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Amplifying the Voice of the Patient in Clinical Research: Development of Toolkits for Use in Designing and Conducting Patient-Centered Clinical Studies

Amplifying the Voice of the Patient in Clinical Research: Development of Toolkits for Use in Designing and Conducting Patient-Centered Clinical Studies

Incorporating patient perspectives into clinical studies is recognized as important to the development of high-quality, safe, and effective fit-for-patient medicines. However, no widely accepted methodology to help design more patient-centered studies has been established systematically. TransCelerate Biopharma Inc., a non-profit organization promoting collaboration across biopharmaceutical companies, organized a Patient Experience (PE) Initiative to create tools to intentionally include the patient perspective into the design and implementation of clinical studies.

The resulting tools include the Patient Protocol Engagement Toolkit (P-PET), to engage patients early in protocol development, and the Study Participant Feedback Questionnaire (SPFQ), to assess patient experiences during clinical studies. To develop these toolkits, TransCelerate conducted a literature review and identified aspects of clinical studies that patients find either valuable or burdensome, or that affect participation, adherence, and engagement in a clinical study. The concepts identified were refined through elicitation of feedback from patient advisors, clinical study site advisors, and subject matter experts from member companies (MCs) of TransCelerate.

This feedback was considered in identifying gaps, defining scientific methodology to understand how to evaluate patients’ needs, and developing and refining the P-PET and the SPFQ. As part of the development process, descriptions/drafts of the tools were shared with patients, clinical site advisory groups, MCs, and the US Food and Drug Administration, and then revised. MCs simulated use of the tools, and feedback was incorporated into the final versions of the P-PET and SPFQ prior to public release. The P-PET and SPFQ are available free on the TransCelerate website.

Current status and future directions of high-throughput ADME screening in drug discovery

During the last decade high-throughput in vitro absorption, distribution, metabolism and excretion (HT-ADME) screening has become an essential part of any drug discovery effort of synthetic molecules. The conduct of HT-ADME screening has been “industrialized” due to the extensive development of software and automation tools in cell culture, assay incubation, sample analysis and data analysis.
The HT-ADME assay portfolio continues to expand in emerging areas such as drug-transporter interactions, early soft spot identification, and ADME screening of peptide drug candidates. Additionally, thanks to the very large and high-quality HT-ADME data sets available in many biopharma companies, in silico prediction of ADME properties using machine learning has also gained much momentum in recent years.
In this review, we discuss the current state-of-the-art practices in HT-ADME screening including assay portfolio, assay automation, sample analysis, data processing, and prediction model building. In addition, we also offer perspectives in future development of this exciting field.
Amplifying the Voice of the Patient in Clinical Research: Development of Toolkits for Use in Designing and Conducting Patient-Centered Clinical Studies
Tucatinib is an oral, small molecule, selective HER2 inhibitor initially developed by Array BioPharma (a subsidiary of Pfizer) and subsequently developed by Seattle Genetics for the treatment of HER2-positive solid tumours, including breast cancer and colorectal cancer. Tucatinib was approved in the USA in April 2020 and in Switzerland in May 2020 for the treatment of HER2-positive breast cancer, and is pending regulatory review in the EU, Australia, Canada and Singapore. This article summarizes the milestones in the development of tucatinib leading to this first approval in patients with advanced unresectable or metastatic HER2-positive breast cancer.

Encochleated Amphotericin B: Is the Oral Availability of Amphotericin B Finally Reached?

As the oldest and for many decades the only available agent for the treatment of life-threatening invasive fungal diseases, amphotericin B (AmB) is known for its broad-spectrum fungicidal activity against a wide range of yeasts and molds. However, the main drawback of the present formulations remains its toxicity, the limited use to intravenous administration, and the higher costs associated with the better tolerated lipid formulations.
The novel nanoparticle-based encochleated AmB (CAmB) formulation encapsulates, protects, and delivers its cargo molecule AmB in the interior of a calcium-phospholipid anhydrous crystal. Protecting AmB from harsh environmental conditions and gastrointestinal degradation, CAmB offers oral availability in conjunction with reduced toxicity. Matinas BioPharma, Bedminster, NJ is on the way to develop CAmB named MAT2203, currently undergoing Phase II clinical trials.
In a decade when Industry 4.0 and quality by design are major technology drivers of biopharma, automated and adaptive process monitoring and control are inevitable requirements and model-based solutions are key enablers in fulfilling these goals. Despite strong advancement in process digitalization, in most cases, the generated datasets are not sufficient for relying on purely data-driven methods, whereas the underlying complex bioprocesses are still not completely understood. In this regard, hybrid models are emerging as a timely pragmatic solution to synergistically combine available process data and mechanistic understanding.
In this study, we show a novel application of the hybrid-EKF framework, that is, hybrid models coupled with an extended Kalman filter for real-time monitoring, control, and automated decision-making in mammalian cell culture processing. We show that, in the considered application, the predictive monitoring accuracy of such a framework improves by at least 35% when developed with hybrid models with respect to industrial benchmark tools based on PLS models.
In addition, we also highlight the advantages of this approach in industrial applications related to conditional process feeding and process monitoring. With regard to the latter, for an industrial use case, we demonstrate that the application of hybrid-EKF as a soft sensor for titer shows a 50% improvement in prediction accuracy compared with state-of-the-art soft sensor tools.

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