David Peloquin discusses the development and future directions of clinical research regulations.
In a conversation with The Regulatory Review, Ropes & Gray partner David Peloquin discusses how clinical research studies are regulated in the United States to protect patients and accommodate changing practices.
In recent years, clinical research studies in the United States have increased in complexity alongside the rise of new trial formats, sources of data, and health technologies. As new ways of conducting research develop, Peloquin argues that regulators must work to keep up with changing research mechanisms and norms.
Peloquin explains how clinical research is shaped by different areas of regulation. For example, he notes how federal and state regulations interact to protect participant safety. Global health events, such as the COVID-19 pandemic, have also affected regulatory measures for clinical research, and Peloquin finds that researchers must adapt to changing standards as pandemic-era policies expire.
Peloquin argues that regulating clinical research today comes with challenges. For example, digital technologies used during the research process require different regulatory approaches depending on whether the technology is classified as a “medical device” or used solely to capture patient data. Moving forward, he argues, regulators must create clear guidelines for research practice that minimize room for uncertainty.
Peloquin is a partner in Ropes & Gray’s health care group. His practice focuses on advising clients—such as academic medical centers, universities, life sciences companies, and clinical laboratories—on compliance with laws and regulations related to clinical research, data privacy, health care licensure, and other related areas. Peloquin has published articles on regulatory and legal developments in health law, data privacy, and federal regulation in the Journal of Health and Life Sciences Law, Science, and the Journal of Law, Medicine & Ethics. Peloquin also served for several years as a Community Member of the Institutional Review Board (IRB) for the Mass General Brigham health system.
The Regulatory Review is pleased to share the following interview with David Peloquin.
The Regulatory Review: How does regulation govern clinical research in the United States?
Peloquin: At the federal level, there are two distinct sets of regulations that govern clinical research. The first is the Federal Policy for the Protection of Human Subjects, also known as the Common Rule, which applies to research conducted or supported by most federal departments and agencies. The second is the regulations protecting human subjects of the U.S. Food & Drug Administration (FDA). These regulations apply to most studies involving human subjects and a “test article” that is regulated by FDA, such as a drug, device, or biologic. It is possible for a single study to be subject to both sets of regulations concurrently, such as a Department of Defense-funded clinical trial of an investigational drug. The Common Rule and FDA regulations are very similar, and FDA issued a notice of proposed rulemaking in September 2022 that seeks to harmonize further the two sets of regulations.
In addition to federal regulations, many states maintain laws that govern human subjects research. These laws can apply in addition to federal regulations. For example, California requires that most study subjects receive an experimental research subjects bill of rights. State laws may also fill the gap in instances in which the federal regulations do not apply, such as when a clinical research study does not receive support from the federal government and does not involve a product regulated by FDA.
TRR: In what ways, if any, are human subjects who participate in clinical research studies protected by current regulation?
Peloquin: The federal regulations governing research involving human subjects are based on the Belmont Report, a document published in 1979 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which had been created by the National Research Act. The report articulated three ethical principles governing research: respect for persons, beneficence, and justice.
Respect for persons requires that people be treated as autonomous agents and that persons with diminished autonomy be afforded protection. The federal regulations apply this principle by requiring that, in most circumstances, individuals provide informed consent before they enroll in a research study. The regulations also provide additional protections for individuals with diminished autonomy, such as children or prisoners. The requirement for informed consent can be waived only if an Institutional Review Board overseeing the research determines that several elements are satisfied.
Beneficence requires researchers to maximize benefits and minimize harms of research. The federal regulations apply this principle by requiring that an IRB overseeing a study determine that the study’s risks to subjects are reasonable in relation to both any anticipated benefits to the subjects and the importance of the knowledge that may reasonably be expected to result from the research.
The principle of justice focuses on who receives the benefits of research and who bears its burden. The federal regulations apply this principle by requiring an IRB to determine that the selection of subjects is equitable by taking into account the purposes of the research and the setting in which the research is conducted.
