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A modeling informed quantitative approach to salvage clinical trials interrupted due to COVID-19.

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.

SUBMITTER: Geerts H

PROVIDER: S-EPMC7606183 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A modeling informed quantitative approach to salvage clinical trials interrupted due to COVID-19.

Geerts Hugo H van der Graaf Piet P

Alzheimer's & dementia (New York, N. Y.) 20201102 1

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, ...[more]

PMID: 33163611

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Project description:ImportanceInformed consent is a fundamental element of research ethics. The COVID-19 vaccine trials are high profile trials that have enrolled more than 100 000 participants. Consent documents must be succinct and understandable to ensure informed voluntary participation.ObjectiveTo assess how well informed consent documents of the COVID-19 vaccine trials achieve the ideal of being succinct and understandable, and to create a shorter, more readable document.Design, setting, and participantsThis quality improvement study collected and analyzed the informed consent documents used in 4 COVID-19 vaccine phase III randomized clinical trials to quantitatively assess readability and length and, based on this analysis, created a measurably more accessible informed consent document. Analysis was conducted from October 2020 to January 2021.Main outcomes and measuresThe main outcomes were number of words (measured as word count), time-to-read (measured at reading speeds of 175-300 words per minute), language complexity (measured using Flesch-Kincaid Grade Level assessment), and readability (measured using Flesch Reading Ease Score). Secondary outcomes included clarity of how the placebo group could access the vaccine if it is proven safe and effective. The study also examined the length and readability of an improved consent document.ResultsThe 4 informed consent documents were a mean (range) of 8333 (7821 to 9340) words long, with a mean (range) 35 (32.6 to 38.9) minutes to read at 240 words per minute. All documents exceeded grade 9 language complexity and scored lower than 60 in the formal reading ease metric, which constitutes difficult. Only 1 document specified that participants in the placebo group might receive vaccine. It was possible to write a document in fewer than 3000 words with a grade 7 to 8 reading level and a formal readability score that was not difficult.Conclusions and relevanceThese findings suggest that existing COVID-19 vaccine informed consent documents were too long, difficult to read, and exceeded grade 9 in language complexity. It was possible to create a shorter, more readable informed consent document for these trials.

Dataset Information

A modeling informed quantitative approach to salvage clinical trials interrupted due to COVID-19.

Publications

A modeling informed quantitative approach to salvage clinical trials interrupted due to COVID-19.

Similar Datasets

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