Originally a college teacher of American studies, then an attorney specializing in representing clients against their insurance companies, Milstein began focusing on medical research abuse litigation after he represented the family of Jesse Gelsinger, an 18-year-old who died during an early gene therapy study at the University of Pennsylvania. Milstein has taken on other high profile medical lawsuits, such as one against the Fred Hutchinson Cancer Research Center in Seattle, and another against the University of Oklahoma, for violations of patient safety. He also represented U.S. military personnel in their case against BioPort Inc., producer of the anthrax vaccine given to our soldiers, for negligence in its manufacture and testing of the vaccine.

All of these cases have a common thread  - Milstein’s deeply held belief that patients who risk their lives volunteering as medical research subjects have the right to be treated with respect and with concern for their well-being. And that is not commonly happening in today’s corporate research environment.

The editors of the Grassroots Connection thank Alan Milstein for participating in this interview. We thank him also for his dedication to patients’ rights, and for representing the GDNF trial participants in New York City and in Kentucky.

GRC editors invited Nan Abraham, Co-Founder of People Living With Parkinson’s, Inc. (PLWP) to join us in this discussion.  PLWP currently has an online petition seeking reinstatement of GDNF to the clinical trial participants at   http://www.plwp.org/GDNFpetition2005.htm

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GRC: To date there have been two denials of immediate reinstatement of GDNF to the patients by Judges Castel and Hood in New York and Kentucky.  Both judges ruled in Amgen’s favor because of contractual (or lack of) issues.  What happens next? 

MILSTEIN:  The two cases will proceed along separate tracks. In New York, the preliminary hearing was an attempt to grant an injunction to reinstate treatment of the drug while court proceedings determined the outcome of the suit. Of the several counts filed in the complaint, the contractual issue was the primary charge through which this injunction could be argued. 

The injunction was denied, and now the New York case will proceed as a civil suit, citing negligence by Amgen in their treatment of the trial participants. There will be questioning, depositions, discussion, and eventually either a settlement or a trial.

In the Kentucky preliminary hearing, which was also held for immediate reinstatement of GDNF, the question was “Who should be responsible for making the decision to stop the drug from being administered?’  Their Informed Consent form was different than the one used in the New York study. It was the participants’ and the trial doctors’ understanding that GDNF would continue to be provided if found safe and effective by the research doctors. 

GRC:  What was the problem with the Informed Consent document?

MILSTEIN:  There are two problems common to all the cases I have been involved in.  One is the Informed Consent is one-sided and written by the sponsor or the research institution.  Patients can't alter them; they have been approved by an IRB (Institutional Review Board) with patients having very little say about what is included or not included.

The second problem that I commonly see is a real “disconnect” between what the researchers tell the subjects, what the subject understands, and what the document says.

Informed Consent documents can be quite misleading to human research subjects, particularly those searching desperately for a cure for their disease. Here’s what is not in the Kentucky document.  Nothing in there says it’s an experiment.  It talks about “therapy” throughout the document , as if GDNF is proven to be effective. This is why the subjects approached this trial as if it were a therapeutic option and one where their physicians would decide what was in their best interests. 

Suppose the document said: “This is a human experiment.  We want you to be a human guinea pig.  You are to have no rights and no say.  We are using your body to see if this drug works and we, Amgen, the company with the commercial interest in this drug, can decide to stop giving it to you at any time.”

Who would sign it? 

GRC:  Do you think, after two hearings, that Amgen has sufficiently presented a case that says GDNF isn’t safe or effective and that they needed to put it on hold?

MILSTEIN:  Those issues haven’t been litigated. No judge or jury should be expected to make scientific decisions.  That’s not what our judicial system is for. The issue is: ‘who has the right to make the decision?’  In  both New York and Kentucky we felt it was the Principal Investigators.

There are two parts to this issue. The first is that the decision on whether GDNF was safe and effective was up to the Principal Investigators - not Amgen. The second is that, even if it were Amgen's decision to make, Amgen made the decision in a manner that departed from standards in the industry.

