Human clinical trials, research with animals, basic research programs, and use of research grant funding are targets for heightened public scrutiny and government enforcement. Ropes & Gray represents many participants in biomedical and scientific research, including universities, pharmaceutical and medical device companies, biotechnology firms, academic medical centers, pediatric and other specialty hospitals, research institutes, and clinical research organizations.
Our research compliance specialists, some of whom have held senior research and legal positions in prominent universities and medical centers, represent these entities in their efforts to achieve and maintain regulatory compliance and assist them in defending their clinical and other research programs. We have special expertise in litigation relating to clinical trial matters and in international research and development projects, including adherence to the Foreign Corrupt Practices Act and securing national research authority approvals for clinical trials.
Our capacities include all North American and European contexts, and we have special expertise in emerging economies and other developing regions of the world.
Examples of our work include:
- Drafting policies to govern the research enterprise of academic medical centers, including institutional review board policies, research conduct policies, conflict of interest policies, and research misconduct policies;
- Negotiating with national governments, including ministries of health, national research oversight offices, and food and drug agencies, in regards to initial approvals for clinical trials or resolving compliance problems or allegations of abuse of human subjects in clinical trials;
- Defending research sponsors and research institutions in litigation and regulatory actions relating to alleged protocol deviations, regulatory violations, lack of informed consent, and subject injuries;
- Fact-finding relating to compliance problems, informed consent issues and serious adverse events in clinical trials of drugs, devices or biotechnology agents;
- Reporting to and negotiating resolutions of regulatory issues with the U.S. Food and Drug Administration (“FDA”), the U.S. Department of Health & Human Services Office for Human Research Protections (“OHRP”) and other national food and drug authorities relating to problems reported in clinical research;
- Negotiating clinical trial and other research agreements and subcontracts between industry and academic medical center clients, on the one hand, and local research sites, on the other;
- Identifying and screening clinical trial sites;
- Negotiating agreements with clinical research organizations on behalf of industry or academic institution clients;
- Compliance monitoring of clinical trials;
- Investigating allegations of animal abuse, including lack of appropriate veterinary care and other compliance issues;
- Investigating possible fabrication or falsification of data relating to any research, including bench-science studies and studies with humans and animals;
- Liaising with academic and scientific journals relating to retraction or correction of articles due to fabrication or falsification of data or other deviations from approved research protocols;
- Fact-finding, negotiation and resolution of research grant and contract issues, particularly related to allegations of misuse or poor performance under U.S. government grants or contracts; and
- Investigating and resolving allegations of inappropriate billing of insurers and other third-party payors for clinical services rendered to research subjects.
Clinical Trials: Regulatory and Litigation Matters. We have represented a variety of research sponsors and research site clients in all regulatory aspects of clinical trial compliance, including defense of FDA, OHRP and other national research authority investigations. Additionally, we assist clients in prophylactic planning of clinical trials, including in emerging economies, in order to minimize legal risk. We have investigated and helped rectify situations of significant noncompliance in clinical trials with ICH and national research laws, including failure to report adverse events or SUSARs, failure to gain informed consent, and falsification or fabrication of CRFs. We also have represented research sponsors in liability litigation relating to alleged protocol deviations and other regulatory violations.
Governmental Investigations and “Whistleblower” Complaints. We advise research sponsors and research institutions in their responses to whistleblowers and other allegations or investigations by federal agencies, including the National Institutes of Health (“NIH”), FDA, OHRP, the Office of Research Integrity, the Office of Laboratory Animal Welfare, the United States Department of Agriculture Animal and Plant Health Inspection Service, the Centers for Disease Control and Prevention, and other federal and state agencies. We have handled many cases initiated by whistleblowers and, working with our colleagues in Ropes & Gray’s white collar defense practice, have particular expertise counseling clients involved in joint whistleblower/governmental cases. We assist clients in analyzing past compliance practices, responding to governmental inquiries, implementing corrective action plans, and negotiating corporate integrity agreements or other settlement agreements to resolve such inquiries. We often coordinate with other consultants and professionals, such as accounting firms, in areas such as forensic and grants accounting.
Compliance Reviews/Client Investigations. We design and conduct routine and focused compliance reviews of research policies and procedures, identifying strengths and weaknesses for our client’s consideration and potential policy revisions. We also conduct targeted internal investigations when the client believes its internal procedures, external regulations, or agreements may have been violated or an issue has been raised by a complaint or allegation. We help research enterprises, institutional review boards (“IRBs”), and investigators determine whether, and in what manner, their practices may not comply with federal regulations and if research activities should be altered or temporarily suspended to achieve an acceptable level of compliance.
