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  • 1
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A672-A673
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A672-A673
    Abstract: Background: Suboptimal adherence to recombinant human growth hormone (r-hGH) treatment can lead to suboptimal clinical outcomes. Being able to identify children who are at risk of suboptimal adherence in the near future, and take adequate measures to support adherence, may maximize clinical outcomes. Our aim was to develop a model based on data from the first 3 months of treatment to identify potential indicators of suboptimal adherence and predict adherence over the following 9 months using a machine learning approach. Methods: We assessed adherence to r-hGH treatment in children with growth disorders in their first 12 months of treatment using a connected autoinjector and e-device (easypod™), which automatically transmits adherence data via an online portal (easypod™ connect). We selected children who started the use of the device before 18 years of age and who transmitted their injection data for at least 12 months. Adherence (mg injected/mg prescribed) between 4-12 months (outcome) was categorized as optimal (≥85%) versus suboptimal ( & lt;85%). In addition to adherence over the first 3 months, comfort settings (needle speed, injection depth, injection speed, injection time), number of transmissions, number of dose changes, age at start and sex were used as potential indicators of suboptimal adherence. Several machine learning models were optimized on a class-balanced training dataset using a 5-fold cross-validation scheme. On the best performing model, machine learning interpretation techniques and chi-squared statistical tests were applied to extract the statistically significant indicators of suboptimal and optimal adherence. Results: Anonymized data were available for 10,943 children. The optimal prediction performances were achieved with the random forest algorithm. The mean adherence and the adherence standard deviation over the first 3 months were the two most important features for predicting adherence in the following 9 months. Not using the system’s features (e.g. not transmitting data often and not changing some of the comfort settings, such as the needle speed setting), as well as starting treatment at an older age were significantly associated with an increased risk of suboptimal adherence (p & lt;0.001). When tested on first-time seen data following the same class distribution as the original data, the model achieved a sensitivity of 80% and a specificity of 81%. Conclusions: We developed a model predicting whether a child’s adherence in the following 9 months will be below or above the optimal threshold (85%) based on early data from the first 3 months of treatment and we identified the indicators of suboptimal adherence. These results can be used to identify children needing additional medical or other support to reach optimal adherence and therefore optimal clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 2
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-6-30)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 3
    In: Endocrines, MDPI AG, Vol. 4, No. 1 ( 2023-03-09), p. 194-204
    Abstract: Worldwide regulations during COVID-19 positively and negatively impacted self-management in paediatric patients with chronic medical conditions. We investigated the impact of regulations on adherence to recombinant human growth hormone (r-hGH) therapy in paediatric patients with growth disorders, using real-world adherence data extracted March 2019–February 2020 (before COVID-19) and March 2020–February 2021 (during COVID-19) from the easypod™ connect ecosystem. Data from three measures of regulations were analysed: stringency index (SI), school closure and stay-at-home. The mean SI, and the proportion of days with required school closure or stay-at-home during COVID-19 were categorised as high versus medium/low based on the 75th percentile. Adherence was categorised as optimal (≥85%) versus suboptimal ( 〈 85%). Adherence data were available for 8915 patients before and 7606 patients during COVID-19. A high SI (mean ≥68) and a high proportion of required school closure (≥88%) resulted in an increase in the proportion of optimal adherence during COVID-19 versus pre-COVID-19 (p 〈 0.001). Stay-at-home requirements showed no statistically significant effect (p = 0.13). Stringent COVID-19 regulations resulted in improved adherence to r-hGH therapy in patients with growth disorders, supported by connected digital health technologies. Insights into patient behavior during this time are useful to understand potential influences and strategies to improve long-term adherence to r-hGH.
    Type of Medium: Online Resource
    ISSN: 2673-396X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 3019981-5
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  • 4
    In: Digital Biomarkers, S. Karger AG
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Digital health technologies (DHTs) provide opportunities for real-time data collection and assessment of patient function. However, use of DHT-derived endpoints in clinical trials to support medical product labelling claims is limited. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 From November 2020 through March 2021, the Clinical Trials Transformation Initiative (CTTI) conducted a qualitative descriptive study using semi-structured interviews with sponsors of clinical trials that used DHT-derived endpoints. We aimed to learn about their experiences, including their interactions with regulators and the challenges they encountered. Using applied thematic analysis, we identified barriers to and recommendations for using DHT-derived endpoints in pivotal trials. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Sponsors identified five key challenges to incorporating DHT-derived endpoints in clinical trials. These included (1) a need for additional regulatory clarity specific to DHT-derived endpoints, (2) the official clinical outcome assessment qualification process being impractical for the biopharmaceutical industry, (3) a lack of comparator clinical endpoints, (4) a lack of validated DHTs and algorithms for concepts of interest, and (5) a lack of operational support from DHT vendors. 〈 b 〉 〈 i 〉 Discussion/Conclusion: 〈 /i 〉 〈 /b 〉 CTTI shared the interview findings with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and during a multi-stakeholder expert meeting. Based on these discussions, we provide several new and revised tools to aid sponsors in using DHT-derived endpoints in pivotal trials to support labelling claims.
