Outpatient treatment system for patients and related methods - Patents.com

Abstract

A system for outpatient treatment using immunotherapy to activate a patient's T cells to combat cancer is provided, which may include an infusion pump, a patient wearable device configured to acquire sensor data related to detection of cytokines released by a patient in response to the patient receiving the immunotherapy to activate T cells, and remote wireless communication with a health care provider based on the acquired sensor data. A computer readable medium having stored thereon computer readable instructions that, when executed by a processor, cause the processor to monitor the health of the patient may include a sensor data receiving module that, when executed by the processor, causes the processor to receive the sensor data, and an alert data generating module that, when executed by the processor, causes the processor to generate at least one alert based on the sensor data, the content of the sensor data being based on the outpatient treatment including the immunotherapy to activate the patient's T cells.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Patent Application No. 63 / 181,002, filed April 28, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to a system and method for integrating outpatient locations with healthcare providers (HCPs) using remote wireless communication with the HCPs. [Background technology]

[0003] Healthcare is experiencing a paradigm shift from reactive in-hospital procedures to proactive community-based care. Today's healthcare systems must deliver improved patient outcomes while lowering costs. Overcapacity in hospitals and pressure to deliver patient care in the community are the driving forces behind unmet demand for care at home. Until recently, healthcare systems lacked the technology to meet this demand. Various aspects of telehealth are becoming increasingly common. However, healthcare laws and regulations, including the Health Insurance Portability and Accountability Act (HIPPA), impose restrictions on patient-specific health information access, transmission, storage, etc.

[0004] As patient demand for outpatient care increases, so does the need for remote patient health monitoring devices, systems, and methods. This increased need for remote patient health monitoring is further fueled by the desire to improve patient outcomes, especially for high-risk patients (e.g., fully outpatient treatment of patients with residual leukemia cells in their body, likelihood of experiencing treatment-emergent adverse events (TEAEs) such as cytokine release syndrome (CRS) and / or neurotoxicity (NT), likelihood of experiencing other serious adverse events (SAEs) requiring hospitalization during the mandatory device monitoring period (MDMP), etc.). Summary of the Invention [Problem to be solved by the invention]

[0005] What is needed are devices, systems, and methods for improving outpatient healthcare outcomes. What is also needed are devices, systems, and methods for improving outpatient healthcare outcomes that improve communication between patients and associated healthcare providers. [Means for solving the problem]

[0006] A system for outpatient treatment may include an infusion pump for delivering a therapeutic agent to a patient. The system may also include a wearable device configured to be worn by the patient before, during, and / or after delivery of the therapeutic agent. The wearable device may include one or more sensors configured to acquire sensor data related to detection of vital signs of the patient. The system may further include a wireless communication module disposed on the wearable device and configured to remotely wirelessly communicate with a healthcare provider based on the acquired sensor data.

[0007] In another embodiment, the computer readable medium may include stored computer readable instructions that, when executed by a processor, may cause the processor to monitor the health of a patient. The computer readable medium may include a sensor data receiving module that, when executed by a processor, may cause the processor to receive sensor data. The computer readable medium may also include an alert data generating module that, when executed by a processor, may cause the processor to generate at least one alert based on the sensor data. The content of the sensor data may be based on an outpatient treatment that includes an immunotherapy that activates the patient's T cells.

[0008] In a further embodiment, a computer-implemented method of treating an outpatient patient with immunotherapy to activate the patient's T cells to kill cancer may include receiving sensor data in a processor in response to the processor executing a sensor data receiving module. The method may also include using the processor to generate alert data based on the sensor data in response to the processor executing an alert data generating module. The content of the sensor data may be based on a likelihood that the immunotherapy will trigger an increased risk factor for cytokine release syndrome.

[0009] A better understanding of the present disclosure will be obtained from the following description taken in conjunction with the accompanying drawings. Some of the drawings may be simplified by omitting selected elements for the purpose of more clearly showing other elements. Such omission of elements in some of the drawings does not necessarily indicate the presence or absence of a particular element in any of the exemplary embodiments, unless expressly indicated in the corresponding written description. Additionally, none of the drawings are necessarily drawn to scale. [Brief description of the drawings]

[0010] [Figure 1] 1 illustrates an example outpatient treatment system. [Figure 2A] 1 illustrates a high-level block diagram of an example outpatient treatment system. [Figure 2B] FIG. 1 shows a block diagram of an example sensor device. [Figure 2C] 1 illustrates an example method of implementing a sensor device. [Figure 2D] FIG. 1 illustrates a block diagram of an example patient-wearable device. [Figure 2E] 1 illustrates an example method of implementing a patient wearable device. [Figure 2F] 1 illustrates a block diagram of an example patient device. [Figure 2G] 1 illustrates an example method of implementing a patient device. [Figure 2H] 1 illustrates a block diagram of an example healthcare provider device. [Figure 2J] 1 illustrates an example method of implementing a healthcare provider device. [Figure 2K] 1 shows a block diagram of an example server. [Figure 2L] 1 illustrates an example method for implementing a server. [Figure 2M] 1 illustrates a high-level block diagram of an example outpatient treatment system. [Figure 2N] 1 illustrates a high level block diagram of an example outpatient treatment system. [Figure 3A] 1 illustrates an example patient-wearable device. [Figure 3B] 1 illustrates an example patient-wearable device. [Figure 3C] 1 illustrates an example patient-wearable device. [Figure 4A] 1 illustrates an example sensor device. [Figure 4B] 1 illustrates an example sensor device. [Figure 4C] 1 illustrates an example sensor device. [Figure 4D] 1 illustrates an example sensor device. [Figure 5A] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5B] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5C] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5D-1] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5D-2] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5E-1] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5E-2] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5F] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5G] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5H] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5J] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5K] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 5L] 1 illustrates various example user interface displays of an outpatient treatment system. [Figure 6A] An example protocol for a Phase 4 trial is shown below. [Figure 6B] An example protocol for a Phase 4 trial is shown below. [Figure 6C] 1 illustrates various example monitoring requirements for an outpatient treatment system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Those skilled in the art will appreciate that the elements in the figures are depicted for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions and / or relative positions of some of the elements in the figures may be exaggerated relative to other elements to improve understanding of the various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown in order to not overly distract from the views of these various embodiments. Furthermore, it will be appreciated that certain acts and / or steps may be described or shown in a particular order of occurrence, but those skilled in the art will appreciate that such specificity with respect to the order is not actually required. Furthermore, it will be appreciated that certain acts and / or steps may be described or shown in a particular order of occurrence, but those skilled in the art will appreciate that such specificity with respect to the order is not actually required. It will also be appreciated that the terms and expressions used herein have the ordinary technical meanings as given to such terms and expressions by those skilled in the art, as set forth above, unless a different specific meaning is explained herein.

[0012] The reliable continuous patient monitoring described herein may enable earlier intervention during patient deterioration events, better patient experience, fewer unnecessary readmissions, shorter hospital stays for clients, reduced readmission rates, and delivery of better patient outcomes. Apparatuses, systems, and methods for improving outpatient healthcare outcomes are provided. Apparatuses, systems, and methods for improving outpatient healthcare with improved communication between patients and associated healthcare providers are also provided. In certain embodiments (described herein as "Test Examples"), a system for outpatient treatment with immunotherapy that activates the patient's T cells to fight cancer is provided. The system may include an infusion pump (e.g., Blincyto® infusion as described in International Patent Application Publication No. WO 2020 / 221792, the entire disclosure of which is incorporated herein by reference). In another embodiment, a system of outpatient treatment with akapatamab (AMG160) as described in International Patent Application No. 2017 / 134158, the entire disclosure of which is incorporated herein by reference, may be provided, including products such as half-life extended (HLE) anti-prostate specific membrane antigen (PSMA) x anti-CD3 BiTE® (bispecific T cell engager). As described in more detail herein,

[0013] In either event, the patient wearable device is configured to acquire sensor data (e.g., patient vital signs data, respiration rate data, heart rate data, oxygen data, blood pressure data, temperature data, patient motion data, patient orientation data, etc.) relevant to detecting symptoms that may be attributable to the administered pharmaceutical agent (e.g., cytokines released by the patient in response to receiving immunotherapy that activates T cells). The system may also include remote wireless communication between the patient and a healthcare provider based on the acquired sensor data.

[0014] As detailed herein, devices, systems, and methods are provided that may acquire sensor data based on the type of treatment being administered to each patient (e.g., based on the type of medication; for AMG160, the wearable device may monitor the patient's vital signs for three days after a 60 minute infusion). As also detailed herein, devices, systems, and methods are provided that generate alert data based on the acquired sensor data. As further detailed herein, devices, systems, and methods are provided that facilitate audio / video communication between the patient and each healthcare provider along with the transmission of sensor data and alert data to the healthcare provider.

[0015] 1, an outpatient treatment system 100 may integrate an outpatient location 101 with a healthcare provider location 102. Details of a particular embodiment of the outpatient treatment system 100 are included herein with reference to a study example (i.e., a Phase 4 feasibility study evaluating outpatient blinatumomab in a subject (patient 105) with MRD of B-precursor ALL). Other embodiments of the outpatient treatment system 100 may relate to ongoing outpatient treatment that benefits from and / or requires, for example, remote access to patient vital signs (i.e., broadly referred to herein as "sensor data"), near real-time remote alarms based on sensor data, and frequent audio / video interaction between the healthcare provider 106 and the patient 105.

[0016] With further reference to FIG. 1 , a patient 105 can be at an outpatient location 101 (e.g., the patient's home, a caregiver's home, etc.). The patient 105 can receive outpatient treatment (e.g., outpatient treatment including immunotherapy to activate the patient's T cells to fight cancer, outpatient treatment that may cause the patient to release cytokines, outpatient treatment that requires a monitoring system, etc.) via, for example, an infusion pump 110. The treatment can include an infusion pump, although any given treatment may not include an infusion pump (e.g., oral intake, infusion via a syringe, etc.). If an infusion pump is included, infusion pump data can be obtained, for example, from the infusion pump and transmitted, for example, to a controller of the infusion pump, and can be communicatively functionally integrated into the outpatient treatment system 100.

[0017] The outpatient treatment system 100 may also include a patient wearable device 115 (e.g., a wearable device available from Current Health Devices (https: / / currenthealth.com / ), a wearable device available from Bio Beat Data (https: / / www.bio-beat.com / ), or any suitable / required remote and / or wearable monitor, etc.). The patient wearable device 115 may include, for example, a lithium ion battery with a battery life of 36 hours. The battery may be charged, for example, using wireless Qi inductive charging with a charging time of 3 hours. Although not shown in FIG. 1, the outpatient treatment system 100 may also include a wireless Qi inductive charger having a form that allows for placement of the CH device sensor. The charger may be plugged into a standard household power outlet. The charger requires no configuration and is buttonless.

[0018] For example, the patient 105 may be provided with a patient wearable device assembly that includes at least three elements: 1) a reusable cradle, 2) a disposable woven strap (in five sizes), and 3) a reusable sensor. The sensor may be inserted into the cradle and may be powered through detection of a magnet in the cradle. The strap may be inserted into the cradle on both sides. The patient wearable device 115 may be slipped up the patient's arm, for example like a tourniquet, and then tightened so that the patient wearable device 115 moves intimately with the skin. The reusable sensor may include a battery with, for example, a 36 hour battery life, and the patient 105 may be instructed to change the sensor every 24 hours, one sensor in the charger and one sensor in the patient's arm. The reusable sensor may be wirelessly charged by placing the reusable sensor on a charging plate.

[0019] The outpatient treatment system 100 may also include a blood pressure monitor 140 (e.g., an Evolv blood pressure monitor available from Omron, etc.). The blood pressure monitor 140 may be, for example, a brachial-worn wireless device that uses optical sensors, thermistors, accelerometers, and gyroscopes to measure the subject's heart rate (HR), respiration rate (RR), axillary temperature, and oxygen saturation. The relevant "vital signs" may be measured, for example, every 2 seconds and transmitted via WiFi every 30 seconds. The BP monitor 140 may be, for example, a brachial or radial oscillometric BP monitor. The BP monitor 140 is applied by the subject himself like a tourniquet and, after pressing a start button, transmits the subject's systolic and diastolic BP via Bluetooth to the subject's "tablet app" (e.g., module 253a of FIG. 2A, etc.) as described herein.

[0020] The outpatient treatment system 100 may also include an axillary temperature sensor 141 (e.g., such as a Fever Scout axillary temperature sensor available from VivaLNK). The axillary temperature sensor 141 may be attached to the patient 105, for example, via adhesion to the patient's axilla. The axillary temperature sensor 141 may be attached to the patient's axilla, for example, for the duration of the associated monitoring requirement period. The axillary temperature sensor 141 may, for example, constantly measure the axillary temperature of the patient 105 and broadcast the data via Bluetooth to the patient wearable device 115. The axillary temperature sensor 141 may, for example, be single subject use and may include a battery with a longer battery life than the device monitoring requirement period. As described herein, the axillary temperature sensor 141 may, for example, be attached to the patient's axilla for the duration of the associated monitoring requirement period (e.g., days, weeks, months, etc.).

[0021] 1 as separate devices, the patient wearable device 115, blood pressure monitor 140, and axillary temperature sensor 141, or any subcombination thereof, may be integrated into a single device (e.g., a single patient wearable device). Additionally, any given patient wearable device 115 may include other sensors (e.g., a heart rate sensor, an oxygen sensor, etc.). As described in more detail elsewhere herein, any given patient wearable device may include a "not feeling well button" that may enable the patient 105 to initiate an alert and / or an audio and / or video conversation with a healthcare provider and / or initiate emergency services.

