Evaluation of a reporting and supporting tool in interventional trials - the KarmApp

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We have developed KarmApp, a smartphone application, to optimize data quality, safety and user-friendliness in our breast cancer prevention trials. The aim of this study was to evaluate the performance and the usage of the KarmApp over time. Methods The KarmApp functions include adverse event reporting, personalized study activity overviews, study questionnaires, and direct communication with study staff. Users are healthy women aged 40 to 74 participating in our randomized interventional trials evaluating risk-reducing medications at different doses and formulations. Development and deployment have followed a systematic, iterative approach, from requirements specification to post-release monitoring. We have calculated the usage frequencies of the various KarmApp features and performed statistical analysis across age groups and respective trials using SAS version 9.4 and R version 4.2.1. Results Of the participants in the randomized clinical trials KARISMA 2 (N = 1,440) and KARMA Creme (N = 90), 1406 (91.9%) used the KarmApp, across all age groups. There were 14,212 user interactions with the KarmApp, with the “Study Activities Overview” being the most frequently used. A total of 2,081 spontaneous adverse event reports collected in the trials. The majority, 1,535 (73.8%), were reported through KarmApp, less via the other reporting channels. Conclusions KarmApp exemplifies the potential for transformative impacts in healthcare and clinical research, which is supported by our data showing trends towards an increased use of the app over time. Our experiences of KarmApp reflects the growing acceptance of mobile technology across age groups, presenting opportunities for further integration in clinical trials. Adverse event reporting smartphone application randomized clinical trials data quality clinical trials. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background In recent decades, society has become increasingly digitalized, and telemedicine has rapidly developed, especially in the management of chronic diseases. The World Health Organization (WHO) defines telemedicine tools as “mHealth” or “eHealth,” which refers to “medical and public health practice supported by mobile devices, such as mobile phones, patient monitoring devices, personal digital assistants, and other wireless devices” [1]. Smartphones are now widely used, and mobile applications (apps) are increasingly being utilized for self-care and tracking health data. Advanced apps offer tools to improve treatment compliance, facilitate questionnaire responses, and report symptoms [2]. As a result, there is a promising trend of using apps and mobile devices in clinical trials, which can empower participants and improve treatment adherence and follow-up [3] [4]. This also supports data collection and communication in clinical trials, ensuring adherence to Good Clinical Practice (GCP) and reducing under- and incorrectly reported adverse events (AE) [5] [6] [7]. Over the past decade, we have conducted several randomized controlled trials involving nearly 2,000 women. These trials focused on breast cancer prevention and tested risk-reducing medications at different doses and formulations [8] [9] [10]. We invited women, attending the Swedish mammography screening program at the Breast Centre Södersjukhuset, Stockholm, to participate in the trials. Early on, we recognized the need to develop a means of two-way communication that was safe, efficient, and compatible with our existing systems. As a result, we created a versatile solution called the KarmApp, a smartphone app designed as a generic platform. Our primary focus was on optimizing data quality and safety while ensuring user-friendliness. In this paper, we describe the development of KarmApp, its features and evolving usage in clinical trials. Methods KarmApp is a smartphone app developed in-house and exclusively for the interventional trials in the breast cancer project known as KARMA (KARolinska Mammography study for Risk Prediction of Breast Cancer) [11]. KarmApp is accessible on Android and iOS platforms. Its primary purpose is facilitating seamless two-way communication between the study staff and participants. The aim of the study was to evaluate KarmApp’s usability and impact in our randomized interventional trials with healthy women aged 40 to 74, assessing its acceptance and effectiveness across age groups in clinical trials. Study Population The population included in the report consisted of women aged 40 to 74 who participated in the KARMA project sub-studies; KARISMA 2 [9], and KARMA Creme (also known as ATOS-010) [10]. Participants were invited before visiting the Breast Centre for the general mammography screening. If interested after reading the written study information they were orally informed by a trial physician and were included after giving informed consent. KARISMA 2 recruited participants from November 2016 to March 2019 and KARMA Creme from August 2018 to October 2018. During the inclusion visit participants got a text message containing the login details and instructions for downloading and installing KarmApp on their mobile devices. Additionally, the study staff provided participants with a user guide and a comprehensive orientation to all sections of the app. The KarmApp platform uses a client-server model with a client app for iPhones and Android smartphones. It employs NodeJS as the server application, which handles communication with a Microsoft SQL Server database through application programming interfaces, ensuring data transmission and retrieval. KarmApp General Architecture The KarmApp platform follows a client-server model architecture [12], comprising a client application that utilizes services provided by a server application ( Figure 1 ). The client side of the app is designed to be compatible with iPhones and Android smartphones, serving as the user interface for interacting with KarmApp's features. For the server application, NodeJS, a JavaScript runtime [13] was employed. The NodeJS application functions as the background server, facilitating communication between the client side and the underlying infrastructure. It interacts with a Microsoft SQL Server database [14] for efficient data storage. Application Programming Interfaces (APIs) were developed to manage the app's functionality, enabling data transmission to, and retrieval from, the database. All logins, messaging and other communication within KarmApp are encrypted to ensure data security and privacy. Importantly, only anonymous data is transferred. Apart from these technically supported safety measures, we acknowledge our ethical responsibility in handling user data, respecting user privacy, obtaining consent for data usage, thus ensuring that the data collection adheres to ethical standards.KarmApp is designed to integrate with Customer Relationship Management (CRM) systems of the different trials for obtaining participants' information and tracking their status in the studies. The described studies utilize Microsoft Dynamics CRM [15] and LIME CRM [16] as CRM systems. The KarmApp's interface elements, including pages, fields, forms, icons, text, buttons, labels, and more, are controlled through the database and server. This minimizes the need for frequent app releases for minor interface changes, eliminating the requirement for users to update the app frequently. As part of KarmApp, an integrated automated system sends text messages to study participants, serving as reminders for various activities during their study participation. Furthermore, KarmApp has been designed as a flexible platform capable of accommodating new interfaces for future KARMA sub-studies. The initial interface development focused on the KARISMA 2 study, and later the app's architecture was redesigned to accommodate additional interfaces for the KARMA Creme study (and later to the ongoing study KARISMA Endoxifen). The current architecture supports the addition of new interfaces specifically tailored for upcoming studies, allowing the use of a single app with a unified login for KARMA participants across different sub-studies ( Supplementary Figure 1 ). KarmApp Features KarmApp offers a range of features that facilitate study participation ( Figure 2 ). Adverse Events Reporting: KarmApp enables participants to report adverse events (AE) spontaneously and continuously during the trial period. Symptoms can be entered as free text or selected from predefined lists. Participants can indicate the severity of symptoms and provide start and stop dates if required by the study protocol. Reporting of side effects can also be done via various other sources such as telephone, email, or during a visit to the study center. Personalized Study Activities Overview: Participants can access an overview of their study activities, dates for their visits and task completion status. The feature provides a comprehensive view of the different activities associated with their study participation. Access to Study Questionnaires: KarmApp includes an embedded link to web-based study questionnaires, allowing participants to conveniently answer them directly within the app. Contact with Study Staff: KarmApp enables direct communication between participants and study staff. Users can initiate phone calls, send text messages, or access the study webpage, facilitating communication and support. Reminders for Study Medications: Participants can configure reminders within the app to ensure the timely administration of study medications. Push notifications serve as reminders for users to take their study medications. Post-Study Feedback: Once a study is completed, participants can view personalized information about their participation. This may include details such as the assigned dose or other relevant study-related feedback ( Supplementary Figure 2 ). Pregnancy Test Report: If applicable, participants can report their pregnancy test results through KarmApp. Ongoing Medication Report: If applicable to the study, participants can report any changes in their ongoing medication and indicate if they were