The Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try (RTT) Act of 2017 became federal law on May 30, 2018. Over the preceding five years, 40 states had enacted related legislation. The goal was to allow individuals with imminently life-threatening diseases or conditions to seek access to investigational drugs without the step of procuring permission from the Food and Drug Administration (FDA). Another goal—held by the Goldwater Institute, which led the initiative toward state bills, and some of the legislative proponents—was focused more on the process: to eliminate government's role in an individual's choice. The effort to publicize the issue and press for a federal solution involved highlighting the poignant situations of individuals who sought access. For example, in March 2014, millions of Americans heard about the plight of a seven-year-old boy with cancer. He was battling an infection no antibiotic had been able to tame. His physicians thought an experimental drug might help. Because the Food and Drug Administration (FDA) had not yet approved that experimental drug, it was not available in pharmacies. But FDA did have the authority to permit the use of an unapproved drug in certain circumstances—a process referred to as expanded access or compassionate use . For FDA to grant that permission, however, the manufacturer must have agreed to provide the drug. The manufacturer, which was still testing the drug that the boy sought, declined. Other stories often pointed toward FDA as an obstacle. Until FDA approves a drug or licenses a biologic, the manufacturer cannot put it on the U.S. market. During this time, Congress faced pressure to act, encouraged by the Goldwater Institute, which framed the issue as one of individual freedom—a right to try. The institute, which news accounts frequently refer to as a libertarian think tank, circulated model legislation. The bill's preface describes its scope: A bill to authorize access to and use of experimental treatments for patients with an advanced illness; to establish conditions for use of experimental treatment; to prohibit sanctions of health care providers solely for recommending or providing experimental treatment; to clarify duties of a health insurer with regard to experimental treatment authorized under this act; to prohibit certain actions by state officials, employees, and agents; and to restrict certain causes of action arising from experimental treatment. After 33 states enacted legislation reflecting the Goldwater Institute-provided model bill, in January 2017, legislators introduced a bill ( S. 204 ) designed to address the issue. Their Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017—named for several individuals facing amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) or Duchenne muscular dystrophy—sought to remove what proponents saw as FDA obstacles to patient access. On May 30, 2018, President Trump signed the bill into law ( P.L. 115-176 ). This report discusses FDA's expanded access program, which many refer to as the compassionate use program, through which FDA allows manufacturers to provide to patients investigational drugs—drugs that have not completed clinical trials to test their safety and effectiveness; obstacles—perceived as the result of FDA or manufacturer decisions—to individuals' access to experimental drugs; a summary of the provisions in the Right to Try (RTT) Act and how they are meant to ease those obstacles; a discussion of selected provisions in the RTT Act and what questions remain unresolved; and comments about the broader implications of the RTT Act. In general, a manufacturer may not sell a drug or vaccine in the United States until FDA has reviewed and approved its marketing application. That application for a new drug or biologic includes data from clinical trials as evidence of the product's safety and effectiveness for its stated purpose(s). After laboratory and animal studies have identified a potential drug or vaccine, a sponsor, usually the manufacturer, may submit an investigational new drug (IND) application to FDA. With FDA permission, the sponsor may then start the first of three major phases of clinical—human—trials. ( Figure 1 illustrates the general path of a pharmaceutical product.) Once the IND application is approved, researchers test in a small number of human volunteers the safety they had previously demonstrated in animals. These trials, called Phase I clinical trials, attempt "to determine dosing, document how a drug is metabolized and excreted, and identify acute side effects." If a sponsor considers the product still worthy of investment based on the results of a Phase I trial, it continues with Phase II and Phase III trials. Those trials look for evidence of the product's effectiveness —how well it works for individuals with the particular characteristic, condition, or disease of interest. Phase II is a first attempt at assessing effectiveness and its experience helps to plan the subsequent Phase III clinical trial, which the sponsor designs to be large enough to statistically test for meaningful differences attributable to the drug. A manufacturer