Model based dose personalization in clinical trials
Kabir Soeny1, Barbara Bogacka1, Byron Jones2
1School of Mathematical Sciences, Queen Mary University of London, UK.
Computer Methods and Programs in Biomedicine
|February 15, 2021
Summary
This study introduces a new method for optimizing drug doses during clinical trials, ensuring patients receive the intended drug exposure while accurately estimating pharmacokinetic profiles. The algorithm achieves high efficiency, minimizing over- and under-dosing for personalized medicine development.
Area of Science:
- Pharmacokinetics and Drug Development
- Personalized Medicine
- Clinical Trial Optimization
Background:
- Personalized medicine aims to tailor therapies to individual patients.
- Therapeutic drug monitoring is crucial for drugs with narrow therapeutic indices but is not feasible for drugs in early development.
- Limited pharmacokinetic data hinders dose optimization for investigational drugs.
Purpose of the Study:
- To present a novel methodology for optimizing drug dose regimens during pharmacokinetic studies.
- To ensure drug blood concentrations remain within a target range for each subject.
- To facilitate individualized dosing and accurate pharmacokinetic estimation.
Main Methods:
- Development of an algorithm for explicit dose regimen optimization.
- Integration of dose individualization with pharmacokinetic estimation.
- Application during the course of pharmacokinetic studies.
Main Results:
- The algorithm successfully estimates pharmacokinetic profiles while individualizing doses.
- Achieved an average relative efficiency of 97% with a standard deviation under 5%.
- Demonstrated ability to minimize subject over- and under-exposure to the therapy.
Conclusions:
- The methodology ensures correct dosing and intended drug exposure for clinical trial subjects.
- Facilitates simultaneous estimation of drug pharmacokinetic profiles.
- Applicable to randomized concentration-controlled trials requiring target concentration maintenance.
Related Concept Videos
01:24Dosage Regimen: Individualization
71
Individualization in dosing regimens is the customization of medication doses for individual patients. Its necessity arises from the goal of maximizing therapeutic benefits while minimizing risks. This approach is pivotal because human responses to drugs can vary widely; what is effective for one person may be inadequate or excessive for another. Interpatient (intersubject) variability refers to differences in drug responses between individuals, while intrapatient (intrasubject) variability...
71
02:50Combination Therapies and Personalized Medicine
5.6K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.6K
01:03Dose-Response Relationship: Overview
4.4K
Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
4.4K
01:28Dosage Regimens: Designs and Approaches
118
Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
118
01:01Dosage Regimens: Partial Pharmacokinetic Parameters
55
It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
55
01:25Dose-Response Relationship: Selectivity and Specificity
9.2K
Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and...
9.2K