Honesty in clinical trials
Big chunks of this article are direct quotations from Dr. Terry Hamblin’s blog, where he has just reviewed the bendamustine clinical trial. Unless you are very newly diagnosed and have not had a chance to look around the CLL scene, you will need no introduction to Dr. Hamblin. It was Dr. Hamblin’s pivotal contribution that dawned the age of prognosis based on cellular understanding. Heard of the IgVH gene mutations status as prognostic indicator? Recognizing the importance of this subtle but very important difference in the B-cell receptors of aggressive versus indolent CLL was the starting point for modern understanding of CLL. Terry Hamblin received the Rai-Binet Award for that important bit of research.
But Dr. Terry plays another and even more important role. He is one of the few CLL experts who tells it like it is.He has no axe to grind, no bosses to please, no professional ladders left to climb, no need for more money, no kudos left to garner from his peers. When he speaks his mind on the subject of CLL, savvy CLL patients drop what they are doing and listen carefully. Here is what he has to say on the subject of bendamustine’s pivotal clinical trial, the basis on which the drug was granted FDA approval for commercial marketing. I have reviewed this trial before, with the somewhat snarky title “Facelift for bendamustine”. The title alone should give you a hint about my feelings on the subject.
Here are quotes from Terry’s blog, reproduced here with his permission. (The highlighting is my contribution). Please read the last paragraph carefully, if you are considering this drug in the near future.
“A paper has appeared in the J Clin Oncol comparing Bendamustine with Chlorambucil in untreated patients with CLL. It shows Bendamustine to be much better than Chlorambucil, but can we believe it?
The trial was conducted by a group of hospitals in Austria, Bulgaria, France, Germany, Italy, Spain, Sweden and the United Kingdom, though the names of the authors do not spring out as CLL experts apart from Marco Montillo from Milan. Very few if any of the patients came from the UK. The trial was funded by the manufactureres and marketers of Bendamustine. The statistics were designed by an outfit in Germany (DSH statistical services) with a record of designing trials in Homeopathy and the data were handled by Cephalon who market Bendamustine as Treanda in the US. In other words this was an industry trial. It is usual with industry trials for the drug manufacturer to pay the hospital participating a fairly large sum of money (perhaps 5000 Euros) for every patient recruited. Of course, I have no access to what financial arrangements were in place for this trial.
319 patients were randomly assigned to receive either Bendamustine or Chlorambucil (162 B, 157 C). The overall response rate was 68% for B and 31% for C. CRs were 31% for B and 2% for C. Median progression-free survival was 21.6 months for B and 8.3 months for C. As I said Bendamustine seems astonishingly better than Chlorambucil, though this does seem a very poor result with Chlorambucil, compared with say the LRF CLL4 trial.
Toxicity was worse with Bendamustine. Grade 3 or 4 adverse events occurred in 40% for B and 19% for C. This level of toxicity was regarded as acceptable. (Editor’s note: Please read about the FDA’s toxicity warning regarding bendamustine, based on post marketing reports.)
This paper is published in JCO which probably means it was turned down by Blood. The criticism which any reviewer would have made would have been that the dose of chlorambucil was too low. (Editor’s comment: Please read Terry’s blog for detailed analysis of the dosing issue)
So my original criticism stands – they seriously underdosed the Chlorambucil compared to what is optimum – just as the fludarabine and alemtuzumab trials did.Moreover they offer no description of modern prognostic markers – something I would regard as essential in a clinical trial in CLL. It may be that mutated and unmutated cases and del 11q and 17p cases were equally distributed among the two groups, but it may be that they weren’t. This might be another explanation of why the Chlorambucil patients did so badly.
The introduction to this paper perpetuates the story that Bendamustine has both alkylating agent and purine analog activities. It is true that it bears superficial structural resemblances to a purine analog, but I have yet to see convincing evidence that it acts as one. I still believe that Bendamustine is just a way of getting adequate doses of an alkylating agent into a patient.”
Editorial
All too often, reports of clinical trial results have become a tool for “data management” (“lying” is such an impolite word, don’t you think? People can get sued for saying things like that!) by powerful and wealthy drug companies. Truth is a rare commodity, statistics are twisted out of kilter to make the drug under study look better than it is. A wag once described after the fact sub-set analysis as shooting an arrow at a dart board, then drawing a bulls eye around it. Drug companies are sore losers, as we have seen all too many times.
We have written before about straw-man comparisons. Bendamustine is not alone in getting FDA approval based on comparison to deliberately low ball dosage of chlorambucil, in poorly defined patient cohorts (no modern prognostic indicators reported). Campath as front-line therapy won FDA approval by using similar tactics, please read our article “Jumping the gun“. If ofatumumab had done the same thing, compared itself to low dose chlorambucil, I think it would have gotten FDA approval by now and not still hanging around waiting for a decision from that self-important body.
