Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(2), P. 403 - 403

Published: Jan. 11, 2024

Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization adjunct DTx the US Food Drug Administration draft guidelines on “prescription drug use-related software” illustrate opportunities to create + combination therapies, ultimately leading towards drug–device products (DTx has a status devices). Digital interventions (mobile, web-based, virtual reality, video game applications) demonstrate clinically meaningful benefits people living with Alzheimer’s disease, dementia, rheumatoid arthritis, cancer, pain, epilepsy, depression, anxiety. In respective animal disease models, preclinical studies environmental enrichment other non-pharmacological modalities (physical activity, social interactions, learning, music) surrogates “active ingredients” also show improved outcomes. this narrative review, we discuss how therapies impact translational research, discovery development, generic repurposing, gene therapies. Market-driven incentives are illustrated Humira® (adalimumab) facing “patent-cliff” competition cheaper more effective biosimilars seamlessly integrated DTx. conclusion, pharma biotech companies, patients, healthcare professionals will benefit from accelerating integration pharmacotherapies.

Language: Английский

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Digital Mental Health for Schizophrenia and Other Severe Mental Illnesses: An International Consensus on Current Challenges and Potential Solutions

JMIR Mental Health, Journal Year: 2024, Volume and Issue: 11, P. e57155 - e57155

Published: May 8, 2024

Background Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe illness (SMI). Objective An international multidisciplinary group was convened reach a consensus on the challenges potential solutions regarding collecting data, delivering treatment, ethical digital SMI. Methods The development panel method used, with an in-person meeting of 2 groups: expert panel. Membership including those lived experience, equal participation at all stages coproduction outputs summary. Relevant literature shared advance meeting, systematic search recent interventions psychosis completed ensure that informed before group. Results Four broad areas challenge proposed were identified: (1) user involvement real coproduction; (2) new methodology health, agreed standards, data sharing, measuring harms, prevention strategies, mechanistic research; (3) regulation funding issues; (4) implementation real-world settings (including collaboration, training, existing service provision, social population-focused approaches). Examples are provided more detail human-centered research design, experience perspectives, biomedical ethics Conclusions by number recommendations: improved approach (with reporting protocols), emphasis population as well biological psychological approaches, meaningful collaborations across varied disciplines have previously not worked closely together, increased focus business model product planning structures whole pathway, (5) issues (6) organizational changes allow true communication This study approach, combining patient public engagement throughout process, methodology, discussion, publication, is way identify directions future clinical rapidly evolving can combined measurements impact over time. Similar initiatives will other similarly fast-evolving fields change effect implementation.

Language: Английский

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Understanding Digital Therapeutics in Disease Self-management: A Systematic Literature Review

Technology in Society, Journal Year: 2025, Volume and Issue: unknown, P. 102831 - 102831

Published: Jan. 1, 2025

Language: Английский

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Levothyroxine personalized treatment: is it still a dream?

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Levothyroxine is a milestone in the treatment of all causes hypothyroidism. From 19th century till today, experienced great advancement, from hypodermic injections an extract thyroid gland sheep to novel formulations, known circumvent malabsorption issue. However, rate patients on suboptimal therapy still high. Current Guidelines are clear, daily dosage should be calculated based body weight. we far away possibility administer right patient, for several reasons. We retrace history with levothyroxine, pointing out strengths and weaknesses different particular attention what keeps us tailored therapy. In age digitalization, pharmaceutical industry has been giving rising importance Digital therapeutics, that effective reaching target therapies. By combining current knowledge hypothyroidism cutting-edge technology, also hypothesized could future strategies developed this field.

Language: Английский

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Quantitative systems pharmacology in the age of artificial intelligence

CPT Pharmacometrics & Systems Pharmacology, Journal Year: 2023, Volume and Issue: 12(12), P. 1823 - 1826

