Wednesday, March 28, 2012

Talking With Dr. Faustman

A few weeks ago I was able to meet Dr. Denise Faustman in person. We had previously exchanged emails, but this was our first face to face meeting. She was in town (together with Russel, her business development guy) to give a presentation on her research to interested parents. A local family was hosting her presentation, including providing wonderful food and wine for a large number of families to come and hear her. A member of brave buddies worked with the host who was kind enough to invite me. The Initial plan was for me to just attend. However, they realized that I would have different questions than the other people at the talk, and her answers to my questions would not be of interest to the others. Therefore, they suggested that I come early, and we have a conversation ahead of the regular talk. This sounded like a great idea to me. I asked Dave Forer, another Brave Buddy, to attend as well. Dave is a statistician who has worked on clinical trials for 20 years (although not for type-1 diabetes), so he brought a lot to the table [d1]. (Throughout this posting, marks like [d1] refer to extra discussion at the end of the post.)

This posting is made up of two parts:
    1. A status update on Dr. Faustman's BCG research.
    2. Some thoughts on speaking directly with Dr. Faustman.

Dr. Faustman is a famous and controversial figure in type-1 research.  You can read more about her research in my previous blog postings:
http://cureresearch4type1diabetes.blogspot.com/2008/10/faustmans-research-part-1-history.html 

http://cureresearch4type1diabetes.blogspot.com/2011/08/dr-faustmans-phase-i-results.html 

but the bottom line is that in November of 2007 she started a 7 month phase-I clinical trial with BCG which she hoped would cure type-1 diabetes, or at least be part of the cure.  Data from that study has not been published.  

Status Update and New Information
  • The paper with the results from phase-I has been submitted for publication, but has not been accepted for publication, as yet.  So no peer-reviewed results (or detailed results of any kind) on the results of her phase-I clinical trial of BCG have been published.  Nothing has changed there.
  • Dr. Faustman is no longer making public the poster that she had presented at the ADA conference last June 2011.  This poster was the most detailed information available on the phase-I clinical trial (including important C-peptide data [d2]) so making it unavailable is a serious step backwards. 
  • Because it was still being designed, Dr. Faustman would not share with me any details of the planned phase-II clinical trial.  (One of her slides said it would include 60 people, but she made it very clear that was a goal, but could change for any number of reasons.) 
So my overall summary of movement in the last 8 months is: no visible forward progress, and an important step backward.

Talking to Dr. Faustman

My strongest impression of Dr. Faustman is that she comes across in person just like her advocates come across on the net.  She is incredibly optimistic about her research, and extremely driven to move it forward.  She is very passionate about it, and that passion comes through everywhere and all the time. She has explanations and reasons for all the delays in her research, all the results that don't quite add up, all the previous failures with BCG, and so on.

However, there is a big difference between talking with Dr. Faustman's advocates on the web, and talking with her in person.  When an advocate says something that doesn't mesh with what I know about research, I just assume that person is confused.   However, when Dr. Faustman herself says things like that, the effect for me is much more jarring.

The most important example of this is her answer to the question: why were only three people dosed with BCG in the phase-I trial?  Read [d3] for discussion of why this is a critical question.  Her answer was that the FDA would not allow more people to be dosed.  Because of it's importance we spent quite a while discussing this, and she was very consistent that the 3 person trial size was because of the FDA.

However, I've followed dozens of trials aimed at curing type-1 diabetes during this time, and every one of those other trials had more than three people.  Some of them involved new drugs, and others involved drugs with known side effects much worse than BCG's side effects.   Additionally, I researched all the trials using BCG.  There are dozens of those as well, and (again) every one of them uses more than 3 people.  Some of those trials involved far larger doses than Dr. Faustman is giving. [d4]

So I am supposed to believe that the FDA went to Dr. Faustman and said something like this:  Lots of other people are studying drugs to cure type-1 diabetes.  Some of these drugs have never been used for anything before, and we allow all of these groups to test more than 3 people in their trials.   Also, lots of other groups are studying BCG specifically for other diseases, sometimes in much higher doses than you are using, and we also allow all those groups to test more than 3 people.  However, Dr. Faustman, for you and you alone, we are limiting your phase-I trial to 3 people.

