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Clinical trials, like new product development in general, are not only time-consuming but are also costly. This brings a dire need to move towards innovative ideas in clinical trials. One such innovative trial idea is suggested by the FDA, i.e., implementing adaptive designs in clinical trials. The innovative trial design cuts the cost and reduces the trial’s turnaround time. In short, it boosts clinical research.
Its flexibility is the most productive aspect of implementing adaptive designs in clinical trials. The adaptive designs make better use of the results gathered in the trial to devise a modification according to the pre-specified rules.
More important is the efficiency that adaptive designs bring into your clinical trials. Not only are they efficient, but they are more principled and informative than the traditional designs that are fixed. This is because adaptive designs make better use of money and time. In short, they maintain the trial’s validity and integrity.
If you are a researcher, there is much more to know about adaptive designs in clinical trials.
Just dive in!
An adaptive design is one that allows changes to the trial or statistical procedures after the trial has begun without jeopardizing the trial’s validity and integrity. In other words, the adaptive design makes necessary changes to the procedure after the trial has begun without compromising the trial’s validity.
To understand an adaptive design and how it is implemented, you must first understand the traditional clinical trial process. The typical clinical trial procedure is straightforward and consistent. During the trial course, there is no room for change. Major steps in traditional trials include:
Now implementing an adaptive design in traditional strategy work as follows:
There are certain pe-planned changes that an adaptive design allows. These are as follows:
Here are three major types of adaptable study designs. Go through them, and you’ll have a better understanding of how they work.
The ideal situation for using a blinded sample size re-estimation trial is when there is no reliable information on parameters in the planning phase. Hence it enables the researcher to control the power in the trial.
Undertaking a planned blinded sample size re-estimation means maintaining the trial power to 90%, even if underlying assumptions for the initial sample size calculation were wrong.
Slightly difficult to grasp? Blinded sample size re-estimation allows you to adjust the study based on empirical estimates derived from real subjects and real data rather than pre-specified estimates for a nuisance parameter.
This adaptable design also allows you to decrease the sample size if your starting estimate is too high for the nuisance parameter. Moreover, with blinded sample size re-estimation, there is a higher chance of trial success. This eventually means less reliability on conservative guesses leading to the reduced potential cost.
Another crucial aspect of the blinded sample size re-estimation is the attainment of greater powered estimates against the fixed terms. In addition to that, you have greater confidence since you can convert the sample size.
The multi-arm multi-stage (MAMS) trial can avoid lengthy studies of treatments for you that have no beneficial effects. A single control group is required against which different experimental treatments will be compared.
The MAMS trial allows a fair one-on-one comparison of treatments within the same study. However, the inclusion of interim analyses increases the efficiency of the study.
Upon each interim analysis, patients are assessed according to the test statistics and are compared with the control. Test statistics actually help to decide which treatment to continue with and which to stop.
An arm will be stopped in either of these cases:
Patients are recruited for the control and experimental arms to make the final decision.
The design is more often used in the early phase of clinical development. It helps identify the minimum effective and maximum dose tolerable for the upcoming phase. In this regard, the clinical research management method is used in conjunction with the Bayesian approach. The trial will give a probability that a drug was effective.
Randomization design revolves around the scheme of adjusting the probabilities of treatment assignment. In other words, adaptive randomization aims at increasing the likelihood of success. It is to be noted that randomization design could not be implemented on long-duration trials.
This is because the proposed modification depends upon the patient’s responses that are already a part of the trial, and it will delay the trial otherwise.
A response adaptive randomization, RAR, allows you to change the randomization probabilities per the observed outcomes. This eventually means shifting the randomization probabilities toward arms showing promising results during the trial course. It also means stopping the arms from performing poorly.
An adaptive design serves as a getaway to perform efficient clinical trials. Furthermore, it is more appealing when considered from a patient’s perspective. Just check out the ways where it overweighs the traditional designs for clinical trials.
So far, you must have got the concept of how major the benefit of adaptive design is in regard to getting more precise conclusions and shortening the trial duration, obviously at a price of being more complex compared to the fixed traditional design.
There are certain key areas that need consideration while using adaptive design. These are discussed as follows:
Running a clinical trial has no cheaper way out. Especially when you are looking forward to adaptive designs in clinical trials, it is necessary that you have already convinced the decision-making concerns that your adaptive design is appropriate for that particular trial.
The decision-makers might not be familiar with the design, so they can be reluctant to accept it. In this regard, explaining the scope of design in non-technical terms is crucial. This way, they will better understand the scope and requisite cost.
Obtaining funds is followed by another challenge: the approval of the adaptive design from stakeholders. This includes ethics approval for that study.
This step may seem pretty smooth but might bring questions regarding making sense of that adaptive design. In this regard, clarification is being done to elaborate on the design aspect.
Patients should be well aware of the specified adaptions. For example, in the case of multi-arm treatment design, separate patient information should be prepared as they might get terminated during interim analysis.
Running the trial is the final step of a challenge that should be overcome successfully. As additional considerations are required compared to that of traditional fixed design, it is important to use easy statistical software to deal with the complexities that come along with adaptions.
Where innovation is encouraged in almost all aspects of the research world, adaptive design has proven to be a productive methodological tool for carrying out effective clinical trials. The adaptive design offers a positive-predictive value in addition to the establishment of the efficacy of the drug.
Knowing all these benefits, it must be ensured that adaptive design in clinical trials should be carried out with proper planning otherwise, it might result in drastic changes. Also, it must be noted that not all trails could undergo adaptive design. Expertise is required to assess the need for implementing the adaptive design in clinical trials.
To make your trials quicker and less expensive, fasten your seat belts at work and implement an adaptive design!
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