Published: Oct. 1, 2023

In this perspective, we briefly review the state-of-the-art covering interface between quantitative systems pharmacology (QSP) and artificial intelligence (AI) machine learning (ML); in particular, how AI/ML are conceived used as many attempts to address methodological pain points of QSP. a second part, invite reader step out from discipline-centric view discuss paradigm shift consisting repurposing AI into 2022, Journal Pharmacokinetic Pharmacodynamic published special issue edited by Cho, Zhang, Bonate with 10 scientific articles illustrating ways for coupling (AI). The Zang et al. summarizes current state-of-the-art1 explains that AI/machine (ML) currently four main applications related QSP: parameter estimation, model structure, complexity reduction, virtual population generations (see Figure 1). What may strike is – although there good reasons think improving on such technical domains will increase impact QSP these speak toward dimensions discipline. Estimation parameters, writing down optimal structures, reducing complexity, or properly generating terms which talk modeling experts but probably only them. Parameter estimation known be an because models often too large respect available data. modelers typically working engineers; equations describe complex high level granularity, elementary biological processes unknown uncertain. addition that, clinical end aim predict remote expend effort accurately describe. We, community, trying issues AI/ML. On one hand, big data, omics and/or imaging can treated inputs supervised parameters outputs ref. 2 explanation approach oncology). other could linked endpoints similar formalism where predicted. Finding structural also issue, often, structure designed hand; thus subjected subjectivity coming whomever wrote it. We use data-driven approaches inform through Boolean networks, Bayesian even physics-based AI. has received attention especially safety prediction, shown recent initiative identify molecular players involved drug-induced peripheral neuropathy.3 Regarding authors propose apply feature selection techniques reduce priori lead parsimonious more amenable tasks 1 further information). Last not least, creation populations (VPs) been rightly focus much interest ML, prevalence weighting Markov Chain Monte Carlo, proposed relevant plausible ensemble order generate patients resembling cohorts.4 speed up simulations computational-demanding efficient VP generation.5 key drug development safe medicine, two them immediately come mind. First, multiscale nature points, some areas incorporate aspects daily living, dementia rating Alzheimer's disease (AD) unified Parkinsons's scale (UPDRS). Leveraging data notoriously challenging. This difficulty spread therapeutic given increasing availability patients' reported outcomes. sometimes highlight problem being "subjective." author's opinion, less than multidimensional measures. lacking methods bridge traditional level, our models. means have urgency double innovation progression way descriptive information contained predict. Second, lack validated biomarkers, responsibility look beyond classical markers measured blood tissue potential surrogates action. Still, field neuroscience, would cognitive, behavioral, functional levels. How do we, points? news repurposed/reframed stick fundamental focus. Indeed, several recently reports suggest taking advantage algorithm capability perform well human basis "mechanistic" An illustrative example around reframing algorithms performing at facial recognition their analysis shed new light mechanisms happening suffering AD losing capabilities.6 After having trained (mimicking healthy individual) perturbed different ways, either modifying weight mimic brain signal weakening cutting neural network nodes lesions. Simulations performed results were put perspective biomarker neuroimaging initiative. paper presents very clearly. However, deep interpretability, question whether indeed "reverse engineering" informative actual pathological remains fully open. Following strategy technique called reinforcement (RL) promising supported theoretical arguments. it experimentally RL valid analyzing humans animals' learning. It following words Richard Sutton Andrew Barto start book RL7: When infant learns walk, fall try again, no explicit teacher does direct sensorimotor connection its environment. Exercising produces wealth about cause effect, consequences actions, what achieve goals. mimics process consists knowing map situations actions so maximize numerical reward signal. represented Decision Process agent takes sense environment, clarity goal achieve. "computerized" led including health. Computationally, aims estimating value function iteratively, experience, updated term "temporal difference" (TD). TD difference currrent expectation state is, after experience. If positive, increased, if negative, should then decreased. happen until convergence. highlighted interesting precision dosing non-pharmacological interventions computational psychiatry.8 Before reporting definition psychiatry, let us illustrate examples. 2004 Science, David Redish repurposed simulate addiction.9 previous concept TD, addiction modeled always positive when specific taken (i.e., subject addicted to). By way, result corresponding value. turn, most likely chosen subject. Earlier, discussed need biomarkers useful analyze cognitive testing 8 examples). Computational psychiatry nascent area defined characterize mental dysfunction aberrant computations. coupled (pharmacological) description intervention, nothing else approach. To envisioned today reinforces "system" component highly beneficial areas, neurodegeneration limited earlier. conclusion, see topic interfacing first inner view, QSP-centric, leverage seems underdeveloped box reframe (Figure 2). Embracing make critical advance modalities. doing tremendous role supporting therapy. Recently, modality emerging, digital therapeutics (DTx), software treat, manage, prevent condition. DTx considered modalities behaviors, disorders, sleep pain. reviewed identified application principles greatly benefit DTx, better characterizing mechanism action, optimize intervention content, right dose patients.10 drive modalities, becoming instrumental overcoming another limitation field, namely selectivity candidates reflecting interactions circuits. So, challenge? author acknowledges Dr. Cristina Santini UK invitation present 4th Exchange Workshop July 12, 2023; workshop participants valuable questions feedback helped perspective. thanks Lucy Hutchinson exchanges help finalizing manuscript. No funding was work. employee shareholder F. Hoffmann-La Roche Ltd.

