The second part of the meeting will address the effect on clinical research of fraud and abuse laws, including the Anti-Kickback Statute and the Beneficiary Inducement provisions of the Civil Monetary Penalty Law, as well as their state law counterparts. Briefly stated, fraud and abuse laws place limitations on remuneration provided to health care providers and patients to prevent third-party payors of healthcare services from paying for medically unnecessary or excessive services and to prevent patients from being induced to select a particular healthcare provider. While these laws are not explicitly directed towards the research environment, they have major implications for clinical research conducted in the United States, affecting practices ranging from research sponsors paying for copayments or deductibles associated with standard of care services required under a clinical trial protocol, to payments from life sciences companies to physicians to collect data for registry studies, to the provision of “smart devices” to patients as part of a research study.
Attendees learned about the impact of fraud and abuse laws on clinical research, overviewing research situations that may violate these laws and discussing how these laws relate to recruitment, compensation, and financial aid for research participants.
Topics: I) Legal and Regulatory Issues Related to COVID-19 in Human Subjects Research, II) Foreign Influence in Clinical Research, and III) Impact of Fraud and Abuse Laws on Clinical Research
The first part of the meeting will address the ongoing National Institutes of Health (NIH) and U.S. Department of Defense (DoD) investigations into foreign influence in American research. The NIH and DoD investigations have focused on scientists in the United States who have received and not properly disclosed foreign appointments and remuneration. The NIH has named 180 scientists at 71 institutions as targets of investigation and asked their respective institutions to investigate them. The government appears concerned that researchers who receive federal funding have failed to disclose foreign financial interests and time commitments, thus misleading the U.S. government when it evaluates research awards, thus harming the federal fisc and the American research enterprise. In addition, the U.S. government fears that foreign influence on scientific research is allowing the transfer of intellectual property to foreign countries without being subject to export regulations set forth by the U.S. Department of Commerce. While the investigations have to date primarily affected academic organizations, their impact may well spread to industry as academic investigators who conduct research for industry sponsors come under investigation and the scope of the government’s investigation widens.
Attendees learned about the NIH and DoD investigations into foreign influence in clinical research and discussed how research activities within academia and industry may have to adapt to accommodate the government’s concerns.
Topics: I) Legal and Regulatory Issues Related to COVID-19 in Human Subjects Research, II) Foreign Influence in Clinical Research, and III) Impact of Fraud and Abuse Laws on Clinical Research
When an academic institution or life sciences company becomes aware of allegations of research misconduct (i.e., fabrication or falsification of data and/or images, and plagiarism) relating to their researchers, a challenging and time-intensive process of review typically ensues. Academic institutions frequently utilize the detailed investigational framework that is required when the allegation relates to federally funded research, while life sciences companies typically are not restricted by these requirements but nevertheless have additional relevant legal and ethical obligations (for example, securities law, FDA and EMA submission implications, and published scientific papers). Throughout the process, issues of privacy, confidentiality, and reputation must be addressed. This session will deal with some of the most vexing problems in complex research misconduct cases, especially those that lie at the intersection of industry and academia.
Attendees discussed the most vexing problems in complex research misconduct cases, especially those that lie at the intersection of industry and academia. For example, how should an academic institution investigate research misconduct allegations in research collaborations between in-house industry labs/scientists and academic investigators? What are the attendant liability risks for informing or not informing the successor employer of a scientist who has been found to have engaged in research misconduct?
Communication between journals, publishers, and institutions on questions of research misconduct is often lacking due to several reasons, including the speed with which journals seek to resolve these questions and institutional hesitancy to breach the confidentiality of an investigation into research misconduct. Representatives of academic journals, journal publishers, and institutions gained an appreciation for how the other parties manage questions of research misconduct and identified strategies to facilitate increased collaboration and communication between journals and institutions.
Research misconduct allegations may trigger reporting obligations to domestic and international funding agencies, health regulatory authorities, and others. R3 attendees, which included representatives from U.S. funding and regulatory agencies, academia, and biopharmaceutical companies, discussed the challenges of varying reporting requirements, including timing, content, and need for confidentiality. Attendees clarified the different responsibilities of the different entities during investigations into research misconduct and identified strategies and solutions to mitigate these challenges.
Decentralized clinical trials (DCTs) are clinical trials that are executed in part or in whole through remote modalities, such as telemedicine, smart phone applications, and health care providers who visit participant homes. Vendors engaged in DCTs may be subject to unfamiliar compliance and regulatory obligations, such as those set forth by the Common Rule or the FDA. Common Rule obligations extend beyond federally funded research if the site’s internal policy or state law require compliance with the Common Rule regardless of the funding source for the study. Part II of the meeting drew from both OHRP and FDA requirements to determine the regulatory requirements for a third-party partner who provides services in connection with a research protocol.
Topics: Part I: Direct Interactions Between Sponsors and Research Participants: A Legal Perspective; Part II: Rethinking the Workforce for Decentralized Clinical Trials: Who is Engaged and Regulatory Requirements
Meeting attendees overviewed and discussed the history of LDT regulation, shifting approaches to LDT regulation before and during the COVID-19 pandemic, strategies for navigating LDT regulation, and the relevance of FDA’s investigational device exemption framework to the regulation of LDTs.
Topics: 1) Legal and Regulatory Challenges with Diagnostic Tests in the United States (US), including Laboratory Developed Tests (LDTs), and 2) The Impact of Emerging US State Privacy Laws on Research
Research that is executed in part or in whole through remote modalities, such as telemedicine and health care providers who visit participant homes, is increasingly commonplace yet complicated. Decentralized research raises novel questions regarding whether and which institutions are engaged in research under the Common Rule and who is a subinvestigator according to United States Food and Drug Administration (FDA) regulations. Mark Barnes, MRCT Center Faculty Director, overviewed the concept of engagement in research subject to the Common Rule and proposed a model to redefine the concept of engagement. David Peloquin, MRCT Center Senior Advisor, overviewed the investigator and subinvestigator designations in research subject to FDA regulations.
The European Union (“EU”) General Data Protection Regulation (“GDPR”) and its effect on research activities was the first topic addressed by the R3 at its initial meetings in 2018. In the four years since those meetings, there have been many developments that have continued to cause complications for trans-Atlantic research. These have included, among others, the invalidation of the EU-U.S. Privacy Shield in June 2020 by the Schrems II decision, Brexit, the release in 2021 of new Standard Contractual Clauses by the European Commission, and the introduction of data transfer impact assessments as a prerequisite for many cross-border transfers of personal data.
On March 25, 2022, the European Commission and the United States announced that they have agreed in principle on a new Trans-Atlantic Data Privacy Framework, intended to foster trans-Atlantic data flows and address the concerns raised by the Court of Justice of the European Union in the Schrems II decision. The discussion at the convened R3 considered these recent developments and identified potential solutions to ease trans-Atlantic research while complying with GDPR.
The core activities of clinical trials are typically conducted at physical locations referred to as “sites.” Traditionally, these sites are hospitals or academic medical centers. While these traditional sites remain important fixtures in the clinical trial landscape, new models including “decentralized” or even “site-less” clinical trials have emerged. David Peloquin, MRCT Center Senior Advisor and Partner at Ropes & Gray LLP, provided an overview of the clinical trial site landscape and how it has changed over time, with a particular focus on the emergence of stand-alone sites, as such sites present unique regulatory issues. He then provided several examples of these stand-alone sites and presented a handful of recent regulatory enforcement cases before moving into a discussion of the relevant legal risks and considerations.
