How tarnished is the crystal ball?
Back in October of 2010 I published a review of FCR versus FC study published in the prestigious journal “Lancet”. This was a multi-center and large scale Phase-III study where patients were randomized to either of two groups. Such double arm studies are considered as good as it gets in terms of credible clinical results. Indeed, in this study the two arms were very well balanced and one can hope the results are therefore a simple case of apples to apples comparison. The author list on the Lancet article was top drawer. The article was introduced in an editorial in the same issue of Lancet by no less than Dr. Peter Hillman. There was very little to dispute in the article, FCR was definitely better than FC. Phew. Finally we had clinical results we could hang our hats on.
Not so fast..
Did I ever tell you that nothing about CLL is either simple or straight-forward? Consider yourself reminded about this simple fact of life.
In recent days there has been a huge brouhaha about the very same Lancet article. Three Australian physicians raised the question of conflict of interest possibly contaminating the study results. Since our very lives depend on how we interpret and understand the value of clinical trial results, this is no small matter for us. Were there conflicts of interest? Were the results compromised? What is a poor CLL patient to do / believe? Here is a link to the story unfolding in the popular press, so you can read all about it. The quote below captures the essential point of their complaint:
Associate Professor Ian Haines, of Cabrini Hospital, Melbourne, and two colleagues said they were concerned that 27 of the 32 authors of the research, published last October, had potential conflicts of interest, given they had declared financial links to drug companies, including Roche, which funded the study. One of these 27 authors was a paid employee of the company.
”The editorial writer shared the same potential financial conflicts of interest as 27 of the 32 study authors and appeared too enthusiastic in his embrace of the study with terms like ‘gold standard‘, ‘heralds fundamental changes in management of CLL‘ and ‘landmark‘.”
A close knit community
What makes this unusual is that there was such a complaint in the first place. Physicians and researchers tend to be a close knit community, with strong professional ties to each other. By the time a researcher is acknowledged to be world-class, he would have worked in several research and clinical institutions, done post doctoral work in a couple more, shared authorship credits with many of his colleagues working in the same area, applied for grants from the same funding agencies. CLL researcher community is not all that large. Everyone knows everyone else, almost incestuous, you might say.
Rocking the boat is not one of the survival traits of researchers who want to climb the professional success ladder. Even when they disagree with each other in public, the sniping tends to be subliminal or couched in such heavy jargon that mere mortals have no idea they are disagreeing about anything. Public solidarity of physicians and clinicians among themselves is quite impressive, even if they indulge in snarky back-biting more often than you think. Whistle blowers tend to be few, and most often they come from outside of the professional ranks. That is what makes this particular situation somewhat unusual.
Conflict of interest
Let us look at the disclosure statement the authors provided at the end of their article. This sort of statement is now mandatory and none of the major journals will accept an article for publication without it.
Conflicts of interest
- MM is a paid employee of Roche. MHa (also from Mundipharma)
- CMW, JM, JC, JFS, UJ, and SS declared consultancy or boardmembership for Roche.
- GHo declared board membership for Mundipharma.
- MHa, BFE, JM, GHo (also from Mundipharma), GHe,JC, JFS, UJ, MT, and SS received payment for educational presentations for Roche.
- GFR, CMW (also from German Cancer Aid), BFE (also from Mundipharma), JM, GHe, MB (also from Celgene and Bayer) JC, JFS (also from Bayer Schering), UJ, BC, MT, PS, TZ, HD, SB, MK, and SS received honoraria or grants from Roche, partly forserving as investigators in Roche-funded research.
- KF, GFR, AMF, AW,CMW, BFE, JM, MHe, GHe, MB, JC, JFS (also from Bayer Schering),UJ, BC, ABe, MT, PS, DW, TZ, SB, MR, and SS received travel grants from Roche.
- RB, UvG, PLZ, FCC, and ABü declare that they have no conflicts of interest.
With the exception of the five individuals cited at the bottom of the list, each and every one of the authors had financial and professional connections with Roche and other drug companies associated with this trial.
How unusual is this level of coziness between researchers and drug companies?
