Hi All,

I found email addresses for the authors and invited them to visit and/or participate in this thought-provoking thread topic. If you have yet to add your two cents, there's no time like the present.

If you would like to be impressed, as I was, by the authors' professional backgrounds, check out:
Ezekiel J. Emanuel, MD, PhD

Ezekiel J. Emanuel is Head of the Department of Bioethics at The Clinical Center of the National Institutes of Health and a breast oncologist. He is on extended detail as a special advisor for health policy to the director of the White House Office of Management and Budget.
After completing Amherst College, he received his M.Sc. from Oxford University in Biochemistry. He received his M.D. from Harvard Medical School and his Ph.D. in political philosophy from Harvard University. His dissertation received the Toppan Award for the finest political science dissertation of the year. In 1987-88, he was a fellow in the Program in Ethics and the Professions at the Kennedy School of Government at Harvard.
After completing his internship and residency in internal medicine at Boston's Beth Israel Hospital and his oncology fellowship at the Dana-Farber Cancer Institute, he joined the faculty at the Dana-Farber Cancer Institute. Dr. Emanuel was an Associate Professor at Harvard Medical School before joining the National Institutes of Health.
Dr. Emanuel developed The Medical Directive, a comprehensive living will that has been endorsed by Consumer Reports on Health, Harvard Health Letter, the New York Times, the Wall Street Journal, and many other publications. He has published widely on the ethics of clinical research, health care reform, international research ethics, end of life care issues, euthanasia, the ethics of managed care, and the physician-patient relationship in the New England Journal of Medicine, The Lancet, JAMA, and many other medical journals. His book on medical ethics, The Ends of Human Life, has been widely praised and received honorable mention for the Rosenhaupt Memorial Book Award by the Woodrow Wilson Foundation. He has also published No Margin, No Mission: Health-Care Organizations and the Quest for Ethical Excellence and co-edited Ethical and Regulatory Aspects of Clinical Research: Readings and Commentary. Dr. Emanuel has written extensively for the popular press, with articles and op-eds appearing in The Atlantic, The New Republic, New York Times, Wall Street Journal, and many other publications.
Dr. Emanuel has received numerous awards including election to the Institute of Medicine (IOM) of the National Academy of Science and the Association of American Physicians. Hippocrates Magazine selected him as Doctor of the Year in Ethics. He received the AMA-Burroughs Welcome Leadership Award, the Public Service Award from the American Society of Clinical Oncology, the John Mendelsohn Award from the MD Anderson Cancer Center, and a Fulbright Scholarship (which he declined).
Dr. Emanuel served on President Clinton's Health Care Task Force, the National Bioethics Advisory Commission (NBAC), and on the bioethics panel of the Pan-American Healthcare Organization. Dr. Emanuel has been a visiting professor at the University of Pittsburgh School of Medicine, UCLA, the Brin Professor at Johns Hopkins Medical School, and the Kovitz Professor at Stanford Medical School.

Curriculum Vitae

Alan Wertheimer, PhD

http://www.bioethics.nih.gov/people/cv/wertheimer.pdf

G. Owen Schaefer

http://www.bioethics.nih.gov/people/cv/owen%20cv.pdf



History

The NIH Clinical Center is the world's largest research hospital and has been the site of NIH clinical research for over 50 years. A bioethicist first served the needs of the NIH research community in 1977. However, when John Gallin became director of the Clinical Center in 1995, bioethics became a major initiative. This single ethics position became a full-fledged program, with the goal of creating a premier center for bioethics that would complement and inform the NIH's cutting-edge program of biomedical research. In this stimulating environment of scientific discovery and burgeoning new technologies, the Department of Bioethics has flourished, wrestling with major policy issues, offering educational and clinical services, and developing numerous research projects to help advance and inform public policy debate.

