Stress and anxiety in university students of the United Kingdom have been steadily rising in the past decade [1]. Research demonstrates that by the midpoint of their course, 9% of previously symptom-free students develop depression and 20% become anxious to clinically significant levels [2]. Nearly half (48%) of the students registered at a UK university-based general practice report high levels of anxiety [3]. Internationally, levels of students’ anxiety are also increasing, with university counseling services experiencing increasingly higher demand since 2010 [4-7]. Longitudinal studies report that students experience higher stress on entering university, which continues to increase during their studies, and does not return to previous levels after graduation [8,9].

Strikingly, only 25% to 36% of students with mental health issues seek treatment [10-12], largely due to the perceived stigma associated with these conditions [11,13]. A study investigating self-reported barriers to help-seeking behaviors and engagement in therapeutic pathways in students at risk of suicide found that a lack of time and a preference for self-management were among the main factors contributing to students’ choice not to seek treatment [14]. Untreated mental health issues among university students have been shown to have immediate and significant repercussions on the overall quality of life, increasing the likelihood of dropping out of university and committing suicide [1]. Importantly, untreated mental health issues during university years also have negative impact following graduation, affecting relationships, levels of productivity, and the likelihood of substance abuse [15].

Although on-site facilities are crucial for managing students’ mental health, their underutilization [16] suggests that novel approaches are needed to overcome accessibility barriers. Studies calling for more timely and preventative therapeutic interventions have highlighted the need for digital interventions [17-19]. The use of digital interventions, such as internet-based self-help resources and mobile apps, have been on the rise in the past decade due to their increased accessibility, availability, and anonymity [20-24], as well as their cost-effectiveness [25]. Owing to the widespread use of mobile phones, mobile apps could constitute effective therapeutic support for periods when students are away from the university, as well as increasing the capacity of on-site counseling services [26,27]. Mobile apps, paired with biosensors and wearable devices, are also effective in gathering passive data (eg, physical activity [28]) and self-report measures (eg, mood journaling). Accordingly, apps are increasingly used as a real-time monitoring tool, with personalized feedback, insights, and therapeutic content offered to users within the context of mental health interventions [29] and illness prevention [30].

A number of these digital interventions have proven effective in treating a variety of mental health disorders, ranging from anxiety and depression, to substance use disorder [31]. For example, an intervention lasting 2 weeks comprising brief, daily conversations and mood tracking with a Cognitive Behavioral Therapy (CBT)-oriented conversational agent (Woebot) found that, in comparison with an information-based digital control group, those in the Woebot group significantly reduced their symptoms of depression, while participants in both groups showed significantly reduced levels of anxiety [32]. Furthermore, an 8-week intervention in US university students with the mobile-app Calm was found to produce a significantly greater degree of stress reduction than that seen in a waitlist control group [23]. Despite these promising results, studies investigating the efficacy of a combined intervention, including both passive data collection and active therapeutic content, are still lacking.

The app BioBase (BioBeats, Ltd) aims at increasing individuals’ well-being by combining elements of mindfulness, biofeedback interventions (such as diaphragmatic breathing exercises), CBT, and behavioral activation theory [33-35]. Specifically, its psychoeducational content is based on the job demands-resources model, which has been shown to be associated with students’ well-being and stress management [36]. Alongside therapeutic content, data on physical activity, sleep quality, and heart rate are collected via a wrist-worn wearable device (BioBeam) and made available to individuals using the app to foster an increased awareness of users’ current well-being. Furthermore, available in-app tools include an ecological momentary assessment tool based on the Circumplex Model of Affect [37], allowing individuals to log their mood in the moment, and reflect back on their entries at a later date to gain insights into longer-term patterns of emotion. The app also includes diaphragmatic breathing exercises and relaxation techniques for in-the-moment stress reduction. In an initial feasibility study conducted with the BioBase app (BioBeats Ltd) in a sample of full-time employees [38], it was found that 4 weeks of usage of BioBase significantly reduced anxiety and increased self-reported mental well-being. The study also found that higher levels of baseline stress were associated with greater reductions in anxiety and increases in mental well-being, suggesting that usage of BioBase could be most beneficial for individuals with increased anxiety. However, the lack of a control group and the specificity of the selected population did not allow us to draw more general conclusions about the effects of using BioBase on self-reported anxiety and stress.

Hence, the purpose of this study was to test the efficacy of a 4-week intervention delivered via a mobile app and wearable device (ie, the BioBase program) in comparison with a waitlist control group on anxiety and general mental well-being in university students with elevated anxiety or stress. The study also examined sustained effects (at 6 weeks from baseline) of the intervention on anxiety and well-being. Finally, in the current study, measures of depression were collected to investigate the impact of the BioBase program on depressive symptoms.

