Assay Guidance Manual: Quantitative Biology and Pharmacology in Preclinical Drug Discovery

Abstract

The Assay Guidance Manual (AGM) is an eBook of best practices for the design, development, and implementation of robust assays for early drug discovery. Initiated by pharmaceutical company scientists, the manual provides guidance for designing a "testing funnel" of assays to identify genuine hits using high-throughput screening (HTS) and advancing them through preclinical development. Combined with a workshop/tutorial component, the overall goal of the AGM is to provide a valuable resource for training translational scientists.

Figure 1

Diversity of the Assay Guidance Manual Editorial Board. The content of the Assay Guidance Manual is managed by an editorial board of 34 members, most with over 20 years of experience in drug discovery and development. The editors work in different settings including industry, academia, and nonprofit research institutes.

Figure 2

Worldwide access to the Assay Guidance Manual (AGM). The AGM was accessed 39,839 times by readers in 131 countries during the month of April 2017. The heat map shows the amount of access per country ranging from low (dark blue) to high (red). The countries colored grey did not access the AGM in April 2017.

Figure 3

Users of the Assay Guidance Manual (AGM) grouped by domain. The total number of AGM users in the United States during April are plotted according to domain over a period of 4 years from 2014 through 2017. Although usage is growing in all cases, the majority of AGM users come from .net, .edu, and .com domains.

Figure 4

Worldwide usage of the Assay Guidance Manual (AGM) since 2012. Usage of the AGM has been steadily growing since it was published as an eBook on the National Library of Medicine, National Center for Biotechnology Information Bookshelf in 2012. Time series decomposition (using a simple moving average (SMA) with a multiplicative model61) was applied to the access counts for the entire AGM and selected chapters. Individual components of the decompositions are shown in each plot, with the y‐axis for all plots representing access counts. The trend component was computed using an SMA with a 12‐month window. The seasonal component was derived from the observed time series by dividing by the trend component. The random component was computed by dividing the observed time series by the seasonal, followed by dividing by the trend components. (a) The total monthly access among all AGM chapters has steadily increased to >30,000 in 2017. (b) A plot of seasonally adjusted web access for all 46 chapters of the AGM, each shown as a different color. (c) Among the most widely‐accessed chapters is Early Drug Discovery and Development Guidelines: For Academic Researchers, Collaborators, and Start‐up Companies, which was accessed an average of 1,776 times per month in 2017. (d) The Immunoassay Methods chapter came from the original Eli Lilly and Company Quantitative Biology Manual and was the second most accessed chapter in 2017. (e) The most popular chapter of the AGM is Cell Viability Assays, which was accessed an average of 11,895 times per month in 2017. (f) The high‐throughput screening (HTS) Assay Validation chapter also originated from the Eli Lilly and Company Quantitative Biology Manual and has continued to grow in popularity over the past 6 years.

Figure 5

Participation in the Assay Guidance Workshop for High‐Throughput Screening and Lead Discovery. Ten assay guidance workshops have been conducted since 2015. (a) The number of participants in the workshops have varied between 23 and 169, with most workshops having <50. It was observed that open discussions and learning are enhanced with smaller group sizes. (b) A total of 549 individuals have participated in all 10 workshops and come from 14 countries in addition to the United States. (c) Participants of the 10 workshops come from a variety of settings, including industry, academia, and government. The first workshop and two largest workshops were only advertised to employees of the US Government, which is why the majority of the workshop participants are from the government. DOD, Department of Defense; EPA, Environmental Protection Agency; FDA, US Food and Drug Administration; NIH, National Institutes of Health; NIST, National Institute of Standards and Technology.