non-compliant with the study medication. Development of KarmApp Developing a successful smartphone application designed to facilitate and support the study participants and keep a high standard for data transfer and user-friendliness is a complex task [17]. Questions regarding security, privacy and human-computer interaction must be answered to protect highly sensitive patient information. KarmApp meets the three key user preferences for mobile technology in clinical trials [17]: Instant Support : Participants can contact the trial staff through KarmApp for technical issues, eliminating the need to contact the device manufacturer or app developer. Secure Data : KarmApp ensures secure data transfer and storage using a database server at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. Participant data remains confidential and accessible only to authorized personnel. User-Friendly : KarmApp has a user-friendly interface, prioritizing ease of use and intuitiveness. The app requires minimal navigation training and is easy to learn, ensuring a positive user experience for participants. The development process involved several stages and followed a systematic and iterative approach [18]. Requirements Specification: The requirements for KarmApp were defined based on the study protocols through extensive consultation with the study staff. A collaborative effort was undertaken to gather a comprehensive list of requirements outlining the app's functionality and features. Design: Considering the defined requirements, the development team created a detailed design and architecture for KarmApp. This included wireframes and user flow diagrams to visualize the app's structure and interface. The visual identity was defined through color schemes, typography, and icons to ensure a consistent and appealing user experience ( Supplementary Figure 1 ). Implementation: The app's functionality was implemented using Angular programming language in the Ionic framework, SQL-server programming scripts, and platform-specific tools for iOS and Android. Regular testing and debugging were conducted throughout the implementation phase to identify and address software defects or usability issues. Testing: KarmApp underwent rigorous testing to ensure its functionality, performance, and user experience met the required standards. This involved system testing, user acceptance testing, and validation of compliance with the defined requirements. Testing ensured the app's stability, reliability, and quality before release. Deployment: KarmApp was deployed to the Apple App Store and Google Play Store, making it available to designated end users. This stage involved preparations and processes to release the app to the public, including submission, review, and approval by app store administrators. Post-Release Maintenance: After the release of KarmApp, continuous monitoring mechanisms were implemented to track its performance and identify areas for improvement. This stage involved releasing updates and bug fixes to enhance functionality and user experience over time. KarmApp Versions The initial version of KarmApp focused on key features such as AE reporting, online questionnaires, participant activity overview, integration with an automated text message system, and direct communication with study staff. In 2017, during its initial development phase, KarmApp underwent evaluation as part of the KARISMA 2 trial [9]. Out of 34 participants contacted, 22 women participated in structured phone interviews, providing feedback on user experiences and user-friendliness. The interviews revealed that 17 out of 22 individuals had downloaded KarmApp, primarily for questionnaires. However, only some discovered the study schedule feature due to insufficient information. Thus, we onwards included that in the user manual. Users also encountered technical issues, with one in three facing login difficulties. Another important finding was that respondents could not provide free-text responses to questions. This evaluation, alongside Patient-Reported Experience Measures [19], contributed to further app development and the creation of a user guide for KarmApp. The second version, launched later in 2017, introduced significant upgrades involving a complete change in source code and interface design. The focus was on improving user-friendliness and performance. The post-study feature "Feedback to participants" was introduced but remained disabled for participants until the completion of the trials. In the third version, the app's architecture was redesigned to accommodate an additional interface for the KARMA Creme study. This version allows for the flexible inclusion of new interfaces for future sub-studies. The current version, the fourth version of KarmApp launched in December 2021, includes new features for reporting pregnancy test results and changes in concomitant medications. The database structure and model underwent a redesign, incorporating changes such as adding new tables, modifying existing relationships, optimizing performance, and enhancing scalability, and the integration with the CRM system LIME was implemented. Data analysis Age at study inclusion was categorized into age groups 40-49, 50–59 and 60-74 years; the number of reported AE was categorized into 1, 2, 3, 4 or 5 and >5 times; the reporting source was categorized into app, phone, email, visit to the study center and SMS; and KarmApp features were categorized into study activities overview, feedback to participants, report of adverse events, request a new PIN code and configure reminders. We utilized exploratory data analysis with descriptive statistics and visualizations, providing graphical representations that aid in understanding patterns, trends and potential outliers. Analyses were conducted using SAS version 9.4 and R version 4.2.1. Results A total of 1,530 women participated in two interventional trials: KARISMA 2 (N = 1,440) and KARMA Creme (N = 90) (see Table 1 ). Descriptive statistics, categorized into three age groups, are presented in Table 2 . Among the participants, 1,406 out of 1,530 (91.9%) used KarmApp, with the highest frequency of usage observed in the two younger age groups. Table 1 Number of Participants using KarmApp, divided by sub-study. Sub-study Yes (%) No (%) Total KARISMA 2* 1324 (91.9) 116 (8.1) 1440 Karma CREME** 82 (91.1) 8 (8.9) 90 1406 (91.9) 124 (8.1) 1530 * Recruited participants November 2016 to March 2019 **Recruited participants August 2018 to October 2018 Table 1 displays numbers of participants using KarmApp, divided by sub-study. Numbers in parentheses represent the proportions specific to each category. Table 2 Number of Participants who Used KarmApp, divided by Age Group. Age Group Yes (%) No (%) Total 40–49 494 (98.2) 9 (1.8) 503 50–59 471 (94.0) 30 (6.0) 501 60–74 441 (83.8) 85 (16.2) 526 1406 (91.9) 124 (8.1) 1530 Table 2 displays numbers of participants using KarmApp, divided by age group. Numbers in parentheses represent the proportions specific to each category. There were 14,212 user interactions with the KarmApp. The most frequently used feature, "Study Activities Overview," was accessed 8,617 times (60.6%). The "Feedback to Participants" feature was used 2,471 times (17.4%). Furthermore, the "Self-Reporting of Adverse Events" feature was used 1,596 times (11.2%) (Fig. 3 ). Figure 3. Frequencies of KarmApp Feature Usage. Diagram plotting the frequencies of user interactions with the different KarmApp features. A total of 2,081 spontaneous AE reports were received from various sources. The majority, 1,535 (73.8%), were reported through KarmApp, while phone calls were the second most common reporting method (17.5%). Other reporting sources accounted for less than 9.0% of AE reports (Fig. 4 ). Figure 4. Frequency of Adverse Events by Reporting Source. Diagram plotting the frequencies of reported adverse events by reporting source. Table 3 shows differences in AE reporting rates between the two trials: KARISMA 2 (31.0%) and KARMA Creme (47.8%) AE reporting rates. When analyzing the participants across three age groups, the highest frequency of KarmApp usage for AE reporting was observed in the two younger age groups (Table 4 ). Table 3 Number of Participants Reporting Adverse Events Using KarmApp, divided by sub-study. Study Yes (%) No (%) Total KARISMA 2* 447 (31.0) 993 (69.0) 1440 Karma CREME** 43 (47.8) 47 (52.2) 90 490 (32.0) 1040 (68.0) 1530 * Recruited participants November 2016 to March 2019 **Recruited participants August 2018 to October 2018 Table 3 display numbers of participants reporting adverse events, divided by sub-study. Numbers in parentheses represent the proportions specific to each category. Table 4 Number of Participants Reporting Adverse Events Using KarmApp, divided by age group. Age Group Yes (%) No (%) Total 40–49 182 (36.2) 321 (63.8) 503 50–59 185 (36.9) 316 (63.1) 501 60–74 123 (23.4) 403 (76.6) 526 490 (32.0) 1040 (68.0) 1530 Table 4 display numbers of participants reporting adverse events, divided by age group. Numbers in parentheses represent the proportions specific to each category. Out of the 1,530 participants 490 (32.1%) reported at least one AE via KarmApp during the study period. Among these 490, 190 (38.8%) AE reported once, 104 (21.2%) and 66 participants (13.5%) more than five times (Fig. 5 ). Figure 5. Frequencies of Adverse Events Reporting from Unique Participants Diagram plotting the frequencies of adverse events reported by unique participants. The numbers on the X-axis represent how many adverse events each unique participant reported during the study period. Monday and Tuesday were the weekdays with the highest frequency of AE reporting, with approximately twice the number of reports compared to Saturday, which had the lowest frequency of AE reporting ( Supplementary Fig. 3 ). The times of day with the most frequent AE reporting were between 7 am and 11 am, with another peak observed at 9 pm. Conversely, the least frequent AE reporting during the day occurred between midnight and 5 am ( Supplementary Fig. 4 ). Discussion We have presented the KarmApp’s development process and our results and experiences. It highlights the importance of choosing a strategy for building a generic tech platform