Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya
Published online by Cambridge University Press: 04 December 2023
Abstract
Wearable activity trackers have emerged as valuable tools for health research, providing high-resolution data on measures such as physical activity. While most research on these devices has been conducted in high-income countries, there is growing interest in their use in the global south. This perspective discusses the challenges faced and strategies employed when using wearable activity trackers to test the effects of a school-based intervention for depression and anxiety among Kenyan youth. Lessons learned include the importance of validating data output, establishing an internal procedure for international procurement, providing on-site support for participants, designating a full-time team member for wearable activity tracker operation, and issuing a paper-based information sheet to participants. The insights shared in this perspective serve as guidance for researchers undertaking studies with wearables in similar settings, contributing to the evidence base for mental health interventions targeting youth in the global south. Despite the challenges to set up, deploy and extract data from wearable activity trackers, we believe that wearables are a relatively economical approach to provide insight into the daily lives of research participants, and recommend their use to other researchers.
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- This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
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- © The Author(s), 2023. Published by Cambridge University Press
References
Author comment: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R0/PR1
Comments
Cover Letter
Dear Prof. Belkin, Prof. Bass, and Dr. Chibanda,
My co-authors and I have enclosed for your review a copy of our manuscript entitled, “Using Wearable Activity Trackers in Low-and Middle-Income Countries: Lessons Learned from Adolescent Mental Health Research in Kenya” for your consideration for publication in the journal Global Mental Health. This manuscript has not been published nor submitted for publication elsewhere and was prepared according to the Instructions for Authors provided on the journal website. The use of wearables for this research was funded by Alchemy Pay and a grant from the Templeton World Charity Foundation (Grant Number TWCF0633).
We believe that our manuscript aligns well with the mission and scope of GMH. In this article, we describe the challenges faced when using wearable activity trackers to determine the long-term health effects of a mental health intervention on youth in Kenya. We then outline strategies that may be useful to other researchers using these devices for research in low-resource settings.
We believe this manuscript may interest both the readership of GMH focused on designing and testing mental health interventions for youth in low-resource settings and the readership of GMH interested in the integration of wearable activity trackers as a measurement device to collect ecological data in lower- and middle-income countries. All authors have approved the final submitted manuscript and have agreed on submitting it to GMH.
Below are the authors’ full names and affiliations:
Natalie Johnson
University Hospital Basel
University of Basel
Basel, Switzerland
Shamiri Institute
Nairobi, Kenya
Natalieelaine.johnson@usb.ch
+41 78 243 8166
Katherine Venturo-Conerly
Harvard University
Shamiri Institute, Inc.
Thomas Rusch, PhD
Vienna University of Economics and Business
Best Wishes,
Natalie Johnson
Review: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R0/PR2
Conflict of interest statement
Comments
This is an excellent article that addresses the challenges (and potential solutions) that many people in LMIC face when trying to use the specified technology in data collection. If we could all collectively find solutions to all these challenges then it will be great for related research in LMIC.
Review: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R0/PR3
Conflict of interest statement
Comments
Thank you for sharing your hard learned lessons. We need more researchers to share this type of experience so that they can, hopefully prevent these challenges.
I am able to understand the target population LMICs, specifically youth in Kenyan secondary schools. I also understand that the WATs were used to complement students self-reported measures with the objective measures attained by the Fitbit Charge.
What I would recommend is for the authors to add more information about the context of the study. For instance, what kind of self-report measures were used? Were the youth trained or experience any difficulties in using or even remembering to wear the WATs? In general, how well did the self-report measures of anxiety and depression agree with the objective measures of Heart Rate and Heart Rate Availability. I recognize that this manuscript is not focusing on results but instead, focuses on lessons learned. One important lesson might also be - for all of the challenges, did the results warrant this approach? Or might you recommend a different approach?
Review: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R0/PR4
Conflict of interest statement
Comments
As the authors rightly state, the use of wearable technologies is on the increase and understanding the potential and limitations of their use in LMICs is essential. I think the manuscript already presents some interesting findings and would be strengthened by some more nuanced discussion. LMICs have quite some national variations as well as diversity. More detailed explanations of country and population level context would be very helpful for readers seeking to apply these lessons.