Research Misconduct and Communicating with Professional Journals regarding Retractions. We assist clients in responding to allegations of research misconduct, which is generally regarded as including the falsification or fabrication of research data, and plagiarism. We are familiar with the extensive array of issues facing clients whose employed scientists, post-doctoral fellows, investigators, faculty or medical staff have been accused of scientific misconduct, including matters relating to the preservation of evidence, the conduct of inquiries and investigations, reporting obligations, the relative responsibilities of participants in regard to jointly awarded grants, duties to notify the FDA, NIH or other governmental agencies, and liability relating to defamation. We have substantial experience in interacting with journals and professional societies that have received presentations or have published articles affected by research misconduct.
Integration of Research and Clinical Care. We advise investigators and clinical sites concerning the integration of research and clinical activities, including proper billing procedures for medical services rendered to patients involved in clinical trials. We help create policies and practices that relate the work of clinical trial staff to that of health provider’s financial offices, thereby ensuring the adequacy of clinical trial budgets and preventing insurance billing that is inconsistent with research protocols or federal reimbursement rules. Billing practices in this area have been the focus of recent increased scrutiny by the federal government.
Research Compliance Program Design and Implementation. We help participants in the research field design and implement compliance programs for all aspects of their operations, including: human research, animal research, external grant and contract funding, export controls, conflicts of interest and commitment, and research misconduct. These programs are often developed and implemented – or materially revised and improved – in connection with government or other funder audits, qui tam suits, corporate integrity agreements, or other agreements reached with various federal authorities.
Government Grants and Contracts. Much of the research enterprise is powered by grant and contract funds that flow from agencies of the federal government, including NIH, Centers for Disease Control, Health Resources Services Administration, Department of Energy, Department of Defense/DARPA, Department of Education, and National Science Foundation (“NSF”). With these funds come complicated terms and conditions for use execution of work scope. We advise clients on policies and procedures to assure compliance with these terms and conditions and defend clients when their grant and contract practices come under external scrutiny. Among the issues on which we advise are: time and effort reporting, indirect cost rates, purchase and management of capital equipment, compliance with grant terms in international contexts, often in developing countries and emerging markets, and other matters under OMB A-21 and A-110.
Conflicts of Interest and Commitment. Our attorneys have drafted policies, procedures and forms to implement internal programs to identify and manage investigators’ and senior officials’ conflicts of interest and conflicts of commitment. These programs are designed to comply with standards issued by NIH/PHS, NSF, FDA and ICMJE, among others, and to be consistent with institutional processes relating to sponsored research applications. We have trained conflict of interest officers and committees to enable their compilations of sets of case precedents by which to assess and manage potential conflicts.
IRB, IACUC and Responsible Conduct of Research Education. Members of the Health Care Practice Group have served as outside counsel to or members of IRBs and IACUCs affiliated with academic medical centers and community hospitals. We are intimately familiar with the IRB and animal research approval processes and with the problems throughout the range of research compliance concerns, from export controls to attribution of authorship to biosafety. We conduct generalized and targeted educational sessions for IRB, IACUC, and biosafety committee members and for investigators as routine compliance training and in response to specific correction plans.
Institutional Research Policies. We develop and revise institutional research policies concerning the rights and responsibilities of grantees and investigators, all aspects of privacy in the research process, conflict of interest issues, commercialization of intellectual property, export controls, retention and maintenance of research data and materials, and sponsored research. Our attorneys analyze complex regulatory requirements and clarify them into actionable guidelines for our clients. We have developed guidelines for billing compliance, time and effort reporting, and other sponsored research administration rules, and have assisted clients in preparing for AAHRPP and AAALAC accreditation.
Business Issues related to Research. We counsel a broad variety of clients on the tax, business, and financing issues related to the research enterprise. These issues include clinical trial agreements and the protection and licensing of technology and intellectual property, joint “incubator” projects between academic medical centers and venture capital funds, exclusive or “first look” arrangements between research institutes and pharmaceutical companies, and advice concerning ways in which the research enterprise can be financed, leveraged, or spun off.
Academic Medical Centers and Research Institutes:
- Designed and drafted a comprehensive set of policies and procedures to govern the research enterprise at an academic medical center located in the Middle East that sought to implement policies and procedures consistent with U.S. regulations in order to conduct research funded by the U.S. federal government and/or research involving FDA-regulated products. This involved creating a research governance manual, an institutional review board/ethics committee manual, and a research conduct manual.
- Assisted a leading pediatric hospital in responding to an OHRP inquiry stemming from a complaint by the parents of a research subject who died while enrolled in an oncology study at the hospital. We worked extensively with the clinicians involved to craft a detailed response showing why the hospital’s treatment of the research subject was clinically appropriate and fully consistent with the federal regulations governing human subjects research.
- Assisted a leading pediatric hospital in responding to a complex FDA Form 483 response, including identifying supporting documentation and relevant corrective and preventative actions and associated timelines.
