Drug Research and Development for Adults Across the Older Age Span Proceedings of a Workshop (2021) / Chapter Skim
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4 Alternative Study Approaches
4 Alternative Study Approaches
Pages 35-48
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From page 35... ...
(Chen) • Mechanistic modeling can make clinical trials less risky and more efficient by improving understanding about the disease process and the mechanism of the drug.
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From page 36... ...
For this process to work, said Berry, important aspects, such as adverse events or differences in outcome by subpopulation, must be learned efficiently so that changes can be made. The hope of adaptive design is that trials are better, more efficient, and more effective at "getting the right answers and treating patients." Berry shared an example of an adaptive trial called the DAWN trial;1 DAWN used an enrichment design to compare thrombectomy to standard of care in stroke patients.
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From page 37... ...
Another adaptive trial, said Berry, is Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) , which was designed to examine whether putting patients into a hypothermic state after cardiac arrest could improve neurological outcomes.2 He noted that while this is a common treatment, and even considered standard of care in many hospitals, there are no large trials that have proven its efficacy or demonstrated optimal cooling time.
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Some assessments are performed via mobile phone or telemedicine, while some testing is conducted at the point of care. Safety monitoring relies on patients reporting adverse events to a central site that is overseen by a doctor 24 hours per day.
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The participant population includes patients with disabilities, and explicitly includes patients with dementia who need a representative to provide consent, he said. Recruitment is conducted in three ways: via neurologists in practice, through electronic medical record (EMR)
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Nurse home visits can also help build a relationship between the participants and the clinical trial staff. REAL-WORLD CLINICAL TRIALS "What are some real-world opportunities for research involving older adults with concomitant illness and polypharmacy?
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The trial showed that clinical pharmacy teams providing comprehensive medication management improved health care quality and medication safety while driving down emergency room visit rates and hospitalization rates for high-risk patients. Community pharmacies are another avenue for real-world trials.
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QUANTITATIVE SYSTEMS PHARMACOLOGY MODELS Mechanistic modeling, said Christina Friedrich, chief engineer at Rosa & Co. LLC, uses biological data and understanding to explore disease and drug mechanisms.
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QSP could also be enormously helpful with patient stratification; different types of virtual patients could be built to test the drug on subtypes of geriatric patients. To build this geriatric QSP model, said Friedrich, the first step would be to create an initial QSP model of the general population using data from in vitro, preclinical, and clinical
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From page 44... ...
Friedrich said this model increased confidence for moving ahead in pediatric populations and also helped Amgen to identify dosing strategies for subpopulations. In conclusion, said Friedrich, QSP modeling "connects the dots between mechanisms and outcomes." A QSP model of non-geriatric adult physiology can serve as a foundation for a geriatric model, and mechanistic impacts of aging, comorbidities, and polypharmacy can all be incorporated.
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Adherence can affect trial outcomes; low adherence can drop concentration levels below the therapeutic threshold, while non-compliance (e.g., double dosing) can lead to adverse events.
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From page 46... ...
as well as wearable sensors to better inform patients and providers on dosing and adherence-related issues. There is a huge opportunity, said Berry, to pair precision dosing applications with machine learning and clinical trial or real-world simulations to better understand the impact of polypharmacy and potential drug interactions in the older adult population.
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From page 47... ...
He noted that there are potentially two types of adaptive randomization that could be used, one in which doses are adjusted based on how previous patients respond to a given treatment, and one in which doses are adjusted for a particular patient based on how that individual has responded to treatment. Chen covered the "nuts and bolts" of engaging pharmacists in adaptive design trial.
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From page 48... ...
He suggested that engaging pharmacists in adaptive trials would be beneficial because of "that extra layer of monitoring." Chen said that pharmacists are required to log adverse drug reactions and that there are platforms available to track and standardize all drug-related problems that are identified. This frequent monitoring, he said, could help prevent dropouts in a trial because drug reactions are caught and managed early, before the participant suffers a serious adverse event.
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