Patent Application
20160001079
The invention relates generally to systems, devices, and methods for using an implantable medical device to deliver therapy to a patient. More specifically, according to one aspect of the invention, systems, devices, and methods according to the invention are used to deliver electrical stimulation to a peripheral, central or autonomic neural structure. In one particular aspect, the invention relates to neurostimulator systems, devices, and methods for treating primary headaches, such as migraines, cluster headaches, trigeminal autonomic cephalalgias and/or many other neurological disorders, such as atypical facial pain and/or trigeminal neuralgias.
Primary headaches are debilitating ailments that afflict millions of individuals worldwide. The specific pathophysiology of primary headaches is not known. Known causes of headache pain include trauma, vascular defects, autoimmune deficiencies, degenerative conditions, infections, drug and medication-induced causes, inflammation, neoplastic conditions, metabolic-endocrine conditions, iatrogenic conditions, musculoskeletal conditions, and myofacial causes. In many situations, however, even though the underlying cause of the headache may be identified and treated, the headache pain itself may persist.
Recent clinical studies in treatment of headaches have targeted the manipulation of sphenopalatine (pterygopalatine) ganglion (SPG), a large, extra cranial parasympathetic ganglion. A ganglion is a mass of nervous tissue found in some peripheral and autonomic nerves. Ganglia are located on the roots of the spinal nerves and on the roots of the trigeminal nerve. Ganglia are also located on the facial, glossopharyngeal, vagus and vestibulochoclear nerves. The SPG is a complex neural ganglion with multiple connections, including autonomic, sensory, and motor connections. The SPG includes parasympathetic neurons that innervate, in part, the middle cerebral and anterior cerebral blood vessels, the facial blood vessels, and the lacrimal glands.
The maxillary branch of the trigeminal nerve and the nerve of the pterygoid canal (also known as the vidian nerve which is formed by the greater and deep petrosal nerves) send neural projections to the SPG. The fine branches from the maxillary nerve (pterygopalatine nerves) form the sensory component of the SPG. These nerve fibers pass through the SPG and do not synapse. The greater petrosal nerve carries the preganglionic parasympathetic axons from the superior salivary nucleus, located in the Pons, to the SPG. These fibers synapse onto the postganglionic neurons within the SPG. The deep petrosal nerve connects the superior cervical sympathetic ganglion to the SPG and carries postganglionic sympathetic axons that again pass through the SPG without any synapses.
The SPG is located within the pterygopalatine fossa. The pterygopalatine fossa is bounded anteriorly by the maxilla, posteriorly by the medial plate of the pterygoid process and greater wing of the sphenoid process, medially by the palatine bone, and superiorly by the body of the sphenoid process. The lateral border of the pterygopalatine fossa is the pterygomaxillary fissure, which opens to the infratemporal fossa.
Various clinical approaches have been used to modulate the function of the SPG in order to treat headaches, such as cluster headaches or chronic migraines. These approaches vary from lesser or minimally invasive procedures (e.g., transnasal anesthetic blocks) to procedures or greater invasiveness (e.g., surgical ganglionectomy). Other procedures of varying invasiveness include those such as surgical anesthetic injections, ablations, gamma knife procedures, and cryogenic surgery. Although most of these procedures can exhibit some short term efficacy in the order of days to months, the results are usually temporary and the headache pain eventually reoccurs.
Ongoing clinical studies evaluate the efficacy, safety, and reliability of new devices and methods for treatment of such headaches. A proposed new therapy requires approval from a regulatory authority before being granted permission to be marketed. Clinical studies normally include prospectively randomized controlled studies, where patients are randomly assigned to control and experimental groups. Such studies typically include a patient group which receives a placebo or sham treatment, as for example when the study relates to a new pharmacological agent. Placebo or sham therapies may be desirable to in order to study the efficacy, safety, reliability, and reproducibility of the proposed therapy during a clinical trial.
In the case of new drugs a patient may be given a placebo compound, making them a control subject. In the case of device therapy, producing a control subject is much more difficult. For example, if the device therapy involves delivery of stimulation that the patient can sense through feel, it would be difficult to produce a control subject, due to the need to produce the sensed feel without providing the stimulation. As such, it can be a challenge to conduct clinical studies of medical devices where patients receiving stimulation from the devices are compared to a control group that does not receive the stimulation, sham stimulation.