Not at all unusual. Large scale trials such as this are incredibly expensive to carry out. No one has the money to do them, unless they are supported by deep pocket drug companies. And since drug companies are in the game to make money, their funding support is usually based on hopes that they can use the clinical information coming out of the trials to further their own marketing or in this case, getting regulatory approval for their drug(s). Here is the disclosure in the Lancet article about who paid for the trial and what role they played in how the study was done.
Role of the funding source
“This trial was planned and initiated in 2003 as an investigator-initiated trial by the German Chronic Lymphocytic Leukaemia Study Group. Since 2004, F Hoff mann-La Roche assumed the sponsorship for this trial, because it intended to use the trial for the approval of rituximab at regulatory agencies. The sponsor was subsequently involved in the first and second amendments of the study protocol. The sponsor of the study was responsible for data gathering, and shared responsibility for medical review of the data with the corresponding author. The corresponding author was responsible for data analysis, data interpretation, writing of the report, had full access to all the data in the study, and had the final responsibility for the decision to submit for publication”.
Does this sound like a bit too much control over the process by the very companies that stand to make a lot of money from the results of the trial? You betcha. Is this out of the normal way of doing things in today’s marketplace? Not at all. Folks, this is how sausages are made, whether you like the process or not.
Editorial
The level of conflicts of interest in the Lancet article are not all that out of the ordinary, what is unusual is that it has been called into question. Take away the profit motive, take away drug company money to do research and carry out expensive drug trials, and that will be the end of new drug discovery process. That is the simple truth of the matter. No money, no new drugs, no improvement in the lives of patients.
I submit to you that clinical researchers are human beings, like you and me. They are not monsters, nor do they wear shiny halos. They put their pants on in the morning one leg at a time, just like you and me. They have their pet peeves, their ambitions, their desire to do something worthwhile with their lives, be recognized for the work that they do. In other words, a complex mix of altruism, selfishness, high minded desire to save lives and need for ego strokes – just like the rest of us. One thing I can say in their favor: majority of them work awfully hard, putting in long hours each and every day over many decades of their lives. Depression and thoughts of suicide are apparently quite high among physicians, especially so for oncologists.
I do not believe the authors of this Lancet article sold their souls to Roche in the process of doing this study. Were they influenced to be overly enthusiastic in their support, perhaps without even being aware they were doing it? Possibly. When was the last time you were guilty of similar behavior in your own life?
All of us love conspiracy theories, finding villains lurking in the background that are taking the whole world to hell in a hand-basket. There are plenty of real life villains, some of them are even medical researchers. But I do not believe that was the case in this study. At most, they may have been guilty of a bit of cheer-leading for the home team. By the way, the home team was winning. FCR is a good therapy option to have for our guys.
Can we afford to be purists in this game? I don’t think so. Not unless you are willing to stand down in your quest for better therapy options, make do with fludarabine and chlorambucil from now on. Right. I did not think so.
Who do you think is paying for CAL-101 and the new generation of kinase inhibitors? The drug companies who stand to make zillions of dollars if their bets pan out, that’s who. Can you reasonably expect them to tweak things just a bit behind the scenes, if they can possibly get away with it? I would be surprised if they did not. When “Genasense” failed to win FDA approval, I got several emails and even a couple of phone calls from the CEO of Genta – to see if I was willing to do a bit of rabble rousing in the patient community, help push the approval through. Frankly, I happened to agree with the FDA on this call. After the fact subset analysis does not meet the smell test and that is all that Genta could point to in favor of “Genasense”.
Will researchers who took the lead in these trials and have a lot of time and effort invested in them be tempted to overlook “minor” deficiencies in the drugs under study? I expect so. Does Cal-101 work only on lymph nodes and blood counts or does it also work on clearing out bone marrow infiltration? This issue has been debated on this website as well as others. Researchers have side-stepped this question as not really important. I beg to differ. Bone marrow clearance is an important issue; perhaps a second drug in combination with CAL-101 will be needed to achieve it. All this and more will be debated and tested in the months and years to come.
Some of our more hasty members want the FDA to approve all drugs as soon as they clear very preliminary early stage studies. I can understand their need for haste, they feel they do not have the time to wait. Their lives hang in the balance.