open to further development and additional features. When comparing experiences from KARISMA 2 and KARMA Creme we observed an increase in usage frequency of KarmApp over time. This can be attributed both to the growing use of smartphones and apps among the public and the continuous optimization of the user-friendliness of KarmApp. The early version of KarmApp used in the KARISMA 2 study underwent iterative improvements based on user feedback from 2017. The positive trends in KarmApp usage were seen across all studied age groups (up to 74 years) (Table 2 ). Of the different functions “Study Activities Overview” was the one most frequently used. This indicates the app's functionality in helping participants manage and adhere to their study schedules, a critical aspect of clinical trial participation. Our data also show that KarmApp offers a more attractive and easily accessible AE reporting tool compared to other reporting channels and underscores an app's potential role in facilitating efficient and accurate AE reporting, a crucial feature for safety and monitoring in clinical trials. Analysis of AE reporting patterns unveiled that a substantial portion occurs during the beginning of the week and in the mornings and evenings. This temporal pattern suggests that participants actively use the app to report events at specific times, possibly aligning with their daily routines ( Supplementary Figs. 2 and 3 ). U sage rates for questionnaire completion with the KarmApp were similar in KARISMA 2 (69.0%) and KARMA Creme (67.1%). Preliminary results from the ongoing KARISMA Endoxifen study [ 20 ] indicate a significantly higher usage rate (97.3%), indicating a positive trend also for more complex tasks using the app ( Supplementary Table 1) . There are however some potential limitations associated with mHealth apps in healthcare and clinical trials, e.g. that not all trial participants have an adequate mobile device. In Sweden, most citizens (92%) owned a mobile device in 2019, with 86% using products that support KarmApp (Android or iPhone). Thus, adding smartphone possession as an inclusion criterion could lead to a selection bias with a risk of skewed results. To address this problem, one possibility is to offer temporary use of devices to non-smartphone-owning participants during the study. On the other hand, in our most recent ongoing trial, KARISMA Endoxifen, initiated in 2021, nearly 100% of the participating women (aged 40–55 years) are using the KarmaApp ( Supplementary Table 1 ). We hope that similar trends would have been seen outside Sweden Implementing apps in clinical trials may face various other challenges, including development costs, legal issues, and negative attitudes among researchers, healthcare professionals, and study participants [ 21 ] [ 5 ] [ 17 ]. Trends in society indicate increased digitalization and the use of mobile technologies. In 2024, there are projected to be 7.13 billion smartphone users worldwide; the current number of smartphone users worldwide is 6.92 billon, accounting for 85.9% of the global population [ 21 ]. In Sweden, smartphone users aged 16–85 years were 7.07 million in 2020 [ 22 ], and the number of monthly active smartphone users is projected to reach 10.82 million individuals by 2028, covering nearly the entire Swedish population [ 23 ]. A vast number of apps are available, with thousands of medical apps (mHealth) being distributed by Google and Apple. The willingness to use mHealth apps and share data for health research is high, and eHealth has been a priority for the World Health Organization (WHO) since 2005. These trends support the exploration and further integration of apps in healthcare and clinical trials. After trial completion, KarmApp offers a channel for relevant feedback to the participants, including the assigned dose and individual and grouped results and quality of life estimates and frequencies of AE) and space for personalized comments, if applicable. Adherence to oral anti-cancer therapies tend to decline over time and is associated with poorer outcomes [ 24 ]. This pose challenges for long-term oral anti-cancer therapies lasting 5–10 years, as in breast cancer treatment and prevention [ 25 ]. To sustain self-care, user-friendly self-management techniques need to be integrated into daily life [ 26 ]. Collecting participant feedback has been useful in the development process conducting a structured evaluation could provide a foundation for further improvements and contribute to a validation of KarmApp. The development process of KarmApp involved several key stages, including requirements specification, design, implementation, testing, deployment, and post-release monitoring. This iterative development approach has ensured that KarmApp has remained effective and user-friendly and fulfilling the needs in our clinical trials. Conclusions KarmApp exemplifies the potential transformative impact in healthcare and clinical research mobile technology can have, which is supported by our data showing trends towards an increased use of the app over time and across age groups. Abbreviations AE Adverse events CRM Customer Relationship Management KARMA KARolinska MAmmography study for Risk Prediction of Breast Cancer WHO World Health Organization Declarations Ethics approval and consent to participate All participants were included after giving informed consent. KARISMA 2 was approved by the ethical review board at Karolinska Institutet, Stockholm, Sweden (dnr 2016/65-31/2). KARMA Creme was approved by the ethical review board Karolinska Institutet, Stockholm, Sweden (dnr 2018/402-31). Availability of data and materials The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Competing interests Not applicable. Funding Not applicable. Authors' contributions JT, MG, MH, YW, AT, ME, KC, PH and MB designed the clinical studies generating the data. JB, PH and MB were active as Investigators during the inclusion of participants. JT and MB designed this study. JT collected and assembled the data. All authors provided major contributions to data analysis and/or interpretation of results. JT drafted the manuscript and JB, KC, PH and MB were major contributors to the writing. All authors consented to publish read and approved the final manuscript. Acknowledgements We sincerely thank all participants in the study. References World Health Organization, "Global diffusion of eHealth: making universal health coverage achievable: report of the third global survey on eHealth," 2016. K. Tabi, A. S. Randhawa, F. Choi, Z. Mithani, F. Albers, M. Schnieder, M. Nikoo, D. Vigo and M. Krausz, "Mobile Apps for Medication Management: Review and Analysis," JMIR Mhealth Uhealth, vol. 7, no. 9, 2019. B. Perry, W. Herrington, J. C. Goldsack, C. A. Grandinetti, K. P. Vasisht, M. J. Landray, L. Bataille, R. A. DiCicco, C. Brandley, A. Narayan, E. J. Papadopoulos, N. Sheth, K. Skodacek, K. Stem, T. V. Strong, M. K. Walton and A. Corneli, "Use of Mobile Devices to Measure Outcomes in Clinical Research, 2010–2016: A Systematic Literature Review," Digit Biomark, vol. 2, no. 1, pp. 11-30, 2018. J. A. Greer, J. M. Jacobs, N. Pensak, L. E. Nisotel, J. N. Fishbein, J. J. MacDonald, M. E. Ream, E. A. Walsh, J. S. Temel, J. Buzaglo, I. T. Lennes, S. A. Safren, A. Muzikansky and W. F. Pirl, "Randomized Trial of a Smartphone Mobile App to Improve Symptoms and Adherence to Oral Therapy for Cancer," Natl Compr Canc Netw, vol. 18, no. 2, pp. 133-141, 2020. K. C. McKenna, C. Geoghegan, T. Swezey, B. Perry, W. A. Wood, V. Nido, S. L. Morin, B. K. Grabert, A. L. Corneli and Z. P. Hallinan, "Investigator Experiences Using Mobile Technologies in Clinical Research: Qualitative Descriptive Study," JMIR Mhealth Uhealth, vol. 9, no. 2, 2021. S. J. Isakoff, M. R. Said, A. H. Kwak, E. Glieberman, E. A. O'Rourke, A. Stroiney, J. M. Peppercorn, L. M. Spring, B. Moy, A. Bardia and N. Horick, "Feasibility of introducing a smartphone navigation application into the care of breast cancer patients (The FIONA Study)," Breast Cancer Res Treat, vol. 199, no. 3, pp. 501-509, 2023. M. M. Vogel, S. E. Combs and K. A. Kessel, "mHealth and Application Technology Supporting Clinical Trials: Today’s Limitations and Future Perspective of smartRCTs," Frontiers in Oncology, vol. 7, no. 37, 2017. M. Bäcklund, M. Eriksson, M. Hammarström, L. Thoren, J. Bergqvist, S. Margolin, R. Hellgren, Y. Wengström, M. Gabrielson, K. Czene and P. Hall, "Time to Mammographic Density Decrease After Exposure to Tamoxifen," Oncologist, vol. 27, no. 7, pp. 601-603, 2022. M. Eriksson, M. Eklund, S. Borgquist, R. Hellgren, S. Margolin, L. Thoren, A. Rosendahl, K. Lång, J. Tapia, M. Bäcklund, A. Discacciati, A. Crippa, M. Gabrielson, M. Hammarström, Y. Wengström, K. Czene and P. Hall, "Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial," Journal of Clinical Oncology, vol. 39, no. 7, pp. 1899-1908, 2021. M. Bäcklund, M. Eriksson, M. Gabrielson, M. Hammarström, S. Quay, J. Bergqvist, R. Hellgren, K. Czene and P. Hall, "Topical Endoxifen for Mammographic Density Reduction-A Randomized Controlled Trial," Oncologist, vol. 27, no. 7, pp. 597-600, 2022. M. Gabrielson, M. Eriksson, M. Hammarström, S. Borgquist, K. Leifland, K. Czene and P. Hall, "Cohort Profile: The Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA)," Int J Epidemiol, vol. 46, no. 6, pp. 1740-1741, 2017. H. Shakirat Oluwatosin, "Client-Server Model," IOSR Journal of Computer Engineering, vol. 6, no. 1, pp. 67-70, 2014. NodeJS, "NodeJS JavaScript runtime," [Online]. Available: https://nodejs.org/en/. [Accessed 2 June 2023]. Microsoft, "Microsoft SQL Server," [Online]. Available: https://www.microsoft.com/en-us/sql-server. [Accessed 2 June 2023]. Microsoft, "Microsoft Dynamics," [Online]. Available: https://dynamics.microsoft.com/en-gb/. [Accessed 2 June 2023]. LIME, "Lime CRM," [Online]. Available: https://www.lime-technologies.com/en/lime-crm/. [Accessed 2 June 2023]. B. Perry, C. Geoghegan, L. Lin, F. H. McGuire, V. Nido, B. Grabert, S. L. Morin, Z. P. Hallinan and A. Corneli, "Patient preferences for using mobile technologies in clinical trials," Contemp Clin Trials Commun, vol. 15, 2019. C. G. Thomas and A. Jayanthila Devi, "A Study and Overview of the Mobile App Development