We hypothesized that university students in the intervention group, but not in the waitlist control, would have significant improvements in anxiety and well-being following a 4-week intervention with BioBase. We also predicted that anxiety and well-being would have sustained effects in the intervention group, but not in the waitlist control, at 2 weeks following the end of the intervention. Furthermore, it was hypothesized that being enrolled in the BioBase program would reduce depressive symptoms after 4 weeks of usage.

This study was approved by an Institutional Ethics Committee at the University of Exeter (UEBS Research Ethics Committee, ethics application number: eUEBS002252). All participants provided informed, electronic consent prior to their enrollment in the study. Data from this study, including the preregistration protocol, are available on the Open Science Framework website (see Trial Registration section).

The current study was a randomized, waitlist control trial with assessments conducted at baseline, 2 weeks, postintervention (4 weeks), and follow-up (6 weeks). Participants randomly assigned to the intervention group took part in a 4-week well-being intervention (the BioBase program). Those assigned to the waitlist control group received the intervention after 8 weeks.

Participants were recruited using institutional participant pools at different UK universities as well as via social media, mailing lists, and flyers and through university staff. Recruitment took place between October and November 2019, and potential participants were screened for eligibility via a Qualtrics survey. Inclusion criteria comprised being a full-time university student attending a university in the United Kingdom and (1) being aged between 18 and 25 years, (2) having scored >14 points on the Depression, Anxiety and Stress Scale-21 items (DASS-21 [39]) stress subscale or >7 points on the DASS-21 anxiety subscale, (3) owning an iPhone 6 or above, (4) not having any previous psychiatric or neurological conditions, (5) not being pregnant at the time of testing, and (6) being able to read and understand English. Participants were also excluded if they were currently in therapy or were using counseling services. Individuals taking part in the initial screening survey were entered into a lottery to win a UK £50 (US $63.93) Amazon Voucher.

The original design was devised as a single-blind study; however, due to logistical reasons (ie, clarity of communications between the research team and participants) it was decided to unblind the design.

Eligible participants (n=262) were sent a reminder email prompting them to confirm their willingness to take part in the study. A total of 130 participants were randomly assigned to the intervention group and 132 participants were randomly assigned to the waitlist control group based on minimization factors: gender (2 categories: male and female), age (7 categories: 18, 19, 20, 21, 22, 23, 24, and 25 years), DASS-21 anxiety subscale (5 categories: normal, mild, moderate, severe, extremely severe), and DASS-21 stress subscale (5 categories: normal, mild, moderate, severe, extremely severe). DASS-21 categories were used for inclusion (ie, participants scoring within the normal range at screening were excluded from the study and those scoring normal at baseline were excluded from the analysis) and minimization purposes only. The first participant was allocated at random. Each subsequent participant’s group membership was allocated such that their addition to that group would lead to a closer match between the groups according to the minimization factors at screening. The random number list used to create the 2 groups was generated using the R Minirand package. Following randomization, the intervention group received their BioBeams (which are not functional until paired with a registered BioBase account) via post at their selected address.

Both groups completed four surveys via an online platform (Qualtrics). The surveys consisted of the following questionnaires: the State-Trait Anxiety Inventory (STAI-S-6 [52]), the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS [53]), the DASS-21, and the Patient Health Questionnaire (PHQ-9 [54]). The DASS-21 Stress and Anxiety Subscales were used as a screening tool for participants’ inclusion in the study, whereas the depression subscale, together with the PHQ-9, was used as an outcome measure for depression. Demographic characteristics of the sample were collected at baseline. At the end of the study, each participant received a monetary incentive of £40 (£10 per each completed set of questionnaires at T0, T1, T2, and T3) plus an additional £5 if they decided to send back the wearable device received as part of the intervention.

Figure 2 illustrates the flow of participants through the study and reasons for exclusion. Of 805 participants that were screened via an online questionnaire for inclusion and exclusion criteria, 262 participants were deemed eligible and were randomized into either the intervention (n=130) or waitlist control (n=132) groups. Of those, 59 participants from the intervention group and 64 from the control group completed the final questionnaire at T3 and were included in the analysis. Engagement data from the participants in the intervention group showed participants engaged with the app 21.9 of 29 days on average (median 26 days, IQR 13 days, range: 2-29 days). On average, participants engaged with the app 5.33 (SD=5.03) minutes per day (range: 2.13-28.68) over the 29 days of the intervention (see Figures 1 and 2, Multimedia Appendix 2). However, no correlation was found between the total amount of engagement with the app and differences, from baseline to T2 (4-weeks), in the main outcome measures (see Figures 3 and 4, Multimedia Appendix 3).

