scholarly journals Estimands: bringing clarity and focus to research questions in clinical trials

BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e052953
Author(s):  
Timothy Peter Clark ◽  
Brennan C Kahan ◽  
Alan Phillips ◽  
Ian White ◽  
James R Carpenter
Keyword(s):  
Clinical Trial ◽  
Sensitivity Analysis ◽  
Clinical Trials ◽  
Clinical Research ◽  
Recent Work ◽  
Treatment Effect ◽  
Research Question ◽  
Probability Of Success ◽  
Research Questions

Precise specification of the research question and associated treatment effect of interest is essential in clinical research, yet recent work shows that they are often incompletely specified. The ICH E9 (R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials introduces a framework that supports researchers in precisely and transparently specifying the treatment effect they aim to estimate in their clinical trial. In this paper, we present practical examples to demonstrate to all researchers involved in clinical trials how estimands can help them to specify the research question, lead to a better understanding of the treatment effect to be estimated and hence increase the probability of success of the trial.

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.

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

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.

scholarly journals The appearance and increase in the quantity and proportion of the clinical research coordinator's service fee in drug clinical trial research fund and its impact on trial quality

2020 ◽  
Author(s):  
Liran Chen ◽  
Zhimin Chen ◽  
Huafang Chen
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Structural Changes ◽  
Continuous Increase ◽  
Clinical Trial Research ◽  
Clinical Research Coordinator ◽  
Research Coordinator ◽  
Drug Clinical Trial

Abstract Objective: The changes of absolute value and relative value of clinical research coordinator service fee and its influence on the quality of drug clinical trial were analyzed.Methods: This study compared the amount and structural changes of drug clinical trial costs in before 3 years and after 3 years of self-examination and inspection initiated by the China Food and Drug Administration, identified the increase number and composition of each individual cost of a clinical trial research funds which including clinical research coordinator service fee, investigator labor fee, subjects examination fee, subjects traffic subsidy, documents management fee, drug management fee, etc.Result: The most significant appearance and increase in volume and proportion were the clinical research coordinator service fee. From the initial few to the global multicenter tumor drug clinical trials RMB31,624 or 34.92% of the proportion and domestic multicenter tumor drug clinical trials RMB16,500,accounted for 33.74%.Discussion: It has become common for more money to be spent on clinical trials to be accompanied by improved quality, but the occurrence and continuous increase of clinical research coordinator service fee were divided into two aspects, On the one hand, the quality of clinical trials was promoted by the large amount of low-skill trivial work undertaken by clinical research coordinator; on the other hand, the quality of clinical trials was undermined by the fact that clinical research coordinator did too much treatment evaluation work that should have been done by the investigator.

scholarly journals Acceptability of Pulse-Fortified Foods by Two Groups: Participants in a Clinical Trial and Participants in a Consumer Acceptability Panel

Foods ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 129 ◽  
Author(s):  
Donna Ryland ◽  
Peter Zahradka ◽  
Carla Taylor ◽  
Rhonda Bell ◽  
Michel Aliani
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Research Question ◽  
Health Benefit ◽  
Influential Factors ◽  
Consumer Acceptability ◽  
Fortified Foods ◽  
Overall Acceptability ◽  
Regular Consumption ◽  
Trial Participants