Industry," International Journal of Applied Engineering and Management Letters, vol. 5, no. 1, 2021. C. W. Bæksted, A. Nissen, A. S. Knoop and H. Pappot, "Patients' experience of communication and handling of symptomatic adverse events in breast cancer patients receiving adjuvant chemotherapy," Research Involvement and Engagement, vol. 5, no. 36, 2019. "Effect of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density," [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT05068388. [Accessed 2 June 2023]. Bankmycell, "HOW MANY SMARTPHONES ARE IN THE WORLD?," [Online]. Available: https://www.bankmycell.com/blog/how-many-phones-are-in-the-world. [Accessed 28 September 2023]. SCB Statistics Sweden, "Use of smartphones and its apps (number of persons) by smartphones and apps, sex, study domain and year," [Online]. Available: https://www.statistikdatabasen.scb.se/pxweb/en/ssd/START__LE__LE0108__LE0108J/LE0108T30/. [Accessed 28 September 2023]. Statista, "Number of smartphone users in Sweden 2019-2028," [Online]. Available: https://www.statista.com/statistics/494638/smartphone-users-in-sweden/. [Accessed 10 November 2023]. J. A. Greer, N. Amoyal, L. Nisotel, J. N. Fishbein, J. MacDonald, J. Stagl, I. Lennes, J. S. Temel, S. A. Safren and W. F. Pirl, "Systematic Review of Adherence to Oral Antineoplastic Therapies," Oncologist, vol. 21, no. 3, p. 354–376, 2016. W. He, F. Fang, C. Varnum, M. Eriksson, P. Hall and K. Czene, "Predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer," J Clin Oncol, vol. 33, no. 20, pp. 2262-2269, 2015. K. Anderson, O. Burford and L. Emmerton, "Mobile Health Apps to Facilitate Self-Care: A Qualitative Study of User Experiences," PLoS One, vol. 11, no. 5, 2016. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigure1.docx SupplementaryFigure2.docx SupplementaryFigure3.docx SupplementaryFigure4.docx SupplementaryTable1.docx Cite Share Download PDF Status: Published Journal Publication published 06 Mar, 2025 Read the published version in BMC Health Services Research → Version 1 posted Editorial decision: Revision requested 14 Feb, 2024 Submission checks completed at journal 13 Feb, 2024 Editor assigned by journal 13 Feb, 2024 First submitted to journal 08 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3939874","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272832886,"identity":"7578291f-85a8-4d58-a581-10902a0700d8","order_by":0,"name":"José Tapia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACxgYog42B+TBDAvFaEkBa2JKJ0wIBYKU8xsQpZm5vf/iA8YddHh/7mc8GDxjq5Ag7rOeMsQFDQnIxG0/u5oQEhsOErWKckcMmwZDAnNjGkLv5QALDgcQGwlrSn/9gSKhPbON/8xiopa6eCC0JZkDvH05sk8hhBjqMOYEov0gkpB0vZpN4ZmyQYHDYkKAthsAQ+/DBpjpPvj/5seSPijp5graADU1ggEWiAUENDAwwQxOIUDsKRsEoGAUjFQAAaGU4jcSITWEAAAAASUVORK5CYII=","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":true,"prefix":"","firstName":"José","middleName":"","lastName":"Tapia","suffix":""},{"id":272832887,"identity":"d9d62e26-76b1-4801-a6f4-530c53f5243b","order_by":1,"name":"Marike Gabrielson","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Marike","middleName":"","lastName":"Gabrielson","suffix":""},{"id":272832888,"identity":"71749bfe-9639-4bba-ae81-5e5e9649749d","order_by":2,"name":"Mattias 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1","display":"","copyAsset":false,"role":"figure","size":200948,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKarmApp Client-Server Architecture\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/d5961b3484d44f8b62a25d4e.png"},{"id":51184952,"identity":"9eec5061-2144-4d93-81a1-a9d94c32a386","added_by":"auto","created_at":"2024-02-15 15:50:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":76645,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKarmApp Features\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIllustration of the features available in KarmApp for collecting data and facilitating two-way communication between study staff and participants.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/286886f7a0accfd3310f76fd.png"},{"id":51184793,"identity":"e57ac213-b2ca-44d6-9ab9-640d631a0471","added_by":"auto","created_at":"2024-02-15 15:50:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":77436,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFrequencies of KarmApp Feature Usage.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiagram plotting the frequencies of user interactions with the different KarmApp features.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/58dd902e95dc70acc6e26173.png"},{"id":51184955,"identity":"3778c7cb-aa0d-43b4-aaa0-3ff6adf4d4dd","added_by":"auto","created_at":"2024-02-15 15:50:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":54883,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFrequency of Adverse Events by Reporting Source.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiagram plotting the frequencies of reported adverse events by reporting source.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/a21b9c5281945aab1182d04e.png"},{"id":51184854,"identity":"edf6bcda-93a5-4cd3-8740-f4ff79467731","added_by":"auto","created_at":"2024-02-15 15:50:09","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":45490,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFrequencies of Adverse Events Reporting from Unique Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiagram plotting the frequencies of adverse events reported by unique participants. The numbers on the X-axis represent how many adverse events each unique participant reported during the study period.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/502b90b26fd828858c99825d.png"},{"id":78181470,"identity":"88058f90-2eeb-437d-892c-bf2671806e10","added_by":"auto","created_at":"2025-03-10 17:46:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1446083,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/db9534ad-f371-4405-8297-e33cab97a60f.pdf"},{"id":51184996,"identity":"6d423d95-7fe6-43ad-afeb-808c72a23bdf","added_by":"auto","created_at":"2024-02-15 15:50:13","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":450354,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.docx","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/a7862cd29e9ed0b6745a5949.docx"},{"id":51184844,"identity":"72a67850-2504-45c9-bc0d-a5ed34e85e1c","added_by":"auto","created_at":"2024-02-15 15:50:09","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":266797,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure2.docx","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/5600cb73141906f20fcb4ab4.docx"},{"id":51184959,"identity":"b3b7a5fc-e449-44be-9009-46466393cbd2","added_by":"auto","created_at":"2024-02-15 15:50:12","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":33851,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure3.docx","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/9d1af5e183480096c1d18c1e.docx"},{"id":51184954,"identity":"5c02e8c6-1d29-4d08-8106-f9bf30e6f1dd","added_by":"auto","created_at":"2024-02-15 15:50:11","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":30523,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure4.docx","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/e443a2e5717c3c842504dd27.docx"},{"id":51184841,"identity":"de1f55a3-0d8c-4789-8e0d-85a403fefa1b","added_by":"auto","created_at":"2024-02-15 15:50:08","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":21496,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-3939874/v1/01e85597296fde2486b0bda7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of a reporting and supporting tool in interventional trials - the KarmApp","fulltext":[{"header":"Background","content":"\u003cp\u003eIn recent decades, society has become increasingly digitalized, and telemedicine has rapidly developed, especially in the management of chronic diseases. The World Health Organization (WHO) defines telemedicine tools as \u0026ldquo;mHealth\u0026rdquo; or \u0026ldquo;eHealth,\u0026rdquo; which refers to \u0026ldquo;medical and public health practice supported by mobile devices, such as mobile phones, patient monitoring devices, personal digital assistants, and other wireless devices\u0026rdquo; [1].\u003c/p\u003e\n\u003cp\u003eSmartphones are now widely used, and mobile applications (apps) are increasingly being utilized for self-care and tracking health data. Advanced apps offer tools to improve treatment compliance, facilitate questionnaire responses, and report symptoms [2]. As a result, there is a promising trend of using apps and mobile devices in clinical trials, which can empower participants and improve treatment adherence and follow-up [3] [4]. This also supports data collection and communication in clinical trials, ensuring adherence to Good Clinical Practice (GCP) and reducing under- and incorrectly reported adverse events (AE)\u0026nbsp;[5] [6] [7].\u003c/p\u003e\n\u003cp\u003eOver the past decade, we have conducted several randomized controlled trials involving nearly 2,000 women. These trials focused on breast cancer prevention and tested risk-reducing medications at different doses and formulations [8] [9] [10]. We invited women, attending the Swedish mammography screening program at the Breast Centre S\u0026ouml;dersjukhuset, Stockholm, to participate in the trials. Early on, we recognized the need to develop a means of two-way communication that was safe, efficient, and compatible with our existing systems. As a result, we created a versatile solution called the KarmApp, a smartphone app designed as a generic platform. Our primary focus was on optimizing data quality and safety while ensuring user-friendliness.\u003c/p\u003e\n\u003cp\u003eIn this paper, we describe the development of KarmApp, its features and evolving usage in clinical trials.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eKarmApp is a smartphone app developed in-house and exclusively for the interventional trials in the breast cancer project known as KARMA (KARolinska Mammography study for Risk Prediction of Breast Cancer)\u0026nbsp;[11]. KarmApp is accessible on Android and iOS platforms. Its primary purpose is facilitating seamless two-way communication between the study staff and participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe aim of the study was to evaluate KarmApp\u0026rsquo;s usability and impact in our randomized interventional trials with healthy women aged 40 to 74, assessing its acceptance and effectiveness across age groups in clinical trials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe population included in the report consisted of women aged 40 to 74 who participated in the KARMA project sub-studies; KARISMA 2 [9], and KARMA Creme (also known as ATOS-010) [10].