TRR: You have written about considerations for researchers when using new digital health technologies. In a nutshell, what are these new advancements, and what challenges may researchers encounter when using them in their studies?
Peloquin: Digital technologies are increasingly used in clinical studies. In some cases, the digital technology may be used in a manner that renders it a medical device that is the object of the study, such as when the technology is intended for use in the diagnosis or treatment of disease or other conditions. In such a case, the technology will generally be subject to FDA’s regulations on investigational devices.
One challenge of studies involving digital technologies is recognizing when the product under study will be regulated as a medical device. FDA’s regulations and guidance in this area have evolved greatly in recent years, and it can be difficult for researchers and their institutions to stay current on the latest requirements.
Even when digital technologies are not used as a device that is the object of a study, digital technologies are increasingly used to capture data. For example, a mobile application may be used to permit study subjects to complete a study subject diary in a study of an investigational drug. In this case, the application would generally not be regulated as a “device” by FDA. Use of the application, however, could raise several questions about how study subjects’ privacy is protected, such as what data are obtained by vendors that supply the application, how those data are used, and what mechanisms are in place to secure the data.
TRR: You have written about the end of pandemic-era IRB requirements for researchers. How did research regulation change during the COVID-19 pandemic? In what ways might regulation continue to change as we move away from the pandemic?
Peloquin: One of the biggest changes was the growth of “decentralized clinical trials” (DCT). A DCT is a clinical trial in which some or all of the activities take place away from traditional clinical trial sites. Such studies may involve study visits at a subject’s home conducted by mobile health care providers or through the use of telemedicine technologies, or visits by study subjects to local health care providers in their community who are not study investigators, such as a pharmacy’s primary care clinic. Early on in the COVID-19 pandemic, FDA released guidance on its approach to regulating such studies. Elements of this guidance were recently finalized in FDA’s final guidance document on “Conducting Clinical Trials with Decentralized Elements,” which was issued in September 2024. This guidance addresses key questions, such as which personnel participating in a DCT qualify as investigators or subinvestigators or what level of supervision the investigator is required to exercise over local health care providers.
Many of the challenges to conducting DCTs come from state law. States generally require that a physician treating a patient located in their state hold a valid medical license to practice in such state. This requirement can limit the use of telemedicine, including in clinical studies, as it restricts a physician located in one state from providing a telemedicine service to a patient located in a state where the physician lacks a license. During the COVID-19 pandemic, many states relaxed these requirements. However, after the pandemic, many states have reinstated such requirements.
TRR: What mechanisms does FDA use to ensure proper research practices in clinical studies?
Peloquin: FDA has several tools at its disposal to ensure proper research practices. The agency maintains regulations that govern the protection of human subjects. These regulations require that an IRB review and approve a clinical investigation before it begins, that subjects either provide their informed consent for participation or that an IRB waive the consent requirement, that financial relationships between the study sponsor and study investigators be disclosed to FDA to identify and manage conflicts of interest, and that electronic records created in clinical investigations adhere to specific standards.
FDA maintains a bioresearch monitoring (BIMO) program through which it evaluates the conduct of FDA-regulated clinical research and pre-clinical research. The BIMO program includes on-site inspections, data audits, and remote assessments both in the United States and internationally. FDA conducts BIMO site visits to IRBs, clinical investigators, sponsors, monitors, contract research organizations, and laboratories.
TRR: How can regulators facilitate ethical and effective clinical research?
Peloquin: Regulators need to balance the need to safeguard human subjects participating in research with streamlining the conduct of clinical studies to ensure that products with the potential to improve the lives of patients are able to reach the market quickly. One way in which regulators can facilitate research is by ensuring that the standards for the conduct of research are clear and understandable to the regulated community. Uncertainty can lead to study sponsors and investigators taking conservative positions that slow the conduct of research.
Another way in which regulators can facilitate research is by staying up-to-date on the evolving models of clinical research. For example, ensuring that regulations and guidance address topics like DCTs and the use of digital technologies in studies can help to ensure that the regulations are fit for their purpose and serve to facilitate important trials while safeguarding research subjects.