Except I don't believe that.  Having Dr. Faustman tell me that the FDA limited her phase-I trial to 3 people created a real credibility gap for me.

There were a total of three issues where things that Dr. Faustman said were not consistent with what I know about research from other sources.  Another example was the question: why won't you make the poster public, which you previously showed at the ADA poster session 8 months ago?  At first the answer was: ADA won't let me.  Neither Dave nor I had ever heard of such a restriction before.  The poster was made public at the conference, what possible reason would they have to restrict it later?   It's completely unbelievable to me.  Dave also expressed his doubts about this explanation [d6], and when he did, the rationale shifted.   There were ADA restrictions, but also the authors of the poster had a meeting and decided jointly not to present the poster data publicly any more.  So then the question was why?  Several reasons were given, all quickly: maybe the data had been misinterpreted by others, maybe they were afraid it would be misinterpreted, maybe they were afraid people would start using BCG off label, maybe the research was limited.  But again, in all the dozens of research projects that I've followed, the researchers are always making more data available, not less data [d7].

Because her paper with phase-I results had been submitted for publication, but had not been accepted, we could not talk about any of the data in it.

I also tried to find out why her phase-I trial took so long.  When the phase-I study started in Nov-2007, it was supposed to end in July-2008.  It actually ended in late 2010 or early 2011.  So a 9 month trial actually took about 36 (or a few more) months.  I asked specifically about why they stopped recruiting patients for an 8 month period.  Read [d8] for more discussion on why this was important.  However, that discussion led nowhere, because Dr. Faustman said she did not know about the recruiting gap, and did not want to comment on any of the information in the FDA's clinical trials record.

The result of all this is a lot of frustration for me.  I ask about data which should be available.  I get reasons why the data is not available.  I ask about different data, I get different reasons why it is not available.  At the end of the evening I have a large number of reasons [d9] why there is no data, but still there is no data; just requests for funding and support.

After our discussion, I listened to her presentation to the other parents.  It was pretty standard stuff about the history of her research including results from her NOD mouse work, and one slide from her human blood work.  But for me, one of the striking parts of the evening, was left out of the presentation:  There was no information on what had happened to people who had gotten BCG in her phase-I trial!  She's trying to raise money for a phase-II trial, without showing the results from her phase-I trial.  And we know the phase-I study has been completed and analysed many months ago, because abstracts were presented at the ADA meeting 8 months ago.

Summary

My wife read a draft of this post, and turned to me, and said:  "It sounds like she didn't have any new data and you were frustrated."   It's a great summary.

I was hoping that speaking directly to Dr. Faustman would give me some understanding on why her phase-I study took so long, was so small, why the results still have not been published, and why she was collecting money for a phase-II study before publication of her phase-I results.  All of these actions can be viewed as signs of possible research failure in her phase-I trial.  However, none of my questions were answered in a way which allayed my worries.

Thanks!

I want to particularly thank the members of Brave Buddies who went out of their way and put a lot of work into making this meeting possible.  I'd also like to thank Dave, who drove a long way, and contributed a lot of knowledge and expertise to the discussion.

Extra Discussion and References


Note that in a couple of cases below, I've quoted Dave from email that he sent me.  He gave permission for each quote and reviewed this posting.  (All mistakes are my own.)

[d1] The company that Dave works for is a small one, and does not do research, sell, or develop any products for the type-1 diabetes market.

[d2] C-peptides were a secondary outcome of the study.  However, they are what the FDA uses to evaluate potential cures for type-1 diabetes, which is why I describe them as an important outcome of the study.  The most important outcome, however, is the primary outcome: the measurement of autoantibodies.  That data is still a complete mystery.

[d3] Except in a few very rare situations (such as complete cures in all cases), a study that only treats three people is very unlikely to provide strong results. When you are looking for slight improvements, or even medium improvements, three people just isn't enough to rule out random chance. All the people who work with statistics, who gave me opinions on this research, commented on this point. This study is the smallest phase-I clinical trial that I have ever seen in all my coverage of type-1 diabetes research.