\u003c/p\u003e\n\u003cp\u003eParticipants were invited before visiting the Breast Centre for the general mammography screening. If interested after reading the written study information they were orally informed by a trial physician and were included after giving informed consent. KARISMA 2 recruited participants from November 2016 to March 2019 and KARMA Creme from August 2018 to October 2018. During the inclusion visit participants got a text message containing the login details and instructions for downloading and installing KarmApp on their mobile devices. Additionally, the study staff provided participants with a user guide and a comprehensive orientation to all sections of the app.\u003c/p\u003e\n\u003cp\u003eThe KarmApp platform uses a client-server model with a client app for iPhones and Android smartphones. It employs NodeJS as the server application, which handles communication with a Microsoft SQL Server database through application programming interfaces, ensuring data transmission and retrieval.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKarmApp General Architecture\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe KarmApp platform follows a client-server model architecture [12], comprising a client application that utilizes services provided by a server application (\u003cstrong\u003eFigure 1\u003c/strong\u003e). The client side of the app is designed to be compatible with iPhones and Android smartphones, serving as the user interface for interacting with KarmApp\u0026apos;s features. For the server application, NodeJS, a JavaScript runtime\u0026nbsp;[13]\u0026nbsp;was employed. The NodeJS application functions as the background server, facilitating communication between the client side and the underlying infrastructure. It interacts with a Microsoft SQL Server database\u0026nbsp;[14]\u0026nbsp;for efficient data storage. Application Programming Interfaces (APIs) were developed to manage the app\u0026apos;s functionality, enabling data transmission to, and retrieval from, the database. All logins, messaging and other communication within KarmApp are encrypted to ensure data security and privacy. Importantly, only anonymous data is transferred. Apart from these technically supported safety measures, we acknowledge our ethical responsibility in handling user data, respecting user privacy, obtaining consent for data usage, thus ensuring that the data collection adheres to ethical standards.KarmApp is designed to integrate with Customer Relationship Management (CRM) systems of the different trials for obtaining participants\u0026apos; information and tracking their status in the studies. The described studies utilize Microsoft Dynamics CRM [15] and LIME CRM [16] as CRM systems.\u003c/p\u003e\n\u003cp\u003eThe KarmApp\u0026apos;s interface elements, including pages, fields, forms, icons, text, buttons, labels, and more, are controlled through the database and server. This minimizes the need for frequent app releases for minor interface changes, eliminating the requirement for users to update the app frequently.\u003c/p\u003e\n\u003cp\u003eAs part of KarmApp, an integrated automated system sends text messages to study participants, serving as reminders for various activities during their study participation.\u003c/p\u003e\n\u003cp\u003eFurthermore, KarmApp has been designed as a flexible platform capable of accommodating new interfaces for future KARMA sub-studies. The initial interface development focused on the KARISMA 2 study, and later the app\u0026apos;s architecture was redesigned to accommodate additional interfaces for the KARMA Creme study (and later to the ongoing study KARISMA Endoxifen). The current architecture supports the addition of new interfaces specifically tailored for upcoming studies, allowing the use of a single app with a unified login for KARMA participants across different sub-studies (\u003cstrong\u003eSupplementary Figure 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKarmApp Features\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKarmApp offers a range of features that facilitate study participation (\u003cstrong\u003eFigure 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse Events Reporting:\u003c/strong\u003e KarmApp enables participants to report adverse events (AE) spontaneously and continuously during the trial period. Symptoms can be entered as free text or selected from predefined lists. Participants can indicate the severity of symptoms and provide start and stop dates if required by the study protocol. Reporting of side effects can also be done via various other sources such as telephone, email, or during a visit to the study center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePersonalized Study Activities Overview:\u003c/strong\u003e Participants can access an overview of their study activities, dates for their visits and task completion status. The feature provides a comprehensive view of the different activities associated with their study participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAccess to Study Questionnaires:\u003c/strong\u003e KarmApp includes an embedded link to web-based study questionnaires, allowing participants to conveniently answer them directly within the app.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContact with Study Staff:\u003c/strong\u003e KarmApp enables direct communication between participants and study staff. Users can initiate phone calls, send text messages, or access the study webpage, facilitating communication and support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReminders for Study Medications:\u003c/strong\u003e Participants can configure reminders within the app to ensure the timely administration of study medications. Push notifications serve as reminders for users to take their study medications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePost-Study Feedback:\u003c/strong\u003e Once a study is completed, participants can view personalized information about their participation. This may include details such as the assigned dose or other relevant study-related feedback (\u003cstrong\u003eSupplementary Figure 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePregnancy Test Report:\u003c/strong\u003e If applicable, participants can report their pregnancy test results through KarmApp.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOngoing Medication Report:\u003c/strong\u003e If applicable to the study, participants can report any changes in their ongoing medication and indicate if they were non-compliant with the study medication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDevelopment of KarmApp\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDeveloping a successful smartphone application designed to facilitate and support the study participants and keep a high standard for data transfer and user-friendliness is a complex task [17]. Questions regarding security, privacy and human-computer interaction must be answered to protect highly sensitive patient information.\u003c/p\u003e\n\u003cp\u003eKarmApp meets the three key user preferences for mobile technology in clinical trials [17]:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eInstant Support\u003c/strong\u003e: Participants can contact the trial staff through KarmApp for technical issues, eliminating the need to contact the device manufacturer or app developer.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSecure Data\u003c/strong\u003e: KarmApp ensures secure data transfer and storage using a database server at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. Participant data remains confidential and accessible only to authorized personnel.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eUser-Friendly\u003c/strong\u003e: KarmApp has a user-friendly interface, prioritizing ease of use and intuitiveness. The app requires minimal navigation training and is easy to learn, ensuring a positive user experience for participants.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe development process involved several stages and followed a systematic and iterative approach [18].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRequirements Specification:\u003c/strong\u003e The requirements for KarmApp were defined based on the study protocols through extensive consultation with the study staff. A collaborative effort was undertaken to gather a comprehensive list of requirements outlining the app\u0026apos;s functionality and features.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign:\u003c/strong\u003e Considering the defined requirements, the development team created a detailed design and architecture for KarmApp. This included wireframes and user flow diagrams to visualize the app\u0026apos;s structure and interface. The visual identity was defined through color schemes, typography, and icons to ensure a consistent and appealing user experience (\u003cstrong\u003eSupplementary Figure 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplementation:\u003c/strong\u003e The app\u0026apos;s functionality was implemented using Angular programming language in the Ionic framework, SQL-server programming scripts, and platform-specific tools for iOS and Android. Regular testing and debugging were conducted throughout the implementation phase to identify and address software defects or usability issues.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTesting:\u003c/strong\u003e KarmApp underwent rigorous testing to ensure its functionality, performance, and user experience met the required standards. This involved system testing, user acceptance testing, and validation of compliance with the defined requirements. Testing ensured the app\u0026apos;s stability, reliability, and quality before release.