Money corrupts. And lots of money corrupts in lots of ways. Terry talks about recruitment fees paid to doctors for each patient they recruit into clinical trials. Let me tell you a story that will make you hesitate before you take everything your doctor tells you as gospel truth, sign up for any clinical trial he recommends without doing your own due diligence. Surely you do that much before you buy a new car, or do you just take the salesman’s word for it? How much more valuable is your life?
Let us take as an example of how corruption spreads. Consider a patient advocacy site on the Internet that has wide following, a ‘hypothetical’ patient advocate that interacts with thousands of patients and has a loyal audience in the CLL patient community. She may even have reviewed a clinical trial or two on her site(s), and by the process of her positive (or negative) reviews she may have actually influenced the rate at which patients were recruited (or not) into the clinical trials she reviewed. What is the market place price for her good reviews? How much money for a patient advocate that sings the tune her masters tell her to sing?
Here is how the calculation was done, quite recently. Let us say she does 5 clinical trial reviews per year, a low ball estimate. And by the power of her influence in the patient community, she is able to help recruit an additional 100 patients into each clinical trial. That is a total of 500 patients recruited, a huge underestimation based on what we saw happen after one of her recent reviews, perhaps of the NIH clinical trial.
Head hunters charge anywhere between $3,000 to $5,000 per patient recruited, that is the going rate these days in the USA. Yes Dorothy, there are shadowy companies that do nothing more than act as go-betweens, hard working “yentl” that negotiate with strip-mall oncology practices, recruiting their patients for large scale clinical trials funded by powerful drug companies that don’t want to have their name directly involved in the recruitment process. And yes, if you have enough money and influence, you can click your heels three times and recruit as many patients as you want, for any number of clinical trials.
Based on these numbers, our ‘hypothetical’ patient advocate can reasonably charge to the tune of two million dollars for each year of her service. She was recently offered 5 million dollars – but the contract required that she not disclose the outright sale of her websites (and her soul too, of course), that she continues to write under her own name (but of course, she will be writing what her masters tell her to write), and she will use “secretarial help” provided by the clinical trial recruitment company in answering hundreds of individual patient emails she gets each week. Sweet deal! She had no idea her soul was worth quite that much. If one is going to be a whore, I guess it is satisfying to be considered an expensive whore. I will leave it up to you to imagine what she told the recruitment company negotiators to do with their business offer – after all, we do insist on polite language on this website.
All too often, clinical trials are a necessary evil as far as drug manufacturers are concerned. Without positive results demonstrated in clinical trials they do not get permission to sell their products in the market place, no way to recover the huge costs of drug development, let alone make a profit. Does this tempt companies to bend the truth just a teensy bit? After all, they have costs to cover, profits to make for their share holders. There are documented cases of companies that fund 10 or so clinical trials; if nine of the trials show nothing positive for their drug (perhaps an anti-depressant), but one trial shows an advantage, the nine negative trials are deep-sixed, the single trial that showed positive results is given huge publicity. No harm done, not unless a bunch of depressed teenagers on their new miracle anti-depression drug commit suicide. “Guest” authors with status as international experts are often recruited to give gravitas and credibility to the industry controlled papers. Peer review process is subtly influenced by well chosen awards of grant money. I say again, money corrupts and large amount of money corrupts even more.
(Me, I am a cheap date. I am pleased that we were able to shut down donations for Updates back in June, six months from when we launched this site. We met our target for revenues for the year and I saw no reason to keep collecting money from you, merely for the sake of collecting more of it. We will re-install the donations button January of next year).
Do we need clinical trials? Yes, if we are to have any progress in treating this and other life threatening diseases, we absolutely positively must have clinical trials with well informed patients participating in them. Ahh. There is the rub. Informed consent is such a hard thing to come by. Trials are getting more and more complex, the science is mind boggling for the innocent layperson patient without a head for medical jargon. Even well meaning researchers find it is next to impossible to teach each and every patient they try to recruit, given the constraints on their own time. In any case, they are trained as scientists and physicians, not teachers trying to teach complex medical jargon to a bewildered and frightened patient audience. Patient information packages are put together by lawyers trying to protect their institutions against potential lawsuits down the road. What is the solution? How do we refrain from throwing out the baby along with the very dirty bathwater?
This is the role that is just right for honest patient advocacy groups, organizations that have no allegiance other than to their patient-members. At their best, advocacy groups can bridge the gap, be the truly honest brokers between the drug / healthcare industry and patient-consumers of their products. With the advent of the Internet and easy to use software, sites like this one can reach thousands of patients with each article. We can take the time to teach, we have terrific leverage, we are not too busy, we don’t have to worry about financial or professional repercussions, we can afford to be honest. Is it easy to do? No. Teaching complex ideas to a lay audience is never easy. But it can be done, if the teacher and the student are both honest in their efforts.
