DOI: 10.25934/pr00007224
title: Early prediction of survival outcome of large-scale randomized clinical trials using artificial intelligence technology

description: 
In a large-scale randomized phase 3 trials, an interim analysis that assesses the survival rate at a certain time during the trial is usually performed to evaluate for early efficacy, futility, or both with using dead and alive patient data that is known as uncensored and censored data, respectively. Each data distribution of the observed time of the uncensored and the censored data is not considered quantitatively in the interim analysis. There are adjustments that need to be made to counter inflation of statistical error and loss of power, or both depending on the focus of the interim analysis. In addition, prespecified decision boundaries can lead to inappropriate conclusions (in either direction: ‘trial success’ or ‘trial failure). Further, the decision of either “go” or “no-go” for the ongoing study is dependent on a single statistic. The single number does not include confidence intervals resulting in a lack of reliability.


The Necessity of the Research;
How many patients/members of the public are potentially affected;

If the lacking data in the large-scale phase 3 trials can be reliably predicted as early as possible, human and financial resources and time will be saved. Therefore, the feasibility of this method is deserving of investigation.

How the research will add to medical science or patient care;

If it becomes possible to accurately predict the results of large-scale comparative studies with a smaller sample size, it will be possible to reduce the number of patients involved in experimental treatments. At the same time, it can be applied to comparative studies of rare diseases.

How the research will be conducted;
We would like to obtain and analyze survival data from five randomized controlled trials in cancer from Vivli. We want to see how fast and how accurately our artificial intelligence (AI)-based method can predict survival in trials with different diseases and different patterns of survival results.
Specifically, for each trial, we will input the patient survival data into the AI program in the order of enrollment and determine the number of cases that are similar to the original survival analysis results.
After that, we will continue to input the data up to the last patient, and in the process, we will verify if there are any fluctuations in the analysis results of the AI program.

What design and methods you have chosen and why (in brief);
The method used here is completely original.
We have developed and published a new method for the prediction of clinical trial results using compressive sensing of artificial intelligence (AI) [1,2]. 
This new method can generate a list of predicted data mimicking a completed clinical trial, and obtained from a smaller number of known data. 
Unlike the contemporary interim analysis algorithms, this method.
1) uses AI that can classify data distributions of not only the known uncensored data but also the known censored data respectively, 
2) can generate predicting time data by compressive sensing for both uncensored and censored data
3) does not assume any distribution regarding with time, 
4) can generate hundreds of P-values calculated by a surviving test such as a log-rank test resulting in robust conclusion presumably, and 
5) if validated, would be able to predict the outcome of survival as the form of P-values distribution profile at any time on the way of the study. 
The boundary value of statistical error as a function of information fraction is designed by using the Lan-DeMets [3] spending function to approximate an O'Brien-Fleming [4] bound.  Power is designed for 0.8