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeployment:\u003c/strong\u003e KarmApp was deployed to the Apple App Store and Google Play Store, making it available to designated end users. This stage involved preparations and processes to release the app to the public, including submission, review, and approval by app store administrators.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePost-Release Maintenance:\u003c/strong\u003e After the release of KarmApp, continuous monitoring mechanisms were implemented to track its performance and identify areas for improvement. This stage involved releasing updates and bug fixes to enhance functionality and user experience over time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKarmApp Versions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe initial version of KarmApp focused on key features such as AE reporting, online questionnaires, participant activity overview, integration with an automated text message system, and direct communication with study staff. In 2017, during its initial development phase, KarmApp underwent evaluation as part of the KARISMA 2 trial [9]. Out of 34 participants contacted, 22 women participated in structured phone interviews, providing feedback on user experiences and user-friendliness. The interviews revealed that 17 out of 22 individuals had downloaded KarmApp, primarily for questionnaires. However, only some discovered the study schedule feature due to insufficient information. Thus, we onwards included that in the user manual. Users also encountered technical issues, with one in three facing login difficulties. Another important finding was that respondents could not provide free-text responses to questions. This evaluation, alongside Patient-Reported Experience Measures [19], contributed to further app development and the creation of a user guide for KarmApp.\u003c/p\u003e\n\u003cp\u003eThe second version, launched later in 2017, introduced significant upgrades involving a complete change in source code and interface design. The focus was on improving user-friendliness and performance. The post-study feature \u0026quot;Feedback to participants\u0026quot; was introduced but remained disabled for participants until the completion of the trials.\u0026nbsp;In the third version, the app\u0026apos;s architecture was redesigned to accommodate an additional interface for the KARMA Creme study. This version allows for the flexible inclusion of new interfaces for future sub-studies. The current version, the fourth version of KarmApp launched in December 2021, includes new features for reporting pregnancy test results and changes in concomitant medications. The database structure and model underwent a redesign, incorporating changes such as adding new tables, modifying existing relationships, optimizing performance, and enhancing scalability, and the integration with the CRM system LIME was implemented.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAge at study inclusion was categorized into age groups 40-49, 50\u0026ndash;59 and 60-74 years; the number of reported AE was categorized into 1, 2, 3, 4 or 5 and \u0026gt;5 times; the reporting source was categorized into app, phone, email, visit to the study center and SMS; and KarmApp features were categorized into study activities overview, feedback to participants, report of adverse events, request a new PIN code and configure reminders.\u003c/p\u003e\n\u003cp\u003eWe utilized exploratory data analysis with descriptive statistics and visualizations, providing graphical representations that aid in understanding patterns, trends and potential outliers. Analyses were conducted using SAS version 9.4 and R version 4.2.1.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 1,530 women participated in two interventional trials: KARISMA 2 (N\u0026thinsp;=\u0026thinsp;1,440) and KARMA Creme (N\u0026thinsp;=\u0026thinsp;90) (see Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Descriptive statistics, categorized into three age groups, are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the participants, 1,406 out of 1,530 (91.9%) used KarmApp, with the highest frequency of usage observed in the two younger age groups.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eNumber of Participants using KarmApp, divided by sub-study.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSub-study\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKARISMA 2*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1324 (91.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e116 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1440\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKarma CREME**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82 (91.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1406 (91.9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e124 (8.1)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1530\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e* Recruited participants November 2016 to March 2019\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e**Recruited participants August 2018 to October 2018\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e displays numbers of participants using KarmApp, divided by sub-study. Numbers in parentheses represent the proportions specific to each category.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eNumber of Participants who Used KarmApp, divided by Age Group.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge Group\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u0026ndash;49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e494 (98.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e503\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u0026ndash;59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e471 (94.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e501\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u0026ndash;74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e441 (83.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e85 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e526\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1406 (91.9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e124 (8.1)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1530\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e displays numbers of participants using KarmApp, divided by age group. Numbers in parentheses represent the proportions specific to each category.\u003c/p\u003e\n\u003cp\u003eThere were 14,212 user interactions with the KarmApp. The most frequently used feature, \u0026quot;Study Activities Overview,\u0026quot; was accessed 8,617 times (60.6%). The \u0026quot;Feedback to Participants\u0026quot; feature was used 2,471 times (17.4%). Furthermore, the \u0026quot;Self-Reporting of Adverse Events\u0026quot; feature was used 1,596 times (11.2%) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 3. Frequencies of KarmApp Feature Usage.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiagram plotting the frequencies of user interactions with the different KarmApp features.\u003c/p\u003e\n\u003cp\u003eA total of 2,081 spontaneous AE reports were received from various sources. The majority, 1,535 (73.8%), were reported through KarmApp, while phone calls were the second most common reporting method (17.5%). Other reporting sources accounted for less than 9.0% of AE reports (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 4. Frequency of Adverse Events by Reporting Source.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiagram plotting the frequencies of reported adverse events by reporting source.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows differences in AE reporting rates between the two trials: KARISMA 2 (31.0%) and KARMA Creme (47.8%) AE reporting rates. When analyzing the participants across three age groups, the highest frequency of KarmApp usage for AE reporting was observed in the two younger age groups (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eNumber of Participants Reporting Adverse Events Using KarmApp, divided by sub-study.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKARISMA 2*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e447 (31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e993 (69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1440\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKarma CREME**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43 (47.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47 (52.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e490 (32.0)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1040 (68.0)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1530\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e* Recruited participants November 2016 to March 2019\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e**Recruited participants August 2018 to October 2018\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e display numbers of participants reporting adverse events, divided by sub-study. Numbers in parentheses represent the proportions specific to each category.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eNumber of Participants Reporting Adverse Events Using KarmApp, divided by age group.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge Group\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u0026ndash;49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e182 (36.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e321 (63.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e503\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u0026ndash;59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e185 (36.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e316 (63.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e501\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u0026ndash;74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e123 (23.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e403 (76.