Accordingly, there exists a great need for improved devices and methods for providing longer term efficacy in patients suffering from headaches and, in particular, methods and devices for conducting clinical studies involving medical devices that provide treatments via stimulation.
The invention relates to systems, devices, and methods for using an implantable medical device (“IMD”) to deliver therapy to a patient. According to one aspect, the invention relates to an IMD for delivering electrical stimulation to a peripheral, central or autonomic neural structure. In this aspect, the IMD may comprise a neurostimulator for treating primary headaches, such as migraines, cluster headaches, trigeminal autonomic cephalalgias and/or many other neurological disorders, such as atypical facial pain and/or trigeminal neuralgias.
According to one aspect, the devices, systems, and methods enable a patient to respond to a therapy regimen during a clinical trial evaluation, so that the efficacy of the therapy regimen can be determined and recorded. The devices, systems, and methods may also enable the evaluation of the patient's response(s), e.g., by a physician. The devices, systems, and methods, further may be useful in treatment of patients in a post-market usage after the clinical trial.
In one embodiment, an IMD and an associated handheld remote controller (“RC”) each may have an operating memory for storing a programmable operating instructions and data, both input and recorded, that govern the operation of each respective device. The IMD and RC each may also include processing hardware, associated with the operating memory, for executing the programmable operating instructions in accordance with the input and recorded data. According to one aspect, the IMD may receive from the RC operating instructions, data, or both operating instructions and data, that at least partially govern the therapies applied via the IMD. The governed therapies may include either or both the clinical trial therapies and the post-market usage therapies.
The IMD administers therapy in accordance with stimulation parameters stored on the IMD. The stimulation parameters may be programmed into the IMD in a variety of manners. For example, the stimulation parameters may be programmed via a programming system, which can be either local to or remote from the device. Local programming of the IMD can be accomplished, for example, with the patient near a physician's workstation, which can communicate wirelessly with the device (e.g., via Bluetooth, long range induction, etc.) or with the RC acting as an interface or wand to the device. Remote programming of the IMD can be accomplished by establishing communication between with the device via one or more communication networks. For example, a remotely located physician's workstation can communicate with a patient's personal computer via an internet connection, which relays the stimulation parameters to the IMD via the RC acting as an interface.
According to another aspect of the invention, the RC is configured to prompt for and elicit from the patient subjective and objective data, which the patient enters via the RC. The RC records the patient input data, and also records data associated with the treatment applied by the IMD. The data can then be transmitted to the physician's workstation or possibly mobile device such as a PDA, cell phone, tablet, etc., so that the physician can use the data to verify the stimulation parameters for current therapy or to determine control or stimulation parameter adjustments for subsequent therapies or determine if the current stimulation parameters provide effective therapy to the patient.
Accordingly, the invention relates to a method for conducting a clinical trial with a medical device. The method comprises the step of providing a medical device to a trial subject, the medical device being capable of providing an adjustable level of therapy. The method also comprises the step of using the medical device to apply therapy to the trial subject. The method further comprises the step of controlling the application of therapy applied to the trial subject according to a clinical trial design.
The invention also relates to an apparatus for applying stimulation therapy to a subject in a clinical trial. The apparatus includes an implantable medical device and a remote controller for inductively powering the medical device and communicating with the medical device. The implantable medical device is adapted to store therapy settings and simulation parameters for applying the stimulation therapy. The remote controller is operative to record therapy data during the application of stimulation therapy.
The invention further relates to a system for conducting a clinical trial on a medical device. The system includes an implantable medical device for applying stimulation therapy and a remote controller which uses radio frequency (RF) for inductively powering the medical device and communicating with the medical device. The implantable medical device is configured to store therapy settings and simulation parameters for applying the stimulation therapy. The remote controller being operative to record therapy data during the application of stimulation therapy. The system also includes a communication network over which the remote controller can transmit the recorded therapy data in order to conduct the clinical trial.