For example, reading the points about validating data output, procurement and piloting, they ultimately can be reduced to a pilot phase was needed. Pilots are standard in many research projects, particularly those involving technology. Why did the authors not consider that it would be essential to pilot the technology before starting?
I also wonder at the time from procurement, is this really expected to be a standard issue in LMICs? In other LMICs where I’ve worked, devices as common as the Fitbit Charge could easily be bought on Amazon UK or US and delivered in about a month. This makes me curious about the causes of delay? Was it due to numbers needed? Country legal restrictions? Budget constraints? When should researchers expect procurement to be a problem
While the discussion of the technology and challenges related to the use of WATs is important, I missed the human perspective. How did adolescents respond to the technology? What were the reasons they had challenges charging the device -i.e. battery drainage? Why was theft and loss common, context specific or more age group related. Did WATs already exist in the population or was their appearance distinct and possibly something that would make adolescents stand out?
I was also surprised that on-site support is needed for adolescents who tend to be very technology savvy. From my read of Smuck et al.2021., I assume they are dealing with an older population of patients. Did the authors expect this problem with their population, for example are there specifics of this adolescent population that means they might struggle with technology
The authors also mention that collecting data from WATs is time consuming in LMICs. Why is this? I would have thought that the advantage of using WATs would be reducing human effort. What made it difficult in Kenya? Are there possibilities that other LMICs without similar constraints would need less human support?
Recommendation: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R0/PR5
Comments
Thank you for submitting your manuscript for review. The reviewers have acknowledged the relevance of your work; however, they have requested additional information concerning the context of the study and the setting. They have also posed pertinent questions and provided valuable suggestions that could enhance the manuscript. We kindly request you to address each comment, question, and suggestion in your response for further consideration.
Decision: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R0/PR6
Comments
No accompanying comment.
Author comment: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R1/PR7
Comments
Dear Profs. Ikenna and Chibanda,
We have enclosed for your review a copy of our revised manuscript entitled, “Using Wearable Activity Trackers in the Global South: Lessons Learned from Adolescent Mental Health Research in Kenya,” MH-23-0138 for your consideration for publication in the journal Global Mental Health. This manuscript has not been published nor submitted for publication elsewhere and was prepared according to the Instructions for Authors provided on the journal website. The use of wearables for this research was funded by Alchemy Pay and a grant from the Templeton World Charity Foundation (Grant Number TWCF0633).
As stated previously, we believe that our manuscript aligns well with the mission and scope of GMH. In this article, we describe the challenges faced when using wearable activity trackers to determine the long-term health effects of a mental health intervention on youth in Kenya. We then outline strategies that may be useful to other researchers using these devices for research in low-resource settings.
We believe this manuscript may interest both the readership of GMH focused on designing and testing mental health interventions for youth in low-resource settings and the readership of GMH interested in the integration of wearable activity trackers as a measurement device to collect ecological data in the global south. All authors have approved the final submitted manuscript and have agreed on submitting it to GMH.
Should you require further changes to the manuscript, please let us know, and we would be glad to make further changes. Below are the authors’ full names and affiliations:
Natalie Johnson
University Hospital Basel
University of Basel
Basel, Switzerland
Shamiri Institute
Nairobi, Kenya
Natalieelaine.johnson@usb.ch
+41 78 243 8166
Katherine Venturo-Conerly
Harvard University
Shamiri Institute, Inc.
Thomas Rusch, PhD
Vienna University of Economics and Business
Best Wishes,
Natalie Johnson
Review: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R1/PR8
Conflict of interest statement
Comments
None
Review: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R1/PR9
Conflict of interest statement
Comments
Many thanks to the authors for their thoughtful responses to the earlier comments. I think the additional reflections have strengthened this piece and will make it a useful resource for other researchers.
Recommendation: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R1/PR10
Comments
Thank you for revising the manuscript and responding to the reviewers’ recommendations.
All the reviewers are satisfied with the revisions and have recommended that we accept the manuscript.