I have a real problem with groups that call themselves advocacy groups with undisclosed financial ties to the drug industry or “educational grants” that they receive. Perhaps their grants are truly unrestricted, no strings attached, no obedience expected. But at a minimum such grants and such ties should be clearly disclosed and highlighted for all to see. Please read the “About Us” section of this website and our “Mission” statement. My only allegiance is to you – no one else. The only money we get is from your voluntary donations. We do not accept a single dime, not a single free gift or boondoggle, no free dinners in expensive restaurants, nothing, nada, zilch from anyone remotely connected with the pharmaceutical or health-care industry.
I cannot guarantee you wisdom in my articles; my educational background, perspective and biases are clearly spelled out for your evaluation. You be the judge of my credentials. I can do no more than the best I can in reading the tea-leaves for you. But this much I can and do promise: I will never sell out, I will never break my promise to you on that front. When I switch off my laptop for good, CLL Topics and Updates will be mothballed; never sold to the highest bidder. As I said, I am a cheap date, and proud of it.
46 comments on "Bendamustine Clinical Trial"
Truly amazing… and oh-so appreciated.
and I appreciate it more than you know.
Dear Chaya,
I am very grateful that I found your site; since having the misfortune of being diagnosed with this cursed affliction, (via breast-screening)I have learnt two very important lessons. (this goes for the UK at least).
There is incredible partiality and self-interest in alot of “testing/screening”. WEhat often starts as a genuine wish to help, becomes a selfperpetuating industry, with a constant need of new material with which to work, ostensibly in order to progress knowledge and chances of “cure” and survival.
It appears that very soon information is “tailored” and restricted to serve the purpose of recruitment rather than honesty. Inconvenient realities are airbrushed out, selectively positive “results” and benefits are trumpeted loudly.
It then becomes a process where the individual as a human being has little or no value, they become numbers in a process, commodities to be utilised.
Personally I have never in my life had so many halftruths and downright lies thrown at me as during this process. Things like “well tolerated” meaning; not having to be hospitalised. Facts like cumulative toxicity being “overlooked”, cumulative effects of exposure to say X-ray, dishonesty as to the realities of conditions, assumptions as to your “needs” and your “wishes”, “you are potentially terminally ill, so your brainfunction and capacity to think and understand has already gone into terminal decline”; the list goes on and on.
The lies and detremantal assumptions are possibly the most injurious, apart from the total negation of human value and individuality and brainpower.
What is frightening is also that the authorities appear to equate any form of attention (being steamrollered through a diagnostic process before being able to draw breath and engage ones brain) as treatment for a disease.
I could go on and on, but….
What this sort of thing does atchieve, is to totally alienate one from trust and belief in those who purport to have ones “best interest” at heart. Mette
Chaya,
This is by far the most eye-opening article you have published. Thank you so much for being so honest – your parents can be ultra proud of how they raised you. Perhaps you can consider re-naming this article (or parts of it) other than a Bendamustine study. Readers who are not particularly interested in this drug might miss the fabulous things you have to say regarding drug companies in general. Nice work.
Lie, Lies and damned Lies…that’s what makes the world go round in business, politics, peace and war.
The ability of statisticians to manipulate numbers to get desired results is compounded by the inability of most of us (including the average practicing physician) to sift through the camouflage.
The other factor of concern is the very human tendency of researchers to color their perceptions based on their own academic needs…they do after all wear more than one hat. I do believe that many researchers are honest to the core, but it is always difficult to battle the underlying conflicts of interest.
The commercial interests of pharmaceutical companies (like any other company) take a life of their own.
I do think, however, that Mette is being overly harsh. The faults that one could ascribe to most healthcare providers on the frontline have more to do with the usual human frailties and deficiencies and much less to do with deceit and dishonesty. We have to be realistic…life is hard in and of itself and dealing with the physical and emotional needs of multiple people with varied problems and expectations is exceedingly challenging. Some do better than others, but almost everyone tries their very best.
Most physicians and nurses take it very personally when a patient feels that the have failed to do a good job or have misled them.
Good luck to all,
Rick
You, dear Chaya, are a class act all the way. Your knowledge gives ME strength. Thanks for allowing me to learn about my disease from the comfort of my own home.
If there is a bottom line here it is that you must do your own research and come to your own conclusions. I believe that the great majority of doctors and nurses do their best – but we should not forget that there are very few “Houses” and at least half of the doctors graduated in the bottom half of their class.