The invention relates to systems, devices, and methods for imparting a therapy on a patient in at least one of a clinical trial and a post-market trial usage. More particularly, the invention relates to devices, systems, and methods for applying patient stimulation therapies to at least one of clinical trial subjects and post-market patients. According to one aspect of the invention, the devices, systems, and methods of the invention allow for conducting a clinical trial via variations in applied stimulation therapies according to a clinical trial design. In one particular example implementation, the devices, systems, and methods of the invention can be used to conduct a clinical trial according to a random insertion of placebo trial design.
The neurostimulator embodying the IMD 20 illustrated and described herein is an example of just one particular IMD that may be implemented in accordance with the systems, devices, and methods of the invention. Those skilled in the art will appreciate that the systems, devices, and methods of the invention can be applied to implantable stimulators other than the neurostimulator illustrated in
The IMD 20 illustrated in
The IMD 20 of the example embodiment of
During a therapy session, the IMD 20, powered by the RC 50, delivers electrical stimulation per the stimulation parameters stored on the IMD. Each of the electrodes 26 is controllable independently, which allows the physician to select which electrodes will serve as anodes and which electrodes will serve as cathodes in any combination. The IMD 20 can apply the stimulation therapy in accordance with the stimulation parameters stored on the IMD. Additionally, the IMD 20 can acquire and transmit to the RC 50 therapy session data gathered during a therapy session. The IMD 20 includes a non-volatile memory for storing the stimulation parameters and other clinical trial or device related information.
The RC 50 provides inductive power to the IMD 20 and communicates (e.g., via radio frequency) with the IMD. Through this communication, the RC 50 can access settings and parameters stored on the IMD 20 and also record therapy session data (in real-time or at a predetermined time). For example, in an embodiment used in a clinical trial, the RC 50 may record therapy session data in real time while also accessing clinical trial specific data (e.g., trial type, specific questions to be asked, therapy randomization strings, language settings, etc.) in real-time or at some predetermined time before, during, or after the therapy session. In another example, in an embodiment used in a post-market patient usage, the RC 50 may record therapy session data in real time while also recording post-market specific data (e.g., specific questions to be asked) in real-time or at some predetermined time before, during, or after the therapy session.
In this description, reference is made to “patients” and “subjects” interchangeably. The term “patients” can be used to describe patients in a clinical trial setting or in a post-market usage. Similarly, the term “subjects” can be used to describe patients in a post-market usage or in a clinical trial setting.
Also, in this description, reference is made to stimulation parameters that may be programmed and/or stored on the IMD 20 and accessed and transmitted to/from the RC 50. The term “stimulation parameters,” as used herein, is meant to encompass the parameters that define the stimulation therapy applied to the patient by the medical device 10. In a clinical trial setting, the stimulation parameters may include parameters for each of several therapy modes or configurations used during the clinical trial. The stimulation parameters include, but are not limited to, the parameters set forth below in Table 1:
Additionally, in this description, reference will be made to therapy settings and clinical trial settings programmed and/or stored on the IMD 20 and accessed and transmitted to/from the RC 50. The term “therapy settings,” as used herein, is meant to refer to patient specific settings that customize the medical device 10 according to patient needs/preferences and physician/clinician or clinical trial requirements. The therapy settings may include post-market patient usage settings, clinical trial settings, or a combination of both. The term “clinical trial settings,” as used herein, is meant to refer to settings and/or data related to a clinical trial conducted using the medical device 10. The therapy/clinical trial settings include, but are not limited to, the settings set forth below in Table 2:
Additionally, in this description, reference will be made to therapy session data that can be recorded, stored and transmitted by the RC 50. The term “therapy session data,” as used herein, is meant to refer to data related to the therapy applied by the medical device 10 during a session. The therapy session data includes, but is not limited to, the data set forth below in Table 3:
Referring to
The RC 50 also includes a power button 68 and I/O ports in the form of a USB/charging port 70. The RC 50 may include multiple ports and other connectivity features for providing flexibility in communications, data transfer, software/firmware uploading/downloading. Such additional ports may also be used to provide for connectivity and expandability with peripheral devices, such as a Bluetooth or other add-on communications module.