[0022] The outpatient treatment system 100 may also include a patient device 150 (e.g., a tablet computer with ePRO software, a smartphone, etc.) and a network device 195 (e.g., a home hub, etc.). The network device 195 may, for example, provide a WiFi signal in the subject's home and send data to the CH's software platform via a cellular network. The network device 195 may, for example, plug into a standard household power outlet. The network device 195 may not require any patient configuration. Similarly, the network device 195 may not include any buttons (e.g., patient input, etc.). The patient 105 may plug the network device 195 into a standard household 110V power outlet. Although not shown in FIG. 1, the network device 195 may, for example, include at least three solid LEDs configured to indicate that the network device 195 is powered and transmitting. The patient device 150 and network device 195 may be configured to support remote wireless communication (e.g., sensor data communication, audio communication, video communication, etc.) with a healthcare provider based on, for example, the acquired sensor data and / or alert data.

[0023] As described in more detail herein, a user interface displayed, for example, on a display of the patient device 150 (e.g., display 254a of FIG. 2A, etc.) may allow the patient 105 to select a “BP reminder,” which may guide the patient 105 through the process of collecting his or her own BP. In particular, the patient 105 is typically seated and relaxed. For example, the BP cuff 140 may be slid up the patient's 105 arm like a tourniquet and then tightened. The patient 105 typically relaxes his or her arm. As described in more detail herein, the patient 105 may press a start button (not shown in FIG. 1) on the BP monitoring device 140. As described in more detail herein, the collected BP may be displayed, for example, on the patient device 150 and transmitted, for example, to a server 265a of FIG. 2A.

[0024] The outpatient treatment system 100 may also include a “software platform” (e.g., the combination of modules 253a and 268a of FIG. 2A, etc.). The software platform may be hosted at least partially on Amazon Web Services (AWS), for example, in United States (US) data servers. As described in more detail herein, the software platform 253a, 268a, when executed by one or more processors (e.g., processors 251a, 266a of FIG. 2A, etc.), may, for example, cause the processors 251a, 266a to receive sensor data (e.g., data representative of vital signs of the patient 105, patient wearable device data, blood pressure monitor data, axillary temperature sensor data, etc.). As described in further detail herein, the software platform 253a, 268a, when executed by one or more processors (e.g., processors 251a, 266a of FIG. 2A, etc.), may, for example, cause the processor 251a, 266a to generate an alert based on the sensor data (e.g., transmit the sensor data, generate warning data, transmit the warning data, initiate an audio / video conversation between the patient 105 and the healthcare provider 106, etc.). For example, the processor 251a, 266a may generate an alert based on a pre-set alarm threshold and then transmit the associated warning data to the healthcare provider (HCP) device 180.

[0025] The module 253a may be configured, for example, as a "subject tablet app" pre-installed on the patient device 150. The patient device 150 may be provided to the patient 105, for example, in a "kiosk mode" (i.e., a mode in which the module 253a is the only "application" accessible by the patient 105). As described in more detail herein, execution of the module 253a by the processor 251a may, for example, cause the processor 251a to capture electronic patient-reported outcome (ePRO) data, capture BP data from an integrated BP monitor 140, and initiate a video call between the patient 105 and the healthcare provider 106.

[0026] The software platform 253a, 268a may further include, for example, a "healthcare provider (HCP) app" (e.g., module 283a of FIG. 2A, etc.). The "HCP app" may be provided to the healthcare provider 106, for example, on an Android phone. Additionally or alternatively, the "HCP app" may be accessible via an internet browser. As described in more detail herein, execution of module 283a by a processor (e.g., processor 281 of FIG. 1A, etc.) may cause processor 281a to receive health alerts of the monitored subject, enable monitoring of associated vital signs, and conduct video calls with the subject.

[0027] As described in more detail herein, the outpatient treatment system 100 may include two independent communication links between the patient location 101 and the healthcare provider location 102. The first communication link 103 (e.g., similar to the combination of communication links 290a, 292a, and 293a in FIG. 2A ) may, for example, route data (e.g., sensor data, alert data, patient initiated call data, etc.) between the patient location 101 and the healthcare provider location 102. The second communication link 104 (e.g., similar to communication link 296a in FIG. 2A ) may, for example, route data (e.g., audio and / or video data, etc.) between the patient location 101 and the healthcare provider location 102.

[0028] Clinical dashboards (e.g., as shown in views 500a-h, 500j-l, etc. in FIGS. 5A-H and 5J-L) may be accessible via web, iOS, and Android and may integrate with EMR for easy access. Prioritization of emergency cases may include stratifying patients by risk with role-based permissions and notification routing to aid in prioritization. Collaboration using a "team-in-app" where team members can easily share notes about specific patients or alarms to improve collaboration. The system may enable: Access to deep clinical insights; tailoring alerts based on clinical pathways; tailoring alerts to clinical pathways and specific patient populations to reduce alert burden; moving away from episodic data points; alarms based on sustained changes in patient vitals over time rather than instantaneous changes; reducing alarm burden, triggering alarms only when multiple signs change simultaneously (e.g., low activity but elevated pulse and respiration rate); improving care delivery using machine learning; customizing patient-focused algorithms; defining configurable algorithms at individual or population level to measure patient baselines; early prediction of patient deterioration; machine learning models to predict patient onset and patient hospitalization risk; accelerating research initiatives; and over 1 million hours of labeled human health data available to research and develop new therapies.

[0029] The associated "kit" assembly may be included, for example, in a soft case that can be easily transported to the patient's home. The kit assembly may include at least one infusion pump 110, at least one sensor device 140, 141, at least one patient wearable device 115, at least one patient device 150, and at least one network device 195. Although not shown in FIG. 1, the kit assembly may be provided to the patient 105 in a pre-prepared or fully configured state. The infusion pump, IV bag and tubing, and supporting materials (e.g., syringes, sterile needles, alcohol pads) may be included in the kit assembly.

[0030] 2A, outpatient treatment system 200a may include patient wearable device 215a, patient device 250a, server 265a, and healthcare provider device 280a communicatively interconnected via network 290a. Outpatient treatment system 200a may be similar to outpatient treatment system 100 of FIG. 1, for example. Patient wearable device 215a may be similar to patient wearable device 115, for example. Patient device 250a may be similar to patient device 150 of FIG. 1, for example. Healthcare provider device 280a may be similar to healthcare provider device 180 of FIG. 1, for example. Network device 250a may be similar to or communicatively connected to network device 195 of FIG. 1, for example.

[0031] Although not shown in FIG. 2A , the outpatient treatment system 200a may include an infusion pump device. The infusion pump device may include, for example, similar structure and functionality to the sensor devices 240a, 241a, the patient wearable device 215a, the patient device 250a, a combination thereof, or any subcombination thereof. Additionally, the infusion pump device may generate and transmit data related to the operation of each infusion pump and / or information related to each medication. Additionally, any one of the sensor devices 240a, 241a, the patient wearable device 215a, the patient device 250a, the server 265a, or the healthcare provider device 280a may transmit data (e.g., infusion pump control data, infusion pump on / off data, infusion pump alarm data, sensor data, alert data, patient initiated call data, audio / video data, etc.) to the infusion pump device.

[0032] As described in more detail herein, server 265a may host at least a portion of a "software platform" (e.g., module 268a, etc.) including, for example, an interface to "Subject Tablet App" 253a and "Health Care Provider (HCP) App" 283a. Server 265a may thereby, for example, acquire sensor data; acquire patient-initiated call input data; generate alarm data based on the sensor data and / or patient-initiated call selection data; receive audio / video data; transmit audio / video data; and generate user interface displays based on the sensor data, patient-initiated call input data, alert data, and audio / video data. Additionally, server 265a may store, for example, the sensor data, patient-initiated call input data, alert data, and / or audio / video data in patient health-related database 269a.

[0033] For clarity, only two sensor devices 240a, 241a, one patient wearable device 215a, one patient device 250a, one server 265a, one healthcare provider device 280a, and one network device 290a are shown in Figure 2A. Although Figure 2A shows only two sensor devices 240a, 241a, one patient wearable device 215a, one patient device 250a, one server 265a, one healthcare provider device 280a, and one network device 290a, it should be understood that any number of sensor devices 240a, 241a, patient wearable devices 215a, patient devices 250a, servers 265a, healthcare provider devices 280a, and network devices 290a may be supported by the outpatient treatment system 200a.

[0034] The patient wearable device 215a may include a memory 217a and a processor 216a that respectively store and execute modules 218a. The modules 218a may be stored in the memory 217a as a set of computer readable instructions and may relate to applications for implementing at least a portion of the outpatient treatment system 200a. As described in more detail herein, the processor 216a may execute the modules 218a to cause the processor 216a to, among other things, receive, generate, and / or transmit data (e.g., sensor data, patient initiated call data, alert data, audio / video data, etc.) to and from the sensor device 241a, the network device 290a, the patient device 250a, the server 265a, and / or the healthcare provider device 280a.

[0035] The patient wearable device 215a may also include a user interface 219a, which may be any type of electronic display device, such as a touch screen display, a liquid crystal display (LCD), a light emitting diode (LED) display, a plasma display, a cathode ray tube (CRT) display, or any other type of known or suitable electronic display along with a user input device. The user interface 219a may present a user interface display (e.g., any of the user interfaces 500a-h, 500j-l, etc. of FIGS. 5A-H and 5J-L), which may, for example, present a user interface for implementing at least a portion of the outpatient treatment system 200a.

[0036] The patient wearable device 215a may also include a patient initiated call button 210a, an alert device 221a, a network interface 222a, and a Bluetooth interface 223a. The network interface 222a may be configured to facilitate communication between, for example, the patient wearable device 215a and the network device 290a via any wireless communication network 291a, including, for example, wireless LAN, MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally, the patient wearable device 215a may be communicatively connected to any other device via any suitable communication system, such as any publicly available or privately owned communication network, including those using wireless communication structures such as wireless LAN and WAN, wireless communication networks including satellite and cellular telephone communication systems.

[0037] The Bluetooth interface 223a may be configured to facilitate communication between, for example, the patient wearable device 215a and the sensor device 241a via any wireless communication network 224a, including, for example, a Bluetooth link, a wireless LAN, a MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally or alternatively, the patient wearable device 215a may be communicatively connected to any other device via any suitable communication system, such as any publicly available or privately owned communication network, including those using wireless communication structures such as wireless LANs and WANs, wireless communication networks including satellite and cellular telephone communication systems.

[0038] The sensor device 241a may be similar to the sensor device 141 of FIG. 1, for example. The sensor device 241a may include a processor 245a and a memory 246a that each store and execute a module 247a. The module 247a may be stored in the memory 246a as a set of computer readable instructions and may relate to an application for implementing at least a portion of the outpatient treatment system 200a. As described in more detail herein, the processor 245a may execute the module 247a to cause the processor 245a to, among other things, receive, generate, and / or transmit data (e.g., sensor data, patient initiated call data, alert data, audio / video data, etc.) to and from the patient wearable device 215a.

[0039] The sensor device 241a may also include a Bluetooth interface 248a. The Bluetooth interface 248a may be configured to facilitate communication between, for example, the sensor device 241a and the patient wearable device 215a via any wireless communication network 224a, including, for example, a Bluetooth link, a wireless LAN, a MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally or alternatively, the sensor device 241a may be communicatively connected to any other device via any suitable communication system, such as any publicly available or privately owned communication network, including those using wireless communication structures such as wireless LANs and WANs, wireless communication networks including satellite and cellular telephone communication systems.

[0040] The patient device 250a may include a memory 252a and a processor 251a that respectively store and execute a module 253a. The module 253a may be stored in the memory 252a as a set of computer readable instructions and may relate to an application (e.g., a "subject tablet app," etc.) for implementing at least a portion of the outpatient treatment system 200a. As described in more detail herein, the processor 251a may execute the module 253a to cause the processor 251a to, among other things, receive, generate, and / or transmit data (e.g., sensor data, patient initiated call data, alert data, audio / video data, etc.) to and from the sensor device 240a, the network device 290a, the patient wearable device 215a, the server 265a, and / or the healthcare provider device 280a.

[0041] The patient device 250a may also include a user interface 254a, which may be any type of electronic display device, such as a touch screen display, a liquid crystal display (LCD), a light emitting diode (LED) display, a plasma display, a cathode ray tube (CRT) display, or any other type of known or suitable electronic display along with a user input device. The user interface 254a may present, for example, a user interface display (e.g., any of the user interfaces 500a-h, 500j-l, etc. of FIGS. 5A-H and 5J-L), which may represent a user interface for implementing at least a portion of the outpatient treatment system 200a.

[0042] The patient device 250a may also include a microphone 255a, a speaker 256a, a camera 260a, a network interface 257a, a Bluetooth interface 258a, and a cellular interface 289a. The network interface 257a may be configured to facilitate communication (e.g., sensor data, alert data, patient initiated call data, etc.) between, for example, the patient device 250a and the network device 290a via any wireless communication network 292a, including, for example, TLS v1.2 WiFi, wireless LAN, MAN or WAN, WiFi, the Internet, or any combination thereof. Additionally, the patient device 250a may be communicatively connected to any other device via any suitable communication system, such as any publicly available or privately owned communication network, including those using wireless communication structures such as wireless LAN and WAN, wireless communication networks including satellite and cellular telephone communication systems.

[0043] While the patient device 250a is shown as a single device in FIG. 2A, it should be understood that the patient device 250a may include, for example, a first patient device 250a configured to remain at the patient location 101 and a second patient device (e.g., a cellular phone, etc.) configured to facilitate data transfer (e.g., sensor data, patient-initiated call data, alert data, audio data, video data, etc.) between multiple devices that remain within the outpatient treatment system 200a when the patient is away from the patient location 101 (e.g., when the patient device 250a is no longer within communication range of a network device 295a, etc.).