Pulses are nutrient-rich ingredients used as interventions in clinical trials to determine their effect on lowering blood lipids, which are risk factors for cardiovascular disease. Acceptability of these foods is critical for compliance by participants in clinical trials as well as regular consumption by those eating them for their health benefit. Commercialisation of foods that prove positive for health is required to make them available to the general population. Since the target for commercialisation would be products that will be procured by as many people as possible, the research question becomes whether or not testing is required by the clinical trial participants, by consumer acceptability testing in a sensory unit, or by both to ensure acceptability. The objective of this study was to determine the acceptability of pulse-based soups and casseroles destined for a clinical trial by both the participants in the clinical trial and by consumer participants not in the clinical trial. Neither group received any training regarding sensory analysis. Acceptability of aroma, appearance, flavor, texture, overall acceptability, and the frequency of eating the samples of five formulations fortified with either peas or beans was measured. Groups differed in their acceptability of foods for different attributes with the clinical trial participants providing less discrimination among the sensory attributes for their acceptability. Influential factors could include motivation for healthy eating, age, number of times the product was consumed, amount of the product consumed, and where it was consumed. In conclusion, acceptance measures from both groups are required in order to gain as much information as possible regarding acceptability of attributes for commercialisation of pulse-fortified foods that provide a health benefit.

Using Social Media to Increase the Recruitment of Clinical Research Participants

2018 ◽  
pp. 7181-7189
Author(s):  
Saliha Akhtar
Keyword(s):  
Clinical Trial ◽  
Social Media ◽  
Clinical Trials ◽  
Clinical Research ◽  
Recruitment Strategies ◽  
Primary Role ◽  
Trial Recruitment ◽  
Recruitment Methods ◽  
Pros And Cons ◽  
Clinical Trial Recruitment

Research has shown that clinical research continues to have difficulty recruiting participants. This problem is expected to increase as the number of clinical trials increases and as there continues to be more focus on complex diseases and treatments. Researchers have typically relied on traditional recruitment methods to recruit participants, which revolve around the physicians and their support staff having the primary role to locate and recruit these participants. However, with individuals using online platforms such as social media to retrieve information, this creates an opportunity for research site personnel to use it as a way to relay information on clinical trial opportunities. Studies that have used social media as a way to recruit participants are discussed. Furthermore, pros and cons of social media for recruitment, along with recommendations that future researchers should consider when deciding whether to implement this type of strategy in their clinical trials will be shared. In general, clinical trial recruitment strategies need to shift to an approach that is not only more targeted, but also has a larger reach. By evaluating the success of studies that have used social recruitment strategies so far, it is evident that future researchers can also achieve recruitment success through social media. Moreover, social media could be a promising new avenue for clinical trial recruitment that allows for a more positive experience for both investigative site personnel and potential participants.

scholarly journals How to design and set up a clinical trial part 1: the research question

2019 ◽  
Vol 12 (3) ◽  
pp. 111-116
Author(s):  
Amarpreet Atwal ◽  
Philip E Benson
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Relevance ◽  
Clinical Care ◽  
Research Question ◽  
Relevant Information ◽  
Evidence Base ◽  
Human Participants ◽  
Set Up

Data from clinical trials involving human participants are essential in establishing an evidence base about the safety and effectiveness of our treatments. This first article describes the steps involved in designing and setting up a clinical trial, from establishing the research question(s) to searching the literature. Acquiring some knowledge about how to set up a clinical trial will allow the conscientious clinician to use the most relevant information to provide the highest possible standards of clinical care for his/her patients. CPD/Clinical Relevance: Even if a clinician is not, has never been, nor is ever planning to be involved in research, he/she should understand and be able to interpret the data from clinical trials.

Underestimation of treatment effects in sequentially monitored clinical trials that did not stop early for benefit

2018 ◽  
Vol 28 (10-11) ◽  
pp. 3027-3041 ◽  
Author(s):  
Ian C Marschner ◽  
I Manjula Schou
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Treatment Effect ◽  
Interim Analysis ◽  
Experimental Treatment ◽  
Final Analysis ◽  
Effect Estimate ◽  
Effectiveness Analysis ◽  
Simulation Results ◽  
Meta Analyses

