Clinical Research Quo Vadis? Trends in Reporting of Clinical Trials and Observational Study Designs Over Two Decades

Statistics is the discipline concerning collection, organizing, analyzing, interpretation and presentation of data as the basis for explanation, description and comparison. In clinical trials and in the drug development process, statistics play a key role, from trial design to protocol development. The credibility of a clinical trial can be upheld and cooperation between physicians and statisticians can be strengthened by providing a fundamental understanding of statistical issues. In any phase of clinical research, including trial design, development of procedures, data management and tracking, data processing, and reporting of clinical trials, biostatistics are involved. Statisticians also have roles in formulate hypothesis, develop statistical analysis plan (SAP), choosing the appropriate test, choose an apt sample size, data collection, perform the tests, generating TLGs (tables, listings, and graphs) and reporting the inferences. It is important that the rest of the research team recognizes the statistical approach suggested by the biostatistician, because statisticians can specialize in study designs, therapeutic areas and statistical methods.

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The Use of Digital Clinical Trial Methods in the Evaluation of Digital Therapeutics: A Scoping Review (Preprint)

10.2196/preprints.17630 ◽

2019 ◽

Author(s):

Allison Hirsch ◽

Mahip Grewal ◽

Anthony James Martorell ◽

Brian Michael Iacoviello

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Clinical Research ◽

Scoping Review ◽

Digital Technologies ◽

Good Clinical Practice ◽

The United States ◽

Clinical Trial Research ◽

Digital Methods ◽

Clinical Trial Methods

BACKGROUND Digital Therapeutics (DTx) provide evidence based therapeutic health interventions that have been clinically validated to deliver therapeutic outcomes, such that the software is the treatment. Digital methodologies are increasingly adopted to conduct clinical trials due to advantages they provide including increases in efficiency and decreases in trial costs. Digital therapeutics are digital by design and can leverage the potential of digital and remote clinical trial methods. OBJECTIVE The principal purpose of this scoping review is to review the literature to determine whether digital technologies are being used in DTx clinical research, which type are being used and whether publications are noting any advantages to their use. As DTx development is an emerging field there are likely gaps in the knowledge base regarding DTx and clinical trials, and the purpose of this review is to illuminate those gaps. A secondary purpose is to consider questions which emerged during the review process including whether fully remote digital clinical research is appropriate for all health conditions and whether digital clinical trial methods are inline with the principles of Good Clinical Practice. METHODS 1,326 records were identified by searching research databases and 1,227 reviewed at the full-article level in order to determine if they were appropriate for inclusion. Confirmation of clinical trial status, use of digital clinical research methods and digital therapeutic status as well as inclusion and exclusion criteria were applied in order to determine relevant articles. Digital methods employed in DTx research were extracted from each article and these data were synthesized in order to determine which digital methods are currently used in clinical trial research. RESULTS After applying our criteria for scoping review inclusion, 11 articles were identified. All articles used at least one form of digital clinical research methodology enabling an element of remote research. The most commonly used digital methods are those related to recruitment, enrollment and the assessment of outcomes. A small number of articles reported using other methods such as online compensation (n = 3), or digital reminders for participants (n = 5). The majority of digital therapeutics clinical research using digital methods is conducted in the United States and increasing number of articles using digital methods are published each year. CONCLUSIONS Digital methods are used in clinical trial research evaluating DTx, though not frequently as evidenced by the low proportion of articles included in this review. Fully remote clinical trial research is not yet the standard, more frequently authors are using partially remote methods. Additionally, there is tremendous variability in the level of detail describing digital methods within the literature. As digital technologies continue to advance and the clinical research DTx literature matures, digital methods which facilitate remote research may be used more frequently.

