Reporting Standards for Clinical and Translational Research

Transparency in reporting the results of clinical and preclinical research is critical for unbiased publications. Funding agencies, publishers, and regulators have the responsibility to advocate and implement reporting standards for rigorous design. While individual study protocols may have included these standards, the items reported in the respective publications have often been inconsistent or lack transparency. This editorial intends to provide some specific guidelines for reporting results of clinical research with standards required for rigorous study design. We recommend that reporting clinical research should include sufficient information on study design and analysis plan that contains data processing, quality assurance, and appropriate methods used for rigorous statistical analysis or modeling. Any discrepancy between publications and original study design should be disclosed and discussed. Additionally, recent advances in the analysis of outcome with repeated measurements and statistical modeling should be employed to obtain unbiased estimates. Finally, we briefly discuss some issues reporting real-world evidence in clinical research.

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Limitations and Flaws of Preclinical Pulmonary Hypertension Studies

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-19.2.47 ◽

2020 ◽

Vol 19 (2) ◽

pp. 47-54

Author(s):

Tsukasa Shimauchi ◽

François Potus ◽

Sébastien Bonnet ◽

Steeve Provencher ◽

Roxane Paulin ◽

...

Keyword(s):

Animal Ethics ◽

Preclinical Studies ◽

Preclinical Research ◽

Funding Agencies ◽

Need Support ◽

Innovative Therapies ◽

Peer Reviewers ◽

Delayed Translation ◽

Rigorous Study ◽

Pulmonary Arterial

Despite advances in our understanding of the disease, significant therapeutic gaps remain for pulmonary arterial hypertension (PAH). Indeed, no cure exists yet for this devastating disease, and very few innovative therapies beyond the traditional pathways of endothelial dysfunction have reached late clinical trial phases in PAH. While there are inherent limitations to the currently available animal models of PAH, the delayed translation of innovative therapies to the clinic may also relate to flawed preclinical research methodologies. The present article discusses the limitations and flaws in the design of preclinical PH trials and discusses opportunities to create preclinical studies with improved predictive value in identifying key mechanisms involved in PAH development and progression and guiding early phase drug development in PAH patients. The implementation of rigorous study design will need support not only from researchers, peer reviewers, and editors, but also from academic institutions, funding agencies, and animal ethics authorities.

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Investigator Initiated Clinical Trials (IICTs): A Systematic Search in Registries to Compare the Czech Republic and Portugal in Terms of Funding Policies and Scientific Outcomes

Therapeutic Innovation & Regulatory Science ◽

10.1007/s43441-021-00293-w ◽

2021 ◽

Author(s):

C. Madeira ◽

L. Hořavová ◽

F. dos Santos ◽

J. R. Batuca ◽

K. Nebeska ◽

...

Keyword(s):

Clinical Trials ◽

Czech Republic ◽

Clinical Research ◽

Systematic Search ◽

European Countries ◽

The Czech Republic ◽

Research Outcomes ◽

Funding Policies ◽

Funding Agencies ◽

First Time

Abstract Objectives Clinical trials provide one of the highest levels of evidence to support medical practice. Investigator initiated clinical trials (IICTs) answer relevant questions in clinical practice that may not be addressed by industry. For the first time, two European Countries are compared in terms of IICTs, respective funders and publications, envisaging to inspire others to use similar indicators to assess clinical research outcomes. Methods A retrospective systematic search of registered IICTs from 2004 to 2017, using four clinical trials registries was carried out in two European countries with similar population, GDP, HDI and medical schools but with different governmental models to fund clinical research. Each IICT was screened for sponsors, funders, type of intervention and associated publications, once completed. Results IICTs involving the Czech Republic and Portugal were n = 439 (42% with hospitals as sponsors) and n = 328 (47% with universities as sponsors), respectively. The Czech Republic and Portuguese funding agencies supported respectively 61 and 27 IICTs. Among these, trials with medicinal products represent 52% in Czech Republic and 4% in Portugal. In the first, a higher percentage of IICTs’ publications in high impact factor journals with national investigators as authors was observed, when compared to Portugal (75% vs 15%). Conclusion The better performance in clinical research by Czech Republic might be related to the existence of specific and periodic funding for clinical research, although further data are still needed to confirm this relationship. In upcoming years, the indicators used herein might be useful to tracking clinical research outcomes in these and other European countries.

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Study design, result reporting and publication of late-stage cardiovascular trials

European Heart Journal ◽

10.1093/ehjci/ehaa946.3568 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Kapelios ◽

H Naci ◽

P Vardas ◽

E Mossialos

Keyword(s):

Study Design ◽

Late Stage ◽

Late Phase ◽

Phase Iii ◽

Open Label ◽

Explanatory Factors ◽

Study Protocols ◽

Study Results ◽

Artery Disease ◽

Design Result

Abstract Introduction Preregistration of study protocols in publicly accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on the characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited. Methods The purpose of this study was to perform a comprehensive analysis of the characteristics of late-stage, cardiovascular disease (CVD) trials registered in Clinicaltrials.gov. We searched for interventional, late-phase (annotated as phase III) CVD studies in adults first posted after 1/1/2013 and completed up to 31/12/2018. Data on study design, result reporting, result spinning and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined. Results The search yielded 352 studies. One hundred were excluded from further analysis because they were misclassified as CVD studies, while 2 were excluded as duplicate entries. In total, 250 CVD trials were included in the analysis. The most commonly studied fields were hypertension, coronary artery disease and heart failure. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. 179 trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P<0.001 and 55.0% vs. 26.3%, P=0.033, respectively). Sixty three studies (25.2%) had results posted on clinicaltrials.gov, and 116 (46.4%) had results published in the scientific literature. No clear indication of result spinning was found in 96 (85%) of published studies. In multivariate analysis, industry sponsorship was statistically significantly associated with results posting (OR: 3.56; 95% CI:1.67–7.60, P=0.001) and publication (OR: 0.41; 95% CI:0.23–0.75, P=0.004). Results spinning was associated with confirmation of the primary hypothesis (OR: 0.23; 95% CI: 0.07–0.75, P=0.015) and results posting (OR: 0.08; 95% CI: 0.01–0.65, P=0.018). Conclusions Among late-stage cardiovascular trials only 1/4 had their results posted on clinicaltrials.gov and less than half had results published. Industry sponsors were more likely to invest in research on patent-protected drugs and devices than were non-industry sponsors. Having industry as a sponsor was independently associated with increased likelihood of results posting, but decreased likelihood of results publication. Results reporting was significantly associated with lower risk of results spinning. Funding Acknowledgement Type of funding source: None