[0044] The Bluetooth interface 258a may be configured to facilitate communication between, for example, the patient device 250a and the sensor device 240a via any wireless communication network 259a, including, for example, a Bluetooth link, a wireless LAN, a MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally or alternatively, the patient wearable device 215a may be communicatively connected to any other device via any suitable communication system, such as any publicly available or privately owned communication network, including those using wireless communication structures such as wireless LANs and WANs, wireless communication networks including satellite and cellular telephone communication systems.

[0045] The cellular interface 261a may be configured to facilitate communications (e.g., audio data, video data, etc.) between, for example, the patient device 250a and the healthcare provider device 280a via any wireless communication network 296a, including, for example, TLS v1.2 cellular, wireless LAN, MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally, the patient device 250a may be communicatively connected to any other device via any suitable communications system, such as any publicly available or privately owned communications network, including those using wireless communication structures such as wireless LAN and WAN, wireless communication networks including satellite and cellular telephone communications systems.

[0046] The sensor device 240a may be similar to the sensor device 140 of FIG. 1, for example. The sensor device 240a may include a processor 249a and a memory 242a that each store and execute a module 243a. The module 243a may be stored in the memory 242a as a set of computer-readable instructions and may relate to an application for implementing at least a portion of the outpatient treatment system 200a. As described in more detail herein, the processor 249a may execute the module 243a to cause the processor 249a to, among other things, receive, generate, and / or transmit data (e.g., sensor data, patient-initiated call data, alert data, audio / video data, etc.) to and from the patient device 250a.

[0047] The sensor device 240a may also include a Bluetooth interface 244a. The Bluetooth interface 244a may be configured to facilitate communication between, for example, the sensor device 240a and the patient device 250a via any wireless communication network 259a, including, for example, a Bluetooth link, a wireless LAN, a MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally or alternatively, the sensor device 240a may be communicatively connected to any other device via any suitable communication system, such as any publicly available or privately owned communication network, including those using wireless communication structures such as wireless LANs and WANs, wireless communication networks including satellite and cellular telephone communication systems.

[0048] The server 265a may include a memory 267a and a processor 266a that respectively store and execute modules 268a. The modules 268a may be stored in the memory 267a as a set of computer readable instructions and may relate to an application (e.g., a “software platform,” etc.) for implementing at least a portion of the outpatient treatment system 200a. As described in more detail herein, the processor 266a may execute the modules 268a to cause the processor 266a to, among other things, receive, generate, and / or transmit data (e.g., sensor data, patient initiated call data, alert data, audio / video data, etc.) to and from the network device 290a, the patient device 250a, the patient wearable device 215a, and / or the healthcare provider device 280a.

[0049] Server 265a may also include a user interface (not shown in FIG. 2A), which may be any type of electronic display device, such as a touch screen display, a liquid crystal display (LCD), a light emitting diode (LED) display, a plasma display, a cathode ray tube (CRT) display, or any other type of known or suitable electronic display along with a user input device. The associated user interface may represent, for example, a user interface display (e.g., any of user interfaces 500a-h, 500j-l, etc., of FIGS. 5A-H and 5J-L), which may represent a user interface for implementing at least a portion of outpatient treatment system 200a.

[0050] The server 265a may also include a patient health-related database 269a and a network interface 270a. The patient health-related database 269a may store, for example, sensor data, patient initiated call data, alert data, audio / video data, etc. The network interface 270a may be configured to facilitate communication between, for example, the server 265a and the network device 290a via any wireless communication network 294a, including, for example, TLS v1.2 cellular, CSV / JSON output, TLS v1.2 REST API, wireless LAN, MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally, the server 265a may be communicatively connected to any other device via any suitable communication system, including those using wireless communication structures, such as wireless LAN and WAN, wireless communication networks including satellite and cellular telephone communication systems, any publicly available or privately owned communication network, etc.

[0051] The healthcare provider device 280a may include a memory 282a and a processor 281a for storing and executing modules 283a, respectively. The modules 283a may be stored in the memory 282a as a set of computer-readable instructions and may relate to applications (e.g., “healthcare provider (HCP) apps,” etc.) for implementing at least a portion of the outpatient treatment system 200a. As described in more detail herein, the processor 281a may execute the modules 283a to cause the processor 281a to, among other things, receive, generate, and / or transmit data (e.g., sensor data, patient initiated call data, alert data, audio / video data, etc.) to and from the network device 290a, the patient wearable device 215a, the patient device 250a, and / or the server 265a.

[0052] Healthcare provider device 280a may also include a user interface 284a, which may be any type of electronic display device, such as a touch screen display, a liquid crystal display (LCD), a light emitting diode (LED) display, a plasma display, a cathode ray tube (CRT) display, or any other type of known or suitable electronic display along with a user input device. User interface 284a may present, for example, a user interface display (e.g., any of user interfaces 500a-h, 500j-l, etc., of FIGS. 5A-H and 5J-L), which may represent a user interface for implementing at least a portion of outpatient treatment system 200a.

[0053] While the healthcare provider device 280a is shown as a single device in FIG. 2A , it should be understood that the healthcare provider device 280a may include, for example, a first healthcare provider device 280a configured to remain at the healthcare provider location 102 and a second healthcare provider device (e.g., a cellular phone, etc.) configured to facilitate data transfer (e.g., sensor data, patient-initiated call data, alert data, audio data, video data, etc.) between multiple devices remaining within the outpatient treatment system 200a when the healthcare provider is away from the healthcare provider location 102.

[0054] The healthcare provider device 280a may also include a microphone 285a, a speaker 286a, a camera 288a, a network interface 287a, and a cellular interface 289a. The network interface 287a may be configured to facilitate communication (e.g., sensor data, alert data, patient initiated call data, etc.) between, for example, the healthcare provider device 280a and the network device 290a via any wireless communication network 293a, including, for example, TLS v1.2 REST API, TLS v1.2 cellular, CSV / JSON output, wireless LAN, MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally, the healthcare provider device 280a may be communicatively connected to any other device via any suitable communication system, including those using wireless communication structures such as wireless LAN and WAN, wireless communication networks including satellite and cellular telephone communication systems, any publicly available or privately owned communication network, etc.

[0055] The cellular interface 289a may be configured to facilitate communications (e.g., audio data, video data, etc.) between, for example, the healthcare provider device 280a and a patient device via any wireless communication network 296a, including, for example, TLS v1.2 cellular, wireless LAN, MAN or WAN, WiFi, TLS v1.2 WiFi, the Internet, or any combination thereof. Additionally, the healthcare provider device 280a may be communicatively connected to any other device via any suitable communications system, such as any publicly available or privately owned communications network, including those using wireless communication structures, such as wireless LAN and WAN, wireless communication networks including satellite and cellular telephone communications systems.

[0056] The sensor devices 240a, 241a, patient wearable device 215a, patient device 250a, healthcare provider device 280a, and / or network device 295a may be configured to store data (e.g., sensor data, patient initiated call data, alert data, audio data, video data, etc.) within their respective memories 246a, 242a, 217a, 252a, etc., for example, when any given device is not capable of communicating data to another device as it would be if it were fully functional within the outpatient treatment system 200a.

[0057] 2B, an outpatient treatment system 200b may include a sensor device 200b having, for example, a patient device synchronization module 243b, a sensor data acquisition module 244b, a sensor data transmission module 245b, a patient initiated call button input receiving module 246b, a patient initiated call button input transmitting module 247b, and an alert data generation module 248b stored in a memory 242b as a set of computer readable instructions. In any event, the modules 243b-248b may be similar to, for example, the modules 243a, 247a of FIG. 2A.

[0058] 2C, the method for implementing the sensor device 200c may be implemented, for example, by a first processor (e.g., one of the processors 245a, 249a of each sensor device 241a, 240a of FIG. 1A) executing at least a portion of the modules 243b-248b of FIG. 2B. In particular, the processor 245a may execute the patient device synchronization module 243b to cause the processor 245a to synchronize, for example, the sensor device 241a with the patient wearable device 215a (block 243c). Similarly, the processor 249a may execute the patient device synchronization module 243b to cause the processor 249a to synchronize, for example, the sensor device 240a with the patient device 250a (block 243c).

[0059] The processor 245a may execute the sensor data acquisition module 244b to cause the processor 245b to receive, for example, sensor data (block 244c). The processor 245a may execute the sensor data transmission module 245b to cause the processor 245b to transmit, for example, sensor data (block 245c). The processor 245a may execute the patient-initiated call button input receiving module 246b to cause the processor 245b to receive, for example, a patient-initiated call button input (block 246c). The processor 245a may execute the patient-initiated call button input transmitting module 247b to cause the processor 245b to transmit, for example, a patient-initiated call button input (block 247c). The processor 245a may execute the alert data generation module 248b to cause the processor 245b to generate, for example, alert data (block 248c). The alert data may be based, for example, on the sensor data and / or the alert data.

[0060] 2D, an outpatient treatment system 200d may include a patient wearable device 200d having, for example, a sensor device synchronization module 218d, a sensor data acquisition module 219d, a sensor data transmission module 220d, a patient initiated call button input receiving module 221d, a patient initiated call button input transmitting module 222d, an alert data generation module 223d, and an alert data transmission module 224d stored in a memory 217d as a set of computer readable instructions. In any event, modules 218d-224d may be similar to, for example, module 218a of FIG. 2A.

[0061] 2E, a method for implementing the patient-wearable device 200e may be performed, for example, by a processor (e.g., processor 216a of FIG. 1A) executing at least a portion of modules 218d-224d of FIG. 2D. In particular, processor 216a may execute sensor device synchronization module 218d to cause processor 216a to synchronize, for example, sensor device 241a with patient-wearable device 215a (block 218e).

[0062] The processor 216a may execute a sensor data acquisition module 219d to cause the processor 216a to acquire sensor data, for example, from the sensor device 241a (block 219e). The processor 216a may execute a sensor data transmission module 220d to cause the processor 216a to transmit, for example, sensor data (block 220e). The processor 216a may execute a patient-initiated call button input receiving module 221d to cause the processor 216a to receive, for example, a patient-initiated call button input (block 221e). The processor 216a may execute a patient-initiated call button input transmitting module 222d to cause the processor 216a to transmit, for example, a patient-initiated call button input (block 222e). The processor 216a may execute an alert data generation module 223d to cause the processor 216a to generate, for example, alert data (block 223e). The alert data may be based, for example, on the sensor data and / or the patient-initiated call button input. The processor 216a may execute the alert data transmission module 224d to cause the processor 216a to, for example, transmit the alert data (block 224e).

[0063] 2F, an outpatient treatment system 200f may include a patient device 200f having a sensor device synchronization module 253f, a sensor data acquisition module 254f, a sensor data transmission module 255f, a patient initiated call button input receiving module 256f, a patient initiated call button input transmitting module 257f, an alert data generation module 258f, an alert data transmission module 259f, an audio / video data receiving module 260f, and an audio / video data transmission module 261f, for example, stored in a memory 252f as a set of computer readable instructions. In any event, modules 253f-261f may be similar to, for example, module 253a of FIG. 2A.

[0064] 2G, the method for implementing the patient device 200g may be implemented by a processor (e.g., processor 251a of FIG. 1A) executing, for example, at least a portion of modules 253f-261f of FIG. 2F. In particular, processor 251a may execute sensor device synchronization module 253h to cause processor 251a to synchronize, for example, sensor device 240a with patient device 250a (block 253g).

[0065] The processor 251a may execute a sensor data acquisition module 254f to cause the processor 251a to acquire sensor data, for example, from the sensor device 240a (block 254g). The processor 251a may execute a sensor data transmission module 255f to cause the processor 251a to transmit, for example, sensor data (block 255g). The processor 251a may execute a patient-initiated call button input receiving module 256f to cause the processor 251a to receive, for example, a patient-initiated call button input (block 256g). The processor 251a may execute a patient-initiated call button input transmitting module 257f to cause the processor 251a to transmit, for example, a patient-initiated call button input (block 257g).

[0066] The processor 251a may execute an alert data generation module 258f to cause the processor 251a to generate, for example, alert data (block 258g). The alert data may be based on, for example, sensor data and / or a patient call start button input. The processor 251a may execute an alert data transmission module 259f to cause the processor 251a to transmit, for example, alert data (block 259g). The processor 251a may execute an audio / video data receiving module 260f to cause the processor 251a to receive, for example, audio / video data from the healthcare provider device 180, 280a (block 260g). The processor 251a may execute an audio / video data transmitting module 261f to cause the processor 251a to transmit, for example, audio / video data from the healthcare provider device 180, 280a (block 261g).

[0067] 2H, an outpatient treatment system 200h may include a healthcare provider device 280h having, for example, a sensor data receiving module 283h, an alert data receiving module 284h, a patient initiated call button input receiving module 285h, an audio / video data receiving module 286h, an audio / video data transmitting module 287h, and an alert data generating module 288h stored in a memory 282h as a set of computer readable instructions. In any event, modules 283h-288h may be similar to, for example, module 283a of FIG. 2A.

[0068] 2J, a method for implementing the healthcare provider device 200j may be performed by a processor (e.g., processor 281a of FIG. 1A) executing, for example, at least a portion of modules 283h-288h of FIG. 2H. In particular, processor 281a may execute sensor data receiving module 283h to cause processor 281a to receive sensor data from, for example, patient-wearable device 115, 215a and / or patient device 150, 250a (block 283j).

[0069] The processor 281a may execute an alert data receiving module 284h to cause the processor 281a to receive, for example, alert data (block 284j). The processor 281a may execute a patient-initiated call button input receiving module 285h to cause the processor 281a to receive, for example, a patient-initiated call button input (block 285j). The processor 281a may execute an audio / video data receiving module 286h to cause the processor 281a to receive, for example, audio / video data from the patient device 150, 250a (block 286j). The processor 281a may execute an audio / video data transmitting module 287h to cause the processor 281a to transmit, for example, audio / video data to the patient device 150, 250a (block 287j). The processor 281a may execute an alert data generating module 288h to cause the processor 281a to generate, for example, alert data (block 288j). The alert data may be based, for example, on sensor data and / or patient call initiation button input.

