It is a perfect day for bananafish.
I remember one summer when I was 14 and I read every single word ever written by J. D. Salinger that I could get my hands on. An intravenous bolus infusion of JDS you might say, that went straight to my head without any sober literary criticism as intermediary to spoil the rush. Several years later I met my husband to be. I never told him this but I think I married him because I thought he was a bit like Seymour Glass. Raise high the roof beam, carpenters.. Like Ares comes the bridegroom, taller far than a tall man.
Today seemed to be a good day to remember the intense need for authenticity and altruism I felt back then. I am sure many of you went through similar periods in your lives. Some vague stirrings of the same feelings still remain but mostly silenced by the ravages of time, chromosomal damage and deletions to my altruism genes that no FISH test can hope to capture.
If you are not a fan of J. D. Salinger and don’t get some of these mantras true devotees know by heart, don’t worry. You may still enjoy reading the rest of this article. I will warn you guys upfront though. Most of this article is my own perspective, editorial comments from yours truly. Take it or leave it, as it seems right to you.
Our life blood draining away
Clinical trials are at the heart of all hope for patients like us inflicted with incurable diseases. Without well conducted clinical trials and the credible lessons and results learned from them, we would still have only chlorambucil as therapy option. Research done in glass dishes or mice does not (repeat, not) guarantee things will pan out exactly as expected when tested in human subjects. Clinical trials are expensive, time consuming and have become very frustrating for all concerned. Really large sums of money ride on the outcome of pivotal drug trials – and that complicates things enormously.
But clinical trials are still the life blood of all future developments. Without well conducted clinical trials there is no hope that CLL and other such incurable diseases would ever be cured. Without patients willing to volunteer for clinical trials the process grinds to a halt.
Our clinical trial process is truly busted
And that is putting it mildly. As the excerpt below from a recent article points out, percentage of patients who volunteer for clinical trials is dropping like a rock. You can read the full length article by clicking on the link.
November 1, 2008
Oncology News International. Vol. 17 No. 11
Clinical trials struggle to recruit, retain patients
BY CAROLINE HELWICK
An alarming 80% of US trials are delayed because of poor enrollment. Experts share what’s being done to close the gap between patients’ awareness of trials and their actual participation.
It’s no secret that enrollment into cancer care clinical trials has reached a level that could be described as anemic. Conventional wisdom puts adult enrollment at 3% to 5%, even though two-thirds of cancer patients say they are receptive to participating.
“Two surveys of cancer survivors conducted in 2000 and 2005 suggest that 4% is probably a real number,” said Robert L. Comis, MD, president and chair of the Coalition of Cancer Cooperative Groups (CCCG) and chair of the Eastern Cooperative Oncology Group (ECOG). A recent survey of 9762 patients by the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) found only a slightly higher rate, 5.5%.
Either way, the number is “distressingly low,” Dr. Comis said.
Why are patients shunning clinical trials?
There are lots of reasons why this is happening. Here are some contributing factors that I would like us to discuss:
- There are too many me-too type clinical trials funded by well heeled drug companies looking for larger market share and bragging rights. Such trials siphon off the bulk of patients that are looking to participate in clinical trials. I am sure many of you have heard of scandals where drug companies do a series of very similar trials – then pick the ones which happened to give the best results to get FDA approvals and market share.
- Major institutions such as the Mayo and M. D. Anderson with heavy flow of patient referrals have a built-in advantage, directing their patients to participate in the specific trials they happen to be sponsoring at that point in time. Smaller trials at less well known institutions suffer by contrast, even if they have good ideas and good science to their credit.
- Not all good therapeutic ideas are necessarily good commercial ideas that will make some one or some company very rich. The EGCG (green tea extract) trial would have languished a lot longer for lack of support if CLL Topics (and our generous patient community!) had not stepped in to support it.
- Science is getting awfully complex. Most patients have no chance of really understanding what is involved in participating in a clinical trial. How do you make informed decisions involving life or death, if you cannot get a good fix on the risks and rewards involved? And no one takes the time to explain things to you in language that can be understood by laypersons?
- Most patients are seen by local health-care providers who have no incentive in recommending clinical trial participation. First, it takes a great deal of effort to stay fully informed about all the various trials out there, for all the different kinds of cancers treated by local oncologists. Second, why would a good businessman (and most doctors’ practices have to be businesses to survive these days) send away a paying customer to someone else? Where is the profit in that?
- Some insurance companies will cover the cost of drugs and therapy that is not covered by the clinical trial itself. But who will pay for all the travel and living expenses incurred? Most trials require you travel to their site several times during the trial itself and for follow-up.
The brand that is on sale today ..
A couple of years ago I got to know a very wealthy and determined member newly diagnosed with rather aggressive CLL. He got disillusioned with his local oncologist pretty quickly, for the usual reasons. He wanted nothing but the best in treating his disease, and he told me he can afford the best. He asked me for the names of the top five CLL expert centers to visit. He wanted to get guidance on his specific case from the best minds in the business.
I gave him the names of the five best centers – most of you who have been round the block for a few years can guess them easily. I also gave him a sealed envelope with the therapy recommendations I expected he would get from each of the five centers he was going to visit: FCR, PCR, flavopiridol, “gene therapy” and Campath.