One final comment: A lot of the ideas that will help all of us come from the minds of individual geniuses. Without a Bill Gates and Steve Jobs, we wouldn’t be able to communicate and the search for an effective treatment and cure. Gates built Microsoft and Jobs built Apple – and they deserve our thanks and, from my perspective, all of the rewards that go with hard work and success. The same goes for the pharmaceutical and insurance companies who were started by an individual with an idea. And, as with any human endeavor, the result is something that is not perfect. Fortunately, creative destruction, otherwise known as competition, continues to advance technology and the industries and businesses that make all our lives better.
Q.Since when is a cheap date worth the world?
A. You are, Chaya. Big thanks yet again!
Lawrence
Dear Chaya,
I can not thank you enough for providing for us, the CLL public a sane and clear and honest evaluation of some of these new meds such as Bendamustine as well as the process for their approval. It is extremely difficult as a patient to evaluate the potential help that a drug in a clinical trial might provide from the needs of the pharmaceutical company which might get permission to market the drug. This is also true of a drug which has FDA approval.
I was told that the drug in the phase 1 clincial trial which I agreed to participate in was “well tolerated” by those who had already participated. It was not “well tolerated” by me and I am still trying to recover my former health six months down the line and my CLL is about the same. Now I have a little more caution in interpreting what my oncologist recommends for my treatment.
Heartfelt thanks for your wise counsel.
Murre
Chaya:
I can’t think right now of a word to describe you that would give you justice. So I will just say thank you. You are a special person.
Dave
The key phrase here is not throwing out the precious baby along with the dirty bathwater.
I agree with Rick. Majority of doctors and researchers work long hours and put their lives on hold while they practice their professions. I have met some ICU nurses that qualify for sainthood each and everyday, and still don’t forget to be human. I will never forget their professionalism and kindness as my beloved husband lay dying.
Someone once said Capitalism is an terrible way to govern a country, except all the other ways of governing we have tried are worse. Just about all the major drug breakthroughs come out of our capitalistic system of investment and profit. It is fundamental human nature that is hardwired into our brains.
So, what is missing? For starters, we need to understand the agenda that drives the various interest groups. No point getting all agitated, it takes a calm awareness of what motivates the different people sitting at the table.
Consider a young and idealistic researcher who spends decades of his life working perhaps on a single concept, a single drug that captures his imagination. It has its good points and its bad points. Do you think it anything other than human nature if his bias is to see the good point magnified and the not so good points diminished? Do most of you think your kids are the brightest, most handsome kids in the neighborhood? It is important for us to remember researchers too are human beings, they too put their pants on one leg at a time.
The problem comes to a head when there is unspoken and unacknowleded conflicts of interest. When an influential expert owns patents or substantial commercial interest in a drug development company and at the same time he is also deeply involved in recruiting for clinical trials that speed up development of his “baby”, that is a conflict of interest situation. It does not matter if the actual recruitment is done by someone else in his group, the guy with the office next door. That is just a fig leaf cover for lawyers to discuss.
I do not know too many experts who 100% finesse this obvious conflict of interest between the needs of the researcher looking to progress his research, and that of the physician sworn to look out for the best interests of the individual patient standing in front of him. When is it OK to sacrifice the interests of the individual for the benefit of the many? When there is informed consent. Pure and simple. Those were the principles agreed to by all civilized nations after the horrors of Nazi Germany, principles codified as the Helsinki agreement. Without informed consent it is human exploitation – no other way of slicing this cake.
What are we to do? Recognize that there are many agendas represented at the table, make sure that OUR AGENDA is represented as well. That we too have a say in how clinical trials are conducted, what laws are passed by our elected officials, what watchdog agencies such as the FDA do to protect us.
I am by no means the first person to have discovered this perspective. Look up consumers’ rights movement pioneered by people like Ralph Nader several decades ago. Fairness and safety dictate that consumers have a say in what they buy, whether it is a car or a newly minted drug protocol. We pay for it, all the research and clinical trials, through our tax dollars and insurance premiums. It is time we got our act together, developed ways in which we can work with the various interest groups.
Let’s not throw out the baby with the bathwater.
Brava!
Chaya,
you are one in a trillion!.
I know from expierence that i was a ginny pig who followed her “expert” drs orders to do a trial for “human Kind’.NO geniune,informed concent.
Now after your advice i read everything.It is sad not to be able to trust the Drs advice.
I undertand that there are many great Drs.
This world of Cll is a tough road to staying alive.
I TREASURE YOUR GENEROUS SPIRIT AND KIND HEART!
ondrea
Just this past weekend I was at a Lymphoma and Leukemia workshop in Seattle, Washington where your name came up Chaya. I do not have permission to quote the doctor – suffice it to say he conducted a CLL specific workshop. He was speaking in regards to clinical trials and informed consent – his advise was to not “just” sign the informed consent after wading through the pages and pages of legal jargon, but to do our own research and be truly “informed”.