[0070] 2K, outpatient treatment system 200k may include server 200k having, for example, sensor data receiving module 268k, sensor data storage module 269k, sensor data transmission module 270k, alert data receiving module 271k, alert data storage module 272k, and alert data transmission module 273k stored in memory 267k as a set of computer readable instructions. In any event, modules 268k-273k may be similar to, for example, module 268a of FIG. 2A.

[0071] 2L, a method for implementing server 200l may be performed, for example, by a processor (e.g., processor 266a of FIG. 1A) executing at least a portion of modules 268k-273k of FIG. 2K. In particular, processor 266a may execute sensor data receiving module 268k to cause processor 266a to receive, for example, sensor data (block 268l). The processor 266a may execute a sensor data storage module 269k to cause the processor 266a to, for example, store sensor data in the patient health-related database 269a (block 269l). The processor 266a may execute a sensor data transmission module 270k to cause the processor 266a to, for example, transmit sensor data (block 270l). The processor 266a may execute an alert data receiving module 271k to cause the processor 266a to, for example, receive alert data (block 271l). The processor 266a may execute an alert data storage module 272k to cause the processor 266a to, for example, store alert data in the patient health-related database 269a (block 272l). The processor 266a may execute an alert data transmission module 273k to cause the processor 266a to, for example, transmit alert data (block 273l).

[0072] Referring to FIG. 2M, the outpatient treatment system 200m may include a first sensor device 241m communicatively connected to a patient wearable device 215m. The outpatient treatment system 200m may also include a second sensor device 240m communicatively connected to a patient device 250m. The patient wearable device 215m and the patient device 250m may be communicatively connected to a network device 295m. The network device 295m may be communicatively connected to a software platform 270m (e.g., server 265a). The software platform 270m may be communicatively connected to a healthcare provider device 280m and a patient health-related database 269m. The outpatient treatment system 200m may be similar to the outpatient treatment system 100 of FIG. 1 or 200a of FIG. 2A, for example.

[0073] 2N, the outpatient treatment system 200n may include a first sensor device 241n communicatively connected to a patient wearable device 215n. The outpatient treatment system 200n may also include a second sensor device 240n communicatively coupled to a patient device 250n. The patient wearable device 215n and the patient device 250n may be communicatively connected to a network device 295n. The network device 295n may be communicatively connected to a software platform 270n (e.g., server 265a). The software platform 270n may be communicatively connected to a healthcare provider device 280n and a patient health-related database 269n. The outpatient treatment system 200n may be similar to the outpatient treatment system 100 of FIG. 1, 200a of FIG. 2A, or 200m of FIG. 2M, for example.

[0074] 3A, the patient wearable device assembly 300a may include a patient wearable device 315a, a display device 319a, and an armband 325a. The patient wearable device assembly 300a may be similar to, for example, the patient wearable device 115 of FIG. 1 or 215a of FIG. 2A.

[0075] 3B, the patient wearable device assembly 300b may include a patient wearable device 315b, an alert indicator 321b, and at least one patient initiated call button 320b. The patient wearable device assembly 300b may be similar to, for example, the patient wearable device 115 of FIG. 1 or 215a of FIG. 2A.

[0076] 3C, the patient wearable device assembly 300c may include a patient wearable device 315c, a display device 319c, a patient initiated call button 320c, and an armband 325c. The patient wearable device assembly 300c may be similar to, for example, the patient wearable device 115 of FIG. 1 or 215a of FIG. 2A.

[0077] The patient wearable device assemblies 300a-c may be designed for in-hospital and remote patient monitoring applications. For example, a multi-function cardiac patch may live stream multiple parameters to a mobile device or the cloud. The patient wearable device assemblies 300a-c may be reusable, rechargeable, and may record data even in the event of a network failure.

[0078] The patient wearable device assembly 300a-c can be a powerful cardiac patch that has been used in many studies including AF detection, coronary artery disease, stress and depression, etc. The patient wearable device assembly 300a-c can include: Rechargeable up to 96 hours; 24 hour cache; IP25 water resistance; BLE network; Size-90x20x7.9mm; Weight: 7.5 grams; 128Hz ECG sensor; Heart rate sensor 40-300bpm; Respiration 5-35brpm, 3-axis ACC 5Hz; FDA / NMPA-ECG; Heart rate, and CE-ECG, Heart rate, and Respiration rate.

[0079] The patient wearable device assemblies 300a-c may include an SpO2 sensor that may provide constant updates of the patient's oxygen saturation level without the patient having to manually initiate a reading. With a safety design that wraps around the patient's thumb, the sensor can remain attached to the patient even in an outpatient setting. Advantages of any given patient wearable device assembly 300a-c may include: live stream or live recording; reusable / rechargeable; IoT enabled; secure thumb strap; data including oxygen saturation, pulse; rechargeable up to 16 hours; 10 hour cache; IP22; BLE network; weight: 47.5 grams; SpO2-70%-100%; pulse: 30-250 bpm; and FDA / CE / NMPA.

[0080] Referring to FIG. 4A, the sensor device assembly 400a may include an axillary temperature sensor 441a and a charging device 442a. The sensor device 441a may be similar to, for example, the sensor device 141 of FIG. 1 or 241a of FIG. 2A. Unlike typical body temperature patches that are not considered FDA clinical thermometers, the VivaLNK axillary temperature patch 400a may be a clinical thermometer that can provide medically accurate (axillary) readings in outpatient and remote patient monitoring settings. This sensor device assembly 400a may be used in clinical studies (e.g., fully outpatient treatment of patients with residual leukemia cells, likelihood of experiencing drug-emergent adverse events (TEAEs) such as cytokine release syndrome (CRS) and / or neurotoxicity (NT), likelihood of experiencing other serious adverse events (SAEs) requiring hospitalization during the mandatory device monitoring period (MDMP), neurological drug discovery, chemotherapy remote patient monitoring, etc.). The sensor device assembly 400a may include: live data stream; data recording option; reusable; rechargeable; IoT enabled; water resistant; BLE booster; clinical grade axillary temperature; rechargeable up to 21 days; 20 hour cache option; IP25 water resistant; BLE network; size-61x41x5.5mm; weight-7.2 grams; ASTM E1112 compliant; range-93.2F to 109.4F; FDA / CE / NMPA; and pediatric and adult use.

[0081] With reference to Fig. 4B, the sensor device assembly 400b may include a respiration rate sensor 441b and a charging device 442b. With reference to Fig. 4C, the sensor device assembly 400c may include a heart rate sensor 441c and a wristband 442c. The sensor device assembly 400b and / or the sensor device assembly 400c may be integrated into, for example, the patient wearable device 115 of Fig. 1 or 215a of Fig. 2A. With reference to Fig. 4D, the sensor device assembly 400d may include a blood pressure sensor 441d. The sensor device 441d may be similar to, for example, the sensor device 140 of Fig. 1 or 240a of Fig. 2A.

[0082] Medications or factors associated with liver damage / impairment and cholestasis or bile duct obstruction may elevate liver enzymes above normal levels even in otherwise healthy individuals. The associated patient wearable device 115 and / or sensor device 140, 141 may generate detailed blood biochemistry tests including, for example: alkaline phosphatase (AP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and liver enzymes such as C-reactive protein (CRP), total bilirubin, gamma glutamyl transferase (GGT), D-dimer, combinations thereof, or any subcombinations thereof. The corresponding sensor data may thereby provide important information related to each patient's liver function in response to drug treatment and may provide drug-induced hepatocellular injury, cholestatic injury, or mixed liver injury. In either case, the content of the sensor data may be based on each medication and / or patient-related bioinformation. In general, the associated patient wearable device 115 and / or sensor device 140, 141 may be configured to sense body chemistry parameters that are predetermined to be likely indicative of a patient's response to a particular treatment and / or medication.

[0083] 5A-H and 5J-L, various user interface displays of outpatient treatment systems 500a-h, 500j-l are shown. As shown in FIG. 5A, healthcare provider display device 500a may include a display of patient 505a having patient wearable device 515a, sensor device 540a, infusion pump 410a, and patient device 550a. Display device 550b may include patient vital signs 554b. Display device 580c may include healthcare provider status information 584c. Display device 580d may include a list of patients with respective patient information 584e. Display device 580e may include a list of patients with respective patient information 584e. Display device 580f may include patient information 584f. Display device 580g may include patient information 584g. Display device 550h may include a patient on a video call with healthcare provider 554h. Display device 580j may include a healthcare provider on a video call with patient 584j. Display device 550k may include a patient initiated call button 554k. Display device 550l may include an incoming video call from a respective care team 554l to the patient.

[0084] Test Example With reference to Figures 6A-C, the devices, systems, and methods of the present disclosure were applied in a Phase 4 multi-center, open-label feasibility study (i.e., a study example) to evaluate exogenous blinatumomab administration in adult subjects with minimal residual disease (MRD) of B-precursor acute lymphoblastic leukemia (ALL) in complete hematologic remission.

[0085] The example test included a first partial study 600a having: a patient testing phase 601a, a patient screening phase 602a, a first drug administration phase 603a, an end of drug administration phase 604a, a second drug administration phase 605a, and an end of first partial study 606a. The example test included a second partial study 600b having: a patient testing phase 601b, a patient screening phase 602b, a first drug administration phase 603b, a second drug administration phase 604b, an end of drug administration phase 605b, a third drug administration phase 606b, and an end of second partial study 607b. The example test included monitoring 600c of a patient 105 having multiple patient monitoring requirements 610c.

[0086] The indication for the phase 4 study included adult subjects with MRD of B-precursor ALL. The rationale for this example study was to determine the safety and feasibility of fully exogenous blinatumomab administration in subjects with MRD of B-precursor ALL. Blinatumomab administration has been demonstrated to be effective in converting subjects to MRD-negative status (MRD < 0.1%) in each population. However, the mechanism of action (MOA) of T-cell activation and cytokine production can potentially result in severe toxicity, particularly cytokine release syndrome (CRS) and / or neurotoxicity (NT). The incidence of these potentially serious adverse reactions has been found to be low. In the BLAST study, 3% and 13% of subjects had severe CRS and NT, respectively (e.g., Goekbuget et al., 2018).

[0087] The objective of this example study was to determine the safety and feasibility of fully outpatient blinatumomab administration in subjects with MRD of B-precursor ALL. The example study used a mobile electronic device (e.g., tablet, smartphone, personal electronic device, etc.) to communicate electronically with the relevant healthcare provider (HCP) and used a Wi-Fi enabled platform to constantly transfer data and communications between the subject and the HCP in real time to detect clinically significant changes. The data provided to the HCP may enable the HCP to identify subjects at risk of developing grade 3 or 4 CRS, NT, or other serious adverse events (SAEs) requiring hospitalization during the mandatory device monitoring period (MDMP). If a subject develops an SAE, the HCP may direct such subject to the appropriate medical facility for hospitalization, if necessary.

[0088] [Table 1]

[0089] [Table 2]

[0090] The experimental study determined the safety and feasibility of fully exogenous blinatumomab administration. Blinatumomab is a novel bispecific T cell inducer (BiTE®) single chain bispecific binding molecule construct that links CD3+ T lymphocytes with CD19+ B cells. This treatment can lead to a significant degree of T cell-mediated immune activation in subjects, which correlates with efficacy but also with significant toxicity. The experimental results included increased T cell activation, release of inflammatory cytokines, and clinical symptoms of CRS. Along with CRS, another potentially severe toxicity observed is NT. It was expected that some subjects may show varying degrees of encephalopathy and may experience delirium, aphasia, lethargy, impaired concentration, agitation, tremors, seizures, and rarely cerebral edema.

[0091] Minimal residual disease (MRD) is defined as the presence of leukemic cells (<5%) not detectable by the use of microscopy with a sensitivity of 0.1%, as measured by either polymerase chain reaction (PCR) or flow cytometry. After achieving hematologic remission, the presence of MRD portends a poor prognosis for patients. In a related Amgen study (i.e., MT103-203 (BLAST)), 78% of subjects with MRD in B-precursor ALL achieved a complete MRD response to blinatumomab treatment. In this study, four subjects (3%) had CRS (Common Terminology Criteria for Adverse Events [CTCAE] v4 grade 1: n=2; grade 3: n=2), all during cycle 1. Twelve (10%) and three subjects (3%) had grade 3 and 4 NT, respectively. Furthermore, the incidence of CRS and NT was similarly low in subjects with relapsed / refractory B-precursor ALL treated with blinatumomab in Amgen study 00103311 (TOWER): the incidence of grade 3 CRS and NT was 4.9% and 9.4%, respectively, with 1% and 4.9% of subjects discontinuing treatment due to CRS and NT, respectively (i.e., Kantarjian et al., 2017).

[0092] At the time of the study, the current recommendation for blinatumomab treatment in subjects with MRD of B-precursor ALL was continuous intravenous infusion (CiVI) over 28 days, administered in an inpatient setting for the first 3 days of cycle 1 and the first 2 days of cycle 2. This hospitalization recommendation is primarily due to safety concerns of CRS, NT, or other serious AEs.

