Vantage Research and Indian Institute of Science (IISc) present Hackathon 2023, an exciting team competition exclusively for the students of IISc, where they solve a problem statement within a stipulated time! Registrations to participate in the competition will be open till 30th August 2023. Students will have a period of two weeks to solve the problem and present their report. Last date to submit the report is 15 September 2023.
HACKATHON RULES
- The competition will consist of groups of three students each.
- Registration is compulsory. To register click here. Students can register on or before 30th of August 2023
- Students are allowed to access any form of information available to them in order to solve the problem.
- Participants are required to submit their final report in PDF format. The report must include the solutions to the problem and any codes involved in the process.
- Late submissions will not be accepted under any circumstances.
- Participants will be evaluated based on the accuracy and effectiveness of their solution, as well as the clarity and organization of their report.
- The competition will be judged by a panel of experts in the relevant fields.
- The winners of the competition will receive recognition for their achievements in the form of cash prize.
Last Date for Submission of Reports: Reports can be submitted until September 15th, 2023.
Problem Statement
In the year 2022, Gotham city, renowned for its high crime rate, experienced a catastrophic event five years ago, namely a viral outbreak that posed a grave threat to the lives of all its inhabitants. The outbreak brought the entire economy of the city to a grinding halt, exacerbating the already dire situation. In light of the calamity, all neighboring countries/cities have ceased providing assistance to Gotham, having lost all hope of salvaging the city.
Against this backdrop, the R&D division of Wayne Enterprises has been engaged in extensive research aimed at discovering a cure for the viral infection for several years. The experts who toiled to gain a better understanding of the infection were able to compile the following comprehensive information about it.
1. Seasonality of infection
The curve below follows a gaussian distribution with following parameters σ = 48 𝑑𝑎𝑦𝑠, μ = 162 𝑑𝑎𝑦𝑠, 𝐴 = 2633, 𝐵𝐿 = 2. 25
(where σ is the standard deviation of the Gaussian curve, μ is the time from August 10th to FOI peak, 𝐴 is the magnitude between the offseason and peak incidence rates, and 𝐵𝐿 is the relative off-season incidence rate.)
2. A promising large molecule has been identified as a potent agent in conferring protection against infections.
To comprehensively characterize the pharmacokinetics of this molecule, it underwent initial testing on 500 mice. The results of this study demonstrated that the molecule’s clearance rate from the system was determined to be 5.1 mL/day/kg, while the incompartmental distribution rate was found to be 43.53 mL/day/kg. Furthermore, the central volume and peripheral volume were calculated to be 52.3 mL/kg and 45.3 mL/kg, respectively.3. Dose studies conducted on animals demonstrated that a minimum concentration of 5ug/mL in the bloodstream is required to provide effective protection against the pathogen.
The scientific community tasked with finding a cure for the virus has been plagued by significant setbacks, with many researchers succumbing to the illness or conceding defeat. However, you and two of your colleagues have been appointed to join the efforts in this crucial endeavor. Leveraging your collective expertise and the available information on the disease, your mandate is to determine the First-in-Human (FIH) dose for the general population, ensuring that at least 75% of the populace can be effectively treated. It is important to note that each individual is required to receive a single dose every 240 days.[HINT TO SOME PUBLICLY AVAILABLE LITERATURE]
To perform a comprehensive analysis for determining the First-in-Human (FIH) dose for the general population, it is imperative to consider inter-individual variability among the population. Assuming a population of 1000 individuals in Gotham, it is important to note that each individual possesses distinct characteristics that may influence drug pharmacokinetics (PK). To account for these differences in PK, reference can be made to the publication at http://dx.doi.org/10.4161/mabs.29095, which provides valuable insights into inter-individual variability. Additionally, to determine the appropriate dose, it is necessary to scale between species using established techniques, as outlined in the article at 10.1111/j.1365-2125.2005.02239.x While inter-individual variability needs to be taken into account, the minimum efficacious blood concentration can be assumed to be uniform across all species. Modelling techniques, as described in the publication at https://pharmacy.ufl.edu/files/2013/01/two-compartment-model.pdf, can be employed to determine the optimal dose.Brief Description on the Approach
The pharmacokinetic parameters of the identified molecule (clearance rate, distribution rate, volumes) provide insights into how the molecule moves through the body. These parameters are fundamental for determining how frequently the molecule needs to be administered to maintain an effective concentration. Mathematical models, such as compartmental models, can help simulate the behaviour of the molecule in the body and inform dosing strategies.
Incorporation of seasonality of Infection
The problem statement presents a Gaussian distribution curve to model the seasonality of infection rates. This type of distribution is commonly used to represent natural phenomena with a peak and variability. Understanding the parameters and how they relate to the infection rates is crucial for creating a realistic model of the disease’s behaviour over time.
Population-Level Modelling
To determine the effective treatment population and ensure that at least 75% of the populace can be effectively treated, a population-level model is needed. This model should integrate the infection rate distribution, dosing strategy, treatment duration, and treatment coverage to estimate the percentage of the population that can be protected over time.
Including inter-individual variability at the population level is an important consideration when tackling complex problems like determining the First-in-Human (FIH) dose for a viral infection. Inter-individual variability acknowledges that different people may respond differently to treatments and have varying characteristics that can impact treatment outcomes.
Instead of assuming fixed values for parameters for pharmacokinetic parameters, consider using probability distributions to describe these parameters. This allows you to capture the range of possible values that individuals in the population might exhibit.