Preferences for Injection Device Settings and the Association with Adherence to Growth Hormone Treatment in Patient with Growth Disorders.

Adherence to recombinant human growth hormone (r-hGH; somatropin, [Saizen®], Merck Healthcare KGaA, Darmstadt, Germany) treatment is important to achieve positive growth and other outcomes in children with growth disorders. Automated injection devices can facilitate the delivery of r-hGH, injections of which are required daily for a number of years. The ability to adjust injection device settings may improve patient comfort and needle anxiety, influencing adoption and acceptance of such devices, thereby improving treatment adherence. Here, we present the results of a retrospective observational study which investigated the association between injection device settings and adherence in the first 3 months of treatment in patients with growth disorders. Patients aged ≥2 and <18.75 years of age at treatment start, with ≥3 months of adherence data from start of treatment with the third generation of the easypod® device (EP3; Merck Healthcare KGaA, Darmstadt, Germany) were selected (N=832). The two most chosen combinations of device settings at treatment start were the default settings for injection speed, depth and time, or a slow injection speed and default depth and time. These combinations also demonstrated the highest adherence rates (94% and 95%, respectively) compared to other device settings (89%). A higher proportion of patients with intermediate/low adherence in the first month of treatment (31%, n=18/59) changed the device settings during treatment compared with those with high adherence (16%, n=128/803) (p=0.005). The ability to adjust injection device settings offers a valuable opportunity for personalizing treatment, improving patient comfort and treatment adherence.

The growzen™ buddy smartphone app to improve adherence in patients receiving recombinant human growth hormone therapy: a retrospective observational study in Argentina.

Introduction: This study in Argentina evaluated the impact of the growzen™ buddy smartphone app on adherence to recombinant human growth hormone (r-hGH) treatment. Methods: The adherence data, invitation dates with a link to the app, app activation dates, and height measurements entered were extracted from the growzen™ digital health ecosystem. Patients with 12 months of adherence data, aged ≥2 years at treatment start, and aged <19 years were selected both before and after app implementation. Mean adherence was classified as optimal (≥85%) versus suboptimal (<85%). Adherence before and after implementation and the pre-post effect on adherence were assessed. Results: Data for 830 patients were available. Prior to app implementation, the proportion of patients with optimal adherence was 68% (n = 348/515). Following the app implementation, out of 315 patients, 302 (96%) received an invitation with a link to the app, 225 (71%) activated their account, and 127 (40%) entered height data in the first year. There was a significant early increase in the proportion of patients with optimal adherence following implementation: 82% (n = 258/315), p < 0.001. After implementation, the proportion of patients with optimal adherence included 80% (n = 78/98) of those with an active account who did not enter height measurements and 89% (n = 113/127) of those who did. There was a significant and positive pre-post app effect on adherence (p < 0.01) in patients with an active account. Discussion: Our results show that using the growzen™ buddy app has a rapid and positive impact on adherence to r-hGH treatment, and patients who were more engaged with the app demonstrated better adherence.

Assessment of adherence to, and persistence with, an electromechanical autoinjector for subcutaneous interferon beta-1a injections for multiple sclerosis treatment over 3 years.

BACKGROUND: Self-administration of subcutaneous interferon beta-1a (sc IFN ß-1a) can be achieved with the RebiSmart® electromechanical autoinjector. This study investigated adherence to, and duration of persistence with, the newest version of the device (v1.6) among 2644 people receiving sc IFN ß-1a for multiple sclerosis (MS). RESEARCH DESIGN AND METHODS: This retrospective, observational study utilized data from RebiSmart® devices, recorded on the MSdialog database, between January 2014 and November 2019. Adherence and persistence were evaluated over a 3-year period and assessed in relation to age, sex, injection type, and injection depth. RESULTS: The population of RebiSmart® users (N = 2644) comprised of 1826 (69.1%) females and mean age was 39 (range 16-83) years. Adherence to RebiSmart® use and data transfer to the MSdialog database was consistently high (mean 91.7%; range 86.8-92.6%), including across all variables (81.6-100%). Mean (±SD) persistence during the study period was 1.35 ± 1.06 years, with a maximum recorded persistence of 5.1 years. In multivariate analysis, the longest durations of persistence were observed among older individuals and males (p < 0.0001 and p = 0.0078, respectively). CONCLUSIONS: People living with MS were highly adherent to use of the RebiSmart® device, with higher persistence generally observed for older and/or male individuals.

