Machine Learning and Artificial Intelligence in Pharmaceutical Research and Development: a Review.

Over the past decade, artificial intelligence (AI) and machine learning (ML) have become the breakthrough technology most anticipated to have a transformative effect on pharmaceutical research and development (R&D). This is partially driven by revolutionary advances in computational technology and the parallel dissipation of previous constraints to the collection/processing of large volumes of data. Meanwhile, the cost of bringing new drugs to market and to patients has become prohibitively expensive. Recognizing these headwinds, AI/ML techniques are appealing to the pharmaceutical industry due to their automated nature, predictive capabilities, and the consequent expected increase in efficiency. ML approaches have been used in drug discovery over the past 15-20 years with increasing sophistication. The most recent aspect of drug development where positive disruption from AI/ML is starting to occur, is in clinical trial design, conduct, and analysis. The COVID-19 pandemic may further accelerate utilization of AI/ML in clinical trials due to an increased reliance on digital technology in clinical trial conduct. As we move towards a world where there is a growing integration of AI/ML into R&D, it is critical to get past the related buzz-words and noise. It is equally important to recognize that the scientific method is not obsolete when making inferences about data. Doing so will help in separating hope from hype and lead to informed decision-making on the optimal use of AI/ML in drug development. This manuscript aims to demystify key concepts, present use-cases and finally offer insights and a balanced view on the optimal use of AI/ML methods in R&D.

Innovative trial designs and analyses for vaccine clinical development.

In the past decades, the world has experienced several major virus outbreaks, e.g. West African Ebola outbreak, Zika virus in South America and most recently global coronavirus (COVID-19) pandemic. Many vaccines have been developed to prevent a variety of infectious diseases successfully. However, several infections have not been preventable so far, like COVID-19, which induces an immediate urgent need for effective vaccines. These emerging infectious diseases often pose unprecedent challenges for the global heath community as well as the conventional vaccine development paradigm. With a long and costly traditional vaccine development process, there are extensive needs in innovative vaccine trial designs and analyses, which aim to design more efficient vaccines trials. Featured with reduced development timeline, less resource consuming or improved estimate for the endpoints of interests, these more efficient trials bring effective medicine to target population in a faster and less costly way. In this paper, we will review a few vaccine trials equipped with adaptive design features, Bayesian designs that accommodate historical data borrowing, the master protocol strategy emerging during COVID-19 vaccine development, Real-World-Data (RWD) embedded trials and the correlate of protection framework and relevant research works. We will also discuss some statistical methodologies that improve the vaccine efficacy, safety and immunogenicity analyses. Innovative clinical trial designs and analyses, together with advanced research technologies and deeper understanding of the human immune system, are paving the way for the efficient development of new vaccines in the future.