[0093] The disclosed devices, systems, and methods were implemented to determine the safety and feasibility of fully outpatient blinatumomab administration in subjects with MRD of B-precursor ALL in this example study. A patient (e.g., patient 105 of FIG. 1) wore a patient wearable device (e.g., patient wearable device 115 of FIG. 1, 215a of FIG. 2A, 215d of FIG. 2D, 215m of FIG. 2M, 215n of FIG. 2N, or 315a-c of FIG. 3A-C, respectively, patient wearable devices 215m, n available from CurrentHealth Devices (https: / / currenthealth.com / ), patient wearable devices 300a, 300b of FIG. 3A and FIG. 3B, respectively, patient wearable device 300c of FIG. 3C available from BioBeat (https: / / www.bio-beat.com / ), etc.). The patient wearable device was worn on the upper arm 115 as shown in FIG. 1.

[0094] Additionally, each patient 105 wore at least one sensor device (e.g., patient-wearable sensor device 140 of FIG. 1, 240a of FIG. 2A, 240b of FIG. 2B, 240m, 241m of FIG. 2M, 240n, 241n of FIG. 2N, or 440a-d of FIG. 4A-D, respectively). Subjects in this test example wore an axillary temperature patch (e.g., similar to Fever Scout axillary temperature patch 441a available from VivaLNK) and a blood pressure cuff (e.g., similar to Evolv sensor device 441d available from Omron).

[0095] Each patient was provided with a WiFi hub (e.g., network 250a in FIG. 2A, hub 295m in FIG. 2M, or 295n in FIG. 2N) configured to securely communicate patient-related data (e.g., sensor data, alert data, call initiation data, audio / video data, etc.).

[0096] Further, each patient was provided with a patient device (e.g., tablet device 150 of FIG. 1, 250a of FIG. 2A, 250f of FIG. 2F, 250m of FIG. 2M, 250n of FIG. 2N, 450a of FIG. 4A, 450h of FIG. 4H, 450j of FIG. 4J, 450k of FIG. 4K, etc.) having software modules (e.g., modules 253a of FIG. 2A, 253f-261f of FIG. 2F, etc.) (e.g., ePRO software module - CLINICAL suite - Ennov ePRO - Electronic Patient Reported Outcome Software available from Ennov, Paris, France, etc.). Software module 253a, when executed by a processor (e.g., processor 251a of FIG. 1A), may cause processor 251a to perform coordinated content, data, and process management (e.g., communication, storage, access to patient specific information - electronic health record - sensor data, etc.). In this test example, module 253a was ISO 9001:2015 certified for all associated apparatus, systems, computer readable media, and methods. Module 253e included Enterprise Document Management (EDM), Regulatory Information Management (RIM), Pharmacovigilance, and Electronic Trial Master File (eTMF).

[0097] Each healthcare provider was provided with a mobile phone (e.g., smartphones 450g, 450j, 450k, respectively, of FIG. 4G, FIG. 4J, and FIG. 4K). Additionally, each patient was provided with a module (e.g., module 283a, FIG. 2A (e.g., a platform available from Current Health devices (https: / / currenthealth.com / ), a platform available from Bio Beat (https: / / www.bio-beat.com / ), or any other suitable remote and / or wearable monitor-based platform) used to monitor the vital signs of the patient (e.g., patient 105, FIG. 1) while the subject 105 is at home (e.g., patient home 100, FIG. 1)).

[0098] This example study included: 1) remote monitoring to measure vital signs (e.g., sensor data) and a mobile electronic device (e.g., patient device 250a with module 253a) and electronically communicate the sensor data to an HCP (e.g., 280a of FIG. 2A, 484h of FIG. 4H, etc.); 2) real-time continuous transfer of patient-related data and audio / video communication between the subject 105 and the HCP 484h using a Wi-Fi enabled platform to identify subjects at risk of developing grade 3 or 4 CRS, NT, or other SAEs requiring hospitalization during the MDMP. This example subject population may require immediate escalation of care and / or hospitalization when a digital monitoring system (e.g., system 200a of FIG. 1A) identifies a change.

[0099] During screening within the study, subjects and caregivers were trained on the patient wearable device 115 and subjects and caregivers were assessed for compliance. Subjects received two cycles of blinatumomab in a completely outpatient setting according to the monitoring and intervention guidelines 510c of FIG. 5C. The study visit ended 30 days (± 3 days) after the last dose of blinatumomab, as shown in FIG. 6A and FIG. 6B.

[0100] After completing the clinical assessment visit for cycle 2, some subjects may continue to receive two additional cycles of blinatumomab (optional). There is no outpatient monitoring in the Health Management System (HMS) 270a during optional cycles 3 and 4. For the purposes of this study, the MDMP is defined as the first 3 days (72 hours) of cycle 1 and the first 2 days (48 hours) of cycle 2 of blinatumomab infusion in subjects with MRD of B-precursor ALL.

[0101] The study visit ends 30 days (± 3 days) after the last dose of blinatumomab is given. For subjects who elect to have optional cycles of cycle 3 or 4, the study visit ends after cycle 3 or 4. During the MDMP, the health management system (HMS) 270a measures vital signs. These vital signs included heart rate (HR), axillary temperature, and oxygen saturation. The health management system (HMS) 270a measures respiration rate (RR) intermittently (sampling every 30 seconds). Subjects take intermittent blood pressure (BP) measurements (using a subject-available BP device) every 3 hours during the MDMP. The schedule of BP measurements could be extended by the HCP after the first 24 hours of the MDMP (up to but not more than every 6 hours). A BP device 140 is provided and transmits BP readings directly to the HCP device 270a via the monitoring platform.

[0102] Threshold vital sign values ​​were established and an immediate alert was generated and sent to the HCP device 280a if the pre-set thresholds were exceeded and sustained for at least 10 minutes. In addition, subjects and caregivers were trained on the usual side effects of blinatumomab infusions (fever, erythematous skin rash, chills, confusion, headache, tremors, myalgia, lethargy, drowsiness, seizures) and could directly contact (phone and video) the HCP or emergency services if any expected or unexpected side effects occurred. Caregivers were expected to be close relatives such as spouses or children, but included any adult (18 years of age) willing and able to participate in the subject's care. Caregivers would remain in the home with the subject throughout the MDMP. Caregivers were trained in the use of and had access to the patient device (e.g., tablet 150 in FIG. 1 ) to contact the HCP if necessary.

[0103] The HCP and staff were trained on the infusion 110, common side effects, and reaction algorithms. The HCP (or designee) is a physician experienced in treating patients with ALL and the use of blinatumomab. The HCP (or designee) carries a smartphone 480h device with them at all times during the MDMP. The smartphone 480h includes a cellular connection to the subject's tablet 150 and the health management system (HMS) 270a to receive vital signs (i.e., sensor data) that are refreshed every 30 seconds throughout the MDMP. Blood pressure measurements were performed manually by the subject (or caregiver) every 3 hours, and the results were electronically sent to the HCP smartphone 480h. In addition to the constant supply of vital signs, an audible alarm sounds whenever a vital sign exceeds a preset threshold and remains above for at least 10 minutes. Additionally, an alarm sounds if there is no data transfer for 15 minutes.

[0104] The health management system (HMS) 270a is not intended to allow the HCP to identify patients experiencing neurotoxicity. The health management system (HMS) 270a is intended to provide remote monitoring of vital signs. Knowing the subject's vital signs provides the HCP with an overall picture of the subject's trends. In addition to vital sign monitoring, the health management system (HMS) 270a includes a video call function between the physician and the subject. This allows the HCP to visually assess the patient for early symptoms of mild neurotoxicity such as kinetic tremor (assessed by finger-nose test), ataxia, onset of disorientation in time or place, reduced attention or short-term memory impairment with attention, naming disorder, paraphasic errors, or verbal perseveration. The HCP also tests the patient's ability to name objects, follow simple commands, and communicate requests. The HCP assesses expressive aphasia by assessing the subject's ability to communicate spontaneously (e.g., the HCP may instruct the subject, "Look directly at the video screen and tell me how you are feeling today") or to name common household objects provided by a caregiver. The HCP assesses apraxia by the subject's ability to write standard sentences (e.g., "Today is Tuesday, January 1, 2001"). The HCP tests receptive aphasia by the subject's ability to follow simple commands (e.g., "Raise your right hand and touch your nose").

[0105] In addition, the caregiver is present with the patient throughout the MDMP and can communicate with and participate in the video call assessment with the HCP during the video call assessment. The HCP uses the video call assessment to determine if the patient's symptoms (defined as neurotoxicity) require immediate transport to a hospital. The HCP schedules video calls with the patient daily during the MDMP at a minimum of every 12 hours (e.g., 8am and 8pm). If there are any concerns by the HCP, the frequency will be increased.

[0106] The monitoring system also provides the ability for the patient or caregiver to activate the "I'm not feeling well" button 320b on the device tablet 170 if the subject is experiencing any neurotoxicity symptoms. Activating the button 320b immediately generates an alarm and notifies the HCP, who can immediately initiate a videophone assessment. The HCP recommends transfer to an inpatient facility if any of the neurotoxicity symptoms are more than mild in severity. Additionally, as part of the screening, patients and caregivers are trained to activate the "I'm not feeling well" button 320b in the event of any moderate symptoms of speech disturbance, impaired consciousness, deterioration of hand writing, confusion or disorientation, hypotension, hypoxia, hypertransaminasemia, hypertension, vomiting, diarrhea, or other symptoms that may be associated with CRS.

[0107] If no response was received from the HCP within 5 minutes, the subject was trained to resend the "I'm not feeling well" signal. If still no response was received after another 5 minutes, for a total of 10 minutes from the initial alarm, the subject was to immediately call emergency medical services (EMS) or 911. Similarly, if the HCP responded to any alarm generated by the subject and the subject or caregiver did not respond within 10 minutes, the HCP made one attempt to call the subject personally. If the subject or caregiver was still not contacted, the HCP immediately dispatched EMS to the subject's location. The HCP's call was configured to sound a loud audible alarm and repeat every 5 minutes until the HCP responded or if data was not transferred for 15 minutes. The HCP then used a summary of absolute vital sign values ​​and / or deviations from baseline (provided by the Health Management System (HMS) 270a) and the subject's clinical status (provided by subject / caregiver's direct phone and video contact) to determine the urgency of response, appropriate intervention, and subject disposition.

[0108] During the MDMP, any device malfunction (e.g., patient wearable device malfunction, sensor device malfunction, axillary temperature patch malfunction, blood pressure sensor malfunction, communication network malfunction, home hub malfunction, etc.) was detected within 15 minutes and generated an alarm to the HCP. The HCP immediately contacted the patient via video call functionality to assess the patient's safety, clinical status, and any specific circumstances associated with the device malfunction (e.g., device inadvertently removed, low battery, intermittent loss of signal transmission, etc.). If the HCP has any concerns about patient safety, they will advise the patient to go to the hospital immediately.

[0109] The patient was provided with a full set of replacement devices to use in case of malfunction. In addition, the patient is provided with a manual oral thermometer as needed or as directed by the HCP. In the event of a device malfunction and the HCP determines via video conference that the patient is safe, the HCP will instruct the patient to immediately switch to a replacement device. In addition, the HCP may contact the health monitoring platform 270a (e.g., Current Health's 24 / 7 hotline, etc.) for troubleshooting for device support and assistance. It is recommended that the HCP maintain contact with the subject until the device malfunction is resolved. If these interventions by the HCP fail to resolve the device malfunction, the HCP will advise the patient to immediately go to the hospital. The United States (US) Food and Drug Administration (FDA) has only permitted the use of vital signs monitoring devices and platforms 270m. During the MDMP, subjects were asked to live within a 1-hour drive of a skilled medical facility. The skilled medical facility included staff trained to manage acutely ill patients, such as those who may have developed CRS. Subjects were allowed to stay in a hotel or other outpatient hospital accommodation to meet the 1-hour transportation requirement. Subjects were trained to call emergency medical services if they had any concerns or if there was any delay in contacting the HCP.

[0110] Subjects were provided with identical Health Management System (HMS) 270a, 270m devices (e.g., BP monitor, axillary temperature patch, Current Health wearable device) in case of unexpected device malfunction. In addition, subjects were provided with identical in-home Wi-Fi devices (Assumption Hub 295m, 295n) solely for uninterrupted transmission of vital signs and for communication, including video communication, with HCPs. Subjects, caregivers, and HCPs have access to a 24 / 7 helpline for any technical issues related to the home digital monitoring device, platform, or communication.

[0111] Alternative monitoring devices may be used, such as the Biobeat monitoring device (https: / / www.bio-beat.com / ), which may be used to measure pulse pressure, continuous blood pressure, blood saturation, pulse rate, respiration rate, total peripheral vascular resistance, heart rate variability, arterial pressure, skin temperature, stroke volume, cardiac output, and cardiac index. The Biobeat device may communicate with a smart device or otherwise provide continuous or semi-continuous wireless monitoring features. The Biobeat device may be self-adhesive and may have a disposable chest patch and / or cuff attachment.

[0112] With further reference to FIG. 6B, study schema 600b includes study example evaluation items. There was no outpatient digital monitoring during optional cycles 3 and 4. Participants in this clinical study shall be referred to as "subjects." Approximately 45 subjects participated in the study example. Adult subjects have MRD of B-precursor ALL in complete hematologic remission (<5% bone marrow blasts). Amgen Study Drug Dose and Administration: Blinatumomab is administered as CiVI. The duration of one cycle of blinatumomab treatment is 6 weeks, including 4 weeks of blinatumomab CiVI followed by a 2-week treatment-free interval. The treatment-free interval was extended for up to 7 days if the investigator deemed necessary. For subjects weighing 45 kg, blinatumomab was administered at a dose of 28 μg / day for all 4 consecutive weeks of treatment. Subjects weighing less than 45 kg were administered blinatumomab at 15 μg / m2 / day (maximum 28 μg / day).