We are happy to accept the manuscript in its present form and look forward to working with you through the publication process
Decision: Using wearable activity trackers for research in the global south: Lessons learned from adolescent psychotherapy research in Kenya — R1/PR11
Comments
No accompanying comment.
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Impact statement
There is a significant need for ecologically valid methods to measure the effects of mental health interventions on youth in the global south, where access to psychological care is limited. Wearables have emerged as powerful tools, providing high-resolution data on mental health markers. This perspective discusses the use of wearable activity trackers, or wearables, in the context of psychotherapy research with youth in Kenya. It highlights several key lessons learned and best practices that are relevant for global mental health researchers. We outline the challenges faced when using wearables in Kenya, such as device selection, procurement, technical issues, and participant support. It offers recommendations, including the importance of validating devices, establishing an efficient procurement process, providing onsite support, designating a full-time team member, and distributing standardized information sheets to participants. The impact of this article extends beyond Kenya, as it provides practical insights that can be applied to similar contexts globally. It underscores the importance of accurate and ecologically valid data collection in mental health research and encourages researchers to consider the benefits of wearable activity trackers while addressing the associated challenges. Ultimately, the lessons shared here can help researchers successfully implement global mental health studies with wearables, contributing to more robust research in these settings.
Introduction
Approximately 90% of youth live in the global south, with children under 15 accounting for 41% of the population in sub-Saharan Africa (United Nations, Department of Economic and Social Affairs, Population Division, 2015). For these youth, access to psychological care is limited (Galagali and Brooks, Reference Galagali and Brooks2020), although an estimated 10–15% of disease in these settings is neuropsychiatric (Patel, Reference Patel2007). Thus, it is important to find economical and ecologically valid methods to measure the effects of mental health interventions. Wearable activity trackers (WATs) have emerged as powerful tools for health research in recent years, enabling the collection of high-resolution data on physical activity, sleep, and other health markers and behaviors (Ryan et al., Reference Ryan, Edney and Maher2019; Cho et al., Reference Cho, Lee, Lee, Seo, Jee, Son, An, Kim and Lee2020; Lewis et al., Reference Lewis, Pritting, Picazo and JeanMarie-Tucker2020; Semaan et al., Reference Semaan, Dewland, Tison, Nah, Vittinghoff, Pletcher, Olgin and Marcus2020; Zahrt et al., Reference Zahrt, Evans, Murnane, Santoro, Baiocchi, Landay, Delp and Crum2023). While most research using these devices with youth has been conducted in high-income countries (HICs; Casado-Robles et al., Reference Casado-Robles, Viciana, Guijarro-Romero and Mayorga-Vega2022), there is growing interest in using them to study health in the global south (Barteit et al., Reference Barteit, Boudo, Ouedraogo, Zabré, Ouremi, Sié, Munga, Obor, Kwaro, Huhn, Bunker, Sauerborn, Gunga and Bärnighausen2021; Neale et al., Reference Neale, Boukhechba and Cinderby2023).
When using these devices in HICs, researchers have met challenges with participant compliance, technology (e.g., synchronization), and logistical issues such as limited battery life (Harrison et al., Reference Harrison, Marshall, Berthouze and Bird2014). One study identified the need for a patient-facing technology support desk when using WATs (Smuck et al., Reference Smuck, Odonkor, Wilt, Schmidt and Swiernik2021). Researchers using these devices in sub-Saharan Africa have encountered technical challenges such as faulty synchronization, logistical challenges such as damaged devices, and issues with data completeness (Huhn et al., Reference Huhn, Axt, Gunga, Maggioni, Munga, Obor, Sié, Boudo, Bunker, Sauerborn, Bärnighausen and Barteit2022a).
Unfortunately, essential details of the implementation process of using WATs for research in global south regions such as those in sub-Saharan Africa are not widely documented (Shin et al., Reference Shin, Jarrahi, Fei, Karami, Gafinowitz, Byun and Lu2019; Huhn et al., Reference Huhn, Matzke, Koch, Gunga, Maggioni, Sié, Boudo, Ouedraogo, Compaoré, Bunker, Sauerborn, Bärnighausen and Barteit2022b). In this perspective, the authors document and reflect on using WATs to conduct psychotherapy research in Kenya. After mentioning some of the challenges faced and strategies to address these challenges, we condense these into lessons learned. Our findings are most relevant to other investigators pursuing global mental health research with WATs.