The RC 50 includes a power source that includes batteries (disposable or rechargeable) and may also be powered externally via a cable connection (e.g., via AC outlet or USB). The antenna portion 54 includes a coil for inductively powering the IMD 20 and for communicating with the IMD. The RC 50 is configured to power and communicate with the IMD 20 when the RC 50 is brought into a predefined proximity (e.g., within 5 centimeters) of the IMD.
The RC 50 is illustrative of one example controller that may be implemented in accordance with the systems, apparatuses, and methods of the invention. Those skilled in the art will appreciate that certain aspects of the systems, apparatuses, and methods of the invention can be applied to controllers other than the RC 50 illustrated in
In operation, the RC 50 transfers energy to the IMD 20 via near field electromagnetic induction. The RC 50 transmits power signals via the power antenna, located in the antenna portion 54, at a specific frequency. The IMD 20 includes a power coil/antenna that is tuned to resonate close to the frequency at which the RC 50 transmits the power signal and thereby generates, through induction, power for the IMD.
The RC 50 also communicates with the IMD 20 to provide, for example, stimulation parameters, software/firmware upgrades, and other operating instructions and data prior to or subsequent to IMD implantation. The RC 50 may also receive from the IMD 20 therapy session data, handshaking communications, and current stimulation parameter settings.
Referring to
Once a communication and power link is established, the IMD 20 administers the therapy in accordance with the instructions of the RC 50 and the stimulation parameters stored on the IMD. During use, the patient may be able to adjust certain stimulation parameters (amplitude, pulse width, frequency, combination thereof, or specific protocols with automatic preset adjustment in two or more parameters at once) or parameters (ramp time, duty cycle, etc.) via the input device 62, e.g., by manipulating the control buttons 64. These adjustments are physician/clinician approved & configurable.
The RC 50 and IMD 20 are components of a system for applying stimulation therapy to a patient. Referring to
The wireless communication/power connection between the RC 50 and the IMD 20 is illustrated in dashed lines at 102. This connection 102 may, for example, employ a medical implant specific communication protocol, such as a medical implant communication system (MICS) protocol. This specialized protocol helps institute a degree of security, safety and reliability in communications between the RC 50 and the IMD 20, especially while the IMD is implanted in the patient.
The physician WS 110, patient PC 120, and remote DB 140 can be interconnected via a communication network 170 that includes wired connections (e.g., a wired internet connection), indicated generally with solid lines and wireless connections (e.g., a WiFi internet connection, a Bluetooth connection, or a GSM/CDMA/LTE mobile network connection), indicated generally with dashed lines. In the embodiment illustrated in
The RC 50 can be connected to the physician WS 110 via a direct wired connection 112 (e.g., via a USB port or docking station), or via a wireless connection 114 (e.g., a WiFi connection, a Bluetooth connection, or a GSM/CDMA/LTE mobile network connection). Connected with the physician's WS 110, the RC 50 may act in a pass-through mode, allowing the physician to access the IMD 20 for programming or data retrieval via the physician WS.
The RC 50 can also be connected to the patient personal computer 120 via a direct wired connection 122 (e.g., via the USB port or docking station), or via a wireless connection 124 (e.g., a WiFi connection, a Bluetooth connection, or a GSM/CDMA/LTE mobile network connection). The RC 50 can also communicate with the remote DB 140 via the network 170. Additionally, the RC 50 can be connected directly to the remote DB 140 via a wireless connection 142 (e.g., a GSM/CDMA/LTE mobile network connection).
From the above, those skilled in the art will appreciate that the system 100 has a highly selectable configuration, and that the communication between the RC 50, physician WS 110, patient PC 120, and remote DB 140 may be configured to occur in various combinations. In this configuration, the network 170 allows for the omission of certain portions or components of the system 100 and also for redundancy in various communication channels through the network.
For example, referring to
In another example communication configuration or mode, referring to
In yet another example communication configuration or mode, referring to
In a further example communication configuration or mode, referring to
Referring to
The system 100 also includes a patient diary 160 in which the patient records data associated with the treatments administered via the IMD 20. The data can be in the form of responses to questions asked by the system, and the questions can be either subjective or objective in nature. The questions can be prompted and answered both prior to, during, and/or after the therapy is applied. In this manner, answering the questions may serve as a gate to patient therapy by which therapy is denied until certain diary questions are answered. Post therapy diary questions can be answered immediately after the stimulation therapy is applied or sometime thereafter. The timing and content of the questions asked both pre and post therapy can be physician/clinician selected. Post therapy diary questions can be answered via the RC 50 directly or via the patient PC 120. The patient diary can be considered a portion of the therapy/clinical trial settings & data (Table 2).
