An excellent interview which shines the light of day on both medical ethics and regulatory issues. While Nancy’s answers lead to more questions than answers, it proves we still will never have clear cut answers in dire situations.

The reality check I continue to remind everyone in healthcare is that “The patients are the reason we are all here. Without them and their needs, we could close up shop and go home.”

And this includes pharma and regulatory.

Thanks for your message.

You are right, it is already affecting each and everyone of us, whether we realize it or not.

We have lost sight of the reason we all exist in pharma, health care, etc. It seems the only reason we exist is to make money.

You said:
“When a federal regulatory system, and the massively powerful financial and professional special interests of the clinical trialing industry, staunchly resist change of any kind (as they have for decades and are furiously doing now) to the way we test and approve drugs, and that resistance stalls progress and holds promising and even solidly proven new drugs away from hundreds of thousands of Americans for many months and even years, and those patients die prematurely waiting for progress to reach them (believe me - this is happening), isn’t it time to start changing things?”

I just lost a very good friend, quite young, to this very situation last week. The drug he was denied was proven to work in patients but the drug company has chosen not to pursue that indication anymore.

“Mistakes” can be buried, dead people do not speak…

To those who think we can’t have both a robust clinical trials system and access to progress for those who can’t continue to wait, it simply isn’t true. In our Citizen’s Petition to the FDA (submited in June 2003 and to which the FDA has never responded), in our lawsuit, and in the Access Act (S. 3046) introduced in May of this year, we have always proposed that access would be available only to those patients ineligible or, for other legitimate reasons, unable to enroll in clinical trials. The protection of the clinical trials system is expressly built-in, which exceeds the protections of the system in current FDA policies and its draft regulations. Given that FDA can and as a matter of routine does, very effectively severely restrict the avilability of a drug like Tysabri, does anyone really doubt their ability to restrict what we now call Compassionate Investigational Approval (CIA) in the Access Act?

There also are some very pragmatic lessons we can take from the very few sizable compassionate use programs that have been run (and we have taken those lessons), where patients are first screened for entry into ongoing clinical trials, and offered access only if they are found ineligible. Folks this is doable and we should be doing it, but first we need a program that works for all concerned, including the sponsors. Our current programs do not, the FDA knows it and prefers it that way, and is in the process of promulgating new regulations that will cement policies into place that have failed miserably for three decades. Their message to most (in fact nearly all) people like Fred Baron who are quite forcefully abandoned by the clinical trials system is - drop dead. The FDA message is to most dying Americans is - the progress being made is not for you.

Folks, the people that is happening to is us - all of us. You and your families may be healthy now - but tomorrow? Next month? Next year? This is going to hit you one way or another, and you are going to have a different view of the faceless bureaucrat sitting at his/her desk near the beltway north of Washington who has decided you (and thousands like you) should die prematurely, untreated, because the FDA wants something called a p-value generated from statistical measurements of the accrual rate and height of two piles of bodies built in a double-blind, randomized, placebo-controlled trial using a drug that was already compellingly proved effective in earlier trials. Sounds like rhetoric, I know (and it is a bit by the choice of words), but it is also true much more often than most people realize.

Also, we are not and never have asked for unfettered access (a favorite disingenuous tactic used by opponents to attack our proposals). CIA drugs would become available only to patients who have run out of approved options and can’t get into a clinical trial, and only after the sponsor filed an application with the FDA for approval of their drug as a CIA treatment and received restricted approval in accordance with the approval standards set forth in the Access Act. Patients receiving the drug could get it only through and under the care of a qualified physician, and would be required to provide informed consent. Folks, this ain’t crazy. It’s rational, humane, and very much needed.

We are not proposing a wild west scenario and never have. I suggest to anyone interested in this issue to take the considerable time required to understand how our system is currently set up at the detail and implementation level, understand why it doesn’t work (these first two steps are critical and what you will learn will probably infuriate you), and then look carefully at our proposals to convert the existing access mechanisms into programs that will in fact work. The “understanding the status quo part is critical to understanding how minimalist and incremental our proposals really are. We are not crazy and we are not trying to crash the clinical trials system.

That said, there is broad and growing agreement that we have a 50-yaer-old, ignorance-based clinical trials and regulatory system that functions as the enemy of delivering progress to patients who have the diseases we hope to better treat. As for randomized trials being the only way to test drugs - we started doing them in 1962 (when Congress directed FDA to start regulating efficacy) as a sort of “best we could do at the time” solution, and we have never tried anything else. They really aren’t that great. In fact, it is very crude, scientifically weak, limited method that doesn’t tell us very much of what we need to know. They can ask only very narrow questions that are unrepresentative of the patient popultaion that will be treated after approval, and they give us answers only about populations and average reposnses within the population. but populations don’t walk in to doctors offices complaining of anything. how is this going to work for disease we now know are genetically diverse and individualized? It isn’t working because it can’t. it is like trying to drive a nail with a kitchen sponge? It is simply the wrong tool.