Testing a school-based intervention for depression and anxiety
Our multicultural team of researchers has created a character strengths intervention with three modules: gratitude, growth mindset, and values (Osborn et al., Reference Osborn, Wasil, Venturo-Conerly, Schleider and Weisz2020). The Shamiri Intervention was delivered to youth with depression or anxiety in Kenyan secondary schools by trained lay providers over 4 weeks in three randomized controlled trials (Osborn et al., Reference Osborn, Wasil, Venturo-Conerly, Schleider and Weisz2020, Reference Osborn, Venturo-Conerly, Arango, Roe, Rodriguez, Alemu, Gan, Wasil, Otieno, Rusch, Ndetei, Wasanga, Schleider and Weisz2021; Venturo-Conerly et al., Reference Venturo-Conerly, Osborn, Wasil, Le, Corrigan, Wasanga and Weisz2021). A follow-up study of the participants is currently underway to determine the long-term effects of this intervention (Venturo-Conerly et al., Reference Venturo-Conerly, Johnson, Osborn, Puffer, Rusch, Ndetei, Wasanga, Mutiso, Musyimi and Weisz2022).
The Shamiri Intervention took place in secondary schools in Nairobi and Kiambu counties with participants of widely ranging sociodemographic backgrounds, representative of the students attending secondary school in these counties. Some schools taking part in this study were located in informal settlements and enrolled students from the surrounding area, while other schools enrolled students from the entire county. The highest caliber of schools that participants were recruited from enrolled gifted students from the entire country.
As part of the long-term follow-up study, youth were asked to wear WATs for 2 weeks to provide insight into the effects of this treatment on their day-to-day lives. Participants may or may not have had prior experience with WATs, but had limited access to them while at school, as students were not permitted to have electronic devices. Special permission for students to wear WATs in school was obtained. Participants were briefed about the protocol individually or in small groups by a trained research assistant. They were instructed to wear the watches as much as possible and not to share them with others.
The wearables were used to complement self-reported measures with more objective measures of chronic states. The Patient Health Questionnaire, 8-item (PHQ-8) was used for depression symptoms (Kroenke et al., Reference Kroenke, Strine, Spitzer, Williams, Berry and Mokdad2009), and the Generalized Anxiety Disorder Screener, 7-item (GAD-7) was used for anxiety symptoms (Spitzer et al., Reference Spitzer, Kroenke, Williams and Löwe2006). We used the WATs to capture heart rate variability, distance, and step count. Heart rate variability has been shown to correlate with stress levels and psychological health, while physical activity has been shown to correlate with depressive symptoms (Kim et al., Reference Kim, Cheon, Bai, Lee and Koo2018; Moshe et al., Reference Moshe, Terhorst, Opoku Asare, Bosse Sander, Ferreira, Baumeister, Mohr and Pulkki-Råback2021).
WATs are an accurate, minimally invasive, relatively affordable, and low-stigma method of gathering ecologically valid, objective data from participants (Evenson et al., Reference Evenson, Goto and Furberg2015; Germini et al., Reference Germini, Noronha, Borg Debono, Philip, Pete, Navarro, Keepanasseril, Parpia, de Wit and Iorio2022). Although there are many benefits to the use of WATs, they are accompanied by several significant challenges. Through the process of deploying these devices in a pilot study, we learned the following lessons.
Lessons learned
Ensure accurate and available data output
Securing suitable devices for research in many countries in the global south can pose a significant challenge. In our study conducted in Kenya, the initial study device was selected based on local availability and low cost. However, after data collection began for our pilot study, it became evident that the chosen device, the Xiaomi Mi, did not measure heart rate in frequent, consistent time intervals, which was critical for our study objectives. Moreover, previous research had yielded mixed results regarding the accuracy and validity of the measurements taken with this band (Chow and Yang, Reference Chow and Yang2020; Pino-Ortega et al., Reference Pino-Ortega, Gómez-Carmona and Rico-González2021; de la Casa Pérez et al., Reference de la Casa Pérez, Latorre Román, Muñoz Jiménez, Zurita, Laredo Aguilera, Párraga Montilla and Cabrera Linares2022). Thus, following the pilot, we decided to change the study device to the Fitbit Charge.