My friend went to each of the five centers in turn, asked each expert he met to do detailed testing and prognosticating, expense be damned, and come up with the best therapy option custom-designed to his particular needs. Each center obliged, at significant cost. My friend is wealthy and did not care about that. Heck, he wore nothing but custom made clothes and custom made shoes, lived in a custom designed home that he shared with an almost-custom sculpted wife (snicker), why should he not get custom made therapy for his cancer?
He came back from his voyage of discovery chagrined and confused, with five completely different recommendations from the five expert centers. He then opened my sealed envelope and I am pleased to say I was spot on in my guesses. I could have saved him all that fuss and expense. I got all five recommendations exactly right and matched each recommendation correctly to the expert center. Each center felt the particular clinical trial they were focused on at that particular time was the best suited therapy option for my friend.
(Pop quiz: can you match each of these therapy recommendations with the expert center most likely to have made the recommendation? If you can, give yourself a pat on the back, you are now a savvy consumer of health-care.)
How can this be?
How can there be such divergence in opinion between different expert centers? How can we trust guidance that is so influenced by local biases?
The answer is complex. First, researchers are human beings too, with their own built in human biases. How can one work for decades at developing a particular drug protocol without developing a certain amount of personal bias in its favor? Heck, each of us thinks our kids are the brightest, prettiest kids on the block!
Second, institutions spend a lot of money running their clinical trials and it is crucial to get a steady flow of volunteers lined up to participate. Institutional prestige and reputation (not to mention large scale endowments) ride on it.
Third, reputations and careers of the scientists involved are made by successful clinical trials that progress rapidly through the various stages and become commercial successes. Ditto for commercial profits of companies that own patent rights for the drugs involved.
Fourth, and this may come as a shock to some of you, some drug companies actually pay head-hunter fees (thousands of dollars per patient recruited) to local oncologists that bring them new recruits. Money buys a whole lot of influence – ever been to one of the ASH conferences?
Where in this dog’s breakfast mess of conflicting agendas does the individual patient’s welfare figure? How many experts are able to wear two or more hats? That of the brilliant scientist and admirable researcher on the one hand, and the caring physician looking for the best custom-fitted therapy option for the patient sitting in front of him – and do justice to both agendas? Where does multi-tasking end and conflict of interest begin? And how can you as the hapless patient tell the difference?
Thinking about it, any wonder there is so little credibility left in the present process and patients are running away in droves from clinical trial participation?
Informed consent that isn’t
If you have ever signed up for a clinical trial or even considered the possibility, chances are you were given a sheaf of papers to sign – giving your “informed consent” to participate in the trial.
Anyone out there who bothered to read the full text of these documents (mostly medical and legal disclaimers aimed to protect the researchers, drug companies supplying the experimental medications and the institutions where the trial is being conducted) and thinks they were therefore truly informed? I mean anyone without advanced degrees in the sciences, preferably a double degree in hematology and oncology?
Much of the language is mandated by law and in my humble opinion, by a desire not to get sued. There is usually a laundry list of potential adverse effects all the way from a mild headache to instant death: a long and all-inclusive list that is all too often accompanied by a wink-and-a-nod by the research nurse handing out the papers. You are a smart patient, you know how these things work – the implication goes – these are just paperwork hurdles that “they” force us to jump.
Every early stage clinical trial disclosure contains language to the effect that participation in such early stage trials is not (repeat, not) meant to be of therapeutic value to the participants, the intent of these early attempts is to establish the right dose and judge toxicity. How many of you are still convinced that participating in early stage trials may still have terrific therapy value for you because the science so sexy and the researcher has a terrific bedside manner? This is what I mean when I talk about the wink-and-a-nod approach to “selling” clinical trials. I have a great deal of admiration for all clinical trial volunteers. But I am old fashioned, I also believe in the individual’s rights to make decisions with his/her eyes wide open. Coerced altruism is another name for a sucker’s game.
Bewildered patients often take the path of least resistance, assuming all the advisories and cautions are just so much bureaucratic nonsense to be disregarded immediately. All of us are guilty of signing on the dotted line without reading the fine print at some point in our lives. Heck, I find the fine print that accompanied a recent credit card application could not be read even when I got me a magnifying glass – justifying the label of “fine” print indeed. Mandatory “Plain English” laws do not help much either. It just forces the researchers to dumb down the disclaimers. The fundamental problem is that the science involved is often just too complex to explain to a lay audience in a few pages of text, or over a 15 minute consultation, by harried healthcare providers.
I believe the law of the land requires banks give customers several days over which to consider the terms and conditions of their mortgage. Customers can take home the full set of documents, mull them over, ask their accountant brother-in-law for his take on it, do a bit of human dithering – and then make the decision that is right for them.
Compared to that, do you know most clinical trial protocols are classified as “confidential” and patients are discouraged (if not forbidden!) to discuss it with their own trusted advisors? In any other industry this approach would be called giving the mark the bum’s rush. Fortunately, a lot of patients trust my promise of confidentiality and do share their clinical trial protocols with me, and when requested to do so I am honored to give them my two cents.