The patient diary 160 is illustrated in
Once entered, when the RC 50 is operatively connected for communication with the system 100 (wired or wirelessly), the data from the patient diary 160 can be transmitted to the remote DB 140, to the physicians WS 120, to the patient PC 110, or to a cloud based storage system. Thereafter, the physician can access the data via the workstation 110. Additionally, the patient may also be able to access certain data from the patient diary 160, such as previously answered diary questions, unanswered diary questions or additional questions, via the patient PC 120. In an internet or cloud-based implementation, the patient can access the patient diary 160 online via web access.
The questions queried to the patient for entry in the patient diary 160 can be subjective questions or objective questions. Subjective questions can serve to help describe or categorize the headache episode in terms of symptoms, severity, duration, lasting effects, etc. The data from the subjective questions in the patient diary thus give patient specific details and sensory perceptions that can be used to evaluate and adjust the therapy regimen for that particular patient. Objective questions elicit from the patient factual details not subject to the patients perception, and thus generate data that can collected along with objective data from other patients and used to evaluate efficacy for the group as a whole. The subjective and objective data collected in the patient diary includes, but is not limited to, the data set forth below in Table 4:
The questions for obtaining the patient diary data can be queried by the RC 50 at times relative to an event or according to a predetermined schedule. For example, when the RC 50 is initially powered on, the patient may be prompted to answer questions regarding headache pain levels, location (side) of the headache pain, acute medications taken, sensitivity to light/sound, the presence of nausea or vomiting, and the presence of autonomic symptoms (e.g., red/tearing eyes, blocked nose, eyelid swelling, etc.). When therapy is stopped, the patient may be prompted to answer questions regarding headache pain. At a predetermined time after therapy stops, such as one hour after therapy, the patient may be prompted to answer questions regarding headache pain levels, rescue medications taken, sensitivity to light/sound, the presence of nausea or vomiting, and the presence of autonomic symptoms.
Additionally, the therapy applied by the medical device 10 may be controlled or otherwise limited or scheduled according to a therapy cycle of a predetermined duration and which includes predetermined intervals according to which therapy is applied. As an example, a therapy cycle may be a 90 minute cycle during which therapy can be applied only during the first 15 minutes. Additionally, prior to beginning therapy, the therapy cycle may require that the headache diary questions be answered. The example therapy cycle may permit continuous or intermittent use during the initial 15 minutes of the 90 minute cycle, and the RC 50 will display the remaining therapy time during the initial 15 minutes of the therapy cycle. Once the 15 minute therapy time expires, no additional therapy is permitted for the remaining 75 minutes of the 90 minute therapy cycle.
According to the invention, the system 100 can facilitate administering stimulation therapy in a post-market setting as a part of an ongoing regimen in combating disorders, such as migraine headaches. The system 100 can also facilitate study of the effectiveness of the stimulation therapy as part of a clinical trial or case study. At the patient level, the physician can program the IMD 20 via the workstation 110 to set the, individualized stimulation parameters, the individualized settings for the RC 50 (e.g., language, diary questions, screen settings, etc.), and any software/firmware updates that may be necessary. The RC 50 then can upload these items to the IMD 20. At home, the patient self-administers, within physician prescribed limits, the stimulation therapy on an as-needed basis, or in accordance with a schedule assigned by a physician/clinician.
The physician WS 110 is outfitted with software that allows the workstation to communicate with the RC 50 when connected thereto via either the wired connection 112 or the wireless connection 114. The physician WS 110 also may communicate with the RC 50 connected remotely to the patient PC 120, via the internet connection 146, 148. The physician WS 110, being additionally connected with the remote database 140, can also access the remote database as a central repository for information relating to clinical trial data for a specific patient and/or other patients enrolled in the trial. Through the remote database 140, administrators, physicians, and clinicians conducting the clinical trial may also transmit stimulation parameters to the RC 50 under the supervision and approval of the patient's physician. If authorized, these settings can then be downloaded to the IMD 20 via the RC 50.