The Fitbit Charge has a proven track record in large-scale research, especially in measuring heart rate variability (Natarajan et al., Reference Natarajan, Pantelopoulos, Emir-Farinas and Natarajan2020), and its accuracy has been demonstrated in various studies (Evenson et al., Reference Evenson, Goto and Furberg2015; Wahl et al., Reference Wahl, Düking, Droszez, Wahl and Mester2017; Germini et al., Reference Germini, Noronha, Borg Debono, Philip, Pete, Navarro, Keepanasseril, Parpia, de Wit and Iorio2022; Irwin and Gary, Reference Irwin and Gary2022). Although the data quality from Fitbits is higher, we found it difficult to extract the data from the devices, specifically, the heart rate variability. To access this data, we required a software developer to build a Fitbit application to request permission from the Fitbit user account of the participant. This gave us access to the data, and then another application was required to compile the extracted data.
To prevent missing or inaccurate data, we recommend researchers validate their chosen devices, ensuring alignment, accuracy, and availability of data. Additionally, before selecting a study device, it is important to ensure the proper technical skills are present to obtain this data. By diligently testing data collection and export procedures, researchers can ensure that the chosen WATs meet their expectations and contribute to robust research.
Establish an internal process for international procurement
Obtaining the necessary study devices in many countries in the global south can present significant challenges, particularly when it comes to their availability in local markets. In our research project, the necessary study devices were not locally available in the required quantity. Thus, we had to navigate the complex processes of sourcing, shipping, and importing, which took 5 months to complete. This delay taught us the necessity of factoring in ample time ahead of planned activities to account for the sourcing, shipping, and customs clearance processes.
In our case working within a new local non-profit, the procurement process for international shipments had not been outlined prior to the WAT purchase. Hence, the WATs used for our study were procured through local vendors who sourced them from several international vendors. This process led to a critical delay in the receipt of our devices. Thus, we recommend that an organization wishing to purchase a large number of WATs for shipping to a country structurally similar to Kenya establishes an internal international procurement channel. By taking on this process in-house, the organizations will have more control over the procurement and import timeline. This strategy can mitigate the risk of delay and ensure the availability of study devices, facilitating the smooth execution of research projects with wearables.
Provide onsite support to participants during the data collection and active study period
Deploying WATs for data collection can prove to be an unpredictable endeavor, particularly when working in study sites located in countries in the global south. This unpredictability arises due to technical issues with the devices and participants’ varying exposure to technology. For instance, during our pilot study, the devices became unpaired, lost their charge more quickly than anticipated, were reset to factory settings and were often unable to be charged due to lack of access to a power point or electricity.
As the use of WATs in countries in the global south is highly context specific, unanticipated and complex problems may also arise during the active data collection period. In our research endeavors, we encountered several unforeseen issues, highlighting the importance of offering on-site support to participants. Recognizing the significance of this support, we established a dedicated technical and logistical support site, ensuring that participants had access to assistance when encountering challenges with their devices. This approach aligns with the recommendations of those operating WAT research in high-income countries (Smuck et al., Reference Smuck, Odonkor, Wilt, Schmidt and Swiernik2021).
To facilitate data completeness and prevent disruption, we suggest that during the data collection and active study phase, researchers designate a specific time and location where participants can easily meet a study team member during implementation. This accessibility ensures that participants can seek immediate assistance for any personal, technical or logistical concerns related to the WATs. By providing on-site support, researchers can enhance participant engagement, troubleshoot device-related issues promptly, and promote the completeness of collected data.