In recent years, there has been a prominent discussion in the literature about the potential for overestimation of the treatment effect when a clinical trial stops at an interim analysis due to the experimental treatment showing a benefit over the control. However, there has been much less attention paid to the converse issue, namely, that sequentially monitored clinical trials which did not stop early for benefit tend to underestimate the treatment effect. In meta-analyses of many studies, these two sources of bias will tend to balance each other to produce an unbiased estimate of the treatment effect. However, for the interpretation of a single study in isolation, underestimation due to interim analysis may be an important consideration. In this paper, we discuss the nature of this underestimation, including theoretical and simulation results demonstrating that it can be substantial in some contexts. Furthermore, we show how a conditional approach to estimation, in which we condition on the study reaching its final analysis, may be used to validly inflate the observed treatment difference from a sequentially monitored clinical trial. Expressions for the conditional bias and information are derived, and these are used in supplied R code that computes the bias-adjusted estimate and an associated confidence interval. As well as simulation results demonstrating the validity of the methods, we present a data analysis example from a pivotal clinical trial in cardiovascular disease. The methods will be most useful when an unbiased treatment effect estimate is critical, such as in cost-effectiveness analysis or risk prediction.

Research with Minors in Germany

2008 ◽  
Vol 15 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Dieter Hart ◽  
Benedikt Buchner
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
German Law ◽  
European Level ◽  
Direct Benefit ◽  
Individual Participant ◽  
Long Time ◽  
The Individual

AbstractThe European GCP Directive has been implemented into German law in sect. 40 ff. AMG (German pharmaceutical law). Unlike the Directive, German pharmaceutical law basically differentiates between three constellations of clinical trials on minors: clinical trials on healthy minors, clinical trials on ill minors with an individual benefit for the individual participant, and clinical trials on ill minors without direct benefit for the individual participant, but with a so-called “group benefit”. Particularly the latter possibility of conducting clinical trials on minors even if no individual benefit can be expected is not a matter of course in Germany since due to historical experiences a sceptical attitude towards clinical research on humans prevailed for a long time. German legislature has availed itself of the option granted by Article 3 of the GCP Directive to establish a higher level of protection of clinical trial subjects than the European level.

Community Equipoise and the Architecture of Clinical Research

1997 ◽  
Vol 6 (4) ◽  
pp. 385-396 ◽  
Author(s):  
Jason H. T. Karlawish ◽  
John Lantos
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Standard Care ◽  
Human Services ◽  
Safety And Efficacy ◽  
Medical Progress ◽  
Essential Condition ◽  
Health And Human Services ◽  
Development Proceeds

Equipoise is an essential condition to justify a clinical trial. The term, describes a state of uncertainty: the data suggest but do not prove a drug's safety and efficacy The only way to resolve this uncertainty is further study In many cases, a clinical trial seems to be the most efficient way to prove safety and efficacy Equipoise is therefore not an esoteric philosophic construct applied to research ethics. Rather, since it is vital for the justification of clinical trials, it is part of how society regulates medical progress. Where there is equipoise, drug design and development proceeds according to Food and Drug Administration (FDA) and Health and Human Services (HHS) regulations. When that equipoise ends, a drug is either not approved or becomes standard care.

scholarly journals The role of a data manager at a clinical trial center: the experience of the Alessandria hospital, Italy

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Fabio Giacchero ◽  
Carolina Pelazza ◽  
Serena Panpa ◽  
Marinella Bertolotti ◽  
Tatiana Bolgeo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Clinical Studies ◽  
Reference Period ◽  
Job Description ◽  
Data Manager

Objectives: To define the Data Manager (DM) job description within the Clinical Trial Center (CTC) of the Alessandria Hospital (AO AL). To identify the number of authorized clinical studies after the implementation of three DMs in the CTC of the AO AL. Methods: The activities of the DM within the CTC of the AO AL take place in the activation, management and conclusion of clinical trials. The activities were monitored through specific indicators from June 01st, 2019 to May 31st, 2020. Results: During the reference period, an increased authorized studies were observed. Conclusion: The implementation of DMs in the CTC of AO AL has been demonstrated the importance of the figure itself, which, although it has not professionally recognized yet, is found to be fundamental in clinical research.

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