scholarly journals BIOSTATISTICS IN CLINICAL RESEARCH: A REVIEW

2021 ◽  
Vol 12 (1) ◽  
pp. 1-9
Author(s):  
Aneesha Chatla ◽  
Bhargavi Neela ◽  
C S Mujeebuddin ◽  
V C Randeep Raj
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Trial Design ◽  
Statistical Approach ◽  
Statistical Analysis Plan ◽  
Design Development ◽  
Protocol Development ◽  
Fundamental Understanding ◽  
Statistical Issues ◽  
Study Designs

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.

scholarly journals Statistical consideration when adding new arms to ongoing clinical trials: the potentials and the caveats

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kim May Lee ◽  
Louise C. Brown ◽  
Thomas Jaki ◽  
Nigel Stallard ◽  
James Wason
Keyword(s):  
Clinical Trials ◽  
Trial Design ◽  
Development Process ◽  
Phase Iii ◽  
Drug Development Process ◽  
Efficient Design ◽  
Methodology Development ◽  
Statistical Consideration ◽  
Statistical Issues ◽  
New Research

Abstract Background Platform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms. Main We explain different statistical considerations that arise from allowing new research interventions to be added in for ongoing studies. We present recent methodology development on addressing these issues and illustrate design and analysis approaches that might be enhanced to provide robust inference from platform trials. We also discuss the implication of changing the control arm, how patient eligibility for different arms may complicate the trial design and analysis, and how operational bias may arise when revealing some results of the trials. Lastly, we comment on the appropriateness and the application of platform trials in phase II and phase III settings, as well as publicly versus industry-funded trials. Conclusion Platform trials provide great opportunities for improving the efficiency of evaluating interventions. Although several statistical issues are present, there are a range of methods available that allow robust and efficient design and analysis of these trials.

Barriers to patient accrual in Ontario oncology clinical trials: Attitudes of oncologists and clinical research personnel.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 36-36
Author(s):  
Ammar Bookwala ◽  
Daisy Dastur ◽  
Audrey Wong ◽  
Christina Marchand ◽  
Jalal Ebrahim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Trial Design ◽  
Demographic Data ◽  
Clinical Trial Design ◽  
Standard Of Care ◽  
Medical Specialty ◽  
Research Personnel ◽  
Patient Accrual

36 Background: The medical specialty of oncology relies heavily on clinical trials to advance policies and practices related to cancer care. However, oncology clinical trial accrual in Ontario has dropped from 12.4% in 2007, to 8.5% in 2009. The objective of this study was to determine barriers experienced by Oncologists and Clinical Research Personnel (CRP) in recruiting patients to oncology trials in Ontario. Methods: In June 2012, an electronic survey was emailed to about 400 oncologists and CRP across Ontario. Variables of interest included demographic data, clinical trial involvement, and perceived barriers to participation in clinical trials amongst three previously identified barrier domains. Barriers were ranked, from 1 (least significant) to 5 (most significant). Statistics were compiled using Graphpad Prism software. Differences in responses were analyzed using the Kruskal – Wallis test and Dunn’s Multiple Comparison Test. Results: Of the 400 emails sent, there were 126 respondents (32%). Of the 126 respondents, 82 fully completed the survey (64.6% useable response rate). Amongst system related barriers, “time related” (Median Agreement (M): 4, Inter Quartile Range (IQR): 3-5), and “resource related” barriers (M: 4, IQR: 3-5) had the most negative effect on accrual (p<0.05). Amongst trial design barriers, “Relevance to patient population” (M: 3, IQR: 3-5), “Deviation from Standard of Care” (M: 3, IQR: 3-5) and “Complexity of Trial Protocol” (M: 4, IQR: 3-5) were the most significant barriers (p<0.05). Lastly, amongst personal barriers, “Commitment of the Principal Investigator/Research Staff” (M: 4, IQR: 3-5) and Drug Safety (M: 4, IQR: 2-4) were the most significant barriers to recruitment (p<0.05). Conclusions: Multiple barriers were identified as having a significant impact on patient accrual in clinical trials. Addressing these barriers prospectively in clinical trial design may benefit future studies to successfully accrue cancer patients. Also, creating clinical trial collaboration vehicles amongst sites in similar geographical areas may contribute to improving patient accrual to clinical trials.

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

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.

Intelligent Drug Development

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.

scholarly journals Improving pragmatic clinical trial design using real-world data

2019 ◽  
Vol 16 (3) ◽  
pp. 273-282 ◽  
Author(s):  
Susan M Shortreed ◽  
Carolyn M Rutter ◽  
Andrea J Cook ◽  
Gregory E Simon
Keyword(s):  
Clinical Trials ◽  
Trial Design ◽  
Suicide Attempts ◽  
Real World Data ◽  
Electronic Health Record Data ◽  
Pragmatic Clinical Trial ◽  
Pragmatic Clinical Trials ◽  
Sample Size Calculations ◽  
Record Data ◽  
Electronic Health

Background Pragmatic clinical trials often use automated data sources such as electronic health records, claims, or registries to identify eligible individuals and collect outcome information. A specific advantage that this automated data collection often yields is having data on potential participants when design decisions are being made. We outline how this data can be used to inform trial design. Methods Our work is motivated by a pragmatic clinical trial evaluating the impact of suicide-prevention outreach interventions on fatal and non-fatal suicide attempts in the 18 months after randomization. We illustrate our recommended approaches for designing pragmatic clinical trials using historical data from the health systems participating in this study. Specifically, we illustrate how electronic health record data can be used to inform the selection of trial eligibility requirements, to estimate the distribution of participant characteristics over the course of the trial, and to conduct power and sample size calculations. Results Data from 122,873 people with patient health questionnaire (PHQ) responses, recorded in their electronic health records between 1 July 2010 and 31 March 2012, were used to show that the suicide attempt rate in the 18 months following completion of the questionnaire varies by response to item nine of the PHQ. We estimated that the proportion of individuals with a prior recorded elevated PHQ (i.e. history of suicidal ideation) would decrease from approximately 50% at the beginning of a trial to about 5%, 50 weeks later. Using electronic health record data, we conducted simulations to estimate the power to detect a 25% reduction in suicide attempts. Simulation-based power calculations estimated that randomizing 8000 participants per randomization arm would allow 90% power to detect a 25% reduction in the suicide attempt rate in the intervention arm compared to usual care at an alpha rate of 0.05. Conclusions Historical data can be used to inform the design of pragmatic clinical trials, a strength of trials that use automated data collection for randomizing participants and assessing outcomes. In particular, realistic sample size calculations can be conducted using real-world data from the health systems in which the trial will be conducted. Data-informed trial design should yield more realistic estimates of statistical power and maximize efficiency of trial recruitment.

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

2021 ◽  
Author(s):  
Elizabeth Biswell R ◽  
Michael Clark ◽  
Michela Tinelli ◽  
Gillian Manthorpe ◽  
Joanne Neale ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Social Care ◽  
Research Nurse

scholarly journals 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

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.

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

Trials ◽  
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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