It is unfortunate that the real risks are often overwhelmed by the long and often trivial list of low impact or low probability risks that are neither here nor there. I mean, as patients facing an incurable cancer, is it really pertinent to worry about the potential risk of grade I headaches that may or may not happen? That you may up-chuck a couple of times? I am far more interested in knowing about, say, Stevens-Johnson syndrome. What the heck is that? My next door neighbor is named Steven Johnson – he is not dangerous at all, in fact he is a real sweetheart and does my lawn for free. Any syndrome named after him cannot be all that dangerous, right? (Wrong!)
Looking at the problem of getting informed consent from the perspective of the researchers, I have to admit they have a valid beef with the whole concept. Science is developing at a dizzying speed. Concepts are getting ever more complex. Even trained MDs are having trouble keeping up. How can doctors explain such complex issues to layperson patients in a reasonable amount of time? Medical school does not train doctors in the art of teaching science to non-scientists. (Tooting my own horn just a little, my doctorate from the University of Michigan was focused on exactly that: teaching science to non-scientists)
You drive this bus. What say you?
Whether or not you are newly diagnosed and in W&W, about to start therapy or happily smoldering away, participating in well designed and well conducted clinical trials are an option worth considering. Here are some of the roadblocks.
- Does your doctor (local guy) bring one or more clinical trial options to your attention? Does he explain the pros and cons to your satisfaction?
- Do you feel when you sign up for participating in a clinical trial you are doing so fully aware and informed about your risks and rewards? Did the researcher do a good job of explaining things prior to your recruitment?
- Do you trust your doctor / researcher / expert to put your welfare ahead of his desire to recruit patients for a clinical trial that he wants to see succeed, for whatever reason?
- Do you get a chance to mull things over, discuss with outside advisors, before you had to make a decision? Was there a sense of getting the bum’s rush?
- Will you volunteer for a clinical trial even if you personally will not benefit from it, but you like the idea of doing something to help other patients? Possibly your kids or grandkids?
Some people are proposing more aggressive marketing targeted directly at patients in order to “sell” clinical trials. How does that concept grab you? Frankly, it scares the living bezeesus out of me.
January 1, 2009
Oncology News International. Vol. 18 No. 1
Clinical trials benefit from aggressive patient outreach
BY CAROLINE HELWICK
Good public relations are part of any successful business, and cancer trials are no exception. Drs. Charles Weaver and Robin Zon discuss their tactics for recruiting patients in this alarming article.
Living the ‘authentic life’
Not everyone gets a chance at redemption and salvation in their lives. If you are a patient who volunteers to participate in early stage clinical trials that may have no therapeutic benefit for you but might, just might, improve the lives of future generations of patients, in my eyes you have become a grown up and responsible version of a “Catcher in the Rye”.
If not you, then who?
If not now, when?
If not with your eyes wide open, why bother?
37 comments on "Do It For The Fat Lady"
Very informative article. Thank you very much. Thank you, too, for recommending the NIH study. It’s true that there are some unreimbursed costs but not too much and the way they treat you there is very nice.
Thanks, Chaya.
Tom in Durham, NC
Hello Chaya,
I probably fall in a safe category which is having my altruism and eating it too. I am in two studies, one at Uof Mich and the other at OSU.
Fortunatley, they just mean more blood vials at each visit to the clinic.
Dunno if I have the courage to undertake true altruism yet. Still feel I have a lot to lose. Please keep up our work.
Dave Mikol
I loved JD Salinger and read every word during my high school years. I am saddened by his death. I am in a trial at NIH for early pre-drug patients. I just fired my local oncologist and will meet with a new one on Monday. I just want someone who will answer my questions and not seem offended. I will do what I need to for my kids, grandkids and other people who may end up with CLL in the future!
At my center the two research projects I participate in required nothing but paperwork and access to prior samples or a blood draw- absolutely no downside to a patient – and yet they may have to consolidate with another center due to lack of sufficient participation. I can appreciate all the issues raised above, but what explains lack of response even when no such negatives apply?
Very thought provoking. Several people have asked me if I would participate in a trial when I first was diagnosed 4 months ago. At first it was like “Hell yeah” even though I am slow and smoldering right now. As a cancer patient with an incurable disease your first thought is “whatever it takes”. Like your wealthy guy, some of us would take whatever if we thought it was a cure. But after thinking about it more, the one’s running the trial funded by big Pharma companies are the ones that will benefit in the end. In fact, a trial with a new drug could basically kill me! All in the name of science. I might have a better chance with a stem cell transplant assuming I was in good health and found a suitable donor. Why take an unknown chance. Maybe that’s a little selfish on my part since after all I might help others down the road potentially and not benefit at all. So why shouldn’t I get compensated for participating in some drug companies lab experiment? These drug companies stand to make hundreds of millions of dollars off a drug that without my and others help may never come to market. Why shouldn’t my wife or kids or grandkids potentially get a small profit windfall. I would like to see a trial where if I participate and the drug comes to the market, a consideration payment is made to me or surviving family. Just maybe that would entice people more. Sounds like a Win-Win for everyone if you ask me. P.S. What’s the pop quiz answers, please.
qb:
I do not know why participation rates are so low even when there is little risk or cost.