    Type of Medium: Online Resource
    ISSN: 2504-110X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 2906645-1
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  • 5
    Online Resource
    Online Resource
    American Chemical Society (ACS) ; 2016
    In:  Langmuir Vol. 32, No. 49 ( 2016-12-13), p. 13009-13019
    In: Langmuir, American Chemical Society (ACS), Vol. 32, No. 49 ( 2016-12-13), p. 13009-13019
    Type of Medium: Online Resource
    ISSN: 0743-7463 , 1520-5827
    RVK:
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2016
    detail.hit.zdb_id: 2005937-1
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  • 6
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A681-A682
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A681-A682
    Abstract: Background: Long-term persistence of use and starting at the earliest possible age are associated with attainment of near-normal adult or final height in children who are treated with growth hormone therapy. However, there are many factors associated with a lack of persistence. Our aim was to study persistence of use in children with growth disorders using the easypod™ connected autoinjector e-device, which automatically records adherence data and can transmit them via an online portal (easypod™ connect). We investigated persistence of use, defined indicators of a long persistence of use, and developed a model to predict and identify children at risk of discontinuing treatment in the following 6 months. Data and Methods: Anonymized data from children transmitting over 10 injections between January 2007 and April 2020 were analyzed. A child was considered to discontinue the use if they had no injection in the last 6 months (before April 2020) or had an injection pause of at least 6 consecutive months. Persistence was estimated by Kaplan-Meier analyses and Weibull accelerated failure time modeling. To predict the individual risk of discontinuing the use in the following 6 months, individual survival probabilities curves were estimated for each patient still using the system, and the survival probabilities were then recalculated such that they were conditional on the fact that a child had already used the device for a certain time. The Harrell’s c-index was used to assess the algorithm performance. Results: Data were available for 17,651 children of whom 11,056 discontinued the use and 6,595 were still persistent in April 2020. Median persistence of use for all patients using the device was 2.1 years. There was a highly significant difference in median persistence of use between the regions: 1.0, 1.5 and 2.8 years in the available countries in the Asia-Pacific, America and Europe regions, respectively. Other indicators that had a significant positive impact on persistence of use were: at least one dose change a year, having auxological measurements recorded in the system (and if ‘Yes’, height standard deviation & lt; -2 at start of use had an additional effect), starting treatment at an early age, adherence ≥85%, customized injection speed setting and being male. For the individual prediction, random survival forests showed the best performance (Harrell’s c-index=0.72). Conclusions: Data from the connected autoinjector e-device showed that the persistence of use was approximately 2 years in children with growth disorders. We were able to define 8 indicators that had a positive impact on persistence of use of which several indicators were related to patient management. Our prediction model can be used to identify children needing support to reach longer persistence of use and subsequently optimal clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 7
    In: BMC Medical Informatics and Decision Making, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1472-6947
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2046490-3
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  • 8
    In: Expert Opinion on Drug Delivery, Informa UK Limited, Vol. 20, No. 6 ( 2023-06-03), p. 863-870
    Type of Medium: Online Resource
    ISSN: 1742-5247 , 1744-7593
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2023
    detail.hit.zdb_id: 2232223-1
    SSG: 15,3
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2006
    In:  European Biophysics Journal Vol. 35, No. 2 ( 2006-1), p. 155-161
    In: European Biophysics Journal, Springer Science and Business Media LLC, Vol. 35, No. 2 ( 2006-1), p. 155-161
    Type of Medium: Online Resource
    ISSN: 0175-7571 , 1432-1017
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 1398349-0
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    SAGE Publications ; 2008
    In:  Tumori Journal Vol. 94, No. 2 ( 2008-03), p. 264-270
    In: Tumori Journal, SAGE Publications, Vol. 94, No. 2 ( 2008-03), p. 264-270
    Abstract: Molecular imaging of receptors expressed on the surface of tumor cells is becoming a major field of investigation in clinical oncology, especially for the detection of cancer at its earliest stages. Nowadays, MRI, microcomputed tomography (microCT), ultrasound, positron emission tomography (PET), optical coherence tomography (OCT), and other major imaging systems are available to scientists and clinicians. Each technique has advantages and limitations, thus making them complementary. We report herein our investigations on the synthesis and use of new probes for small animal imaging as well as on the preparation and use of targeting complexes to deliver specific gene in tumors cells.
    Type of Medium: Online Resource
    ISSN: 0300-8916 , 2038-2529
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
    detail.hit.zdb_id: 280962-X
    detail.hit.zdb_id: 2267832-3
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