But sad as it may be, public policy cannot be made on the basis of single individual needs. Compassionate use programs may be advanced to take care of special needs, but I would be strongly against taking away the power of regulatory authority and oversight when it comes to drug approvals. There is too much money riding on these decisions, too much power and capitalistic greed. We badly need a few protections watching out for us, make sure there is more truth and less hype in the drug approval process. Brakes are needed even on the sexiest of cars. Time for reflection, debate, looking things over by fresh pairs of eyes – all of this slows down the process. But it also protects us from runaway disasters that have done so much harm in the past. Just look up “thalidomide babies“, to see the harm that can be done when drugs are approved / prescribed too quickly. It is estimated that around 20,000 children were born with horrific abnormalities.
Maybe this is the reason why we need patient education and advocacy websites – someplace you can go to try and understand what is going on, where some of the jargon is translated into normal English. Not every CLL patient has science education, not all of us have the time to sort through hundreds of professional journal articles each month.
Patients facing tough therapy decisions are not always the most objective of people. Often they are too needy, too scared, too prone to post-purchase regret if things don’t work out the way they hoped. Should you bet the farm based on a single anecdotal story of a patient who is unhappy with the remission he got? Are heavy-handed attempts of “true believers” of herbal healing to proselytize others to their way of thinking any more dependable? Beware of hidden agendas. Conflict of interest does not always mean big $$ signs.
My potential conflicts of interest
Since we are discussing potential conflicts of interest, it is only fair that I disclose my personal conflicts of interest. Here they are, every single last one of them.
- Money received as honoraria from pharmaceutical industry: $ 0.00
- Research grants from anyone: $ 0.00
- Educational grants from anyone: $ 0.00
- Board memberships: none.
- Advertisement revenue: $0.00
- Stock ownership: 200 shares in Genmab (original owner of ofatumumab). I bought these shares in 2006 in a fit of solidarity because PC had responded so nicely to ofatumumab. So far I have lost $3,946.18 on this lot (hey, never said I was a good stock picker!) but I have not had the heart to sell these 200 shares.
- There have been no expense account lunches, no golf trips, no all paid trips to attend conferences. The only exception was when I attended the CLL patient advocacy meeting in Canada in 2009. The organizers paid for my tickets and hotel charges. There were no guest speaker fees.
- Every dime we get comes from you – our generous members.
You may question my hard nosed attitude, my take on alternative medicines etc. But monetary conflicts of interest is not one of the issues. I read the full articles, try to sort out the methodology and results to the best of my ability. Often I come away less than impressed (as in the case of a recent review of FC + Campath study for previously treated patients), pissing off a few people in the process. Sometimes I am happy to be proven wrong. I was not an early fan of FCR, I did not think this high impact combination had enough positives to off-set the admittedly high toxicity. More recent work (including the work reported in this Lancet article) has convinced me otherwise.
How much of the hoopla do I buy? I try not to get too sucked into it. But you would be foolish if you thought I was entirely unaffected by the verbiage I read in articles and editorials extolling them. I too am guilty of using “gold standard” to describe FCR, more than a couple of times. The best I can promise you is that I try to be as objective and fair as I can in my reading of the tea-leaves.
If you are looking for an honest reporter that does not benefit financially from the healthcare industry, you have found one. If you are looking for an all-knowing and eternally wise seer that has all the answers to what ails you, keep looking. I don’t fit the description.
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34 comments on "FCR Study: Conflicts of Interest?"
Chaya, what can I say about this outstandingly lucid, honest, sensible, generous article, other than thank you once again.
Mary Connell
I know a little about this trial. I was approached by Roche to act as chairman of the data monitoring committee for the parallel REACH trial which compared FC with FCR in previously treated patients. The deal was that they would pay for my travel and hotel costs for each meeting of the committee and a small fee for my time. They asked me to recruit the other members of the committee from European experts who were not involved in the trial. From their point of view I was a good choice since I was a known opponent of FCR, which like, Chaya, I thought too toxic for a large proportion of patients. I think in the way I approached my role I might have been too stringent for them, because they sacked me when it came to the DMC for CLL 8, though they took the rest of my committee.
For both the REACH trial and CLL8 the data were handled independently by a statistics department of a German University, members of which had no financial arrangement with Roche.
When we met as a committee there was no Roche representative present and they had no influence on our report. In fact we asked them to make extra investigations into the possibility of secondary MDS that would not have been their choice to do.
