The LiveWell intervention aims to decrease episode relapse, reduce symptom burden, and improve quality of life by assisting individuals with managing target behaviors proposed to underlie the impact of existing therapies [57-60]. LiveWell therefore engages users to support managing the signs and symptoms of relapse, taking psychiatric medications as prescribed, obtaining adequate sleep duration, and maintaining regular routines. LiveWell also addresses strengthening social support, managing stressors, and engaging in healthy habits regarding diet, exercise, and substance use.

The intervention consists of technological and human support components including a smartphone app, a secure server and website, and a coach [57-60]. The smartphone app consists of the following 5 primary components: foundations, toolbox, wellness plan, daily check-in, and daily review [57-60]. The app provides information on bipolar disorder self-management (foundations) along with self-assessment surveys and skills content (toolbox). The foundations and toolbox components support developing a personalized wellness plan for managing signs and symptoms and maintaining a healthy lifestyle. The core of the intervention is a daily check-in, where users monitor medication adherence, sleep duration, routine, and wellness levels. Based on their daily check-in data, daily review provides adaptive content and directs users to relevant app content in the foundations, toolbox, and wellness plan. A coach provides human support to facilitate app use adherence, self-management strategy use, and communication with mental health providers [58]. The secure server and website provide data summaries and alerts to providers and coaches to facilitate and support clinical care communication (Multimedia Appendix 4).

The LiveWell intervention thus has both fixed and adaptive components. In terms of fixed components, users are asked to attend an initial face-to-face meeting with a coach, complete 6 scheduled coaching calls (weeks 1-4, 6, and 16), read 2 foundations lessons per week (weeks 1-4), and use the daily check-in each day (weeks 1-16). At an initial face-to-face meeting, a coach helps users identify personalized wellness anchors to assist them in using the daily check-in’s wellness rating scale [58,59]. During the scheduled coach calls, users review progress toward their goals and receive guidance on app use (weeks 1-4), develop (week 4) and review (week 6) their personalized wellness plan, and then review their progress and commitment to ongoing use of helpful strategies (week 16). The week 16 scheduled call ends the active phase of the intervention, but users continue to have access to the app and ad hoc coaching support for 48 weeks. While the target behavioral goals and wellness plans are personalized, this personalization is determined by the user in conjunction with the coach without following a predefined algorithm and is thus operator driven and not algorithmically driven [57-60].

The adaptive components of the intervention consist of a rule-based expert system primarily embedded in the daily check-in and daily review components of the intervention. The daily check-in provides the primary user interface for populating the database containing facts about the user’s current status, but data are also collected via a weekly check-in consisting of the Patient Health Questionnaire-8 (PHQ8) and Altman Self-Rating Mania (ASRM) scales [61,62]. The knowledge base for the expert system contains the adaptive smartphone app content. It utilizes a clinical status state machine and hierarchical decision tables (if-then/elseif-then) to govern content delivery via the daily review. The daily review comprises the explanatory system and also serves as the user interface providing adaptive content delivery. The inference engine combines the current data from the user database with the knowledge base to determine the adaptive content to deliver in the moment. In addition to varying the content provided via the daily review, the expert system also controls the delivery of smartphone app pop-up messages requesting users to reach out to their clinical care providers by phone. Additionally, the expert system controls the delivery of emails to providers and coaches to stimulate clinical care communication via phone calls, and flags data in daily reports generated for coaches to promote coach clinical reach out and app use adherence phone calls [57-59].

Decision points are the times when the frequency, mode, or content of the intervention (ie, intervention options) is adapted [49,51,52]. For LiveWell, the decision points occur daily upon user completion of the daily check-in, as well as weekly upon completion of the weekly check-in. During a pilot study of the intervention, users were initially given the option to complete the daily check-in multiple times a day. However, allowing multiple check-ins each day did not appear to elicit user reflection about their wellness status. Instead, multiple check-ins a day seemed to be capturing momentary reactions to daily hassles and uplifts [63]. To encourage users to engage in reflective monitoring rather than in the moment rating, the daily check-in was restricted to allow only 1 check-in per day [59]. The app prompts users to check-in each day by delivering an alert in the smartphone’s notification panel. Users can select the time they first receive a daily notification in the app settings. They receive their first notification to check-in at their designated time of the day and then every 2 hours until they check-in or until they receive 3 alerts. The daily review is only accessible each day after completion of the daily check-in. As a result, no adaptive content is delivered via the daily review on days when users do not complete the daily check-in. Similarly, no adaptive content is delivered if users do not complete the weekly check-in.

