This is a painful story to write.
A close friend of mine, in his 40’s, had a persistent light cough for many months. Finally, when he had an X-ray taken, it showed a large tumor on his lungs. He was diagnosed with stage 4 lung cancer. As a non-smoker and strapping, physically fit man, he was shocked, as you can imagine.
He went to his non-Boston-based medical practice, and he was told the prognosis was 12 to 18 months before he would die. They offered him, though, the chance to enroll in a clinical trial, based on a cocktail of chemotherapy agents.
Meanwhile, he wrote to me and another hospital-based friend in Boston, and our cancer experts in both places pointed out that there is a particular genotype of tumor that is susceptible to an oral chemotherapy drug. This type of tumor is present, in the case of non-smokers, about 17% of the time. Folks here recommended that he have a biopsy to see if he was “lucky.”
When he went back to his local medical practice and relayed this information from two of the world’s greatest oncologists, the local doctor discouraged him from getting the biopsy. He said that recovery from the biopsy operation would delay the start of the clinical trial by a month. The doctor intimated that there were very few slots left in the trial and that my friend might be excluded if he waited.
My friend chose to ignore the local doctor’s recommendation, relying on the advice of the Boston doctors. He came here and had the biopsy. It was a match. He started the chemotherapy regime, and it shrunk the tumor by 90%. This enabled it to be surgically removed, with good pathology results in the surrounding tissues. After surgery, he returned home in good shape and has started a maintenance chemotherapy program.
Upon returning home, too, he discovered that the local clinical trial actually was not at all fully subscribed, that they have been having trouble getting enough subjects.
The conclusions I draw from this are very distasteful. Perhaps I am too close to this because it involved a friend, and perhaps others of you see this differently; but I see a medical practice that intentionally put one its patients at risk to support the professional advancement of one of its doctors, and perhaps the financial advancement of that person or the practice, too.
Am I being unfair in my characterization?
Paul Levy is the President and CEO of Beth Israel Deconess Medical Center in Boston. Paul recently became the focus of much media attention when he decided to publish infection rates at his hospital, despite the fact that under Massachusetts law he is not yet required to do so. For the past three years he has blogged about his experiences in an online journal, Running a Hospital, one of the few blogs we know of maintained by a senior hospital executive.
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The fact is that when it comes to terminal cancer, there are some choices to be made and i am glad to hear that your friend ended up making the right one. This was a very inspirational story, since this subject is close to my heart as well..
rbar,
Thanks for the clarification about “vague conflict of interest.” If you read my blog regularly, you will see many stories about where our hospital fails to do things right, too. BTW, in this case, the patient actually did not go to our hospital, but to one of our neighbors and competitors in Boston.
On the broader questions of disclosure, I don’t know the right answer. As I mentioned, it is a subject often debated within all academic medical centers, and there are a variety of approaches adopted.
Jeff B
I agree about the FDA approved indication as not being the gospel for a drug. I know very well the efficacy of Taxol was dismal to say the least, and it still was used to treat ovarian cancer, to the detriment of many patients.
Despite the fact that when clinically relevant and accepted drugs have the same efficacy, and a tumor is resistant to one of them, it is within the standard of care to give the drug with the least resistance and/or the drug with the most sensitivity.
Greg,
Please don’t mistake the “FDA approved indication” as the gospel for a drug. The fact that the trials were not targeted against EGFR mutations, at best, represents a lack of a complete understanding at the time of trial design (many years ago). At worst, it is the manifestation of another conflict of interest. After all, the drug may be more profitable for the manufacturer if it is used on more patients (even those for whom it will provide no benefit). If either of these companies wanted to have an EGFR mutation specific indication approved, they would have to start the phase III process anew, which could take several years and several million dollars. In my opinion, this is an unfortunate unintended consequence of a rigorous randomized control trial process.
It is standard of care and personal judgment, not the fact that the FDA has approved a broad indication that dictates what should have been done. There is nothing that requires a clinician to prescribe a drug that he or she believes will not work for a given patient. The original post did not dispute that a test for the mutation was warranted.
While the recommendation to forgo testing may have been tainted by a conflict of interest, I just think that we aren’t ready to light the torches and bring out a lynch mob quite yet. I am simply arguing that if we must judge a clinician’s decision, we must stick to the facts known a priori at the point where their decision was made.
Large academic cancer institutions that are soulfully involved in clinical trials feel a subtle pull towards getting patients involved in those trials. It is the mindset of rewarding academic achievement and publication over all else. The present system exists to serve academic achievement and publication, but not to serve the best interests of patient.
If the drug was a tyrosine kinase inhibitor like Tarceva, the FDA approved indication for Tarceva did not limit prescribing specifically to EGFR positive patients. In the registration trial, only one third of the patients were tested for EGFR and determing response based on EGFR was not a major endpoint of the study.
Sequencing the genome of cancer cells is explicitly based upon the assumption that the pathways – network of genes – of tumor cells can be known in sufficient detail to control cancer. Each cancer cell can be different and the cancer cells that are present change and evolve with time.
Tarceva and Iressa target EGFR protein-tyrosine kinases. But all an EGFR mutation study can tell you is whether or not the cells are potentially susceptible to this mechanism of attack. It cannot tell you if Tarceva is better or worse than Iressa or other drugs which may target this. In different tumors, either Tarceva or Iressa, or some other drug, might do better or worse than the other.
Unfortunately, this is still a “trial-and-error” approach as conventional chemotherapy is. Why this when we have the ability to take a cancer specimen, analyze it, and follow those genetic changes that influence particular pathways, then use two, three, four or more targeted therapies, perhaps simultaneously, and be able to completely interrupt the flow of the cancer process.
To back Paul on the “vague conflict of interest” comment.