The CLL8 trial was up and running before Roche were involved, but they realized that it would be a useful study for them to get FDA approval from. For that reason it had to be upgraded with an idependent DMC and other features. This is why Roche put money into it. Peter Hillmen was made chairman of the DMC, but my committee provided the rest of the members. From what they tell me there was no interference from Roche in their deliberations. Some members of that committee have accompanied me to work on other DMCs. This seems to me a suitable job for retired hematologists since we have no axes to grind and no clinical practice to influence.
Apart from the support Roche gave me, I have had occasional travel and hotel costs to attend meetings. About 500 British hematologists have had the same. I should say that when I am asked to do a similar job for the government or the NHS, similar arrangements apply. In my opinion Roche hospitality has not been extravagant and I own no shares or stock options. Roche has not made me rich. My opinion cannot be bought; I tell it like I find it.
I think it is extremely unlikely that anyone concerned with the CLL8 trials was in any way influenced by the pharmaceutical company. I know most of them very well. All they are biased about is finding the best treatment for their patients. If they were in it for the money they would find a different profession. These doctors are a lot brighter than your average financial expert and could have made themselves extremely rich in the City of London if money were their motive.
Sometimes we have to believe what we read, in reality because we have no other option. Our only options are to try to find alternative opinions and to weigh them. Not easy without knowledge.
It is nice to think that we are intelligent people but even with disclosure and being able to sense the sincerity of the writer by what he writes or by earned reputation, it is very difficult to make informed opinions without actual experience.
Not everyone in this world is influenced by money, though few are those who can say I have enough with a home to buy and children to educate & even a job to keep. Maybe people in health which is essentially about helping others are essentially more concerned about people than most.
We are very grateful to Chaya for casting a cynical eye on this small sector of medicine and helping us to understand.
chaya:
another great article. after being diagnosed with stage 4 cll and being very ill, i “readily” participated in a clinical trial for fcr-lite. this was several ago when rituxan (which is now widely used and accepted and is now a part of the “gold standard of care”) was not approved/covered/paid for by the insurance companies. So,, my option them was to either receive it, or not! Based upon the information available at that time, our decision was easy for us to make! Proceed!
it was full discussed (aka “disclosed”) to us up front that the pharmaceutical company that produced rituxan would pay for me to receive the rituxan (for free) during my care/treatment. it was also disclosed that the oncologist has some financial relationship with the company. so be it, it was not a big deal! even though i had some very severe reactions to rituxan (and it was finally discontinued), i firmly believe that participating in this trial saved my life!
without rituxan – who knows what would have happened to me! so, these types of “conflicts of interest” are really nothing more than avenues for funding sources to develop and try and study new treatments. so be it! if these “conflicts” are properly disclosed and everyone is “legal, morale and ethical” – what’s the big problem?
Thanks
Cll
Pittsburgh, PA
Once again we get an intelligent dissection of information from the best patient advocate in the WORLD. And thank you too Dr. Hamblin, for providing your unique background information. Drug company sponsorship is the necessary “evil” if you will for progress in drug development. Personally, I don’t see the problem with drug company research sponsorship under controlled conditions.
What is the bigger problem is drug company sales reps visiting your local practitioner to push the prescribing of their drugs. Remember when hypertension was defined as pressure >140/90? What is HTN now? 130/80??? Drug company sponsorship showed that lower blood pressure decreased other problems. So here: take this pill. Cholesterol too high? Here take this pill. Trouble performing in bed? Here take this pill. Want to perform better in bed? Take the same pill. Remember Dorothy Hammill and Vioxx? All that jumping and twirling on skates hurt her joints. She didn’t have a heart attack but lots of other people did.
Now I understand widespread usage in the general population will bring unforeseen consequences of FDA approved drugs. That is not our issue…time is of the essence. In my opinion, under the conditions Dr. Hamblin describes, we are not dancing with the devil. Drug company sponsorship is reality. Physician researcher “potential conflict of interest” is reality. We are a lucky group that we have Chaya who can sort this for us. Her motives are as pure as it gets.
