Concordance of Animal and Human Toxicity Workshop

The HESI Non-Clinical/Clinical Safety Correlations Technical Committee hosted a workshop September 20-21, 2007 in Washington, DC to develop a better understanding of the extent to which toxicities manifested in preclinical animal studies correlate with those seen in clinical trials.

Workshop Background

There is a widespread perception that laboratory animals are appropriate models for predicting the adverse effects of chemicals in humans.  For many classes of chemicals, testing this assumption is not practical.  By contrast, for pharmaceuticals, an extensive body of relevant data exists to explore the validity of this assumption.  Pharmaceuticals are evaluated both in animals and in humans; however, these data are generally not published.  Thus, it has generally been difficult to perform a comprehensive and systematic evaluation of the utility of the animal models for predicting human outcomes.  In addition, it has also been challenging to determine whether the range of preclinical tests performed to evaluate pharmaceuticals produce data that are relevant for the design and/or interpretation of human studies.  In light of continuing societal pressure to develop pharmaceuticals that are safe and efficacious while also minimizing animal use, a unique opportunity exists to conduct an examination of the value of animal studies as surrogates for predicting the toxicity of drugs to humans and to address how non-clinical studies can be optimized to improve drug safety.

In an effort to address these challenges, the HESI Non-Clinical / Clinical Safety Correlations Technical Committee has developed a database to evaluate the concordance of animal toxicity and safety pharmacology data with actual human toxicities (HTs) for a number of pharmaceutical agents exhibiting clinical toxicity during Phase I, II or III clinical trials.  The database includes over 85 separate human toxicities arising in clinical trials to evaluate over 125 compounds. The database contains compounds for which development programs were started after 1998 to ensure that studies were performed in a manner consistent with good laboratory practices (GLP). For each human toxicity in the database, the details for the corresponding animal toxicities have been fully documented.  The database also includes detailed compound information including toxicokinetic and metabolic interspecies comparison data.

The database was developed as a result of an earlier project which addressed the concordance between animal and human toxicities using a less detailed dataset. Consequently, the first stage of the project has been extended into a second stage to broaden the scope of the data collected and to generate additional data in a prospective manner.

Workshop Objective

The Non-Clinical / Clinical Safety Correlations Technical Committee was organized to develop an improved understanding of the extent to which various types of human toxicities (HTs) manifested during clinical trials could be predicted from standard toxicology studies.  Accordingly, the primary objective for the workshop is to evaluate the extent to which various types of human toxicities manifested during clinical trials can be predicted from standard preclinical animal toxicology studies.

The workshop was organized to provide an opportunity for review and discussion of the project database.  The outcome of the workshop will be a consensus report describing the findings from the database relative to a number of specific toxicity endpoints, and assessing the animal-human toxicity correlations for each endpoint. The report will also identify gaps in understanding and deficiencies based on the database analysis.

The specific goals of the workshop are:

• • Provide an opportunity for review and discussion of the database and its findings.
• • Develop a consensus report describing the conclusions from the database evaluation.
• • Identify gaps in understanding whose resolution might facilitate the development of animal models more predictive of the human experience.
• • Make recommendations regarding future study design.
• • Describe future opportunities for method development (in vivo, in vitro, models, etc.).

Workshop Audience

The workshop brought together clinicians and toxicologists with broad experience and backgrounds to address the salient issues raised by the analyses of the database.  Scientists from government, industry, and academia that have an interest in the correlation between animal and human toxicities are encouraged to participate.

Workshop Program

The workshop began on Thursday, September 20, 2007 at 8:00 a.m., and concluded at approximately 4:30 p.m. on Friday, September 21, 2007.  The workshop began with a summary of the development of the project dataset and the range of information included in the database.  The workshop  also featured breakout sessions that focused on the data associated with specific toxicity endpoints.  These breakout sessions provided workshop participants with an opportunity to work directly with the project data.

Click Here for Workshop Program

About HESI

The ILSI Health and Environmental Sciences Institute (HESI) is a global branch of the International Life Sciences Institute, a public, non-profit scientific foundation with branches throughout the world. ILSI HESI provides an international forum to advance the understanding and application of scientific issues related to human health, toxicology, risk assessment and the environment. ILSI HESI is widely recognized among scientists from government, industry and academia as an objective, science-based organization within which important issues of mutual concern can be discussed and resolved in the interest of improving public health. As part of its public benefit mandate, ILSI HESI’s activities are carried out in the public domain, generating data and other information for broad scientific use and application. ILSI HESI’s programs are supported primarily by its industry membership. ILSI HESI also receives support from a variety of government agencies from the U.S. and internationally.

Workshop Location

The Doubletree Hotel, 1515 Rhode Island Avenue NW, Washington, District of Columbia, 20005, (phone) 202-232-7000, is located at the crossroads of 15th Street and Rhode Island Avenue.  The hotel is centrally located 3 blocks from Dupont Circle and 3 miles from Reagan National Airport (DCA).  Capital Hill, the White House, Union Station, monuments, museums and metro stations are just a short walk away.

For additional information contact:
Dr. James Kim
ILSI Health and Environmental Sciences Institute
1156 15th Street, NW
Washington, DC 20005 USA
Tel: (202) 659-3306
Fax:(202) 659-3617

Email: jkim@hesiglobal.org