We wanted to know what the current pre clinical drug development challenges were so we asked Phil Birch, Corporate Brand Manager at Aptiv Solutions what his thoughts were. Here is what he had to say.
The Key Challenges in Clinical Development are:
- - R&D productivity continues to decline
- - Development costs continue to rise
- - Late-stage Phase III terminations remain a major issue
- - Health-economic pressures mount
- - The justification of true cost/benefit is becoming more challenging
- - Revenue forecasts remain flat or shoe minimal growth
Strategies to Expedite Drug Development
Adaptive Clinical Trials
The design and implementation of Adaptive Clinical Trials (ACTs) offers significant potential to improve the efficiency of product development programmes. ACTs rely on the timely collection of data in defined interim analysis steps providing the opportunity for the trial to adapt to emerging data (i.e. real time learning). For example, following an interim analysis, a decision may be made to re-estimate the size of the trial, stop the overall trial for futility, drop ineffective treatments, or change the randomization allocation in favour of more effective treatments in defined populations of patients. Importantly, these are not ad-hoc changes but are design changes that are pre-specified and planned in advance. Adaptive design concepts are applicable from phase I through phase IV, and importantly regulatory agencies in US and Europe have published specific guidance documents on adaptive trials which support their use in exploratory Phase I to Phase IIb ("Learn") trials and in adequate and well controlled Phase III ("Confirm") trials.
Although adaptive design concepts have been available for some time, only recently has implementation (especially for complex design trials) been achievable. This breakthrough has been possible because of the development of integrated technologies specifically designed to support the execution of ACTs. The utilization of adaptive execution technologies alongside specific adaptive processes governing biostatistics, data management, project management and monitoring has opened up the potential for wider use of adaptive designs in clinical development. Importantly, these processes have to meet the requirements specified in agency guidance and hence an intimate knowledge of these guidelines and their interpretation is essential to regulatory success.
The essential requirements for successful design, implementation and execution of ACTs are multi-fold and include:
â€¢ Expertise to develop innovative adaptive methodologies including new validated design software (e.g. ADDPLANÂ®, FACTSâ„¢)
â€¢ Expertise and experience in developing robust solutions to address implementation challenges
â€¢ Integrated technologies designed specifically to manage the interim analysis steps central to the adaptive trial process (e.g. AptivAdvantageâ„¢)
â€¢ SOPs, processes & work practices designed specifically to support adaptive trial execution
Expertise in this area has grown steadily over the last decade not only within the pharma companies but also through the emergence of certain service provides who have specific expertise in adaptive trial design and execution. These service providers are enabling sponsor companies implement complex design trials that were once thought too difficult to achieve. The integrated execution environment required to support adaptive designs will also increase the number and complexity of designs available to industry, leading to trials that more robustly identify critical components of success.
Some of the key benefits will include:
- Improved decision-making driven by significant increases in the value of information gained per $ invested
- Increased R&D productivity in which â€˜winning' treatments will be selected over treatments that are destined to fail – and a dramatic decrease in the need to repeat trials that just fall short of significance
- More effective dose selection at Phase II leading to a much higher success rate at phase III
- The application of enrichment designs to robustly identify specific patient sub-populations to treat with targeted therapies – leading to much improved health economic measures and stronger arguments for successful pricing and reimbursement
These factors will change the landscape of R&D and contribute significantly to pharma industry recovery and sustained future success.
Aptiv Solutions are sponsors of Exploratory Clinical Development World Europe 2012.