Thursday, February 25, 2010

Adaptive design clinical trials - now comes the FDA's draft guidance

For last several years, 'adaptive design' and 'adaptive clinical trials' are hot topics in biostatistics and clinical trial fields. The industry seems to think that 'adaptive design' is the solution for lengthy and costly drug development program. There are workshops, symposiums, many publications and books about the adaptive design in last several years. However, in reality, many examples, case studies are post hoc and  based on the simulation from the historical non-adaptive clinical trial data ("had we implemented the adaptive design, we would have saved xxx time/cost/sample size..."). Recently we do see some implementation of adaptive designs in real clinical trials, but
these are mainly in early stage studies.
This month, FDA issues its guidance for industry on "adaptive design clinical trials for drugs and biologicals". This lengthy guidance contains plenty of references (perhaps with most references for a FDA guidance). Overall tone of this guidance seems to advise the sponsors be cautious in adopting the adaptive design especially those not well established designs. If you don't want to read the entire guidance, slides by two of the FDA working group members summarize the key points in the guidance.

Ahead of FDA, EU has already issued its guidance on adaptive design (or flexible design) . Their opinions have been laid out in EMEA’s REFLECTION PAPER ON METHODOLOGICAL ISSUES IN CONFIRMATORY CLINICAL TRIALS WITH FLEXIBLE DESIGN AND ANALYSIS PLAN issued in 2006. 
There was also a well publicized workshop on adaptive design in 2006 in US. However, we have to wait for four years to see FDA's draft guidance. For documentation, all materials from 2006 workshop are now on the web.
Some of the topics are on technical sides, but there are also talks about the perspectives from FDA regarding the adaptive designs.


Rich said...

Do you know of any organization whose sole responsibility is managing a DMC? I work for a small biotech company and currently utilize a large CRO to manage all DMC activities. We are interested in utilizing a DMC CRO for a phase 1/2 study. Does such a company exist?
Best regards,
Rich Brotherton

Anonymous said...

I am not aware of any CRO specifically for DMC activities.
but you may try Dr Ed Lakatos at

Tom Parke said...

At my company we have done a lot of work supporting companies running adaptive clinical trials, in particular supporting the DMC.

We work with trials where the adaptation is prospectively defined and an algortihm is coded up and put inplace to run every interim (e.g. every week). This is used to generate a report to be reviewed by the DMC - which for early phase trials may include someone from the sponsor and a specialist statistician who understands the design, and often designed it in the first place.