[0113] Non-investigational drug doses and administration included the following:Dexamethasone-Premedication with dexamethasone (or prednisone): Dexamethasone 16 mg (or equivalent prednisone 100 mg) intravenous (IV): Up to 6 hours prior to the start of treatment in each treatment cycle, subjects weighing 45 kg received two additional 8 mg doses (subjects under 45 kg received two doses of 5 mg / m2 rounded to the nearest mg) oral dexamethasone to be used as needed to treat CRS symptoms, only if directed by the HCP.Hospitalization was strongly recommended for subjects who required interruption of blinatumomab for more than 4 hours.

[0114] Written informed consent was obtained from all subjects before performing any study-specific screening procedures. Study-specific procedures were performed according to the assessment schedule shown in Figure 6A and Figure 6B. Forty-five patients were planned to be enrolled in the study. The sample size was based on feasibility rather than statistical considerations. Given that the true probability of a primary endpoint event was 38%, the expected 95% upper confidence limit for 45 subjects was 53.5%. The subject incidence of 38% was based on the SAE rates in the first 3 days of cycle 1 and the first 2 days of cycle 2 from the previous MRD study (BLAST). Based on these assumptions, when outpatient blinatumomab is administered in conjunction with remote digital monitoring, it is expected to observe approximately 17 subjects experiencing the primary endpoint, providing an early indication of the timeliness of therapeutic intervention. Safety data was reviewed on an ongoing basis. A Data Review Team (DRT), within Amgen but external to the study team, assessed safety each time five subjects had an opportunity to complete the required device monitoring period. The primary analysis was performed when all subjects had completed the study, which was also the final analysis.

[0115] Descriptive statistics for demographics and safety were summarized where appropriate. For categorical variables, the number and percentage of subjects in each category were summarized. Continuous variables were summarized by n, mean, standard deviation, median, Q1 (25th percentile) and Q3 (75th percentile), minimum, and maximum.

[0116] The study determined the safety and feasibility of fully exogenous blinatumomab administration in subjects with minimal residual disease (MRD) of B-precursor acute lymphoblastic leukemia (ALL). Blinatumomab administration has been demonstrated to be effective in this population in converting subjects to MRD-negative status (MRD < 0.1%). However, the mechanism of action (MOA) of T cell activation and cytokine production can potentially result in severe toxicity, particularly cytokine release syndrome (CRS) and / or neurotoxicity (NT). The incidence of these potentially serious adverse reactions has been found to be low. In the BLAST study, 3% and 13% of subjects had severe CRS and NT, respectively (e.g., Goekbuget et al., 2018).

[0117] The purpose of the example study was to determine the safety and feasibility of fully outpatient blinatumomab administration in subjects with MRD of B-precursor ALL. The study used a mobile electronic device (tablet 170) to communicate electronically with the HCP and a Wi-Fi enabled platform 200a to allow real-time, constant transfer of data and communication between the subject and the HCP 250a to detect clinically significant changes. The data provided to the HCP allows the HCP to identify subjects at risk of developing grade 3 or 4 CRS, NT, or other serious adverse events (SAEs) requiring hospitalization during the mandatory device monitoring period (MDMP). The HCP then directed such subjects to the appropriate medical facility for hospitalization, if necessary. The incidence of severe CRS and NT was low in this study population (MRD of B-precursor ALL), making it a reasonable target population to evaluate the feasibility of fully outpatient blinatumomab administration.

[0118] The study used the Current Health (CH) System 270m and platform for outpatient monitoring. Subjects in high-acuity environments such as operating rooms (ORs) or intensive care units (ICUs) or subjects who were acutely ill and developed emergency life-threatening arrhythmias were excluded from the CH platform and did not enroll in the study. As shown in Figures 6A and 6B, the primary endpoint of the study was the incidence of grade 3 or 4 CRS, NT, or any adverse event (AE) requiring hospitalization during MDMP. The CH device detects abnormal vital signs or changes in baseline vital signs to determine whether a subject developed CRS. In addition, the CH device includes a video call function between the HCP and the patient, allowing the HCP to visually assess the patient for early symptoms of mild neurotoxicity. All vital signs were monitored by a Health Management System (HMS) 270a, whose performance has been assessed by the United States (US) Food and Drug Administration (FDA) and found to be non-inferior to both Graeger and Philips vital sign monitoring devices. Therefore, the CH device was suitable and valid for monitoring abnormal vital signs in the home environment.

[0119] B-precursor ALL is a malignant disease of lymphoid precursor cells in bone marrow or lymphoid sites. Immature lymphoblasts rapidly proliferate in the bone marrow and infiltrate other organs. As a result, normal hematopoiesis in the bone marrow is suppressed. Acute lymphocytic leukemia is a rare malignant disease with an overall incidence of 1.1 / 100,000 per year. Acute lymphocytic leukemia has a bimodal distribution with an initial peak at age 4 to 5 years (incidence 4.5 / 100,000 per year) followed by a second incremental increase at age 50 years (incidence 2 / 100,000 per year). Acute lymphocytic leukemia represents 80% of acute leukemia in children and 20% of acute leukemia cases in adults (i.e., Pui and Evans, 1998; Jabbour et al., 2005; Larson, 2005; Howlader et al., 2012).

[0120] Seventy-five percent of adult subjects with ALL are of B-cell lineage and roughly 25% are of T-cell lineage origin. The majority of subjects with B-cell lineage ALL have an immature immunophenotype and are classified as B-precursor ALL. CD19 is expressed in all subtypes of B-ALL (Bassan et al., 2004). The Philadelphia chromosome (Ph) represents the most frequent cytogenetic abnormality in adult ALL and is found in 20-30% of subjects with B-precursor ALL. Adult ALL can be stratified into risk groups, which are the basis for risk-adapted treatment strategies. Selection of prognostic factors in B-precursor ALL: Prognostic factors for risk stratification in adult B-precursor ALL.

[0121] [Table 3]

[0122] A white blood cell count (WBC) less than 30,000 / μl at diagnosis and young age were favorable factors in adult ALL. In addition, a short interval to the achievement of complete remission (CR) and complete molecular remission following induction (MRD negativity; less than 1 leukemic cell is detectable in 104 bone marrow cells) were favorable factors. Treatment outcomes in adult patients with ALL have improved significantly over the last decade, with CR rates of 85-90% and overall survival (OS) rates of 40-50% (Goekbuget and Hoelzer, 2010). Pediatric protocols have been the guide for creating treatment regimens for adult ALL. These regimens consist of three phases: induction, consolidation, and maintenance. In general, the "state of the art" modalities of treatment for adult leukemia can be summarized (Goekbuget and Hoelzer, 2011). A four- to five-drug induction regimen using vincristine and prednisone with the addition of an anthracycline, cyclophosphamide, and asparaginase (or a combination of these drugs) to achieve CR. Intensive consolidation therapy based on repeated cycles and induction of cytarabine, an anthracycline, methotrexate, and asparaginase to reduce MRD levels.

[0123] Long-term maintenance therapy (approximately 2 years) using methotrexate in combination with mercaptopurine; allogeneic stem cell transplantation in first CR in high-risk patients. Allogeneic hematopoietic stem cell transplantation (HSCT) is the most thorough option for consolidation in first CR in high-risk patients. Advances in therapy that allow for patient-tailored treatment and optimization of risk stratification have been important factors contributing to improved treatment outcomes. Despite frontline treatment successes, the outcome for most adults with recurrent disease, regardless of prior treatment, is dismal, as they cannot be helped with currently available therapies (Fielding et al., 2007). Therefore, prevention of relapse is the primary treatment goal in patients who are resistant to or unable to tolerate chemotherapy.

[0124] The platform shown in Figures 2M and 2N and implemented in the test example is an FDA-cleared platform for wireless wearable health monitoring of patients at home and in the hospital. The CH product entered the US market in December 2018 after receiving FDA clearance. For the test example, Current Health's FDA-cleared indications for use were: The Health Management System (HMS) 270a was intended for reusable bedside, mobile, and centralized multi-parameter physiological patient monitoring of adult patients in a hospital or skilled nursing facility or in the patient's home. It was intended for monitoring of patients by trained HCPs. The Health Management System (HMS) 270a was intended to provide visual and audio physiological multi-parameter alarms. The Health Management System (HMS) 270a was intended for continuous monitoring of the following parameters in adults: heart rate (HR), axillary temperature, oxygen saturation, skin temperature (not assessed in this study), movement (not assessed in this study), and spirometry (not assessed in this study).

[0125] In the test example situation, the health management system (HMS) 270a was intended for intermittent or spot check monitoring of adults for: respiration rate (RR) (every 30 seconds); non-invasive blood pressure (BP); pulmonary function and spirometry (not collected in this study); and weight (not collected in this study). The health management system (HMS) 270a generated intermittent respiration rates by sampling sensor data every 30 seconds. This meant that every 30 seconds a new respiration rate was provided for use by the alarm system and for presentation on the associated dashboard. This functionality was assessed using physician-enhanced end-tidal CO2 in CH510(k)K182453. The health management system (HMS) 270a acted as a hub with seamless wireless integration. Data flowed directly through the CH wearable and through integrated third-party devices such as an axillary temperature monitor and a BP monitor. In the test example, the following were monitored and collected: heart rate (HR), axillary temperature, respiration rate (RR), oxygen saturation, and blood pressure (BP). The Health Management System (HMS) 270a is not intended for use in critical care environments such as ICU or OR, or in acutely ill cardiac patients with the potential to develop life-threatening arrhythmias, such as rapid atrial fibrillation, and is not intended for peripheral capillary oxygen saturation (SpO2) monitoring in high exercise or low perfusion situations. These excluded patients and situations were not eligible for this test example.

[0126] Additional details related to the Health Management System (HMS) 270a and integrated platform are described herein. Blinatumomab is a CD19-targeted bispecific single-chain bispecific binding molecule construct designed to link B and T cells to generate T cell activation and cytotoxic T cell responses against CD19-expressing cells. As mentioned above, blinatumomab is approved for the treatment of MRD in B-precursor ALL and has shown efficacy in the recently completed BLAST trial (Goekbuget et al., 2018). The approval of blinatumomab recommends that the initiation of cycle 1 (first 3 days) and the initiation of cycle 2 (first 2 days) be given while the patient is hospitalized. This trial is testing the hypothesis that blinatumomab can be given on an outpatient basis for the entire 28 days if subjects are monitored during the initiation days. The infusion, dose, and indications for use of blinatumomab are consistent with the relevant FDA-approved label.

[0127] Results from the previous pivotal study M103-203 and supportive study M103-202 showed similarly high (up to 80%) MRD response rates after blinatumomab treatment in subjects with ALL in complete hematologic remission (<5% bone marrow blasts) who were MRD positive at the start of blinatumomab treatment baseline. Minimal residual disease response is a strong prognostic factor for relapse after achieving CR, regardless of treatment choice or risk classification system (Lussana et al., 2016; van Dongen et al., 2015; Goekbuget et al., 2012; Goekbuget and Hoelzer, 2011; Bassan et al., 2009; Brueggemann et al., 2006). At the time of relapse, the strongest prognostic factors for OS are duration of initial remission and age (i.e., Oriol et al., 2010; Fielding et al., 2007; Thomas et al., 1999).

[0128] A published meta-analysis of 16 trials in adults with ALL has solidified the association between MRD-negative status and improved clinical outcomes (relapse-free survival [EFS] and OS), which to this point have been based primarily on reports of individual trials with variable sample sizes. Of particular interest, EFS and OS in MRD-negative (MRD < 0.1%) subjects have been shown to be remarkably consistent across diverse subgroups (e.g., MRD detection by flow cytometry vs. polymerase chain reaction (PCR), post-induction MRD assessment vs. post-consolidation MRD assessment, definition of MRD positivity, Ph status, and B-cell or T-cell phenotype) (i.e., Berry et al., 2017).

[0129] The major safety factors identified in the clinical trial were NT, CRS, and medication errors. Most AEs occurred within the first few weeks of the first cycle and were mitigated by appropriate measures such as temporary interruption without adversely affecting the treatment effect. Based on the short half-life of blinatumomab, blinatumomab can be quickly discontinued and removed if AEs are present, which may enhance the ability to efficiently manage AEs. In addition, the rate of serious AEs, especially CRS, is low enough to warrant evaluation of fully outpatient administration of blinatumomab. This is especially true in the MRD-positive population, which by definition has a low tumor burden. Furthermore, the CH system is FDA-cleared to accurately assess vitals and efficiently transmit vital signs to HCPs. In addition to the benefits of MRD treatment, fully outpatient blinatumomab is expected to be more convenient for patients.

[0130] The favorable risk assessment described above supports the conduct of this clinical trial (i.e., the example study). For further data on blinatumomab, the Investigator Brochure was consulted. Training materials were provided by CH along with further information on the digital devices used in the study. The example study used a Health Management System (HMS) 270a to measure and transmit vital signs to the HCP, a mobile electronic device (e.g., tablet 150 in FIG. 1) to communicate electronically with the HCP, and a Wi-Fi enabled platform (e.g., platforms 500m, 500n in FIG. 5M and FIG. 5N) to transfer data and communication in real time between the subject and the HCP to detect clinically significant changes to determine the safety and feasibility of fully outpatient blinatumomab administration in subjects with MRD of B-precursor ALL. The data provided to the HCP allows the HCP to identify subjects at risk of developing grade 3 or 4 CRS, NT, or other SAEs requiring hospitalization during the MDMP. The HCP directed such subjects to the appropriate medical facility for hospitalization, if necessary.

[0131] During screening, subjects and caregivers were trained in the Health Management System (HMS) 270a and assessed for compliance. Once enrolled, subjects received two complete cycles of blinatumomab in an outpatient setting according to the monitoring and intervention guidelines. After the cycle 2 clinical assessment visit is completed, some subjects may continue to receive two additional (optional) cycles of outpatient blinatumomab. The end of the study visit occurs 30 days (± 3 days) after the last dose of blinatumomab (606a, 607b). This end coincides with the end of cycle 2 clinical assessment for subjects who end after cycle 2, or after cycle 3 or 4 if the subject and PI choose to undergo optional consolidation cycles 3 and / or 4 as shown in FIG. 6A.