Language: Английский

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Novel Therapeutic Modalities: The Future is Now

Clinical Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 114(3), P. 493 - 496

Published: Aug. 18, 2023

In the past 20 years, we have seen a wave of innovative technology and novel drug modalities that may overcome limitations classical therapeutic approaches, such as small molecules. 2021 alone, ~ 100,000 journal articles were published on these new approaches.1 However, only 10% recent original research (ORAs) in Clinical Pharmacology & Therapeutics (CPT) focus modalities, which at least part be reflection fact many emerging approaches are still early stages discovery development their clinical benefits remain to established.2 landscape has been changing rapidly several "new" advancing through registration years. For example, cell therapy emerged cancer treatment approach, with 12 approvals chimeric antigen receptor (CAR)-T therapies since 2017, including 4 2022.3 Likewise, number antibody-drug conjugates reaching trial stage increased by nearly 5-fold last 5 21 currently late-stage development.4 Whereas there handful bispecific antibody (bsAb) candidates per year first decade this century, years remarkable growth for modality class, more than 50 bsAbs trials 2021.5 One example is rozibafusp alfa, first-in-class IgG2-peptide fusion designed inhibit inducible T-cell costimulator ligand B-cell activating factor, results patients rheumatoid arthritis reported issue.6 Additionally, 2022, US Food Drug Administration (FDA) approved therapeutics modify gene expression or function (2 therapies, 2 gene-modified 1 interfering RNA) microbiota Clostridium difficile infection.7 European Union United Kingdom, "advanced medicinal products" marketed March 2022 another 482 development.8 This revolution requires pharmacology scientists, educators, practitioners quickly adapt develop skill sets expertise.9-11 If modest contribution date ORAs focusing overall content CPT2 also perhaps somewhat limited role our discipline nontraditional therapeutics,12 then now time (re)position ourselves clearly. light, current CPT themed issue (Figure 1) can call action. We invited key opinion leaders review knowledge experience (including cancers rare disease, vaccines, targeted protein degraders, oncolytic viruses, digital therapeutics) throughout process. The coronavirus disease 2019 (COVID-19) pandemic dramatically affected people's lives countries' health systems, but it was an emergency-driven opportunity advanced from bench bedside unprecedented speed.10, 13 Heaton et al.14 highlight lessons COVID-19 importance trust, collaboration, transparency care vaccine production. They stress innovations system capacities advances technologies, identify 3 factors facilitated timely development, suggest other areas improve communication build trust. Cell (CGTs), viral vector-based CAR-T potential transformational efficacy treating diseases high unmet needs. tend higher rate disruption after conclusion pivotal before regulatory submission, disruptions during conventional therapeutics, monoclonal antibodies.15 Therefore, crucial use careful, yet innovative, strategies CGTs. perspective, Jodele co-workers report dose optimization strategy eculizumab could beneficial adeno-associated virus (AAV) thrombotic microangiopathy, suggesting apply contemporary precision medical care.16 parallel, White Paper, Mitra al.17 present comprehensive overview applications model-informed selection design AAV-based products. address challenges trials, patient sample size equivocal natural history various tools support future development.17 Mody collaborators International Consortium Innovation Quality Pharmaceutical Development industry perspective best practices T study modeling simulation strategies, underscoring unique critical pharmacology.18 further exemplified Masilamani al.,19 who compare bioanalytical methods characterization cellular kinetics. Unlike proteins antibodies, "living cell" whose pharmacokinetics (PKs) characterized expansion, distribution, contraction, persistence. different approach quantitation compared binding assays implemented most biologics. With regard authorities, agencies encourage interaction sponsors align elements CGT programs, because each will specific risk–benefit profile depending upon its platform mode delivery, indication, demography participants. Walford coworkers FDA Medicine Agency (EMA) guidelines relating entering into clinic should therefore resource.20 Targeted degradation (TPD) potentially modulates "undruggable" molecules.21 Since TPD molecule harnesses ubiquitin–proteasome degrade target reported, biotech pharmaceutical companies entered field disclosed programs preclinical development. date, information guidance made available aspects TPDs. State-of-the-Art entitled "Clinical Translation Protein Degraders,"22 Kong Jones Dana-Farber Cancer Institute provide TPDs learned human data. useful source pharmacologists working growing field, specifically PK-pharmacodynamic (PK-PD) profiling, biomarkers, safety, emergence class E3 ligases reliance hijacked ligase cause resistance. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems caused breakthrough genomic editing clinic. mechanism action CRISPR translation selection. Abdelhady colleagues status emphasis mechanistic, quantitative uncertainties empirical design.23 Physiologically-based PK (PBPK) (QSP) evolving modalities. Parra-Guillen al.24 describe application mechanistic PBPK model linked tumor response assess virus. Renardy al.25 demonstrate value models entirely modalities: microbiome therapies. Describing kinetics behavior live biotherapeutic products (LBPs) poses challenge pharmacologists, they expand, contract, colonize host digestive tract. A kinetic-PD QSP LBP developed describes bacterial competition, vancomycin effects, unbinding epithelial surface, production clearance butyrate metabolite. provides basis used inform decision making around antibiotic pretreatment regimens. Ribba al.26 show how silico themselves become own right. review, make case fundamental principles benefit (generally known software embedded within accessible technologies–such smartphones–to treat, manage, prevent pathological condition) three areas: action, intervention, dosing. propose conclusions applied any editorial leadership expects publish examples coming No funding received work. author declared no competing interests