Tailoring variables are the values containing information about the user, such as clinical status or health behaviors, which are used to determine the delivery of intervention options [49,51,52]. For LiveWell, the primary tailoring variables are the target behaviors and wellness levels monitored by the daily check-in and include users self-reported psychiatric medication adherence (all, some, and none), sleep duration (hours), routine (bedtime/risetime), and wellness rating (0 balanced, −1/+1 daily hassles/uplifts, −2/+2 prodromal/residual symptoms, −3/+3 episode, and −4/+4 crisis). These variables were selected for daily monitoring because they are consistently addressed in the core content of adjunctive psychotherapy interventions [3,16,24,31,64-66] and are readily amenable to goal setting and self-monitoring. LiveWell also contains content addressing building and using supports, managing stressors, and maintaining healthy habits regarding diet, exercise, and substance use [57-60]. However, to simplify the daily check-in and make it quick and easy to complete, these additional targets were not included for daily monitoring and use in adapting delivery of intervention options. Because of the importance of clinical status in bipolar disorder, 2 additional tailoring variables were also utilized based on data obtained from the weekly check-in (PHQ8 and ASRM scores). In addition, adherence to completing the daily and weekly check-ins was also used as a tailoring variable.

Decision rules link delivery of intervention options and tailoring variables systematically. They include the values of tailoring variables (states, thresholds, and ranges) that determine which intervention option to deliver when and for whom [49,51,52]. LiveWell utilizes algorithm-driven adaptation based on fixed rules to standardize intervention option delivery [52]. In developing the decision rules for LiveWell, it was necessary to consider how variation in medication adherence, sleep duration, routine, and wellness ratings should result in the adaptation of intervention options. In addition, it was also necessary to consider how to rank the importance of variation in each variable. Because pharmacotherapy is the primary treatment for bipolar disorder [3-7], medication adherence was ranked above sleep duration in prioritizing feedback. Sleep duration was then ranked above routine because sleep duration variation is frequently identified as an early warning sign of impending episode relapse, and assisting people with identifying and making plans for managing early warning signs of relapse is an important target of most adjunctive bipolar disorder psychotherapies [67-69]. In fact, many face-to-face bipolar disorder psychotherapy studies have restricted participation to individuals in asymptomatic recovery, and the primary goal of these interventions has been relapse prevention [8-13,16]. However, an important goal of LiveWell is to increase access to self-management techniques derived from empirically supported therapies, so individuals were enrolled in the intervention as long as they were not in a current episode [57].

Because individuals with varying clinical statuses were included initially and people may enter an episode while engaged with LiveWell, clinical status was ranked as the highest priority tailoring variable. This allows the need for substantial adaptation of the treatment approach for individuals with bipolar disorder in various clinical states to be appropriately addressed. As a starting point for developing decision rules to manage clinical status variation, existing criteria for bipolar disorder episodes (mania, hypomania, depression, and mixed) and for nonepisode clinical statuses (asymptomatic and symptomatic recovery, prodromal, continued symptomatic, and recovering) were examined (Table 1 and Table 2). The Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM4) criteria were used because prior face-to-face psychotherapy trials for bipolar disorder primarily used DSM4 episode criteria [8-16]. They were used for LiveWell’s outcome assessments [57]. Criteria for nonepisode clinical statuses were derived from the clinical monitoring form (CMF) used in a large bipolar disorder intervention study (STEP-BD) where nonepisode clinical statuses were clearly defined [70,71]. These combined criteria were used to define a clinical status state machine where transitions between the 9 possible clinical statuses for bipolar disorder are defined by 10 decision rules derived from DSM4 and the CMF (Figure 1).

The DSM4/CMF state machine highlights the relatively narrow focus of most adjunctive psychotherapies for bipolar disorder (Figure 1). These therapies primarily assist people with remaining in asymptomatic recovery by maintaining medication adherence, adequate sleep duration, and a regular routine, as well as attending to healthy habits and stressors [3,8-13,16,24,31,64,65]. In addition, these therapies assist individuals with recognizing and managing early warning signs and symptoms to avoid transitioning from asymptomatic recovery to a prodromal state and to support transitioning from a prodromal state to asymptomatic recovery rather than entering an episode (Figure 1). This state machine also highlights how entry into an episode can lead to prolonged periods of problems with symptoms; individuals can cycle between episode types, and into and out of continued symptomatic and recovering states during which they are at increased risk for episode relapse [7,72-74]. While this state machine clearly delineates different clinical states and transitions, assessment is complex because of the need to determine the number of symptoms as well as their type and intensity over widely varying durations (4-56 days), and the additional need to assess impairment level and the presence of psychotic symptoms or hospitalization. The DSM4/CMF data necessary to determine the clinical status states for the DSM4/CMF state machine are obtained every 8 weeks during the intervention via telephone assessments delivered by trained assessors blinded to the study arm [57]. However, because the severity of each symptom and the level of impairment due to both symptoms of mania and depression must be assessed, it was decided that this level of assessment via the app would unduly burden the user.

