Image of medications spilled on a table.

Denying the Dying or Protecting the Vulnerable? Compassionate Use of Experimental Drugs

Lynn Adams
Feb 1, 2016

A headline recently caught my eye, “Why the FDA shouldn’t bow to parental pressure over Duchenne drug.” The article was about the pending and apparently unlikely FDA approval of a drug called eteplirsen, which was developed for the treatment of Duchenne muscular dystrophy (DMD).

Here we go, I thought. Another case of greedy drug companies denying human rights for the almighty dollar. DMD is a truly debilitating disease which leads to progressive muscle weakness and eventual death, usually by the age of 25. But a company called Sarepta gave patients and their families some hope in July 2012, when it released reports stating that eteplirsen may slow disease progression, giving the drug immediate miracle status. Now why, I wondered, would FDA deny a chance for the rare disease community to have a potential win when they get so few? After all, unlike so many others, this drug has no side effects. However, as I prepared to write this blog, I researched the many aspects of this debate, which has spanned many years, diseases, and spawned innumerable games of ethical tennis, and I began to see a picture with many more dimensions that I initially assumed.

In the normal life cycle of a new drug, it goes through rigorous, methodical testing. Phase I trials look at small samples of healthy volunteers and measure metabolism, excretion, side effects and help determine dosing. Phase II studies ramp up the numbers and enroll patients with the disease targeted by the drug; they focus on side effects and potential positive effects of the drug. Most drugs don’t make it to the third step: Phase III trials that study the drug in much larger populations of ill individuals and further test effectiveness, monitor side effects and compare the effect to that of a standard treatment for the disease, if one is available. It’s a good system that usually results in the release of effective drugs at mostly safe dosages, or at the very least, known side effects.

Unfortunately for those people with little time left, the traditional testing and approval process is just too slow. But, there is precedent for people taking the system to task and lobbying for access to experimental drugs outside of clinical trials. The HIV/AIDS crisis in the 80s spawned the “compassionate use” exemption (also known as expanded access) which allows the use of an investigational new drug (IND) by patients with serious or life-threatening illness, without enrolling in a clinical trial - when these individuals do not meet the enrollment criteria for the trial. This method was useful in the development of effective HIV drugs, and was also helpful in the 90s for breast cancer patients with a mutation that was highly responsive a new experimental drug, Herceptin (now a standard of practice for this type of breast cancer). Unfortunately, some patients are not eligible for clinical trials or expanded access programs, or sometimes an expanded access program doesn’t exist for the desired drug. In this case, the patient can apply for Single Patient Access, via request from their physician. More recently, “Right to try” laws have been passed in 21 states. These state-level laws allow terminally ill patients who have no other options to obtain unapproved drugs that have been through Phase I testing directly from the manufacturer and without FDA approval.

Problem solved then, right? Everyone can have access to any drug as long as it makes sense for their disease. Wrong. Many drug companies deny compassionate use requests, and the FDA can’t make them provide the drug. So, the illusion of access is granted from the perspective of the patient and many times, this doesn’t happen. But why? Are the drug companies really so heartless as to deny dying people a chance at survival?

Well, no. Here’s the reality. First is the issue of limited supply: the company may not have the ability to create enough of the drug to go beyond that needed for the trials they have underway. Second, drugs are expensive to manufacture, which can make compassionate access to large groups prohibitive for the company. In the case where the company passes that cost along to the patients, they just may not be able to afford it. Third, the drug may not be at the point where effective and safe dosage is known, so patients may suffer horrific side effects or hasten their own death. Although, if you’re dying anyway, most people would take that chance. Some would argue that unethical doctors could take advantage of patients who are in a fragile mental state just to sell them the drug, or to see if it works. A lesser-known fact is that many of the right to try laws don’t protect the patient if they do suffer an adverse event, and insurance companies may be under no obligation to pay for care related to the taking of the experimental drug.

This brings us to the reality that compassionate access can actually jeopardize the chance of FDA approval for a truly effective, game-changing drug. Variability in people and within conditions is one reason clinical trials require large numbers of participants. One person may respond to a drug where someone with the same disorder won’t. Similarly, a drug may cause a serious negative reaction in one person and not another. Unknown side effects are a reality with new drugs, and due to the often very public nature of these cases, one bad outcome in a compassionate use case will raise alarms. Alternatively, if 1 in 1000 patients experience an adverse effect in a controlled clinical trial, the outcome would be viewed very differently. Another potential scenario is one of a false negative: if a patient granted compassionate use is too far along in the disease trajectory to show a benefit, the perception would be that the drug doesn’t work; when in a controlled clinical trial it might have. So some would argue that due to compassionate use scenarios gone wrong, potentially life-changing drugs could be unjustly shelved or at the very least, testing could be significantly delayed.

Another important issue is that of equity, who should have access? Many times, compassionate use pleas are successful when people have the education, money, and/or access to social media to get elected officials and other famous people to lobby on their behalf. These people are also usually the ones who have the financial means to pay for the drugs. Is this fair?

Based on the discussion so far, I think it is safe to say that the best way to provide widespread and safe access to new drugs is to put them through the necessary testing to gain FDA approval. So is the answer to find a way to get new drugs through testing quicker? I think so, and it just so happens that in the early 90s, the FDA began allowing promising new drugs to skip the phase III testing (and in some cases, the phase II) to allow the drug to get to the market faster.

So I now see that the answer to this particular problem is not purely about denying terminally ill people hope in the form of a miracle drug. It is so much more complicated. But I recognize that there is a human side to this issue, and I empathize with those who need hope. Would I try to get a drug that could potentially save my life or that of a family member? You bet. I think people should still lobby because in some cases, this has resulted in a positive outcome. One mother lobbied for eteplirsen for her son who was not eligible for the clinical trial because he was already in a wheelchair. Instead of allowing just him access to the drug, Serepta started a new clinical trial for patients at his stage of the disease – with him as the first patient. It must be recognized though, that when the drug companies say no, it’s not purely out of greed.

So what of the drug eteplirsen? In reviewing the study data, FDA scientists determined that there was no definitive clinical benefit of the drug, and expressed concerns over study design –  one of which is that the study was carried out in only 12 boys. Anyone who knows anything about clinical trials will tell you that this is a very small sample on which to base any conclusions – much less those that could affect the lives of so many vulnerable people and their families. Serepta has appealed the decision, and the FDA was to have convened an independent panel to pass judgement. That meeting was cancelled due to the recent blizzard. Until the meeting is rescheduled, hope remains for the boys on the study who would like to continue the treatment, and the fate of eteplirsen is for now unknown.

Image: Public Domain Photo via


Lynn Adams

Lynn S. Adams, Ph.D. is an Alumni Fellow. She blogs about nutrition policy, the connections between nutrition and disease risk, the health effects of environmental exposures and the cancer prevention potential of natural products at Sci on the Fly. If you want Lynn to share her posts with you, follow her on Twitter: @lstedda68.


This blog does not necessarily reflect the views of AAAS, its Council, Board of Directors, officers, or members. AAAS is not responsible for the accuracy of this material. AAAS has made this material available as a public service, but this does not constitute endorsement by the association.

Comments (1)

Nicholas Brown (not verified)
February 15, 2016 at 11:58 am
Thanks for taking an unbiased approach to addressing this issue, this was very interesting and informative.

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