The physician WS 110 can be a PC based system used by the physician to configure the IMDs 20 prior to implantation or post implantation. The programmer (physician) can interface with the RC 50 wirelessly or through the USB connection. In an embodiment, the RC 50 communicates with the physician WS 110 through the wired connection 112, and the controller may enter a pass-through mode in which all or some of the controls are disabled, leaving the controller to simply serve as a communication bridge between the physician WS 110 and the IMD 20. The RC 50 may also communicate with the physician WS wirelessly via the wireless connection 114. Through this communication, the programmer can instruct the RC 50 to communicate with the IMD 20, transmitting and receiving data via their built-in, bi-directional telemetry capabilities. This allows the programming physician to, for example, install or update software/firmware and to set and adjust the stimulation parameters and therapy settings in the IMD 20.
The patient PC 110 can be a PC based system with installed proprietary software that provides for communicating with the RC 50 and relaying data to the remote DB 140. The patient PC 110 is not, however, limited to a PC based system. The system 100 can be adapted to provide for charging and communicating with the RC 50 in a variety of manners. For example, the system 100 may include a standalone charging/docking station with wireless internet communication capabilities for transmitting data to the remote DB 140. In this configuration, a PC is not necessary. As another example, the RC 50 could be fitted with a simple AC power cord for charging and short-range wireless communication capabilities (e.g., Bluetooth) for transmitting data to the remote DB 140 via an external device, such as a Bluetooth enabled PC or cell phone, or a PDA type device.
The remote DB 140 may be built on any platform that allows information to be stored, read, and updated. For example, the remote database can be an industry standard such as Oracle, Microsoft SQL Server, etc., that permits standard SQL (Structured Query Language) commands and queries to store, access, and manipulate the data contained therein. The database can include a table or tables that contain the serial numbers of all IMDs 20 that have been implanted in patients, and can also contain the therapy status of those patients. For example, the database may include all the results of the clinical trial for all patients enrolled in the trial including, but not limited to, the patients' histories, therapy protocol for the patients, therapy efficacy, and treatment regimens for the patients and results to-date. To address privacy concerns, the data stored on the remote DB 140 may be blind to the identity of the patients. The remote DB 140 may, however, may store non-identifying clinically relevant patient data, such as height, weight, blood pressure, sex, and age of the clinical trial participants.
According to one aspect of the invention, the stimulation parameters and therapy settings programmed onto the IMD 20 can include all of the patient and device specific information necessary to perform the stimulation therapy on the patient. It is not necessary to include any patient or therapy specific data (e.g., stimulation parameters/therapy settings) on the RC 50 itself. Due to this, the RC 50 is necessary only to inductively power the IMD 20. This offers a great advantage in that any RC 50, whether it is the patient's personal unit, a physician's unit, or a replacement unit can be used to apply stimulation therapy via the IMD 20 without any pre-programming or set up. The RC 50 may thus be a turn-key unit ready to operate right out of the box.
As another advantage, the RC 50 can also perform its querying and recording functions without any preprogramming either. The RC 50 reads the patient diary questions and schedule from the IMD 20, administers the diary questions, and records the patient diary data accordingly. The RC 50 also reads and records the therapy session data and clinical trial data in real time during the therapy session. The RC 50 thus additionally initiate and administers the patient diary questions, records the therapy session data, and records the patient diary data without pre-programming any patient or trial specific parameters, settings, or data into the RC.
As a further advantage, storing the stimulation parameters and therapy settings on the IMD 20 helps ensure that the therapy will be applied according to the correct patient specific parameters and settings. This also helps ensure that the correct therapy type, patient language, and diary questions are applied/queried to the patient. All of these features advantageously improve the reliability and accuracy of the medical device 10 over a device that includes patient specific settings or parameters on the remote unit.
According to one aspect of the invention, the system 100, and the devices and methods implemented therein, enable a patient to respond to a therapy regimen during a clinical trial and during a post-market usage. In the clinical trial, the stimulation therapy is applied and the patient's responses to the therapy are recorded in an experimental setting according to a clinical trial protocol defined by a clinical trial design so that the efficacy of the therapy can be validated, recorded, studied, and improved.
