HIGH SCHOOL BIOETHICS PROJECT COMPASSIONATE USE OVERVIEW PROCEDURES AND ACTIVITIES This module encourages students to think This unit uses a student-centered and interactive through ethical and social issues surrounding the approach to teaching. Activities are designed to compassionate use of experimental drugs and de- allow for a maximum degree of student partici- vices. Students will be exposed to the process of pation and collaboration. Each activity is marked testing and licensing new drugs with the US Food as an individual-, partner-, or group activity, or as and Drug Administration in an effort to understand a teacher-directed class discussion. the motivations for compassionate use and the ethical issues it raises. The module relies on a The following icons are used to designate the case-based approach to learning. Three cases are different types of activities: presented, and students will be led in an analysis of the issues presented in the cases. Individual Activity CONTENTS Partner Activity 1. Introduction to Topic 2. Definitions Group Activity 3. Case Study: The Effects of Social Media 4. Case Study: When the Drug Fails 5. Case Study: Unequal Access 6. Conclusion Teacher-Directed Class Discussion 7. References and Additional Resources LEARNING OUTCOMES 1. Learn the basics of compassionate use 2. Understand the motivations and ethical dilem- mas behind the development of compassion- ate use 3. Examine case studies and formulate opinions about the current state of compassionate use 4. Brainstorm possible solutions for the future of compassionate use DC 1/27/2020 1. INTRODUCTION TO TOPIC want access to a new drug. Some people in this position turn to social media outlets to find support from well-connected friends who might be able to help by intervening with ex- ecutives at a company. Sometimes, patients will use social media and news outlets to pub- Suppose you have a disease or illness that can’t licly pressure drug companies into providing be treated. You’re going to get worse. Perhaps the unapproved medication. you’re even dying. There is no drug available in a pharmacy that can help. Maybe your doctor In general, the public is supportive of patients has already prescribed many medications, and who are out of other options, gaining access to nothing has worked. What’s left to do? possible benefits from an investigational drug. However, this method of obtaining unapproved Some patients in this position might learn medication works best for patients who are about a new medication that might help. It’s wealthy, connected, and socially savvy. Pa- still being developed, so your doctor can’t just tients who are well-off and well-connected are prescribe it to you. But you still may be able likelier to have access to better healthcare. The to get to try it. best medical professionals are more likely to be aware of compassionate use, and ongoing Maybe the drug is being tested on volunteers drug development. In fact, there is no reliable who are healthy or in patients who have the online resource for medical professionals to condition or disease or in animals. These tests find which drugs are available for compassion- are known as “clinical trials,” a series of stud- ate use. To find out about compassionate use, ies done to make sure that a new drug is safe, you must have access to someone in the know effective, and either equivalent to or better than about what’s in the development pipeline, or other already-available options. In this case, you being tested in clinical trials. might decide to volunteer for one of the clinical trials in order to try to get the new drug. But, Access is not the only ethical problem raised if you are too sick for the clinical trial, live too by compassionate use. Without patients partic- far away from where it is being conducted, or ipating in clinical trials, we won’t get the data decide you do not want to join the clinical trial needed to prove that a new drug is safe and for fear of being assigned to a placebo arm, you effective. In fact, without people participating in may choose to ask the company developing the clinical trials, the federal Food and Drug Ad- drug to let you use it. This is called “compas- ministration (FDA) won’t have enough data to sionate use” of an unapproved medication or decide whether to approve a new drug, and un- treatment. However, the company developing less it’s approved, a drug can’t be sold or used the new medical product is not required to say in the United States. If fewer people participate ‘yes’ to requests for compassionate use. Some in clinical trials, that means it will take longer drug companies have laid out procedures for to conduct those studies, which means it will “compassionate use” requests. However, these take longer for the FDA to make a decision. This guidelines are often vague and confusing, and could cause a delay for future patients to have sometimes companies don’t follow them. access to new, potentially life-saving drugs. If you’re sick or dying from an untreatable So, what will happen when it becomes easier disease, you could imagine how badly you’d for patients, who otherwise would be en- rolling in clinical trials, to access the drug in development through compassionate use? DC 1/27/2020 In using an unapproved drug, device, or treat- fects us all. Even if you are healthy now, you may ment, you are potentially causing more harm someday need a drug that is still in development. than good. It is even possible that you could die prematurely from using an unapproved drug. However, drug development is a long and Even a drug that seems promising in early clinical complex process without a guaranteed posi- trials can act differently in sicker patients, which tive outcome. As you can see from the chart could be the case for many people requesting below, the entire process of drug develop- Compassionate Use. Perhaps if you are getting ment-- from discovering a medicine to finish- sicker every day, and you know that you will ing late stage clinical trials-- can span many probably die anyway, you’re willing to take the years on average. In some rare cases, the pro- risk. Still, compassionate use is a complex issue cess can last twenty years or more. What’s that affects not only the patient, but also drug even more alarming is how unlikely it is that a companies, the drug development process, and drug in development will even make it to the the entire healthcare system. In fact, because market. On average, only 1 in 5,000 new early nobody knows what diseases or conditions they stage potential drugs successfully make it to may someday develop, compassionate use af- the pharmacy shelves. 10,000-15,000 Compounds Drug Pre- FDA Clinical Trials Discovery Clinical Review Manufacturing 20--100 100-500 1,000-5,000 Volunteers Volunteers Volunteers Pre-Discovery IND Submitted NDA Submitted *Source: ACRO DC 1/27/2020 2. DEFINITIONS agnosis, monitoring, or treatment of a serious disease or condition if the following condi- tions are met. 1. The person’s physician determines that there is no comparable or satisfactory alternative therapy available to diagnose, Compassionate Use monitor, or treat the person’s disease or Compassionate use describes the treatment of condition, and that the probable risk to the a seriously ill or terminal patient who has ex- person from the investigational product is hausted all possible approved drugs and thera- not greater than the probable risk from the pies. These patients seek access to unapproved disease or condition; investigational drugs as a last resort, often 2. FDA determines that there is sufficient accepting risk that the treatment may not work, evidence of the safety and effectiveness or that it may even do more harm than good. of the investigational product to support its use in the particular circumstance The term Compassionate Use was designed 3. FDA determines that providing the investi- to make clear that the drug was being admin- gational product will not interfere with the istered primarily to help the patient, not to initiation, conduct, or completion of clinical gain data, as in formal clinical trials. However, investigation to support marketing approval sometimes data are collected from people 4. The sponsor (generally the company de- who get drugs through compassionate use. veloping the investigational product for Also, drug companies and others do not like commercial use) or the clinical investigator the term Compassionate Use. After all, if they submits a clinical protocol (a document decline a patient’s request, that makes them that describes the treatment plan for the seem automatically non-compassionate! How- patient) that is consistent with the FDA’s ever, there may be very good reasons to de- statute and applicable regulation for INDs cline a request. For example, the supply of the or investigational device exemption appli- drug-in-development may be so limited that cations (IDE’s), describing the use of the there is already barely enough to go around. investigational product. So, there are a variety of other terms for Com- Also under FDA’s statute, a sponsor or a phy- passionate Use. The FDA calls it “Expanded sician may submit a protocol intended to pro- Access.” Other terms include “Early Access vide widespread access to an investigational Cohort Programs,” “Single Patient IND,” “Sin- product. In this scenario, FDA will permit the gle Patient Requests,” and “Emergency IND.” investigational product to be made available Internationally, Compassionate Use is referred under a treatment IND or treatment IDE if cer- to as “Named Patient Program,” “Temporary tain criteria are met.