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Intelligent Drug Development

10.1093/oso/9780199974580.001.0001 ◽

2014 ◽

Author(s):

Michael Tansey

Keyword(s):

Clinical Trials ◽

Cost Effectiveness ◽

Drug Development ◽

Clinical Research ◽

Development Process ◽

Drug Development Process ◽

Individual Trial ◽

Specific Technology

Clinical research is heavily regulated and involves coordination of numerous pharmaceutical-related disciplines. Each individual trial involves contractual, regulatory, and ethics approval at each site and in each country. Clinical trials have become so complex and government requirements so stringent that researchers often approach trials too cautiously, convinced that the process is bound to be insurmountably complicated and riddled with roadblocks. A step back is needed, an objective examination of the drug development process as a whole, and recommendations made for streamlining the process at all stages. With Intelligent Drug Development, Michael Tansey systematically addresses the key elements that affect the quality, timeliness, and cost-effectiveness of the drug-development process, and identifies steps that can be adjusted and made more efficient. Tansey uses his own experiences conducting clinical trials to create a guide that provides flexible, adaptable ways of implementing the necessary processes of development. Moreover, the processes described in the book are not dependent either on a particular company structure or on any specific technology; thus, Tansey's approach can be implemented at any company, regardless of size. The book includes specific examples that illustrate some of the ways in which the principles can be applied, as well as suggestions for providing a better context in which the changes can be implemented. The protocols for drug development and clinical research have grown increasingly complex in recent years, making Intelligent Drug Development a needed examination of the pharmaceutical process.

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Beyond clinical trials: Extending the role of the clinical research nurse into social care and homeless research

Journal of Clinical Nursing ◽

10.1111/jocn.15911 ◽

2021 ◽

Author(s):

Elizabeth Biswell R ◽

Michael Clark ◽

Michela Tinelli ◽

Gillian Manthorpe ◽

Joanne Neale ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Social Care ◽

Research Nurse

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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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Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

Trials ◽

10.1186/s13063-021-05273-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ciska Verbaanderd ◽

Ilse Rooman ◽

Isabelle Huys

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Financial Support ◽

Social Impact ◽

Grey Literature ◽

Economic Incentives ◽

Phase Iii ◽

Medical Needs ◽

The Future ◽

Funding Mechanisms

Abstract Background Finding new therapeutic uses for existing medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in research with approved medicines, especially when they are out of basic patent or regulatory protection. Consequently, potential new uses for these medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes, or collaborative groups. Yet, additional financial support is needed to conduct expensive phase III clinical trials to confirm the results from exploratory research. Methods In this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms. Results Traditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, only little research has focused on the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds, crowdfunding or public-private partnerships. Interviewees stated that there is a substantial need for additional financial support in health research, especially in areas where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, interviewees highlighted the need for increased collaboration and centralisation at a European and international level to make clinical research more efficient and reduce the need for additional funding. Conclusions New funding mechanisms to support clinical research may become more important in the future but the unresolved issues identified in the current study warrant further exploration.

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Shared-Task Worklists Improve Clinical Trial Recruitment Workflow in an Academic Emergency Department

Applied Clinical Informatics ◽

10.1055/s-0041-1727153 ◽

2021 ◽

Vol 12 (02) ◽

pp. 293-300

Author(s):

Kevin S. Naceanceno ◽

Stacey L. House ◽

Phillip V. Asaro

Keyword(s):

Clinical Trial ◽

Emergency Department ◽

Clinical Trials ◽

Clinical Research ◽

Substantial Reduction ◽

Text Message ◽

High Volume ◽

Text Messages ◽

Shared Task ◽

Clinical Research Coordinators

Abstract Background Clinical trials performed in our emergency department at Barnes-Jewish Hospital utilize a centralized infrastructure for alerting, screening, and enrollment with rule-based alerts sent to clinical research coordinators. Previously, all alerts were delivered as text messages via dedicated cellular phones. As the number of ongoing clinical trials increased, the volume of alerts grew to an unmanageable level. Therefore, we have changed our primary notification delivery method to study-specific, shared-task worklists integrated with our pre-existing web-based screening documentation system. Objective To evaluate the effects on screening and recruitment workflow of replacing text-message delivery of clinical trial alerts with study-specific shared-task worklists in a high-volume academic emergency department supporting multiple concurrent clinical trials. Methods We analyzed retrospective data on alerting, screening, and enrollment for 10 active clinical trials pre- and postimplementation of shared-task worklists. Results Notifications signaling the presence of potentially eligible subjects for clinical trials were more likely to result in a screen (p < 0.001) with the implementation of shared-task worklists compared with notifications delivered as text messages for 8/10 clinical trials. The change in workflow did not alter the likelihood of a notification resulting in an enrollment (p = 0.473). The Director of Research reported a substantial reduction in the amount of time spent redirecting clinical research coordinator screening activities. Conclusion Shared-task worklists, with the functionalities we have described, offer a viable alternative to delivery of clinical trial alerts via text message directly to clinical research coordinators recruiting for multiple concurrent clinical trials in a high-volume academic emergency department.

