FDLI Colloquium Series White Paper #1: Whose Life Is It, Anyway? Abigail Alliance at the Crossroads
White Paper Article, by David Welch

Introduction
I was busy in an entrepreneurial career of co-founding a thriving software company. A grand mal seizure on 12/6/04 changed this quickly. At the Inova Fairfax Hospital, an MRI revealed a tumor the size of a lemon in my left frontal and left temporal lobes. This tumor is basically in the center of my brain, amidst eloquent functions that handle such things as walking, talking, and thinking. By respected medical institutions across the nation, I was told that this infusive, cancerous brain tumor was inoperable. I likely had 5-6 years to live. I was 38.

Fast forward to 5/5/05. Professor and Chairman of the New York University of Neurosurgery, Dr. Patrick J. Kelly -- who is considered one of the top three neurosurgeons in the world – undertook this controversial surgery. As Dr. Kelly said afterwards, this surgery required a "tour de force" because of its location. Out of about 7,000 brain surgeries in his career, I was only his 41st patient who has undergone this kind of brain surgery. No matter, Dr. Kelly and his team successfully removed about 50% of my brain tumor. It was an operation that could not be done had he not invented tools in 1999 to deal with rare diagnoses such as mine.

Then, on 10/31/05, I started chemotherapy at the National Institutes of Health (NIH), under the auspices of the Chief of the Neuro-Oncology Branch, Dr. Howard A. Fine. I am off-label for use of Temozolomide (Temodar) chemotherapy medication, made by Schering-Plough. Further, I did not have the 1p/19q gene deletion in my brain, so I was (statistically) not expected to do well with this drug. But over a year later, I am still on chemo, and my brain tumor has not only stabilized, it has shrunk. To date, quite a success story – especially in the fickle and unforgiving world of brain cancer.

As a patient, why the Abigail Alliance Decision important to me?
Given the above introduction, I embrace the innovators in the medical community who are years ahead of WHO (World Health Organization) standards. My medical team at NYU falls into this category, I believe. If they were not so innovative, surgery would not have been a treatment option for me. At the same time, I embrace the WHO standards in place with my neuro-oncology team at NIH. What Dr. Howard Fine is doing as he leads the Neuro-Oncology Branch of the NCI (National Cancer Institute) is world-class, and the only way he can get the best data about brain cancer drugs is to do so in a scientific manner, vis-à-vis standard protocols and clinical trials.

In short, I have embraced "both sides of the fence" in my overall medical treatments. My surgical team absolutely stretched the limits with my brain surgery. In comparison, my neuro-oncology team leads the nation when it comes to clinical trials of new drugs, walking hand-in-hand with WHO standards and the FDA (Food & Drug Administration). Aggressive and more standard approaches have both worked for me during various stages of my brain cancer treatment.

Given all this, what I would do if all standard protocols of treatment and all available clinical trials were exhausted during the treatment of my brain cancer? What would I do then? I am attending this colloquium so that I can have good answers to such questions.

Am I terminally ill?
"The Court of Appeals, Rogers, Circuit Judge, held that terminally ill, mentally competent adult patients had a due process right to informed access to potentially life-saving investigational new drugs that had been determined to be sufficiently safe for expanded human trials, where there were no alternative government-approved treatment options." – 5/2/06

As I read the above information, there is one phrase that caught my attention -- "terminally ill." In fact, that is what first grabbed my attention when I learned about this colloquium. "In the end, are (terminally ill) patients better or worse off as a result of this decision?" This is one of the driving and important questions being asked.

To find out whether or not I am medically considered to be terminally ill, I went straight to my neuro-oncologist, Dr. Fine, and asked this question. How did he respond? Here are some paraphrased notes:

• My particular form of illness should first be qualified. I have brain cancer. Specifically, I have a grade 2 astrocytoma in the subinsular and basal ganglia region of the left frontal and left temporal lobe. It has been partially resected (approximately 50%), and I have had 1 year of Temodar chemotherapy with about 1 cm of shrinkage of the visible brain tumor mass.
• The above brain cancer diagnosis is an illness that could kill me.
• However, my particular illness is not something that necessarily will take my life.
• The issue of having a "terminal illness" can be seen in another way. For Dr. Fine and his medical team at NCI, it is not about being "terminal." Rather, it is more about managing the quality of life for each patient.

