What is a single arm clinical trial?
treatment arm Active arm Clinical trials In a placebo- controlled trial, the arm that receives a particular therapy
What is the “control arm” of a clinical trial?
Arms, Groups, and Cohorts. In a clinical study, participants are often divided into groups. In interventional studies, participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. Arm refers to each group or subgroup of participants in a clinical …
What is a clinical study arm?
Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised.
What are the requirements for a clinical trial?
Methods: In this paper we propose an adaptive design, the aim of which is to adapt the sample size of the trial when the new treatment arm is added to control the family-wise error rate (FWER) in the strong sense, whilst maintaining the marginal power of each treatment-to-control comparison at the level of the original study. We explore optimal allocation for designs where a …
What is the difference between cohort and arm?
Participants in a control arm may receive no intervention, placebo, or an intervention with a known effect. In observational studies, a pre-defined population may be observed over time and is termed, a cohort.May 17, 2009
What is an arm in an experiment?
Some study participants will be assigned to an “experimental arm” in the study. An arm is another term for a group. Those who are in the experimental arm will actually test the new medication, device or treatment that is under study, while others may receive a placebo.
How many arms can a clinical trial have?
The two arms in this case generally include the treatment arm and the control arm (alternative treatment/placebo arm). But RCTs can have more than two arms (multiple-armed RCT). One example would be a three-armed RCT comparing a treatment arm with an inactive control/placebo arm, and alternative active treatment.
What is a 2 arm study?
For a two-arm study, with two short-term outcomes, study participants are randomised to either the control or active intervention arms.Dec 9, 2019
Is a single-arm study a clinical trial?
The simplest trial design is a single-arm trial. In this design, a sample of individuals with the targeted medical condition is given the experimental therapy and then followed over time to observe their response.
What is an intervention in a clinical trial?
An intervention is defined as a manipulation of the subject or subject's environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.Oct 27, 2020
What does single arm mean?
Single-arm or non-randomized trials, in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing.
What is a 3 arm trial?
Abstract. A 3-arm trial design that includes an experimental treatment, an active reference treatment, and a placebo is useful for assessing the noninferiority of an experimental treatment.
What is 2 arm randomized controlled trial?
Study design In trials with randomized and controlled design (e.g., a two-armed study with parallel groups), the effects of the study treatment (intervention) are compared with those of a control treatment and the patients are randomly assigned to the two groups.
What is a four arm trial?
A Four Arm Study to Evaluate the Safety and Efficacy of 3 Different Doses of RVX-100 Versus Placebo in Subjects With Irritable Bowel Syndrome Accompanied by Diarrhea (IBS-D) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.Feb 26, 2010
What are the 4 phases of clinical trials?
Each stage of a clinical trial has its own purpose in ensuring that a treatment is safe and effective for use by the public.Phase 1 Clinical Trial. ... Phase 2 Clinical Trial. ... Phase 3 Clinical Trial. ... Monitoring Post-FDA Approval.Sep 2, 2021
Abstract
Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised.
Background
Confirmatory clinical trials can take many years to run, requiring considerable resources. During this time, evidence for a new promising treatment may emerge. It may be advantageous to incorporate the emerging treatment into the ongoing trial as a new randomisation arm.
Review
A comprehensive literature review was conducted to obtain and assess all current literature regarding statistical methods and design considerations when adapting an ongoing trial by adding a new treatment arm. A protocol was written in advance to fully define the aims, methods and search strategy.
Conclusions
Recent initiatives in clinical trials are aimed at speeding up research by making better use of scarce resources.
Acknowledgements
DRC is funded by a National Institute for Health Research Doctoral Research Fellowship. This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Rights and permissions
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
About this article
Cohen, D.R., Todd, S., Gregory, W.M. et al. Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice. Trials 16, 179 (2015). https://doi.org/10.1186/s13063-015-0697-y
What is clinical trial?
A clinical trial is a research study conducted with human beings to see if a new medical device, medication or other treatment is effective and safe. Some study participants will be assigned to a “control arm” or “control group” in the study. Those who are in the control arm will not receive the new medication, ...
How many children have autism?
Continue Learning about Medical Research. Autism, a developmental disorder that affects about one out of 68 U.S. children, typically involves communication and learning difficulties. It’s a sp.
What is a sponsor in a clinical trial?
Sponsor: The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. Often, the sponsor will also provide financial support for the trial. Subject: Any participant in a study. Treatment Arm: A group or subgroup of participants in a clinical trial.
What is adverse event in clinical trials?
Adverse Event: Any undesirable experience associated with a drug or procedure, also sometimes described as a side effect or negative reaction. Adverse events can range from mild to severe.
What is clinical research?
Clinical trials, also known as clinical studies or clinical research, are studies that explore whether a medical strategy, treatment, or device is safe and effective for humans. When deciding whether to enroll in a clinical trial, you will likely encounter many terms related to clinical research and what the specific trial entails.
How many phases are there in a clinical trial?
There are typically four phases of a clinical trial. Phase I is the administration of a drug or device to a small group to identify possible side effects and determine proper dose. Phase II is done to gauge whether the treatment is effective while continuing to evaluate safety. Phase III compares a new drug or device against the current standard ...
What are serious adverse events?
Serious adverse events are those that can cause temporary or permanent disability and may result in hospitalization or death. Baseline Characteristics: Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, race, and gender, ...
What is a first in human study?