• The Blossoming of Bioethics at NIH, a history of the department

Happy reading
Rose

The Center for Bioethics & Human Dignity
EXPLORING THE NEXUS OF BIOMEDICINE, BIOTECHNOLOGY, & OUR COMMON HUMANITY
2065 Half Day Road, Deerfield, IL 60015 USA
v 847.317.8180 | f 847.317.8101 | e info@cbhd.org

Hi all,

I’m Owen Schaefer, one of the authors of the article being discussed here. Rose was kind enough to e-mail us about your discussions here, and I thought I’d respond to a few of the points people have brought up.

First of all, it’s great to see so many of you have thoughtful and insightful comments into this interesting issue. I’m a philosopher by training, and so I love a good discussion and can’t help but feel the article did its job when others feel encouraged by it to engage critically in our work and consider the larger issue of clinical trial participation.

Quick disclaimer: my comments below solely reflect my own opinion and not those of the NIH, which employs me, or the AMA, which runs JAMA, where the article was published. The article similarly solely reflects the authors’ opinions, not those of the NIH or JAMA. It’s analogous to an op-ed piece in the newspaper, as opposed to an editorial.


So, I should clarify the way I take the delay in generic drug availability to work vis-à-vis public goods. When a study is published proving the effectiveness of a patented drug, that knowledge becomes a public good essentially immediately, or at least after a few weeks. That’s because the good of knowledge is public not through the general population knowing about it – even if the journals were free, most people probably wouldn’t have the time, energy or expertise to become familiar with all the new advances – but rather through new or improved options becoming available via one’s physician, nurse-practitioner, etc.

The price of drugs, then, has bearing not directly on the good being public, but on how useful it is. Knowledge concerning very expensive treatments count as public goods, too – but ones that are less important, since fewer people will have access to the treatment. There are, indeed, many who would support shortening patent lengths for pharmaceuticals as a way to make such drugs more useful to society – after all, thanks in part to those patent laws, pharma is more absurdly profitable than almost any other major US industry – including oil, financial services and computing.

Even so, those who cannot currently afford cutting-edge patented products should think on this: without participants in the past who contributed to research, we would have fewer and know much less about generic medications available right now. You may have to wait until the patent expires in 2012 for generic Azilect, but what about currently-generic drugs like Sinemet (generic: Levodopa) or Parlodel (generic: Bromocriptine)? Nearly all of them underwent clinical trials with patient volunteers at some point. It might be true that by participating in a trial, you won’t be able to take advantage of that trial’s resultant medication due to cost and time, but you can take advantage of drugs that will soon become generic, thanks to previous individuals’ willingness to participate in trials. There’s an obligation, I think, to do one’s fair share in getting reliable, useful knowledge on such drugs.

There may be a subset of the population for whom the following is true: overall, recent and projected developments in medical knowledge will be of only minimal benefit, such that it would not be worth the trouble of participating in a trial to support those benefits. And for those people, there wouldn’t be an obligation to participate. However, it isn’t likely many such people would be found in the U.S., even with our large swathe of uninsured individuals. Consider the swine flu: everyone, including the uninsured, will benefit from a safe and effective vaccine through direct prevention as well as herd immunity. And many drugs given in the ER, where the uninsured often go for treatment, are the result of previous clinical trials – if the ER docs didn’t know about effectiveness of various options, treatment even for the uninsured suffers. Our system may be very inefficient at getting care to people, but people of all walks of life still benefit greatly from many medical advances.

To reiterate an important point raised by Rose, people may interpret our article as supporting compulsion to participate research, but that is not so. There are often cases when one might have a moral obligation to do something, but it would also be wrong to compel a person to do that. Free speech cases are like this – it might be wrong to, for instance, make a speech in favor of a political position when in fact you don’t believe in that position at all – but we usually think it would also be wrong to disallow that speech to be made. The right to privacy over one’s body offers similar protections - while it may be obligatory to participate in trials, it would in standard cases be wrong to compel people to participate.