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e526\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e490 (32.0)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1040 (68.0)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1530\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e display numbers of participants reporting adverse events, divided by age group. Numbers in parentheses represent the proportions specific to each category.\u003c/p\u003e\n\u003cp\u003eOut of the 1,530 participants 490 (32.1%) reported at least one AE via KarmApp during the study period. Among these 490, 190 (38.8%) AE reported once, 104 (21.2%) and 66 participants (13.5%) more than five times (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 5. Frequencies of Adverse Events Reporting from Unique Participants\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiagram plotting the frequencies of adverse events reported by unique participants. The numbers on the X-axis represent how many adverse events each unique participant reported during the study period.\u003c/p\u003e\n\u003cp\u003eMonday and Tuesday were the weekdays with the highest frequency of AE reporting, with approximately twice the number of reports compared to Saturday, which had the lowest frequency of AE reporting (\u003cstrong\u003eSupplementary Fig.\u0026nbsp;3\u003c/strong\u003e). The times of day with the most frequent AE reporting were between 7 am and 11 am, with another peak observed at 9 pm. Conversely, the least frequent AE reporting during the day occurred between midnight and 5 am (\u003cstrong\u003eSupplementary Fig.\u0026nbsp;4\u003c/strong\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe have presented the KarmApp\u0026rsquo;s development process and our results and experiences. It highlights the importance of choosing a strategy for building a generic tech platform open to further development and additional features. When comparing experiences from KARISMA 2 and KARMA Creme we observed an increase in usage frequency of KarmApp over time. This can be attributed both to the growing use of smartphones and apps among the public and the continuous optimization of the user-friendliness of KarmApp. The early version of KarmApp used in the KARISMA 2 study underwent iterative improvements based on user feedback from 2017.\u003c/p\u003e \u003cp\u003eThe positive trends in KarmApp usage were seen across all studied age groups (up to 74 years) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Of the different functions \u0026ldquo;Study Activities Overview\u0026rdquo; was the one most frequently used. This indicates the app's functionality in helping participants manage and adhere to their study schedules, a critical aspect of clinical trial participation. Our data also show that KarmApp offers a more attractive and easily accessible AE reporting tool compared to other reporting channels and underscores an app's potential role in facilitating efficient and accurate AE reporting, a crucial feature for safety and monitoring in clinical trials.\u003c/p\u003e \u003cp\u003eAnalysis of AE reporting patterns unveiled that a substantial portion occurs during the beginning of the week and in the mornings and evenings. This temporal pattern suggests that participants actively use the app to report events at specific times, possibly aligning with their daily routines (\u003cb\u003eSupplementary Figs.\u0026nbsp;2 and 3\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eU\u003c/b\u003esage rates for questionnaire completion with the KarmApp were similar in KARISMA 2 (69.0%) and KARMA Creme (67.1%). Preliminary results from the ongoing KARISMA Endoxifen study [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] indicate a significantly higher usage rate (97.3%), indicating a positive trend also for more complex tasks using the app (\u003cb\u003eSupplementary Table\u0026nbsp;1)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThere are however some potential limitations associated with mHealth apps in healthcare and clinical trials, e.g. that not all trial participants have an adequate mobile device. In Sweden, most citizens (92%) owned a mobile device in 2019, with 86% using products that support KarmApp (Android or iPhone). Thus, adding smartphone possession as an inclusion criterion could lead to a selection bias with a risk of skewed results. To address this problem, one possibility is to offer temporary use of devices to non-smartphone-owning participants during the study. On the other hand, in our most recent ongoing trial, KARISMA Endoxifen, initiated in 2021, nearly 100% of the participating women (aged 40\u0026ndash;55 years) are using the KarmaApp (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). We hope that similar trends would have been seen outside Sweden\u003c/p\u003e \u003cp\u003eImplementing apps in clinical trials may face various other challenges, including development costs, legal issues, and negative attitudes among researchers, healthcare professionals, and study participants [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Trends in society indicate increased digitalization and the use of mobile technologies. In 2024, there are projected to be 7.13\u0026nbsp;billion smartphone users worldwide; the current number of smartphone users worldwide is 6.92 billon, accounting for 85.9% of the global population [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In Sweden, smartphone users aged 16\u0026ndash;85 years were 7.07\u0026nbsp;million in 2020 [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and the number of monthly active smartphone users is projected to reach 10.82\u0026nbsp;million individuals by 2028, covering nearly the entire Swedish population [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA vast number of apps are available, with thousands of medical apps (mHealth) being distributed by Google and Apple. The willingness to use mHealth apps and share data for health research is high, and eHealth has been a priority for the World Health Organization (WHO) since 2005. These trends support the exploration and further integration of apps in healthcare and clinical trials.\u003c/p\u003e \u003cp\u003eAfter trial completion, KarmApp offers a channel for relevant feedback to the participants, including the assigned dose and individual and grouped results and quality of life estimates and frequencies of AE) and space for personalized comments, if applicable.\u003c/p\u003e \u003cp\u003eAdherence to oral anti-cancer therapies tend to decline over time and is associated with poorer outcomes [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This pose challenges for long-term oral anti-cancer therapies lasting 5\u0026ndash;10 years, as in breast cancer treatment and prevention [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. To sustain self-care, user-friendly self-management techniques need to be integrated into daily life [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCollecting participant feedback has been useful in the development process conducting a structured evaluation could provide a foundation for further improvements and contribute to a validation of KarmApp.\u003c/p\u003e \u003cp\u003eThe development process of KarmApp involved several key stages, including requirements specification, design, implementation, testing, deployment, and post-release monitoring. This iterative development approach has ensured that KarmApp has remained effective and user-friendly and fulfilling the needs in our clinical trials.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eKarmApp exemplifies the potential transformative impact in healthcare and clinical research mobile technology can have, which is supported by our data showing trends towards an increased use of the app over time and across age groups.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdverse events\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCustomer Relationship Management\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKARMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKARolinska MAmmography study for Risk Prediction of Breast Cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eAll participants were included after giving informed consent.\u003c/p\u003e\n\u003cp\u003eKARISMA 2 was approved by the ethical review board at Karolinska Institutet, Stockholm, Sweden (dnr 2016/65-31/2). KARMA Creme was approved by the ethical review board Karolinska Institutet, Stockholm, Sweden (dnr 2018/402-31).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003eJT, MG, MH, YW, AT, ME, KC, PH and MB designed the clinical studies generating the data. JB, PH and MB were active as Investigators during the inclusion of participants. JT and MB designed this study. JT collected and assembled the data. All authors provided major contributions to data analysis and/or interpretation of results. JT drafted the manuscript and JB, KC, PH and MB were major contributors to the writing. All authors consented to publish read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe sincerely thank all participants in the study. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWorld Health Organization, \u0026quot;Global diffusion of eHealth: making universal health coverage achievable: report of the third global survey on eHealth,\u0026quot; 2016.\u003c/li\u003e\n \u003cli\u003eK. Tabi, A. S. Randhawa, F. Choi, Z. Mithani, F. Albers, M. Schnieder, M. Nikoo, D. Vigo and M. Krausz, \u0026quot;Mobile Apps for Medication Management: Review and Analysis,\u0026quot; \u003cem\u003eJMIR Mhealth Uhealth,\u0026nbsp;\u003c/em\u003evol. 7, no. 9, 2019.\u003c/li\u003e\n \u003cli\u003eB. Perry, W. Herrington, J. C. Goldsack, C. A. Grandinetti, K. P. Vasisht, M. J. Landray, L. Bataille, R. A. DiCicco, C. Brandley, A. Narayan, E. J. Papadopoulos, N. Sheth, K. Skodacek, K. Stem, T. V. Strong, M. K. Walton and A. Corneli, \u0026quot;Use of Mobile Devices to Measure Outcomes in Clinical Research, 2010\u0026ndash;2016: A Systematic Literature Review,\u0026quot; \u003cem\u003eDigit Biomark,\u0026nbsp;\u003c/em\u003evol. 2, no. 1, pp. 11-30, 2018.\u003c/li\u003e\n \u003cli\u003eJ. A. Greer, J. M. Jacobs, N. Pensak, L. E. Nisotel, J. N. Fishbein, J. J. MacDonald, M. E. Ream, E. A. Walsh, J. S. Temel, J. Buzaglo, I. T. Lennes, S. A. Safren, A. Muzikansky and W. F. Pirl, \u0026quot;Randomized Trial of a Smartphone Mobile App to Improve Symptoms and Adherence to Oral Therapy for Cancer,\u0026quot; \u003cem\u003eNatl Compr Canc Netw,\u0026nbsp;\u003c/em\u003evol. 18, no. 2, pp. 133-141, 2020.