Language: Английский

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Practical application of digital therapeutics in people with mood disorders

Current Opinion in Psychiatry, Journal Year: 2023, Volume and Issue: 37(1), P. 9 - 17

Published: Nov. 1, 2023

Digital therapeutics (DTx) offer evidence-based digitally-delivered high quality standards applications and/or softwares in the prevention, management and treatment of several medical conditions, including mood disorders. Nowadays, there are only three DTx officially approved by Food Drug Administration for mental conditions still very few developed context The current comprehensive overview aims at providing a summary currently published studies on clinical major depressive disorder (MDD), symptomatology bipolar (BD), using PubMed/MEDLINE Scopus databases. Fifteen have been selected (10 MDD; 4 BD; 1 MDD BD). Literature disorders is lacking, being mostly constituted feasibility acceptability rather than efficacy/effectiveness outcomes, particularly BD. More focused compared to Most based cognitive behaviour therapy interventions while BD psychoeducation. All assessing symptom severity improvement pre- vs. postinterventions demonstrated significant postintervention improvement. Therefore, despite preliminary encouraging results here retrieved, their methodology too heterogeneous allow comparisons generalizability findings. Further warranted, more larger samples involving multiple sites, measures both specific effects as well acceptability, effectiveness real-world settings.

Language: Английский

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Digital Mental Health for Schizophrenia and Other Severe Mental Illnesses: An International Consensus on Current Challenges and Potential Solutions (Preprint)

Published: Feb. 7, 2024

Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe illness (SMI). An international multidisciplinary group was convened reach a consensus on the challenges potential solutions regarding collecting data, delivering treatment, ethical digital SMI. The development panel method used, with an in-person meeting of 2 groups: expert panel. Membership including those lived experience, equal participation at all stages coproduction outputs summary. Relevant literature shared advance meeting, systematic search recent interventions psychosis completed ensure that informed before group. Four broad areas challenge proposed were identified: (1) user involvement real coproduction; (2) new methodology health, agreed standards, data sharing, measuring harms, prevention strategies, mechanistic research; (3) regulation funding issues; (4) implementation real-world settings (including collaboration, training, existing service provision, social population-focused approaches). Examples are provided more detail human-centered research design, experience perspectives, biomedical ethics by number recommendations: improved approach (with reporting protocols), emphasis population as well biological psychological approaches, meaningful collaborations across varied disciplines have previously not worked closely together, increased focus business model product planning structures whole pathway, (5) issues (6) organizational changes allow true communication This study approach, combining patient public engagement throughout process, methodology, discussion, publication, is way identify directions future clinical rapidly evolving can combined measurements impact over time. Similar initiatives will other similarly fast-evolving fields change effect implementation.

Language: Английский

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Redesigning Pharmacy to Improve Public Health Outcomes: Expanding Retail Spaces for Digital Therapeutics to Replace Consumer Products That Increase Mortality and Morbidity Risks

Pharmacy, Journal Year: 2024, Volume and Issue: 12(4), P. 107 - 107

Published: July 12, 2024

United States healthcare outcomes, including avoidable mortality rates, are among the worst of high-income countries despite highest spending per capita. While community pharmacies contribute to chronic disease management and preventive medicine, they also offer consumer products that increase risks prevalence cardiovascular diseases, diabetes, cancer, depression. To resolve these contradictions, our perspective article describes opportunities for major pharmacy chains (e.g., CVS Pharmacy Walgreens) introduce digital health aisles dedicated prescription over-the-counter therapeutics (DTx), together with mobile apps wearables support self-management, wellness, well-being. We provide an evidence-based rationale replace spaces devoted sugar-sweetened beverages other unhealthy commodities (alcohol, tobacco) may premature death. discuss how can serve as marketing patient education resources, informing customers about commercially available DTx technologies healthy lifestyles. Since practice requires symbiotic balancing between profit margins patient-centered, value-based care, replacing health-harming health-promoting could positively impact prevention well physical mental patients caregivers who visit neighborhood in order pick up medicines.

Language: Английский

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