First-In-Human Study: A clinical trial where a medical procedure or medicinal product that has been previously developed and assessed through laboratory model or animal testing is tested on human subjects for the first time. Food and Drug Administration (FDA): An agency within the U.S. Department of Health and Human Services.
What is an observational trial?
Observational Study: In an observational study, investigators assess health outcomes in groups of participants according to a research plan or protocol.
What is the purpose of clinical trial design?
Clinical trial design is an important aspect of interventional trials that serves to optimize, ergonomise and economize the clinical trial conduct. The purpose of the clinical trial is assessment of efficacy, safety, or risk benefit ratio. Goal may be superiority, non-inferiority, or equivalence.
What is parallel arm design?
Parallel arm design is the most commonly used study design. In this design, subjects are randomized to one or more study arms and each study arm will be allocated a different intervention. After randomization each participant will stay in their assigned treatment arm for the duration of the study [ Figure 5 ]. Parallel group design can be applied to many diseases and allows running experiments simultaneously in a number of groups, and groups can be in separate locations. The randomized patients in parallel groups should not inadvertently contaminate the other group by unplanned co-interventions or cross-overs.
What is controlled trial?
Controlled trials allow discrimination of the patient outcome from an outcome caused by other factors (such as natural history or observer or patient expectation). Choosing a right control at the right dose and right frequency is pivotal to trial success. The controls which can be used are:
What is an add on design?
Add-on design – This design denotes a placebo-controlled comparison on top of a standard treatment given to all patients. If the improvement that is achievable in addition to that obtained from the standard treatment is small, the size of such trial may need to be very large
What is randomization in RCT?
In randomized controlled trials, trial participants are randomly assigned to either treatment or control arms. The process of randomly assigning a trial participant to treatment or control arms is called “randomization”. Different tools can be used to randomize (closed envelopes, computer generated sequences, random numbers). There are two components to randomization: the generation of a random sequence and the implementation of that random sequence, ideally in a way that keeps participants unaware of the sequence (allocation concealment). Randomization removes potential for systematic error or bias. The biggest upside of an RCT is the balancing of both the known and unknown confounding factors which leads to wrong conclusions.
What is split body trial?
Randomization by body halves or paired organs (Split Body trials) – This is a scenario most often used in dermatology and ophthalmic practice where one intervention is administered to one half of the body and the comparator intervention is assigned to other half of the body.
What is a 2 x 2 factorial design?
This design can answer two or more research questions with one trial and delivers more “bang for the buck” with limited sample sizes. In a 2 × 2 factorial design with placebo, patients are randomized into four groups: (i) to treatment A plus placebo; (ii) treatment B plus placebo; (iii) both treatments A and B; or (iv) neither of them, placebo only. Outcomes are analyzed using two-way analysis of variance (ANOVA) comparing all patients who receive treatment A (groups 1 and 3) with those not treated with A (groups 2 and 4), and all patients who receive treatment B (groups 2 and 3) with those not treated with B (groups 1 and 4). The sample size requirement reduces by almost 50% as compared to carrying out drug A and drug B comparison with placebo in 2 different trials. However, a prerequisite requirement is that there is no interaction between treatments A and B. If interaction exits, then loss of power is possible in case of separate analyses of the four different combinations. If an interaction is anticipated, then that has to be factored into the sample size in addition to estimated sample size. Hence, it is not suited for rare diseases where interaction between A and B are likely. The limitations of this trial design are complexity of trial, difficulty in meeting inclusion criteria of both drugs during study subject recruitment, inability to combine two incompatible interventions, complex protocols, and statistical analytical complexities. Incomplete factorial designs are used when it is deemed unethical to exercise a non-intervention option and here the placebo only arm is eliminated.
Methods
- A comprehensive literature review was conducted to obtain and assess all current literature regarding statistical methods and design considerations when adapting an ongoing trial by adding a new treatment arm. A protocol was written in advance to fully define the aims, methods and search strategy. Search terms were defined for the following major electronic databases: M…
Literature on The Methodology of Adding Arms
- Only seven publications were identified that discussed any methodological considerations when adding an arm to an ongoing trial. These were reviewed in detail to assess and summarise the research previously carried-out and the recommendations or methodology discussed. Phillips et al. [8] summarise discussion points on adaptive designs from the Statisticians in the Pharmaceu…
Literature on Adaptive Designs in General
- The assessment of summary, regulatory, guidance and review documents on flexible or adaptive designs in general was undertaken as described in the methods section. In addition to the documents previously referenced [3-8], a further 13 were identified for detailed review from the MEDLINE search [19-31]. None of these documents discussed the addition of a trial arm. The st…
Key Statistical Considerations When Adding A Treatment Arm to An Ongoing Trial
- This literature review on methodology when adding arms and on adaptive designs in general generated the identification of a number of statistical considerations with relevance when amending ongoing clinical trials by adding a new treatment arm based on external evidence. The main considerations identified are illustrated in Figure 2, and summarised here. This section is i…
Practical Examples of Ongoing Trials in Which An Arm Has Been Added
- A search of the literature only identified three examples of trials in which an arm had been added, two results papers and the Sydes et al. publication, which also includes the methodological discussion [14]. However, the direct contacts described in the Methods section suggested 30 unique trials. Eight trials were identified to be within scope. All of these trials had obtained appro…
Statistical Considerations in Practice
- The statistical considerations that were identified within the methodological literature have been addressed to varying extents in practice. Note that not all considerations need to be addressed in each case because of the nature of the trials and their objectives. When designing or critically evaluating the results of different trials, it should be determined for each trial whether the conditi…