How did your name come up? He mentioned the internet as being an invaluable source of info – and specifically advised we check out Chaya Venkat’s website – “she is spot on.”
I do so agree with you – your analogy of the researcher and a parent is so appropriate – not all glowing reports are completely money driven – our human ego also gets in the way.
Let the “buyer” beware.
Thank you for your diligence in helping us make informed decisions.
Lillian
Well Said Chaya,
You focus on the right issues as usual with insight as to how we patients should properly navigate our way on the CLL journey. Your clear headed analysis of the Bendamustine hype is of immeasurable value to those who would otherwise be led down a primrose path devoid of reality.
I am currently in some dangerous rapids on my own journey which touches heavily on comments by 11qRick where in he says “The faults that one could ascribe to most healthcare providers on the frontline have more to do with the usual human frailties and deficiences ……”. The issues I am dealing with don’t fit here but I’ll be writing on the ACOR List serv concerning my latest adventure in CLL land.
WWW
Chaya,
Many thanks for your wonderful insight and constant research that you so tirelessly put forth for those of us who are not as knowledgeable in the medical arena. I am truly grateful for all the information I receive here on this forum. You are the best. I pass your insight onto my family as well so they are more informed also about this disease and how they can effectively be a part of it for us the patients.
Many Blessings to you.
Anita
Chaya,
I feel so lucky to have you in my corner. You are my hero. And, I’m sure all will agree, we are in your corner as well, should you need us.
Take good care of yourself,
Lynn
This is an amazingly eye-opening article. I have a good friend who was an executive for one of the major pharmaceutical companies for several decades and who has been educating me about some of their incredibly deceptive practices. But we haven’t touched on this topic to date. Thanks for the flags.
Marshall
Chaya, it is truly comforting to know that you are here with us on this difficult journey. You truly are special. If I did not have this curse called CLL, I would happily continue with my life,undistracted, and gladly try to forget about it.
Just to confirm what others have already expressed, THANK YOU FOR BEING YOU!
Chaya,
I’m disappointed they didn’t offer to buy my wife’s transplant blog:) I KNEW I should have paid more attention in HS English class:)
Seriously, ethics are often a very cheap commodity. It is good to see an instance where that is not the case!
I have thought about commenting many times after reading your editorials. After reading this one I had to let you know how much I appreciate what you do and how fortunate we are to have you advocating for us. You are one of a kind.
Dottie
As Chaya has pointed out repeatedly, patients need to stay on their toes. And this applies particularly to clinical trials. It seems to be hard for some patients to understand that their personal interest and that of their own doctor or principal investigator in a trial can diverge. I do not think many patients would agree to join a trial like the Bendamustine/chlorambucil trial discussed here if they had a clue that they might get randomized to the trial arm with a less than robust therapeutic dose of chlorambucil. One has to wonder also about the doctors who recommended joining such a trial. Chaya’s site can help keep us from falling into such traps.
Diane MacKinnon
Thank you so much for your high ethics & morality that do us such a great service. Without you we would not know who to believe. You are our advocate & we are so very fortunate to have you!
Anne
Chaya,
Thank you for the very very helpful informations.
Monique
Dear Chaya,
Since I have lived most of my life in the atmosphere of “Ivory Tower Research”, I am well aware of the problems of the clay feet suffered by the gods as they dance around trying to “win” some small advantage over their fellows. It is so very sad, but not at all surprising, that drug companies also suffer this defect when so much money is up for grabs. A little ethics and honesty go a long way; thanks so much for the heads-up.
Betty
First, I will say that it was an honor to meet you in Nigiara Falls.
Second, Thank you for your honesty and straight-foreward talk.
I am not in treatment yet, but because or you, I am better informed than I was or ever could be.
Patti
WillB425
HIGH FIVES on your excellent/informative article.
William
MJH
Dear Chaya,
I was on Treanda a very short time and it wasn’t working. Dr .switched me to Compath and it has worked well. I’m set up now for a mini-alo stem cell transplant in Seattle the first of Dec. and yes I’m very nerveous. It was Seattle that recomended Treanda. How do I check out what they are giving me without offending them or making a bad move myself?
Thank you Myrna
Myrna:
You ask an important question. How to participate in your own healthcare without becoming a stumbling block in the process?
For starters, I am pleased that your doctor switched you from Treanda to Camapth, when the former did not work well for you. That is how it is supposed to happen, doctors doing what it takes to find the right drug for the right patient. I have also heard from patients who did not do well on Campath and did better on Treanda. It is a question of what works for the patient. I have a problem with how the Treanda clinical trials were conducted. But that does not mean the drug itself is useless, that it has no role to play in CLL therapy. It is always good to have more drug choices and Treanda is a welcome addition.