Conflict of interest is endemic in this industry — almost everyone stands to benefit in some way, shape or form when an issue is being discussed.
We need to apply a reasonable standard both here and in general.
Ask yourself this question: Has the person doing the talking established their credibility? I think Paul has. He’s been talking about these issues publicly for years. Both when they help his institution and when the hurt it – which is important.
Call me a fascist, but I actually don’t think there is an inherent evil in talking about your own organization and saying ‘I’ve considered it and think the way we do things is pretty good on balance.’
As long as you don’t conceal your agenda, you’re being above board. The problem is the people who actively conceal potential conflict of interest and hide their agendas behind self serving science and claims of objectivity.
That’s how I see things anyway, but of course I’m sure others will define things differently and seek a much more rigid definition. — John Irvine
Mr. Levy,
Let me preface this by saying that I am sorry about what happened to your friend, and also about the conslusions one might draw from that episode.
However, you are a high level administrator and you are commenting about care in your very own backyard. It makes your institution look good and an unnamed doc very, very bad. That’s what I meant with “vague conflict of interest”.
But I believe my previous post made it obvious that I in fact believe that these and similar stories do happen. But I also believe that the problem is pervasive in the US medical system, and wonder what you think about how to fix the problem. I am unsure whether just disclosure is enough, as you seem to think.
Hi Paul
You asked, ‘Am I being unfair in my characterization?’
No, sadly, I don’t think you are.
In most non healthcare professions such efforts to deceive “clients” for the gain of the vendor professional could be the basis for criminal action. It is an interesting issue that in this medical instance it is even appropriate to question the ethics.
Dear rbar,
I don’t think the issue is whether a doctor is salaried or not. (Indeed, in this case, I have good reason to believe the doctor was salaried.)
I published this story because it is a compelling story and telling it might cause people (patients and doctors) to raise questions that they might not otherwise raise.
The Harvard system (which includes BIDMC, the Partners hospitals, and others) has conflict-of-interest policies and disclosure rules. There is often a debate as to whether they are too strict or not strict enough. I think that debate is more or less typical of academic centers, and it is a healthy one to have.
I am not sure why you talk about me as having a “vague conflict of interest.” I don’t know what that term means. Maybe you could explain further.
A lung cancer biopsy is no small matter, I do understand why the clinician was hesitant to perform this for a less than 1 in 5 chance that the mutation would be found.
Life is like poker in that sometimes a fool wins a hand he should have folded and a tight player gets handed a bad beat. We can’t retrospectively analyze this decision based solely on the outcome.
I’ll go out on a limb here and guess that this oral chemotherapy drug is a tyrosine kinase inhibitor that only works when a specific EGFR mutation is present. Most probably, the same blockbuster drug whose sister compound failed to show efficacy in phase III trials because due to pure bad luck, the trial designers didn’t have enough non-smokers, Asians, or females in the sample (the mutation is more prevalent in these populations).
The ethical questions are:
1. Is testing for this EGFR mutation in a non-smoking male (not sure if he’s Asian from the post) the standard of care in the majority of clinical settings where trials are not taking place? A lung cancer biopsy is no small undertaking and a 1 in 5 shot is in the minority.
2. Did the doctor really believe that the trial would fill up in the month that would be lost in the greater than 80% chance that he did not have the EGFR mutation?
But a more interesting question is this (and sorry to get even more technical with the science here):
Given that a K-Ras mutation is highly negatively correlated with an EGFR mutation, and K-Ras expression can be detected in the serum, why isn’t the standard of care to test for an absence of K-Ras? I would bet that would turn that 1 in 5 chance to at least 4 in 5, if not more, and we’re talking about drawing a little blood, instead of going in and cutting out lung tissue.
Paul, in my opinion your characterization of the medical care your friend received in the non-Boston-based practice is accurate.
I worked for a short time in an academic-based medical practice in which patients, who had a partial response to an antidepressant, were offered the chance to participate in clinical trials. The problem was that other standard treatment options, such as psychotherapy, were not offered to patients prior to clinical trial recruitment.
The doctor-trainees and their supervisors had dual roles as clinician-researchers, and they had much to gain from recruiting their patients for clinical trials. This arrangement set the stage for scenarios similar to the one you described in your post.
Mr. Levy – I would be interested why you relate that story in this blog, and what conclusions you draw from it … you are influential in the health care field (and BTW, one could even raise the issue of a vague conflict of interest).
My conclusion from the story is that too many medical decisions in the US are tied to strong financial incentives, and that logically, these incentives have to be be taken away or minimized. My suggestion would be to have salaried doctors, with only small incentives to see more patients than usual, or to do that extra surgery. Most people within the health care system who keep their eyes open know of surgeons operating on any warm body, as long as there is a 3rd party payor (this is just one example of unproductive incentives).
So I am curious, what is Harvard/Beth Israel Deconess Medical Center/Partners doing or planning in that regard?
Congratulations to your friend. He made right decision. In another article about – ‘gimme my dam data’, Merl B in comments section made a point about second opinion industry.
Having data is very helpful for second opinion industry and then taking ownership and your friend took his own decision.
A question worthwhile asking is how frequently do such things happen? Since this was a question of life and death outcome was very obvious. But at smaller levels, how often do doctors get it right?
Sorry to hear about your friend. Did he work in smoky environments (e.g., restaurants, concert halls)?
DISCLOSURE is the issue.
In something like this — information (except personal) should be DISCLOSED — in REAL TIME.
MDs and others should be FOR DISCLOSURE — reduces accusations of SELF-DEALING.
This is PROBLEM with the elites — think the masses cannot deal with HARD FACTS.
WRONG! Masses are so much WISER than the “experts,” it is not amusing.