If I were to guess, I think it is because our modern culture seems to breed apathy. Cynicism is cool and not as many people step up to the plate. We want the other guy to do the heavy lifting while we sit on the sidelines doing a bit of armchair quarterbacking. Gone are the days of strong community spirit, we are a nation of footloose wanderers. It is my hope that the cyber communities we are building will give us back that sense of community and inter-connectedness. We are each one of us our brother’s keeper.
Thats my two cents and I am sticking to my story :)
Chaya,
You continue to write articles that directly help me to keep my eyes wide open! My husband’s first treatment in 2003 was with FCR – a clinical trial at that time and it definitely proved to be the right choice for him – a person diagnosed with only 5 months of watch and wait due to many of the prognostic markers. 4 years of remission, treatment early 2009 with Treanda (unsuccessful) and was about to start a new clinical trial at MD Anderson this past December when HIA and ITP (both at 7) happened. Currently trying to get that under control before we find out the next step. We do trust our CLL expert and believe he proposes trials in my husband’s best interest – and, we’re fortunate to have a local oncologist who works cooperatively with him. Bottomline – you help us to really think about our decisions – and not just leap into what we’re being given. Thank you for that!
CClaver:
Here are the answers to the pop quiz:
FCR: M. D. Anderson
PCR: Mayo Clinic
flavopiridol: Ohio State University
“gene therapy”: UCSD
Campath: Long Island Jewish Hospital.
But please remember this was a few years ago and some of the choices have changed. “Gene therapy” is no longer available, but an updated version of it – now called an equally sexy name of “vaccine therapy” – is offered at UCSD and M. D. Anderson. I think LIJH has moved on from their earlier devotion to Campath.
Chaya,
As a Genitope alumni, I have to say I enjoyed your article. I am still a fan of trials and would still participate but I share your concerns. Read the fine print, do your homework, make your own decision. I think the best advice in this situation applies to many – Think for yourself!
suz
It is not only hard to choose which treatment, but which version. I have heard Kanti Rai (LIJH) debate with Michael Keating (MD Anderson) about the dose of Rituxan appropriate at one of those ASH meetings. Kanti was worried about the cost and MD Anderson chose the dose for maximal effect in their trials. Kanti argued there was no data to support the higher dose. How to know in advance who is right?
The patient confidentiality laws were initiated, mainly, to stop people from joining clinical trials in the hopes of having a cell line named after themselves, and de-identifiers and codes were born. In her speech at this same ash meeting Clara Bloomfield railed against the obstacles to good science presented by the Institutional Review Boards who oversee these huge packets few read fully or understand.
I would like to see these clinicians have published “batting averages”. What patient would not like to know how many deaths vs cures their potential clinicians have? Why not release thd statistics about how long a person will live on average when they present with CLL at a given center or with a certain doctor. A common thread is their nice bedide manner, but I am sure most people want the best doctor not the nicest. They all have these numbers and they could easily be put out without violating existing regulations. They know there is only 1 Best clinician. Kipps and Neil Kay both seem brilliant, Byrd seems the most independent thinker. If I had to bet on the best, it would be Kanti. He has the most experience and the least incentive to try for fame and fortune. He can afford to put the patient first. I would still like to see the numbers.
Chaya,
You present a very thought provoking article. It is appreciated. I have developed a healthy skepticism regarding drug trials as a result of my travel through my one and only drug infusion. I am convinced your quiz is still appropriate as I follow the work of the five institutions you list.
I always appreciate your take on what is going on with CLL research and drug development.
Barry
Of the many discussion roads we travel together, I think this is a most compelling one in our traffic pattern. It provokes much thought and pondering. I have travelled two clinical trial highways out of seven therapies over the years. I am blessed to have responded well to both. In choosing trials I was influenced by some “for the team” thinking, but I also wanted, and got, assurances this was my best option at the time. Looking back I now see there was some “my model car” salesmanship … what did I know then? Not much. I wish the clinical trial process could isolate trials to a more cooperative consensus among expert providers (big five, etc.), and chosen trials be infuluenced FIRST by potential efficacy. Commerce, which I’m not against, can come later. I think trial participation is fading because they are too scattered and mysterious…… just my personal ramblings!
Chaya, your Seymour Glass snippet was touching. Thanks for sharing that. “Catcher” caught me too. I think it owns a piece of a lot of us. J.D knows it for sure now.
Clinical trials may be either “treatment” or “non-treatment”.
Chaya’s article was focused mostly on treatment (drug) clinical trials.
In drdave333’s comment above, he mentioned simply donating a few extra vials of blood at each clinic visit. Thus, he is participating in “non-treatment clinical trials.
Even CLL patients in “watch and wait”, can help researchers and fellow patients by participating in non-treatment trials.
I have been in watch and wait since I was diagnosed in February 1998. Thanks to having a tiny melanoma removed in 1999, my CLL reversed its advance and began smoldering. When I noticed my white blood counts dropping, I did not know the reason but I thought researchers might be able to learn something from my case. Therefore, I went on-line and ultimately found a non-treatment clinical trial at Ohio State University for the CLL Consortium. So far, I have participated in three non-treatment clinical trials at OSU and the “quality of life” trial done by CLL Topics and the Mayo Clinic. In total, I spent maybe an extra twelve hours spread over ten years to:
1. Complete some consent forms
2. Agree once to provide a little larger sample if I ever have another bone marrow biopsy.
3. Answer questions about cancer in my family
4. Make my CLL records available to researchers
5. Provide some oral DNA (painless)
6. Provide some extra vials of blood during routine draws
7. Answer an on-line survey.
Especially because CLL is a rare and often serious disease with many different variations, clinical trials are very important. Considerable progress has been made in the last fifteen years but more is obviously needed.