When it comes to stem cell transplants, I am reluctant to ask you to be deeply involved in all the drug decisions as and when they happen in real time. This is a complex procedure, still bit of an art form rather than a cut and dry science. The best advice I can give you is to do your due diligence upfront in your selection of the transplant center and the team that will work with you. But once you have chosen your center and your team, then try to sit back a bit and have trust in your chosen experts. Transplants are complex affairs that need fast decision making, not exactly right for layperson dithering.
dmackinnon:
You have hit the nail on the head. Patients recruited into the control arm of these straw-man comparison trials are the ones that got screwed, by getting a less than therapeutic dose of chlorambucil and with poor response rates as a consequence.
Of course, all of us pay for it down the road whenever truth is distorted and clinical trial results given a corporate “spin”. As Rick pointed out, even practicing physicians are hard pressed to catch all the subtle nuances, they too depend on journal articles for making therapy decisions for their patients. The only answer I can think of is the old mantra “Buyer Beware”.
Chaya
Thanks for your up to date information and its cutting through the hype and telling the truth on this trial.
I have started my first FCR. It is not for the faint of heart but is actually going pretty well. A friend with CLL and another that has chemo for colon cancer told me how they would go from chemo and walk an hour. I have begun this and it made an enormous difference in quality of life for the day and subsequent days. Your reports helped me to enter FCR with a clear idea of risks, benefits and what the future might hold without making me anxious. Realism is pretty healthy and actually leads to hope.
Thanks again
Jerry
Chaya
When the report was published re: treanda tops chlorambucil, I was really down. Did I make a mistake refusing the drug for all the right reasons? I didn’t think so.
I thank you so much for your updated and honest information. I am giving a copy to my oncologist.
rita
Chaya:
I am, as usual, late in reading this paper and the comments that follow. So…I have little to add, but wanted you to know that your effort is more than just appreciated. I have used your research with no fewer than three oncologists, and I have backed them off on more than one occasion on their recommendation for a drug infusion.
Barry
Chaya,
Thank you for this! I long ago took myself off lists of so-called advocacy and information services after it became obvious to me that they were promoting particular drugs, or products of particular companies, or their doctor ‘experts’ (and/or their research) were clearly being subsidized by pharmaceutical companies, in one way or another. After years of reading these folks, I have come to the conclusion that yours is the only site I trust. Thank you for being there, through your own hard times and ours.
Valerie
Just want to add my thanks and appreciation for all your work for the patients with CLL.
Loretta
Wow. I mean … wow.
Thank you so much for all you do for our community, Chaya. All your efforts are truly appreciated!
Dear Chaya:
In business you see “overnight successes” in all fields being touted by the media on a daily basis. What outsiders don’t know is that it took people years if not decades of persistence, of shortening a learning curve, of fruitful and failed partnerships, investing own and borrowed money, mortgaging the farm, the list is long.
The same can be said for CLL Topics. If the (current)value of your following is so high (congratulations, a multi-million dollar figure!), it means that there has been a tremendous amount of hard work over a long period of time to earn our trust.
This is the reward for being in tune with her audience and our needs (information, guidance, interpretation, interactivity); for teaching us how to fish (how many of us can now read a trial recruitment prospect and immediately come up with a list of questions for our oncologists?); for urging us to take responsibility and be empowered. At the same time, Chaya has been very clear about what she can and is willing to be involved in and what she is not. This site does not evaluate botanicals and supplements, nutrition, exercise and the like- end of story (for now?). That gives us a very clear picture of what to expect from CLL Topics. It is not a panacea (we wish!), and the rest of the work is up to us. That is what makes a succesful business venture. But long term success comes with ethics and transparency. In this case, we are the consumers that validate and value the product that Chaya and P.C. created.
Sorry for the business jargon, that is my field.
Chaya, it is hard enough to navigate our CLL waters with the wealth of information you provide. Still, each of us has to make difficult and sometimes irreversible decisions on a regular basis, so anything you and your readers provide is always helpful. Not to mention insightful comments and additions by CLLers (thank you all who make such wonderful clarifications, and comments!)
Doctors, labs and research centers are corporations that invest, employ, make profits. Like the analogy I made with CLL Topics, they have consumers– but their constituencies are more complex because they answer to the almighty dollar in terms of Wall Street valuation and stockholder votes, and god knows how many government programs, depending on the company, and rely on a “distribution system” which are the doctors and clinics. (CLL Topics’ distribution system is the internet — CLL Topics sites.) They can only make money if we, the final consumer, consume the drug. If we can now discuss with doctors whether or not to have this drug, or discuss treatment alternatives, the labs have now lost a little bit of power from within the distribution system they largely control. That is what they want to buy back when they value a certain site at $5 million (btw, that is a very low-ball offer based on the assumptions you delineated above –if you use a typical a 10-year valuation criteria, that certain site could be valued by as much as 5 times that–$25 million!).