[0132] The overall study design is described by the study schema in Figure 6A or Figure 6B. The endpoints were defined as 604a, 606a, 605b, 607b. The treatments defined in the example study included any IP, procedure or process, non-IP, placebo, or medical device intended to be administered to study subjects according to the study protocol. The nature of the investigation in this example study was the use of blinatumomab in a completely outpatient setting. Both blinatumomab and the Health Management System (HMS) 270a were approved for use and were on-label use. The modular Investigational Medicinal Product Instructions (IPIM), a document external to this protocol, contains detailed information regarding the storage, preparation, disposal, and administration of each treatment, as shown in Table 3.

[0133] [Table 4]

[0134] A therapeutic intervention is any measurable action taken by or on a subject as a result of the onset of a stated clinical parameter. Such actions may include interventions such as advice from an HCP to immediately call emergency medical services i.e. 911, discontinuation of the blinatumomab infusion, oral medication intake by the subject, receipt of any emergency or hospital medical services medication or intervention by the subject, administration of any medication (IV, PO, or PR) or IV fluids or oxygen, etc. Time to therapeutic intervention (TTI) is the measured time from unscheduled contact by the subject / CG with the HCP to issue a device alert or report a change to the start of the defined therapeutic intervention.

[0135] [Table 5]

[0136] The medical devices provided by Amgen for use in this study include an infusion pump and infusion lines (e.g., infusion 110 in FIG. 1) and a Health Management System (HMS) 270a. These devices are non-Amgen investigational devices. A detailed description of the devices is provided herein. Blinatumomab was administered in an outpatient setting using an infusion pump approved for use by the appropriate regulatory agency in the United States. Blinatumomab solution for infusion was prepared in an intravenous (IV) bag for IV infusion 110 and delivered through an IP compatible infusion line as described in the IPIM. The final Blinatumomab solution for infusion should not come into contact with the pump at any time. Additional details on the use of the above medical devices are provided in the IPIM.

[0137] If not possible to provide on-site, the infusion pump 110, IV bags and tubing, and ancillary materials (e.g., syringes, sterile needles, alcohol pads, etc.) were provided, at least in part, by Amgen. Additional non-investigational medical devices that are commercially available were not provided or reimbursed by Amgen. The principal investigator overseeing the execution of the study cases at each site was responsible for obtaining these supplies. If on-site supplies were used, the principal investigator was responsible for obtaining and maintaining these supplies.

[0138] The central element of the Health Management System (HMS) 270a was a patient wearable device 115, 215a, 315a-c (i.e., accessible from Current Health, Biobeat, etc.). In each case, the patient wearable device 115, 215a, 315a-c was worn on the upper arm. The wearable device 115 monitored the subject's HR, RR, skin temperature, oxygen saturation, step count, and activity level at a maximum rate of every 2 seconds. In this test example, the following vital signs were collected and evaluated: HR, RR, axillary temperature, and oxygen saturation.

[0139] The patient wearable device 115 is integrated with an axillary temperature sensor (e.g., axillary temperature sensor 241m in FIG. 2M, 441a in FIG. 4A, etc.) via Bluetooth to measure axillary temperature as well. In addition, the patient device (e.g., tablet device 150 in FIG. 1, 250m in FIG. 2M, etc.) allows the capture of systolic and diastolic BP via Bluetooth integration with an approved and integrated BP monitor (e.g., blood pressure monitor 140 in FIG. 1, 240m in FIG. 2M, 441d in FIG. 4D, etc.) that the subject applies to his / her other arm / wrist to capture BP. The patient wearable device 215m transmits encrypted data via WiFi, for example, according to the health monitoring system 200m, 200n in FIG. 2M and FIG. 2N.

[0140] Blinatumomab was administered at the site according to FDA-approved guidelines. Toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1 and grade 2 events will be managed supportively with temporary interruption of blinatumomab (if deemed necessary by the investigator). Investigators will intervene according to the alert algorithm for other AEs.

[0141] [Table 6]

[0142] [Table 7]

[0143] Compliance with the use of the devices 110, 115, 140, 150, 200a, 200m, 200n was determined from the data transmitted by the devices. If data was not being transmitted from the devices (i.e., patient wearable device 115, axillary temperature monitor 241m, and blood pressure monitor 240m), a device alert was confirmed. If an alert was received that data was not being transmitted from the devices 115, 240m, 241m, the subject was instructed to call the HCP. If data was not being received, the HCP or designee was advised to contact the subject immediately. Assessment of compliance with the blinatumomab therapy per protocol and IPIM was performed by the study center and clinical research associate. If the subject did not follow the device use instructions, the subject was re-educated / retrained on the use of the device. If the subject failed to comply a second time, the subject was removed from the study and recommended to be hospitalized to complete the remainder of the MDMP as per the product FDA label.

[0144] Digital health device monitoring of the patient's vital signs during the mandatory monitoring period was performed. During the MDMP, subjects wore the patient wearable device 115 at all times, 24 hours per day. After the first 24 hours, subjects were allowed to remove one or more of the devices for up to one hour per day. This allowed the subject to perform personal activities such as bathing or showering. The subject had normal vitals, no evidence of NT, and was clinically stable prior to the start of the 60-minute period. During this period, no data was transmitted, so the break was coordinated with the HCP. It was recommended that the subject use this time to change one or more devices and place them on a charger (e.g., charger 442a in FIG. 4A). It was also strongly recommended that subjects change (to recharge) their CH wearable devices at approximately the same time each day.

[0145] Vital signs (HR, RR, oxygen saturation, and axillary temperature) were measured at all times using the Health Management System (HMS) 270a as specified in the activity schedule. Data was not transmitted to the HCP while the subject was transferred from the outpatient facility to home. Vital signs data (i.e., sensor data) was stored but not transmitted in real time. Non-invasive BP was performed as specified in the activity schedule. Vital signs were provided as a live feed at all times to the HCP or designee throughout the MDMP. If vital signs were outside of pre-set parameters, an alarm / alert was generated to indicate when vital signs were outside of pre-set parameters. Details of the data monitored using the devices 115, 140 are detailed herein.

[0146] The digital health tool used in this study collected data beyond that specified for analysis in this protocol. The digital health tool was capable of collecting HR, RR, axillary temperature, skin temperature, oxygen saturation, step count and activity level, and non-invasive BP. The patient device 150 also supported the collection of subject responses according to the QLQ-C30.

[0147] The above description describes various devices, assemblies, elements, subsystems, and methods of use related to drug delivery devices such as prefilled syringes. The devices, assemblies, elements, subsystems, methods, or drug delivery devices (i.e., prefilled syringes) may also include or be used in conjunction with drugs, including but not limited to the drugs identified below, as well as their generic and biosimilar counterparts. The term drug as used herein may be used interchangeably with other similar terms and may be used to refer to any type of pharmaceutical or therapeutic material, including conventional and non-conventional pharmaceuticals, nutraceuticals, supplements, biologics, bioactive substances and compositions, macromolecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectables are also of interest. Drugs may be in liquid, lyophilized, or reconstituted from lyophilized form. The following list of example drugs should not be considered exhaustive or limiting.

[0148] The drug will be contained in a reservoir, for example, in a pre-filled syringe. In some examples, the reservoir is a primary container that is filled or pre-filled for treatment with the drug. The primary container may be a vial, a cartridge, or a pre-filled syringe. In some embodiments, the reservoir of the drug delivery device is filled with or the device can be used with a colony stimulating factor, such as granulocyte colony stimulating factor (G-CSF). Such G-CSF formulations include, but are not limited to, Neulasta® (pegfilgrastim, pegfilgrastim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), UDENYCA® (pegfilgrastim-cbqv), Ziextenzo® (LA-EP2006; pegfilgrastim-bmez), or FULPHILA (pegfilgrastim-bmez).

[0149] In other embodiments, the drug delivery device may contain or be used with an erythropoietin stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoiesis. In some embodiments, the ESA is an erythropoietin stimulating protein. As used herein, "erythropoietin stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor (e.g., by binding to the receptor and causing receptor dimerization). Erythropoietin stimulating proteins include erythropoietin and its variants, analogs, or derivatives that bind to and activate the erythropoietin receptor; antibodies that bind to and activate the erythropoietin receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoietin stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), Epoetin alpha, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, PEGylated erythropoietin, carbamylated erythropoietin, and molecules or variants or analogs thereof.

[0150] Particularly exemplary proteins include the specific proteins listed below, including fusions, fragments, analogs, variants or derivatives thereof: OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies, related proteins, etc., including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies; myostatin-binding proteins, peptibodies, related proteins, etc., including myostatin-specific peptibodies; IL-4 receptor-specific antibodies, peptibodies, related proteins, etc., which particularly inhibit activities mediated by binding of IL-4 and / or IL-13 to its receptor; Interleukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies, related proteins, etc.; Ang2 specific antibodies, peptibodies, related proteins, etc.; NGF specific antibodies, peptibodies, related proteins, etc.; CD22 specific antibodies, peptibodies, related proteins, etc., in particular a dimer of human-mouse monoclonal hLL2 gamma chain disulfide bound to human-mouse monoclonal hLL2 kappa chain, e.g., epratuzumab (CAS Registry Number 501423-23-0). human CD22-specific antibodies, including but not limited to, humanized and fully human monoclonal antibodies, including but not limited to, human CD22-specific IgG antibodies, particularly including but not limited to, human CD22-specific fully humanized antibodies of HuMax; IGF-1 receptor-specific antibodies, peptibodies and related proteins, including but not limited to, anti-IGF-1R antibodies; B-7-related protein 1-specific antibodies, peptibodies, related proteins, including but not limited to, those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells, including but not limited to, a B7RP-specific fully human monoclonal IgG2 antibody, including but not limited to, a fully human IgG2 monoclonal antibody that binds to an epitope in the first immunoglobulin-like domain of B7RP-1; IL-15 specific antibodies, such as humanized monoclonal antibodies, peptibodies, related proteins, and the like, including, but not limited to, IL-15 antibodies and related proteins;IFN gamma specific antibodies, including, but not limited to, human IFN gamma specific antibodies, including, but not limited to, fully human anti-IFN gamma antibodies; TALL-1 specific antibodies, peptibodies, related proteins, and the like, as well as other TALL specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, and the like; thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, and the like; fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter factor (HGF / SF) hepatocyte growth factor ("HGF") specific antibodies, peptibodies, related proteins, etc., including those that target the HGF / SF:c-Met axis (HGF / SF:c-Met), such as monoclonal antibodies; TRAIL-R2 specific antibodies, peptibodies, related proteins, etc.; activin A specific antibodies, peptibodies, proteins, etc.; TGF-beta specific antibodies, peptibodies, related proteins, etc.; amyloid-beta protein specific antibodies, peptibodies, related proteins, etc.; proteins that bind to c-Kit and / or other stem cell factor receptors, including, but not limited to, including, but not limited to, c-Kit specific antibodies, peptibodies, related proteins, etc.; OX40L specific antibodies, peptibodies, related proteins, etc., including, but not limited to, proteins that bind OX40L and / or other ligands of the OX40 receptor; Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa), erythropoietin [30-asparagine, 32-threonine, 87-valine, 88-asparagine, 90-threonine], darbepoetin alfa, stimulating de novo erythropoiesis Protein (NESP); Epogen® (epoetin alfa or erythropoietin); GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, an anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, an anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb);MLN1202 (anti-CCR2 chemokine receptor mAb); Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker); Eprex® (epoetin alfa); Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb); Kanjinti™ (trastuzumab-anns) anti-HER2 monoclonal antibody, a biosimilar of Herceptin® or another product containing trastuzumab for the treatment of breast or gastric cancer; Humatrope® (somatropin, human growth hormone); Humira® (adalimumab ;Vectibix® (panitumumab), Xgeva® (denosumab), Prolia® (denosumab), immunoglobulin G2 human monoclonal antibody against RANK ligand, Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™ (eculizumab); pexelizumab (anti-complement C5); Numax® (MEDI-524);Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (vigilizumab); cantuzumab mertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega® (oprelvekin, human interleukin-11); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFα monoclonal antibody); Reopro® (abciximab, anti-GP lIb / Ilia receptor monoclonal antibody); Actemra® (anti-IL6 receptor mAb); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Mvasi™ (bevacizumab-awwb); Rituxan® (rituximab, anti-CD20 mAb);Tarceva® (erlotinib);Roferon-A®-(interferon alpha-2a);Simulect® (basiliximab);Prexige® (lumiracoxib);Synagis® (palivizumab);145c7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507);Tysabri® (natalizumab, anti-α4 integrin mAb);Valortim® (MDX-1303, anti-B. anthracis protective antigen mAb);ABthrax®;Xolair® (omalizumab);ETI211 (anti-MRSA mAb);IL-1 trap (Fc portion of human IgG1 and extracellular domain of both IL-1 receptor components (type I receptor and receptor accessory protein));VEGF trap (IgG1 Ig domain of VEGFR1 fused to Fc; Zenapax® (daclizumab);Zenapax® (daclizumab, anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFα mAb); HGS-ETR1 (mapatuzumab; human anti-TRAIL receptor-1 mAb); HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22 dsFv-PE38 conjugate (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019); anti-CTLA4 mAb; anti-eotaxin 1 mAb (CAT-213); anti-FGF8 mAb; anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; Anti-GDF-8 human mAb (MYO-029); Anti-GM-CSF receptor mAb (CAM-3001); Anti-HepC mAb (HuMax HepC); Anti-IFNα mAb (MEDI-545, MDX-198); Anti-IGF1R mAb; Anti-IGF-1R mAb (HuMax-Inflam); Anti-IL12 mAb(ABT-874); Anti-IL12 / IL23 mAb(CNTO 1275); Anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5 receptor mAb; anti-integrin receptor mAb (MDX-018, CNTO 95);Anti-IP10 ulcerative colitis mAb (MDX-1100); BMS-66513; anti-mannos receptor / hCGβ mAb (MDX-1307); anti-methelin dsFv-PE38 conjugate (CAT-5001); anti-PD1 mAb (MDX-1106(ONO-4538)); anti-PDGFRα antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL receptor-2 mAb (HGS-ETR2); anti-TWEA; K mAb; anti-VEGFR / Flt-1 mAb; and anti-ZP3 mAb (HuMax-ZP3).