Both treatment and non-treatment clinical trials in the United States may be found at http://www.cancer.gov/clinicaltrials .
My sister and I are enrolled in a study at NIH/NCI on familial CLL. We are both boring patients, asymptomatic (still stage 0 after 13 years) but our father had CLL and we both have children. We know that we will not be “cured” by this research, but it might help our children, grandchildren, or a great-grandchild. I have no local oncologist, I am worried that I can’t find one that can spell CLL, and I really have no need for one at present. My internist orders the lab work that monitors my condition, and I forward this to my clinicians at NIH/NCI. I believe this study is looking for participants also. Being in this study is the least I can do to honor my father, and possibly help my family and others.
A Covell
As a potato, potarto/ tomato, tomarto Brit, could you please translate ‘bum’s rush’ for me? In English as opposed to American, it would be some kind of rash on your backside!
I gave my son Catcher in the Rye to read 4 years ago when he was 14. He loved it and it’s launched him on the wonderful world of finding a true friend between the pages of a book.
The problem of finding organ donors in Britain has been resolved by saying people have to opt out rather than in. So if they DONT want to donate, if say they were in an car accident, they have to carry a card saying so, otherwise it’s assumed that they have given consent. Could clinical trials be run on the same principle? Obviously with participant’s welfare being protected, perhaps it could be like jury service where you are chosen at random and have to do your bit, because in the end everyone in society benefits from the results of successful clinical trials.
Dear Chaya,
Your discussion hit home hard with me as I have been agonizing about my participation in two clinical trials, especially the second one, both at a major teaching hospital. I read all the small print and agree that it is for the safety of the institution. My oncologist introduced the trial to me, brought it to me in the waiting room with the words, “you might be interested in this.” It was a phase I trial for clofarabine. I wasn’t interested as I had no good results from my first clinical trial at the same institution. But to give it a fair consideration, I asked my oncologist what he thought and he described it as a good opportunity for me to get six months of treatment at a time when I was in good health, at a good time of year and be ahead of the game.
I wondered why a single drug would be better than combinations, and I could see from others studies that this was a powerful drug. But I decided to sign and participate, in part because of my sense of obligation in the bigger picture as well as my oncologists statements to me about his expectations for the trial. And others had taken such risks for me.
To summ up, the drug caused great damage to my bone marrow, requiring two blood transfusions, one platelet transfusion, injections of Aranesp, (which I later learned was not a good drug), hospitalization with an infection and treatment there with antibiotics. When I came home I had extreme pain in my knee, and developed chronic stomach problems which I am still coping with and don’t know what they really are. I have lost 15 pounds.
I regret deeply, having participated in this trial, but I have only myself to blame. I don’t think that it was appropriate for me to participate in a phase 1 clinical trial. I would have been much better off to have declined.
Maybe science has learned something useful from my experience.
I have read alot about clinical trials and through the process of participation am much more knowledgeable. But there is no way that as a patient one can know enough to make a correct decision. I depended on the opinion of my doctor – I trusted him to be honest with me, and I think he was from his perspective, but things did not turn out that way.
I also feel that the allegiance of the doctor is split between his research goals and clincal responsibilities for the patient. As a patient, it is difficult to clarify these possibly divergent responsibilities in determining one’s decision.
I also agree so strongly with you that the lack of thanks for participation from the research hospital is a glaring deficit. The participant in a clinical trials give so much, participation should be at least acknowledged.
I can’t thank you enough for your candid discussion on this subject.
Murre
My local oncologist suggested FCR. Dr. Byrd at OSU suggested FR saying that the C had been linked to secondary skin cancers – this is not good for someone who likes to garden, play tennis and take long walks in the sunshine. In the near future I will be going to Duke for consult and treatment, and it will be interesting to listen to their suggestions to see if they match up with OSU. At this point, since I have yet to be treated and actually run a business, I am focused on risk and reward. I want the maximum outcome for the least risk. In the future, I may be more open to trials, but I do not like the idea of being a guinea pig just to advance science as a whole as my experience working in DOD science and technology is that breakthrough advances come from individual insights.
I would also like to speak in defense of pharmaceutical companies and that awful word “profit”. Frankly, the advances we all benefit have come from a successful American free enterprise system that has been built one brick at a time by individual entrepreneurs – I note the likes of Thomas Edison and Steve Jobs. The value of the individual as an engine of success is all too often despised. The free market and the opportunity to profit is both kind and cruel. Without profit, there is no economic measure of success and the individuals who come up with good ideas do not benefit for their efforts – and if you do not benefit from your efforts why bust your butt 70, 80 or even 100 hours per week? What needs to be decried is crony capitalism not moral capitalism.
