A modeling informed quantitative approach to salvage clinical trials interrupted due to COVID-19.
Alzheimers Dement (N Y)
; 6(1): e12053, 2020.
Article
em En
| MEDLINE
| ID: mdl-33163611
ABSTRACT
Many ongoing Alzheimer's disease central nervous system clinical trials are being disrupted and halted due to the COVID-19 pandemic. They are often of a long duration' are very complex; and involve many stakeholders, not only the scientists and regulators but also the patients and their family members. It is mandatory for us as a community to explore all possibilities to avoid losing all the knowledge we have gained from these ongoing trials. Some of these trials will need to completely restart, but a substantial number can restart after a hiatus with the proper protocol amendments. To salvage the information gathered so far, we need out-of-the-box thinking for addressing these missingness problems and to combine information from the completers with those subjects undergoing complex protocols deviations and amendments after restart in a rational, scientific way. Physiology-based pharmacokinetic (PBPK) modeling has been a cornerstone of model-informed drug development with regard to drug exposure at the site of action, taking into account individual patient characteristics. Quantitative systems pharmacology (QSP), based on biology-informed and mechanistic modeling of the interaction between a drug and neuronal circuits, is an emerging technology to simulate the pharmacodynamic effects of a drug in combination with patient-specific comedications, genotypes, and disease states on functional clinical scales. We propose to combine these two approaches into the concept of computer modeling-based virtual twin patients as a possible solution to harmonize the readouts from these complex clinical datasets in a biologically and therapeutically relevant way.
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MEDLINE
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En
Ano de publicação:
2020
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Article