Ultimately, however, an educated patient group makes for a good long-term consumer base for the drug industry (distinction on educated versus manipulated). In a simplified version, advocacy sites like CLL Topics are like having a free market research that are very nasty and nagging. This represents a very expensive short term roadblock that is telling them what we consumers want and need. Ralph Nader was almost crucified in the 60’s by the auto industry, but most if not all of the issues he fought for have long, long been incorporated into the cars we take for granted today. It seems obvious that we have seat belts, airbags, right? Well, it seems obvious that nurses today wear X-ray protective aprons right? Not so in the past. Now there is a powerful and lucrative side industry that provides these protective, complementary equipment. The same for drug companies. They will (we wish more quickly!)develop other protocols, tests and substances (if thinking outside the box) that will address toxicity, side effects, diagnostics, etc, develop vaccines, and other preventive therapies to prolong our good health and cure our CLLs. However, they will put up a huge fight and draw out all their ammunition if they feel threatened in the short term (read article above!! the design of the study is an example of not so fair play to get the drug in the market so they can cover their financial needs of the upcoming fiscal year.)
It is extremely frustrating to have to make CLL decisions. We have so much, yet it is so little when it comes to a decision that applies to each individual. That implies having to think for ourselves, and that is a very lonely process. After you read, discuss with trusted doc, ultimately, it’s our decision. (Chaya, I too envy the fact that P.C. had you beside him on his journey, but eternally grateful that you are willing to share a large bit of yourself with us.)
So, it is with my utmost gratitude that I thank Chaya for being a cheap date, a brilliant one at that, and all of you CLLers that continue to learn, question and make yourselves heard to the community, to your doctors and clinics.
Cristina
Christina:
Your comment is worth more to me than all the money I can make by selling out. Thanks for understanding my role so clearly. I worry about promising more than I can deliver. “Do no harm” is a very important precept to me and part of doing no harm in the process of trying to do good is avoid becoming a “cancer-guru”.
I cannot CURE CLL (PC would be alive today if I could)! Best I can do is help you cope with it – for as long as I can, as best as I can. Comments such as this one are welcome validation for me. Thank you.
Bendamustine associated AIHA (autoimmune hemolytic anemia).
Since we are on the subject, here is a very recent warning based on post marketing surveillance of bendamustine. This is the first I have seen, talking about potential risk of autoimmune disease following use of bendamustine. It fits, since bendamustine has structural similarity to both fludarabine and alkylating agents. Fludarabine is especially infamous for increasing risk of AIHA, hence it is contraindicated for patients with pre-existing vulnerability on this front. Here is a quote from the abstract of the bendamustine article:
“Based on bendamustine’s structural similarity to fludarabine and fludarabine’s association with causing hemolytic anemia, we considered exposure to bendamustine to be the most likely contributory factor for her diagnosis. According to the Naranjo probability scale, a probable likelihood was reflected in bendamustine causing the hemolytic anemia. CONCLUSIONS: Continued monitoring of postmarketing data is necessary to correlate this occurrence of hemolytic anemia with bendamustine therapy”
PMID: 19809007
Your excellent critique of—commercially sponsored—clinical trials was right on! Thanks for alerting the community in your usual clear and concise manner. Also thanks for bringing Terry Hamblin’s update to our attention.
However, on the secondary subject of your note, I want to make a case for Bendamustine—as you say, ‘don’t throw out the baby with the bath water’. First off, I have no ax to grind. I’m just a patient (retired Chemist) that had good results with the drug. Here is a brief of my case.
I was DX with CLL in Jan. 2003. After W & W for about 3 years my WBC had gone up to 500+k and my Dr. put me on Chlorambucil (granted it was a minimal dose of 10 mg per week). The dose was slightly increased—then decreased back to 10—over the 19 months. At that point my WBC had leveled off around 150k. After consulting with a 2nd Dr., I agreed to go on Bendamustine. Started a regime of 6 rounds in Jul. 08 (100mg/m^3 on successive days) administered over the next 7 months (dosage was reduced to 70mg/m^3 for last 4 rounds). At the conclusion of this regime in Jan. 09, my WBC was in the normal range and I felt very good. It has remained normal through summer 09. Also my lymphnodes remained barely palpable through my most recent exam, 7/09. As my Dr. said, I remain in Chemical remission. Will see him again next week.
In addition, I had absolutely no side effects from any of the 6 treatment rounds and remain an active 75 year old in good physical shape—this may partly explain the lack of side effects. Almost forgot: there has been one change. I’ve become extremely hypersensitive to mosquito bites—major swelling. (In checking the literature I found a 1965 article in “Blood” by Robert I. Weed pointing out this CLL anomaly.)