Participants in the two groups did not differ significantly with respect to age, gender, nor their levels of stress and anxiety at baseline (see Table 1). A total of 59 participants from the intervention group and 70 from the control group partook in the second questionnaire (intervention group: 38 females, age range: 18-25 years, mean 19.9 years, SD 1.9; waitlist control: 48 females, age range: 18-25 years, mean 19.9 years, SD 1.89; Figure 2), 55 and 61 (respectively) in the third (intervention group: 36 females, age range: 18-25 years, mean 19.9, SD 1.82; waitlist control: 43 females, age range: 18-25 years, mean 19.93 years, SD 1.95); and finally 59 and 64 participants completed the follow-up questionnaire (intervention group: 38 females, age range: 18-25 years, mean 19.92 years, SD 1.86; waitlist control: 43 females, age range: 18-25 years, mean 20, SD 1.90).

The aim of the current study was to investigate the efficacy of BioBase, a 4-week app-based intervention, in reducing anxiety and increasing well-being in university students with high self-reported levels of stress or anxiety. Results revealed that using the BioBase program for 4 weeks led to reduced self-reported anxiety and increased self-reported well-being. Such results were sustained at follow-up, with participants in the intervention group maintaining lower levels of self-reported anxiety and higher levels of well-being at 6 weeks from the study start date. Effect sizes ranged from moderate to large throughout the different outcomes.

The primary hypotheses of the current study were that in the intervention group only, levels of anxiety would decrease following enrollment in the BioBase program and that this reduction would be sustained after 2 weeks from the end of the intervention. In line with our first primary hypothesis, we found that self-reported levels of anxiety were significantly reduced in the intervention group after 4 weeks of app usage. This finding is in line with results from previous studies using digital interventions in both student [23] and nonstudent [32] populations. As mentioned in the Introduction section, Huberty et al [23] found that the mobile app Calm, consisting of a guided mindfulness meditation program, was effective in reducing stress levels among university students. In contrast to the BioBase 4-week program of 5 min a day; however, the Calm intervention was an 8-week program, requiring participants to first complete a 1-week course and then actively engage with the therapeutic content for at least 10 min a day. The efficacy of the BioBase program despite the reduced dosage may be related to the nature of the BioBase program: the therapeutic content is only one aspect of the hypothesized factors at play in anxiety reduction. Interactions with the app dashboard (showing participants their levels of activity, sleep quality, mood declarations over time, and heart rate), as well as usage of the tools, are hypothesized to be causally efficacious in addition to the traditional therapeutic content. Future studies using BioBase could shed light on the individual contribution of each of these aspects in reducing anxiety levels.

These results are also in line with previous findings [38], suggesting a significant reduction in anxiety following a 4-week intervention with the BioBase program in a sample of full-time employees. However, in this previous study, the effect of the intervention was not assessed beyond the end of the program. In the current study, we showed that the effect of the intervention persisted for 2 weeks following the end of the program. This result, in line with previous research [23], highlights the efficacy of mobile apps to reduce stress and anxiety over time, and their potential to supplement existing therapeutic support [18,27,29,30]. Future studies should investigate the extent to which these effects persist over longer timeframes, with the aim of identifying optimal guidelines for engagement to maximize outcomes.

A secondary hypothesis was that reduction in anxiety would be present following 2 weeks of enrollment in the BioBase program in the intervention group (but not in the waitlist control group). However, we did not find evidence of efficacy at 2 weeks. This finding is in contrast with a previous study conducted in the young adult population [32], using a CBT-based intervention to reduce anxiety and depression, which found significant results following 2-week long interactions with a Web-based conversational agent. Nevertheless, the current study significantly differed in both methods of delivery (app vs Web-based) as well as type of intervention. Although Fitzpatrick and colleagues employed a daily intervention, comprising specific time windows of interaction with the therapeutic content, the current study had a more ecological approach, with the BioBase program being available to participants at all times yet not being a daily commitment. Thus, the reason behind the lack of efficacy following a 2-week enrollment in the program may be due to differences in perceived benefit from the participants’ perspective, that is, it may be easier to recognize the impact of a daily conversational intervention versus a natural, progressive engagement with a multidimensional program. Further research, comparing different kinds of interventions, would be needed to shed light on these findings.