Thus, the clinical status state machine for the LiveWell expert system was simplified owing to the complexity of the data required for the DSM4/CMF state machine and the corresponding user assessment burden (Table 3 and Figure 2). Instead of having users rate individual symptom severity, the daily check-in uses a personalized 9-point wellness rating scale to allow users to rapidly assess their symptom burden using the daily check-in [58,59]. The clinical status assessment window was also limited to users’ last 7 daily check-ins to reflect user self-report data covering approximately the prior week depending on daily check-in adherence (Table 3). Consistent with the focus of LiveWell on episode relapse prevention, this time window aims to allow relatively rapid adjustment of intervention option delivery with clinical status variation. In addition to limiting the time window, the LiveWell state machine was also simplified by considering only the following 4 clinical states: well, prodromal, unwell, and recovering (Table 3 and Figure 2). Reducing the number of clinical states allows the daily check-in wellness ratings to be readily used to identify clinical status state transitions using the same time window for symptoms of depression and mania, thereby reducing the number of decision rules needed and providing more rapid feedback to users when they identify changes in their wellness ratings. In addition, the focus of the LiveWell intervention is on mood episode relapse prevention. The intervention thus aims to assist individuals who have recovered from a mood episode on transitioning from well to prodromal and from prodromal to unwell. If an individual enters a mood episode, the intervention aims to support the individual in working with their providers for treatment. For individuals in the recovering state, the LiveWell intervention adapts techniques developed primarily for mood episode relapse prevention [3,8-13,16,24,31,64,65], with the aim of assisting individuals in transitioning from recovering to well and avoiding transitioning from recovering to unwell. The use of only 4 clinical states for the LiveWell state machine is thus consistent with the focus of the intervention and existing studies from which the intervention content is derived.

To aid in defining the thresholds for varying clinical states and to address thresholds for medication adherence and sleep duration, an online electronic survey was sent to practicing psychiatrists to obtain their input on when intervention options should be varied (Multimedia Appendix 1). This questionnaire emphasized identifying the number of days after which psychiatrists felt individuals with bipolar disorder should shift from relying mostly on individual self-management skills and instead engage in self-management via communication and recruiting support from mental health providers. The survey thus asked when the app should deliver a prompt to users requesting that they call their psychiatrist and when the app, via the server, should send an email alert directly notifying the psychiatrist of potential issues (Multimedia Appendix 1). Most psychiatrists indicated that the app should instruct users to call them after 2 to 3 days of experiencing multiple symptoms of mania and after 3 to 4 days of experiencing multiple symptoms of depression or 1 to 2 early warning signs of mania or depression (Multimedia Appendix 2 and Multimedia Appendix 5). In terms of medication adherence, most psychiatrists indicated that the app should instruct users to call them if they reported only taking their psychiatric medications for 3 out of 7 days (43% adherence). For sleep duration, most psychiatrists indicated that the app should instruct users to call them if they reported sleeping less than 4 hours a day for 2 to 3 days and if sleeping less than usual by 3 to 4 hours or more than usual by 4 hours over 7 days. The results were less clear with regard to when psychiatrists would want to receive an email alert (Multimedia Appendix 5), which may be related to most psychiatrists (80%) preferring that their patients contact them via phone rather than via email (Multimedia Appendix 2).