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Use of connected digital products in clinical research following the COVID-19 pandemic: a comprehensive analysis of clinical trials

BMJ Open ◽

10.1136/bmjopen-2020-047341 ◽

2021 ◽

Vol 11 (6) ◽

pp. e047341

Author(s):

Caroline Marra ◽

William J Gordon ◽

Ariel Dora Stern

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Outcome Measures ◽

Remote Monitoring ◽

Search Algorithm ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Digital Products ◽

Clinical Trial Registry ◽

Before And After

ObjectivesIn an effort to mitigate COVID-19 related challenges for clinical research, the US Food and Drug Administration (FDA) issued new guidance for the conduct of ‘virtual’ clinical trials in late March 2020. This study documents trends in the use of connected digital products (CDPs), tools that enable remote patient monitoring and telehealth consultation, in clinical trials both before and after the onset of the pandemic.DesignWe applied a comprehensive text search algorithm to clinical trial registry data to identify trials that use CDPs for remote monitoring or telehealth. We compared CDP use in the months before and after the issuance of FDA guidance facilitating virtual clinical trials.SettingAll trials registered on ClinicalTrials.gov with start dates from May 2019 through February 2021.Outcome measuresThe primary outcome measure was the overall percentage of CDP use in clinical trials started in the 10 months prior to the pandemic onset (May 2019–February 2020) compared with the 10 months following (May 2020–February 2021). Secondary outcome measures included CDP usage by trial type (interventional, observational), funder type (industry, non-industry) and diagnoses (COVID-19 or non-COVID-19 participants).ResultsCDP usage in clinical trials increased by only 1.65 percentage points, from 14.19% (n=23 473) of all trials initiated in the 10 months prior to the pandemic onset to 15.84% (n=26 009) of those started in the 10 months following (p<0.01). The increase occurred primarily in observational studies and non-industry funded trials and was driven entirely by CDP usage in trials for COVID-19.ConclusionsThese findings suggest that in the short-term, new options created by regulatory guidance to stimulate telehealth and remote monitoring were not widely incorporated into clinical research. In the months immediately following the pandemic onset, CDP adoption increased primarily in observational and non-industry funded studies where virtual protocols are likely medically necessary due to the participants’ COVID-19 diagnosis.

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Cancer clinical research in Latin America: current situation and opportunities. Expert opinion from the first ESMO workshop on clinical trials, Lima, 2015: Table 1

ESMO Open ◽

10.1136/esmoopen-2016-000055 ◽

2016 ◽

Vol 1 (4) ◽

pp. e000055 ◽

Cited By ~ 8

Author(s):

Christian Rolfo ◽

Christian Caglevic ◽

Denisse Bretel ◽

David Hong ◽

Luis E Raez ◽

...

Keyword(s):

Clinical Trials ◽

Latin America ◽

Clinical Research ◽

Expert Opinion ◽

Current Situation

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Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update

Medicina ◽

10.3390/medicina57010058 ◽

2021 ◽

Vol 57 (1) ◽

pp. 58

Author(s):

Arrigo F. G. Cicero ◽

Federica Fogacci ◽

Masanari Kuwabara ◽

Claudio Borghi

Keyword(s):

Clinical Trials ◽

Uric Acid ◽

Clinical Research ◽

Safety Profile ◽

Therapeutic Strategies ◽

Evidence Based ◽

Acute Management ◽

Efficacy And Safety ◽

Uricosuric Agents ◽

Xanthine Oxidase Inhibitors

This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that further well-designed clinical research is needed to deepen their efficacy and safety profile.

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