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Analysis of repeated measurements in clinical studies: departures from study design

1999 Third International Conference on Knowledge-Based Intelligent Information Engineering Systems. Proceedings (Cat. No.99TH8410) ◽

10.1109/kes.1999.820186 ◽

2003 ◽

Author(s):

S. Wagenpfeil ◽

M. Hennig ◽

R. Kates ◽

A. Neiss

Keyword(s):

Study Design ◽

Clinical Studies ◽

Repeated Measurements

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Advances in Oncology Clinical Research: Statistical and Study Design Methodologies

Lung Cancer ◽

10.1007/978-1-60761-524-8_18 ◽

2010 ◽

pp. 467-481

Author(s):

B. Nebiyou Bekele

Keyword(s):

Clinical Research ◽

Study Design ◽

Design Methodologies

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Review of Clinical Research Informatics

Yearbook of Medical Informatics ◽

10.1055/s-0040-1701988 ◽

2020 ◽

Vol 29 (01) ◽

pp. 193-202

Author(s):

Anthony Solomonides

Keyword(s):

Artificial Intelligence ◽

Clinical Research ◽

Big Data Analytics ◽

Medical Knowledge ◽

Data Models ◽

Research Areas ◽

Personal Awareness ◽

Real World Evidence ◽

Clinical Research Informatics ◽

Active Research

Objectives: Clinical Research Informatics (CRI) declares its scope in its name, but its content, both in terms of the clinical research it supports—and sometimes initiates—and the methods it has developed over time, reach much further than the name suggests. The goal of this review is to celebrate the extraordinary diversity of activity and of results, not as a prize-giving pageant, but in recognition of the field, the community that both serves and is sustained by it, and of its interdisciplinarity and its international dimension. Methods: Beyond personal awareness of a range of work commensurate with the author’s own research, it is clear that, even with a thorough literature search, a comprehensive review is impossible. Moreover, the field has grown and subdivided to an extent that makes it very hard for one individual to be familiar with every branch or with more than a few branches in any depth. A literature survey was conducted that focused on informatics-related terms in the general biomedical and healthcare literature, and specific concerns (“artificial intelligence”, “data models”, “analytics”, etc.) in the biomedical informatics (BMI) literature. In addition to a selection from the results from these searches, suggestive references within them were also considered. Results: The substantive sections of the paper—Artificial Intelligence, Machine Learning, and “Big Data” Analytics; Common Data Models, Data Quality, and Standards; Phenotyping and Cohort Discovery; Privacy: Deidentification, Distributed Computation, Blockchain; Causal Inference and Real-World Evidence—provide broad coverage of these active research areas, with, no doubt, a bias towards this reviewer’s interests and preferences, landing on a number of papers that stood out in one way or another, or, alternatively, exemplified a particular line of work. Conclusions: CRI is thriving, not only in the familiar major centers of research, but more widely, throughout the world. This is not to pretend that the distribution is uniform, but to highlight the potential for this domain to play a prominent role in supporting progress in medicine, healthcare, and wellbeing everywhere. We conclude with the observation that CRI and its practitioners would make apt stewards of the new medical knowledge that their methods will bring forward.

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Experimental replications in animal trials

Laboratory Animals ◽

10.1177/0023677220907617 ◽

2020 ◽

pp. 002367722090761 ◽

Cited By ~ 1

Author(s):

Florian Frommlet ◽

Georg Heinze

Keyword(s):

Statistical Analysis ◽

Experimental Design ◽

Animal Models ◽

Study Design ◽

Recent Discussion ◽

Preclinical Research ◽

Animal Trials ◽

Scientific Results

The recent discussion on the reproducibility of scientific results is particularly relevant for preclinical research with animal models. Within certain areas of preclinical research, there exists the tradition of repeating an experiment at least twice to demonstrate replicability. If the results of the first two experiments do not agree, then the experiment might be repeated a third time. Sometimes data of one representative experiment are shown; sometimes data from different experiments are pooled. However, there are hardly any guidelines about how to plan for such an experimental design or how to report the results obtained. This article provides a thorough statistical analysis of pre-planned experimental replications as they are currently often applied in practice and gives some recommendations about how to improve on study design and statistical analysis.

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Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: a systematic review and international Delphi consensus

Rheumatology ◽

10.1093/rheumatology/keaa457 ◽

2020 ◽

Author(s):

Francesca Ingegnoli ◽

Ariane L Herrick ◽

Tommaso Schioppo ◽

Francesca Bartoli ◽

Nicola Ughi ◽

...

Keyword(s):

Systematic Review ◽

Clinical Research ◽

Rheumatic Diseases ◽

Musculoskeletal Diseases ◽

Delphi Process ◽

Reporting Standards ◽

Delphi Consensus ◽

Delphi Exercise ◽

Patient Preparation ◽

Research Studies

Abstract Objectives The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

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