Pharmaceutical companies will accelerate adoption of adaptive clinical trial designs, according to the Tufts Center for Drug Development, to reduce clinical development timelines and costs while increasing success rates.
Adaptive design varies intervention based on patient response, refining the gold standard of randomized clinical trials.
These trial designs, which can alter patient sample size or dosing during a trial, require new technology or working practices to implement changes in randomization and manage its supply chain.
Wade Wirta and Steven Schwager discuss the strengths and weaknesses of adaptive design and the logistical considerations to manage these complex trials. Wade is a managing director of randomization and trial supply management at Medidata Solutions, and Steven is a research fellow at Medidata and professor emeritus of statistics and biological statistics at Cornell University.
What are the advantages of adaptive trials?
Wade Wirta: Adaptive trials have two primary advantages. They shorten trial timelines and they reduce the patient population and thus, the supply. Our industry understands the need to change the clinical development paradigm to yield greater efficiency. We are enabling clinical trials of the future.
Cost pressures on R&D dictate maximizing effectiveness in executing clinical trials, and adaptive trial designs can be a major contributor in increasing productivity.
Also, futile treatments or doses or endeavors are dropped early in adaptive trials, so there really is an ethical advantage by exposing patients to better treatments as quickly as possible.
Steven Schwager: An adaptive trial can be more efficient and more likely to detect a treatment effect when one exists. In addition, it benefits patients by reducing the number who receive the less effective treatment. This can increase the success rate – ex., the rate of complete remission by day 50 in a cancer trial – among the subjects in the trial by more than 20 percent.
What are the disadvantages of adaptive trials?
Steven Schwager: A major disadvantage is additional complexities in determining whether to make a change, when, and what kind. There are lots of ways to modify a trial, and it’s possible, if not done carefully, for changes to make the design worse.
Wade Wirta: Some of the complexities Steve described also lead to operational challenges in adaptive trials, like in the clinical supply chain. This area must be much more flexible, because changes in the study dictate changes in the supply chain.
Adaptive trials must be thought of not just as statistical methodology, but really as a change in the overall process and technology used to execute the trial. This adds complexities to trial conduct.
When should you use adaptive trials?
Steven Schwager: Conceptually, we modify trial design when it becomes clear that the optimal trial differs from the current trial, because of what we have learned in the trial’s early stages. The greater the difference between what we are doing and what we now know we should be doing, the more we can gain by changing the design to reflect our best current knowledge.
What is involved in the actual planning of an adaptive trial?
Steven Schwager: Planning an adaptive trial requires thinking ahead to anticipate the changes we want. Knowing we can’t plan for every contingency, we want to do the best we can.
Wade Wirta: Because of theese complexities, there really is a need for more coordination from a planning perspective. Clinical operations are about defining the protocol, defining the study and executing with precision. It’s very important for the supply chain to be an integral part.
Running supply chain simulations helps you understand the impact to supply chain logistics during the adaptation process.
Forecasting and planning are critical for functions like packaging and labeling. Drugs need to be packaged so you can change treatments or allocation and still utilize existing drug supply. Procedures like just-in-time labeling help introduce the required flexibility in drug supply that these designs require.
This applies to external interactions, as well. The interim analysis process from a procedural perspective must be clearly articulated, along with the process for interacting with data monitoring committees. Understanding roles and responsibilities, timelines and the technical implications for these external interactions is key to reducing the risk of disruptions once the trial begins.
Steven Schwager: Yes, keeping everyone on the trial team in the loop is an additional complexity because, as Wade said, many people and organizations are involved in a trial. Everyone needs to know when a change is made. Communication truly matters here.
Ultimately, adaptive trial designs are the face of the future. They improve overall trial efficiency – in timelines, cost, and safety – but their complexities make trial management difficult without a technology platform that supports changes in supply chain or patient randomization. Gaining real time insights can affect real change, enhancing trials and improving patients’ lives.