After each completion of the daily check-in, the LiveWell inference engine assesses the user’s current clinical status and last 7 daily check-in wellness ratings and applies the knowledge base rules to update the user’s clinical status (Table 3 and Figure 2). The user’s initial clinical status is set by the coach using baseline study assessment data and is then updated after each check in. For example, if a user’s clinical status is well and the absolute value of their wellness ratings are 2 or greater for 4 or more of the last 7 check-ins, the user’s clinical status is updated to prodromal (decision number 1 in Table 3, Figure 2). The coach assists users in understanding and identifying personalized anchors indicating that a wellness rating of +2 or −2 corresponds to the presence of early warning signs or symptoms when doing well or some residual symptoms when improving from being in an episode [58]. The threshold of 4 check-ins corresponds to the DSM4 criteria for hypomania (Table 1) and to psychiatrist feedback from the survey indicating psychiatrists would like their patients to contact them when experiencing manic or depressive symptoms or early warning signs (Multimedia Appendix 5). For the transition from prodromal or recovering to unwell, a count of 5 or more for the last 7 check-ins with an absolute wellness rating value of 3 or greater was used (decision number 3 in Table 3, Figure 2). A wellness rating of 3 is defined for users as corresponding to multiple symptoms day to day, with some impairment likely indicating a mood episode. The threshold of 5 counts out of 7 corresponds to the CMF threshold for a depressive episode using DSM4 criteria (Table 1), which captures the DSM4/CMF criteria of depressive symptoms being present most days for 2 weeks (ie, 10/14 days). However, for the LiveWell clinical status state machine, the count has been reduced by half to reflect the approximately 1 week window of the state machine (ie, 5/7 days).

After the state machine determines clinical status, a hierarchical decision table is used to decide which of the 26 content categories should be delivered by the daily review (Figure 3, Multimedia Appendix 3, and Multimedia Appendix 6) [57]. Because clinical status and wellness ratings are prioritized, the daily review decision table starts by examining these variables and proceeds using an if-then/elseif-then decision tree. Thus, if a user enters a wellness rating of +4 or −4, the crisis content categories severe up or down are selected. After these 2 categories, the next 15 content categories are selected by examining the clinical status and the current wellness rating (Multimedia Appendix 3 and Multimedia Appendix 6). These content categories address continuing or improving in the clinical states unwell, prodromal, and recovering, as well as worsening symptoms (wellness ratings +3 or −3) while not in the unwell state (well, prodromal, and recovering), and the presence of early warning signs (wellness ratings +2 or −2) while in the well state (Figure 3). The decision rules for the remaining 9 categories examine user self-report data regarding medication adherence, sleep duration, and routine using data from the 4 last check-ins (Figure 3). This approximately 4-day window for deciding when to deliver content addressing these targets was selected based on the psychiatrist survey feedback (Multimedia Appendix 5).

In addition to varying the content of the daily review, the LiveWell expert system also utilizes separate decision tables to prompt users to communicate with their psychiatrists by phone and to deliver emails to activate coaches and enrolled mental health providers to reach out to users via phone (Multimedia Appendix 3 and Multimedia Appendix 7). For daily check-in data, a hierarchical decision table organizes selection of clinical reach out messages based on the presence of crisis wellness ratings (+4 or −4), transition to unwell or prodromal states, worsening symptoms when not unwell, or more severe problems with medication adherence and sleep duration (Multimedia Appendix 7). The daily check-in clinical reach out decision table thresholds are primarily derived from the psychiatrist survey feedback. A separate set of decision rules trigger clinical reach outs after the weekly check-in if the user’s score indicates new onset of a manic or depressive episode (Multimedia Appendix 7). The thresholds for the weekly check-in are set based on the published thresholds indicating the possible presence of manic or depressive episodes for the ASRM and PHQ8 scales [61,62]. The psychiatrist survey feedback indicated that most psychiatrists felt a higher threshold might be used (Multimedia Appendix 2), but the published thresholds were selected based on the request of the Northwestern University Institutional Review Board. In a report generated for coaches each day (Multimedia Appendix 8), an additional set of decision rules also flags data indicating problems with daily or weekly check-in adherence (Multimedia Appendix 7).

Intervention options include variation in intervention frequency, mode, or content implemented at the decision points following the decision rules [49,51,52]. For LiveWell, the daily review provides the primary user interface and explanatory system delivering adaptive content to the user. The daily review utilizes a fixed format of 3 to 6 app display pages to adaptively present content for the 26 categories determined by the daily review decision rules (Multimedia Appendix 3 and Multimedia Appendix 6) [57]. The first page of the daily review provides brief feedback about the content category being addressed and the user data indicating why that content category is deemed relevant (Figure 4). In addition, the first page of the daily review provides visual feedback regarding target goal achievement using bar graphs to display the percent of days over the last 7 days that the user met the goal for each target. The daily review then delivers additional pages of content addressing the selected category with 1 to 4 pages presented depending on the category (Multimedia Appendix 3). The final page of the daily review then reiterates the content category being addressed and provides suggestions and links to other sections of the app for review of the selected content category (Figure 4).

