Ethics and Adaptive Design
June 1, 2012
Note: This article is one of a series about adaptive design that come from a blog written by Dr. Karen Kesler from 2010 to 2011. That blog is no longer active, but it contained some great information, so we wanted to re-post it here.
It seems like periodically our culture goes through a phase where it’s cool to only discuss things in terms of money and not touch on the much more slippery issues of what’s good for people. Even the pharmaceutical industry, which is built upon making people healthier and therefore improving their lives, follows this notion. Luckily, statisticians never rank very high on anybody’s “coolness” scale, so we can discuss the issues we’re facing in designing studies or analyzing data in terms of “what’s the right thing to do” to our heart’s content. And it’s a good thing, because we’re always running into problems like how many people do we need in a study so we get a solid answer without exposing more subjects than necessary to this potentially harmful therapy.
Adaptive designs can help us with this moral dilemma, which is a really good reason to consider them. The whole concept of an adaptive design in a Phase II clinical trial means that instead of exposing a hundred or so subjects to a new compound and waiting to see what happens, we stop at 25 or 50 subjects, look at what’s going on and make appropriate changes as needed. If we’ve really got an unsafe or completely ineffective compound, maybe we decide to stop it and we’ve saved a bunch of people from getting those nasty side effects, or, ensured they got something that will help them. Specific designs illustrate how much of an impact the adaptive aspect can have–take pruning designs for example. By eliminating unsafe or ineffective doses throughout the trial, we end up with fewer subjects taking those “bad” or “less effective” doses. And by starting with a wider range of doses than used in a classical design, we increase the probability that we’ll find that golden “safe and effective” dose that will benefit patients. Another kind of adaptive design is the Seamless Phase II/III studies — an example of a broader issue—getting to market faster means that the population at large gains access to a new, effective therapy. If we can use the seamless design to eliminate wasted, bureaucratic time, that’s certainly the right thing to do.
We’re lucky, really, in our industry, a lot of the cost of developing a new therapy is driven by the per subject costs, so when we’re being cost effective, we’re also being patient effective. And if a new compound works, getting it approved earlier means that more people can reap the health benefits as well as the sponsor having more time on patent to make a profit. Saving money by developing faster and using subjects more effectively not only makes the stockholders happy, it makes the ethicists happy, too.