Regulatory structures surrounding clinical research in the United States represent the accretion of more than a century’s worth of efforts to ensure the safety and trustworthiness of medical products and to protect patients and consumers from fraud and abuse. However, the multiple regulatory regimes that currently govern research and the related bureaucracies that create and enforce these regulations have been criticized as complex, unclear, inconsistent, and increasingly and unsustainably burdensome (Institute of Medicine 2009; Department of Health and Human Services 2011; Kramer et al. 2012; Reith et al. 2013). In addition, critics have charged that regulations can hinder important research (Reith et al. 2013), and contribute significantly to the expense (Califf 2006) and difficulty of conducting trials (McMahon et al. 2009). A key challenge is how to evolve a regulatory structure that protects patients and the public while remaining efficient and flexible enough to facilitate needed research and methodological innovation. Here we describe key regulatory agencies and regulatory frameworks. We also discuss challenges and recent developments in the regulatory sphere that affect the ability to conduct effective, efficient, and affordable research.
US Regulatory Agencies
The Department of Health and Human Services
The Department of Health and Human Services (HHS) is the United States government’s principal agency for protecting the health of all Americans. Most of the agencies and institutes within DHHS are bound by a regulatory system known as the Common Rule, which is described in detail in the Appendix: Regulatory Frameworks.
Agency for Healthcare Research and Quality (AHRQ)
The Agency for Healthcare Research and Quality is responsible for supporting research designed to improve the quality of healthcare, reduce its costs, address patient safety and medical errors, and broaden access to essential services.
The National Institutes of Health (NIH)
The National Institutes of Health (NIH) supports biomedical and behavioral research domestically and abroad, conducts research in its own laboratories and clinics, trains promising young researchers, and promotes acquisition and distribution of medical knowledge. The NIH comprises 27 individual institutes, each with its own specific focus on a disease area, organ system, or patient population.
The Office of Human Research Protections (OHRP)
The OHRP is a part of the Office of the Assistant Secretary (OASH) in the Department of Health and Human Services (HHS). It oversees the system that protects the rights, welfare, and well-being of research participants and ensures that research is carried out in accordance with regulations described in the Code of Federal Regulations (CFR).
The US Food and Drug Administration (FDA)
Among its many responsibilities, the US Food and Drug Administration (FDA) oversees the safety of food, drugs, medical devices, and products that emit radiation:
FDA is responsible for
- Protecting the public health by assuring that foods (except for meat from livestock, poultry and some egg products which are regulated by the U.S. Department of Agriculture) are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drugs, and vaccines and other biological products and medical devices intended for human use are safe and effective
- Protecting the public from electronic product radiation
- Assuring cosmetics and dietary supplements are safe and properly labeled
- Regulating tobacco products
- Advancing public health by helping to speed product innovations
FDA regulates all clinical trials that are performed with the intent of bringing a new medical product to market, or of expanding marketing approval for an existing, approved therapy to a new indication. Although the FDA is part of DHHS, unlike other DHHS agencies and institutes it does not use the Common Rule as the basis for its regulations but is governed by a largely similar regulatory framework, described in Section 8.
- Informed Consent
- Alternative Approaches to Disclosure and Authorization
- Non-disclosure of Research Activities
- Data on Different Approaches to Disclosure
- Appendix: US Regulatory Agencies
- Appendix: Regulatory Frameworks
- Appendix: Institutional Regulatory Oversight
- Appendix: Emerging Regulatory Issues
Califf RM. 2006. Clinical trials bureaucracy: unintended consequences of well-intentioned policy. Clin Trials. 3:496–502. doi:10.1177/1740774506073173. PMID: 17170032.
Department of Health and Human Services. 2011. Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators.
Institute of Medicine. 2009. Beyond the HIPAA Privacy Rule: Enhancing Privacy, Improving Health Through Research. Nass SJ, Levit LA, Gostin LO, editors. Washington, DC: National Academies Press. http://www.ncbi.nlm.nih.gov/books/NBK9578/. Accessed December 15, 2013. PMID: 20662116.
Kramer JM, Smith PB, Califf RM. 2012. Impediments to clinical research in the United States. Clin Pharmacol Ther. 91:535–541. doi:10.1038/clpt.2011.341. PMID: 22318614.
McMahon AD, Conway DI, Macdonald TM, McInnes GT. 2009. The unintended consequences of clinical trials regulations. PLoS Med. 3:e1000131. doi:10.1371/journal.pmed.1000131. PMID: 19918557.
Reith C, Landray M, Devereaux PJ, et al. 2013. Randomized clinical trials—removing unnecessary obstacles. N Engl J Med. 369:1061–1065. doi:10.1056/NEJMsb1300760. PMID: 24024845.