In terms of secondary outcomes, it was hypothesized that perceived well-being would increase following a 4-week intervention with BioBase and that this effect would be sustained at follow-up (6 weeks). As predicted, we found that participants in the intervention group reported higher levels of perceived well-being after 4 weeks, which were still significant at 2 weeks from the end of the intervention. Nevertheless, we also found a main effect of time, with levels of perceived well-being being higher at T2 and T3, regardless of the grouping. Further studies with single- or double-blind designs could investigate the impact of being enrolled in a study on perceived well-being.

Finally, additional measures of depression were obtained via the PHQ-9 questionnaire and DASS-21 Depression subscale to assess the feasibility of the BioBase program in reducing depressive symptoms. Results showed that participants taking part in the current study reported lower depression levels after 4 weeks of BioBase usage and sustained effects at follow-up (as measured via the PHQ-9). Nevertheless, despite showing the same pattern of reduction, the same results were not significant for the DASS-21 Depression subscale. Such a discrepancy may be due to differences in sensitivity of the 2 measures, given the focus on periods of different length, and further research is needed to shed light on these findings. Furthermore, given that the trial was conducted in November 2019 through December 2019, it is possible that the reduction in DASS Depression scores observed in the waitlist control group could be due to changes in university work demands, such as coursework deadlines and exams, over this period.

This result is nonetheless particularly relevant when assessing the lack of engagement of individuals at risk of suicide with established pathways of support. Specifically, the possibility to access a digital mental health intervention, which could be efficacious in reducing depressive symptomatology could, represent a novel approach in students at risk of suicide [1,14]. Future studies should specifically investigate the efficacy of such intervention in a student population with individuals suffering from self-reported depressive symptoms.

A limitation of the current study is the lack of a blinding procedure. As mentioned in the Methods section, the current study was an unblinded, randomized controlled trial, with participants in the control group being aware of the fact that they were not currently partaking in the intervention. This was a consequence of the type of control group employed. However, both groups received the same kind of communications and were prompted to respond to the questionnaires in the same way. A targeted standardized email was sent every week, with the timeline of the study and key dates as a reminder to participants. Although these measures reduced the possibility that unblinding could influence the results of the current study, future studies should investigate the extent to which being enrolled in an intervention leads to improvements in anxiety and well-being by employing a single-blind design, with an information-based control group.

Moreover, owing to lack of data on ethnicity, or information on the characteristics of the students underusing mental health services, it was not possible to assess the generalizability of our sample. Further studies should further investigate this, by replicating the current study while controlling for these variables.

Furthermore, in the current study, it was not possible to differentiate the effect of the different components of the BioBase program. Although this is a characteristic of digital interventions [60], future studies should explore what components of the BioBase program are most efficacious for which individuals.

In addition, the current study targeted subclinical levels of anxiety; therefore, participants with a psychiatric diagnosis of anxiety were excluded. This decision was made to explore symptom reduction and well-being increase without the confounding factors of being currently in treatment for anxiety. It could be the case, however, that effect sizes were underestimated if BioBase is more efficacious in participants with higher anxiety levels. Further research is needed to better understand the potential effects of BioBase in individuals with a clinical diagnosis of anxiety or stress.

In terms of the follow-up measure, the current study employed a 6-weeks follow-up, aimed at investigating the sustained effects of the intervention. However, it should be noted that further research is needed to explore long-lasting effects of the intervention (eg, 8 weeks).

Finally, in the current study, no specific criterion was used with regard to app usage. Given that we wanted to observe how participants would naturally engage and interact with the program, there was no strict indication nor control on participants’ way to use the app. Nevertheless, the majority of the sample engaged with the intervention, with only 3 people not downloading or installing the app. Future research could explore whether a more controlled intervention, with specific engagement criteria, could lead to more efficacious results while still maintaining ecological validity.

In this study, we showed that a 4-week digital intervention was efficacious in reducing anxiety and increasing well-being in a student population with high levels of self-reported stress and anxiety. These effects were sustained after 2 weeks from the end of the intervention, thus suggesting prolonged efficacy over time. To the best of our knowledge, this is the first study showing the efficacy of a multidimensional digital program, comprising therapeutic content, biofeedback, and mood-journaling, in reducing anxiety and increasing well-being in a student population. These findings are particularly relevant given the documented preference of students to self-help, rather than accessing on-site facilities, when facing mental health issues. Furthermore, the common use of mobile phones makes this type of intervention both accessible and scalable for higher education institutions who aim to extend the support provided to their students [27]. Future research should investigate the feasibility of including digital mental health interventions in the existing therapeutic pathways, thus encouraging preventative as well as intervention-driven approaches to mental health, tailored to the needs of the individuals.