[d4] For comparison, phase-I trials of already approved drugs (similar to BCG) include: Anakinra which dosed 15, Etanercept dosed 18, AAT dosed 15, etc. So a 3 person study really stands out as being much smaller than the others. 


[d6] In later email, Dave repeated that point: "any poster presented at a scientific meeting is henceforth 'public' and should be disseminated on request. This is a basic convention of science in America and in clinical trials."

[d7] Not showing us the data from the poster did not sit well with Dave, either.  Days later he sent me these two quotes: 
If she had commercial interest in the drug, there would be more of an argument for confidentiality of the results. But she is very vocal at saying that she wants this drug to be available to all. Therefore she should feel free to show any and all data.
Also, she says that the treatment approach she is pursuing here is one for which the rest of the experts in the field are bearish [negative] on. In all history of science, if a scientist is in disagreement with the rest of their peers, it has always been the case that they show their data to any and all who would spend their time looking at it. They need to convince the rest that they are correct and should jump on any chance they get to show they’re data. That’s science! [emphasis in original]
[d8] Obviously, long delays in a research project are a bad sign.  Research is fundamentally uncertain, and while  it is common for trials to last a little longer than expected, it is very rare for a type-1 diabetes trial to last more than twice as long as expected, and this trial lasted more than four times as long as expected.  The only objective information available to the public on this trial is the clinical trial record, and the record shows that there was an 8 month time period when they officially stopped recruiting patients for the trial, and then started again afterwards.   This is very unusual for the type-1 trials that I follow.  Only one other study had something similar to this, and it was such a big deal, that they issued a press release to announce it.  So asking Dr. Faustman directly about this 8 month hiatus seemed like a good idea.


[d9] I'm deliberately not using the term "excuses" here, because of the negative connotations.  But when you are sitting across the table, and asking for data that was publicly shown 8 months ago, and you get this song-and-dance about why it's not available now.  Boy, does it sound like an excuse.

The Clinical Trials record, complete with a history of every change made to it, can be seen here:
http://www.clinicaltrials.gov/ct2/show/NCT00607230

Scott King's blog on this research which describes what he saw on the poster: 
http://www.hanumanmedicalfoundation.org/blog/2011/07/04/highlights-of-ada-scientific-sessions-i-bgc-trial/

Dr. Faustman's ADA abstract from 2011 is no longer available at the conference web site, but you can see the body here:  http://forums.childrenwithdiabetes.com/showpost.php?p=740311&postcount=2

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My blog contains a more complete non-conflict of interest statement. 
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

18 comments:

Anonymous said...

Big “Dislike”!

After all these years of badmouthing Dr. Faustman, you’ve only, now, just met her!! How could you possibly get the answers you are hoping for, when you made up your mind a long time ago that you want to find fault with this research.

When I read your blog – all I see is a whiny, narrow minded opinion from a man with something to prove. What that is exactly, I have no idea?

GabLarConBriCar said...

Josh, this must have been a quite intense experience at a personal level, thanks for sharing your impressions.

It seems to me we go back to our discussions when you first analyzed the Phase I results, which by the way are legitimate questions i.e. why only 3 people, why Phase I design changed dramatically as compared to the original, why don't we see a full Phase I paper, why so little information overall.

At that time, we may have not gotten perfect answers, but I did feel reasonably satisfied with Dr. Faustman's answers in the sense that Phase I was actually designed for safety and tolerability purposes. So I didn't expect to see autoantibody information in the ADA poster or the to-be-published paper. It is quite obvious to me that Dr. Faustman felt so certain about tolerability and safety that when FDA accepted (or imposed) to do it with only 3 people she said "fine".

In this sense, I see Phase II as the phase to focus on efficacy and don't think further discussion on safety and tolerability is really necessary. My real question here is why Phase II design takes so long, as I understand recruitment will start by the end of 2012 meaning 20 months after the end of Phase I which seems incredibly long to me.

Finally, thanks once again for the passion and hard work on this blog!

Cowkitty said...

I wanted to take a moment to thank you for this blog. I usually don't comment on blogs, but after reading the ignorant first comment, I felt compelled to reply.