Finally, I’d like to say a few words on a separate issue some brought up – the therapeutic misconception. Many people enter trials in the hopes of getting access to an effective, cutting-edge treatment. However, it is important to remember this: for a clinical trial to be ethical, it must be unknown in the profession whether or not the new treatment is more effective than standard treatment. If people knew beforehand one treatment was better, then we shouldn’t be wasting time, money and patients’ health in clinical trials. Indeed, in a trial, one is subjected to additional tests and procedures that impose risks and burdens one wouldn’t encounter in usual treatment. Hence, ethicists often talk about the “therapeutic misconception” – the idea that a clinical trial is done for the benefit of the subjects, when in fact it is to benefit future patients. In some cases, it may be in one’s best interest to participate – perhaps when the side-effects of the trial are small, ancillary care one wouldn’t otherwise get is provided, or there is a grim prognosis and the patient has ‘nothing to lose’ on a long shot – but participants should keep in mind the sharp distinction between the goals of research (to gather information for future use) and treatment (to care for the patient in front of you).

Again, thanks for your comments on this article – I’ll be thinking of them when preparing for a panel discussion on this topic at the American Society for Bioethics and Humanities conference in the fall.


G. Owen Schaefer
Fellow
NIH Clinical Center Department of Bioethics
10 Center Drive
Bldg. 10 room 1C118
Bethesda, MD 20892

Thank you for the comfortable, thorough, and easy to understand post. It seems to me that we don't have serious differences of opinion on this; we are just coming from different perspectives.

Some of us, as patient advocates, have worked toward improving clinical trials and recruiting for them, specifically for pd. We feel that patients should be at the table when it is decided what to research and during trial design....throughout the entire process. This document was written by patients and the Parkinson Disease Foundation.

http://www.pdpipeline.org/advocacy/rights.htm

Communication leads to trust. Thanks for responding in the spirit of learning.
paula

[QUOTE=G. Owen Schaefer;547960]
Participants should keep in mind the sharp distinction between the goals of research (to gather information for future use) and treatment (to care for the patient in front of you).

How long did we struggle to explain this distinction in the DOR? This is so amazingly succinct and clear. Thank you for this.

This point leads back to my original statement about the goals/agendas of the different constituencies served by the national PD orgs. Successsful marketing depends on correctly identifying audiences and their unique wants and needs. So, if we are going to make headway with the DOR, maybe we start here.

Any thoughts?

Sheryl

Kudos to Rose for taking the initiative to open up communications with "people you should know." Her resourcefulness elicited proof that we don't need intermediaries (though sometimes it is easier with them) to connect with people we need to talk with to bring about change. We have the power, so let's use it before we lose it.

sheryl

Great thread and discussion/ I thank Dr. Owen Schaefer for his post. In the spirit of science and hoping for a good discussion I say that I fail to see a sharp distinction between the goals of research and treatment. In fact, I see them overlapping. The goals of research, particularly in biology are to understand a given problem and solve it, gain information for both immediate as well as future use. Future use may be the bigger picture and so its easy to forget the immediate use. \

In many fields of biology, patients and treatments or lack there of drive research. Research and treatment feed into each other. For example, Phase 1 clinical trials are for saftey (research, data collection), but don't we all look for efficacy (treatment+ data)? Whether its Phase 1 or 3, as a researcher, I gather info, and as a patient it is an experimental treatment for me. The anticipation and the goals of a researcher and a patient are same i.e., that the drug works. Yes, there is a possibility it might not work, but one cannot participate in a clinical study if she/he thinks its a futile exercise.

Sheryl,
From my point of view, there should be an effort to bridge the gap between research and treatment that exists now and the DOR (which is new to me and i know nothing about it) or the advocates need to do that. I am a researcher,developed/developing products for clinical studies and as a PWP participate in clinical studies I believe, the goals/agendas of two parties overlap a lot. Its just that there is very little communication between the two groups and that seems to be problem from my point of view. Patients have an obligation to participate in research and the scientists have an obligation to make them partners in treatments. Its the obligation/duty of the drug company/Govt to reward and care for the person who participates in studies.

thats my two cents worth on this topic....
girija
Sheryl[/QUOTE]

the therapeutic misconception. Many people enter trials in the hopes of getting access to an effective, cutting-edge treatment. However, it is important to remember this: for a clinical trial to be ethical, it must be unknown in the profession whether or not the new treatment is more effective than standard treatment. If people knew beforehand one treatment was better, then we shouldn’t be wasting time, money and patients’ health in clinical trials. Indeed, in a trial, one is subjected to additional tests and procedures that impose risks and burdens one wouldn’t encounter in usual treatment.