Thank you Chaya for opening this conversation and Terry for your additional input. Four years from diagnosis and having the 11q deletion and unmutated IgVH and a big jump over the past 3 mos. in my WBC to 175k along with a painful neck, I’m embarking on my first treatment course of FCR (FC the first week to bring down the white cell count abit before adding R). I was fortunate to have a consult with Kanti Rai last Spring and he and my MD and I are all on the same page relative to our goals of treatment. I have confidence in their combined wisdom. Nevertheless, at 61 yrs. of age, I have anxiety and concerns about getting it right regarding treatment and appreciate the education I continually receive from this site. I would like to continue to enjoy a good quality of life, the longer the better, as do we all. I’m fortunate to be an RN with some additional public health education, so at least know some of the questions to ask. I have an older brother diagnosed with Stage II CLL this year, who does not have this advantage and I see a big difference in how we communicate with our physicians.
I’ve rambled abit, but really just meant to say thank you for all you continue to do for the CLL community.
Kathy
Chaya and Terry,
I LOVE your contributions! Not only for enlightenment on vital matters, but also I enjoy reading your words. Sausage analogies bring it home far more effectively and enjoyably than straight results (which I probably have enough science to read, but it wouldn’t be so much fun!)
And a word for Kathy: Be of good cheer, because I am 64, I’ve been treated with FCR when it was very new in the UK, and it wasn’t ALL plain sailing (I got herpes virus reactivation a.k.a. Shingles – they KNOW to prescribe antivirals now!!!) but a few years on I have my life back – at least for a while! And I remain VERY grateful to the Haematology team at North Devon District Hospital, UK. Hopefully the treatment will be AT LEAST as good for you.
And a final word about money. I believe in “Giving something back” and for that reason I make my time and knowledge/experience available to the team with overall responsibility to fight cancer in the southwest of the UK. I don’t expect to be paid for that, but given the distances to be travelled around here, and the fact that I am retired on a pension, I do expect to be offered money for mileage. I hope that I provide good value as the constructive critical patient.
And one last thing: The FDA-equivalent body in the UK, called NICE, has approved FCR for initial use, but you only get it once! So if anyone spots and info on where to go after FCR, I’d appreciate it. I don’t need it yet, but some time, maybe…..
THANKS AGAIN Chaya and Terry, and BEST WISHES to everyone.
Lawrence
I’m a Stage 3/4 CLL patient receiving FCR-Lite (one kidney) at Cleveland Clinic, Cleveland, Ohio. Cycle 3 of 6 is next week.
Yes, drug companies must sponsor these studies and trials because if they don’t our tax dollars must. Can you imagine congress being in a position to influence study and trial choices. That scares me to death. It truly is the lesser of two evils but I think there may be a way to minimize the problem to something more manageable.
As I understand it the FDA has been underfunded and understaffed since Busch (the Senior)cut federal budgets and decided, in this case, to let drug companies police their testing themselves thereby lessening the work, funding, and staff required by the FDA. The only thing the FDA had to do was “review the findings” using understaffed and overworked FDA employees. It’s also my understanding that the recent spat of drugs being withdrawn from the retail market is primarily due to the FDA’s inability to throughly investigate drug companies submitted findings prior to the drug’s approval and release. And “fast tracking” doesn’t help either. In essence what has been created is an “implied” Phase IV trial category where a drug is released to the public and then both doctors and their patients become unknowing Phase IV trial subjects by using the new drugs and then reporting their “findings” by either doing well, getting sick, or dying.
The bottom line: The FDA has to police the drug companies, they can’t police themselves. I think it’s possible to significantly minimize this problem by investing more money in the FDA so more trained staff can be hired to throughly investigate drug company findings and not just review them. And, although open to debate, minimizing “fast tracking” would probably be a net benefit too.
-Ken Dunn-
Chaya and Terry,
Thank you both for your wonderful insight. I am glad that there are so many eyes out there and systems in place that would most likely flush out harmful conflicts, therefore protecting us as patients. This is another example of how important you both are to us. We simply could never do it on our own. YOU BOTH have contributed to the well being and quality of life for all of us. For what it is worth – I make a good living as a professional (non med) based on commissions/incentive compensation, which can easily pose a conflict as interest. However, I like most others – including most all of the very bright CLL docs – live by integrity, which is the human nature of most people thankfully, and have confidence that the German Trial results on FCR are very reliable. As a CLL patient who just went through 4 cycles of FCR – and great results – I am grateful to both of you for watching out for us!!