Designate a full-time study team member to operate the wearables
The collection of data using WATs in the global south presents a complex and time-consuming endeavor that heavily depends on the chosen device and context. Adequate allocation of human resources is crucial to their successful deployment. To ensure smooth operations, it is important that there is a study team member who is trained in depth to manage WAT tasks. In the case of our study, we did not anticipate the amount of human support that was required. Due to the intricacies and time-intensive nature of the setup, implementation, and data retrieval, we required a full-time staff member at the peak of activity. When researchers plan to issue WATs to participants as part of the research study, we emphasize the importance of employing a full-time research assistant who possesses expertise in device setup, data extraction, and troubleshooting. This individual plays a critical role to support the completeness and availability of data. Their dedicated focus on managing the intricacies of WAT operations enhances the overall effectiveness and efficiency of data collection efforts.
Distribute standardized information sheets to participants
Access to electricity and technology can vary drastically for youth in the global south. While it is possible that youth will encounter no challenges adhering to study procedures related to WATs, researchers should thoroughly prepare participants for any potential issues that may arise. The challenges youth in Kenya encountered during our study were with sharing of the devices, charging them and keeping them functional. For instance, many devices became unpaired from the smartphone that they were linked to, rendering them unable to collect data. Regarding the charging of devices, several participants reported that they did not have access to electricity or a charging point. Other participants encountered very rapid battery drainage.
In our study, many youth were excited to wear the WATs. However, as secondary schools in Kenya do not allow electronic devices, wearing the smart watches during school would have made the students stand out. Wearables are popular in Kenya, and many times the youth reported that their friends or family members wanted to borrow the device, which was against the protocol. One participant who was living in a dormitory with other students lost the device. Several youth asked if they could keep the watches following the study period.
While all youth were briefed on study procedures, there was a wide variation in the difficulty youth faced when following them. Researchers using WATs for research with youth in the global south should provide a paper-based information sheet to participants that gives a step-by-step explanation of the procedures, basic troubleshooting instructions, and contact information for the study team in case of challenges. This information sheet should also contain graphics of key messages, i.e., sharing of the watch with others. Provision of this sheet will ensure that the participants have a resource to refer to as they navigate study procedures.
Conclusion
The use of WATs for treatment research in the global south holds promise as an ecologically valid data collection method. However, researchers must be aware of the challenges they may face when using WATs, such as the time taken to procure devices and manage the implementation of their use, unforeseen technical and logistical failures, as well as data reliability and validity. Strategies to overcome these challenges include to validate data input and output before deployment, establish a trusted and robust international supply channel to procure the devices, train a specific team member to be an expert in WATs, set up onsite technical support for study participants, and provide participants with standardized information sheets.
What we discussed constitutes best practices derived from psychotherapy research in secondary schools with Kenyan youth. These lessons may be most relevant to researchers working with WATs in contexts similar to Kenya. However, certain aspects may apply globally, for example, data extraction. Despite the challenges, data from wearables provides key insight into participant’s daily physiological states; an invaluable perspective when considering treatment effects. The unique insights offered by wearable data warrant the difficulty. Thus, we encourage other researchers to consider the benefits of using wearable data alongside careful planning for their use. Ultimately, we believe our findings can contribute to other researchers successfully setting up and undertaking global mental health research with WATs.
Open peer review
To view the open peer review materials for this article, please visit http://doi.org/10.1017/gmh.2023.85.
Acknowledgments
The authors would like to acknowledge Nina Kahura for her support to implement the use of wearable devices during this study.
Author contribution
N.E.J.: conceptualization and original draft manuscript. K.E.V.-C.: supervision and draft manuscript edits. T.R.: supervision and draft manuscript edits.
Financial support
WAT devices were funded by Alchemy Pay, a blockchain organization with the mission to bridge fiat and cryptocurrencies. The implementation of study activities was funded by Templeton World Charity Foundation (Grant No. TWCF0633, 2021).
Competing interest
K.E.V.-C. is an executive of Shamiri Institute, a 5,013(c) non-profit organization focused on increasing access to mental health care for youth in sub-Saharan Africa. T.R. is a consultant and member of the Science Board of Shamiri Institute. The remaining author declares no competing interests exist.
Ethics statement
This study was approved by Kenyatta University’s Ethical Review Committee (PKU/2392/E1528).