference was calculated for each pairwise comparison 8. Forty subjects were required to ensure that 34 subjects (n = 17 per group) completed the study. The sample size was chosen to obtain less than 1 × standard deviation (SD) half-width for the 95% CI of difference to placebo in change from baseline of AUEC(0,36 h) for CSF concentrations of A β 1–40 15. In a previous study, a within-subjects coefficient of variation (CV) of 21% was detected for AUC(0,230 min). Other CVs of free testosterone, total testosterone and DHT for AUC(0,230 min) and Cmax were lower. Therefore, this CV was used for the sample size calculations 16. A minimum of 12 PK-evaluable patients were planned to be enrolled to each of the normal hepatic function, moderate hepatic impairment and severe hepatic impairment groups in order to have adequate data to characterize the PK of ixazomib in each hepatic function group 7. As their key finding, the working group feels that reporting methodology in appropriate levels of detail is most important to ascertain the validity of clinical pharmacology trial results published in peer-reviewed journals and the level of evidence the presented conclusions offer. The focus on methodological aspects is important in particular in exploratory trials, as they make the reports reproducible and transparent to understand the level of evidence that has been produced by the results and their presentations. We would like to indicate that there had already been some activities to develop particular guidelines for pharmacokinetic trials 17 and Pop-PK analyses 18. However, both recommendations had not been developed within the CONSORT framework and, more importantly, are not available as open access documents, which limits their value as guidelines for authors. Additionally, a “10-D assessment” has recently been proposed as a guidance for authors and reviewers 19, which combines both methodological aspects (such as “design,” “dosage,” or “data collected”) as well topics specific in the field of clinical pharmacology (such as “drug molecule” or “drug hypersensitivity syndrome” [denoting risk assessment in the context of this guidance]). Some researchers might argue that such guidelines might only be an additional burden for authors, and merely an administrative exercise. However, the easier a publication is to read and to understand, the larger the chance for it to be recognised and remembered, for example, when other researchers discuss their studies. Additionally, we would expect that the time between first submission of a manuscript and final acceptance could be shortened (and the chance of rejection would be reduced) because reviewers already get the important information early and in a reasonably standardised format. Hence, we believe that such guidelines indeed would rather be more beneficial than tiresome to authors. Even with such guidelines, we would not expect that the format of all pharmacological publications would be “equalised” – the variety of areas only covered by BJCP, such as early and late phase clinical trials, pharmacometric analyses, systematic reviews, drug safety and pharmacoepidemiology, is very large. Good guidelines, however, appropriately tailored to the task they are to fulfil may help to make life easier for authors as well as for readers. Authors of papers on clinical pharmacology trials might find it useful to gather examples for high-quality presentations of the methodological details of their research. We can only recommend it as a worthwhile task to engage in academic research as well as in appropriate presentation of one's scientific work. There are no competing interests to declare. The results of the pilot phase were presented as a poster at the annual meeting of the International Society of Clinical Biostatistics (ISCB) in Munich in 2014. The poster is available online as Supporting Information to this Editorial (see Data S1). Data S1 CONSORT ClinPharm poster Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article." @default.
• W2793479504 created "2018-03-29" @default.
• W2793479504 creator A5046134265 @default.
• W2793479504 creator A5050453842 @default.
• W2793479504 date "2018-02-09" @default.
• W2793479504 modified "2023-09-23" @default.
• W2793479504 title "How publication guidelines for clinical pharmacology trials may help to accelerate knowledge transfer" @default.
• W2793479504 cites W1851688783 @default.
• W2793479504 cites W1960238200 @default.
• W2793479504 cites W1981902086 @default.
• W2793479504 cites W1996131030 @default.
• W2793479504 cites W2008023699 @default.
• W2793479504 cites W2042378780 @default.
• W2793479504 cites W2180942848 @default.
• W2793479504 cites W2202895441 @default.
• W2793479504 cites W2263831482 @default.
• W2793479504 cites W2282835285 @default.
• W2793479504 cites W2343506332 @default.
• W2793479504 cites W2346650315 @default.
• W2793479504 cites W2367844700 @default.
• W2793479504 cites W2411766674 @default.
• W2793479504 cites W2414123635 @default.
• W2793479504 cites W2418575726 @default.
• W2793479504 cites W2419517407 @default.
• W2793479504 cites W2725553080 @default.
• W2793479504 cites W4291236667 @default.
• W2793479504 doi "https://doi.org/10.1111/bcp.13489" @default.
• W2793479504 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5867096" @default.
• W2793479504 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29427380" @default.
• W2793479504 hasPublicationYear "2018" @default.
• W2793479504 type Work @default.
• W2793479504 sameAs 2793479504 @default.
• W2793479504 citedByCount "1" @default.
• W2793479504 countsByYear W27934795042023 @default.
• W2793479504 crossrefType "journal-article" @default.
• W2793479504 hasAuthorship W2793479504A5046134265 @default.
• W2793479504 hasAuthorship W2793479504A5050453842 @default.
• W2793479504 hasBestOaLocation W27934795041 @default.
• W2793479504 hasConcept C126322002 @default.
• W2793479504 hasConcept C19527891 @default.
• W2793479504 hasConcept C535046627 @default.
• W2793479504 hasConcept C63433958 @default.
• W2793479504 hasConcept C71924100 @default.
• W2793479504 hasConcept C98274493 @default.
• W2793479504 hasConceptScore W2793479504C126322002 @default.
• W2793479504 hasConceptScore W2793479504C19527891 @default.
• W2793479504 hasConceptScore W2793479504C535046627 @default.
• W2793479504 hasConceptScore W2793479504C63433958 @default.
• W2793479504 hasConceptScore W2793479504C71924100 @default.
• W2793479504 hasConceptScore W2793479504C98274493 @default.
• W2793479504 hasIssue "4" @default.
• W2793479504 hasLocation W27934795041 @default.
• W2793479504 hasLocation W27934795042 @default.
• W2793479504 hasLocation W27934795043 @default.
• W2793479504 hasOpenAccess W2793479504 @default.
• W2793479504 hasPrimaryLocation W27934795041 @default.
• W2793479504 hasRelatedWork W1693630015 @default.
• W2793479504 hasRelatedWork W178704668 @default.
• W2793479504 hasRelatedWork W1965554264 @default.
• W2793479504 hasRelatedWork W1991907429 @default.
• W2793479504 hasRelatedWork W2050916106 @default.
• W2793479504 hasRelatedWork W2137091304 @default.
• W2793479504 hasRelatedWork W2138471292 @default.
• W2793479504 hasRelatedWork W4246638128 @default.
• W2793479504 hasRelatedWork W4249726644 @default.
• W2793479504 hasRelatedWork W2002431581 @default.
• W2793479504 hasVolume "84" @default.
• W2793479504 isParatext "false" @default.
• W2793479504 isRetracted "false" @default.
• W2793479504 magId "2793479504" @default.
• W2793479504 workType "article" @default.