\u003c/li\u003e\n \u003cli\u003eK. C. McKenna, C. Geoghegan, T. Swezey, B. Perry, W. A. Wood, V. Nido, S. L. Morin, B. K. Grabert, A. L. Corneli and Z. P. Hallinan, \u0026quot;Investigator Experiences Using Mobile Technologies in Clinical Research: Qualitative Descriptive Study,\u0026quot; \u003cem\u003eJMIR Mhealth Uhealth,\u0026nbsp;\u003c/em\u003evol. 9, no. 2, 2021.\u003c/li\u003e\n \u003cli\u003eS. J. Isakoff, M. R. Said, A. H. Kwak, E. Glieberman, E. A. O\u0026apos;Rourke, A. Stroiney, J. M. Peppercorn, L. M. Spring, B. Moy, A. Bardia and N. Horick, \u0026quot;Feasibility of introducing a smartphone navigation application into the care of breast cancer patients (The FIONA Study),\u0026quot; \u003cem\u003eBreast Cancer Res Treat,\u0026nbsp;\u003c/em\u003evol. 199, no. 3, pp. 501-509, 2023.\u003c/li\u003e\n \u003cli\u003eM. M. Vogel, S. E. Combs and K. A. Kessel, \u0026quot;mHealth and Application Technology Supporting Clinical Trials: Today\u0026rsquo;s Limitations and Future Perspective of smartRCTs,\u0026quot; \u003cem\u003eFrontiers in Oncology,\u0026nbsp;\u003c/em\u003evol. 7, no. 37, 2017.\u003c/li\u003e\n \u003cli\u003eM. B\u0026auml;cklund, M. Eriksson, M. Hammarstr\u0026ouml;m, L. Thoren, J. Bergqvist, S. Margolin, R. Hellgren, Y. Wengstr\u0026ouml;m, M. Gabrielson, K. Czene and P. Hall, \u0026quot;Time to Mammographic Density Decrease After Exposure to Tamoxifen,\u0026quot; \u003cem\u003eOncologist,\u0026nbsp;\u003c/em\u003evol. 27, no. 7, pp. 601-603, 2022.\u003c/li\u003e\n \u003cli\u003eM. Eriksson, M. Eklund, S. Borgquist, R. Hellgren, S. Margolin, L. Thoren, A. Rosendahl, K. L\u0026aring;ng, J. Tapia, M. B\u0026auml;cklund, A. Discacciati, A. Crippa, M. Gabrielson, M. Hammarstr\u0026ouml;m, Y. Wengstr\u0026ouml;m, K. Czene and P. Hall, \u0026quot;Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial,\u0026quot; \u003cem\u003eJournal of Clinical Oncology,\u0026nbsp;\u003c/em\u003evol. 39, no. 7, pp. 1899-1908, 2021.\u003c/li\u003e\n \u003cli\u003eM. B\u0026auml;cklund, M. Eriksson, M. Gabrielson, M. Hammarstr\u0026ouml;m, S. Quay, J. Bergqvist, R. Hellgren, K. Czene and P. Hall, \u0026quot;Topical Endoxifen for Mammographic Density Reduction-A Randomized Controlled Trial,\u0026quot; \u003cem\u003eOncologist,\u0026nbsp;\u003c/em\u003evol. 27, no. 7, pp. 597-600, 2022.\u003c/li\u003e\n \u003cli\u003eM. Gabrielson, M. Eriksson, M. Hammarstr\u0026ouml;m, S. Borgquist, K. Leifland, K. Czene and P. Hall, \u0026quot;Cohort Profile: The Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA),\u0026quot; \u003cem\u003eInt J Epidemiol,\u0026nbsp;\u003c/em\u003evol. 46, no. 6, pp. 1740-1741, 2017.\u003c/li\u003e\n \u003cli\u003eH. Shakirat Oluwatosin, \u0026quot;Client-Server Model,\u0026quot; \u003cem\u003eIOSR Journal of Computer Engineering,\u0026nbsp;\u003c/em\u003evol. 6, no. 1, pp. 67-70, 2014.\u003c/li\u003e\n \u003cli\u003eNodeJS, \u0026quot;NodeJS JavaScript runtime,\u0026quot; [Online]. Available: https://nodejs.org/en/. [Accessed 2 June 2023].\u003c/li\u003e\n \u003cli\u003eMicrosoft, \u0026quot;Microsoft SQL Server,\u0026quot; [Online]. Available: https://www.microsoft.com/en-us/sql-server. [Accessed 2 June 2023].\u003c/li\u003e\n \u003cli\u003eMicrosoft, \u0026quot;Microsoft Dynamics,\u0026quot; [Online]. Available: https://dynamics.microsoft.com/en-gb/. [Accessed 2 June 2023].\u003c/li\u003e\n \u003cli\u003eLIME, \u0026quot;Lime CRM,\u0026quot; [Online]. Available: https://www.lime-technologies.com/en/lime-crm/. [Accessed 2 June 2023].\u003c/li\u003e\n \u003cli\u003eB. Perry, C. Geoghegan, L. Lin, F. H. McGuire, V. Nido, B. Grabert, S. L. Morin, Z. P. Hallinan and A. Corneli, \u0026quot;Patient preferences for using mobile technologies in clinical trials,\u0026quot; \u003cem\u003eContemp Clin Trials Commun,\u0026nbsp;\u003c/em\u003evol. 15, 2019.\u003c/li\u003e\n \u003cli\u003eC. G. Thomas and A. Jayanthila Devi, \u0026quot;A Study and Overview of the Mobile App Development Industry,\u0026quot; \u003cem\u003eInternational Journal of Applied Engineering and Management Letters,\u0026nbsp;\u003c/em\u003evol. 5, no. 1, 2021.\u003c/li\u003e\n \u003cli\u003eC. W. B\u0026aelig;ksted, A. Nissen, A. S. Knoop and H. Pappot, \u0026quot;Patients\u0026apos; experience of communication and handling of symptomatic adverse events in breast cancer patients receiving adjuvant chemotherapy,\u0026quot; \u003cem\u003eResearch Involvement and Engagement,\u0026nbsp;\u003c/em\u003evol. 5, no. 36, 2019.\u003c/li\u003e\n \u003cli\u003e\u0026quot;Effect of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density,\u0026quot; [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT05068388. [Accessed 2 June 2023].\u003c/li\u003e\n \u003cli\u003eBankmycell, \u0026quot;HOW MANY SMARTPHONES ARE IN THE WORLD?,\u0026quot; [Online]. Available: https://www.bankmycell.com/blog/how-many-phones-are-in-the-world. [Accessed 28 September 2023].\u003c/li\u003e\n \u003cli\u003eSCB Statistics Sweden, \u0026quot;Use of smartphones and its apps (number of persons) by smartphones and apps, sex, study domain and year,\u0026quot; [Online]. Available: https://www.statistikdatabasen.scb.se/pxweb/en/ssd/START__LE__LE0108__LE0108J/LE0108T30/. [Accessed 28 September 2023].\u003c/li\u003e\n \u003cli\u003eStatista, \u0026quot;Number of smartphone users in Sweden 2019-2028,\u0026quot; [Online]. Available: https://www.statista.com/statistics/494638/smartphone-users-in-sweden/. [Accessed 10 November 2023].\u003c/li\u003e\n \u003cli\u003eJ. A. Greer, N. Amoyal, L. Nisotel, J. N. Fishbein, J. MacDonald, J. Stagl, I. Lennes, J. S. Temel, S. A. Safren and W. F. Pirl, \u0026quot;Systematic Review of Adherence to Oral Antineoplastic Therapies,\u0026quot; \u003cem\u003eOncologist,\u0026nbsp;\u003c/em\u003evol. 21, no. 3, p. 354\u0026ndash;376, 2016.\u003c/li\u003e\n \u003cli\u003eW. He, F. Fang, C. Varnum, M. Eriksson, P. Hall and K. Czene, \u0026quot;Predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer,\u0026quot; \u003cem\u003eJ Clin Oncol,\u0026nbsp;\u003c/em\u003evol. 33, no. 20, pp. 2262-2269, 2015.\u003c/li\u003e\n \u003cli\u003eK. Anderson, O. Burford and L. Emmerton, \u0026quot;Mobile Health Apps to Facilitate Self-Care: A Qualitative Study of User Experiences,\u0026quot; \u003cem\u003ePLoS One,\u0026nbsp;\u003c/em\u003evol. 11, no. 5, 2016.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Adverse event reporting, smartphone application, randomized clinical trials, data quality, clinical trials.","lastPublishedDoi":"10.21203/rs.3.rs-3939874/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3939874/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn an increasingly digitalized world, telemedicine and mobile health tools have emerged as powerful resources in clinical trials and in managing chronic diseases. We have developed KarmApp, a smartphone application, to optimize data quality, safety and user-friendliness in our breast cancer prevention trials. The aim of this study was to evaluate the performance and the usage of the KarmApp over time.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe KarmApp functions include adverse event reporting, personalized study activity overviews, study questionnaires, and direct communication with study staff. Users are healthy women aged 40 to 74 participating in our randomized interventional trials evaluating risk-reducing medications at different doses and formulations. Development and deployment have followed a systematic, iterative approach, from requirements specification to post-release monitoring. We have calculated the usage frequencies of the various KarmApp features and performed statistical analysis across age groups and respective trials using SAS version 9.4 and R version 4.2.1.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOf the participants in the randomized clinical trials KARISMA 2 (N\u0026thinsp;=\u0026thinsp;1,440) and KARMA Creme (N\u0026thinsp;=\u0026thinsp;90), 1406 (91.9%) used the KarmApp, across all age groups. There were 14,212 user interactions with the KarmApp, with the \u0026ldquo;Study Activities Overview\u0026rdquo; being the most frequently used. A total of 2,081 spontaneous adverse event reports collected in the trials. The majority, 1,535 (73.8%), were reported through KarmApp, less via the other reporting channels.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eKarmApp exemplifies the potential for transformative impacts in healthcare and clinical research, which is supported by our data showing trends towards an increased use of the app over time. Our experiences of KarmApp reflects the growing acceptance of mobile technology across age groups, presenting opportunities for further integration in clinical trials.\u003c/p\u003e","manuscriptTitle":"Evaluation of a reporting and supporting tool in interventional trials - the KarmApp","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-15 15:49:55","doi":"10.21203/rs.3.rs-3939874/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-14T12:57:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-13T15:14:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-13T15:14:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Health Services Research","date":"2024-02-08T12:05:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a5b2c45-ea7f-4b47-990c-fff672b76fbf","owner":[],"postedDate":"February 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-10T17:09:26+00:00","versionOfRecord":{"articleIdentity":"rs-3939874","link":"https://doi.org/10.1186/s12913-025-12471-9","journal":{"identity":"bmc-health-services-research","isVorOnly":false,"title":"BMC Health Services Research"},"publishedOn":"2025-03-06 15:57:10","publishedOnDateReadable":"March 6th, 2025"},"versionCreatedAt":"2024-02-15 15:49:55","video":"","vorDoi":"10.1186/s12913-025-12471-9","vorDoiUrl":"https://doi.org/10.1186/s12913-025-12471-9","workflowStages":[]},"version":"v1","identity":"rs-3939874","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3939874","identity":"rs-3939874","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}