by Craig Klugman, Ph.D.

Johnson & Johnson’s Janssen Pharmaceutical Company announced that it has contracted with New York University’s Division of Medical Ethics to assemble an external Compassionate-Use Advisory Committee (CompAC) to examine requests for investigational new drugs (INDs) outside of clinical trials. Arthur Caplan will lead this group, which will be composed of bioethicists, physicians, and patient advocates. The goal of this group is to provide recommendations on which patients should be given compassionate use access to experimental drugs.

This step is a reaction to increasing publicity on compassionate use as well as 17 states having passed “Right to Try” laws that allow residents of those states to directly contact drug companies to request experimental drugs.

Compassionate use is also known as expanded access, a program created by the FDA in 1987 that allows people with life-threatening disease to request access to investigational new drugs outside of clinical trials. These are drugs that have not been approved by the FDA, have not been proven safe, and have not been proven effective.

To be considered for compassionate use, the FDA requires that the patient has a serious disease/condition or has an immediately life-threatening condition and:

• “There is no comparable of satisfactory alternative therapy
• “The patient cannot obtain the drug under another IND or [research] protocol
• “The potential patient benefit justifies the potential risks
• “Providing the investigational drug will not interfere with the initiation, conduct, or completion of clinical investigations”

Then the company has to agree to provide the drug under a physician that will closely monitor the patient.

This program began with the HIV/AIDS pandemic in the 1980s, when advocates fought for access to experimental drugs because there were no drugs to treat this new disease. An experimental drug may not help, may indeed hurt, but was viewed as better than nothing. The FDA cites that 99% of all requests are approved. An average of 932 requests are made annually. However, even if approved by the FDA, the pharmaceutical company has to agree to make the drug available and they need to have enough stock of the drug to make it available.

That such a board was created should surprise no one. Caplan and former Chimerix CEO Kenneth Moch wrote an article in August 2014 for Health Affairs in which they argued that an independent review board was needed for compassionate use decisions. Their idea was that this independent board would not be swayed by appeals to emotion and the social media campaigns that are often used to coerce companies into releasing INDs.

For the patient, the cost of such drugs can be high. Since they are experimental, few insurance plans will cover costs. These drugs are often in short supply with limited production runs, making them more expensive. There is also the cost of a physician and medical resources to administer the drug.

I have been quoted as not being in favor of the CompAC. I actually am not against CompAC and think that it is a noble attempt to deal with an increasing number of requests. The project calls back to the Seattle God Committee proceedings after the development of the Scribner shunt made access to the limited number of artificial kidneys a possibility for a much larger population of patients with end stage renal diseases. This is a grand experiment that may change how compassionate use decisions are made.

My concern is compassionate use itself. Here is a method that allows individuals to appeal to emotion about the desperation of their situation in hopes of a miracle. And it is just that, hope for a miracle. These investigational drugs have not been proven safe or efficacious. But those who are desperate for help may not realize the risks involved. When the public is told “compassionate use,” what they here is “unavailable cure.” And that could not be further from the truth. If the patient was in the clinical trial, he or she would be not receiving a life-giving cure, but rather would most-likely be randomized to receiving a placebo or a drug. The goal is to collect data not to improve the patient’s health.

The first danger of compassionate use is that it may harm patients. In desperation, patients may have their hopes set on an experiment to cure them and this is unlikely. These are drugs with unknown side effects that may actually cause the patient to be sicker. In addition, the patient may simply be too far along in the disease process to benefit from the drug.

My second concern is that often these investigational drugs are in short supply and are very expensive. What if a person granted compassionate use cannot afford the drug. Or what if the doses that patient uses mean there are not enough for a clinical trial to continue? As I discuss below, this could harm a greater number of people.

A third factor is that compassionate use is unjust. The individual who has the education, access, and money to go through the application process, to put together and sustain a social media campaign, to get elected officials and celebrities advocating on the patient’s behalf, and to afford the drug and cost of treatment means that those of higher socioeconomic status are more likely to benefit. A person who lacks means, technology, or influence is far less likely to be able to benefit from compassionate use.

Fourth, compassionate use can harm the clinical trials science, thus delaying approval of a potentially life saving drug. A negative outcome to a compassionate use patient could have an outsized effect on the trial. For example, consider the case of 7-year-old Josh Hardy who received an IND from Chimerix after a social media campaign (that cost the Moch his CEO job). Although he appears to be doing well, what if Josh had died or had a horrible reaction to the drug. Because of the publicity of this case, the negative outcome would have been known widely. The PR damage to Chimerix would have been huge resulting in a drop of stock prices and very likely, a need to withdraw the drug form clinical trials or to at least halt the trials until the PR nightmare passed. The company could even have to close its doors.

If this negative outcome had been in one person out of 1,000 enrolled in a Phase 3 trial, then statistically the drug may have been successful and earned approval. But, because this one case is so public, that single bad outcome could derail millions of people from having access to a potential cure.

The emotional reaction of saving a single person could have a longer term harm to the general public who might lose out on the scientific data and the eventual access to a potentially useful drug.

It is important to note that the CompAC provides recommendations and J&J is free to ignore them. While Dr. Caplan is not being paid for his services, J&J is paying NYU for the committee’s work.

In a rational risk/benefit analysis, compassionate use makes no sense. A sick person is placed in the path of unknown harm. And the public risks harm of missing out on a drug if this one very public case has a bad reaction from the drug. The chances of harm far outweigh the potential for benefit. No one wants to watch a child die. No company wants to be known as the business that wouldn’t save a person’s life. But there is too high a cost to the system and to a far greater number of future patients’ lives.