It is important for people living with multiple sclerosis (MS) to take their medication regularly ­ and to keep doing so ­ in order to control their symptoms. Some people with MS receive a medication called interferon beta-1a (Rebif®) as a subcutaneous injection (given just under the skin), and the RebiSmart® electromechanical autoinjector was designed to help them to self-inject such medication. This study aimed to find out whether people were using the RebiSmart® device as often as they should be, and how long they continued to use it for. Information was taken from the MSdialog database, which recorded peoples' use of the RebiSmart® device between January 2014 and November 2019. Records for 2644 people using the device were analyzed. Results showed that the RebiSmart® device was used most of the time (around 91.7%). On average, people kept using the device for around a year and 4 months before stopping. This duration was generally longer for men compared with women, and longer for older people than younger people. These results increase our understanding of how people are using the RebiSmart® device to treat their MS symptoms.

Curve matching to predict growth in patients receiving growth hormone therapy: An interpretable & explainable method.

Curve matching may be used to predict growth outcomes using data of patients whose growth curves resemble those of a new patient with growth hormone deficiency (GHD) and those born small for gestational age (SGA). We aimed to investigate the validity of curve matching to predict growth in patients with GHD and those born SGA receiving recombinant human growth hormone (r-hGH). Height data collected between 0-48 months of treatment were extracted from the easypod™ connect ecosystem and the easypod™ connect observational study. Selected patients with height standard deviation scores (HSDS) [-4, <-1] and age [3, <16y] at start were included. The 'Matching Database' consisted of patients' monthly HSDS obtained by the broken stick method and imputation. Standard deviation (SD) was obtained from the observed minus the predicted HSDS (error) based on matched patients within the 'Matching Database'. Data were available for 3,213 patients in the 'Matching Database', and 2,472 patients with 16,624 HSDS measurements in the observed database. When ≥2 HSDS measurements were available, the error SD for a one-year prediction was approximately 0.2, which corresponds to 1.1 cm, 1.3 cm, and 1.5 cm at 7, 11, and 15 years of age, respectively. Indication and age at treatment start (<11 vs ≥11 years) had a small impact on the error SD, with patients born SGA and patients aged <11 years at treatment start generally having slightly lower values. We conclude that curve matching is a simple and valid technique for predicting growth in patients with GHD and those born SGA.

Integrated Digital Health Solutions in the Management of Growth Disorders in Pediatric Patients Receiving Growth Hormone Therapy: A Retrospective Analysis.

Digital health has seen rapid advancements over the last few years in helping patients and their healthcare professionals better manage treatment for a variety of illnesses, including growth hormone (GH) therapy for growth disorders in children and adolescents. For children and adolescents requiring such therapy, as well as for their parents, the treatment is longitudinal and often involves daily injections plus close progress monitoring; a sometimes daunting task when young children are involved. Here, we describe our experience in offering devices and digital health tools to support GH therapy across some 40 countries. We also discuss how this ecosystem of care has evolved over the years based on learnings and advances in technology. Finally, we offer a glimpse of future planned enhancements and directions for digital health to play a bigger role in better managing conditions treated with GH therapy, as well as model development for adherence prediction. The continued aim of these technologies is to improve clinical decision making and support for GH-treated patients, leading to better outcomes.

Use of machine learning to identify patients at risk of sub-optimal adherence: study based on real-world data from 10,929 children using a connected auto-injector device.