In a post-market usage, the stimulation therapy is applied as an ongoing treatment regimen tailored by the physician to treat the patient's specific medical condition. The system 100, the medical device 10, and the methods by which the stimulation therapy is applied enable the evaluation of the patient's response by the physician so that the efficacy of that particular patient's treatment regimen can be monitored, adjusted, and improved.
According to the invention, the system 100 can be used to administer a clinical trial that evaluates and tests the effectiveness of the IMD 20 and RC 50 in treating a patient. In the clinical trial setting, the RC 50 and IMD 20 are adapted to apply stimulation therapy according to a clinical trial design that is used to study the effectiveness of the medical device 10 in accordance with established scientific methods of experimentation.
Those skilled in the art will appreciate that there are many different clinical trial designs that may be used to determine the safety and efficacy of the medical device 10, such as a randomized clinical trial design, a blind/double blind clinical trial design, and a placebo (sham)-controlled clinical trial design. According to the invention, the medical device 10 can be adapted to conduct a clinical trial conducted in accordance with any of these designs alone or in combination with each other, and with or in combination with any other clinical trial design.
As an example, the system 100 may be used to employ a random insertion of placebo clinical trial design for evaluating the efficacy and safety of the medical device 10. According to this design, the IMD 20 is programmed to apply stimulation therapy to clinical trial subjects/patients in one of several therapy modes, one of which is a placebo or sham mode, that are selected at random and that are unknown (blind design) to the participant. The therapy modes differ from each other in terms of one or more of the stimulation parameters, such as the frequency, duration, amplitude, pulse width, pulse interval, electrode set, duty cycle and patient limits. In the particular example clinical trial design described herein, there are three therapy modes: full therapy mode, placebo or sham therapy mode, and sub-perception therapy mode.
The full therapy mode applies the full therapeutic stimulation to the subject/patient. In the full therapy mode, the IMD 20 applies stimulation therapy in accordance with the values of the stimulation parameters on the IMD, which are indicated or selected as being the proper values for that particular patient. When the patient receives stimulation therapy in the full therapy mode, the patient receives full therapy and thus may experience all of the sensory perceptions typically associated with receiving this type of (neuro)stimulation. Such sensory perceptions may include, for example, tingling or tickling, sensations commonly associated with neurostimulation. The full therapy mode is the same mode or essentially the same mode that is used as the post clinical trial usage of the system.
The placebo or sham therapy mode applies no stimulation to the subject/patient. Thus, in the placebo therapy mode, the IMD 20 applies no stimulation to the patient. In the placebo therapy mode, the RC 50 may be adapted to provide feedback to the patient indicating that stimulation therapy is being applied. When the patient receives stimulation therapy in the placebo therapy mode, the patient receives no therapy and thus should not experience any of the typically associated sensory perceptions (e.g., tickling, tingling, pain). The placebo therapy mode is transparent to the patient, i.e., in appearance, it is no different that the full therapy mode, expect the patient may not perceive any sensations.
The sub-perception therapy mode applies some therapeutic effect to the subject/patient that is less than that of the full therapy mode. In the sub-perception therapy mode, however, the values for some or all of the stimulation parameters are selected such that the patient experiences no, or substantially no, sensory perceptions (e.g., tickling, tingling,) that would indicate to the patient that full stimulation therapy is being applied. Thus, the sub-perception therapy mode may apply as much stimulation therapy as possible without being perceived by the patient. The use of sub-perception stimulation is that the patient is effectively blinded to whether he/she is receiving placebo or active, albeit non perceived stimulation.
According to the example embodiment of the invention, when the system 100 is used to conduct the clinical trial, the medical device 10 administers stimulation therapy to the trial subject according to a predetermined randomized schedule that dictates which of the therapy modes is applied during any given therapy session. The randomized schedule is part of the therapy settings (see Table 2) stored on the IMD 20. The stimulation parameters for each of the therapy mode is also stored on the IMD 20. The physician can adjust the stimulation parameters for any of the therapy modes.