Based on this intelligent yet empathetic discussion with Dr. Fine, I can now say that with assertion that I would generically fall into the category of being a patient with a terminal illness. The thing that is a bit unique, though, is that I have the relative luxury of more time as compared to many other patients.

A patient's perspective
Why am I concerned with the issues addressed at the FDLI Colloquium? Good question. The Temodar chemotherapy medication I am taking is FDA approved. However, I'm taking it "off-label," which means that the manufacturers of this drug do not yet have supporting data to confirm it is effective for patients with slow-growing forms of cancer. Still, I'm taking this drug and having good results so far, even though I have a slow-growing form of brain cancer. Admittedly, this is a different issue than taking an unapproved drug. However, the reason why I am concerned about taking a non-FDA approved drug is because I may well be facing this issue in the future.

In my personal approach to my brain cancer, I plan for the worst and hope for the best. As such, I am concerned about not being able to continue with my Temodar chemotherapy protocol any longer. When this (eventually) happens, what will my next treatment be?

I could end up being on a Phase II or Phase III clinical trial under the auspices of NCI. Neurologist Dr. Michael Gruber (NYU) was speaking at the 5th Annual Brain Tumor Awareness Day where he reported that there are about 50 new drugs in the pipeline right now for treating brain tumors. All these are being tested to see which are most likely to be effective and approved by the FDA.

Given all the above, what happens if I am in a situation where I do not fit into a profile needed to participate in Phase II or Phase III clinical trial and I have no other course of action? Should I be allowed to take a drug that looks very promising, anyway? How would that work? Would I not be allowed to take such a drug under any circumstance, even if my situation is spiraling out of control? Should I have a constitutional right to take such unapproved drugs?

Sum it up this way. I am on the front edge of being impacted by the Abigail Alliance Decision. Decisions being made today don't impact me immediately, but these could impact my last options in life at some point in the future. It is not a difficult extrapolation to see that far ahead.

Neuro-oncologist's perspective
In tackling such questions as a patient, I turned to my medical team. It took significant time to build this team. Now that they are in place, I have well-grounded trust in their medical opinions – even though I still scrutinize just about everything they tell me. Here is what Dr. Fine had to say about the Abigail Alliance Decision, all of which is interesting fodder:

• He has thought about these issues for years. He has many thoughts about the Abigail Alliance Decision and can see arguments on both sides.
• Dr. Fine "lives with both sides" of this decision. I could really see the complexity of this issue by his responses, as well as his body language. This is tough stuff.
• Dr. Fine's prevailing question is this. Could a drug be killed that could otherwise be effective? The reason for this line of questioning is as follows. Sick patients start taking a drug they are not otherwise eligible for. Then, a patient does not tolerate drug well. Then, the toxicity profile for that drug gets a bad mark, if you will, because this patient did not tolerate it well. Then, a bad toxicity profile makes it difficult for the drug to ultimately get approved.

Pharmaceutical consultant's perspective
I also turned to someone I know who is a respected pharmaceutical consultant, J. Paul Waymack, M.D., Sc.D. Dr. Waymack's perspective is all the more insightful given that he was also a surgeon for many years and once worked at the FDA as a medical reviewer. I took pages of notes when talking with Dr. Waymack, most of which was fascinating. Boiling these notes down to the most relevant issues, here is a quick summary:

• If non-approved drugs are used, it could slow the process of obtaining data about whether or not drugs really work. Why? Because a large number of patients may choose to take a non-approved drug rather than be part of a clinical trial.
• Most drugs do not work. That is why clinical trials are needed in order to get FDA approval. These clinical trials just try to break out drugs into one of two camps: which drugs work and which drugs do not work.
• A bioethics issue involved with the FDA approval process is that if a patient takes a drug that does not work, then it may be at the expense of taking a drug that could work for them. As well, there may be side-effects from taking these unapproved drugs that could have serious implications to overall health.
• What happens when drugs are in use that are ultimately of no benefit to a patient?