I spent half of my career in DOD science and technology. My experience was with scientists and engineers who had great ideas and were driven to get them into practice because they hoped to profit and increase their personal wealth. Collectivist thinking seldom produced anything but average results not the blindingly brilliant advances that come from unique insights. One of my criteria for funding science was uniqueness, while others were focused on cost, schedule, performance and risk.
Thank you Chaya —
Ruth/Clinical Research Coordinator/Durham, NC
molly fletcher:
You are right; I do tend to write in American rather than English. Used to be the other way around. I had to get my doctoral thesis re-typed because I had used British spelling – remnants of a “Raj” education that persist until today, but growing fainter.
Here is the definition of a “bum’s rush“: Hurrying someone out of a place. (As someone might quickly escort a vagrant from a fancy restaurant). How many of you have felt yourself rushed out of the doctor’s office because you are taking up too much time, gone over your allotted 15 minutes or whatever?
I forgot one comment. The clinical trial process is agonizingly slow and costly – presumably to make things as safe as possible. Yet drugs get into the general population that can still do some harm – I note tylenol overuse as an example. All drugs are poisons, and their use is one of how much risk for how much reward. In the case of tylenol, far too many people think there is no risk and this is foolish. (I know of a guy who would bum extra tylenol off of friends as well as going to an emergency room to get more. He took so much tylenol that he destroyed his liver and needed a transplant. He blamed the emergency room folks for not warning him about overuse. Of course, there was a lawsuit and he lost.)
What is needed is some real streamlining of the FDA processes to get costs down and encourage individual entrepreneurs to take risks. If it takes too much money to get into the game, then far too many great ideas are lost because of regulatory and legalistic restraints. For example, the FDA was originally constituted to prevent snake oil salesmen from abusing an uninformed public, yet snake oil salesmen still ply their wares and the FDA is unable to stop them because they operate just inside or may just outside the law. The streamlining processes created for homosexuals with HIV/AIDS went a long way in adjusting the risk/reward model of the FDA because the logic used was that the old FDA process was of little use to someone who would likely die before a trial could be completed.
Life is not risk free – and we are all going to die at some point regardless of what we do. Just give me the information and let me decide. If I goof, then I lose.
molly fletcher:
A good source of American slang definitions is the on-line “Urban Dictionary”.
I was asked to participate in a phase 3 trial for maintenance therapy but declined because of possible side effects, and the number of bone marrow tests and CT scans that might be required.
I was surprised at the number of clinical trials available for CLL, but some of them are very small, and I strongly suspect are of dubious potential value.
The variety of expert opinions on treatment suggests to me that there is little to be gained in searching for an “optimal” treatment. It wasn’t so long ago that one expert suggested that there has been no significant improvement in lengthening life expectancy since Leukeran.
An excerpt from “Catcher”, in case you forgot (fat chance!)
“Anyway, I keep picturing all these little kids playing some game in this big field of rye and all. Thousands of little kids, and nobody’s around – nobody big, I mean – except me. And I’m standing on the edge of some crazy cliff. What I have to do, I have to catch everybody if they start to go over the cliff – I mean if they’re running and they don’t look where they’re going I have to come out from somewhere and catch them. That’s all I do all day. I’d just be the catcher in the rye and all. I know it’s crazy, but that’s the only thing I’d really like to be.”
Great article. Thank you Chaya.
Monique
I’ve been in a trial (lenalidomide) for nearly 18 months and thus far things are looking pretty good (I was diagnosed 10 years ago, at age 52). I don’t know if I’m just lucky, or the drug is actually working, but at the end of the day, there’s a whole lot of trust and optimism (wishful thinking?) that goes into participation. I really wouldn’t know what else to do at this stage other than trust my doctor.
Standing ovation Chaya and warnac999. As Chaya knows this is a topic that I am pasionate about.
Before doctors there were Cancer Patients. Before pharmacuetical companies there were cancer pateints. Some of the situations correctly described by you Chaya seem to be examples of the tail wagging the dog instead of the dog wagging the tail.
My own local hemotologist said “I don’t believe in clinical trials” and I responded, “even though you are telling me today i will be dead at age 55 or so?” he had no response.It was easy to walk out and never return.Personally, imo I don’t see how a hemotologist can be ethical with out recommending clinical trials at some point in the disease fighting process. I have no problem with my doc or pharacuetical making money in the service they give me, provided that my personal need to survive is the primary objective.
I am a strong believer that the internet through activism and highly informed patients eventually will get things tipped back towards the needs of the patient.
Chaya is our hero for her work in this regards, yet as she often points our lots of heavy lifting still needs to be done.
Warmac9999 is hitting the nail on the head when he brings up what happened with the HIV community and the FDA. FDA lossens the barriers and guess what……….HIV patients are for the most part managing their disease now. maybe oversimplification to a degree.but not much imo.
I suppose that we in our CLL family can agree that we need to fill trials whenever it makes sense. It would be nice to know more about a trial than “a study to test drug XYZ” as we often find at the NCI clinical trial site. And most importantly, as Chaya has stated, we can do more heavy lifting in moving that eventual cure closer to today.
I have accepted that despite fighting to my last breath, CLL may deprive my young twins of a Dad. I will do all I can to make sure that in the future CLL will have no such power.
Chaya has done a marvelous job to get the ball rolling. Just so much more to be done.
