Path to Clinical Trials: Trial Design, Development of the Clinical Product, and Safety Concerns in the Implementation of Clinical Trials

2019 ◽  
pp. 681-698 ◽  
Author(s):  
Jerry R. Mendell ◽  
Louise R. Rodino-Klapac ◽  
Christopher J. Shilling
Keyword(s):  
Clinical Trials ◽  
Trial Design ◽  
Design Development ◽  
Safety Concerns

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 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 Informing selection of drugs for COVID-19 treatment through adverse events analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjing Guo ◽  
Bohu Pan ◽  
Sugunadevi Sakkiah ◽  
Zuowei Ji ◽  
Gokhan Yavas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Safety Concern ◽  
Clinical Practices ◽  
Safety Concerns ◽  
Post Market ◽  
Z Scores ◽  
Favorable Safety ◽  
Effective Drugs ◽  
Selection Of

AbstractCoronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveillance. We collected 296 drugs that have been evaluated in clinical trials for COVID-19 and identified 28,597,464 associated adverse events at the system organ classes (SOCs) level in the FDA adverse events report systems (FAERS). We calculated Z-scores of SOCs that statistically quantify the relative frequency of adverse events of drugs in FAERS to quantitatively measure safety concerns for the drugs. Analyzing the Z-scores revealed that these drugs are associated with different significantly frequent adverse events. Our results suggest that this safety concern metric may serve as a tool to inform selection of drugs with favorable safety profiles for COVID-19 patients in clinical practices. Caution is advised when administering drugs with high Z-scores to patients who are vulnerable to associated adverse events.

scholarly journals Review of major trials of acute blood pressure management in stroke

2021 ◽  
pp. 0271678X2110043
Author(s):  
Thompson G Robinson ◽  
Jatinder S Minhas ◽  
Joseph Miller
Keyword(s):  
Blood Pressure ◽  
Clinical Trials ◽  
Acute Stroke ◽  
Trial Design ◽  
Haemorrhagic Stroke ◽  
Pressure Management ◽  
Blood Pressure Management ◽  
Multiple Trials ◽  
Hypertensive Crises ◽  
Improve Patient

Over the last two decades, there have been a number of major landmark clinical trials, classified as “major” as they sought to address clear clinical practice driven questions, in a pragmatic yet robust trial design, using a large powered sample size (n > 1000), in order to help improve patient outcome through informing guidelines. A commonality across all stroke sub-types included in these trials is the tendency to acute hypertensive crises within the acute stroke period. This phenomenon is associated with greater stroke complications and worsened overall prognosis. Multiple trials have attempted to address the issue of acute blood pressure management during the acute stroke period, with consideration for timing, magnitude of lowering, agent and relationship to other interventions. This review will consider the major clinical trials performed in ischaemic and haemorrhagic stroke that test the hypothesis that acute BP reduction improves clinical outcomes.

scholarly journals Conceptual Framework to Support Clinical Trial Optimization and End-to-End Enrollment Workflow

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Neha M. Jain ◽  
Alison Culley ◽  
Teresa Knoop ◽  
Christine Micheel ◽  
Travis Osterman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Knowledge Representation ◽  
Conceptual Framework ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Prospective Clinical Trial ◽  
Future Trends ◽  
Current State ◽  
Evaluation Strategies

In this work, we present a conceptual framework to support clinical trial optimization and enrollment workflows and review the current state, limitations, and future trends in this space. This framework includes knowledge representation of clinical trials, clinical trial optimization, clinical trial design, enrollment workflows for prospective clinical trial matching, waitlist management, and, finally, evaluation strategies for assessing improvement.

scholarly journals Edaravone in Amyotrophic Lateral Sclerosis’Lessons from the Clinical Development Program and the Importance of a Strategic Clinical Trial Design

US Neurology ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. 47 ◽  
Author(s):  
Said R Beydoun ◽  
Jeffrey Rosenfeld
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Trial Design ◽  
Development Program ◽  
Clinical Trial Design ◽  
Clinical Development ◽  
Disease Heterogeneity ◽  
Clinical Development Program ◽  
Lateral Sclerosis

Edaravone significantly slows progression of amyotrophic lateral sclerosis (ALS), and is the first therapy to receive approval by the Food and Drug Administration (FDA) for the disease in 22 years. Approval of edaravone has marked a new chapter in pharmaceutical development since the key trial included a novel strategic clinical design involving cohort enrichment. In addition, approval was based on clinical trials that had a relatively small patient number and were performed outside of the US. Edaravone was developed through a series of clinical trials in Japan where it was determined that a well-defined subgroup of patients was required to reveal a treatment effect within the study period. Amyotrophic lateral sclerosis is associated with wide-ranging disease heterogeneity (both within the spectrum of ALS phenotypes as well as in the rate of progression). The patient cohort enrichment strategy aimed to address this heterogeneity and should now be considered as a viable, and perhaps preferred, trial design for future studies. Future research incorporating relevant biomarkers may help to better elucidate edaravone’s mechanism of action, pharmacodynamics, and subsequently ALS phenotypes that may preferentially benefit from treatment. In this review, we discuss the edaravone clinical development program, outline the strategic clinical trial design, and highlight important lessons for future trials.

scholarly journals Factors Contributing toDe Qiin Acupuncture Randomized Clinical Trials

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Yi Yang ◽  
Lin-Peng Wang ◽  
Lei Zhang ◽  
Li-Chen Wang ◽  
Jia Wei ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Therapeutic Effect ◽  
Trial Design ◽  
Randomized Clinical Trials ◽  
Consort Statement ◽  
Core Concept ◽  
The Consort Statement ◽  
De Qi

De qiis a core concept of acupuncture and is necessary to produce therapeutic effect. In 2010,de qihas been received as a term in the official extension of the CONSORT Statement. However, there are few articles that discuss which factors have influences on obtainingde qiin clinical trials. This paper aims to explore these factors and give advice on trial design in order to optimizede qiin acupuncture RCTs.

Clinical Trial Design and Statistics

2018 ◽  
Author(s):  
Julie Ann Sosa
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Data Analysis ◽  
Trial Design ◽  
New Technologies ◽  
Drug Application ◽  
Clinical Trial Design ◽  
Double Blind Study ◽  
Type I ◽  
End Points

A clinical trial is a planned experiment designed to prospectively measure the efficacy or effectiveness of an intervention by comparing outcomes in a group of subjects treated with the test intervention with those observed in one or more comparable group(s) of subjects receiving another intervention.  Historically, the gold standard for a clinical trial has been a prospective, randomized, double-blind study, but it is sometimes impractical or unethical to conduct such in clinical medicine and surgery. Conventional outcomes have traditionally been clinical end points; with the rise of new technologies, however, they are increasingly being supplemented and/or replaced by surrogate end points, such as serum biomarkers. Because patients are involved, safety considerations and ethical principles must be incorporated into all phases of clinical trial design, conduct, data analysis, and presentation. This review covers the history of clinical trials, clinical trial phases, ethical issues, implementing the study, basic biostatistics for data analysis, and other resources. Figures show drug development and clinical trial process, and type I and II error. Tables list Food and Drug Administration new drug application types, and types of missing data in clinical trials. This review contains 2 highly rendered figures, 2 tables, and 38 references

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