The days of simple clinical trials are numbered, recent history has shown a steady increase in the duration, complexity and overall cost, this has been exemplified by a continued decrease in the number of New Molecular Entities Being approved by the FDA over the past few years.

Clinical trials have increase in duration by approximately 10% in the last 5 years, the number of patients and the number of interventions per patient are steadily increasing, this has lead to a steady increase in per patient costs and overall trial costs increasing. In addition to this phase III clinical trial failure rates have increase by 10% over the past 5 years.  The overall result of these trends has been the gradual reduction in the return on R&D investment. The industry has been looking for a new way of doing things and adaptive clinical trial design has been providing some of the answers.

Adaptive Clinical Trials offer the following benefits.

Reduced attrition

• Careful selection of drug candidates and target indications
• Disposal of unsuccessful products earlier
• Working closely with regulatory agencies.

Optimized clinical trial design

• Minimizing, duration, complexity, and size,
• without compromising quality of data output

All done via

• Dose optimisation
• Patient selection and sub-grouping
• Placebo/comparator utilization

The regulators are keen for companies to pursue development with these techniques:

Janet Woodcock, Director of FDA’s CDER, in 2006, “improved utilization of adaptive and Bayesian methods” could help resolve low success rate of and expense of Phase 3 clinical trials.

There are a number of different types of Adaptive Clinical Trials: the thing that adaptive trials have in common is that you are developing your trial as you progress, altering the dose of patietns, the mix of patient types, changing or cancelling treatment arms but all done by design. Adapting your design as you progress means you can optimise in response to the data generated.

Types of Adaptive Trial

• Stopping early (or late) for efficacy or futility
• Dose finding (& dose dropping)
• Seamless Phases
• Indication Finder
• Adaptive randomisation
• Adapting treatment to population
• Modifying accrual rate.

You can’t just jump in with adaptive trial designs there is allot more preparation that is required, this preparation time should be rewarded in the long run many times over.

Methods

Lots of modelling is required to ensure your designs are robust, you can get a feel for how your adaptations will impact the outcomes and which outcomes are going to drive your decisions and adaptations, and that you have all the logistics in place that you need to support this chaning trail.

The data needs to be gathered quickly and reviewed, often prior to cleansing (reconsilation required later), ongoing statistical analysis needs to be taken care of and a data monitoring board needs to be onbaord and capable of dealing with this fast flow of data.

Also logistics needs to be managed flexibly, doses can change, recruitment rates can change, patient mixes can adjust and different clinical centres need to be responsive.

If you would like to know more how these programmes can help you speed up your development, reduce your costs and manage your risks just get in touch.

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology), we work with our clients to define a development target, define a development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch using the contact form or email Damien at damien.bove@idaconsultants.com