THANK YOU!
Please do keep pissing them off, when appropriate. Our bone marrow clearance may depend on it!
Thanks for offering us independent information and a forum (thanks again Dr. Hamblin)so we can have what we need to make informed decisions- re treatments, conflicts etc.!
We are all lucky to have folks like you and Dr. Hamblin looking out for our interests.
Chaya and Terry,
Authoritative perspectives with excellent analysis of the issue. Am I wrong or did I hear correctly that Rituximab will soon go off patent opening the way for a cheaper generic replacement? If so, it would further weaken the money motive of Roche to rig the result.
WWW
Chaya and Terry, thank you.
I think most of what I have read (on these postings) are from those with CLL. When its your loved one with CLL and they are letting you (the spouse) help guide the treatment option – we depend on honest and forthright information. Chaya – your website is the place I go. I read the articles, I read the postings, I even email the experts – and I struggle with our decisions. We recently had to make the decision (spouse needed treatment) between FCR or PCO. We went with PCO (in December). I don’t know if we made the right decision. Our hope is that O will do a better job than R in the end. And we were scared of the F with toxicity even at the age of 53.
Please, continue keeping us informed (as I know you will), especially when something as important as the results of these studies is being questioned.
Thank you for what you do.
Thanks, Chaya for this important article. When FCR was being touted as the gold standard, I still had some concerns re. the toxicity issue. I think about further chromosome damage often. I already have damage to 3 chromosomes (that I know of , could be others) and do not want to incur more if I don’t have to. I am very interested in the Cal-101 trials and the other similar meds in trial now but my CLL is manifested in the bone marrow and so far no sign of it in my lymph system. You have pointed out an important point. When tx. time comes for me, I will need to choose something that has some potential for clearing my bone marrow, a tall order.
Chris R.
Great article,Chaya. Thank you.
Be well,
Monique
Thank you so much for your presentation, Chaya, and for your remarks, too, Terry. It is so comforting and educational to read opinions and facts from such clear writers.
Since 1997 Rituxan sales have topped $20 billion ($20,000,000,000). It a colossal money maker. It has long ago paid off development costs and is now huge “cash cow”. The obstacle of mass producing such a sophisticated “drug” was enormous but I question the price today. Lets hope some of those profits are being plowed back into research for better next generation therapies for CLL instead of obscene multimillion dollar compensation to marketers and bean counters holding on to a patent. Rituxan indiscriminately knocks down B cell populations so in conditions where B cells are causing a problem- it will usually give relief… kind of like like aspirin can relieve swelling. It does not address the underlying fundamental causes of CLL but for many it obviously enhances quality of life and maybe overall survival. My very personal opinion reading hundreds anecdotal reports and taking a lay view of these studies is that its price is no longer justified and it is prescribed too soon, too often, too much and its long-term benefits are somewhat exaggerated. Some of this in the U.S. Comes from aggressive sales reps. Because CLL is such a unique disease, there is still much we don’t understand about Rituxan dosing and combinations with other drugs. Still, no matter how many flaws, frustrations, and aggravations we find in the capitalist system that provides this drug, it is another very valuable arrow in the quiver for CLL specialists. It is a comfort for me to hear an insider with integrity like Dr. Hamblin express assurances of the independence of these kinds of studies. Now hopefully onward to new, better, longer lasting therapies with more specificity and fewer side effects. God bless the researchers, drug companies with integrity, doctors and patient guinea pigs in the trenches fighting this battle every day. Thank you Chaya.
Chaya,
This article is so important to me. Actually it started in 2009. My doctors and I had words re: fludara. I was just plain scared. In 2002 I had R/F with some uncomfortable complications. It took a long time for me to recover. Why would I want that mess all over again.
My thoughts were F was not for older people who are immunosuppressed.
Thanks Chaya for an important article. And to you and Dr. Hamblin for your research and honesty.
Blessings,
Rita
On an ACOR post, Dr. Hamblin is suggesting that the Australian physicians should be sued for their comments.