Debate meets reality
So far, I've mention several perspectives:

• My personal experience with controversial surgery and off-label drugs.
• A perspective from neuro-oncologist Dr. Howard A. Fine.
• A perspective from pharmaceutical consultant Dr. Paul Waymack.

However, I have seen all this play out in person, too.

Every month, I attend the Inova Fairfax Hospital Brain Tumor Support Group Meeting. Patients and caregivers gather in moderated sessions to share knowledge and experiences in their treatments. A patient by the name of Ellsworth Irvin ("Jack") Coburn, Jr. was at every meeting. He was beating the odds as he fought a glioblastoma (GBM) brain tumor, which is the most aggressive form of brain cancer there is. After a period of dormancy, his brain cancer became aggressive once again, but Jack had already exhausted all standard protocols for treating his GBM.

Then, the support group pointed Jack to Dr. Howard A. Fine at NCI. Jack qualified for a Phase II Clinical Trial for Avastin. Avastin is an FDA approved drug, so its toxicity profile is already known. However, Avastin is not approved for treatment of brain tumors. Clinical trials are needed to see if the anti-angiogenesis effects of Avastin work in treating brain tumors.

For two months, Jack had tremendously positive results. His visible brain tumor mass reduced in size by 90%, which was jaw-dropping to the members of the support group. However, Jack then had a known side-effect from Avastin. Jack developed a blood clot in his leg and could no longer participate in this clinical trial.

At that point, decisions were being made that are at the very crux of the Abigail Alliance Decision. Should Jack have had the right to continue Avastin, despite the blood clot in his leg? If so, would that blood clot have broke loose and killed him immediately? Or, was it the correct bioethical decision to remove him from this clinical trial (as was done)? Should he have been allowed into another clinical trial for which he did not quality? If Jack had a constitutional right for expanded access to unapproved drugs, then how would he have gotten these drugs in short order? Such issues instantly mounted for Jack, which ended sadly when he died at the age of 59 – shortly after being removed from the Avastin clinical trial.

Sum it up this way. Jack was on the back end of being impacted by the Abigail Alliance Decision. Decisions being made at present would have impacted Jack immediately. While my situation is on the front end of things, Jack faced the precise situation that is being so vigorously debated. Seeing a face on both ends of the spectrum has impact, in my estimation.

Conclusion
When the dust settles and all is said and done, I know that I am the fortunate recipient of what has been learned by doctors and patients over the past several decades. Taking an extreme position, I can say that many people have died because of brain cancer, and all the information learned in trying to treat them has been funneled into my current treatments. What was learned in treating Jack Coburn directly relates to my current and future treatments.

It is pretty humbling to think that successes I have had so far would not have been possible 10 years ago. It is only because of the combination of medical rigor, human loss, and human success that better treatments exist today.

Speaking for myself, I have to look at what I do as I medically inherit what has been given to me. I cannot make medical decisions for others, nor do I want to. But as a brain cancer patient, I have a hard time seeing myself doing something that could potentially harm the process of finding better medical treatments for generations to come. Convince me otherwise. I'm open, but as a patient, I've done my homework on this stuff.

Parting questions
In recap, these are the questions that weigh most heavily on me as a metaphoric patient in these discussions:

1. Could a drug be killed that could otherwise be effective? – Dr. Fine

2. What happens when drugs are in use that are ultimately of no benefit to a patient? – Dr. Waymack

3. I have medically inherited treatments that have led to relative success (to date) in the treatment of my brain cancer. I have a bioethical decision to be a good steward. Should I make decisions that potentially harm other patients in the future, all for my personal benefit?

In short, I think there are bioethical decisions that need to be made by all parties involved, including patients. As a brain cancer patient, I feel strongly that there is a "medical inheritance" to which I am fundamentally and ethically obligated. If decisions I make are in conflict with efforts at NCI, for example, I will have great reservations and concern.