- Counseled a leading AMC in its response to an FDA inspection of alleged clinical investigator misconduct during the conduct of clinical trials. We reviewed extensive source documents, case report forms, medical charts, and IRB records, and conducted detailed interviews with study staff, including the clinical investigator, study coordinators, research compliance staff, supervising physicians, and the IRB administrators. We assisted the institution in developing and implementing corrective and preventive actions (“CAPAs”) to address the FDA-identified deficiencies, and the recurrence of those and similar issues and helped draft a robust and comprehensive response to the FDA, including identifying supporting documentation and relevant CAPAs and associated timelines.
- Advised a leading pediatric hospital and AMC in a collaboration agreement by which the AMC licensed certain of its pediatric genetic data to a genomics company in consideration of an up-front payment, milestones and royalties. Under the terms of the agreement, the genomics company will pay for an exclusive license to use the rare and orphan disease samples taken from the AMC’s biobank for purposes of developing and commercializing therapeutic treatments and diagnostic targets for rare and orphan diseases.
- Served as regulatory counsel to a major research university conducting medical research involving fetal tissue. Following concerns raised by a member of the university’s board regarding fetal tissue research, we conducted a review of the university’s policies and procedures to determine whether such research was consistent with applicable state and federal law.
- Represented a major research university in connection with an investigation by the Federal Select Agents Program concerning the inadvertent release of a Select Agent from a research facility.
- Assisted a drug manufacturer with an internal investigation into a Phase III clinical trial site in Central America. The investigation team is examining protocol deviations that occurred at the study site and is assessing the overall conduct of the site's principal investigator. The investigation is also examining reporting of adverse events, as well as the conduct of study monitors who interfaced with the principal investigator.
Pharmaceutical and Biotechnology Companies:
- Achieved highly favorable settlement for two multinational pharmaceutical companies regarding their joint venture drug after a widely publicized investigation by 36 state attorneys general into whether the companies had intentionally delayed the release of clinical trial results. Our clients agreed to reimburse costs associated with the investigation with no additional penalty. We also succeeded in securing a declination of a parallel Department ofJustice investigation.
- Represented a major pharmaceutical company in connection with a civil subpoena issued by the New York Attorney General’s Office seeking information about: drug safety and clinical trial results, off-label uses and off-label promotion of drugs, remuneration and kickbacks, sales and prescription data, and pricing information.
- Represented a major pharmaceutical company in an internal investigation into the origin of inaccurate clinical trial data and the inclusion of that data in external presentations, academic publications, and regulatory submissions. After completing the factual investigation, we assisted the client with remedial steps, including discipline decisions and improvements to internal controls. We also advised the client on outreach to various external stakeholders, including regulators, authors, and investigators.
- Drafted policies to govern the registration of clinical trials and reporting of results pursuant to FDAAA and have also assisted a multinational pharmaceutical company in an audit of FDAAA compliance.
- Assisted a multinational pharmaceutical company in crafting worldwide regulatory and risk management strategies with respect to clinical trial results involving one of its drugs.
- Conducted an internal investigation of alleged clinical trial violations at a subsidiary of a major pharmaceutical company.
- Assisted a leading biotechnology company in analyzing requirements relating to registration of clinical trials under the FDAAA of 2007.
- Advised a leading pharmaceutical company in connection with a number of clinical trials under investigation by the U.S. Attorney’s Office, resulting in restitution for the company.
- Assisted a major manufacturer in revising clinical research policies, procedures and forms to ensure research compliance.
- Assisted a global pharmaceutical company in developing policies and procedures concerning clinical trials, such as revising publication policies and adapting existing informed consent document templates to reflect international standards and FDA requirements.
- Negotiated clinical trial agreements with clinical sites in the European Union on behalf of a biotechnology company. Negotiations included ensuring that agreements included all regulatory requirements necessary to submit clinical trial results to authorities in the U.S. and collaborating with local counsel.
- Advised a specialty pharmacy manufacturer on issues relating to its plan to conduct clinical trials in Europe and Russia while supporting a U.S. marketing application.
- Represented a principal investigator in the U.S. accused of serious regulatory violations in connection with a study conducted in Costa Rica, becoming familiar with the local legal requirements and prevailing practices for managing clinical trials.
- Represented Pfizer Animal Health on various regulatory and litigation matters in both the U.S. and Europe.
- In anticipation of litigation, conducted an audit of a client’s clinical trial practices to assess the risk of liability and to develop programs designed to ensure compliance with good laboratory and clinical practice guidelines.
- Assisted a leading biotechnology company in devising regulatory strategies for FDA clearance of new products and in complying with FDA regulations relating to the conduct of clinical trials in foreign countries.