When the patient initiates a therapy session via the RC 50, the RC retrieves from the IMD 20 the appropriate diary questions based on the therapy type determined by the randomization string. The RC 50 can record the stimulation parameters and therapy settings (see Tables 1 and 2) for the therapy type from the IMD 20. The patient answers the required diary questions, the RC 50 records the patient diary data (see Table 4), and the IMD 20 applies the stimulation therapy according to the therapy mode selected according to the randomized string. As the therapy is applied, the RC 50 records the appropriate therapy session data and clinical trial data (see Tables 3 and 4). Once the stimulated therapy is completed, the patient can complete any necessary patient diary questions. Thereafter, the stimulation parameters, therapy settings, therapy session data, clinical trial data, and patient diary data can be transmitted to the remote DB 140 via the various communication means provided in the system 100. The collected data may remain stored in non-volatile memory of the RC 50 for a predetermined period of time, until more memory registers are needed, until transferred wired or wirelessly to the remote DB 140 via the patient PC 120 or physician WS 110, or the data is erased manually.
Referring to
As shown in
As shown in
As shown in
As shown in
As shown in
For example, an additional step could be implemented in which the application of therapy described in
Referring to
The process 300 then proceeds to step 310, where the RC 50 prompts the patient for answers to any pre-treatment questions. These questions can be designed to elicit from the patient the patient diary data set forth in Table 4. This step 310 may be optional, as it is conditioned on whether the supervising physician/clinician has opted to require pre-treatment questions as a gateway to therapy. The process 300 then proceeds to step 312, where the patient initiates and conducts the therapy session. During the therapy session, if permitted by the supervising physician/clinician, the patient can adjust any adjustable parameters within the physician defined limits. The therapy session ends at step 314 due to either expiration of a timeout period or due to cessation by the patient.
The process 300 proceeds to step 320, where the RC 50 records the therapy session data (Table 3) and/or any necessary clinical trial settings/data (Table 2). The process 300 then proceeds to step 322, where the RC 50 prompts the patient for answers to any post-treatment questions, if the prompting for answers to such questions is enabled by the supervising physician/clinician. At step 342, the IMD 30 records the therapy session data. The process 300 proceeds to step 324, where the RC 50 transmits the recorded data, if this function is enabled. Alternatively, the recorded data may be stored until such a time that transmission of the data is convenient to the patient.
When the RC 50 transmits the recorded data to the remote database, the remote database updates its records and analyzes the data. The database can be utilized to compare the data to pre-programmed data and determines whether an appropriate party, e.g., the patient's physician or an administrator of the clinical trial, should be contacted. If so, the party is contacted and can take the appropriate action, as needed.
From the above description of the invention, those skilled in the art will perceive improvements, changes and modifications. Such improvements, changes and modifications within the skill of the art are intended to be covered by the appended claims.
This application claims the benefit of U.S. Provisional Application No. 61/578,337. This application is also a continuation-in-part of U.S. patent application Ser. No. 12/688,524, filed Jan. 15, 2010, titled “APPROVAL PER USE IMPLANTED NEUROSTIMULATOR,” which claims the benefit of U.S. Provisional Application No. 61/145,003 filed Jan. 15, 2009. This application is also a continuation-in-part of U.S. patent application Ser. No. 12/765,712, filed Apr. 22, 2010, titled “IMPLANTABLE NEUROSTIMULATOR WITH INTEGRAL HERMETIC ELECTRONIC ENCLOSURE, CIRCUIT SUBSTRATE, MONOLYTHIC FEED-THROUGH, LEAD ASSEMBLY AND ANCHORING MECHANISM,” which claims the benefit of U.S. Provisional Application No. 61/171,749 filed Apr. 22, 2009, and U.S. Provisional Application No. 61/177,895 filed May 13, 2009. The full disclosures of these applications are hereby incorporated by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61578337 | Dec 2011 | US | |
| 61145003 | Jan 2009 | US | |
| 61171749 | Apr 2009 | US | |
| 61177895 | May 2009 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 13722260 | Dec 2012 | US |
| Child | 14850986 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12688524 | Jan 2010 | US |
| Child | 13722260 | US | |
| Parent | 12765712 | Apr 2010 | US |
| Child | 13722260 | US |