I understand and fully support what you're trying to do here-- approaching all the research data from an unbiased, unemotional scientific perspective.

You're not trying to "badmouth" Faustman or squash hope-- you're simply looking for reasonable answers, and it is disappointing that she can't answer them. While I remain optimistic, I do see the obvious problem with the clinical study she conducted, and lack of information so long after the conclusion.

Thank you incredibly much for being brave enough to post the good AND the bad of all the research you come across. Not many people try to look at these things from a rational level, and I am truly grateful for the unbelievably amount of time and effort you put into this research.

Thank you.

Joshua Levy said...

For cowkitty:
Whenever I see a post like the Anonymous one I think to myself:
If I made a mistake in logic, he would surely point it out.
And if I made a factual mistake, he would surely have pointed that out, too.
But if you don't like what I say, and can't find a logical or factual mistake, then you say that I'm a "whiny, narrow minded opinion from a man with something to prove".

Truly, Anonymous's comments makes it clear that even he could not find a substantive error in my post.

Joshua

Paul said...

Joshua. As with another poster here, I review a range of T1 websites, but rarely post. If I feel I have something to offer, then yes. You have received knocks for this, and other posts.
When a family member was diagnosed, I started searching the net, as most will do, and I came upon your site. It is the best site I have found in collating and summarising things that have reached actual study stage 1+. Sadly, yes, nothing concrete in the pipeline yet.
I am a fan of Dr Faustman, but you raise very valid points in your critical analysis with your conversation. As with any other field, dedicated fans can be critical of anyone who they perceive to criticise their hero. Thus you may cop some flak for this post. However, as you have said, if people have valid points to make to rebut your post, then let them say it.
Otherwise, I appreciate very much your efforts in what is obviously a continuing effort in bringing together a composite of ongoing research.
If I can PM you, I would be interested in your take on Zhoa et al. If you wish to, let me know the best way we could do this.

mk said...

Has no one noticed that Dr. Faustman's clinical trial entirely misses her own model of a cure? She did not reverse diabetes in mice by giving them doses of BCG. She reversed their diabetes by giving them BCG only PREPARATORY to "re-educating" (a la Zhao)their immune systems with a protein "mask" of sorts. One wonders why Faustman did not form her trial on an identical basis as her mouse cure--or, as she indicated to me years ago when I questioned her about this, if the FDA would not allow a two-pronged procedure (despite BCG's long and wide safety record), why,then, would she stake her claim (and millions in research money) on the oft-exposed failure of BCG instead of on the evident linchpin of her experimental success? The protein path seems to be going very well for Zhao and his fellows. With them, one only wonders whether their trial participants might show even more rapid and/or thorough improvement had they been started out with a shot of BCG...

Julie Colvin said...

Hello Josh,

I’m a prominent advocate for the T1 Cure… Founder of the Facebook Community: “T1 Diabetes Cure – Global Headquarters”, with direct posts from JDCA, TrialNet, JDRF, DRI & Dr. Faustman…. Author of “A Cure for Emma”… Administrator for the support group “Parents of Children with Type 1 Diabetes” to name of few of my endeavors.


I have kept my eye on your reports as we both have the same objective in mind… the T1 Cure, only I believe we have opposite approaches – I go with the “cup half-full” approach; You tend to go with the “cup half-empty”.

Regarding the post from “Anonymous” – I believe that comment was an equally frustrated opinion that mirrored the energy of your blog… which was frustration. The facts are, you did get answers from Dr. Faustman, you just didn’t like them. I was left curious if you were actually trying to say that Dr. Faustman must have been flat out lying to you?


Can you imagine Dr. Faustman’s frustrations over the years to get her research to this point? It took five years for her to be allowed to print that the pancreas can “in fact” regenerate. This has now been proven from many sources and is accepted. Dr. Faustman knew this to be true, but her hands were tied with red tape - she could not use the word “regeneration” in her papers, again… for five years!

History will show that many of the world’s most controversial discoveries were actually met with flat out refusal to stay open to its possibility. Take the theory of hand washing to reduce the spread of disease as an example:

Dr. Ignaz Semmelweis from Hungary discovered in his obstetrics practice back in 1847 that when he washed his hands in chlorinated lime solution, the mortality rate of his patients went from 35% to 1%. But – because the germ theory was not yet discovered, he was ridiculed by his peers for such wild claims and eventually institutionalized, where he actually died, ironically, from septicemia!