Sorry for the lengthiness but some elaboration is needed to support positive results.
Keep up the good work, Chaya.
Al
Chaya,
Your article was most informative — thanks so much for your honesty and integrity.
John
absully
I whole-heartedly agree with your perspective. Bendamustine has its role in treating CLL, we appreciate each and every therapy option our patients have. Lord knows the FDA is slow in drug approval, only two major drugs have been approved as frontline drugs in the past decade: Campath and bendamustine. Time will tell whether bendamustine is yet another purine analog / alkylating agent or whether it works by a different mechanism and therefore may have greater value to patients.
My beef is with over-the-top commercialization of the process of getting drug approvals. We need an FDA that uses commonsense, does not let itself get flummoxed by strawman comparisons like this one, that insists on post marketing surveillance with some teeth to it. We need muscular patient advoacacy groups that ask the tough questions. We need to have drug companies held accountable for questionable practices in patient recruitment.
Are bendamustine and its manufacturers unique in the problems I discuss? Hardly. This was just one example that I used to illustrate the points I wanted to make. I am glad your experience with this drug has been good. I have no doubt you are not unique in that respect.
Chaya,
Thank you for the information you provide and the great way you do it! You speak in great “lay” terms that are so understandable. My husband received 5 months of treatment this year with Treanda – the last one was cancelled as he had a lot of complications and it was not being effective. It did, however, knock down the white and lymphocyte counts enough to allow him now to recuperate for approximately 4 months when he will participate in another clinical trial at MD Anderson. So, for those who have had success with the treatment, I am very happy that this drug has been approved and is successful and hope that you continue to be in remission.
A couple of people have mentioned swelling from bug bites and I find that particularly interesting – are you really getting bitten? The reason I ask is that for 6 months before my husband was diagnosed in 2003 with CLL, he started having “bites” appearing on his back primarily and then his arms and chest. At first, the dermatologist kept saying it was spider bites, etc. – but, of course, we knew that wasn’t the case. It was biopsied at one point and confirmed it was a bug bite. Well, 6 months later a blood test revealed otherwise and he started on FCR later that year when it was in clinical trial. (did have a 4 year complete remission from that). My husband does swell up when he is really bitten by a mosquito now – but I’m curious if anyone else had that as an initial symptom of CLL like he did?
I’d like to add my perspective to the thread on bendamustine. I agree with everything said about the clinical trial. And in fact this is the norm with most drug company sponsored clinical research. The research would never see the light of day were the results anything but positive.
And spinning the results is an artform of the statisticians, particularly those under contract with the drug companies.
And I know Dr. Hamblin is not sanguine about bendamustine. But for those CLL patients (like myself) who are refractory to Fludarbine and FCR combinations, Bendamustine offers a reasonably effective alternative that apparently works better to both clear the bone marrow and reduce swollen lymph nodes as compared to Campath.
I scrutinized the choice between bendamustine and Campath very carefully. I was set to go forward with the Campath until I spoke with Dr. Joseph Rosenblatt of Miami/Slyvester Cancer Center who has treated CLL patients with both. He did not like the Campath based on his limited clinical experience, and much preferred the bendamustine. He told me that the standard dose of 100 mg/mt2 however is much too high.
Finding the right dosage is the critical variable. It’s not a one size fits all situation. And better to start on the low side and go up if necessary than start high and, because of toxicity, have to go down. I started at 50 mg/mt2 and plan to remain at 50 so long as my results continue to go in the right direction.
Biggest drawback? Highly myelosuppressive–takes a pretty big hit on platelets and hemoglobin. Other than that the treatment appears to be working.
Only time will tell whether or not I made the right choice. I will have another bone marrow biopsy a month or so after the 4th cycle.
But don’t let a fraudulent trial tar a potentially useful drug. And for FCR refractory patients, a combo of low-dose bendamustine and Humax CD-20 (when it’s approved) might be just the ticket.
Chaya – I just finished 6 months of Treanda and it did everything it was supposed to. This was my 1st relapse after treatment 3 years ago with single agent Rituxan. I have no idea if my side effects (and there were many) were any different than any other comparable chemo, but I got thru it mostly unscathed.
Point is that I am still reading as much as I can about Treanda from other patients who were treated because I was more or less talked into it by my Oncologist. He thinks it is the “coming” gold standard.
Me – I feel a little like a guinea pig now that all is said and done.
But my internal lymph nodes were creating mayhem and I had to act.
In hindsight would I have done it different if I had the luxury of time?
Probably not. You have to trust somebody. Anyway, all follow ups indicate a CR….for however long it may be.
Hope my experience helps somebody out there wrestling with this issue.
And by the way, I’ve read CLL Topics since I was diagnosed.
I use your information constantly to ask the important questions.
Thank you for everything.
Mark – NYC
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