may distribute a drug or vaccine in the United States only if FDA has (1) approved its new drug application (NDA) or biologics license app lication (BLA) or (2) authorized its use in a clinical trial under an IND. Under standard procedures, individuals outside of the sponsor-run clinical trials do not have access to the investigational new drug. The Federal Food, Drug, and Cosmetic Act (FFDCA), however, permits FDA in certain circumstances to allow access to an unapproved drug or to an approved drug for an unapproved use. One such mechanism is expanded access , commonly referred to as compassionate use , through individual or group INDs. The primary route for an individual to obtain an investigational drug is to enroll in a clinical trial testing that new drug. However, an individual may be excluded from the clinical trial because its enrollment is limited to patients with particular characteristics (e.g., in a particular stage of a disease, with or without certain other conditions, or in a specified age range), or because the trial has reached its target enrollment number. Through FDA's expanded access procedure, a person, acting through a licensed physician, may request access to an investigational drug—through either a new IND or a revised protocol to an existing IND—if a licensed physician determines (1) the patient has "no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat" the serious disease or condition; and (2) "the probable risk to the person from the investigational drug or investigational device is not greater than the probable risk from the disease or condition"; the Secretary (FDA, by delegation of authority) determines (1) "that there is sufficient evidence of safety and effectiveness to support the use of the investigational drug" for this person; and (2) "that provision of the investigational drug ... will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval"; and "the sponsor , or clinical investigator, of the investigational drug ... submits" "to the Secretary a clinical protocol consistent with the provisions of" FFDCA Section 505(i) and related regulations. FDA makes most expanded access IND and protocol decisions on an individual-case basis. Consistent with the IND process under which the expanded access mechanism falls, it considers the requesting physician as the investigator. The investigator must comply with informed consent and institutional review board (IRB) review of the expanded use. The manufacturer must make required safety reports to FDA. FDA may permit a manufacturer to charge a patient for the investigational drug, but "only [for] the direct costs of making its investigational drug available" (i.e., not for development costs or profit). Expanded access could apply outside of the clinical trial arena in these situations: (1) use in situations when a drug has been withdrawn for safety reasons, but there exists a patient population for whom the benefits of the withdrawn drug continue to outweigh the risks; (2) use of a similar, but unapproved drug (e.g., foreign-approved drug product) to provide treatment during a drug shortage of the approved drug; (3) use of an approved drug where availability is limited by a risk evaluation and mitigation strategy (REMS) for diagnostic, monitoring, or treatment purposes, by patients who cannot obtain the drug under the REMS; or (4) use for other reasons. The widespread use of expanded access is limited by an important factor: whether the manufacturer agrees to provide the drug, which—because it is not FDA-approved—cannot be obtained otherwise. FDA does not have the authority to compel a manufacturer to participate. Many highly publicized accounts of specific individuals' struggles with life-threatening conditions and efforts by activists influenced public debate over access. Another development was the model bill circulated in 2014 by the Goldwater Institute. Examples of public attitudes included news accounts of specific individuals' struggles with life-threatening conditions. Some found the process of asking FDA for a treatment IND too cumbersome. Others question FDA's right to act as a gatekeeper at all. Some point to manufacturers' refusal to provide their experimental drugs. Most critics, therefore, see solutions as within the control of FDA or pharmaceutical companies. This section lays out key perceived obstacles and issues—both FDA- and manufacturer-related. Have FDA's procedures discouraged patients and their physicians from seeking treatment INDs? For example: Does FDA ask for so much information that physicians or patients do not begin or complete the application? Does the FDA application process take too much time given the urgent need? In February 2015, FDA issued draft guidance (finalized in June 2016) on individual patient expanded access applications, acknowledging such difficulties. It developed a new form that a physician could use when requesting expanded access for an individual patient. It reduced the amount of information required from the physician by allowing reference (with the sponsor's permission) to the information the sponsor had already submitted to FDA in its IND.