Finding the cure and navigating through a system that is not actually set up to “Find a Cure”, but to “Disprove it”, is a challenge that many scientists fail to overcome. Yet… Dr. Faustman perseveres. For what purpose? Because she believes that what she is doing is real and will be a significant piece to the Cure Puzzle. What other motive could she have?


It has been my experience that one’s outlook and approach to life will create what you will find in your future. Whether you look for the problems in a situation or the opportunities, either way… you’ll be right.


I personally would love to see the incredible energy and devotion you most definitely have towards our shared goal, put towards a more “cup half-full” approach. With that intention behind you, combined with your research– you’ll move mountains my friend!!


Most Sincerely,


Julie Colvin

Joshua Levy said...

Julie, here is my reply to one small part of your posting. I expect to reply to other parts over the next few days:

You said "I was left curious if you were actually trying to say that Dr. Faustman must have been flat out lying to you?"

I did not say that, and I can not say that, because I don't know what is happening in her mind. However, my opinion really doesn't matter anyway. Each person must decide for themselves, and here is the information, which I provided in my blog posting, which you (and everyone else) can use to decide for yourselves:

1. Dr. Faustman said specifically and repeatedly that the FDA limited her 3 patients in her phase-I clinical trial. That was the only reason she gave for that design decision, and we spoke about this for several minutes; it was a major topic in our conversation.
2. I've studied dozens of phase-1 clinical drug trials for type-1 diabetes, and none of the others were limited to 3 people by the FDA or anyone else.
3. I've studied dozens of clinical trials of BCG, and none of the others that I found were limited to 3 people by the FDA or anyone else.
4. The paperwork that Dr. Faustman's clinical trial team submitted to the FDA, and is published on the FDA's clinicaltrial.org web site, says the experiment will dose 12 people.
5. I checked with several people who had worked with the FDA on clinical trials in different fields, and they all said that they had never heard of the FDA limiting the trials in this way, under these circumstances, and that it didn't make sense to them.

I don't even think any of those facts are particularly controversial. Based on them, you can decide for yourself. And you should decide for your self. Whatever your explanation for the five items listed above, it needs to cover all of them. For example, it needs to explain why the FDA (which allowed hundreds of 3+ person BCG trials) did not allow Dr. Faustman's, while at the same time explaining why Dr. Faustman's own paperwork said she was going to dose 12 people, and that paperwork has been up on the site for years, and so on.

Note that when I talk about the clinical trials I've studied in items 2 and 3: those are clinical trials aimed at curing type-1 diabetes that have started since 2000. I'm not including trials which were stopped in the middle (cancelled or terminated), or trials which were testing surgical procedures.

Elaine said...

Thanks for all your work.

It is important to emphasize that a phase I trial is only designed to show safety, not efficacy.

It's a valid question about why the size of the trial changed from the original proposal. It might be worth filing a Freedom of Information Act request to the FDA so see what communication occurred before the trial started. Clinical trial results are not releasable via FOIA, but the IND should be.

Maurizio said...

Thanks for your informative post. I see on Dr. Faustman's website a copy of paper:

http://www.faustmanlab.org/docs/academic/Diabetes%20Care_March%202012_CPeptide_Faustman%20et%20al.pdf

published on DIABETES CARE, VOLUME 35, FEBRUARY 2012.

I do not see this paper mentioned in your commentary. What do you think of it?

Thanks,
Maurizio

Joshua Levy said...

Elaine, please don't repeat things that are not true. The phase-I trial was designed to test effectiveness (not safety) The FDA paperwork, which is one line for all to see, says specifically that the trial had no safety end points at all. That's a specific check-box that the group submitting the paperwork had to check.

I'm very curious as to who told you it was designed to be a safety study, because the paperwork that Dr. Faustman's lab submitted when they started the study is very clear that it was not. (Some people think all phase-I studies are safety studies, but that is only true of untested treatments. The first phase-I ever done is always a safety study, but BCG has 100s of studies already done.)