[0151] In some embodiments, the drug delivery device may contain or be used in conjunction with sclerostin antibodies, such as, but not limited to, romosozumab, brosozumab, BPS 804 (Novartis), Evenity™ (romosozumab-aqqg), another product containing romosozumab for the treatment of postmenopausal osteoporosis and / or fracture healing, and in other embodiments, monoclonal antibodies (IgG) that bind to human proprotein convertase subtilisin / kexin type 9 (PCSK9). Such PCSK9-specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may contain or be used in conjunction with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib niphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with, or the device may be used in conjunction with, IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV, including but not limited to OncoVEXGALV / CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; and NV1042 for the treatment of melanoma or other cancers. In some embodiments, the drug delivery device may include, or be used in conjunction with, an endogenous tissue inhibitor of metalloproteinases (TIMP), such as but not limited to TIMP-3. In some embodiments, the drug delivery device may include, or be used in conjunction with, Aimovig® (erenumab-aooe), anti-human CGRP-R (calcitonin gene-related peptide type 1 receptor), or another product containing erenumab for the treatment of migraine. Antagonistic antibodies to the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab, and bispecific antibody molecules targeting the CGRP receptor and other headache targets, may also be delivered using the drug delivery devices of the present disclosure.

[0152] Additionally, the disclosed sensors, devices, systems, and methods may be particularly advantageous for outpatient procedures that may be associated with certain adverse side reactions caused by similar molecules with specific mechanisms of action (MOAs). For example, bispecific T cell engager (BiTE®) molecules, such as, but not limited to, BLINCYTO® (blinatumomab), may be used in or with the disclosed drug delivery devices. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 160 or a half-life extended (HLE) anti-prostate specific membrane antigen (PSMA) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 199 or another product containing a half-life extended (HLE) bispecific T cell engager construct (BiTE®). In some embodiments, the drug delivery device may contain or be used with AMG 330 or another product containing an anti-CD33 x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 427 or another product containing a half-life extended (HLE) anti-fms-like tyrosine kinase 3 (FLT3) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 509 or another product containing a bivalent T cell engager and designed using XmAb® 2+1 technology. In some embodiments, the drug delivery device may contain or be used with AMG 562 or another product containing a half-life extended (HLE) CD19 x CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 596 or another product containing CD3 x epidermal growth factor receptor vIII (EGFRvIII) BiTE® (bispecific T cell engager) molecules.In some embodiments, the drug delivery device may contain or be used with AMG 673 or another product containing a half-life extended (HLE) anti-CD33 x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 701 or another product containing a half-life extended (HLE) anti-B cell maturation antigen (BCMA) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 757 or another product containing a half-life extended (HLE) anti-delta-like ligand 3 (DLL3) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 910 or another product containing the half-life extended (HLE) epithelial cell tight junction component protein claudin 18.2 x CD3 BiTE® (bispecific T cell engager) construct.

[0153] In some embodiments, the drug delivery device may contain or be used in conjunction with an APJ large molecule agonist, such as, but not limited to, apelin or an analog thereof. In some embodiments, a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody is used in or with the drug delivery device of the present disclosure. In some embodiments, the drug delivery device may contain or be used in conjunction with Avsola™ (infliximab-axxq), an anti-TNF alpha monoclonal antibody, a biosimilar of Remicade® (infliximab) (Janssen Biotech, Inc.), or another product containing infliximab for the treatment of autoimmune diseases. In some embodiments, the drug delivery device may contain or be used in conjunction with Kyprolis® (carfilzomib), (2S)-N-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide, or another product containing carfilzomib for the treatment of multiple myeloma. In some embodiments, the drug delivery device may contain or be used in conjunction with Otezla® (apremilast), N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide, or another product containing apremilast for the treatment of various inflammatory diseases. In some embodiments, the drug delivery device may contain or be used in conjunction with Parsabiv™ (etelcalcetide HCl, KAI-4169) or another product containing etelcalcetide HCl for the treatment of secondary hyperparathyroidism (sHPT), such as in patients with chronic kidney disease (KD) on hemodialysis.In some embodiments, the drug delivery device may contain or be used with ABP 798 (rituximab), a biosimilar candidate for Rituxan® / MabThera™, or another product containing an anti-CD20 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used with a VEGF antagonist, such as a non-antibody VEGF antagonist, and / or a VEGF trap, such as aflibercept (Ig domain 2 from VEGFR1 and Ig domain 3 from VEGFR2 fused to the Fc domain of IgG1). In some embodiments, the drug delivery device may contain or be used with ABP 959 (eculizumab), a biosimilar candidate for Soliris®, or another product containing a monoclonal antibody that specifically binds to complement protein C5. In some embodiments, the drug delivery device may contain or be used in conjunction with rogivafusp alfa (formerly AMG 570), a novel bispecific antibody-peptide conjugate that simultaneously blocks ICOSL and BAFF activity. In some embodiments, the drug delivery device may contain or be used in conjunction with omecamtib mecarbil, a small molecule selective cardiac myosin activator or myotrope that directly targets the contractile machinery of the heart, or another product containing a small molecule selective cardiac myosin activator. In some embodiments, the drug delivery device may contain sotorasib (formerly known as AMG 510), a KRAS. G12C Small molecule inhibitors or KRAS G12CIt may contain or be used with another product containing a small molecule inhibitor. In some embodiments, the drug delivery device may contain or be used with another product containing tezepelumab, a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), or a human monoclonal antibody that inhibits the action of TSLP. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 714, a human monoclonal antibody that binds to interleukin-15 (IL-15), or a human monoclonal antibody that binds to interleukin-15 (IL-15). In some embodiments, the drug delivery device may contain or be used with another product containing AMG 890, a small interfering RNA (siRNA) that reduces lipoprotein (a), also known as Lp(a), or a small interfering RNA (siRNA) that reduces lipoprotein (a). In some embodiments, the drug delivery device may contain or be used with ABP 654 (human IgG1 kappa antibody), a biosimilar candidate of Stelara®, or another product that contains a human IgG1 kappa antibody and / or binds to the p40 subunit of the human cytokines interleukin (IL)-12 and IL-23. In some embodiments, the drug delivery device may contain or be used with Amjevita™ or Amgevita™ (formerly ABP 501) (mab anti-TNF human IgG1), a biosimilar candidate of Humira®, or another product that contains a human mab anti-TNF human IgG1. In some embodiments, the drug delivery device may contain or be used with AMG 119 or another product that contains delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy. In some embodiments, the drug delivery device may contain or be used in conjunction with another product containing AMG 119 or a delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy.In some embodiments, the drug delivery device may contain or be used with AMG 133, or another product containing a gastric inhibitory polypeptide receptor (GIPR) antagonist and a GLP-1R agonist. In some embodiments, the drug delivery device may contain or be used with AMG 171, or another product containing a growth differentiation factor 15 (GDF15) analog. In some embodiments, the drug delivery device may contain or be used with AMG 176, or another product containing a small molecule inhibitor of myeloid cell leukemia 1 (MCL-1). In some embodiments, the drug delivery device may contain or be used with AMG 256, or another product containing an anti-PD-1 x IL21 mutein and / or an IL-21 receptor agonist designed to selectively activate the interleukin 21 (IL-21) pathway in programmed cell death-1 (PD-1) positive cells. In some embodiments, the drug delivery device may contain or be used with AMG 404 or another product containing a human anti-programmed cell death-1 (PD-1) monoclonal antibody being investigated as a treatment for patients with solid tumors. In some embodiments, the drug delivery device may contain or be used with AMG 430 or another product containing an anti-Jagged-1 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used with AMG 506 or another product containing a multispecific FAPx4-1BB targeted DARPin® biologic being investigated as a treatment for solid tumors. In some embodiments, the drug delivery device may contain or be used with efavalukin alfa (formerly AMG 592) or another product containing an IL-2 mutein Fc fusion protein.

[0154] The drug delivery devices, assemblies, elements, subsystems, and methods have been described in terms of exemplary embodiments, but are not limited thereto. The detailed description should be construed as exemplary only and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, which would still fall within the scope of the claims defining the invention disclosed herein.

[0155] It will be appreciated that those skilled in the art may make a wide range of modifications, variations, and combinations with respect to the above-described embodiments without departing from the concept and scope of the invention disclosed herein, and such modifications, variations, and combinations should be considered to be included within the scope of the inventive concept.

Claims

1. 1. A system for outpatient treatment, comprising: an infusion pump for delivering a therapeutic agent to a patient; a wearable device configured to be worn by the patient at least one of: (a) prior to delivery of the therapeutic agent; and (b) during delivery of the therapeutic agent, the wearable device comprising one or more sensors configured to acquire sensor data related to detection of a patient vital sign; a wireless communication module disposed on the wearable device and configured to remotely wirelessly communicate with a healthcare provider based on the acquired sensor data; A system comprising:

2. The system of claim 1 , wherein the infusion pump comprises a therapeutic agent.

3. The system of claim 1 or 2, wherein the therapeutic agent is known to trigger an immune inflammatory response in the patient, potentially leading to increased risk factors for (a) cytokine release syndrome (CRS) or (b) neurotoxicity (NT).

4. 3. The system of claim 1 or 2, wherein the therapeutic agent comprises at least one of: (a) an immunotherapy agent that activates the patient's T cells to fight cancer; (b) an immunotherapy agent comprising blinatumomab; and (c) an immunotherapy agent comprising acapatamab.

5. The system of claim 1 or 2, wherein the at least one sensor of the wearable device includes an optical sensor configured to measure oxygen of the patient.

6. 3. The system of claim 1 or 2, wherein the at least one sensor of the wearable device is configured to measure at least one indicator of cytokine release syndrome selected from: (a) heart rate (HR), (b) axillary temperature, (c) respiration rate (RR), (d) oxygen saturation, and (e) blood pressure (BP).

7. The system of claim 1 or 2, wherein the at least one sensor continuously measures at least one of: (a) heart rate; (b) body temperature; (c) respiration rate; and (d) oxygen saturation.

8. 3. The system of claim 1 or 2, wherein the wireless communication module of the wearable device is configured to at least one of: (a) send messages to the healthcare provider in real time; (b) send periodic messages to the healthcare provider based on a predetermined interval of seconds, minutes, or hours; (c) send periodic messages every 10 minutes; (d) send an alarm message when the patient's oxygen falls below a predetermined threshold; and (e) send an alarm if the communication is interrupted.

9. The system of claim 1 or 2, further comprising an axillary temperature sensor for detecting a body temperature of the patient during delivery of the treatment, the axillary temperature sensor being communicatively coupled to the wearable device.

10. The system of claim 9 , wherein the axillary temperature sensor includes a wireless communication module configured to communicate with the wireless communication module of the wearable device.

11. 3. The system of claim 1 or 2, further comprising a blood pressure cuff for detecting a blood pressure of the patient during delivery of the therapy, the blood pressure cuff being communicatively coupled to the wearable device.

12. The system of claim 1 or 2, wherein the healthcare provider comprises a mobile device configured to wirelessly communicate with the wireless communication module of the wearable device.

13. 13. The system of claim 12, further comprising a wireless device assigned to the patient that includes a mobile application configured to support audio and / or video communication with the mobile device of the healthcare provider.

14. 1. A computer-implemented method for treating an outpatient patient with immunotherapy to activate the patient's T cells to kill cancer, comprising: receiving, at a processor, sensor data in response to the processor executing a sensor data receiving module; generating, using a processor, alert data based on the sensor data in response to the processor executing an alert data generation module, the content of the sensor data being based on a likelihood that the immunotherapy will trigger an increase in a risk factor for cytokine release syndrome; 23. A computer-implemented method comprising:

15. 15. The computer-implemented method of claim 14, further comprising: using a processor to transmit the sensor data to at least one of: (a) a healthcare provider device in response to the processor executing a sensor data transmission module; and (b) a patient device, wherein the sensor data represents vital signs of the patient.

16. 16. The computer-implemented method of claim 14 or 15, further comprising: using a processor to transmit the alert data to a healthcare provider device: (a) in response to the processor executing an alert data transmission module; or (b) in response to the processor executing an alert data transmission module when the sensor data exceeds a threshold.

17. 16. The computer-implemented method of claim 14 or 15, further comprising using a processor to transmit audio / video data between the patient device and the healthcare provider smartphone over a cellular connection in response to the processor executing an audio / video data transmission module.

18. 16. The computer-implemented method of claim 14 or 15, further comprising using a processor to transmit patient-initiated call input data to at least one of a healthcare provider or a health care system in response to the processor executing the patient-initiated call input receiving module.

19. 20. The computer-implemented method of claim 18, wherein the healthcare provider's phone is configured to sound a loud audible alarm at regular intervals based on the alert data until the healthcare provider responds.

20. 16. The computer-implemented method of claim 14 or 15, wherein the sensor data represents at least one indicator of cytokine release syndrome selected from heart rate (HR), axillary temperature, respiration rate (RR), oxygen saturation, and blood pressure (BP).

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