The U.S. Environmental Protection Agency (EPA) has a mission and regulatory responsibility to protect human health and the environment. EPA's pursuit of that goal includes a variety of research activities involving human subjects, such as epidemiologic studies and surveys. Those research activities also involve studies of individuals who volunteer to be exposed to air pollutants intentionally in controlled laboratory settings so that measurements can be made of transient and reversible biomarker or physiologic responses to those exposures that can indicate pathways of toxicity and mechanisms of air-pollution responses. The results of those controlled human inhalation exposure (CHIE) studies, also referred to as human clinical studies or human challenge studies, are used to inform policy decisions and help establish or revise standards to protect public health and improve air quality.

Controlled Human Inhalation-Exposure Studies at EPA addresses scientific issues and provides guidance on the conduct of CHIE studies. This report assesses the utility of CHIE studies to inform and reduce uncertainties in setting air-pollution standards to protect public health and assess whether continuation of such studies is warranted. It also evaluates the potential health risks to test subjects who participated in recent studies of air pollutants at EPA's clinical research facility.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• COMMITTEE ON ASSESSING TOXICOLOGIC RISKS TO HUMAN SUBJECTS USED IN CONTROLLED EXPOSURE STUDIES OF ENVIRONMENTAL POLLUTANTS
• BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
• OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
• Preface
• Abbreviations
• Summary
  • THE COMMITTEE'S STUDY
  • THE DEVELOPMENT OF CONTROLLED HUMAN INHALATION-EXPOSURE STUDIES
  • VALUE OF CONTROLLED HUMAN INHALATION-EXPOSURE STUDIES
  • POTENTIAL SOCIETAL BENEFITS OF FUTURE STUDIES
  • RISKS TO PARTICIPANTS IN PAST CONTROLLED HUMAN INHALATION-EXPOSURE STUDIES
  • THE CONTINUED CONDUCT OF CONTROLLED HUMAN INHALATION-EXPOSURE STUDIES BY THE ENVIRONMENTAL PROTECTION AGENCY
  • CHARACTERIZING RISKS TO SUBJECTS IN FUTURE STUDIES
  • COMMUNICATION WITH POTENTIAL STUDY SUBJECTS ABOUT INFORMED CONSENT
  • CONCLUDING REMARKS
• 1. Introduction
  • A PRIOR NATIONAL RESEARCH COUNCIL REPORT ON CONTROLLED HUMAN EXPOSURE STUDIES
  • CHIE STUDIES AT EPA
  • EPA'S OFFICE OF INSPECTOR GENERAL REPORT
  • COMMITTEE'S STATEMENT OF TASK
  • TERMS FOR REFERRING TO INDIVIDUALS EXPOSED IN CHIE STUDIES
  • ORGANIZATION OF THE REPORT
• 2. Foundational Aspects of Human-Subjects Research
  • INTRODUCTION
  • AIR POLLUTION HEALTH EFFECTS SCIENCE FOR MANAGING AIR QUALITY
  • HUMAN-SUBJECTS RESEARCH
  • RISK–BENEFIT FRAMEWORK
• 3. Value of Controlled Human Inhalation Exposure Studies
  • INTRODUCTION
  • A FRAMEWORK FOR EVALUATING CHIE STDUIES
  • SENSITIVE GROUPS
  • CHIE STUDIES IN THE CONTEXT OF TOXICOLOGIC AND EPIDEMIOLOGIC STUDIES, AND THE LARGER RESEARCH AGENDA
  • USE OF BIOMARKERS IN CHIE STUDIES
  • COMPARING CHIE STUDY EXPOSURES WITH AMBIENT POLLUTANT EXPOSURES
  • CONSIDERATIONS OF CHIE STUDY VALUE FOR EPA DECISION MAKING
  • CHIE OZONE STUDIES
  • CHIE PM STUDIES
  • CONCLUSIONS
• 4. Assessment of Controlled Human Inhalation Exposure Studies at EPA and Associated Adverse Events
  • INTRODUCTION
  • THE EIGHT STUDIES IDENTIFIED BY EPA FOR CONSIDERATION BY THE COMMITTEE
  • EVALUATION OF EVIDENCE FOR ADVERSE EVENTS RESULTING FROM PARTICIPATION IN A CHIE STUDY
  • ADVERSE EVENT REPORTING
  • RELATIONSHIP OF SHORT-TERM CHIE STUDY EXPOSURE TO CHRONIC DISEASE RISKS
  • CONCLUSIONS
• 5. The Continued Conduct of Controlled Human Inhalation Exposure Studies by EPA
  • SCIENTIFIC CONTRIBUTIONS OF PAST CHIE STUDIES
  • PAST BENEFITS TO SOCIETY
  • STUDY PARTICIPANT SAFETY
  • POTENTIAL FUTURE SOCIETAL BENEFITS
  • ADDITIONAL EXTERNAL SCIENTIFIC INPUT
  • CONCLUSION AND RECOMMENDATION
• 6. Characterizing Risks to Subjects in Controlled Human Inhalation Exposure Studies
  • AUDIENCES FOR RISK CHARACTERIZATION ASSOCIATED WITH CHIE STUDIES
  • EXCLUSION CRITERIA FOR SCREENING STUDY SUBJECTS
  • FACTORS THAT MIGHT TRIGGER AN ADVERSE OUTCOME
  • WHAT ADVERSE OUTCOMES MIGHT BE EXPECTED AND WHEN? REASONABLY FORESEEABLE RISKS
  • CHARACTERIZATION OF RISKS ASSOCIATED WITH CHIE POLLUTANT EXPOSURES
  • USE OF THE EXPOSURE COMPARATOR APPROACH FOR CHARACTERIZING RISK
  • RECOMMENDATIONS
• 7. Communication about Informed Consent in Controlled Human Inhalation Exposure Studies
  • INTRODUCTION TO INFORMED CONSENT AND THE COMMON RULE
  • RESEARCHER COMMUNICATION AND PARTICIPANT UNDERSTANDING OF INFORMED CONSENT
  • RECOMMENDATIONS
• References
• APPENDIXES
  • Appendix A. Biographical Information on the Committee on Assessing Toxicologic Risks to Human Subjects Used in Controlled Exposure Studies of Environmental Pollutants
  • Appendix B. Public Information-Gathering Sessions
  • Appendix C. Assessment of Eight Controlled Human Exposure Studies

Suggested citation:

National Academies of Sciences, Engineering, and Medicine. 2017. Controlled Human Inhalation-Exposure Studies at EPA. Washington, DC: The National Academies Press. doi: 10.17226/24618.