Hence, ethicists often talk about the “therapeutic misconception” – the idea that a clinical trial is done for the benefit of the subjects, when in fact it is to benefit future patients. In some cases, it may be in one’s best interest to participate – perhaps when the side-effects of the trial are small, ancillary care one wouldn’t otherwise get is provided, or there is a grim prognosis and the patient has ‘nothing to lose’ on a long shot – but participants should keep in mind the sharp distinction between the goals of research (to gather information for future use) and treatment (to care for the patient in front of you).

my comments below solely reflect the facts:
links to recall:why we have no cures in the USA -...zero ethics!

www.monkeysinthemiddle.com/
_____________
the truth about aspartame - Dr Russell Blaylock

http://www.youtube.com/watch?v=lqIFDoOwSFM
~~~~~~~~`
Profit over life - German death camps WWII
Telford Taylor, US-Chief Prosecutor, in his Opening Statement in the trial against IG Farben (BAYER, BASF, Hoechst) executives at the Nuremberg War Crimes Tribunal 1947:
http://www.profit-over-life.org/

Thank you to Mr. Schaefer for responding to our discussion and to girija for responding from a researcher's perspective. Perhaps my thought process is hindered by the fact that I don't have a background in science or philosophy, so what girija states above, to me, is just plain common sense. Why does the goal of scientific research have to be mutually exclusive from one of its tested outcomes which is often improved treatment? In other words, some trials are designed specifically to test new treatments: safety, dosage efficacy, etc. A desire for novel new treatments and the advancement of scientific knowledge are generally symbiotic, are they not? If Mr. Schaefer is saying that participants, in later trial phases, should not expect to continue receiving the treatment because it will skew data, then I fully understand.

I have never questioned that the goal of research is to treat the participant in the here and now with a potentially novel, effective therapy- this negates the whole idea of scientific control to know efficacy in the first place. Furthermore, if most people hold this therapeutic misconception, why do less than 1% of the 100,000,000 PWP participate in research? (NPF stat) Wouldn't we be then tripping, albeit rather slowly, over our fellow PWP for access to novel treatments? I would argue for a new model of research, one that continues the goal of advancing knowledge, but acknowledges that in many diseases, none of us has time to wait for patents to run out, or for trial outcomes to "trickle down" to us in the neurologist's office or on the operating table.

I would like to see, and I don't know how this conforms to any current philosophical thought on medical or bio ethics, a research paradigm that primarily advances knowledge but that also acknowledges the reality of human suffering in the here and now, and uses the results, all the brain power, funding, etc. we can muster in applying potentially beneficial treatments as soon as possible. What concerns me with the discussed line of ethics is what might happen if someone has a "Eureka moment" very soon and a cure is discovered. How long will it take us merely average PWP to receive curative treatment? Would the FDA super fast track a potential curative? Will our insurance immediately cover its cost? Has anyone ever entertained this thought using the current research model? Really, can anyone with knowledge of how this works be able to draw up research phase to patient benefit timeline? I'm 42, I daresay at my age, I'd be long buried before I had access to a cure if we continue to deny the practical need for treatment in the current model of research .

My thoughts,

Laura

This is strictly my opinion (and please note that I think this is a wonderful discussion), but I don’t believe we can do justice in answering the original question, “Do we have an obligation to participate in biomedical research?” unless we drop the discussion of health reform. That’s a no brainer – we definitely need major health reform, but I am not sure we need a system of social medicine or just how that should be approached. One thing for certain, it should not be rushed. We got into this mess over many years, and it will not be appropriately solved if done so hurriedly. Enough said about that. I would like to answer the original question. And I am assuming the question is addressing whether or not one should actually be a clinical trial participant, differentiating that from the many of us here who are definitely “participating” in biomedical research, but not necessarily first-hand as a clinical trial participant.