After almost 50 years of using a system that has barely worked for the diseases that are still killing us, one would think we would have reciognized that we need new methods and come up with more scientific, more effective, less expensive, and less barbaric ways to determine whether drugs work. One might wish we had also come up with new approaches that allowed our progress delivery system to accomodate the needs of real patients, who do not fit into the FDA’s one-size-fits-all approaches.

Fred Baron is one of those people who doesn’t fit, and all he wanted was to try an approved drug off label - something he could have done without even a phone call to the FDA or the drug company with hundreds of other approved drugs that weren’t, in the judgement of his highly-qualified physicians, the one he needed.

When a federal regulatory system, and the massively powerful financial and professional special interests of the clinical trialing industry, staunchly resist change of any kind (as they have for decades and are furiously doing now) to the way we test and approve drugs, and that resistance stalls progress and holds promising and even solidly proven new drugs away from hundreds of thousands of Americans for many months and even years, and those patients die prematurely waiting for progress to reach them (believe me - this is happening), isn’t it time to start changing things?

We have a big, big problem here. We have lost sight of why we started out looking for cures in the first place. Was it to perpetuate obsolete science and a stagant regulatory system? Was it to preserve stagnant regulation supported by professional and financial special ineterests? Or was it to make progress in the only place that really matters - in people who actually have these diseases?

So what should happen? Should all those people simply continue to wait and die prematurely, or should we consider this to be the major regulatory failure it actually is, and start implementing solutions? That is what we, our dying and late constituents and their families, and our advocate allies have been trying to do, and we could use your help.

Steve Walker
Abigail Alliance

I think I disagree with a number of people who seem to believe this is a good example why compassionate use access should be more widely avialable.

To give an example say a hypothetical drug moved into a phase 2/3 trial with a placebo group and enrolled 120 patients (60 in each arm). All other patients are now ineligible for the trial. Using the compassionate use reasoning all these extra patients outside of the trial should also recieve the active treatment. This means that the only people that dont get access to the experimental treatment are the people randomised to the placebo group(not really a spectacular incentive to particpate!!!!)

My point could probably be stated better but hopefully people can understand what I am trying to say.

I really admire the work you are doing with the Abigail Alliance.

Thanks for the informative post and clearing the air.

The world would be a much better place if our current system could be updated to allow every person with no other options left an opportunity to try experimental drugs. The information it provides could be invaluable and although it would not be from within a study protocol, it could be considered (bad or good) and add to the data.

I agree with what you are saying regarding Oncology doctors, they are not prone to flights of fancy and wouldn’t suggest a drug like this unless they felt it would help at all.

While I do believe the FDA has fumbled more often than not, I cannot let the role pharma has to play off the hook. There are famous cases of data suppression, manipulation, missing. So it’s happening on both sides and now neither one completely trusts the other. Because whether we agree or not, our systems are based a lot on trust and we have seen how the actions of one or the other has eroded that trust.

When both sides start dealing fairly and honest with one another, maybe the system will improve.

The blame for the broken system of today must be shared equally.

Good comments. I say, both sides have good arguments. I think your bottom line is correct but maybe, more compassion on the part of those that say, live by the rules and make no exception. I just can’t go along with that. I have had personal experiences and, to see someone die (denied the drug) that “may” have saved them with just maybe a miracle, is very painful.

Amgen did it with their Parkinsons study and the repercussions to this day still ring, including law suits, because they stopped the trials.

Maybe, someday we will have a meeting of the minds and work out a better system.

As I’m sure you are well-aware, there is a significant amount of mistrust of the pharma industry right now. The scientific method requires a carefully designed study that is geared towards answering a specific question. Only then can we really have confidence in the efficacy results. I feel that a system in which people are allowed to take a drug prior to proper experiments being done creates an uncontroled experiment which may undermine what little trust people still have in the pharma industry.

will create an environment that easily could create even more mistrust and ultimately delay the development of approved medications.

Just to clarify, I may not have been clear when I spoke with Nancy about the fact that Baron was not eligible for the trial. If so, I will take responsibility for that. And while I won’t speak for her, to an extent, some of her remarks were aimed at such unfortunate situations, in general, not just Baron.

Also, I would disagree with the notion that a blog isn’t the place to cover this or any complex subject. This amounts to the third post here on Pharmalot about the Baron episode and these have managed to inform the audience about the issue and provided an opportunity to discuss it as well. The overriding issue has been on full display here.

In any event, thanks much for stopping by and filling us in some of the details and your views. The participation is always appreciated.

Ed