Joshua

Joshua Levy said...

Maurizio, the paper you ask about had been published just a few days before Dr. Faustman and I spoke. So it did come up in discussion, but we did not spend a huge amount of time on it. I have since read it.

Basically, it does not report on any patients who were treated with BCG. So therefore, it does not (and can not) provides any evidence for or against Dr. Faustman's cure theory.

It's central theme is that type-1 diabetics generate a tiny amount of their own insulin even decades after diagnosis. This theory is already widely believed. This paper is good, solid support of that theory. (In particular, Dr. Faustman's team tested more people more times each person than previous research that I know of.) However, the basic idea is not new. A book published last year by DiaTribe has almost the exact same graph in it that is the center piece of the study.

Some people have said that this study has something to do with natural regeneration of beta cells. That is certainly not true in a "net" sense. This study shows very specifically that the older a type-1 is, the fewer beta cells they have. The number slowly drops over the decades. (The full story of beta cell regeneration is too complex to discuss here, but this study does not show that type-1 diabetics at any time regenerate more beta cells than they had in previous years.)

Since this paper does not report on people who were given the drug that Dr. Faustmann hopes will cure, or help to cure, type-1 it does not support her theory. It still is valuable in other ways, however. At a minimum, it suggests that Dr. Faustman could have published her BCG data if she wanted to, but she chose not to. (For example: she could have included it in this paper. The data in that paper came from the same patients and same procedures as her BCG data. In a sense, this paper is the results of her phase-I trial, except that she removed everyone who got the drug being tested, and only reported on the various untreated groups!)

Joshua

Joshua Levy said...

Julie, here is my reply to another part of your posting. The part about half-full vs. half-empty. It is too big to be one comment, so I divided it in half:

I think if you look at my blogging, you will see clearly that I'm very optimistic. However, I believe that optimism is only appropriate when you don't have information. In those cases, I'm very optimistic; I always hope for the best. But once you have information, then for me things change, and realism is the only proper approach.

My blog is committed to optimism for the unknown, but realism when information is known.

Now Dr. Faustman has been working at this for years, and we do know many things about her research, so neither optimism nor pessimism is the right attitude now, but rather we must realistically evaluate the information we have. So, lets consider what is known about her phase-I clinical trial (facts, not opinions and not speculation):

1. In the non-peer reviewed abstract that Dr. Faustman published did not include any data on the primary outcome (autoantibodies).
2. The abstract did mention an important secondary result (C-peptides) and the poster had some of those numbers. However, even this news had huge problems: (a) the results were far too tiny to be of clinical significance. (b) they did not come from comparing treated to untreated patients, (as is standard in research). Instead they moved one person from the untreated group to the treated group for purpose of data analysis. Put another way: they did their data analysis as though as though one of their untreated patients actually had gotten the drug, even though that patient did not. (I've never seen anything like this in any other clinical trial I've covered.) Since the study only had 3 patients getting the drug, this could have a huge effect on their outcome. (c) the poster isn't being distributed any more at all, so no one can even see this data any more. And (d) this data has never been peer reviewed.
3. The trial which was supposed to dose 12 people, actually dosed 3, so shrunk in size to 25% of the original.
4. The trial which was supposed to take 7 months to complete, actually took 19 months.
5. Peer reviewed publication of the results, which usually takes 4-15 months for successful results, has so far gone 21 months, and still hasn't happened.
6. The most positive information we have on the phase-I trial is that it showed safety. However, it tested a drug which has already been shown safe in decades of use, in over 100 clinical trials, and in at least 3 previously completed trials specifically on type-1 diabetes! So saying it was safe is just repeating something that was already very well known.

Joshua Levy said...

So anyone who wants to be optimistic about Dr. Faustman's research is in a bad spot. They need to either explain away all that bad news, or ignore it. Obviously, some do. They say things like: it really doesn't matter that she hasn't yet published her results, or they say that the C-peptide numbers are important and hope no one notices the non-standard data analysis used to get those numbers, or even more vaguely, things like: I'm sure she has a very good reason for that.