Love to all,
Leo
J.D.Salinger has, no doubt, been on many a mind since news of his death first appeared. “Catcher in the Rye” was a doorway for me to Philosophy and specifically existentialism. That doorway has remained open as the unfinished business of awareness that Salinger’s writing inspired.
Clinical trials and patient participation will only get more difficult for a variety of reasons, one of which is the choice factor as more targets are identified for which drugs are designed. I would like to see some form “winnowing tree” that could help some patients identify the likely-hood that a trial will be of benefit or potential harm. I am somewhat concerned, from anecdotal accounts of patients entering trials without in-depth screening, that such lack of screening deprives a patient of crucial decision making info. Particularly, in early phase trials, unpredictable but valuable data from bad reactions might challenge some DRUG COMPANY/RESEARCHERS with scarce participants, to not WANT to know too much about a patient prior to a given trial. The onus is clearly with the patient to try and get as much detail and anticipate potential reactions.
When a patient thinks of buying time with an unproven drug “Caveat emptor” should be the starting point. I have participated in the NIH natural history trial for untreated patients in which the principal investigator told me, when I informed him that I decided to seek treatment though I was technically free from “B” symptoms, that while I was “qualified” to receive treatment it was his opinion that I had “an option” to Wait & Watch longer. Was this a Researcher’s bias? because another prominent CLL Onc urged treatment as soon as possible. Sometimes you, as patient, must make the tough decisions on insufficient grounds and conflicting expert opinion so well described by this article.
I am now contemplating a Treatment clinical Trial with the added complication that the last cycle of a standard treatment put me into stage 4 renal failure officially described as Acute Tubular Necrosis. Having achieved a stable partial remission the looming questions are; How long do I wait? Do I ride out another W&W or jump into a trial now that the kidneys have recovered reasonably good function? Is there something about the kidney failure event that would be good to know before consenting to a given trial? What about the characteristics of my cancer profile, such as the heavy and profuse node involvement, that might pose an unacceptable risk with a drug like Lenalidomide (Revlimid) that is known to cause tumor flare? These and other considerations like co-morbidities for many patients are not so easy to make judgments on, either for patients or many doctors.
Having CLL we all need a “Catcher” at the “Crazy Cliff” in the “Rye fields” in which we dance. You, Chaya, are such a “Catcher”.
Thanks!
Chaya,
Another home run! Thank you Chaya for your excellent article about clinical trials. I’m a newly diagnosed W&W stage 0 (mutated IgVH, dim Zap-70, 13q deletion (bialle), CD38 negative). I believe a CLL patient needs to be pro-active in order to continue to study and learn about CLL.
So far my local hemotologist/oncologist is willing to let me be a pro-active participant in the process. When I first saw him last Oct. I had seen my WBC increase and my neutrophils decrease gradually over several years. My primary care doc then tested for atypical lympocytes which were 3%. I did some research which pointed to CLL or lymphoma. My guess was CLL. So I studied some more about CLL (thanks to Chaya’s websites) then went to see the hem/onc. With CLL data to support my request for bloodwork (flow cytometry, IgVH analysis, FISH, Zap-70, etc.) the doctor agreed to do the tests. He also agreed with my guess that I had CLL. The tests came back and confirmed I had CLL.
Again due to the excellent data on Chaya’s websites I learned about the CLL Research Consortium and that UCSD was one of the members (and closest to where I live). So I made an appointment and saw Dr. Castro at UCSD. All the folks at UCSD were very helpful and Dr. Castro agreed with the diagnosis. Dr. Castro was open and willing to work with my local hem/onc in the ongoing process of monitoring my situation. For now I will have follow up visits every 3 months (alternating between my local doc and UCSD). They of course will share all my test results.
Thank you again Chaya. And a special thank you to all the wonderfull CLL folks who participate in these discussions. You are such an inspiration and help to me. Bless you all.
Patti Kruse
Chaya, Thanks for an excellent article.
My husband’s local oncologist said he has a nurse working full time to match their patients to clinical trials. After 5 yrs with him and as many more years of W&W there’s been no mention of trials. I looked into the trials at their internet site. There was one trial for CLL listed:
“FCR vs PCR in untx’d & tx’d CLL
A Prospective, Randomized, Open-label, Phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in previously untreated or treated b-cell chronic lymphocytic leukemia.”
I saw one company on the clinic’s site, US Oncology, who’s website mentions Comprehensive Strategic Alliance team. It sounded like a large commercial enterprise involved in trial monitoring, physician education, trial patient management, Rx transport and others.
It could be my lack of knowledge, but it didn’t sound like a trial I’d like to see my husband in if both use cyclophosphamide. Perhaps the info is old. I didn’t see mention of NCI or any trial numbers.
During his oncologist’s recent, brief discussion of treatment, to be continued after a recent CT scan, he said he recommended FCR. We’ll talk more Feb. 9. Maybe it will be FCR or maybe he’ll go to OSU and do FR or enter the new trial recruiting now at several centers: CALGB 10404, at Clinicaltrials.gov, study number NCT00602459. There is lots to think about.
I’d be interested in your thoughts on this last study.