Thank you Chaya, I liked what Dr. Hamblin said about an independent statistics company collecting data and the fact that Roche was not present during the committee meetings. Are there regulations that determine this sort of quality control? Thank you Chaya for interpreting all this information. You are amazing. Sandra
Again it is impossible to minimize the value of an objective patient advcate with a large following. There are many temptations in research that stress the most moral compass. Many doctors are 2nd and 3rd generation, so to argue they could have been richer in economics defies the reality that most clinicans start preparing for this life in high school. The pay for doctors is certaianly an issue. In 1961 the doctors of the world made 100-200 grand while Mickey Mantle made 50k. Now the Mickey Mantles of the word make 50 million a year, while many doctors still make 200k. This is a huge cut in pay given the dollars demise. What choice did they have in this massive paycut? They are also driven by ego. They want the best lab, the most grant funding, the most private funding. It is a very closed community and these figures are known to all the top players. They all may have started with the best intentions but the process is very corrupting. I presonally know of several instances of shortcuts, cherry picking and outright data faking in CLL. It is very real, all the more reason patients need unbiased advicates.
Although I also had questions about this study and agree the price of rituxan is obscene, gold standard does not seem to be a huge exaggeration.
I would like to add one note of optimism, with a bit of a nitpick:
“No money, no new drugs, no improvement in the lives of patients.”
While this is certainly true for the short term, I think there are several promising areas of research that could benefit CLL patients.
1. Better biomarkers to determine who will respond to which drug, who will progress if left untreated etc. We have many markers but the outliers are large most of the time. Potential new markers could be RNA, microRNA, methylation patterns and protein markers.
2. A recent paper claimed they could detect sinlge cll cells in almost everyone. How to use this information in otherwise healthy people before they present with CLL and are forced into the maze of treatments when the conversion rate is so low? Better markers are clearly needed here.
3. Lifestyle/environmental choices: Does exercise or a certain type of exercise help? Cell phones, living by the nuclear plant etc. Is CLL really caught from a specific antigen, virus or infection?
Of course much of this has been discussed at CLL topics and the lion’s share of progress has been in the clinical setting, using patients as guinea pigs (since there are still really no good mouse models). There is still a need for basic research in these other areas.
Thank you Chaya for opening up a discussion on the complex subject of conflict of interest and its perceived impact on research findings. Also, a huge note of gratitude to Dr. Hamblin for his unique perspective. I think many people have a fantasy notion of medical research, that researchers leap into their shiny Ferrari, plug in Find the Cure into their GPS and head out on the highway. The fact is research requires tremendous diligence, intellectual ability and analytical discipline and lots and lots of long (and often discouraging) hours at the lab. It seems to me there are easier and faster ways to be bought off by corporate interests! I’m mid-point in reading “The Emperor of All Maladies” by Siddartha Muhkerjee, a kind of “biography” of cancer. This is a book that is engrossing on many levels but is particularly (from my CLL perspective) fascinating about the history of medical efforts to “cure” cancer. What comes through to me is the heroic, (and sometimes painfully prideful) efforts of many now forgotten scientists. Your article, Chaya, ties in nicely with this very human story.
WillB425
Chaya,
Wow, what great discussions from all of the above. Great stuff.
Many thanks to all.
WillB
I also forgot to mention most docotrs lost their tuesdays off to play golf. I think the suicide thoughts mentioned above are the result of the vast changes in this noble profession in the last few decades. The health care changes from “obamacare” which add another level of red tape will not help the mood of doctors, imo.
I think I need work on my analogies, but one conclusion that is not in dispute is how great a resource patients have in an objective site like this.
Azzy, I like much of what you said in your first post. However, I find this last post offensive. It’s very rude to call the health care reform bill “obamacare”. I suggest we leave that for Fox news and not for Chaya’s site.
Azzy:
Lynn is right.
“Obamacare” is a divisive political term that can easily hijack this entire discussion thread. It does not belong on this website. Please refrain from such provocations.
Thank you Lawrence, for your encouragement and words of hope.
Kathy
Thank Chaya for this important article. CLL Topics is very important and very helpfull for all of us. We know your integrity and your honesty.No question about potencial conflits of interest.
Thank you also Dr. Terry Hamblin for yor testimony. You are one the best(for me the best) CLL expert, also honest and a man of integrity.
Both of you are wonderfull, and are precious for us that wants fight this disease, that as Chaya says, nothing about CLL is either simple.