GRC:  Amgen met with the FDA about GDNF in January, but has not disclosed the outcomes of this meeting.  Is there any information you can share about the FDA’s input into the decision to halt the trial and/or grant continued use (compassionate use) to the patients?

MILSTEIN:  I don’t know if there are any actual minutes available from that FDA meeting, but the FDA didn’t object to continued compassionate use.  They did not instruct Amgen to halt the trial, but left the decision up to Amgen.  To my knowledge, no one asked the FDA specifically for compassionate use at that meeting.  It might have been granted.

GRC:  The Parkinson’s Pipeline Project has been working on a Research Participants’ Bill of Rights, which would provide for patient input on Informed Consent documents.  Do you have any suggestions about what should be included?

MILSTEIN:  I’ve lectured at several research institutions about this and have several thoughts about it.

1. Tell it like it is.  Be completely honest and explain it thoroughly, including any possible reasons for terminating the trial.

2. Allow the subjects to participate in critical care decisions.  Allow them to be participants, not mere objects of study. 

3. Use patient advocates who can understand the nature of the experiment and explain the benefits and the risks to the subjects.

4. And lastly, the focus should be on what is in the best therapeutic interest of the subjects not what is in the best commercial interest of the drug company. 

These are human beings.  The GDNF trial was a really unusual trial compared to most I have been involved with.  Usually the case involves the patient taking a drug.  But it includes nothing like having holes drilled in your head, pumps and catheters inserted, and then some only receiving a placebo.  Many people have trouble with some participants only getting the placebo in such trials.

The subjects invested much and had no other options.  Typically in clinical trials, the drug company must list alternative treatments in the Informed Consent document.  It is quite remarkable that in this document, there are no alternatives.

GRC:  Should the patients be given the decision to continue in a trial, providing they receive full disclosure all along the way?

MILSTEIN:  There’s a problem with that.  Having the “inmates running the asylum” would cause an Informed Consent document to lose credibility.  It doesn’t work.  The decision about whether or not to continue the experiment and to provide the drug must be left up to the scientists, but it must be done with the patients’ best interests at heart, not the commercial interest of the drug company .

Should it have been Amgen,  in this instance,  or the Principal Investigators?  That is the critical question. 

GRC:  New delivery systems for GDNF are being investigated.  The time factor concerns us as patients, because other methods of delivery are years away from being available.  In the time it takes for a delivery method such as gene therapy to be developed, a generation of Parkinson’s disease patients will needlessly suffer, while a drug that might have saved them is sitting on the shelf.

MILSTEIN:  It doesn’t seem like Amgen is going to give up on GDNF.  I’d be shocked if they use gene therapy; it's a long way off.  Although it probably will happen someday, people should not count on it in our lifetime.  There has never been a gene therapy yet - only experimentation.  This is a misrepresentation.

GRC:  Many other diseases are affected by Amgen’s trial halt and many patients are following what’s happening, looking for ways to help and protect each other.  Can you think of any other ways to help improve patient treatment in clinical trials?

MILSTEIN:  That’s a very good question.  The legal system isn’t the best means of establishing these rights of human subjects.  You’ve got to go through the technical hoops and every time you try something new, you meet with resistance from the courts.  I think Congress needs to get involved. 

One of the interesting things resulting from the Gelsinger case was a Senate hearing in which the focus was on the rights of human subjects. The proposal was to revive a bill originally written by Senator Glenn and then taken up by Senator Kennedy.

Another hearing was scheduled that would have gone a long way towards establishing what was needed, but it was scheduled for 9-12-01.  Momentum stopped on 9-11 that year.

The public needs to understand more about this important unique enterprise called human subject research . No one questions that we need this enterprise to make advancements in medicine and science. But there were terrible abuses in the past and some of those abuses, though perhaps without the same evil motives, continue today. Human subjects need to become real participants in the process and no longer viewed as merely a means to an end, however important that end is for the greater good. The research must never compromise the essential human dignity of any single human subject.