What are treatment arms in clinical trials?
Treatment Arm: A group or subgroup of participants in a clinical trial. Each group receives a specific intervention, study drug dose, or sometimes no intervention, according to the study protocol.
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 a reference arm in a clinical trial?
The reference arm in this design was intended to only act as a check on the similarity of the current patients to the historical controls with respect to clinical outcome when given the standard treatment.Mar 10, 2009
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
What is a clinical arm?
Arm refers to each group or subgroup of participants in a clinical trial that receives specfic interventions (or no intervention) according to the study protocol. This is decided before the trial begins.
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 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 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 three arm randomized controlled trial?
Three-arm trials that include an active control group as well as a placebo group can establish whether a failure to distinguish a test treatment effect from placebo implies ineffectiveness of the new test treatment or is simply the result of a trial that lacked the ability to identify an active drug.Jul 20, 2021
What is a 4 arm study?
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
What is an arm in a clinical trial?
Arm refers to each group or subgroup of participants in a clinical trial that receives specfic interventions (or no intervention) according to the study protocol. This is decided before the trial begins.
What is interventional study?
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.
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 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 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.
Who sponsors clinical trials?
Clinical trials can be sponsored by organizations (such as a pharmaceutical company), Federal offices and agencies (such as the National Institutes of Health or the U.S. Department of Veterans Affairs), or individuals (such as doctors or health care providers).
What to do before joining a clinical trial?
Before joining a clinical trial, it is important to learn as much as possible. Discuss your questions and concerns with members of the health care team conducting the trial. Also, discuss the trial with your health care provider to determine whether or not the trial is a good option based on your current treatment.
Why do we do clinical trials?
Clinical trials are conducted for many reasons: 1 to determine whether a new drug or device is safe and effective for people to use. 2 to study different ways to use standard treatments or current, approved treatments so that they will be more effective, easier to use, or decrease certain side effects. 3 to learn how to safely use a treatment in a population for which the treatment was not previously tested, such as children.
Why do people participate in clinical trials?
Some people participate in clinical trials because none of the standard (approved) treatment options have worked, or they are unable to tolerate certain side effects. Clinical trials provide another option when standard therapy has failed.
What is a protocol in clinical research?
Clinical trials are conducted according to a plan, called a protocol, which describes: what the researchers hope to learn from the study. Volunteers who participate in the study must agree to the rules and terms outlined in the protocol. Similarly, researchers, doctors, and other health professionals who manage the clinical trials must follow ...
How does the FDA work?
FDA works to protect participants in clinical trials and to ensure that people have reliable information before deciding whether to join a clinical trial. The Federal government has regulations and guidelines for clinical research to protect participants from unreasonable risks.
Why is it important to test drugs and medical products in the people they are meant to help?
It is also important to conduct research in a variety of people, because different people may respond differently to treatments. FDA seeks to ensure that people of different ages, races, ethnic groups, and genders are included in clinical trials.
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, method…
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…
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…