Functional imaging in the respiratory field
Unmet need in respiratory drug development
Recent economic studies [1] have shown that the development of respiratory drugs is the most expensive one with more than 1.2 billion $ per registered product. This can be in part attributed to the lack of sensitive outcome parameters to describe the effect of new therapies. Often the existing outcome parameters fail to clearly demonstrate the added value of a newly developed product resulting in a very difficult and long registration process.
Functional imaging has the potential to improve respiratory products by decreasing the cost and development time in the pre-clinical and clinical phase and facilitate the transition between these two stages. Cost can be decreased in the pre-clinical phase by speeding up the process through the use of realistic animal and patient specific models. These models can be used to assess aerosol deposition patterns as a function of the different parameters (inhaler, inhalation profile,…) without the need for patient involvement. In the clinical phase a cost reduction can be achieved by using more sensitive measures, such as segmented airway volume changes or changes in CFD-based resistance, that provide more information. Subsequently the costly phase III study designs can be optimized or inefficient therapies can ‘fail early”.
Workflow demonstrating how functional imaging in pre-clinical and clinical phases can enhance the translational process
Having a common parameter, such as animal or patient specific models, in the pre-clinical and the clinical phases can result in an optimization of the translational process. Internal iterations can be performed for instance on inhaler design or particle formulation, resulting in products with a high chance of improving the conditions of the targeted patient population. Furthermore this approach makes it possible to provide feedback from the clinical trials to the preclinical phases such that updated models could be used for the development of the next product.
Potential cost reduction through process optimization by means of functional imaging
The figure above graphically illustrates how the cost can be potentially reduced by using more sensitive outcome parameters. Within each phase the more sensitive outcome parameters lower the cost by reducing the number of required subjects for a well powered study. By using an integral approach that covers both pre-clinical and clinical activities, the translational process, which is responsible for a steep increase in expenditure, can be optimized. If one can achieve a reduction in the cost increase from pre-clinical to clinical this effect will be felt throughout the entire cycle.
References
[1] Estimating the cost of new drug development: is it really 802 million dollars?
Adams CP, Brantner VV.
Health Aff (Millwood). 2006 Mar-Apr;25(2):420-8.
[2] Functional imaging using computer methods to improve respiratory drug development
De Backer JW
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