M. E. Blair Holbein

Understanding Food and Drug Administration Regulatory Requirements for an Investigational Device Exemption for Sponsor-Investigators

Clinical investigators in academic medical centers often perceive federal regulations as a significant obstacle to conducting clinical research. The regulatory authority of the Food and Drug Administration (FDA) extends to clinical studies of medical devices. Consequently, researchers wishing to conduct device research using FDA-approved as well as nonapproved devices must comply with federal regulations for investigational device exemptions (IDE) as described in Title 21 of the Code of Federal Regulations Part 812. FDA regulatory oversight is structured to match the risk to the subject to the risk of the device. Medical device studies can be categorized as follows: meeting exemption criteria, being a nonsignificant risk device, or being a significant risk device. All IDE studies must meet regulations for the protection of human subjects, but no additional federal filing on the part of the investigator is necessary for those that meet exempt criteria. Nonsignificant risk device studies require meeting abbreviated IDE regulatory requirements for the conduct of the study, but no previous FDA approval is required. Significant risk device studies require that the investigator also function as a sponsor and to file an IDE with the FDA for approval before starting. A sponsor-investigator filing an IDE follows the format and content described in 21 CFR 812.20. The study may begin 30 days after the date of submission receipt unless the FDA notifies the sponsor otherwise. While the IDE is active, the sponsor-investigator must meet the requirements for the conduct of the study and the required monitoring and reporting to the FDA.

Access to Investigational Drugs: FDA Expanded Access Programs or "Right-to-Try" Legislation?

The Food and Drug Administration Expanded Access (EA) program and “Right‐to‐Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access.

Recommendations From the Investigational New Drug/Investigational Device Exemption Task Force of the Clinical and Translational Science Award Consortium: Developing and Implementing a Sponsor-Investigators Training Program

Objective The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers. Background A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role. Methods The participants who developed the recommendations were representatives of institutions with IND/IDE support programs. Through an informal survey, the task force determined that a variety and mix of models are used to provide support for IND/IDE holders within CTSA institutions. In addition, a CTSA consortium-wide resources survey was used. The participants worked from the models and survey results to develop consensus recommendations to address institutional support, training content, and implementation. Recommendations The CTSA IND/IDE Task Force recommendations are as follows: (1) Institutions should assess the scope of Food and Drug Administration–regulated research, perform a needs analysis, and provide resources to implement a suitable training program; (2) The model of training program should be tailored to each institution; (3) The training should specifically address the unique role of sponsor-investigators, and the effectiveness of training should be evaluated regularly by methods that fit the model adopted by the institution; and (4) Institutional leadership should mandate sponsor-investigator training and effectively communicate the necessity and availability of training.

Access to Investigational Drugs

The Food and Drug Administration Expanded Access (EA) program and “Right‐to‐Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access.

Right now, in the right way: U. S. Food and Drug Administration’s expanded access program and patient rights

Based on approval data, the U. S. Food and Drug Administration (FDA) program that allows for early access to drugs and medical devices before marketing approval, is a very effective means for seriously ill individuals to be treated with investigational agents. Currently the FDA receives, reviews, and approves >99% of over 1000 requests each year [1]. This program is called “expanded access” (EA), also referred to as “compassionate use” [2, 3]. In addition, recent changes in the FDA EA process have streamlined the application to further decrease the timeline and surmount procedural barriers [3]. For individual patient access, a 2-page form is submitted and reviewed within days. If the request represents an emergency, this can be done over the phone (often within hours of the request). The EA approval rate and abbreviated application process suggest that the FDA is not an impediment to patients gaining access to experimental therapeutics. Nonetheless, a United States federal Right-to-Try (RtT) law was passed and signed by President Trump [4, 5]. This legislation, first at the state and now at the federal level, evolved from the efforts of the libertarian Goldwater Institute to make experimental drugs available to patients who seek them by removing oversight of the FDA and local Institutional Review Boards (IRB; ethics committees) [6]. Parties that support the RtT legislation identify the FDA as the primary obstacle to accessing experimental therapies. What seems to have been lost in the public discussions is a clear presentation of the critical benefits and protections afforded the patient by the current EA system that are missing in RtT (Table 1). Lawmakers and RtT advocates do not appear to understand or acknowledge the inherent risk in experimental therapies, which may have been tested in as few as a dozen patients in a phase 1 trial. Rather than serving as an impediment, the FDA serves as a safeguard for patients facing desperate, complex situations. While much of the current literature focuses on the redundancy and ethical arguments about the legislation [7–10], there are pragmatic and unacknowledged issues surrounding patient rights that are maintained by EA. Importantly, there is a real value to patients that the FDA, as well as other partners in the current EA system, bring to the process. The RtT law, as written, does not preclude the use of the existing EA process. We believe that is very important to make providers aware of EA and that it offers the best option for patients. The FDA, IRBs, and research institutions play critical roles in the EA process by providing patients with the safest possible access to investigational agents. Table 1 Comparison of patient rights under US Food and Drug Administration (FDA) expanded access program and Right-to-Try law

Access to Investigational Drugs: FDA Expanded Access Programs or “Right-to-Try” Legislation?: Access to Investigational Drugs

The Food and Drug Administration Expanded Access (EA) program and “Right‐to‐Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access.