I try to learn as much as I can about the most effective treatment and the best initial therapy for CLL with mutated IGHV genes.
With gratitude.
Jorge
Chaya, thank you for sharing this info with us. This is all new for my husband & I. He was diagnosed in November. He is currently stage I, but I’m concerned, given what the doctors are saying & not saying, that it may not be stage I for long. They have mentioned both FC & FCR as possible treatment options, so again, thank you for providing this info. I have an unrelated question, though, that I’m hoping someone out there can help me with. Since the cold weather has begun (we live in New England), my husband is having a terrible time with the cold weather. He is 59 years old and this has never been an issue in the past. But, now, he turns pale, pale white (especially his fingers & hands) & just can’t seem to get warm. I haven’t read anything about this being a symptom of CLL. I’ve read about hot flashes & night sweats…which he doesn’t have at this point. I clearly don’t have any kind of medical background & I’m not looking for medical advice, but wondering if anyone else has had similar symptoms or can explain why this would be happening???
Joan
“If you are looking for an all-knowing and eternally wise seer that has all the answers to what ails you, keep looking.”
This sounds like a great idea…please tell us where to look. ;)
More seriously, though it is clear that drug companies need supervision, it is not so clear that the FDA has achieved a proper balance in the judgement of risk between protecting us from bad drugs and preventing from getting drugs that might salvage us in an already risky situation. Everyone knows about thalidomide. But has over caution caused more than 20k deaths that could have been prevented or delayed? I am in not position to know the answer. However, I do believe once toxicity has been proved to be low, it seems there could be less than the gold standard of proof for establishing efficacy. One proof fits all seems to me less good judgement and more like covering one’s rear politically. This is especially so, to my mind, when acceptable proven treatments includes things like FC and Campath. Maybe we should let individual oncologist have more rope to tailor treatment to the cases they evaluate…even if drug salesmen may try to put them under their spell.
Many of us pay for review agencies like Consumer Reports to sort out potential dangerous products that the govt allows. If the FDA was a little less rigid, maybe such NGOs would spring up to help supplement FDA decisions…and our docs and we could take more responsibility for the choices that affect our own lives.
Chaya and Dr Terry Hamblin
I would also like to thank you for your comments. Very educational and helpful. Yesterday, my daughter asked me how I was doing as we were snow-shoeing. I told her I am fine. But I think the reason why I feel I am fine is that all the things you teach me calm me down. When and if I have treatment are not known to me at this time; but I can assure you that because of what I have learned from you both is very comforting. Also the comments from the CLL community are enlighting. Thank you again for all that you do. I count my blessings every day.
For Just Joan
A friend of mine has cll and this disease along with it
http://en.wikipedia.org/wiki/Cold_agglutinin_disease She has to stay warm or she experiences terrible effects.
You may want to study this and ask questions about this.
Bravo, again! Thanks for taking a courageous stand on a very sensitive topic. The very fact that there is a profit motive at the heart of medical science necessitates vigilance. Despite the best of intentions and presumptions of integrity in research, the need for safeguards from an independent source is paramount.
Calls for speeding up drug approval and complaints about FDA slowness, regulations and bureaucracy should always be met with sound questioning, if not skepticism.
Andreas
Thank you MarilynHL for the link to Cold agglutinin disease. I believe, based on what I read, that this may be what my husband has.
After reading the info in this link & others, although we saw his oncologist only a month ago, I think it’s time to touch base again as it seems to be getting worse.
Again, thank you for bringing this to my attention.
Without getting into the politics of it, as CLL patients and their advocates we should stay informed about proposed changes to the treatment of “orphan drugs” in any health reform legislation and tax legislation.
When it comes to pharmaceutical R&D, CLL is a disease “of the few” – there just aren’t a lot of patients (market size)to support drug development. And with recent research showing the promise of treatments tailored more closely to specific deletions, etc. the slice of pie gets smaller and smaller. At the time when science is able to identify distinctions among subsets of CLL patients, we are seeing the possibility (reality?)of regulatory changes that may deter drug development that takes advantage of this new insight and opportunity.
It would be too bad if only large scale/large market “moon shot” product development becomes the only option in the future, when smaller, more agile ones would result in better outcomes.
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