To reduce the potential for user fatigue when viewing the same content category multiple times, the first and last pages of the daily review randomly present one of a number of pages providing similar content stated in varying ways (Figures 4 and 5). In addition, for pages 2 to 5 of the daily review, a given page number (eg, page 2) may have multiple permutations of similar content or multiple unique pages of content that are randomly selected for presentation each time a user views a content category [57]. In some cases, a unique page of content (page 2) is linked to a subsequent unique page of content (page 3) so that only the prior page is randomly selected, but in other cases, subsequent unique pages are randomly selected. Randomly combining permuted and unique pages of content addressing a selected category allows the daily review to vary provided content about a given category over multiple views.

The content of each page is typically varied by providing information or suggesting tools to address different motivational, volitional, environmental, or capability-based determinants relevant to the selected category (Figure 5). To provide additional personalization with the aim of maintaining user engagement, some of the daily review content categories also present pages where users can select choice options which then determine the content of the subsequent daily review page. For instance, if the low-risk category is selected by the inference engine, then page 2 of the daily review allows the user to learn more about enhancing self-awareness, building a healthy lifestyle, coping with symptoms, or forming an effective team to assist with staying well (Figure 5). If the user selects lifestyle on page 2, then page 3 allows the user to select 1 of 6 categories (sleep, medication, attend, routine, tranquil, and social) to learn more about supporting different aspects of a healthy lifestyle while living with bipolar disorder.

Although 26 content categories are adaptively delivered via the daily review, the content as a whole can be grouped into the following 3 tiers: (1) low, moderate, and high risk categories where the user’s clinical status is well and early warning signs or worsening symptoms are not endorsed; (2) categories where the user’s clinical status is well and early warning signs or worsening symptoms are endorsed or where the user’s clinical status is prodromal or recovering; and (3) categories where the user is in an episode or crisis (Figure 3). The first-tier categories contain most of the daily review content (71% of available pages), and their content addresses the targets sleep duration, medication adherence, managing signs and symptoms, building support, and keeping a regular routine (30%, 22%, 20%, 9%, and 8% of tier content, respectively) and the following determinants underlying engagement in these target behaviors: attitudes and perceptions, knowledge, support, evaluation, and planning (18%, 15%, 13%, 11%, and 10% of tier content, respectively). For the second-tier categories, the daily review content (22% of available pages) addresses the targets managing signs and symptoms and using supports (86% and 6% of tier content, respectively) and the following determinants: evaluation, skills, knowledge, adjustment, and practice (22%, 16%, 16%, 10%, and 7% of tier content, respectively). For the third-tier categories, the daily review content (7% of available pages) only addresses managing signs and symptoms (99% of tier content) and the following determinants: evaluation, skills, adjustment, knowledge, and support (22%, 18%, 16%, 15%, and 13% of tier content, respectively). Thus, as users move up the tiers to more acute content categories, the focus of the content shifts to managing signs and symptoms and utilizing supports (Multimedia Appendix 3). In fact, the crisis categories triggered by user entry of a wellness rating of +4 or −4 are the only categories that do not follow the general format of daily review content delivery. For these 2 categories, a single page of content without bar graphs is presented requesting that users take immediate action and contact their psychiatrists and supports, and if in danger of self-harm, call 911 or go to the nearest emergency room.

The expert system also prompts clinical care communication to reinforce the importance of engaging supports when having difficulties (Multimedia Appendix 3 and Multimedia Appendix 7). When these decision rules activate a clinical reach out, a pop-up is provided to the user asking the user to call their psychiatrist to address the selected category. To facilitate the user making this call, the pop-up includes a button linked to the psychiatrist’s phone number (Figure 6). In addition, an email is sent to the coach and enrolled providers alerting them to the situation (Multimedia Appendix 3). The coach acts on these alerts following structured protocols described in detail elsewhere [58]. Finally, when user adherence with completing daily and weekly check-ins falls below predetermined thresholds (Multimedia Appendix 7), coaches are also prompted via flagged data in the daily coaching reports (Multimedia Appendix 8). Coaches then follow-up with phone calls, texts, or emails to address adherence issues using a motivational interviewing approach [58]. Overall, the clinical reach out rules aim to shift the mode of intervention delivery from self-management using individual skills to engaging in self-management via effective communication and elicitation of support from mental health care providers and other supports.