However, no amount of rationales or explanations is going to make the FDA approve a drug. And no amount of rationales or explanations should convince you that a treatment is effective. Only actual results should do that.

So let me ask you the question back: Do you know of any other positive results from her phase-I? Because if you look at the list above, it has 4 pieces of seriously bad news, 1 piece of possibly good news with serious problems, and 1 piece of repeating previously known good news. To put it bluntly: the facts we already known about Dr. Faustman's phase-I trial make your optimism completely unfounded; the worst kind of wishful thinking (meaning wishful thinking in the face of facts showing the contrary).

Let my try to illustrate my point with a story. I've tried to include all six points from above:

You are an optimist, who has left your car to be fixed. You come to pick up your car, and it looks like it is in great shape, and you think it's all working great. (You are an optimist, after all.) Then the mechanic comes out. He says "We were planning to fix 12 things, but only actually fixed 3 (i3). Also, we thought the work would take 7 hours, but it actually took 19 hours (i4). After we finished the work, there is a break in period, which we also do. That usually takes 4-9 hours after a successful repair, but sometimes up to 15 hours. We've been doing that for 21 hours, and it is still not done (i5). So your car isn't ready yet. The most important thing you want fixed, we don't know if that was fixed or not (i1). The second most important thing you wanted fixed, we think we see some improvement. When we measure it using the standard technique, we did not see any improvement, but we measured it using a different, non-standard technique, and we see a very, very small improvement, so we're happy with that (i2). When you brought in the car, you said the tires were in great shape. We tested those, and you're right: they are in great shape (i6).

Are you still optimistic about your car? Should you be?

In a sense, we are discussing the difference between optimism (when you hope for the best because you don't have any evidence to the contrary), and blind optimism (when you need to ignore all the known bad stuff). I'm optimistic, but not blindly so.

Joshua

GabLarConBriCar said...

Joshua, we had discussed before the issue of original design versus actual design. The fact of the matter is Phase I was in the end conducted with safety as a primary endpoint as declared by Dr. Faustman herself here:

http://www.faustmanlab.org/docs/clinicalt/Phase%20I%20Trial%20FAQ.pdf

In this sense, I don't really see the point in trying to assess the (few) published results as if the primary endpoint had been effectiveness.

As indicated in my March 29th comment (to which you answer indirectly in your reply to Eliane on April 12th), the fact that Phase I was performed differently than originally designed is indeed a legitimate question and a source of frustration. But I believe we are distracted from the real issue here, which is to focus on the efficacy-oriented Phase II. I want to know more about it, i.e. why is it taking 18 months to design, when is it really going to start, etc.

Anonymous said...

Most scientists who have changed our world were not believed or validated until they persevered through to the end product. Would you have funded Steve Jobs in his garage oh so many years ago? I think Dr. Faustman should be funded and she should get on with phase 2 of human trials and we'll see what happens. Debating about whether she is right or wrong, altruistic or self serving, etc... is a waste of time. Most people who change the world have minds to which are difficult for the lay person to relate. We need these people and we need to believe in their research to see it through to the end. The cure that she believes in would bring in no money for all of the pharmaceutical companies invested in Type 1 Diabetes. It's big business. Big business has power and I am assuming she cannot reveal particular aspects of her study because she does not want them obliterated before they even make it to the testing phase. Sometimes, we just have to believe and support without knowing every single detail along the way.

Anonymous said...

In your paragraph at the end, you wrote, "I want to particularly thank the members of Brave Buddies who went out of their way and put a lot of work into making this meeting possible."

As it turns out, the host of this event was not a member of Brave Buddies at the time and hosted it and funded it without any connection to any specific organization. If you cannot get these simple facts straight, I question the accuracy of your reporting. _Tammy

Anonymous said...

I think that the proof is in the pudding. I am read to try any commercially available BCG vaccine and calibrate any changes in HA1c and visual changes in my psoriasis.
there is a difference between scientific rigor and empirical self experimentation. one might also look at end stage blind diabetics and administer BCG and look at the retina for visual changes in leakage etc. a simple and harmless observation. there are many possibilities.

too much yapping and not enough human experminentation by those who are suffering and rotting and disintegrating now.