Why Adaptive Trial Designs Should Become the Norm for Your Trials

The cost for new drug approvals has risen to $2.9 billion, including the expense of the required post-approval studies. Why are new drug approvals so expensive? Because 90 percent of test drugs that enter clinical trials don’t ever make it to approval. So, the cost is so enormous because of the high failure rate.

Clinical development is the single biggest category of spending in Research & Development; Elliott Levy, Senior Vice President of Global Development at Amgen explains, “The overwhelming majority of money that is spent on clinical trials goes towards programs that fail. As an industry, we need to increase the amount we spend on drugs that reach the market and decrease the amount we spend on those that don’t.”

How do we do that, though?

Amgen has taken on this challenge by focusing on human genetics; this area is able to help pinpoint drugs that have the best chance at leading to new medicines. Another promising approach, however, could also increase the success rates in clinics by altering the way that clinical trials are initially designed.

“Clinical research is seen as more of a box-checking exercise, where we run fairly cut-and-dried randomized, placebo-controlled studies based on established protocols. But things are actually changing very rapidly in the world of drug development,” said Levy. “Truly innovative methods for clinical trial design are maturing or mature.”

The Key: Moving from Fixed to Flexible Designs

Far too often, the protocol of clinical studies is set before the first participant is even enrolled.

However, new methods are more flexible. Levy explains that with adaptive designs, incoming data can be monitored and protocol can be modified based on what is learned as the study progresses. It’s important that the potential changes be mapped out before the trial starts. Some of these changes might include increasing the size or duration of the trial, dropping or adding doses, and enriching the study population.

Adaptive design also is beneficial to patients because the sooner a drug is determined to work or not work, the sooner it can be advanced, stopped, or altered and the sooner it can become available to help patients, if approved.

It’s an exceptional example of patient centricity.

Rob Lenz, Head of the Center for Design and Analysis said, “Simulating clinical trials can’t make a drug work if it isn’t going to work, but it can help you design an optimized trial with the highest likelihood of providing meaningful and actionable answers.”

The Tradeoffs

Certainly, tradeoffs are required if companies want to prioritize cost, the likelihood of success, or speed. For example, you often gather more data at each stage of the program when a company optimizes for success, but that also makes the program go slower. Optimizing for speed usually will increase your costs, and optimizing for costs can slow your trials down. Adaptive strategies provide some balance to these tradeoffs, however. Levy explains, “We can simultaneously increase our odds of success, reduce our spend, and get to an answer more quickly. That’s what makes these new methodologies so attractive.”

How can adaptive clinical trials boost the chance of trial success?

The main way that adaptive designs can improve success rates is by correcting assumptions that would otherwise cloud the true potential of a drug. A fixed design doesn’t allow for adaptation as assumptions turn out to be incorrect. Lenz explains, “We assume the patients will look a certain way; the disease will progress at a certain rate; the doses will perform a certain way; the treatment effect will be a certain amount. Invariably, some assumptions are wrong.”

Being able to adjust clinical trials to adapt to incorrect assumptions minimizes the risk of wrong assumptions sinking a drug that otherwise might have succeeded. Many failures in clinical trials are due to choosing the wrong drug targets. Levy states that “As we get better at picking targets by using human genetics, clinical trial design will become the next variable we need to optimize to improve success rates.”

Making Adaptive Trials More Practical

One of the reasons adoption of adaptive trials has been slow until recently is that they’re still considered by many to be novel and risky; it’s also easier to stick with familiar methods.

However, there are many features of adaptive methods that are working to help speed implementation up with pharma companies. These include:

•         Data needed for accurate trials comes from two sources, real-world data from health records and patient-level data from previous trials.
•         The FDA is now required to provide guidance on how adaptive trial designs can be used in a way that satisfies companies’ evidence standards.
•         More companies are able to combine the advantages of big and small organizations, thanks to technological advances; they are able to put muscle and money behind innovation like a big company and also move quickly like smaller organizations can.

Companies understand the new direction and the benefits that adaptive trials provide, but there are still myths and challenges that need to be addressed. “We need our physicians and statisticians to know that we encourage them to adopt these methodologies, and they will be honored for their efforts even in cases where the outcome isn’t successful,” Levy reassures.

Stockholders, pharma companies, physicians, and ultimately patients will reap the benefits that adaptive trial designs provide. Attending a clinical ops executives summit is a great way to gain powerful takeaways to implement at your company for improving your success with clinical trials.