I guess since I have made what I consider the “ultimate” sacrifice,” I am “obligated” to respond. Nearly a decade ago I became the second person in the world to participate in an experimental surgical procedure for Parkinson’s. The hypothesis being that by transplanting retinal cells (from a donor eye) into the area of my brain where “normal” dopamine production was deficient, the cells would continue to produce and sprinkle dopamine and relieve me of some or all PD symptoms. This was done unilaterally (one side – opposite side of the most affected side) using a system of microcarriers upon which these retinal cells would “stick.”

The trial (Spheramine) was in Phase I – the safety phase - and was open-label, meaning the small number of participants (3 men – 3 women) knew we were getting the “real thing.” At the time of my surgery, I knew next to nothing about the clinical trial process. Since that time I have learned more than the average person through first-hand experience as a participant and having friends who were participants in a number of trials and as a charter member of the Parkinson Pipeline Project, a grassroots effort to speed up the drug and treatment approval process ( www.pdpipeline.org ). Additionally, I have been working with the Parkinson’s Disease Foundation (PDF) through the Accelerating Parkinson’s Therapies collaboration (APT program) at www.pdtrials.org ) and served on the planning committee and attended PDF’s Clinical Research Learning Institute. Other areas where I have gained knowledge and experience is through volunteer work with the Michael J. Fox Foundation, the Parkinson’s Action Network, and the Parkinson Alliance. I also have volunteered to give presentations of my clinical; trial experiences at conferences sponsored by NPF and APDA, along with several other reputable organizations.

I give you my background because of what I am about to say: In my opinion the drug approval process at present is antiquated, often handled by those with only profit in mind, is not transparent, and is NOT patient-centered. To use an over-used quote: WE NEED CHANGE . . . adding . . . BUT NOT WITHOUT THE PATIENT VIEWED AS THE SINGLE MOST IMPORTANT STAKEHOLDER!

The question of whether or not we have an “obligation” to participate in biomedical research might best have been asked as “Why do people participate in biomedical research?” In 2005, a Harris Poll was conducted by PDF for the APT program. . The poll’s results showed that only one percent of PWPs participated in clinical trials; of those PWPs surveyed who were aware of trials, only 11 percent of them had received information about trials from their doctors.

Survey results such as the 2005 Harris Poll reinforce my earlier comment that the approval process is not patient-centered, or they would be the first to be made aware of relevant trials. Another factor is the difficulty of recruiting and retaining trial participants. The aforementioned “DOR or “Declaration of Clinical Research Rights & Responsibilities for People with Parkinson’s,” was written as a result of patients not being at the center of trials. Horror stories of patients picking up the newspaper and reading that a trial in which they were participating had been halted or hearing through the grapevine that the stockholders had cancelled further work in a study are just some examples why the DOR was written. (although a work still in progress this is a draft copy: http://pdpipeline.org/advocacy/rights.htm )

We hope that advocates of finding a cure or better ways to manage Parkinson’s disease will unite in the effort to educate others in what is the only acceptable and humane way to view the trial participant – i.e. as the single most important stakeholder in the approval process. If there are no trial participants, there will be no improvement or steps made forward in eradicating Parkinson’s disease. With 80 million babyboomers hitting age 60 (the average age of PD onset), I believe that Parkinson’s will be a force to be reckoned with on an equal plane as AIDS or the H1N1 virus.

By the way, in Phase II of the trial in which I participated (double-blind, sham surgery, placebo-controlled multi-facility design), the 72 participates were measured at 12 months and told that Spheramine did not meet its end points, meaning the treatment did not show efficacy over the participants receiving sham surgery. At this point of this “game” the big pharmaceutical company pulled its sponsorship, leaving the small biotech company who created the treatment high and dry – almost to the point of bankruptcy. It was then that I realized the trial was no longer a service or humanitarian act for the Parkinson’s community, but was a “business venture” gone sour. Whether or not the study will be revived or even salient points preserved for future studies remains to be seen.

Peer reviewed results of Spheramine, also known as the STEPS trial, have not yet been published – the trial was halted July 8, 2008. But that’s another story!

Sorry this was so long.
Peggy