Oh Sheep! Clinically Relevant Sheep Neurological Surgical Models for Safety and Efficacy

Presenter: Darcy Gagne, Becton Dickinson – Interventional Surgery

Introduction:

After receiving a request to demonstrate safety and efficacy for a device to come into contact with neurologic tissues, much thought in the design is necessary for maximum clinical relevance.   The model includes a partial dorsal laminectomy with durotomy and another of craniectomy with durectomy and intraparenchymal injury before treatment with a device.  This enables the ability to demonstrate safety and efficacy both acutely and chronically in two spaces.

Materials & Methods:

With request from Regulatory bodies to demonstrate acute and chronic safety and efficacy, it was determined the most clinically relevant models include the dorsal laminectomy with durotomy and a separate study which includes a craniectomy with durectomy and intraparenchymal injury.  Much exploration and refinement to the surgical techniques was performed throughout.  This most closely resembles the ability to apply a device in the several tissue planes of the neurologic tissues, as well as evaluate the ability to monitor the animals post-operatively via clinical and neurological examinations over time, including histological evaluation to consider the host body response.

Results:

Careful literature searches, communication with internal and external experts and considering historical data requires much attention to detail to ensure that the data demonstrates safety and efficacy for the end user and recipient.  Considering that the brain and spinal cord are connected and have unique properties with regard to the intended use, it is necessary to generate the clinically relevant models to apply a device into these tissues and enable exposure of the device into the subdural and extradural spaces.  Since the material is applied to the spinal cord of a quadruped, the dura can be left open, unlike a human to enable the ability to test a worst-case scenario of direct application of the device to the spinal cord.  It also enables the ability to create an injury into the parenchymal tissue in the same two spaces along with the bony edges of a craniectomy.  Both models are of similar tissues and clinically relevant amounts of device.  Furthermore, these models enable the ability to study the animals clinically and neurologically over time. This chronic data allows for a better understanding the response to the tissues as well as host body response via histology.  During development of these very inclusive models, errors took place, which were utilized while refining the model.

Discussion:

To bring a device to the market for clinical use, the most clinically relevant animal model(s) are required to demonstrate safety and efficacy endpoints.  In this case of the device to be intended to come into contact with neurologic tissue, the brain and spinal cord must be evaluated over time.  The animal is observed for neurologic evaluations through the duration of the resorption of the device and post-euthanasia.  Careful considerations during planning and communications are imperative to success.

Conclusion:

Much important research must be considered when planning sheep studies utilizing clinical relevance to demonstrate safety and efficacy for a device that will be in contact with neurological tissues.  There are careful planning, method development details, refinement and post-completion evaluations required with this complex goal.  Following the patients through their In-Life duration helps refine the model for the next study.