Thanks, Linda
Here’s a few random thoughts:
1.) It would be really nice if life were black and white. But it isn’t! Imagine where we (cancer patients) would be if there were no drug companies selling drugs? Uh oh!!! Now think of the dirty, unethical conduct in which some drug companies have participated in order to sell their drugs. That isn’t right either. In my opinion, we can’t throw the book at the drug companies. We need them. We also need to demand that they do things right. This takes education (thank you Chaya) and proactiveness.
2.) When I first was diagnosed a few months back, I was mad as hell. I was approached for participation in genetic studies and my initial answer was heck no. I have changed my tune. I am now participating in three studies: NIH (thank you Jim for telling me about it), Ohio State University and Harvard/DFCI. As previous people have mentioned, all I’ve had to do is fill out some forms and allow them to take a sample of my blood. EASY!!! NO HARM DONE!!! If you can’t find the contact information for these studies, you may email me and I’ll send it to you: doggeedoc@gmail.com
In my opinion, the more people we can get talking about CLL (doctors, patients, drug companies, journals, EVERYONE), the faster we can advance progress on this disease.
3.) This discussion has reminded me of a common frustration that I see daily amongst my students at university. The students are always looking for the best answer/the best treatment and they get very frustrated when they ask me how to treat a particular case and then ask another doctor the same thing and the answer’s are different. The reason this happens is because there is more than one right answer; there is more than one way to treat many diseases.
I don’t know enough about CLL to tell you the same is true for CLL. I just thought it was worth mentioning.
Stay healthy.
Chaya,
I read “Catcher” twice. Plan to read it again now while dealing with Bendamustine, rituxan, decodran, etc.
A very informative article. Your other article re: clinical trials which depend on which institution your oncologist is affiliated and which pharmaceutical company pays for it, etc.
Quite an eye opener.
Thanks for keeping us informed.
Rita
Here’s my problem: I’d love to enroll in a trial. I’m 83, a 13-year 11Q CLL vet and running out of options. But I live in a rural area hundreds of miles from two major cancer centers. A one day visit to either center requires 3 days for travel, overnight accommodations plus car rental to boot. I also need to find someone reliable to care for my special needs 4-legged companion while I’m gone. From previous experience going to UCSD to see Tom Kipps, I know this kind of travel can be exhausting for the older patient. The last trial I attempted to enter required weekly, then semi-monthly and finally monthly visits for the better part of a year. Lots of opportunities for travel plans to go wrong.
Is it not possible for the trial sponsors to work with reputable oncology practices in different regions and allow the trial to be performed there in coordination with major cancer centers? If their PR efforts aren’t producing enough bodies, why not try to make the trial sites more accessible to patients.
Fred H
I briefly researched some numbers on this before commenting. It seems that all the available figures about low participation are percentages – briefly, number of patients in trials divided by number of patients needed. I could find no indication of which number is changing faster. Are fewer patients enrolling? Or are more patients needed? Or a combination of both?
On the optimistic side, it is likely a good sign if the denominator (number needed) is increasing faster than the numerator (number participating). More patients are needed as drugs look promising because the number of patients increases with the phase – phase 1 clinical trials need the fewest patients, phase 2 more, etc. Also, more promising drugs mean more trials, which also means more patients are needed. I could find no data to prove or disprove this, but it is possible that the change in percentage indicates a positive trend for patients.
Chaya,
I’ve been searching the NCI clinical trial data base for a trial close to me, for the “untreated” as I think it’s going to be my turn soon. Do you have any thoughts on NCT00602459? It appears to be looking at variations on FR, FCR and and possibly lenalidomide, then adding, for the 11Q deleted, a fourth arm with addition consolidation at the end. It is randomized for all but the 11Q.
As I look at the requirements for these trials, I’m not sure if they will accept me .. some seem to require B symptoms that I don’t have, even thought I have (as my derm doc says) “Impressive” WBC of almost 200k.
The study requires:
” * Massive or progressive splenomegaly, hepatomegaly, and/or lymphadenopathy
* Presence of weight loss > 10% within the past 6 months
* Grade 2 or 3 fatigue
* Fevers > 100.5° F or night sweats for > 2 weeks without evidence of infection
* Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of < 6 months"
If my spleen has gradually grown to be 13cm, do you think that could qualify me?
Thanks,
Lynn
Hi Chaya and thank you for this great article. You are fantastic at writing articles on “teaching science to non-scientists”. You should seriously consider writing primers for publication on the context, background, and interpretation of: a)FISH tests (is the same as the Flow Cytometry test?); b)Bone Marrow biopsies; c) Cytogenetic tests; d) . When one reads these test results, one is overwhelmed with the vocabulary and concepts involved with trying to understand what the test results really mean, which one has to do if one is to be a pro-active manager of the disease in collaboration with the oncologist.
bob235:
Thanks. In an earlier article I tried to demystify (1) FISH test (2)Flow cytometry (3) pcr testing. Here is the link: http://updates.clltopics.org/423-three-important-blood-tests
No, FISH and flow cytometry are different tests done to get different information. I know what you mean about test results being hard to read. It helps to have years of experience. I have read so many FISH and flow cytometry results over the years that now I can almost read them in my sleep. There is no magic involved, just practice.
thank you, once again.
Leave a Comment