BACKGROUND: Our aim was to develop a machine learning model, using real-world data captured from a connected auto-injector device and from early indicators from the first 3 months of treatment, to predict sub-optimal adherence to recombinant human growth hormone (r-hGH) in patients with growth disorders. METHODS: Adherence to r-hGH treatment was assessed in children (aged < 18 years) who started using a connected auto-injector device (easypod™), and transmitted injection data for ≥ 12 months. Adherence in the following 3, 6, or 9 months after treatment start was categorized as optimal (≥ 85%) versus sub-optimal (< 85%). Logistic regression and tree-based models were applied. RESULTS: Data from 10,929 children showed that a random forest model with mean and standard deviation of adherence over the first 3 months, infrequent transmission of data, not changing certain comfort settings, and starting treatment at an older age was important in predicting the risk of sub-optimal adherence in the following 3, 6, or 9 months. Sensitivities ranged between 0.72 and 0.77, and specificities between 0.80 and 0.81. CONCLUSIONS: To the authors' knowledge, this is the first attempt to integrate a machine learning model into a digital health ecosystem to help healthcare providers to identify patients at risk of sub-optimal adherence to r-hGH in the following 3, 6, or 9 months. This information, together with patient-specific indicators of sub-optimal adherence, can be used to provide support to at-risk patients and their caregivers to achieve optimal adherence and, subsequently, improve clinical outcomes.

Adherence to Growth Hormone Treatment Using a Connected Device in Latin America: Real-World Exploratory Descriptive Analysis Study.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy is an effective treatment for children with growth disorders. However, poor outcomes are often associated with suboptimal adherence to treatment. OBJECTIVE: The easypod connected injection device records and transmits injection settings and dose data from patients receiving rhGH. In this study, we evaluated adherence to rhGH treatment, and associated growth outcomes, in Latin American patients. METHODS: Adherence and growth data from patients aged 2-18 years from 12 Latin American countries were analyzed. Adherence data were available for 6207 patients with 2,449,879 injections, and growth data were available for 497 patients with 2232 measurements. Adherence was categorized, based on milligrams of rhGH injected versus milligrams of rhGH prescribed, as high (≥85%), intermediate (>56%-<85%), or low (≤56%). Transmission frequency was categorized as high (≥1 per 3 months) or low (<1 per 3 months). Chi-square tests were applied to study the effect of pubertal status at treatment start and sex on high adherence, and to test differences in frequency transmission between the three adherence levels. Multilevel linear regression techniques were applied to study the effect of adherence on observed change in height standard deviation score (∆HSDS). RESULTS: Overall, 68% (4213/6207), 25% (n=1574), and 7% (n=420) of patients had high, intermediate, and low adherence, respectively. Pubertal status at treatment start and sex did not have a significant effect on high adherence. Significant differences were found in the proportion of patients with high transmission frequency between high (2018/3404, 59%), intermediate (608/1331, 46%), and low (123/351, 35%) adherence groups (P<.001). Adherence level had a significant effect on ∆HSDS (P=.006). Mean catch-up growth between 0-24 months was +0.65 SD overall (+0.52 SD in patients with low/intermediate monthly adherence and +0.69 SD in patients with high monthly adherence). This difference translated into 1.1 cm greater catch-up growth with high adherence. CONCLUSIONS: The data extracted from the easypod Connect ecosystem showed high adherence to rhGH treatment in Latin American patients, with positive growth outcomes, indicating the importance of connected device solutions for rhGH treatment in patients with growth disorders.

High Engagement of Patients Monitored by a Digital Health Ecosystem Indicates Significant Improvements of Key r-hGH Treatment Metrics.

The early adoption of digital health solutions in the treatment of growth disorders has enabled the collection and analysis of more than 10 years of real-world data using the easypod™ connect platform. Using this rich dataset, we were able to study the impact of engagement on three key treatment-related outcomes: adherence, persistence of use, and growth. In total, data for 17,906 patients were available. The three features, regularity of injection (≤2h vs >2h), change of comfort setting (yes/no), and opting-in to receive injection reminders (yes/no), were used as a proxy for engagement. Patients were assigned to the low-engagement group (n=1,752) when all of their features had the low-engagement flag (>2h, no, no) and to the high-engagement group (n=1,081) when all of their features had the high-engagement flag (≤2h, yes, yes). The low-engagement group was down-sampled to 1,081 patients (subsample of n=37 for growth) using the iterative proportional fitting algorithm. Statistical tests were used to study the impact of engagement to the outcomes. The results show that all three outcomes were significantly improved by a factor varying from 1.8 up to 2.2 when the engagement level was high. These results should encourage the promotion of engagement and associated behaviors by both patients and healthcare professionals.